SatuRday, SePtemBeR 13

Transcription

T he R e t in a S oc ie t y
Design: Barbara Lande
The Retina Society
The 47th Annual Scientific Meeting
PHILADELPHIA, PENNSYLVANIA | September 11 – 14, 2014
P HI LA D E LP HIA , P ENN SY LVANIA
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The Retina Society
47th Annual Scientific Meeting
1968
etina S
The Retina Society
P.O. Box 6305, 50 Staniford Street, 7th Floor, Boston, MA 02114
Tel: 617.227.8767 Fax: 617.367.4908 [email protected] www.retinasociety.org
Schuylkill River
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The Retina Society
Contents
President’s Welcome Letter .
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Officers of The Retina Society . . . . . . . . . . . . . . . . . . . 7
Committees of The Retina Society . . . . . . . . . . . . . . . . . 7
Members of The Retina Society . . . . . . . . . . . . . . . . . . 8
Charter Members of The Retina Society .
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In Memoriam .
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New Members of The Retina Society .
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CME Information . . . . . . . . . . . . . . . . . . . . . . . 17
Program-in-Brief . . . . . . . . . . . . . . . . . . . . . . . 19
Social Program .
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Guests of Honor .
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Retina Research Foundation Award of Merit . . . . . . . . . . . . . . 30
J. Donald M. Gass Award .
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Fellowship Research Award .
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Raymond R. Margherio Award . . . . . . . . . . . . . . . . . .
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Map of Exhibitors and Poster Locations .
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Interesting Cases and Video Conference . . . . . . . . . . . . . . . 44
Scientific Sessions . . . . . . . . . . . . . . . . . . . . . .
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Poster Program . . . . . . . . . . . . . . . . . . . . . . .
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Friday Abstracts . . . . . . . . . . . . . . . . . . . . . . . 63
Saturday Abstracts .
Sunday Abstracts .
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Poster Abstracts . . . . . . . . . . . . . . . . . . . . . . . 177
Corporate Supporters .
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Exhibitors .
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Index of Authors . . . . . . . . . . . . . . . . . . . . . . . 215
Future Meeting . . . . . . . . . . . . . . . . . . . . . . .
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Broad Street
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The Retina Society
Welcome
Dear Colleagues,
W
elcome to Philadelphia! The Host Committee and I are thrilled to have you join
us in this city so rich in history and art—a most appropriate setting for the historic
47th meeting of The Retina Society, a group focused not only on the Science,
but also on the Art of Medicine. We have sprinkled the program and evening events with a
liberal selection of tastes and sounds and sights that characterize the City of Brotherly Love,
realizing that we can only just barely scratch the surface, and hope that you will have time
before and after to delve more deeply, from the museums and galleries and concerts to the
historic sites and architectural gems, to the vibrant restaurant scene, sports teams, unique
shopping, and much more. Use our website for clues and links! The meeting will be a little
different from the usual hotel-based program, housed instead at the architecturally significant
and tradition-rich Union League of Philadelphia, rated the #1 city club in the nation.
We kick off on September 11 in an appropriately patriotic spot, the Liberty View ballroom
of the Constitution Center’s Visitors’ Center, overlooking Independence Hall, with our always
popular Interesting Cases Conference, and then board trolleys for our welcoming reception
on the balcony of the Pantheon-inspired domed lobby of the Ritz Carlton. Scientific sessions
start Friday morning, with an impressive line-up of full-length and rapid-fire presentations,
and conclude a bit early so that we can take advantage of a once-in-a-lifetime opportunity:
the face-to-face installation at the famed Philadelphia Museum of Art of the two groundbreaking “Clinics” paintings by native Philadelphian Thomas Eakins, with a lecture beforehand
by Eakins biographer, documentary filmmaker, and noted historical author Sidney Kirkpatrick.
His book is our party favor, and we hope you will take advantage of the evening with the
author and his wife to have your copy personally signed! The Union League Lincoln Hall will
host our lively cornucopia of Philadelphia-themed entertainment Friday night, with spirited
music, historical figures including Ben Franklin himself and a bevy of taproom singers, photo
souvenirs of you with city backgrounds, “Taste of Philadelphia” food stations, and much more!
Another twist on our usual routine will be moving the black-tie dinner gala to
Saturday night, when we travel just a few blocks to the hottest new museum on the art
scene, the Barnes, home of the world’s largest private collection of Impressionist art,
controversially relocated to center city, and just opened to a worldwide chorus of critical
acclaim. Not only will the galleries be ours alone that evening, but also the special
exhibition of Cezanne’s still life paintings. Feast both eyes and body: world-famed artwork,
and a sumptuous banquet, punctuated by a brief dinner talk by our own Bill Tasman on
Dr. Barnes himself, whose original fortune was based on eye drops! And then we dance!
We will be toasting Dr. Harry Flynn and Dr. Ralph Eagle as our special Guests of Honor at
this meeting, celebrated for their many years of service to our field. Drs. Peter Campochiaro and
Sandy Brucker are our distinguished award recipients and we look forward to their featured
presentations, as well of those of up-and-coming retinal specialists presenting the Fellowship
and Margherio Award talks, Drs. Francisco Folgar and John Miller. Congratulations to all
these well-deserving friends and colleagues!
Quite a line up!! Take a deep breath and step up to the plate—we hope you relish every
aspect of the 47th annual meeting of The Retina Society.
Sincerely,
Julia A. Haller, MD
President, The Retina Society, for the Host Committee
Host Committee: Bill Annesley, Bill & Linda Benson, Gary & Lissa Brown, Sandy & Terry Brucker, Jay Federman &
Sylvia Beck, David & Paula Fischer, Sunir Garg & Stella Luo, Dick & Arlene Goldberg, Julia Haller & John Gottsch,
Allen Ho, Rick & Jackie Kaiser, Al & Joan Lucier, Joe & Patti Maguire, Carl & Teresa Regillo, Lov & Carol Sarin,
Jerry & Carol Shields, Arunan Sivalingam & Chris Chung, Bill & Alice Lea Tasman, Jim Vander & Janice Gault
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Historic Betsy Ross House
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The Retina Society
2014 officers
O F T HE R E T INA S OCIE T Y
President
Vice-President Secretary
Treasurer
Julia A. Haller, MD
Mark W. Johnson, MD
Allen C. Ho, MD
Bernard H. Doft, MD
PAST P RE S IDENTS
1968 – 1969Charles L. Schepens*
1970 – 1971 Robb McDonald*
1972 – 1973L. Harrell Pierce*
1974 – 1975 Samuel Adams*
1976 – 1977Charles Regan*
1978 – 1979 Alice R. McPherson
1980 – 1981 Ariah Schwartz*
1982 – 1983 Robert B. Welch
1984 – 1985H. MacKenzie Freeman
1986 – 1987 J. Graham Dobbie*
1988 – 1989 William S. Tasman
1990 – 1991 Alain P. Rousseau
1992 – 1993 D. Jackson Coleman
1994 – 1995 J. Wallace McMeel
1996 – 1997 Raymond R. Margherio*
1998 – 1999 Wayne E. Fung
2000 – 2001 Felix N. Sabates
2002 – 2003Harry W. Flynn Jr.
2004 – 2005C. Pat Wilkinson
2006 – 2007 Michael T. Trese
2008 – 2009 Donald J. D’Amico
2010 – 2011 Mark S. Blumenkranz
2012 – 2013 Charles C. Barr
*deceased
Com m i t t e e s
Executive Committee
Finance Committee
Julia A. Haller
Charles C. Barr
Bernard H. Doft
Jeffrey S. Heier
Allen C. Ho
Mark W. Johnson
Timothy G. Murray
Bernard H. Doft, Chair
David S. Boyer
Gary C. Brown
Julia A. Haller
Steven D. Schwartz
David F. Williams
Nominating Committee
David M. Brown, Chair
Bernard H. Doft
Dean Eliott
Mark W. Johnson
Alan E. Kimura
Julia A. Haller (ex officio)
Credentials Committee
Jeffrey S. Heier, Chair
Audina M. Berrocal
Anne E. Fung
Allen C. Ho
Michael S. Ip
Judy E. Kim
Julia A. Haller (ex officio)
Program Committee
Charles C. Barr
Bernard H. Doft
Julia A. Haller
Allen C. Ho
Mark W. Johnson
By-Laws Committee
Daniel M. Miller, Chair
Kimberly A. Drenser
Sunir J. Garg
SriniVas R. Sadda
Socio-Economic Committee
Antonio Capone Jr., Chair
J. Michael Jumper
Alan J. Ruby
Reginald J. Sanders
James F. Vander
AAO Representative
Jennifer I. Lim
Anne E. Fung, Alternate
Executive Secretary
Judith Cerone Keenan
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2014 members
A
Thomas M. Aaberg Jr., MD
Thomas M. Aaberg Sr., MD, MSPH
Gary W. Abrams, MD
David H. Abramson, MD
Albert L. Ackerman, MD
Anthony P. Adamis, MD
Ron Adelman, MD, MPH, MBA
Anita Agarwal, MD
Everett Ai, MD
Lloyd M. Aiello, MD
Lloyd P. Aiello, MD, PhD
Daniel M. Albert, MD, MS
Thomas A. Albini, MD
Daniel V. Alfaro III, MD
Arthur W. Allen, MD
Penelope J. Allen, FRANZCO
Arghavan Almony, MD
John S. Ambler, MD
Rajiv Anand, MD
W. Banks Anderson Jr., MD
William H. Annesley Jr., MD
Rajendra S. Apte, MD, PhD
J. Fernando Arevalo, MD, FACS
Neva P. Arribas, MD
Jorge G. Arroyo, MD, MPH
Neal H. Atebara, MD
Leyla S. Atmaca, MD
James J. Augsburger, MD
Albert J. Augustin, Prof. Dr.
Marcos P. Avila, MD
Carl C. Awh, MD
Claudio Azzolini, MD
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Sophie Bakri, MD
Florian Balta, MD
Francesco Bandello, MD, FEBO
Adiel Barak, MD
Gaetano R. Barile, MD
Charles C. Barr, MD
Ziad F. Bashshur, MD
Caroline R. Baumal, MD
Steven R. Bennett, MD
William E. Benson, MD
Matthew S. Benz, MD
Brian B. Berger, MD
Daniel M. Berinstein, MD
Audina M. Berrocal, MD
José A.H. Berrocal, MD
Maria H. Berrocal, MD
Eliot L. Berson, MD
Neelakshi Bhagat, MD, MPH, FACS
Robert B. Bhisitkul, MD, PhD
Susanne Binder, Prof. MD
Michael P. Blair, MD
Norman P. Blair, MD
George W. Blankenship, MD
Kevin J. Blinder, MD
Christopher F. Blodi, MD
Michael A. Bloome, MD
Mark S. Blumenkranz, MD
Edwin E. Boldrey, MD
James P. Bolling, MD
Arnaldo F. Bordon, MD, PhD
Claude Boscher, MD
Jerald A. Bovino, MD
David S. Boyer, MD
Rosario Brancato, MD
Oswaldo M. Brasil, MD
Periklis D. Brazitikos, MD
Neil M. Bressler, MD
Susan B. Bressler, MD
Gregory S. Brinton, MD
Mariel Brittis, MD
Roy D. Brod, MD
H. Logan Brooks, MD
David M. Brown, MD
Gary C. Brown, MD, MBA
Alexander J. Brucker, MD
Helmut Buettner, MD
Dean B. Burgess, MD
Thomas C. Burton, MD
Brandon G. Busbee, MD
Sheldon M. Buzney, MD
Norman E. Byer, MD
Gordon Byrnes, MD
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Peter A. Campochiaro, MD
Herbert L. Cantrill, MD
Antonio Capone Jr., MD
Jose A. Cardillo, MD
Renato Cardoso, MD
Marcia D. Carney, MD
Petros Carvounis, MD
Antonio M. Casella, MD, PhD
Colleen M. Cebulla, MD
Osman Cekic, MD, PhD
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The Retina Society
Clement K. Chan, MD
R.V. Paul Chan, MD
Suresh R. Chandra, MD
Louis Chang, MD
Stanley Chang, MD
Susie Chang, MD
Tom S. Chang, MD
Devron H. Char, MD
Steve Charles, MD
Nauman A. Chaudhry, MD
Sai H. Chavala, MD
Eric Chen, MD
Emily Y. Chew, MD
Lionel D.J. Chisholm, MD, FRCS(C)
Lawrence P. Chong, MD
David R. Chow, MD, FRCS(C)
Itay Chowers, MD
John B. Christoforidis, MD
Arnaldo P. Cialdini, MD
Antonio P. Ciardella, MD
Thomas A. Ciulla, MD
W. Lloyd Clark, MD
John G. Clarkson, MD
Walter D. Cockerham, MD
D. Jackson Coleman, MD
Michael Colucciello, MD
Brian P. Conway, MD
Michael J. Cooney, MD, MBA
Scott W. Cousins, MD
Glynne C. Couvillion, MD
Alan F. Cruess, MD
Karl G. Csaky, MD
Eduardo Cunha de Souza, MD
Emmett T. Cunningham, MD, PhD, MPH
D
James P. Dailey, MD
Francisco Max Damico, MD
Donald J. D'Amico, MD
Arup Das, MD, PhD
Taraprasad Das, MD
Frederick H. Davidorf, MD
Janet L. Davis, MD
Matthew D. Davis, MD
Pouya N. Dayani, MD
Serge de Bustros, MD
Eugene de Juan Jr., MD
Lucian V. Del Priore, MD, PhD
Angelos Dellaporta, MD
Vincent A. Deramo, MD
2014 Members
Uday R. Desai, MD
Sundeep Dev, MD
James G. Diamond, MD
Kenneth R. Diddie, MD
J. Paul Dieckert, MD
Ricardo Dodds, MD
Bernard H. Doft, MD
Larry A. Donoso, MD
Kimberly A. Drenser, MD, PhD
Sander R. Dubovy, MD
Pravin U. Dugel, MD
Elia J. Duh, MD
Jean Dumas, MD
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Justis P. Ehlers, MD
Martin Ehrenberg, MD, GCP, FACS
Charles W.G. Eifrig, MD
Dean Eliott, MD
Andrew W. Eller, MD
Susan G. Elner, MD
Harry Engel, MD
William G. Everett, MD
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Christiane I. Falkner-Radler, MD
Michel E. Farah, MD
David M. Fastenberg, MD
Amani A. Fawzi, MD
Jay L. Federman, MD
Sharon Fekrat, MD
Stephen S. Feman, MD, MPH, FACS
Frederick L. Ferris, MD
Philip J. Ferrone, MD
Howard F. Fine, MD MHSc
Stuart L. Fine, MD
Paul T. Finger, MD, FACS
David H. Fischer, MD
Gary Edd Fish, MD
Yale L. Fisher, MD
Christina J. Flaxel, MD
Harry W. Flynn Jr., MD
Michael H. Foerster, MD, PhD
James C. Folk, MD
Donald S. Fong, MD
Bradley S. Foster, MD
Robert E. Foster, MD
Donald A. Frambach, MD
Robert N. Frank, MD
Hal M. Freeman, MD
William R. Freeman, MD
Dennis B. Freilich, MD
K. Bailey Freund, MD
Thomas R. Friberg, MD
M. Wallace Friedman, MD
Scott M. Friedman, MD
Arthur D. Fu, MD
Dwain G. Fuller, MD
Anne E. Fung, MD
Wayne E. Fung, MD
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Donald A. Gagliano, MD, MHA
Brenda L. Gallie, MD FRCS(C)
Charles A. Garcia, MD
Enrique Garcia-Valenzuela, MD, PhD
Thomas W. Gardner, MD, MS
Seema Garg, MD, PhD
Sunir J. Garg, MD, FACS
Michael W. Gaynon, MD
William S. Gilbert, MD
Kurt A. Gitter, MD
Bernard F. Godley, MD, PhD, FACS
Michael H. Goldbaum, MD
Morton F. Goldberg, MD
Richard E. Goldberg, MD
John R. Gonder, MD
Christine R. Gonzales, MD
Victor H. Gonzalez, MD
Fred Gottlieb, MD
Evangelos S. Gragoudas, MD
M. Gilbert Grand, MD
Ninel Z. Gregori, MD
Craig M. Greven, MD
Jeffrey G. Gross, MD
Froncie A. Gutman, MD
David R. Guyer, MD
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William S. Hagler, MD
Barrett G. Haik, MD, FACS
Julia H. Haller, MD
Mark E. Hammer, MD
G. Robert Hampton, MD
Dennis P. Han, MD
James T. Handa, MD
Anne H. Hanneken, MD
Thomas A. Hanscom, MD
J. William Harbour, MD
Seenu M. Hariprasad, MD
Gordon S. Harris, MD
Mary Elizabeth Hartnett, MD
Tarek S. Hassan, MD
W. Rex Hawkins, MD
Hideyuki Hayashi, MD
Sohan S. Hayreh, MD, PhD, DSc FRCS, FRC Ophth
John R. Heckenlively, MD
Jeffrey S. Heier, MD
Tatsuo Hirose, MD
Allen C. Ho, MD
Nancy M. Holekamp, MD
Eric R. Holz, MD
Kenneth R Hovland, MD
Peter Hovland, MD, PhD
Jason Hsu, MD
G. Baker Hubbard III, MD
Jean-Pierre Hubschman, MD
Mark S. Humayun, MD, PhD
William T. Humphrey, MD
Deeba Husain, MD
William L. Hutton, MD
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Raymond Iezzi, MD, MS
Michael S. Ip, MD
Alexander R. Irvine, MD
Milan Ivanisevic, MD, PhD
J
Douglas A. Jabs, MD
Robert Jack, MD
Harold N. Jacklin, MD
Timothy L. Jackson, PhD, FRCOphth
Glenn J. Jaffe, MD
Alex E. Jalkh, MD
Lee M. Jampol, MD
William H. Jarrett, MD
Leonard Joffe, MD
Mark W. Johnson, MD
Robert N. Johnson, MD
Glen P. Johnston, MD
Jost B. Jonas, MD
Brian C. Joondeph, MD
Daniel P. Joseph, MD, PhD
Bradley F. Jost, MD
J. Michael Jumper, MD
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2014 members
K
Peter K. Kaiser, MD
Richard S. Kaiser, MD
Robert E. Kalina, MD
Jennifer J. Kang-Mieler, PhD
Henry J. Kaplan, MD
Joel A. Kaplan, MD
David B. Karlin, AB, MD, MSc (Ophth.)
Shalesh Kaushal, MD, PhD
Rahul N. Khurana, MD
Gibran Khurshid, MBBS, MD
Hyung Chan Kim, MD, PhD
Ivana K. Kim, MD
Judy E. Kim, MD
Rosa Y. Kim, MD
Stephen J. Kim, MD
Alan E. Kimura, MD
James L. Kinyoun, MD
Szilárd Kiss, MD
Michael L. Klein, MD
Robert C. Kleiner, MD
Frank H.J. Koch, MD
Gregg T. Kokame, MD, MMM
Jaclyn Kovach, MD
Allan E. Kreiger, MD
Ingrid Kreissig, MD
Louis P. Kruger, FRCS Ed, FRC Ophth
Baruch D. Kuppermann, MD, PhD
Oh W. Kwon, MD
Jan A. Kylstra, MD
L
Francis L'Esperance Jr., MD
James Lai, MD
Michael Lai, MD, PhD
Timothy Lai, MD, FRCS, FRCOphth
Wico Lai, MD, FACS
Rohit Lakhanpal, MD
Vinod Lakhanpal, MD
Geeta Lalwani, MD
Linda A. Lam, MD
H. Michael Lambert, MD
Maurice Landers III, MD
John Lean, MD
Peter Leaver, FRCS, FRCOphth
Bailey Lee, MD
Carol Lee, MD
Ji Eun Lee, MD, PhD
King Lee, MD
Thomas Lee, MD
Theodore Leng, MD, MS
Brian Leonard, MD
Mary Lou Lewis, MD
Helen Li, MD
Peter Liggett, MD
Jennifer Lim, MD
Luiz Lima, MD
Harvey Lincoff, MD
Hunter Little, MD
Louis Lobes, MD
Anat Loewenstein, MD
John Loewenstein, MD
Lawrence Lonn, MD
Robert Lopez, MD
David Lozano-Elizondo, MD
Alfred Lucier, MD
Alice Lyon, MD
M
Alan L. Maberley, MD
David A.L. Maberley, MD
Mathew W. MacCumber, MD, PhD
J. Christopher Macdonald, MD
Cynthia J. MacKay, MD
Steven A. Madreperla, MD, PhD
Joseph I. Maguire, MD
Tamer H. Mahmoud, MD, PhD
James C. Major Jr., MD, PhD, FACS
Enrique S. Malbran, MD
Robert N. Mames, MD
Naresh Mandava, MD
Eric S. Mann, MD
Dennis Marcus, MD
Michael F. Marmor, MD
Adam Martidis, MD
Daniel F. Martin, MD
Vicente Martinez-Castillo, MD
John O. Mason III, MD
G. Philip Matthews, MD, PhD
Donald P. Maxwell Jr., MD
Donald R. May, MD, FACS
Ian L. McAllister, MD
Colin A. McCannel, MD
Tara A. McCannel, MD, PhD
Brooks W. McCuen II, MD
H. Richard McDonald, MD
Edward B. McLean, MD
J. Wallace McMeel, MD
Alice R. McPherson, MD
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The Retina Society
Ugo Menchini, MD
Travis A. Meredith, MD
Carsten H. Meyer III, MD, FEBO
Sanford M. Meyers, MD
Michel Michaelides, BSc, MB, BS MD(Res), FRCOphth, FACS
Edoardo Midena, MD, PhD
William F. Mieler, MD
Daniel M. Miller, MD, PhD
Joan W. Miller, MD
Robert A. Mittra, MD
Jordi Monés, MD, PhD
Lemuel T. Moorman, MD
Virgilio Morales-Canton, MD
Robert E. Morris, MD
Lawrence S. Morse, MD, PhD
Peter H. Morse, MD
Andrew A. Moshfeghi, MD, MBA
Darius M. Moshfeghi, MD
Prithvi Mruthyunjaya, MD
Shizuo Mukai, MD
Robert P. Murphy, MD
Timothy G. Murray, MD, MBA, FACS
Frank L. Myers, MD
N
Perumalsamy Namperumalsamy, MD
Sumit K. Nanda, MD
Fadi P. Nasrallah, MD
S. Natarajan, MD
Marcio Nehemy, MD, PhD
Quan Dong Nguyen, MD, MSc
Kousuke Noda, MD
T. Michael Nork, MD, MS
Michael A. Novak, MD
Julian J. Nussbaum, MD
O
Michael D. Ober, MD
Richard R. Ober, MD
Guy E. O'Grady, MD
Annabelle Okada, MD
Edward Okun, MD
R. Joseph Olk, MD
Karl R. Olsen, MD
Timothy W. Olsen, MD
Patrick F. O'Malley, MD
E. Mitchel Opremcak, MD
Juan Orellana, MD
David H. Orth, MD
2014 members
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Andrew J. Packer, MD
Kirk H. Packo, MD
Alan G. Palestine, MD
Stephen S. Pappas, MD
Jean-Marie A Parel, PhD
Donald W. Park, MD
Kyu Hyung Park, MD
Susanna S. Park, MD, PhD
David W. Parke II, MD
Leonard M. Parver, MD
Fabio Patelli, MD
Peter R. Pavan, MD
Alfredo Pece, MD
John W. Pemberton, MD
Samuel R. Pesin, MD
Michael R. Petersen, MD, PhD
Gholam A. Peyman, MD
Dante J. Pieramici, MD
Stefano Piermarocchi, MD
A. Raymond Pilkerton Jr., MD
Lon S. Poliner, MD
Ayala Pollack, MD
John S. Pollack, MD
Michael J. Potter, MD, FRCSC
Vasiliki Poulaki, MD
Constantin J. Pournaras, MD
Jonathan Prenner, MD
Ira A. Priluck, MD
Ronald C. Pruett, MD
James E. Puklin, MD
Carmen A. Puliafito, MD, MBA
Jose S. Pulido, MD
Q
Giuseppe Querques, MD, PhD
Hugo Quiroz-Mercado, MD
R
Norman D. Radtke, MD
Firas M. Rahhal, MD
Robert C. Ramsay, MD
Prabakar Kumar Rao, MD
Pamela P. Rath, MD
Franco M. Recchia, MD
Frederick H. Reeser, MD
Carl D. Regillo, MD
Elias Reichel, MD
Vincent S. Reppucci, MD
Kourous A. Rezaei, MD
Thomas A. Rice, MD
Christopher D. Riemann, MD
Jeffrey S. Rinkoff, MD
Guido Ripandelli, MD
Kelvin N. Rivett, FRCS
Stanislao Rizzo, MD
Dennis M. Robertson, MD
Joe E. Robertson Jr., MD
Alvaro Rodriguez, MD
Mario R. Romano, MD, PhD
Richard B. Rosen, MD, ScD
Philip J. Rosenfeld, MD
William H. Ross, MD
Daniel B. Roth, MD
Alain P. Rousseau, CM, MD, FRCSC
Melvin L. Rubin, MD, MSc
Patrick E. Rubsamen, MD
Alan J. Ruby, MD
Richard S. Ruiz, MD
Stephen R. Russell, MD
Edwin H. Ryan, MD
S
Felix N. Sabates, MD
Nelson R. Sabates, MD
Roland Sabates, MD
SriniVas R. Sadda, MD
Norman Saffra, MD
Taiji Sakamoto, MD
George Sanborn, MD
Reginald J. Sanders, MD
Delia N. Sang, MD
Steven R. Sanislo, MD
David A. Saperstein, MD
Lov K. Sarin, MD
David Sarraf, MD
Shlomit Schaal, MD, PhD
Andrew P. Schachat, MD
William M. Schiff, MD
Ursula Schmidt-Erfurth, MD
Lawrence H. Schoch, MD
Hendrik P. Scholl, MD, MA
Robert P. Schroeder, MD
Hermann D. Schubert, MD
Daniel M. Schwartz, MD
Stephen G. Schwartz, MD
Steven D. Schwartz, MD
Ingrid U. Scott, MD, MPH
Jerry Sebag, MD, FACS, FRCOphth
Johanna M. Seddon, MD, ScM
Morton H. Seelenfreund, MD
Anwar Shah, MD
Gaurav K. Shah, MD
Saad A. Shaikh, MD
Eric P. Shakin, MD
Jeffrey L. Shakin, MD
Shwu-Jiuan Sheu, MD
Carol L. Shields, MD
Jerry A. Shields, MD
Yossi Sidikaro, MD, PhD
Paul A. Sieving, MD, PhD
Michael A. Singer, MD
Lawrence J. Singerman, MD
Arun D. Singh, MD
Rishi P. Singh, MD
Robert A. Sisk, MD
Arunan Sivalingam, MD
Raymond N. Sjaarda, MD
Stephanie A. Skolik, MD
Jason S. Slakter, MD
M. Madison Slusher, MD
Kent W. Small, MD
William E. Smiddy, MD
William B. Snyder, MD
Güngör Sobaci, MD
Lucia Sobrin, MD
Elliott H. Sohn, MD
Sharon D. Solomon, MD
John A. Sorenson, MD
Richard F. Spaide, MD
Harold F. Spalter, MD
Rand Spencer, MD
Scott M. Steidl, MD
Robert L. Steinmetz, MD
Walter H. Stern, MD
Paul Sternberg Jr., MD
Jay M. Stewart, MD
Michael W. Stewart, MD
Mario Stirpe, MD
Glenn L. Stoller, MD
Bradley R. Straatsma, MD, JD
Jennifer Sun, MD
Ivan Suner, MD
Jennifer U. Sung, MD
T
Homayoun Tabandeh, MD, MS
Minoru Tanaka, MD, PhD
Howard L. Tanenbaum, MD, FRCSC
Johnny Tang, MD
William S. Tasman, MD
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11
2014 members
David G. Telander, MD
Asheesh Tewari, MD
Tongalp H. Tezel, MD
Panagiotis G. Theodosiadis, MD
Matthew A. Thomas, MD
John T. Thompson, MD
James S. Tiedeman, MD, PhD
Felipe I. Tolentino, MD
Harvey W. Topilow, MD
Trexler M. Topping, MD
Paul E. Tornambe, MD
Cynthia A. Toth, MD
Giora Treister, MD
Clement L. Trempe, MD
Michael T. Trese, MD
Irena Tsui, MD
V
Albert Vaiser, MD
Wichard A.J. van Heuven, MD
James F. Vander, MD
Raul R.N. Vianna, MD, PhD
Andrew K. Vine, MD
Tamara Vrabec, MD
Charles M. Vygantas, MD
Keye L. Wong, MD
Gloria Wu, MD
Lihteh Wu, MD
Y
Jiong Yan, MD
Lawrence A. Yannuzzi, MD
Steven Yeh, MD
Young Hee Yoon, MD
Akitoshi Yoshida, MD, PhD
Marc O. Yoshizumi, MD
Lucy H-Y. Young, MD, PhD
Seung-Young Yu, MD, PhD
Z
David N. Zacks, MD, PhD
Z. Nicholas Zakov, MD
Hadi Zambarakji, FRCOphth DM
Marco A. Zarbin, MD, PhD
Hernando Zegarra, MD
Ingrid E. Zimmer-Galler, MD
Keith M. Zinn, MD
Leonidas Zografos, MD
W
Joseph B. Walsh, MD
Christopher Walton, MD
Keith A. Warren, MD
Robert C. Watzke, MD
Eric D. Weichel, MD
Daniel T. Weidenthal, MD
David V. Weinberg, MD
Thomas A. Weingeist, MD, PhD
David J. Weissgold, MD
John J. Weiter, MD, PhD
Robert B. Welch, MD
John A. Wells III, MD
Howard L. Wilder, MD
C. Pat Wilkinson, MD
David F. Williams, MD, MBA
George A. Williams, MD
R. Geoff Williams, MD, FRCSC
R. Sloan Wilson, MD
C. Douglas Witherspoon, MD
Robert A. Wiznia, MD
Sebastian Wolf, MD, PhD
Thomas J. Wolfensberger, MD
Jun S. Wong, MD
12
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The Retina Society
Charter Members — 1968
I.D. Okamura
Edward Okun
Stephen S. Pappas
John W. Pemberton
L. Edward Perraut
L. Harrell Pierce
Dohrmann K. Pischel
Charles D. J. Regan
Morton L. Rosenthal
Nathan H. Roth
Alain P. Rousseau
Richard S. Ruiz
Felix N. Sabates
Charles L. Schepens
Ariah Schwartz
Donald M. Shafer
Anwar Shah
Michael Shea
Taylor R. Smith
Bradley R. Straatsma
Thomas P. Stratford
William S. Tasman
Robert C. Watzke
Daniel T. Weidenthal
Robert B. Welch
Howard Wilder
Fred M. Wilson
Albert L. Ackerman
Samuel T. Adams
William H. Annesley Jr.
Robert J. Brockhurst
Charles J. Campbell
Lionel D.J. Chisholm
Graham Clark
Bayard H. Colyear Jr.
George B. Corcoran
Morton S. Cox Jr.
Matthew D. Davis
J. Graham Dobbie
William G. Everett
Hal M. Freeman
Dennis B. Freilich
William S. Hagler
William H. Havener
William H. Jarrett
David O. Jesberg
Otto M. Jungschaffer
Joel A. Kaplan
Harvey A. Lincoff
Harry M. McAllister
P. Robb McDonald
J. Wallace McMeel
Alice R. McPherson
Delbert P. Nachazel
Edward W. D. Norton
In Memoriam
David E. Eifrig
October 2013
Thomas P. Stratford
Charter Member
February 2014
R. David Sudarsky
March 2014
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13
New Members 2014
Arghavan Almony, MD
Southern Pines, SC
Pouya N. Dayani, MD
Beverly Hills, CA
Active Members
Jason Hsu, MD
Philadelphia, PA
Linda A. Lam, MD
Los Angeles, CA
Mountain View, CA
Theodore Leng, MD, MS
Palo Alto, CA
Prabakar K. Rao, MD
St. Louis, MO
14
Shaker Heights, OH
|
James C. Major Jr., MD, PhD
Houston, TX
Richard B. Rosen, MD
New York, NY
The Retina Society
Ji Eun Lee, MD
Busan, S. Korea
Virgilio Morales-Canton, MD
Mexico City, Mexico
Steven Yeh, MD
Atlanta, GA
Irena Tsui, MD
Los Angeles, CA
Michel Michaelides, BSc, MB, BS, MD(Res),
FRCOphth FACS
London, UK
Kousuke Noda, MD
Sapporo, Japan
Kyu H. Park, MD
Gyeonggi, S. Korea
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15
corresponding Members
Elliott H. Sohn, MD
Iowa City, IA
Active Members
New Members 2014
Liberty Bell
16
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The Retina Society
CME INFORMATION
DISCLOSURE: All speakers have been asked to disclose any significant relationships they
may have with commercial companies. The presence or absence of relationships as well as
off-label discussion of projects will be disclosed at the time of the meeting.
TARGET AUDIENCE: Vitreoretinal ophthalmologists who are members and guests of
members of The Retina Society, as well as fellows-in-training.
GOALS OF MEETING: This annual meeting is intended to increase the physician’s
knowledge, skills and performance to provide services for patients. Topics for discussion will
include but are not limited to age-related macular degeneration, diabetic retinopathy, tumors,
infections, surgery for retinal detachment and macular disease, pediatrics, anti-VEGF agents.
At the Interesting Retinal Cases Session and Video Conference, physicians will be able to
participate in discussion and reach a conclusion on treatment of various interesting vitreoretinal
cases presented by participants. The attendee’s basic knowledge and treatment skills will be
enhanced by the information presented and subsequent discussions.
OBJECTIVES: Upon completion of this conference, attendees can expect to achieve the
following overall program objectives:
1. Review the outcomes when using small incision surgery, and for which conditions it can
be useful.
2. Review how small incision surgery may be of help in retinal detachment surgery.
3. Review outcomes of small incision surgery and indications for epiretinal membranes.
4. Review the outcomes of treat and extend protocols for age-related macular degeneration
(AMD).
5. Compare Treat and Extend approaches to PRN approaches for AMD.
6. Review how the vitreoretinal interface affects Treat and Extend protocols.
7. Review aflibercept for macular edema and how it works in long standing disease.
8. Review the effects of combination of laser and anti-VEGF treatment for macular edema
associated with vascular occlusive disease.
9. Review the effects of adding dexamethasone implants with adjunctive therapy.
CME Accreditation
This activity has been planned and implemented in accordance with the accreditation
requirements and policies of the Accreditation Council for Continuing Medical Education
through the joint providership of William Beaumont Hospital and The Retina Society. William
Beaumont Hospital is accredited by the ACCME to provide continuing medical education for
physicians.
CME Credit Designation
William Beaumont Hospital designates this live activity for a maximum of 17.5 AMA PRA
Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of
their participation in the activity.
(CME Credit Breakdown: Thurs-2.5, Fri 6.0, Sat 5.75, Sun 3.25)
Staff and Content Validation Reviewer Disclosure
The CME Committee members and CME staff involved with this activity as content validation
reviewers have reported no relevant financial relationships with commercial interests.
Resolution of Conflicts of Interest
In accordance with the ACCME Standards for Commercial Support of CME, William Beaumont
Hospital implemented mechanisms, prior to the planning and implementation of this CME
activity, to identify and resolve conflicts of interest for all individuals in a position to control
content of this CME activity.
NOTE: See separate CME handout for instructions on how to claim CME credits.
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17
Pennsylvania Academy of the FIne Arts
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The Retina Society
Program-in-Brief
Thursday, September 11 — Up to 2.5 CME credits
12:00 noonExhibit set-up — Meade/Grant Rooms, Union League
12:00 – 2:00 pmExecutive Committee Meeting — Conference Room, Independence Visitor Center
3:00 – 7:00 pmExhibitor and Meeting Registration — Union League
Trolleys will be available from Union League to Independence Visitor Center for Interesting Case/Video program.
4:30 – 7:00 pmInteresting Retinal Case Presentations/Videos — Liberty View Ballroom,
Independence Visitor Center
7:30 – 9:30 pm
Welcoming Reception — Petite Ballroom, The Ritz-Carlton
Trolleys will be available from Independence Visitor Center to the Ritz at 7:00 pm with conclusion of session
FRIday, September 12 — Up to 6.0 CME credits
7:00 am
Meeting Registration — Union League
Continental Breakfast — Meade/Grant Rooms
7:30 – 11:00 am Spouses/Guests Hospitality Suite — Banquet Room, Second Floor,
Union League
8:00 – 11:45 am
Scientific Session — Lincoln Hall, Union League
9:00 am – 3:00 pm
SPOUSES TOURS/LUNCH — see details pages 21 – 23
11:45 am – 12:45 pm Scientific Session Attendees Lunch — Union League
12:45 – 3:54 pm
Scientific Session — Lincoln Hall, Union League
4:00 – 6:00 pm
Trolleys to Philadelphia Museum of Art for lecture/tour and return
to Union League
7:00 – 10:00 pm
Reception/Dinner — Union League
Saturday, September 13 — Up to 5.75 CME credits
7:00 am
Continental Breakfast — Meade/Grant Rooms
7:30 – 11:00 am Spouses/Guests Hospitality Suite — Banquet Room, Second Floor,
Union League
8:00 – 11:40 am
Scientific Session — Lincoln Hall
9:30 am – 3:00 pm
SPOUSES TOUR — see details pages 23 – 24
11:40 am – 12:15 pm
Annual Business Meeting — Lincoln Hall
12:15 – 1:00 pm
Scientific Session Attendees Lunch — Union League
1:00 – 1:30 pm
Dedicated Poster Session — Meade/Grant Rooms
1:30 – 5:10 pm
6:30 – 11:30 pm
Barnes Museum Dinner
Buses will be departing Union League beginning at 6:00 pm
and will run as a continuous shuttle throughout the evening
Sunday, September 14 — Up to 3.5 CME credits
7:30 am
Continental Breakfast/Exhibits — Meade/Grant Rooms
8:00 – 11:38 am
Adjourn
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19
swann Memorial fountain — Logan Square
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The Retina Society
Social Program
THURSDAY, September 11
7:30 – 9:30 pm
Welcome Reception—Ritz-Carlton
(ALL)
J
oin us on the balcony level of the rotunda
at the Pantheon-inspired Ritz Carlton
to greet friends old and new, while
enjoying the young and exciting sounds of the
Philadelphia String Quartet, known for their
concert quality classical training, admixed with
a fresh and modern approach and repertoire.
Tempting cuisine, delicious beverages, and a
warm and invigorating kickoff to our 47th annual
Retina Society meeting, calibrated to meet the
needs of those rallying for an evening out, or
winding up a busy day.
Friday, September 12 & Saturday, September 13
7:30 – 11:00 Am
HOSPITALITY SUITE — Guests
A Hospitality Suite, in the Banquet Room on the second floor
of the Union League, will be open for coffee, tea, and continental
breakfast, as well as a place to meet friends and regroup for Philly
forays! On Sunday, spouses and guests are welcome to continental
breakfast in the Meade/Grant Rooms.
FriDAY, September 12
9:00 am – 3:00 pm
AMERICAN HISTORY & ART (Guests)
Enjoy a visit to Independence Hall, including a
guided interior visit to the Assembly Room, site of
the signing of the Declaration of Independence
and the United States Constitution. Included in the
morning is a visit to the National Constitution
Center featuring The Story of We the People, a
main museum exhibit and Freedom Rising, from
1787 to the present. Freedom Rising is a multimedia
theatrical experience that brings the Constitution to
life through 360-degree projection, state-of-the-art
sound and lighting, and a dynamic live actor who
illuminates the American quest for freedom. En
route to the National Constitution Center, we will
have a peek at the world-famous Liberty Bell, a
hallowed symbol of freedom around the world, and
Ben Franklin’s grave, the final resting place of this
American genius.
continued on next page
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21
Social Program
continued from previous page
Lunch will be served at the colonial City Tavern. It’s been said
that more elements of the Declaration of Independence and the
framing of the United States Constitution were discussed over a
tankard of ale at the City Tavern than inside Independence Hall.
After lunch, we will visit the Pennsylvania Academy of the Fine
Arts, America’s first Art Museum and School, for a docent-led tour
of the highlights of the Historic Landmark Building. The Museum
is internationally known for its outstanding collections of 19th and
20th century American paintings, sculptures, and works on paper
and its historically significant archives. Throughout the year, PAFA
presents special exhibitions and work by some of the region's
talented contemporary artists.
4:00 – 6:00 pm
Lecture AND TOUR OF THE SPECIAL EAKINS EXHIBIT & AMERICAN GALLERIES
Philadelphia Museum of Art (ALL)
A
t 4:00 pm we will board trolleys (complete with
mobile bars!) to take us to the world-famous
Philadelphia Museum of Art for a special lecture by
Sidney D. Kirkpatrick, award-winning documentary filmmaker
and bestselling historical writer. Mr. Kirkpatrick is the definitive
biographer of Thomas Eakins, native Philadelphian and
painter widely acknowledged as one of the most important
in American art history. You will have ample opportunity to
have your personal gift copy of the Eakins biography signed
by the author, and to interact with him and his wife during
the course of the evening. Following the lecture there will
be time to view the exciting new PMA installation offering
a once-in-a-lifetime opportunity for us to see Eakins' two
unparalleled medical historical paintings, hung for the first
time face to face. These are the most ambitious paintings
Thomas Eakins would ever create, and were ground-breaking
and highly controversial when originally unveiled. "The Gross
Clinic" and "The Agnew Clinic”, portraying two of the most
famous surgeons (who also did eye surgery!) of the time, in
their element, are now juxtaposed for this exhibit. Shown at
the Centennial of 1876, "The Gross Clinic" was a landmark
work that inaugurated a tradition of paintings which celebrate
the medical arts and prominent doctors such as Dr. Gross
from the Jefferson Medical College and Dr. Agnew from the
University of Pennsylvania Medical School. Docents from the
museum will also be available in the adjacent American art
galleries opened for us. Remember that your museum ticket
is good for another day as well! Trolleys will then return us
to the Union League for an evening of delicious food and
musical entertainment.
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The Retina Society
Social Program
7:00 – 10:00 PM
a taSte of philadelphia old and new — Union LeAGUE (all)
T
he Union League's Lincoln Hall will be transformed into a time-spanning city fair for
the evening to host our lively cornucopia of
Philadelphia-themed entertainment, food, and personalities, with spirited music, historical figures including
Ben Franklin himself and a bevy of taproom singers,
and a host of fun activities including photo souvenirs of
you with your favorite city landmark background, "Taste
of Philadelphia" food stations, and much more! Music
by our local ophthalmologist colleague Joe Markoff,
Renaissance man and trumpeter for the Philadelphia
Orchestra (and physician to our own Phil Rosenfeld's
famous Philadelphia Orchestra trumpet-playing father!),
and his noted Beaux Arts Brass quintet will liven up our
cocktails and savory delights, as we chat with founding
father Ben, sing along with the colonial drinking songs,
and enjoy a panoply of activities while sampling food
from famed Philadelphia locales such as the Italian
Market and Reading Terminal. This is a nice opportunity
to explore the Union League and its many offerings as
well, including the Templeton Heritage Center, and get
your Eakins biography autographed by author Sidney
KIrkpatrick, celebrity documentary filmmaker and historical author, who will join us with his wife. The perfect
way to relax and stretch your bandwidth with friends as we cap off a jam-packed day where the
medical, visual, musical, and historical arts have intertwined!
SATURDAY, September 13
9:30 am – 3:00 pm
The Charms of Fairmount Park and Rodin Museum (Guests)
F
irst, enjoy a guided
tour of Woodford,
an elegant Georgian
country home and its
magnificent American
antiques, which presents
both the struggles of the
American Revolution and
Reading
Terminal
the riches of a prosperous city, through its unique story. Next, visit Strawberry
Mansion
. The
largest of the Fairmount Park Charms houses, Strawberry Mansion illustrates three distinct phases
in American Architecture as well as the lives of two important and distinguished Philadelphians.
Following the visits to the Mansions, we will continue on to the Philadelphia Museum of Art
where we will enjoy a guided tour. Lunch will follow at the Cafe in the Philadelphia Museum of Art.
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23
Social Program
Following lunch, we will enjoy a fascinating
tour of the Rodin Museum and Gardens. In
2012, the Rodin Museum opened the doors to
a fully renovated interior, complemented by
the gorgeous redesigned outdoor sculpture
garden. The museum holds the most extensive
public collection of Auguste Rodin’s work
outside Paris, including The Thinker and a
bronze cast of The Gates of Hell.
SATURDAY, September 13
6:30 – 11:30 pm
Barnes Foundation Dinner/Dancing (ALL)
Opened in 2012, the B a r n e s
Foundation architects Tod Williams
and Billie Tsien designed a “gallery
within a garden and a garden within
a gallery”—a blend of art, nature,
education and aesthetics. The museum
features the eccentric Dr. Albert
Barnes’ famed collection of Renoirs,
Matisses, Monets and Cézannes—
the largest private Impressionist
collection in the world. Originally
highly controversial, the relocation of
the Barnes from its original suburban
location was lambasted in the awardwinning documentary, “The Art of
the Steal”, so the new museum’s
opening was highly anticipated,
and widely covered by media in this
country and abroad. The brilliant
new design, resolving the host
of challenges inherent in keeping
the best of the old while meeting
the needs of the new opened to
blockbuster reviews in The N.Y. Times
Review and Wall Street Journal, and
has in its brief existence become a
top international “must see” for aficionados of art, art history, architecture, curatorial innovation,
and landscape design. We will have all the galleries to ourselves for the entire evening, as well as the
exciting new featured Cezanne exhibition. Delicious cocktails will culminate with a performance by the
famed Mummers, whose New Year's Day parade is one of the quintessentially Philadelphian highlights
of the holiday season, strutting as only they can do, and leading us into our scrumptious banquet.
Dinner will be punctuated by a brief and illuminating talk on Dr. Albert Barnes himself by our own
Bill Tasman, as the well-known Jon Lewis Orchestra tunes up to get our toes tapping to dance
the night away!!
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The Retina Society
The Thinker — Rodin Museum and Garden
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25
Philadelphia skyline
26
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The Retina Society
GUEST OF HONOR
Ra lp h C . E agle J r., M D
Ralph C. Eagle Jr., MD, was born in the Philadelphia suburb of
Chester, Pennsylvania where he attended public school. He majored
in Biology at the University of Delaware and received his M.D. from
the University of Pennsylvania School of Medicine in 1970, where his
grandfather, ophthalmologist Charles I. Stiteler, had trained. After
interning at Temple University Hospital, he was an ophthalmology
resident at the University of Pennsylvania under Dr. Harold Scheie,
where he also completed an initial ophthalmic pathology fellowship
with Dr. Myron Yanoff. He was certified by the American Board
of Ophthalmology in 1976. He spent two additional years as an
NEI sponsored ophthalmic pathology fellow at the Armed Forces
Institute of Pathology in Washington, D.C. under the tutelage of
Drs. Lorenz Zimmerman and Ramon Font. Prior to his AFIP fellowship, he spent seven months
at the Wills Eye Hospital as a retinal research fellow and observer on the Ocular Oncology
Service. He joined the staff of the Scheie Eye Institute in 1978 where he served as Director
of the Ophthalmic Pathology Laboratory and practiced general ophthalmology. In 1986,
he became Director of the Department of Pathology at the Wills Eye Hospital, and was
appointed Professor of Ophthalmology and Pathology at Thomas Jefferson University. He
became the Noel T. and Sarah L. Simmons Professor of Ophthalmic Pathology at Wills in 1999.
Dr. Eagle has served as director of pathology at the Wills Eye Hospital for nearly three
decades.
Dr. Eagle pioneered the use of scanning electron microscopy in ophthalmic pathology as
an educational aid and as an adjunct to standard pathology techniques. His original description
of the iridocorneal endothelial or ICE syndrome in 1979, an important histopathologic study
of Fundus Flavimaculatus and his AOS thesis on iris pigmentation and pigmented lesions
used scanning electron micrographs as illustrations. He is noted for the quality of his macroand microphotography of eye disorders, which illustrate his popular single author atlas and
textbook of eye pathology.
A dedicated teacher, Dr. Eagle provides onsite training in his laboratory for residents from
Wills and several other programs as well as numerous medical students and interns. He has
lectured at major ophthalmic institutions on five continents, typically presenting intensive,
day-long reviews of ophthalmic pathology. A faculty member of Harvard’s Lancaster Course
in Ophthalmology since 1979, Dr. Eagle has served as the Coordinator of the Section on
Ophthalmic Pathology since 1992. He also was a faculty member AFIP’s ophthalmic pathology
course for more than three decades. He received Golden Apple Awards for teaching from
both the Wills Eye Hospital and the Scheie Eye Institute.
Dr. Eagle is a member of the Eastern and Verhoeff-Zimmerman Ophthalmic Pathology
Societies and served as the Verhoeff-Zimmerman Society’s representative on the Board of the
American Registry of Pathology for two decades. He subsequently was appointed to the ARP’s
Executive Board of Directors and served as the ARP’s Secretary-Treasurer. An active member
and officer of the American Association of Ophthalmic Pathologists, he organized and directed
the AAOP’s successful campaign to revise misguided federal laboratory legislation (CLIA ‘88),
which would have decimated ophthalmic pathology by legally disqualifying ophthalmologists
from the practice of that specialty. He served as AAOP President in 2000 – 2002. Dr. Eagle
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27
GUEST OF HONOR
became a member of the American Ophthalmological Society in 1988 and has served as the
organization’s Archivist-Photographer since 1996. His honors include AAOP’s Zimmerman
Medal and Lecture and the Macula Society’s W. Richard Green Lecture.
Dr. Eagle was appointed Director of the Department of Continuing Medical Education at
Wills in 1995 and oversees the Hospital’s extremely popular Ophthalmology Review Course,
which is attended by more than 300 ophthalmologists yearly. He also serves as Chair of the
Wills Institutional Review Board.
He likes to travel and is an avid photographer. Hobbies and interests include art, photography
and fossil collecting. His wife, ophthalmologist Ewa Lewandowski Eagle, died in 2006.
Dr. Ralph Eagle is honored by the Retina Society as a Guest of Honor this year
in recognition of his mammoth contributions to our field, delineating and clarifying the
histopathology of a legion of posterior segment conditions, notably his collaborative work
with the Shieldses in ocular tumors, and his remarkable career as an educator and mentor.
28
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The Retina Society
GUEST OF HONOR
H a rry W. F lynn Jr., MD
Harry W. Flynn Jr., MD is the J. Donald M. Gass Distinguished
Chair in Ophthalmology at the University of Miami, Miller School of
Medicine. He is Professor of Ophthalmology at the Bascom Palmer
Eye Institute and specializes in medical and surgical treatment of
diseases of the retina and vitreous. He received a Bachelor of Science
Degree at Wake Forest University and his Doctor of Medicine Degree
at the University of Virginia, School of Medicine. After an internship
at the California Pacific Medical Center in San Francisco, Dr. Flynn
returned to UVA for residency and to CPMC for retina fellowship.
Dr. Flynn completed two years of active duty in the United States
Army at the Brooke Army Medical Center in San Antonio. He joined
the faculty at Bascom Palmer Eye Institute in 1978.
Dr. Flynn has a special interest in endophthalmitis, diabetic retinopathy, cataract surgery
complications and retinal detachment surgery. He has been author or co-author of more
than 415 peer-reviewed publications as well as 74 book chapters. He has edited or co-edited
four books including Diabetes and Ocular Diseases: Past, Current, and Future Therapies and
Vitreoretinal Disease: The Essentials. Dr. Flynn had held numerous administrative positions
including President: The Vitreous Society (1992 – 1993), President: The Miami Ophthalmological
Society (1999) and President: The Retina Society (2002 – 2003). Dr. Flynn has served as Senior
Editor for Section 12 (Retina) of the Basic and Clinical Science Course for the American Academy
of Ophthalmology. He has also served as Co-Director of the Retina Subspecialty Day for the
American Academy of Ophthalmology. He serves on the Editorial Board of numerous journals
including the American Journal of Ophthalmology, RETINA, OSLI: RETINA, and Evidence Based
Ophthalmology. He has served on the Data and Safety Monitoring Committees for DRCR
Network, SCORE Study, Regeneron VIEW 1 and VIEW 2 Studies and Neurotech MacTel Study.
He received the AAO Life Achievement Honor Award in 2008. Dr. Flynn received the Shaler
Richardson, M.D “Service to Medicine Award” from the Florida Society of Ophthalmology
and “the Faculty Hero Award” from the University of Miami in 2011. He received the Hermann
Wacker Award from the Club Jules Gonin in 2012. He was voted “Professor of the Year” by
the Bascom Palmer Residents in 2012. He has delivered 24 named lectures including the
“J. Donald M. Gass Lecture” at The Retina Society in 2012. In 2014, he received the “Mentorship
Award” from the Vit Buckle Society and “Honorary Alumnus” recognition from AOA of UVA
School of Medicine.
Dr. Flynn has been married to his wife Donna Flynn for 40 years. They have two children,
Mollie and Patrick, and two grandchildren, Parker and Lily.
Harry Flynn is recognized by The Retina Society as a special Guest of Honor in well-deserved
tribute to his leadership in our field throughout his career, his tremendous contributions to
the advancement of retinal knowledge, his consummate integrity, and splendid mentorship
of a generation of retina physicians and surgeons.
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29
The Award of Merit in Retina Research
Presented in Conjunction with the Charles L. Schepens Lecture
The Award of Merit in Retina Research was created in
1978 by Retina Research Foundation, Houston, Texas, to recognize
outstanding vision scientists whose work contributes to knowledge
about the retina and retinal diseases. Each year, the Awardee is
invited to give the Charles L. Schepens Lecture, a highlight of The
Retina Society annual meeting that was established in honor of the
founder of the Society.
The award offers a $50,000 cash prize that includes a $5,000
honorarium and a $45,000 research grant. The recipient is chosen
by the Awards Committee of The Retina Society.
Funding for the Award of Merit is provided by Retina Research
Foundation through a series of endowed gifts that are dedicated to the Award. The Retina
Research Foundation of Houston, Texas presents the Award of Merit in Retina Research to a
vision scientist whose work represents: 1. A single outstanding achievement in retina research,
or; 2. A potentially significant contribution to new knowledge about the retina, its role in the
visual process and/or vitreoretinal diseases or disorders.
Prior Recipients of the Award
1978
Charles L. Schepens, MD, Boston, MA
1996 Gabriel Coscas, MD, Paris, France
1979 Richard W. Young, PhD, Los Angeles, CA
1997 Stuart L. Fine, MD, Philadelphia, PA
1980 Robert Machemer, MD, Durham, NC
1998 Joe G. Hollyfield, PhD, Cleveland, OH
1981
John E. Dowling, PhD, Boston, MA
1999 Lawrence A. Yannuzzi, MD, New York, NY
1982 Harry G. Sperling, PhD, Houston, TX
1983 Arnall Patz, MD, Baltimore, MD
2000 Barbara E. K. Klein, MD, MPH, and
Robert Klein, MD, MPH, Madison, WI
1984 Werner K. Noell, MD, Kansas City, MO
2002 Bradley R. Straatsma, MD, Los Angeles, CA
1985 Oleg Pomerantzeff, Dipl. Eng., Boston, MA
2003 Stephen J. Ryan, MD, Los Angeles, CA
1986 J. Donald M. Gass, MD, Miami, FL
2004 Emily Y. Chew, MD, Bethesda, MD and
Frederick L. Ferris III, MD, Bethesda, MD
1987 Harris Ripps, PhD, Chicago, IL
1988 Harvey A. Lincoff, MD, New York, NY
2005 Anthony P. Adamis, MD, Boston, MA
1989 Matthew D. Davis, MD, Madison WI
2006 Carol Shields, MD, Philadelphia, PA
1990 Matthew M. LaVail, PhD, San Francisco, CA
2007 Lloyd Paul Aiello, MD, Boston, MA
1991
2008 William S. Tasman, MD, Philadelphia, PA
Ronald Michels, MD and
Bert Glaser, MD, Baltimore, MD
2009 Mark S. Humayun, MD, PhD, Los Angeles, CA
1992 Ingrid Kreissig, MD, Tubingen, Germany
2010 Eliot L. Berson, MD, Boston, MA
1993 W. Richard Green, MD, Baltimore, MD
2011
1994 Dr. Kathleen Dorey and
Dr. Francois Delori, Boston, MA
2013 Cynthia A. Toth, MD, Durham, NC
Michael F. Marmor, MD, Stanford, CA
2012 Richard F. Spaide, MD, New York, NY
1995 D. Jackson Coleman, MD, New York, NY
Award Selection Committee
Charles C. Barr, MD, Chair
30
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The Retina Society
the 2014 Recipient of The Award of Merit in Retina Research
Pe t e r A . C am p ochia r o, M D
Peter Campochiaro, MD, clinician-scientist par excellence, is
the George S. and Dolores Doré Eccles Professor of Ophthalmology
at the Johns Hopkins University School of Medicine. One of the most
loyal sons the University of Notre Dame has ever educated, Peter
went on to a distinguished four years of medical school at Johns
Hopkins where he graduated AOA and stayed on for an Osler internship in medicine. He then completed his Ophthalmology residency
at the University of Virginia. Following residency he returned to
Hopkins as a Fight for Sight Research Fellow in retinal neurochemistry, and then pursued a fellowship in vitreoretinal surgery and retinal
cell biology with Drs. Ronald G. Michels and Bert Glaser. Returning
to the University of Virginia, he rose through the ranks to Professor,
maintaining both an active clinical practice, and a vibrant laboratory. Dr. Campochiaro has the
remarkable record of continuous NIH funding since 1984.
Peter was recruited back to Hopkins in 1991 as professor of Ophthalmology and
Neuroscience, and received his endowed chair honor in 1999. He has published hundreds of
papers and book chapters, and received many of the most prestigious awards in our field,
including the Rosenthal Award from the Macula Society for contributions to macular diseases,
the Alcon Research Institute Recognition Award, the Lew L. Wasserman Merit Award from
Research to Prevent Blindness, the Steinbach Foundation Merit Award, the Macula Vision
Research Foundation Merit Award, the Senior Research Award from Research to Prevent
Blindness, and the Senior Research Achievement Award from the Macula Society
Dr. Campochiaro's laboratory has been responsible for some of the seminal contributions
to our understanding and current treatment of retinal diseases. His research is directed toward
three major areas, ocular neovascularization and macular edema, ocular gene transfer, and the
mechanism of cone cell death in retinitis pigmentosa (RP). By developing a mouse model of
CNV, the team took advantage of knockout and transgenic mice to better define the molecular
pathogenesis of ocular neovascularization. His laboratory helped to determine that VEGF
plays a critical role and showed that there are increased levels of hypoxia-inducible factor-1
(HIF-1) in eyes with retinal or choroidal neovascularization which drives increased production
of VEGF as well as several other hypoxia-regulated gene products including platelet-derived
growth factor-B (PDGF-B), stromal-derived factor-1 (SDF-1), and angiopoietin 2 (Ang2).
Dr. Campochiaro demonstrated dramatic effects on NV with blockage of these factors. Recently,
Dr. Campochiaro and his collaborators determined that vascular-endothelial protein tyrosine
phosphatase (VE-PTP) is also increased in hypoxic retina and dephosphorylates Tie2, hence
acting like Ang2. Antagonists of VE-PTP keep Tie2 phosphorylated which activates it, hence
acting like Ang1, and markedly suppressing ocular neovascularization and vascular leakage.
In early phase clinical trials, Dr. Campochiaro’s clinical trial group was the first to show the
benefits of suppressing VEGF for DME and macular edema due to retinal vein occlusions.
Recently, Dr. Campochiaro’s clinical trial group has directed a small trial showing the promise
of a small molecule antagonist of VE-PTP in DME.
Dr. Campochiaro’s laboratory performed many of the early proof-of-concept studies
demonstrating the value of ocular gene therapy to express protein inhibitors of neovascularization
and leakage, demonstrating that gene delivery of pigment epithelial-derived factor (PEDF)
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31
the 2014 Recipient of The Award of Merit in Retina Research
was effective in animal models which led to a clinical trial which provided proof-of-concept
for gene delivery of antiangiogenic proteins for NVAMD. They also showed the benefits of
expressing endostatin which is now being tested in a clinical trial. Dr. Campochiaro’s clinical
trials group is playing a major role in two gene therapy clinical trials which will report results
soon. The laboratory has worked to unravel the pathogenesis of RP, showing that in this group
of diseases, after rods die, oxygen utilization in the outer retina is reduced, oxygen levels rise,
and there is progressive oxidative damage to cones and gradual cone cell death. Treatments
that inhibit oxidative damage increase cone survival and function and one such treatment is
working its way into the clinic.
Dr Campochiaro married his beautiful and multitalented high school sweetheart Betsy,
who trained as a nurse and has gone on to master a thousand other skills as well, from
clinical coordinator to amateur architect and landscape designer. Together they have reared
a wonderful family of three children, Michael, Paul, and Laura, now completing her MD/PhD
at Northwestern.
32
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The Retina Society
Benjamin Franklin BENCH
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33
The J. Donald M. Gass Award
In 2006, The Retina Society inaugurated the J. Donald M. Gass
lectureship. Dr. Gass was a peerless observer of the fundus. His
unique and repeated ability to identify fundamental patterns
of disease from the mass of seemingly chaotic details invites
sincere comparison to Michelangelo working in marble. With
this lectureship, we honor his memory as a warm and cherished
member and friend as well as his inestimable importance to our
patients and our field.
2013
2012
2011
2010
2009
2008
2007
2006
Michael T. Trese, MD, Royal Oak, MI
Harry W. Flynn Jr., MD, Miami, FL
Mario Stirpe, MD, Rome, Italy
Ursula Schmidt-Erfurth, MD, Vienna, Austria
Philip J. Rosenfeld, MD, Miami, FL
Lawrence A. Yannuzzi, MD, New York, NY
Lee M. Jampol, MD, Chicago, IL
Carmen A. Puliafito, MD, Los Angeles, CA
Charles C. Barr, MD, Chair
34
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The Retina Society
Recipient of The J. Donald M. Gass Award
Alexand e r J. Bruc ker, MD
Alexander Brucker, MD,
was educated at the University
of Maryland and received his M.D. degree at New York Medical
College. After completing a residency at the Friedenwald Institute
of Maryland General Hospital, he did a Fellowship in Diseases of the
Retina and Vitreous under the mentorship of Dr. Arnall Patz and
Dr. Ronald G. Michels at The Wilmer Ophthalmological Institute of
the Johns Hopkins Hospital in Baltimore, Maryland.
In 1977, Dr. Brucker relocated to the University of Pennsylvania
School of Medicine where he was appointed to the faculty as
Assistant Professor of Ophthalmology, and in 1994 became Professor
of Ophthalmology, a position which he holds since that time. He
serves as Chief of the Retina and Vitreous Service at the Scheie Eye Institute/Department of
Ophthalmology.
During the course of his career, Dr. Brucker has served in many leadership capacities, too
numerous to list in this short biography. He is a member of multiple societies and organizations
such as the Macula Society of which he served as President, The Retina Society, the American
Society of Retina Specialists, Club Jules Gonin, and the American Uveitis Society. He has served
as Chairman of the Board of the Juvenile Diabetes Foundation of Philadelphia.
Dr. Brucker has received numerous awards which have acknowledged his leadership in
education, research, and patient care. He has been named one of Philadelphia’s “Best Doctors”
by Philadelphia Magazine every year for the past 30 years. He has received the Golden Apple
Award for outstanding teaching in the Department of Ophthalmology of the University of
Pennsylvania on three occasions and was the recipient of the Albrecht von Graefe Award
for distinguished contributions in ophthalmology by the American Society of Contemporary
Ophthalmology. He was the recipient of the Life Achievement Award from the Ophthalmic
Club of Philadelphia and received the Life Achievement Honor Award from the American
Academy of Ophthalmology. He was the recipient of the J. Donald M. Gass Medal from the
Macula Society at its meeting in Phoenix, Arizona in 2010 and was recently a guest of honor
of the American Academy of Ophthalmology.
Dr. Brucker has been invited to give numerous Named Lectureships throughout the world,
some of which include the C.S. O’Brien Professorship Lecture at Tulane University, the Nachazel
Lecture at William Beaumont Hospital, the Albert C. Snell Memorial Lecture at the University
of Rochester as well as the Professor Guy H. Chan Lecture at the International Symposium
in Hong Kong.
Dr. Brucker is the Editor-in-Chief of the international journal RETINA, the Journal of Retinal
and Vitreous Diseases, a position he has held since 1981. He is also Editor of Retinal Cases and
Brief Reports and is a member of the Editorial Board of The Chinese Journal of the Ocular
Fundus as well as Advisor to the Journal of the Asia-Pacific Academy of Ophthalmology.
Dr. Brucker has received innumerable invitations to be moderator of panels and an honored
guest lecturer locally as well as worldwide in such venues as Cape Town, Berlin, Sydney, Milan,
Geneva, Bali, and Bangkok, just to name a few.
He has authored over 100 papers which have been published in peer-reviewed journals
and has been the author of published books, texts, and chapters, the list too long to mention.
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35
Recipient of The J. Donald M. Gass Award
His special interests have been the surgical treatment of vitreoretinal disorders, diabetic
retinopathy, age-related macular degeneration and vascular occlusive diseases.
Dr. Brucker has taken a special interest in randomized clinical trials to evaluate treatment of
retinal diseases. Dr. Brucker has been Principal Investigator of multiple clinical trials including
the Diabetes Control and Complications Trial (DCCT), the Age-Related Eye Disease Study II,
the MacTel Study, and a multitude of other randomized controlled trials of retinal and vitreous
diseases. He has served as the Principal Investigator of two recent diabetic retinopathy trials
sponsored by the DRCR.net of the National Eye Institute. He has served on the Executive
Committee of that organization for five years.
Dr. Brucker has also served for seven years as a voting member of the Department of Food
and Drug Administration’s (FDA) Ophthalmic Device Panel, an important regulatory panel for
ophthalmology and continues to serve on their list of consultants.
Dr. Brucker has been a role model for generations of medical students, residents, fellows,
and colleagues, with many of whom he continues to be in contact. He takes great pride in his
enduring relationships with his past residents and fellows.
36
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The Retina Society
BoatHouse Row
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37
The Fellowship research Award
The Retina Society Fellowship Research Award was established in 1996 to encourage academic
pursuit in young vitreoretinal surgeons and to acquaint them with the scientific and social
aspects of the Society. Applicants must be sponsored by an active member of The Retina
Society. Each paper is judged on originality, quality of investigation methods and merit of
scientific contribution.
R ec i p i en t o f The 18 t h F e llows hi p resear ch Award
F r anci s co A . Fo lg ar , M D
Durham, NC
Sponsor:
Congratulations!
Emily Y. Chew, MD
2013
2012
2011
2010
2009 2008
2007 2006 2005 2004 2003 2002
2001
2000
1999
1998
1997
Glenn Yiu, MD, PhD, sponsored by Glenn Jaffe
Lejla Vajzovic, MD, sponsored by David Abrmson
Cagri Besirli, MD, sponsored by David Zacks
Brian L. VanderBeek, MD, PhD, sponsored by David Zacks
Sandra Rocio Montezuma, MD, sponsored by Joan Miller
Mehran Taban, MD, sponsored by Peter Kaiser
Sai Chavala, MD, sponsored by Thomas Lee
Polly A. Quiram, MD, sponsored by George Williams
Francisco Max Damico, MD, sponsored by Lucy Young
Sean S. Ko, MD, sponsored by Shizuo Mukai
Seenu M. Hariprasad, MD, sponsored by William Mieler
Franco M. Recchia, MD, sponsored by Allen C. Ho
David N. Zacks, MD, sponsored by Joan Miller
Magdalena Krzystolik, MD, sponsored by Evangelos Gragoudas, and
Enrique Garcia-Valenzuela, MD, PhD, sponsored by James Puklin
Thomas C. Lee, MD, sponsored by Shizuo Mukai
Ingrid U. Scott, MD, sponsored by Timothy Murray
Andrew Chang, MD, sponsored by Lawrence Morse
David N. Zacks, MD, Chair, Emily Y. Chew, MD, Timothy G. Murray, MD, Lucy H-Y. Young, MD
We
would like to thank all members who have sponsored
applicants and ask that all members continue to support this award.
38
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The Retina Society
The Raymond R. Margherio Award
The Raymond R. Margherio Endowed Memorial Fund was established to support research into
macular disease and development of new techniques of macular surgery. The Fund supports
an award presented annually to a vitreoretinal fellow of an active member of The Retina
Society. The fellow presents his work at the Annual Meeting of The Retina Society. The winner
is selected by the Research Award Committee.
R e c i p ie n t o f The 13 t h Ma rg he r i o Award
John B. M i ll e r , M D
Boston, MA
Sponsor:
Congratulations!
2013
Dimitra Skondra, MD, sponsored by Joan Miller
2012
Anthony B. Daniels, MD, sponsored by Ivana Kim
2011
Marc-Andre Rheaume, MD, sponsored by Shizuo Mukai
2010 Daniel F. Kiernan, MD, sponsored by William Mieler
2009 Catherine Cukras, MD, PhD, sponsored by Frederick Ferris
2008 Edward F. Hall, MD, sponsored by David Zacks
2007 Stephen J. Kim, MD, sponsored by Baker Hubbard
2006 Jasmine R. Elison, MD, sponsored by D. Jackson Coleman
2005 Michael D. Ober, MD, sponsored by Lawrence Yannuzzi
2004 Howard S. Ying, MD, sponsored by Morton Goldberg
2003 Antonio P. Ciardella, MD, sponsored by Stanley Chang
2002 Eugene S. Lit, MD, sponsored by Donald J. D’Amico
Raymond R. Margherio, MD
1939 – 2000
President,
The Retina Society
1996 – 1997
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39
Exhibitors by Name
See page 212 for more information.
Alcon — PATRONBOOTH 21 Grant
Alimera SciencesBOOTH 2 Meade
Allergan — PATRONBOOTH 18 Grant
Bausch + LombBOOTH 10 Meade
Carl Zeiss MeditecBOOTH 9 Meade
Dutch Ophthalmic USABOOTH 4Meade
Elsevier
TABLE
4 Grant
Genentech — GOLD PATRONBOOTH 20 Grant
Heidelberg EngineeringBOOTH 3Meade
Insight Instruments, Inc.BOOTH 12 Meade
Janssen Pharmaceutical of J&JBOOTH 17 Grant
L W & W | Wolters
TABLE 2 Grant
Notal VisionBOOTH 15 Meade
Oculus Surgical, IncBOOTH 1Meade
OMIC TABLE 1 Grant
Optos, IncBOOTH 13 Meade
Optovue, IncBOOTH 5 Meade
Pine PharmaceuticalBOOTH 8 Meade
Quantel MedicalBOOTH 6 Meade
Regeneron — GOLD PATRONBOOTH 7 Meade
Retina Today
TABLE 3 Grant
Retinal Physician
TABLE 5 Grant
ThromboGenics — PATRON BOOTH 16 Meade
Topcon Medical SystemsBOOTH 11Meade
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The Retina Society
Exhibitors by BOOTH/TABLE NUMBER
See page 212 for more information.
Oculus Surgical, IncBOOTH 1Meade
Alimera SciencesBOOTH 2 Meade
Heidelberg EngineeringBOOTH 3Meade
Dutch Ophthalmic USABOOTH 4Meade
Optovue, IncBOOTH 5 Meade
Quantel MedicalBOOTH 6 Meade
Regeneron — GOLD PATRONBOOTH 7 Meade
Pine PharmaceuticalBOOTH 8Meade
Carl Zeiss MeditecBOOTH 9 Meade
Bausch + LombBOOTH 10 Meade
Topcon Medical SystemsBOOTH 11Meade
Insight Instruments, Inc.BOOTH 12 Meade
Optos, IncBOOTH 13 Meade
Notal VisionBOOTH 15 Meade
ThromboGenics — PATRON BOOTH 16 Meade
Janssen Pharmaceutical of J&JBOOTH 17 Grant
Allergan — PATRONBOOTH 18 Grant
Genentech — GOLD PATRONBOOTH 20 Grant
Alcon — PATRONBOOTH 21 Grant
OMIC TABLE 1 Grant
L W & W | Wolters
TABLE 2 Grant
Retina Today
TABLE 3 Grant
Elsevier
TABLE
Retinal Physician
TABLE 5 Grant
|
4 Grant
41
42
|
12
89
1
8
16
16
910
23
1011
34
1213
56
6
7
13
7
1 6
25
Quantel Quantel
Regeneron Regeneron3 4
Medical Pharmaceuticals
Optovue
Medical Pharmaceuticals
Insight
Optos,
Topcon
InsightInc. Optos, Inc.
Instruments
Medical Instruments
Systems
1112
45
Dutch
Alimera
Dutch
Heidelberg Heidelberg
Ophthalmic Ophthalmic
Optovue
Sciences
15
Pine
Carl
Topcon
+ Lomb
PineZeiss Bausch
Carl Zeiss
Bausch
+ Lomb
Pharmaceutical
Meditec
Medical
Pharmaceutical Meditec
Systems
Alimera
Oculus
Sciences
Surgical
Oculus
Surgical
15
Notal Vision Notal VisionThromboGenics
ThromboGenics
MEADE
ROOM
MEADE
ROOM
17 612
28 511
39 410
7 12
8 11
9 10
Meade Room Exhibits & Posters
The Retina Society
POSTERS
POSTERS
5
4
3
Retinal Physician
Elsevier
Retina Today
15
22
28
31
29
30
27
32
26
33
14
23
25
34
13
24
20
Genentech
GRANT ROOM
16
21
17
20
POSTERS
18
17
18
19
Allergan
Janssen Pharma
of J&J
Lippincott
2
OMIC
21
Alcon
1
Grant Room Exhibits & Posters
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43
Interesting retinal Cases/Video conference
Thursday, September 11
Independence Visitor Center
Liberty View Ballroom
Moderators: Anita Agarwal, MD, Carl D. Regillo, MD
4:30 pm A Broken Foot in a Child
4:35
Resolution of Massive Peripheral Retinoschisis Cavities in Severe
X-Linked Retinoschisis by Topical Dorzolamide
Robert A. Sisk, MD
4:40
Papillophlebitis, Disc Neovascularization and Candida Endophthalmitis
Alan G. Palestine, MD
4:45
Asymptomatic Syphilitic Retinitis
Shlomit Schaal, MD
4:50
A Routine Case of Diabetic Macular Edema for Anti-VEGF or Was It?
Antonio M. Casella, MD
THURSDAY, SEPTEMBER 11
4:55
Pediatric Pigmented Fundus Lesions
5:00Unilateral MEWDS with Persistent Visual Loss
5:05
Pericentral Retinal Degeneration
5:10
Mystery Case
Mark W. Johnson, MD
5:15
The Oldest Living Heart Transplant Recipient Has Eye Problems
Edwin H. Ryan, MD
5:20
Temporal Retinal Thinning
Pamela P. Rath, MD
5:25
Paradoxical Reattachment of a Previously Separated Posterior
Hyaloid After Dexamethasone Intravitreal Implant Injection
Jay M. Stewart, MD
5:30
Mystery Case
David Sarraf, MD
5:35New Retinal Findings in a Case of Heimler Syndrome
Luiz Lima, MD
5:40
Pediatric Atypical Vasculopathy
5:45Uncommon Features of an Inflamed Eye: Lessons from Philadelphia
5:50
Decreased Vision After Carotid Artery Stent
Helen K. Li, MD
44
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The Retina Society
Interesting retinal Cases/Video conference
5:55 pm
Mystery Case
6:00
Retinal Arterial Occlusion
Ron Adelman, MD
6:05
Peripheral Retinal Lesion
6:10
The Key to Badness: Self-Induced Laser Maculopathy in an
Adolescent Boy Using a Mirror
Christina Weng, MD
6:15
Reverse Perspective
Jose S. Pulido, MD
6:20
This is AZOOR, Right?
J. Peter Campbell, MD
6:25
Twelve Year-old Girl with Bilateral Chorioretinal Lesions
Anita Agarwal, MD
Pigmented Intraocular Mass. A Clinical and Diagnostic Dilemma
VIDEOS
6:35
Management of Combined Rhegmatogenous Retinal Detachment and Retinoschisis
Kirk H. Packo, MD
6:40
PPV for Non-Clearing Vitreous Hemorrhage with a Twist
Raymond Iezzi, MD
6:45ILM Peeling with Vitrectomy Probe
6:50
Successful Surgical Treatment of Persistent Optic Disc Pit
Maculopathy with Platelet Rich Plasma
Lejla Vajzovic, MD
7:00
ADJOURN
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45
THURSDAY, SEPTEMBER 11
6:30
Scientific Sessions
FRIday, September 12
7:00 am
Registration — Lincoln Hall Foyer
7:55
Welcome: Julia A. Haller, MD, President SURGERY
Presiding Officer: Donald J. D’Amico, MD Moderator: Maria H. Berrocal, MD
8:00 amCharacteristics and Outcomes of Sequential Rhegmatogenous
Retinal Detachments
Harpreet S. Walia, MD
8:05
Visual and Anatomic Outcomes of Epiretinal Membrane Peeling After
Previous Complex Retinal Detachment Surgery
Christina Weng, MD, MBA
8:10
Vitrectomy Techniques with 27g Instrumentation in Complex
Detachments
FriDAY, SEPTEMBER 12
8:15
Dual Port Cutter Vitrectomy for Dense Vitreous Hemorrhage:
Preliminary Study
Luiz Lima, MD
8:20Evaluating Small Gauge Instrumentation from a New “Intraocular”
Perspective
Kirk H. Packo, MD
8:25Collaborative Multi-Center Study of Macular Holes: The European
Vitreo-Retinal Society Macular Hole Study
8:30
Results and Complications of Vitrectomy for Pseudohole/Lamellar
Macular Holes
8:35
Anterior Chamber Migration of the Dexamethasone Implant May
Result in Corneal Decompensation
8:40
Fellow Eyes of Giant Retina Tears: Effectiveness of Prophylactic
Laser Treatment Compared to Untreated Fellow Eyes
Guido Ripanelli, MD
8:46
Discussion
8:49
Small Incision Vitreoretinal Surgery without Scleral Depression
Shaving of Vitreous Base for Rhegmatogenous Retinal Detachment
8:55
Discussion
8:58
Para Plana Vitrectomy-Scleral Buckle versus Pars Plana Vitrectomy
Alone for Patients with Rhegmatogenous Retinal Detachment at
High Risk of Proliferative Vitreoretinopathy
Philip Storey, MD, MPH
9:04
Discussion
46
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The Retina Society
Scientific Sessions
9:07 am
The DISCOVER Study: Prospective Analysis of Real-time
Intraoperative OCT During Vitreoretinal Surgery Utilizing a
Microscope-Integrated Prototype with a Heads-up Display Surgeon
Feedback System
9:13
Discussion
9:16
Sustained Release Dexamethasone Intravitreal Implant (DEX) for
Persistent Macular Edema (ME) After Vitrectomy (PPV) for Epiretinal
Membrane (ERM)
9:22
Discussion
9:25
Vitrectomy After Ocriplasmin for Vitreomacular Adhesion or Macular
Hole (VAVOOM) Study
Margaret A. Greven, MD
9:31
Discussion
9:34
Subretinal Air Displacement of Submacular Hemorrhage:
Initial Experience
9:40
Discussion
9:43
One-year Outcomes of Eyes Treated with Sutureless Scleral Fixation
Technique for Intraocular Lens Placement or Rescue
9:49
Discussion
9:52
Advances in Vitreoretinal Evaluation and Surgery with Permanent
Keratoprosthesis
Donald J. D’Amico, MD
9:58
Discussion
PRACTICE MANAGEMENT
10:01
Quality Measures Within a Group Retina Practice—Cultural Shift and
Clinical Outcomes
10:06 – 10:36
REFRESHMENT BREAK/EXHIBITS — Meade/Grant Rooms
INFLAMMATION
Presiding Officer: Bernard H. Doft, MD
Moderator: Sunir J. Garg, MD
10:36
Analysis of Birdshot Choroiretinopathy Abnormalities using
SD-OCT and Fundus Autofluorescence Imaging
David Sarraf, MD
10:41Initial Choroidal Thickness as a Predictor for Short-term Response to
Anti-Vascular Endothelial Growth Factor (Anti-VEGF) Treatment in
Diabetic Macular Edema
Nika Bagheri, MD
10:47
Discussion
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47
Michael D. Ober, MD
Scientific Sessions
10:50 am
Torque Teno Virus is Associated with Culture-negative
Endophthalmitis
Sunir J. Garg, MD
10:56
Discussion
10:59
The Current Face of Endophthalmitis: 107 Consecutive Cases
Bernard H. Doft, MD
11:05
Discussion
11:08
FELLOWSHIP RESEARCH AWARD PRESENTATION
Optical Coherence Tomography Drusen Volume and Retinal Pigment
Epithelium Abnormal Thinning Volume Predict 2-Year Progression of
Age-Related Macular Degeneration
Introduction: David N. Zacks, MD
Francisco A. Folgar, MD
11:20
J. DONALD M. GASS AWARD
Introduction: Lawrence J. Singerman, MD
In Memoriam of the Art of Scleral Buckling
11:45
LUNCH
AGE-RELATED MACULAR DEGENERATION — I
Presiding Officer: Charles C. Barr, MD
Moderator: Susan B. Bressler, MD
12:45 pm
A Value-Based Medicine® Analysis of Genetic Testing for Neovascular
Age-Related Macular Degeneration—Patient Value Gain and
Financial Return-on-Investment
12:51
Discussion
12:54
Detection Rate of New CNV in Eyes with AMD and Visits Prompted
by Home Monitoring Device, Symptoms and Standard Care
1:00
Discussion
1:03Concentration of Vitamins C, Vitamin E, Zinc and Copper in Dietary
Supplements
Charles C. Barr, MD
1:09
Discussion
1:12Combined Complement Factor H (CFH) and Age-Related
Maculopathy Susceptibiity 2 (ARMS2) Risk Predicts Response to
AMD Nutritional Prophylaxis: A New Analysis of AREDS Data
Carl C. Awh, MD
1:18
Discussion
1:21
Preliminary Results of Phase I Study with AAV2-sFLT01 as Gene
Therapy for Treatment of Exudative AMD
1:27 Discussion
48
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The Retina Society
Scientific Sessions
1:30 pmComparison of Distance and Near Vision in the Better-seeing
Eye versus Both Eyes in Neovascular Age-Related Macular
Degeneration
1:36 Discussion
1:39 – 2:09
AGE-RELATED MACULAR DEGENERATION — I continued
Presiding Officer: Jennifer J. Kang-Mieler, PhD
Moderator: James F. Vander, MD
2:09
Baseline Retinal Pigment Epithelial Elevation (RREE) Size and
Intra-Retinal Fluid (IRF) Status Effect on Visual Acuity (VA)
Outcomes in the VIEW 1 and VIEW 2
Chirag Shah, MD, PhD
2:14
Toward a Lean Intravitreal Injection Clinic: Implementation of the
Rapid Access Vitreal Injection Guide (RAVI-Guide)
2:19Cost Accounting and Prescribing Patterns of Bevacizumab Before
and After Enforcement of Patient-Specific Prescription Rules
2:24Influence of Vitreomacular Interface on Anti-VEGF Therapy
using Treat and Extend Treatment Protocol for Neovascular
Samuel K. S. Houston III, MD
2:30
Discussion
2:33
A Systemic Review (Meta-Analysis) of Pro re nata (PRN) versus Treat
and Extend Anti-Vascular Endothelial Growth Factor (Anti-VEGF)
Regimens for Neovascular Age-Related Macular Degeneration
(AMD)
David S. Chin Yee, MD
2:39
Discussion
2:42Long-Term Treatment Outcomes for Neovascular Age-Related
Macular Degeneration using a “Treat and Extend” Regimen
Nadim Rayess, MD
2:48
Discussion
2:51
Bioactive Lysophospholipids Generated by Hepatic Lipase
Degradation of Lipoproteins Activate Complement via the Classical
Pathway
2:57
Discussion
3:00Controlled Extended Release of Ranibizumab from Novel Ocular
Drug Delivery System
3:06
Discussion
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49
Dennis P. Han, MD
Scientific Sessions
3:09 pm
Macular Morphology and Visual Acuity in the Second Year of the
Comparison of Age-Related Macular Degeneration Treatments Trials
(CATT)
Sumit Sharma, MD
3:15
Discussion
3:18
Morphological Biomarkers Associated with Visual Acuity Gain and
Loss in Eyes with Neovascular Age-Related Macular Degeneration
Treated with Dual Antagonism of an Anti-PDGF Aptamer, E0030 (1.5
mg), and an Anti-VEGF agent, Ranibizumab (0.5 mg)
Glenn J. Jaffe, MD
3:27
LATE BREAKING PRESENTATION:
Interim Results from a Phase 2 Study of Squalamine Lactate
Ophthalmic Solution 0.2% in the Treatment of Neovascular
Age-Related Macular Degeneration (AMD)
3:33
Discussion
3:36
Vitrectomy Induced Cataracts May Well Be Prevented
3:42
Discussion
3:45
Macular Edema from Retinal VEin Occlusion (CRAVE): Results of a
Prospective Multicenter Randomized Clinical Trial
Gaurav K. Shah, MD
3:51
Discussion
3:54
ADJOURN
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The Retina Society
Scientific Sessions
saturday, September 13
7:00 am
AGE-RELATED MACULA DEGENERATION — II
Presiding Officer: Mark W. Johnson, MD
Moderator: Mark S. Blumenkranz, MD
8:00 amEvidence that Macular Degeneration is not Simply a Disease of the
Posterior Pole
8:05
Diagnosis of Cognitive Impairment and Alzheimer’s Disease Using
Integrated Assessments of Retina Structure and Function
8:10Incidence of Sustained Ocular Hypertension Using Prepackaged
versus Freshly-prepared Intravitreal Bevacizumab Injections for the
Treatment of Neovascular Age-Related Macular Degeneration (AMD)
8:15
One-year Results of a Phase 1 Study of the Safety and Tolerability
of Combination Therapy Using Sustained Release Intravitreal
Triamcinolone Acetonide and Ranibizumab for Subfoveal
Neovascular Age-Related Macular Degeneration
Jennifer I. Lim, MD
8:20
Systemic Review of Safety Across the Phase 2 and 3 Clinical Trials
of Intravitreal Aflibercept Injection
David S. Boyer, MD
8:26
Discussion
8:29Intravitreal Aflibercept Decreases the Volume of Vascularized PEDs
Better than Frequent Retreatment with Intravitreal Bevacizumab or
Ranibizumab
8:35
Discussion
8:38
One-year Results from the ROLL Trial: Aflibercept for Patients with
Recalcitrant PEDs Related to Wet Age-Related Macular
Degeneration
8:44
Discussion
8:47
Type 3 Neovascularization: Evolution, Association with Pigment
Epithelial Detachment, and Response to Therapy as Revealed by
Spectral-Domain Optical Coherence Tomography
Aaron Nagiel, MD, PhD
8:53
Discussion
8:56Gap Between BCVA and Low-luminance VA at Baseline Predicts
Treatment Response to Ranibizumab at Year 2 of the HARBOR Study
Ronald Frenkel, MD
9:02 Discussion
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51
SATURDAY, SEPTEMBER 13
Jason Hsu, MD
Scientific Sessions
OTHER MACULA — I
Presiding Officer: Jennifer I. Lim, MD
Moderator: Shlomit Schaal, MD
9:05 am
Ocular Coloboma Classification and Examination of Ultrasound as
a Supplementary Measure of Prognosis
9:10
Acute Macular Neuroretinopathy Following Non-Ocular Trauma:
A New Proposal Regarding Pathogenesis
Mark W. Johnson, MD
9:16
Discussion
9:19
Validation of the Accuracy and Precision of Out-of-Office Testing for
Retinal Disease: New Developments and Clinico-Pathologic
Correlations
SaturDAY, SEPTEMBER 13
9:25
Discussion
9:28
Anatomic and Functional Outcomes of Symptomatic Vitreo-Foveal
Adhesion. A Pilot Study from the Pan American Collaborative Retina
Study Group
Lihteh Wu, MD
9:34 am
Discussion
9:37
Vitreomacular Traction: Clinical Course and Outcomes Managed by
Initial Observations
9:43
Discussion
9:46
Variations and Racial Differences in the Pattern of
Hydroxychloroquine Retinopathy
9:52
Discussion
9:55Choroidal Flecks in Stargardt’s Disease Shown by High Definition
Optical Coherence Tomography Imaging Correlate with Disease
Severity
10:01
Discussion
10:04 – 10:34
REFRESHMENT BREAK AND EXHIBITS — Meade/Grant Rooms
10:34
RAYMOND R. MARGHERIO AWARD PRESENTATION
Introduction: David N. Zacks, MD
Iron Rescue of Deferoxamine Toxicity in Human RPE Cells
John B. Miller, MD
10:46
RETINA RESEARCH AWARD OF MERIT —
CHARLES L. SCHEPENS LECTURE
Introduction: Julia A. Haller, MD
Development of Treatments for Retinal/Choroidal Vascular Diseases
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The Retina Society
Scientific Sessions
*11:20 am
INTRODUCTION OF GUESTS OF HONOR: Julia A. Haller, MD Ralph C. Eagle Jr., MD
*11:40
ANNUAL BUSINESS MEETING
*12:15 – 1:00 pm ATTENDEES LUNCH
*1:00 – 1:30
* Non-CME
DEDICATED POSTER SESSION/DESSERT — Meade/Grant Rooms
TUMORS
Presiding Officer: Jerry A. Shields, MD
Moderator: Ivana K. Kim, MD
1:30Initial Treatment and Outcomes of Unilateral and Bilateral
Retinoblastoma in a Midwestern University Pediatric Oncology
Center 1999 – 2013
1:35Clinical Characteristics of Uveal Melanoma in Patients with Germline
BAP1 Mutations
1:40
Ranibizumab in Combination with Proton Beam Irradiation for
Choroidal Melanoma: Interim Results
Ivana K. Kim, MD
1:45
Treatment of Radiation-Induced Maculopathy
1:50
Retinal Metastasis from Systemic Cancer in Eight Cases
1:56
Discussion
1:59
Tumors of the Non-Pigmented Epithelium of the Ciliary Body.
The Zimmerman Classification Revisited
2:05
Discussion
2:08Cytological Characteristics of Uveal Melanoma
Carlos A. Medina, MD
2:14
Discussion
2:17
Micro-incisional Vitrectomy Surgery (MIVS) Enables Laser Tumor
Ablation and Fine Needle Aspiration Biopsy (FNAB) Potentially
Avoiding Radiotherapy in Small Uveal Malignant Melanoma
Timothy G. Murray, MD, MBA
2:23
Discussion
2:26
The American Brachytheraphy Society (ABS) Consensus Guidelines
for Plaque Brachytherapy of Uveal Melanoma and Retinoblastoma
Paul T. Finger, MD
2:32 Discussion
2:35
Ruthenium Eye Plaques for Uveal Melanoma: Long-Term Clinical
Outcome
Arun D. Singh, MD
2:41 Discussion
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53
SATURDAY, SEPTEMBER 13
Mrinali Patel, MD
Scientific Sessions
2:44 pmLong-Term Visual Prognosis After Proton Irradiation of Uveal
Melanomas in Patients at High Risk of Vision Loss
2:50
Discussion
GENETICS
Presiding Officer: Kimberly A. Drenser, MD, PhD
Moderator: Steven D. Schwartz, MD
2:53Genotype- Phenotype- Correlation of Patients with Wnt Pathway
Mutations Associated with Familial Exudative Vitreoretinopathy:
A Basis for Genetically Tailored Management
2:58
Retinal Nerve Fiber Dysfunction in Retinal Degeneration
3:03Comparison of Circulating microRNAs in Aqueous and Vitreous as
Putative Novel Diagnostic Biomarkers for Diabetic
Retinopathy
3:08
Vision Improvement After Retreatment with an Oral Synthetic
cis-Retinoid (QLT091001) in Subjects with Inherited Retinal Disease
Caused by Mutations in RPE65 or LRAT
3:14
Discussion
3:17
Safety and Technical Aspects of Subretinal Injection for Delivery of
Cell and Gene Therapy
3:23
Discussion
3:26 – 3:56
IMAGING
Presiding Officer: Judy E. Kim, MD
Moderator: Richard B. Rosen, MD, ScD
3:56Ultra-Widefield Imaging with Autofluorescence and Indocyanine
Green Angiography in Central Serous Chorioretinopathy
Claudine E. Pang, MD
4:01Inner Retina and Vascular Imaging in Macular Telangiectasis Using
Adaptive Optics
Judy E. Kim, MD
4:06 Outer Retinal Tubulation in Advanced Age-Related Macular
Degeneration: Optical Coherence Tomographic Findings Correlate
with History
Karen B. Schaal, MD
4:12
Discussion
4:15 pm
Feasibility of Dynamic Optical Coherence Tomography and Infrared
Imaging
Edwin H. Ryan, MD
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The Retina Society
Scientific Sessions
4:21 pm
Discussion
4:24
Quantitative Dynamics of Retinal Microvascular Disease Revealed by
Adaptive Optics Scanning Light Ophthalmoscopy
4:30
Discussion
4:33
Rapid Grading of Fundus Photos for Diabetic Retinopathy Using
Crowdsourcing: External Validation
Christopher Brady, MD
4:39
Discussion
PEDIATRICS
Presiding Officer: Antonio Capone Jr., MD
Moderator: Mary Elizabeth Hartnett, MD
4:42
Selective Immediate Sequential Bilateral Pediatric Vitreoretinal
Surgery
4:47Identification of the Fovea and Diagnosis of Zone by Fluorescein
Angiography in Patients with the Diagosis of Retinopathy of
Prematurity (ROP)
R. V. Paul Chan, MD
4:52
Vascular Endothelial Growth Factor (VEGF) Receptor Activates and
Interacts With the Erythropoietin Receptor to Cause Pathologic
Angiogenesis
4:58
Discussion
5:01Newborn Eye Screen Testing: Evaluation of Retinal Hemorrhage,
Localization and Timing of Resolution
5:07
Discussion
5:10
ADJOURN
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55
Scientific Sessions
SUNday, September 14
7:30 am
Continental Breakfast/ Exhibits — Meade/Grant Rooms
OTHER MACULA — II
Presiding Officer: Nancy M. Holekamp, MD
Moderator: Franco M. Recchia, MD
8:00 amCanadian Assessment of Real-world Efficacy and Safety of
Dexamethasone Intravitreal Implant (0.7 mg) in Patients with
Macular Edema
David A.L. Maberley, MD
8:05
A Pilot Study of Intravitreal Aflibercept for the Treatment of
Chronic Central Serous Chorioretinopathy: The CONTAIN Study
John D. Pitcher III, MD
8:11
Discussion
8:14
Mineralocorticoid Antagonist in the Treatment of Central Serous
Retinopathy
SunDAY, SEPTEMBER 14
Kapil Kapoor, MD
8:20
Discussion
VASCULAR
8:23
Aflibercept for Recalcitrant Central Retinal Vein Occlusion-Associated
Macular Edema Despite Prior Anti-VEGF Therapy
(The ARChiMEDES Trial)
8:28Effect of Aflibercept on Refractory Macular Edema Associates with
Central Retinal Vein Occlusion
Allen Chiang, MD
8:33
REVOLUTIONARY: A Pilot Trial of Combination Peripheral Scatter
Laser and Ranibizumab for Macular Edema Secondary to Branch
Retinal Vein Occlusion
Ivan J. Suner, MD
8:38
Real World Vision Outcomes in RVO Treated with Anti-VEGF
Injections—An Analysis of EMR Data from a Large Integrated
U.S. Health System
8:43
Two or More Dexamethasone Intravitreal Implants Used Alone Versus
with Adjunctive Therapy in Patients with Macular Edema Secondary
to Retinal Vein Occlusion
Daniel B. Roth, MD
8:49
Discussion
8:52Long-Term Effects of Combination Therapy Using Anti-VEGF Agents
and Dexamethasone Intravitreal Implant for Retinal Vein Occlusions
(RVO)
8:58
Discussion
56
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The Retina Society
Scientific Sessions
9:01 am
52-Week Results of the VIBRANT Study on Intravitreal Aflibercept
Injection in Macular Edema Secondary to Branch Retinal Vein
Occlusion
Julia A. Haller, MD
9:07
Discussion
9:10
Multimodal Imaging Analysis of Deep Capillary Plexus Ischemia in
Central Retinal Vein Occlusion
Ehsan Rahimy, MD
9:16
Discussion
9:19Early Visual Acuity Improvement in RVO Patients Treated with
Ranibizumab in the SHORE Study
W. Lloyd Clark, MD
9:25
Discussion
9:28 – 9:58
REFRESHMENT BREAK/ EXHIBITS — Meade/Grant Rooms
9:58
Real World Vision Outcomes of DME Treated with Anti-VEGF
Injections—An Analysis of EMR Data From a Large Integrated U.S.
Health System
Szilard Kiss, MD
10:03
Automated Identification and Quantification of Fluorescein Leakage
in Patients with Diabetic Macular Edema
Thiran Jayasundera, MD
10:08Intravitreal Aflibercept for Diabetic Macular Edema: 24-Month
Results from VISTA-DME and VIVID-DME
David M. Brown, MD
10:14
Discussion
10:17Evaluation of Rescue Treatment with Intravitreal Aflibercept Injection
(IAI) in Patients with Diabetic Macular Edema (DME) Receiving Laser
in the VISTA-DME and VIVID-DME Studies
Dennis Marcus, MD
10:23
Discussion
10:26Intravitreal Aflibercept in the VISTA-DME and VIVID-DME Studies:
Subgroup Analysis by Baseline Demographics and Systemic Disease
Characteristics
Charles C. Wykoff, MD
10:32
Discussion
10:35
Anti-VEGF Therapy for Diabetic Macular Edema (DME): Comparison
of Year 1 Results from Prospective, Randomized, Controlled Clinical
Trials
Allen C. Ho, MD
10:41
Discussion
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57
DIABETES
Presiding Officer: Allen C. Ho, MD
Moderator: Ingrid U. Scott, MD, MPH
Scientific Sessions
10:44 amIntravitreal Ranibizumab for Diabetic Macular Edema with Prompt
versus Deferred Laser Treatment: 5-Year Randomized Trial Results
10:50
Discussion
10:53
Open-Label Extension of the Phase III RIDE and RISE Trials—
Characteristics of DME Patients Associated with Treatment
Frequency
Carl D. Regillo, MD
10:59
Discussion
11:02
Repeated Ranibizumab Injections and Incidence of Sustained IOP
Elevations or Initiation of Ocular Hypotensive Treatment in Eyes with
Diabetic Macular Edema
Seema Garg, MD, PhD
11:08
Discussion
11:11Long-term Efficacy and Safety of Dexamethasone Intravitreal
Implant for Treatment of Diabetic Macular Edema in Phakic and
Pseudophakic Eyes
Victor H. Gonzales, MD
11:17
Discussion
11:20Effect of Doxycycline versus Placebo on Retinal Function
and Diabetic Retinopathy Progression in Patients with Severe
Nonproliferative or Non-High-Risk Proliferative Diabetic Retinopathy:
A Randomized Trial
11:26
Discussion
11:29
Topical Nepafenac to Manage Non-central Diabetic Macular Edema
11:35
Discussion
11:38
ADJOURN
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The Retina Society
Poster Program (NON-CME)
POSTER 1
Fellow Eye Comparison of Area of Geographic Atrophy (GA) In Patients
Undergoing Long-Term Anti-VEGF Therapy for Nvamd In One Eye
Michelle V. Carle, BSc(Hons), MD
POSTER 2
Squalamine Lactate Then and Now: A Review of IV and Topical Formulation Data and Comparison of Pharmacokinetics
POSTER 3Induced Pluripotent Stem (iPS) Cell-Derived RPE Transplants Induce Immune Response in Pigs
Elliott H. Sohn, MD
POSTER 4
Retinal Drusen in the Morbidly Obese
Katherine Whalen, MD
POSTER 5
Practice Preference Survey: Anti-VEGF in the Treatment of Diabetic Eye Disease
Mary Champion, MD
POSTER 6Comprehensive Analysis of Retinal Function and Structure in Proliferative Diabetic Retinopathy
POSTER 7Comparison of the Outer Retina in Diabetics and its Correlation with Visual Acuity Using Four Different OCT Machines
Veronica Kon Graversen, MD
POSTER 8
Macular Hole and Mid-Peripheral Retinoschisis in Alport Syndrome
Justin Baynham, MD
POSTER 9Influence of Risk Alleles Associated with Age-Related Macular Degeneration on Recessive Stargardt Disease Phenotypes
Robert A. Sisk, MD
POSTER 10Genetic Interaction Mapping of Age-Related Macular Degeneration Susceptibility Genes and their Expression in Human Vitreous
Lee Kiang, MD, PhD
POSTER 11
Retinal Astrocytoma: Diagnosis by Multimodality Imaging
Ekaterina Semenova, MD
POSTER 12 Automated Choroidal Thickness Map Generation Using Image Segmentation Analysis
Sabin Dang, MD
POSTER 13
Microaneurysm (MA) Wall Hyperreflectivity on Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) Imaging is Associated with Worse Vision and MA Persistence over Time in Diabetic Eyes
Jennifer K. Sun, MD, MPH
POSTER 14Intraocular Inflammation Following Aflibercept Injection
Howard F. Fine, MD MHSc
POSTER 15Intravitreal Aflibercept for Treatment of Radiation Retinopathy
James R. Singer, DO
POSTER 16 Visual and Anatomical Improvement Following Dexamethasone Intravitreal Implant in Eyes with Anti-VEGF Resistant Macular Edema
due to Retinal Vein Occlusion
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59
POSTER 17Efficacy and Tolerability of Bilateral Dexamethasone Intravitreal Implant (DEX) for the Treatment of Non-Infectious Posterior Uveitis and Macular Edema Secondary to Retinal Vein Occlusion
Steven J. Ryder, MD
POSTER 18Inpatient Ophthalmology Consultation for Fungemia: Prevalence of Ocular Involvement and Necessity of Funduscopic Screening
Murtaza K. Adam, MD
POSTER 19 White Dot Syndromes, How to Diagnose and Treat Tropical Cases: Diffuse Unilateral Subacute Neuroretinitis (DUSN) and Punctacte Outer Macular Toxoplasmosis
POSTER 20Endophthalmitis Caused by Streptococcal Species: Clinical Settings, Microbiology, Management, and Outcomes
Ajay E. Kuriyan, MD, MS
POSTER 21
Killer Cell Immunoglobulin-like Receptor (KIR) Genes, HLA Genes, and Parasite Serotypes Among Individuals Infected with Toxoplasma Gondii
David C. Reed, MD
POSTER 22Histopathology of Streptococcus Mitis/Oralis Endophthalmitis After Intravitreal Injection with Bevacizumab: A Report of 7 Patients
POSTER 23
Streptococcalmitis Endophthalmitis Presenting as Occlusive Vasculitis Following Intravitreal Injection of Ranimizumab
Alan J. Ruby, MD
POSTER 24Endophthalmitis Rates and Clinical Features Following Intravitreal Anti-Vascular Endothelial Growth Factor Injections for Diabetic Eye Disease Versus Neovascular Age-Related Macular Degeneration and Retinal Vein Occlusion
Eric Chen, MD
POSTER 25Uses of the Word “Macula” in Written English, 1400 – Present
Stephen G. Schwartz, MD, MBA
POSTER 26Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis (Irvan) Syndrome: A Case Report
POSTER 27Cystoid Macular Edema After Cataract Surgery in Eyes with Previous Vitrectomy for Epiretinal Membrane Removal
Tanuj Banker, MD
POSTER 28
Silicone Oil Behavior: Emulsified Imaging (15 Cases) and
“Non-Emulsified” Extracted Analysis
Yale L. Fisher, MD
POSTER 29Evaluation of an Adhesive Biopolymer for the Treatment of Retinal Detachment in Rabbit Eyes to Evaluate the Safety and Efficacy of a Newly Developed Biopolymer for the Treatment of Rhegmatogenous Retinal Detachment
POSTER 30
Outcomes of Diabetic Vitrectomy in a County Hospital Population
Annal D. Meleth, MD, MS
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The Retina Society
POSTER 31Combined DSEK and Transconjunctival Pars Plana Vitrectomy
Saad Shaikh, MD, MBA
POSTER 32 A Systematic Review and Meta-Analysis Comparing Same-Day vs. Delayed Vitrectomy Clinical Outcomes for Intravitreal Retained Lens Fragments After Age-Related Cataract Surgery
Elizabeth A. Vanner, PhD
POSTER 33
Postmarketing Surveillance Survey of Adverse Events of Ocriplasmin Sumit P. Shah, MD
POSTER 34Comparing Retina Quality Performance Measures Publicly Reported by Ophthalmic Organizations
Monica M. Michelotti, MD
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61
Philadelphia museum of Art
FRIDAY
62
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The Retina Society
friday, September 12 | 8:00 am
Characteristics and Outcomes of Sequential Rhegmatogenous
Retinal Detachments
Harpreet S. Walia, MD
St. Louis, MO
Gaurav K. Shah, MD, Kevin J. Blinder, MD
purpose: This study reviews the largest series of patients with sequential
rhegmatogenous retinal detachments to evaluate baseline presenting features and surgical
outcomes of the initial compared with subsequent eye.
Methods: This is a retrospective review of a cohort from a large, retina-only practice
from 1/1/2009 through 12/31/2013. Charts were included if rhegmatogenous retinal
detachments (RRD) underwent repair with either pneumatic retinopexy, scleral buckling,
pars plana vitrectomy, or combined pars plana vitrectomy/scleral buckling. Charts were
excluded if RRD was secondary to penetrating trauma or ROP. A total of 1,249 patients
with RRD repair were identified and 44 patients had sequential RRD repair in this five year
period. Baseline features recorded were demographics, presenting visual acuity, duration of
symptoms, prophylactic treatment, macula status, and presence of PVR. Surgical outcomes
recorded included method of repair, redetachment, and final visual acuity.
Results: Eighty-eight eyes from 44 patients were included. Median age was 57 years
old. Twenty-two patients were myopic and 15 had lattice degeneration. Seventeen patients
had repair by the same surgeon. Mean presenting logMAR visual acuity was 1.0495 for the
intial eye and 0.44 for the subsequent eye. The initial eye was symptomatic of an average
of 21.11 while the subsequent eye was for 3.95 days. Ten (22.72%) of the initial eyes had prior
prophylactic treatment while 16 (36.36%) of subsequent eyes did. Twenty one (47.73%) of
the initial eyes were macula-off while 8 (18.18%) of the subsequent eyes were. Ten of the
initial eyes presented with PVR while no subsequent eyes did. For repair of the initial eyes,
17 had PPV, 17 had SB/PPV, 9 had SB, and 1 had pneumatic retinopexy. Of the subsequent
eyes, 23 had PPV, 10 had PPV/SB, and 11 had SB. Eleven (25%) of the initial eyes redetached
while 3 (6.81%) of the subsequent eyes did. Final visual acuity averaged 0.89 in the initial
eye and 0.3 in the subsequent eye.
Conclusions: We present the data of the largest series of sequential RRD reported. In
our series, the initial eyes were more likely to present with worse initial visual acuity, longer
duration of symptoms, macula-off status and concurrent PVR. The initial eye was more
likely to redetach and have worse final visual acuity. Subsequent eyes tended to progress
to RRD despite prophylactic retinopexy.
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63
friday, september 12 | 8:05 am
Visual and Anatomic Outcomes of Epiretinal Membrane
Peeling After Previous Complex Retinal Detachment Repair
Christina Weng, MD, MBA
Miami, FL
Ninel Z. Gregori, MD, Stavros M. Moysidis, MD, Wei Shi, MS, William E. Smiddy, MD,
Purpose: To assess visual and anatomic outcomes after epiretinal membrane (ERM)
peeling surgery in patients with multiple prior retinal detachment (RD) repair surgeries.
Methods: Chart review was used to identify patients who had undergone vitrectomy/
membrane peel for ERM after prior complex RD repair (multiple rhegmatogenous,
tractional, combined rhegmatogenous-tractional, or history of trauma or endophthalmitis)
Snellen best-corrected visual acuity (BCVA), optical coherence tomography (OCT)
characteristics at pre- and post-op visits (1, 3, 6, 12 months), lens status, surgical dates, and
characteristics of prior RD repair were collected. Visual acuities (VA) were converted to
ETDRS letter scores. OCTs were analyzed for the presence and location of fluid and retinal
layer appearance
Results: Eighteen patients who had been seen at Bascom Palmer from January 2005 –
December 2011 were identified. 15 had rhegmatogenous RDs (1 trauma-related); 1 had a
tractional RD; 2 had combined rhegmatogenous-tractional RDs (1 endophthalmitis-related).
The mean number of retinal detachment repairs was 2.33 (range 1-5). Mean BCVA was
18.63 (SD=25.68) letters at pre-op and 19.00 (SD=19.63, P=0.96), 22.72 (SD=24.60, P=0.73),
15.55 (SD=19.43, P=0.56), and 19.29 (SD=25.69, P=0.74) letters at 1, 3, 6, and 12 months,
respectively. Mean central foveal thickness (CFT) improved from 338.50 (SD=27.58)
microns at pre-op to 728.50 (SD=277.89, P=0.27), 538.00 (SD=179.21, P=0.23), and 395.00
(SD=349.01, P=0.90) at 3, 6, and 12 months, respectively. Mean macular volume improved
from 9.34 mm3 (SD=4.62) at pre-op to 13.82 (SD=3.60, P=0.10), 12.04 (SD=1.85, P=0.13),
and 8.88 (SD=6.39, P=0.98) at 3, 6, and 12 months, respectively. No OCT data at 1 month
was available.
Conclusions: In this study, visual acuity did not improve significantly after ERM
peeling in patients with complex history of multiple retinal detachment repairs. Significant
anatomic improvement was not documented by OCT postoperatively. Given the
complexity of pathology and limited number of patients, further studies are needed to
draw a conclusion of whether patients with a significant ERM following complex retinal
detachment repair may benefit from ERM peeling surgery.
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The Retina Society
friday, september 12 | 8:10 am
Vitrectomy Techniques with 27g Instrumentation in Complex
Detachments
San Juan, PR
Purpose: To describe the utilization of the 27g vitrectomy system in the management of
retinal detachments.
Methods: Six eyes with retinal detachment were surgically managed with 27g
pars plana vitrectomy. Pathologies included diabetic traction detachment, combined
traction and rhegmatogenous detachment and retinal detachment with proliferative
vitreo-retinopathy(PVR). Pre-operative VA ranged from 20/400-HM. All eyes underwent
vitrectomy with 27g instrumentation exclusively. Surgical techniques and specific
challenges were recorded. Intra-operative and postoperative complications were assessed.
Follow-up period was six months.
Results: All six eyes had anatomic reattachment with just one surgical intervention. Final
visual acuity ranged from 20/70-20/400. Intra-operative complications included bending of
the vitrectomy probe in one case. Post-operative complications included rebleeding in one
eye eight weeks postoperatively. No suturing of the sclerotomies was required, no cases
of hypotony at post-op day one were noted and no redetachments occurred in the postoperative period.
Conclusions: Vitrectomy with 27g instrumentation appears to be safe and effective
in the management of complex retinal detachments. The smaller instrumentation confers
distinct advantages in these challenging pathologies. More experience with this modality is
warranted.
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65
Dual Port Cutter Vitrectomy for Dense Vitreous Hemorrhage:
Preliminary Study
Luiz Lima, MD
Sao Paulo, Brazil
Charles DeBoer, MD, Prashant Bhadri, PhD, Mark Humayun, MD
Purpose: Usually, the removal of dense vitreous hemorrhage using the traditional single
port (SP) cutter is lengthy. Because this standard vitreous cutter tip has only one port, the
surgeon typically performs several movements to cut and remove the vitreous gel. The
addition of a second port to the outer tube of the vitreous cutter tip may decrease bulky
vitrectomy time by increasing flow rate and reducing surgeon’s movements around the
vitreous cavity.
The purpose of this study was to compare the impact of a 180 degrees dual port (DP)
cutter on dense vitreous hemorrhage removal and the advantages of having an additional
cutter tip port over the current SP cutter technology.
Methods: Thirty-six consecutive eyes of 36 patients underwent bulky vitrectomy
surgery by six surgeons using the 180 degrees DP (18 eyes) and the SP (18 eyes) cutters.
With both study cutters, the bulky vitrectomy was performed at 2,500 cuts per minute
(CPM) and at vacuum level of 300 mmHg. The 180 degrees DP cutter tip was fabricated
from a standard 23-gauge SP cutter tip with the same sized port. The second port of
0.020-inch diameter port was machined at the distal end of the tip and 180 degrees
opposite of the original port.
Vitreous hemorrhage was classified as dense when the red reflex was absent without
visualization of any retinal structure. The main etiologies for dense vitreous hemorrhage
were diabetic retinopathy (16/36; 44.4%), retinal tears (9/36; 25%), neovascularization from
branch or central retinal vein occlusion (7/36; 19.5%), sickle cell retinopathy (3/36; 8.3%),
macroaneurism (1/36; 2.8%).
The surgeons graded the 180 degrees DP cutter tip as better, worse, or the same as
the standard SP tip for bulky vitrectomy. Mean operative time (specifically for bulky
vitrectomy), and intraoperative and postoperative complications were recorded.
Results: For bulky vitreous removal, all surgeons (100%) classified the 180 degrees DP
cutter tip as better than the SP cutter. Regarding safety, most surgeons (76%) considered
the 180 degrees DP cutter as safe as the standard SP cutter.
Mean bulky vitrectomy time was 10.6 minutes and 17.2 minutes for the 180 degrees DP
cutter and the SP cutter, respectively. Transient postoperative hypotony was the most
common complication (180 degrees DP cutter: 12.3%; SP cutter: 11.9%), resolving without
treatment in both study groups. Only 3 phakic eyes (180 degrees DP cutter: 2.8%; SP
cutter: 5.5%) developed cataracts. None of the study patients developed retinal break or
detachment, choroidal effusion, postoperative endophthalmitis, or glaucoma.
Conclusions: The 180 degrees DP cutter system seems to be safe and effective
for dense vitreous hemorrhage removal, and may allow the surgeon to perform bulky
vitrectomy more quickly. Further studies are needed to compare both 180 degrees DP and
SP cutters in larger series.
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The Retina Society
Evaluating Small Gauge Instrumentation from a New
“Intraocular” Perspective
Kirk H. Packo, MD
Chicago, IL
Dina J. Abulon, MS
Purpose: To gain an extraordinary high magnification and high definition intraocular
view of vitrectomy surgery from the inside the eye and compare vitreous behavior
associated with different instrument designs and vitrectomy system settings.
Methods: A modified Zirm technique was used to visualize the anterior segment from
inside the eye of freshly enucleated human eyes. High definition video recordings captured
surgical technique using 23, 25, and 27-gauge dual-pneumatic 7500 cpm or spring-return
vitrectomy probes with valved or non-valved trocar-cannulas. Recordings are performed
real time and in slow motion. Various styles of cannula introduction are examined at
internal high magnification. High speed particle tracking measured vitreous motion at
various cut rates.
Results: Less vitreous motion was associated with the dual-pneumatic cutters and
high speed cut rates. Smaller gauge instrumentation minimized surgical impact on tissue
structures. Overly tangential cannula insertion can catch pars plana epithelium leading to
suprachoroidal infusion. Smaller gauge instruments caused less disruption of the pars plana
and peripheral vitreous base. Valved cannulas maintained IOP stability and showed less
vitreous and retinal incarceration than non-valved designs.
Conclusions: Small gauge, dual pneumatic probes with high speed cut rates and
valved trocar-cannulas showed optimal performance and may ultimately help improve
surgical outcomes. Intraocular viewing gives greater insight to this new technology and
how best to employ it for the safest vitreous surgery approach.
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Collaborative Multi-center Study of Macular Holes:
The European Vitreo-Retinal Society Macular Hole Study
New Haven, CT
Barbara Parolini, MD, Zosia Michalewska, MD, Didier Ducournau, MD
Purpose: To evaluate factors associated with success or failure of macular hole
surgery.
Methods: A multi-center non-randomized clinical study involving 140 retina
specialists from 28 countries. Clinical manifestations, techniques, staining, tamponades,
post-operative care, success rate and complications were analyzed.
Results: One-hundred-forty retina specialists from four continents submitted 4207
cases of idiopathic macular hole. 85.7% of holes closed following vitrectomy and 59%
gained at least 3 lines of visual acuity. Factors associated with hole closure include
earlier stage, shorter duration of hole and staining (p<0.001). There was no statistically
significant difference among dyes including ICG, trypan blue, brilliant blue. Staining
improved anatomical success, but did not improve visual success. There was no statistically
significant difference in success rate among a variety of tamponades. Better visual
outcome was associated with following factors: hole closure, better baseline visual acuity,
earlier stage and shorter duration of hole (p<0.001). Inverted ILM flap technique was
associated with good anatomical and visual outcome.
Conclusions: Repair of early macular hole is associated with a better visual outcome.
Dyes improved anatomical success but not visual success. However, there was no
statistically significant difference among dyes. For large macular holes, Inverted ILM flap
technique may be helpful. Long term positioning may not be necessary.
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Results and Complications of Vitrectomy for Pseudohole/
Lamellar Macular Holes
Baltimore, MD
Erica A. Conlan, BA
Purpose: To evaluate the visual results and complications of vitrectomy in eyes with
macular pseudoholes/lamellar macular holes and symptomatic decreased visual acuity.
Methods: Vitrectomy was performed in a retrospective, consecutive case series of
55 eyes with macular pseudoholes/lamellar macular holes. Epiretinal membranes were
removed in all eyes and perimacular internal limiting membrane (ILM) was removed in
65.5% eyes.
Results: The mean preoperative logMAR visual acuity was 0.68 (20/100 +1). The mean
postoperative logMAR visual acuity was 0.5 (20/63) at 1 year (P=.003), 0.36 (20/50 +2)
at 2 years (P<.001) and 0.46 (20/63 +2) at the final examination (mean 2.6 years, P<.001).
Visual acuity improved 0.3 logMAR or more (3 lines) in 35% eyes at 1 year, 45% eyes at
2 years and 35% eyes at the final examination. The preoperative spectral domain OCT
appearance of the outer retina was helpful in identifying eyes most likely to experience
improvements in visual acuity. Only 4% of eyes were 20/40 or better preoperatively
compared to 32% at 1 year, 48% at 2 years and 40% at the final examination. There was
no difference in mean visual acuity in eyes where ICG was used to remove perimacular
ILM versus eyes with no ILM removal (mean gain +0.22 logMAR in each group at the final
examination). Visual acuity decreased 0.3 logMAR or more (loss of 3 lines) in 6 eyes by the
final examination. Decreased acuity occurred as a result of choroidal neovascularization,
recurrent epiretinal membrane and nuclear sclerotic cataracts each in 2 eyes (3.7% eyes
for each cause). There were no cases of postoperative full-thickness macular holes, retinal
detachment or infectious endophthalmitis.
Conclusions: Vitrectomy for macular pseudoholes/lamellar macular holes in eyes with
decreased visual acuity is beneficial in most eyes with acceptable rates of complications.
Spectral domain OCT was useful in predicting postoperative visual potential.
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Anterior Chamber Migration of the Dexamethasone Implant
May Result in Corneal Decompensation
Mountain View, CA
Suri N. Appa, MD, Colin A. McCannel, MD, Michael J. Elman, MD,
Susan E. Wittenberg, MD, David J. Parks, MD, et al.
Purpose: To describe the risk factors, clinical course and complications of migration
of a dexamethasone intravitreal implant (DEX implant) into the anterior chamber and
subsequent management strategies.
Methods: Fifteen patients with eighteen episodes of anterior chamber migration of the
DEX implant were retrospectively reviewed.
Results: DEX implant anterior chamber migration occurred in six patients who were
aphakic, four patients with anterior chamber intraocular lenses, two patients with scleral
fixated posterior chamber intraocular lens (PCIOL), two patients with PCIOL, and one
patient with an iris fixated PCIOL. All fifteen patients had prior pars plana vitrectomy and
fourteen (93%) had no lens capsule. The average interval from DEX implant injection to
detection of the implant migration into the anterior chamber was 13 days (range, 5-44
days). In 14 patients, corneal edema developed. Among those eyes undergoing surgical
removal of the implant, earlier intervention reduced the likelihood of permanent corneal
edema (0.5 days versus 5.5 days, p=0.04). Aspiration was necessary to remove the implant
in six patients. Among the fourteen patients with corneal edema, the corneal edema did
not resolve in ten patients (71%) and six patients (43%) required corneal transplantation.
Conclusions: Absence of lens capsule and prior vitrectomy are risk factors for
anterior chamber migration of the DEX implant. Early implant removal maybe necessary to
minimize the risk of chronic corneal edema.
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The Retina Society
Fellow Eyes of Giant Retinal Tears: Effectiveness of
Prophylactic Laser Treatment Compared to Untreated
Fellow Eyes
Guido Ripandelli, MD
Rome, Italy
Mario Stirpe, MD
Purpose: To evaluate the effectiveness of 360 degrees peripheral retinal photocoagulation in the prevention of retinal detachment (RD) in the fellow eye of patients with giant
retinal tears (GRTs).
Methods: The study included 164 fellow eyes of 164 patients (121 male, 43 female)
underwent previous surgery for spontaneous GRTs between 1982 and 2004. Age of
patients ranged from 19 to 41 years (mean 33.4 years) and refraction of the studied fellow
eyes ranged from – 7 to – 20 negative diopters (D, mean -13 D). Follow up ranged from 7 to
20 years (mean 12.7 years).
Results: At baseline observation 98 on 164 fellow eyes had 360 degrees peripheral
photocoagulation (treated eyes, group 1) while 66 on 164 fellow eyes had no prophylactic
treatments (non-treated eyes, group 2). During follow-up, 11 on 98 (11.2%) eyes of group 1
developed a RD extended from 20 to 90 degrees due to retinal breaks occurred peripherally to prophylactic treatments. In all these 11 eyes the RD at follow up controls did not
exceeded the prophylactic laser rows. Only 1 out of these 11 eyes underwent pars plana
vitrectomy (PPV) due to the eversion of the retinal flap. Ten out of 66 ( 15.1%) eyes of group
2 had a GRT and underwent PPV.
Conclusions: On a long term follow up the group of fellow eyes treated by 360
degrees peripheral laser photocoagulation showed a little difference on the rate of RD
compared to the group of untreated fellow eyes, however the anatomical characteristics of
the retinal lesions and their sight-threatening implications resulted different by far between
the 2 groups.
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Small Incision Vitreoretinal Surgery without Scleral
Depressed Shaving of Vitreous Base for Rhegmatogenous
Retinal Detachment
Beverly Hills, CA
Nikolas J.S. London, MD, David S. Boyer, MD
Purpose: To describe the outcomes of small incision pars plana vitrectomy (PPV)
without scleral depressed trimming of vitreous base for treatment of rhegmatogenous
retinal detachment (RRD).
Methods: Retrospective consecutive case series. Inclusion criteria: all cases of
rhegmatogenous retinal detachment who underwent PPV between January 2007 through
August 2013. During the study period the surgical technique included small incision PPV
(25G or 23G) in all cases. Wide-angle vitrectomy viewing system was used in all cases.
Scleral depressed vitreous base dissection was performed only in cases with anterior
proliferative vitreoretinopathy (PVR). Exclusion criteria: age < 18, follow-up < 3 months,
proliferative diabetic retinopathy, and open globe injury. Outcome measures included
retinal re-attachment and Snellen best corrected visual acuity (BCVA).
Results: 225 eyes of 221 patients, mean age 61.5 years (range 19-90 years), were
included in the study. The mean follow-up was 15.4 months (range 3-52 months). The retina
detachment involved the macula in 153 (68%) eyes. Eighty-six eyes were pseudophakic.
Forty-eight eyes were highly myopic. Giant retinal tear was present in 10 eyes. PVR ranged
from none to closed-funnel total RD. The retina was reattached with one procedure in 212
(94%) cases. Final reattachment was achieved in 222 (99%) eyes. The BCVA at baseline was
 20/40 in 52 (23%) eyes, 20/50-20/100 in 28 (12%) eyes, 20/200-20/400 in 40 (18%) eyes,
and < 20/400 in 105 (47%) eyes. At the last follow-up the BCVA was  20/40 in 113 (50%)
eyes, 20/50-20/100 in 56 (25%) eyes, 20/200-20/400 in 33 (15%) eyes, and < 20/400 in 23
(10%) eyes.
Conclusions: Current wide-angle vitrectomy viewing systems allow visualization of
retina to the vicinity of the vitreous base region in most cases. Using wide-angle viewing
systems, small incision PPV without routine scleral depressed trimming of vitreous base is
associated with good anatomic outcomes and functional improvement. Pros and cons of
scleral depressed vitreous base shaving will be discussed.
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Pars Plana Vitrectomy-Scleral Buckle versus Pars Plana
Vitrectomy Alone for Patients with Rhegmatogenous Retinal
Detachment at High Risk for Proliferative Vitreoretinopathy
Philip Storey, MD, MPH
Philadelphia, PA
Rayan Al Shareef, MD, Mohammed Khuthaila, MD, Nikolas London, MD,
Benjamin Leiby, PhD, Char DeCroos, MD, Richard Kaiser, MD
Purpose: To compare using pars plana vitrectomy (PPV) combined with a scleral buckle
(SB) versus primary vitrectomy alone in patients with rhegmatogenous retinal detachment
(RRD) at high risk for postoperative proliferative vitreoretinopathy (PVR).
Methods: Billing data was used to identify all patients surgically treated for RRD
between April 1, 2010 and August 1, 2012 at one large retina practice. Charts were reviewed
to record patient demographics, surgical approach, and treatment outcomes. Patients
were considered at high risk for PVR if they presented with retinal detachment in 2 or more
quadrants, retinal tears larger than 1 clock hour, preoperative PVR grade B-C, or vitreous
hemorrhage. Single surgery anatomical success (SSAS) was defined as 1 operation to
anatomically attach 100% of the retina for a minimum of 3 months’ duration. Patients were
excluded if they were previously treated with a SB or PPV in the study eye, received a SB
without PPV, or had less than 3 months of follow-up.
Results: 678 patients were identified as receiving surgical treatment for RRD during the
study period. Sixty-five patients were found to be at high risk for postoperative PVR. For
this high-risk group, 13 surgeons performed PPV-SB on 36 patients and PPV alone on 29
patients. Mean age, gender, lens status, baseline visual acuity, duration of follow-up, RRD
in > 2 quadrants, total RRD, tears > 1 clock hour, preoperative PVR, vitreous hemorrhage,
macular detachment and use of intraocular gas vs. silicone oil did not differ between the
PPV-SB and PPV alone groups. The SSAS rate was 63.1% overall: 75.0% (27/36) for patients
treated with PPV-SB and 48.3% (14/29) for patients treated with PPV alone. The use of
PPV-SB was associated with a significantly higher surgical success rate compared to
patients treated with PPV alone, with an odds ratio of 3.24 (95% confidence interval 1.129.17; p=0.029). Overall, 23.1% of patients developed postoperative PVR with no difference
between surgical approaches.
Conclusions: For patients with RRD at high risk for postoperative PVR, the
combination of pars plana vitrectomy and scleral buckle may have higher surgical success
rates than pars plana vitrectomy alone.
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The DISCOVER Study: Prospective Analysis of Real-time
Intraoperative OCT During Vitreoretinal Surgery Utilizing a
Microscope-Integrated Prototype with a Heads-up Display
Surgeon Feedback System
Shaker Heights, OH
Sunil K. Srivastava, MD, Peter K. Kaiser, MD, Daniel F. Martin, MD
Purpose: Optimal OCT integration into ophthalmic surgery remains an area of need
and active research. In order to better understand insights into integrative solutions, the
DISCOVER study was initiated. The focus of this abstract will be the RESCAN 700 arm of
the DISCOVER study and the vitreoretinal surgery results.
Methods: DISCOVER is an IRB-approved prospective multi-surgeon single-center
investigational device study examining the utility of a microscope-integrated prototype
with real-time surgeon feedback through a heads-up display system. The RESCAN 700 is
a prototype microscope-integrated OCT system that is built on the Lumera 700 platform
that includes heads-up display feedback of the OCT data stream within the oculars of the
microscope. The surgeon has foot-pedal control of OCT scan location, angle, and size.
Additionally, the surgeon can initiate OCT scanning, image capture, and review through
independent control features. Real-time iOCT and static iOCT were performed at various
surgical milestones. A surgeon feedback questionnaire was utilized in each case to assess
the impact on surgical decision-making and intrasurgical workflow.
Results: Anterior and posterior segment iOCT imaging were successfully obtained with
the RESCAN 700. Anterior segment imaging was achieved with the standard optics of the
system, whereas vitreoretinal imaging was accomplished with both the RESIGHT system
and a contact lens viewing system. Surgical indications included macular holes, epiretinal
membranes, vitreomacular traction, retinal detachment and intraocular lens subluxation.
Real-time feedback to the surgeon regarding anatomic configurations during surgery and
allowed for visualization of instrument-tissue interactions was achieved with the heads-up
display system. Shadowing of underlying tissues was a major limitation with standard
instrumentation for visualizing subtle details of instrument-tissue interaction. Utilizing the
iOCT, surgeons identified unrecognized residual membranes, occult formation of fullthickness macular holes, and optimal intraocular lens positioning that resulted in alterations
to surgical decision-making.
Conclusions: Real-time iOCT with heads-up display provided immediate feedback to
surgeons regarding tissue architecture and surgical milestone achievement and represents
a significant iterative advance for integrative technology. Continued research is needed in
OCT-compatible instrument design and tracking, as well as additional outcomes research to
target iOCT for optimal value utilization.
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The Retina Society
Sustained Release Dexamethasone Intravitreal Implant
(DEX) for Persistent Macular Edema (ME) after Vitrectomy
(PPV) for Epiretinal Membrane (ERM)
Boston, MA
Lauren S. Taney, MD, Jay S. Duker, MD
Purpose: Due to mechanical effects exerted by ERM, concurrent ME does not usually
respond to local anti-inflammatory therapy. Despite complete surgical removal of ERM,
retinal thickening may persist post-operatively and impede visual recovery. The sustained
release dexamethasone intravitreal implant (DEX) was used to treat unresolved ME after
PPV for ERM, and the visual and anatomic results as well as complications were evaluated.
Methods: Retrospective review of all eyes treated with DEX from January 2010 to
January 2014 at New England Eye Center, Boston, MA to identify eyes that received DEX
specifically to treat persistent ME after PPV with ERM removal. Spectral-domain optical
coherence tomography (OCT), best corrected Snellen acuity (BCVA), intraocular pressure
(IOP) and clinical examination were assessed pre and post DEX.
Results: Five eyes with refractory ME on OCT after ERM surgery were treated with DEX.
Prior to DEX, all five eyes received alternative therapies for ME without clinical response
including topical prednisolone (n=5), topical non-steroidal anti-inflammatory (n=5),
subtenons triamcinolone 40 mg (n=5), intravitreal triamcinolone 4 mg (n= 1), intravitreal
bevacizumab 1.25 mg (n=3) and intravitreal ranibizumab 0.5 mg (n=1).
Four of the five eyes demonstrated reduction in macular thickness after DEX on OCT
(mean 106 um, range 56 to 155 um) with a mean percentage reduction in central foveal
thickness of 25% (range 13% to 37%). One eye with residual post-surgical ERM and ME
responded to DEX with reduced thickness on OCT. Visual acuity improved by 1 or more
Snellen line in four or five eyes. The duration of DEX effect lasted between 3 to 9 months
before ME recurred. One of two phakic eyes developed cataract requiring surgery after 4
DEX and one eye developed elevated IOP that was controlled with topical drops. Two eyes
which demonstrated both OCT and visual improvement following initial DEX subsequently
received multiple DEX implants (7 and 9 DEX) for recurrences of ME.
Conclusions: Inflammatory factors may play a role in unresolved anatomical changes
and persistent retinal thickening after vitrectomy and ERM removal. DEX may be an option
to treat vision-limiting macular thickening that persists after ERM surgery.
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Vitrectomy After Ocriplasmin for Vitreomacular Adhesion or
Macular Hole (VAVOOM) Study
Margaret A. Greven, MD
Philadelphia, PA
Sunir Garg, MD, Sumit P. Shah, MD, Jeremy Wolfe, MD, Howard F. Fine, MD,
Carl Regillo, MD, Allen Ho, MD, Julia Haller, MD
Purpose: To describe the results of pars plana vitrectomy (PPV) for persistent
symptomatic vitreomacular adhesion (VMA) and macular hole (MH) after intravitreal
ocriplasmin.
Methods: Multi-center retrospective chart review of patients at three institutions from
January 2013 to January 2014 who received intravitreal ocriplasmin for symptomatic
VMA with/without MH, and then went on to PPV. Patient age, phakic status, presence of
epiretinal membrane (ERM) or other visually significant pathology were recorded. LogMAR
visual acuity (VA) pre-ocriplasmin injection, post-ocriplasmin but pre-PPV, and post-PPV
one month, 3 months, 6 months, and final visual acuity were recorded. Intra-operative use
of ICG, ILM peeling, and intraoperative complications were recorded. Spectral-domain OCT
(SD-OCT) images from pre-ocriplasmin injection, post-ocriplasmin but pre-PPV, and post
PPV were reviewed. Size of adhesion, stage and size of MH, and presence and dimensions
of subretinal fluid were recorded.
Results: 39 eyes of 39 patients underwent PPV after receiving ocriplasmin. 29 patients
were female and 10 were male, with an average age of 70+/-9 years. Length of follow-up
ranged from 3 to 9 months post-vitrectomy. 25/39 (64%) patients were phakic, and 17/39
(44%) patients had epiretinal membrane. Visually significant pathology included cataract
in 11/39 (28%) eyes. 93% of patients underwent intra-operative ICG-assisted ILM peeling.
Average VA pre-ocriplasmin injection was 0.75±0.37 (20/112 Snellen), post-ocriplasmin
but pre-vitrectomy 0.84±0.37 (20/138), one-month post-PPV 0.76±0.53 (20/115) (p=0.47),
3 months post-PPV 0.62±0.32(20/83) (p=0.054), 6 months post-PPV 0.61±0.34 (20/81)
(p=0.055), and average final VA was 0.58±0.30 (20/76) (p=0.004). At final follow-up,
compared to pre-ocriplasmin injection, 24/39 (62%) patients had improvement in VA, 11/39
(28%) had worsening of VA, and 4/39 (10%) patients had no change in VA. One patient
developed RD post-ocriplasmin injection and then went on to develop recurrent RD postPPV requiring further surgery. One patient developed RD with PVR post-PPV requiring
further surgery. Two patients developed retinal tears intraoperatively that were treated.
Conclusions: Patients who have persistent symptomatic VMA with/without MH
despite ocriplasmin injection gain VA on average after vitrectomy without added risk of
surgical complications related to treatment with ocriplasmin.
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The Retina Society
Subretinal Air Displacement of Submacular Hemorrhage:
Initial Experience
Michael D. Ober, MD
Southfield, MI
Pouya N. Dayani, MD, Cameron M. Stone, MD, Judy E. Kim, MD,
Tamer H. Mahmoud, MD, PhD
Purpose: To assess the role of subretinal air in displacement of subretinal hemorrhage.
Methods: Surgeons with initial experience with the use of subretinal air injection to
assist in displacement of submacular hemorrhage (SMH) were surveyed to evaluate the
utility of this new technique.
Results: Ten eyes of 10 patients were identified. Eight eyes developed SMH secondary
to age-related macular degeneration, one from proliferative diabetic retinopathy (PDR)
with macroaneurysm, and one from trauma. In all, the SMH reached beyond the arcades,
and included foveal center with visual impairment. Timing from initial symptom to
intervention ranged between 1 week in 4 eyes, 2-3 weeks in 5 eyes, and 10 weeks in 1 eye
(due to delayed surgical clearance). Eight patients received a combination of subretinal tPA
12.5 micrograms/0.1 ml, bevacizumab 1.25 mg/0.05 ml, and filtered subretinal air of varying
volumes (range: 0.3-0.5 ml). Two patients without choroidal neovascularization received
subretinal tPA and air without bevacizumab. Nine patients had partial fluid-air exchange
and sulfur hexafluoride gas ranging from 20-24%, and one patient was left with 50% air.
Positioning included upright in 3 patients and a combination of upright and face down in
7 patients. Most of the SMH was displaced beyond the arcades in all eyes. Submacular fluid
and air were seen initially in all eyes on day 1, and spontaneously resolved thereafter except
in 1 patient. Rebleeding was seen in 2 eyes, one at 2 weeks with recurrent extensive SMH,
which was displaced again with the same technique, and a second with thin SMH treated
with intravitreal bevacizumab injections. A third patient with history of trauma and initial
posterior break developed subsequent proliferative vitreoretinopathy requiring additional
reattachment surgery. Compared to pre-operative visual acuity (range: 20/400 to HM),
vision improved in all patients after the procedure with a mean of 6.3 lines and a median of
6 lines (range 20/32 to CF), and approached, in most cases, visual acuity prior to SMH.
Conclusions: Limited initial experience with the use of subretinal air injection and tPA
to displace SMH seems to indicate more consistent displacement, resulting in improved
visual outcome in a debilitating complication with poor natural history.
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One-year Outcomes of Eyes Treated with a Sutureless
Scleral Fixation Technique for Intraocular Lens Placement
or Rescue
New Brunswick, NJ
John D. Wilgucki, BS, MD, H. Matthew Wheatley, MD, Leonard Feiner, MD, PhD,
Mark V. Ferrone
Purpose: To report the one year results of a novel surgical technique for sutureless
scleral fixation of a three-piece intraocular lens (IOL).
Methods: Retrospective, consecutive series of patients who underwent sutureless
scleral fixation of a three-piece IOL. All patients were required to have at least one year
of follow up to be included in the series. Outcomes data were obtained and treated with
simple statistical analyses.
Results: A total of 24 patients were included in the study population. The average age
was 75 years (range 44-87). Short-term complications were few, and included vitreous
hemorrhage (n=2), elevated intraocular pressure (n=1) and hypotony (n=1). Long-term
complications included IOL dislocation (n=3), cystoid macular edema (n=1) and haptic
dislocation (n=1) Mean visual acuity improved from LogMAR 1.298 (20/397) to 0.518
(20/66) at one year.
Conclusions: This novel technique for sutureless scleral fixation of a 3-piece IOL was
well tolerated at one year after surgery.
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The Retina Society
Advances in Vitreoretinal Evaluation and Surgery with
Permanent Keratoprosthesis
Donald J. D'Amico, MD
New York, NY
Szilárd Kiss, MD, Kimberly C. Sippel, MD, Ana Alzaga-Fernandez, MD,
Mark I. Rosenblatt, MD, PhD, Christopher Starr, MD
Purpose: To report our findings and experience regarding vitreoretinal diagnosis as well
as surgical techniques and outcomes in eyes with a Dohlman permanent keratoprosthesis.
In addition, we report out initial experience with surgery involving the newly revised type 2
device in which implantation is combined with permanent lid closure to maximize retention
in eyes with a severely altered ocular surface environment.
Methods: Forty cases of type 1 keratoprosthesis and one type two device were
retrospectively reviewed for vitreoretinal diagnostic and surgical issues during the
preimplantation evaluation, during the implantation surgery itself, or in the postoperative
course. Follow up ranged from two weeks to over 5 years, with a mean follow up of over
two years post implantation. These findings were compared with historical results from
earlier series to permit assessment of changes in technique and outcomes.
Results: K-Pro placement in our center has evolved to routinely include an extensive
vitrectomy at the time of initial surgery, and our preference is overwhelmingly for an
aphakic implantation. Preoperative and postoperative widefield camera evaluation often
produces a surprisingly informative view and is included when feasible. For some eyes,
an initial endoscopic evaluation of the optic nerve and retina is performed to determine
if the eye has visual potential prior to performing the more extensive corneal procedure,
and all eyes undergoing K-Pro placement have intraoperative visualization of the retina by
one of several methods. Small (25) gauge instruments are preferred, although removal of
the crystalline lens by an open sky technique is used in cases that are phakic. Intravitreal
steroids are used to suppress retro-K-Pro membrane, and repair of retinal detachment
has improved. Biointegration of the device by a partial layer of surface epithelium is
noted more frequently in recent cases and undoubtedly serves to protect the host/device
interface. Postoperative hypotony, formerly untreatable, has been successfully managed by
injection of viscoelastics and, if necessary, ligation of existing glaucoma shunt tubes. When
visual results are poor, it is usually due to advanced glaucoma with disc damage, frequently
present in these severely diseased eyes, or retinal detachment and scarring.
Conclusions: Small gauge instruments, advances in surgical technique, and widefield
visualization have improved the diagnosis and management of vitreoretinal issues in
association with permanent keratoprosthesis.
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Quality Measures within a Group Retina Practice—Cultural
Shift and Clinical Outcomes
Denver, CO
Purpose: The purpose of this project is to demonstrate the feasibility of a group
medical practice instituting several quality measures, both clinical and nonclinical. This
involves not only the actual measures, but also the cultural shift within the practice, which
supports quality measurement and improvement.
Methods: Clinical data within an 11-physician retina-only practice was obtained over
the year 2012 through the electronic medical record system. Specifically the one operation
success rate for surgical repair of uncomplicated retinal detachment (RD) and macular hole
(MH) were recorded, namely success 3 months following surgery. Nonclinical measures
were based on two survey questions, measuring patient satisfaction with the practice
and their individual physician, using a survey of 3% of patient visits for the year. Serious
reportable events (SPE) for the year were collected, specifically intravitreal injections
performed on the wrong eye or using the wrong medication.
Results: Physicians within the practice showed little interest in the project but offered
no resistance. The single operation success rates for repair of RD was 80% and for MH was
88%, with significant variation between physicians. Patient satisfaction scores noted 95%
satisfaction with the practice and physicians. SPEs occurred with an incidence of 0.0125%.
Fewer than half of the physicians wanted to know their surgical outcomes upon completion
of the project.
Conclusions: Quality can be measured within a group retina practice but the cultural
shift toward systematic quality measurement remains challenging. Measures of quality
and value are important new metrics under healthcare reform and such data may provide
advantages to practices under new payment mechanisms. Ultimately it is better for medical
practices to proactively measure quality than to allow the government or payers to perform
these measures using arbitrary or flawed metrics.
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The Retina Society
Analysis of Birdshot Chorioretinopathy Abnormalities Using
SD-OCT and Fundus Autofluorescence Imaging
David Sarraf, MD
Los Angeles, CA
Christian Boeni, MD, Gary Holland, MD, Ralph Levinson, MD, Richard Spaide, MD,
Trucian Ostheimer, MD, et al
Purpose: To evaluate the spectrum of retinal and choroidal abnormalities in Birdshot
Chorioretinopathy (BCR) using detailed multimodal analysis including spectral domainoptical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging.
Methods: This study was a prospective, cross-sectional, multicenter investigation
that recruited patients with HLA A29 positive BCR. All patients received a standardized
questionnaire regarding disease-related symptoms and detailed visual function testing. The
imaging protocol included macular and extra-macular enhanced depth imaging (EDI) and
SD-OCT volume scans, FAF and color fundus photography. Meticulous analysis of the entire
imaging repertoire was performed in each patient to identify the spectrum of structural
abnormalities in the retina and choroid of eyes with BCR.
Results: A total of 49 patients and 97 eyes were evaluated. Retinal OCT abnormalities
included epiretinal membrane in 29% (28/97), ganglion cell layer atrophy in 36% (35/97),
prominent hyper-reflective foci in inner nuclear layer in 10% (10/97), outer nuclear
layer atrophy in 45% (44/97), disruption of external limiting membrane in 44% (44/97),
disruption of ellipsoid layer in 48% (47/97), hyper-reflective foci above the retinal pigment
epithelium in 28% (27/97), and intraretinal cystoid edema in 7% (7/97) of eyes. Choroidal
imaging revealed characteristic hypo-reflective lucencies in 26% (25/96), choroidal thinning
(400µm) in 8% (8/97) and presence of a suprachoroidal space in 17% (16/93) of eyes. FAF
findings included hypoautofluorescent macular spots in 35% (34/96), hypoautofluorescent
extramacular spots in 83% (80/96), hypoautofluorescent peripapillary ring in 88% (84/96),
hypoautofluorescence along the retinal vessels in 23% (22/96) and hyperautofluorescent
foci in 53% (51/96) of eyes.
Conclusions: Detailed analysis of SD-OCT and EDI and FAF imaging findings in HLA
A29 positive patients with BCR revealed a large spectrum of both inner and outer retinal as
well as choroidal abnormalities that may all contribute to progressive vision loss.
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Initial Choroidal Thickness as a Predictor for Short-term
Response to Anti-Vascular Endothelial Growth Factor
(anti-VEGF) Treatment in Diabetic Macular Edema
Nika Bagheri, MD
Philadelphia, PA
Nadim Rayess, MD, Ehsan Rahimy, MD, Gui-shuang Ying, PhD, Eric Chen, MD,
Jason Hsu, MD
Purpose: To determine the influence of initial subfoveal choroidal thickness (SFCT)
on response to intravitreal anti-vascular endothelial growth factor (VEGF) therapy in
treatment-naïve patients with diabetic macular edema (DME).
Methods: Retrospective, consecutive case series of treatment-naïve (no prior
intravitreal therapy, panretinal or focal laser photocoagulation) patients diagnosed with
DME and treated with 3 initial monthly injections (month 0, 1, and 2) of ranibizumab or
bevacizumab followed by assessment of response at 3 months. Responders were defined
as patients having either a decrease in central macular thickness (CMT) of greater than
50 µm (anatomical responders) or visual gains greater than or equal to 1 line at 3 months
(functional responders). Pertinent clinical data, including age, gender, and visual acuity
(VA) was obtained and serial enhanced depth imaging optical coherence tomography
(EDI-OCT) scans were used to measure SFCT and CMT.
Results: Fifty-seven eyes of 40 patients were included in the study. Initial measurements
were compared to those after 3 monthly injections of ranibizumab/bevacizumab. The
anatomical responder group (n=32) had a greater baseline SFCT (243 ± 15 µm) than
the non-responder group (n=25) (188 ± 12 µm; P=0.002). They also had significant
improvement in vision at 3 months (PP=0.34). Similarly the functional responder group
(n=28) had a greater baseline SFCT (239 ± 12 µm) than the non-responder group
(n=29) (199 ± 15 µm; P=0.02). Multivariate analysis for baseline predictors of 1 line visual
improvements was significant for SFCT (P=0.005) and baseline visual acuity (P=0.01).
Multivariate analysis further showed baseline SFCT and CMT were the strongest predictors
for anatomical improvements of CMT 50 µm (P=0.053 and P=0.008, respectively).
Conclusions: Baseline SFCT may help predict which eyes with DME will respond
more favorably in the short term to intravitreal anti-VEGF pharmacotherapy. In this study,
eyes with thicker baseline SFCT had greater anatomic and visual gains after three serial
intravitreal anti-VEGF injections.
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The Retina Society
Torque Teno Virus is Associated with Culture-negative
Endophthalmitis
Sunir J. Garg, MD, FACS
Philadelphia, PA
Michael Tibbetts, MD, Aaron Y. Lee, MD, Lakshmi Akileswaran, PhD,
Adam Gerstenblith, MD, Russell N. Van Gelder, MD, PhD
Purpose: To search for potential pathogens in culture–negative endophthalmitis using
deep DNA sequencing techniques.
Methods: Single center consecutive prospective observational study. Aqueous or
vitreous biopsies from 21 consecutive patients presenting with presumed infectious
endophthalmitis, and seven vitreous samples from patients undergoing surgery for
non-infectious retinal disorders were examined for potential pathogen DNA in ocular
samples. Traditional bacterial and fungal culture, 16S quantitative polymerase chain
reaction (qPCR) and a representational deep-sequencing method (Biome Representational
in Silico Karyotyping [BRiSK]) were applied in parallel to samples to identify DNA
sequences corresponding to potential pathogens.
Results: None of 7 controls yielded positive results for bacteria or virus by culture, 16S
PCR, or BRiSK. Fourteen of the 21 samples (66.7%) were culture-positive for bacterial
species, the most common being Staphylococcal and Streptococcal species. There was
good agreement among culture, 16S bacterial PCR, and BRiSK methodologies for culturepositive cases (Fleiss’ kappa of 0.621). 16S PCR did not yield a recognizable pathogen
sequence in any culture-negative sample, while BRiSK suggested presence of Steptococcus
in one culture-negative sample. Surprisingly, using BRiSK, 57.1% of the culture-positive and
100% of the culture-negative samples demonstrated presence of Torque Teno Virus (TTV)
sequences, compared to none in the controls (Fisher exact, p = 0.0005). Presence of TTV
viral DNA was confirmed in seven cases by qPCR with levels as high as 4 x 107/ml. No other
known viruses or potential pathogens were identified in these samples.
Conclusions: Culture, 16S qPCR, and BRiSK provide complementary information in
presumed infectious endophthalmitis. The majority of culture-negative endophthalmitis
samples did not contain significant levels of bacterial DNA; thus ‘culture-negativity’
does not appear to be due to failure of growth of prevalent, fastidious bacteria. TTV is a
prevalent, small non-enveloped single stranded DNA anellovirus which has been implicated
in pathogenesis of a number of human inflammatory conditions including seasonal
hyperacute panuveitis syndrome. The current study cannot distinguish whether TTV is a
direct intraocular pathogen, an adjuvant for inflammation, a general marker of inflammation,
or a commensal finding, but rather provides a testable hypothesis for the pathogenesis of
culture-negative endophthalmitis.
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83
The Current Face of Endophthalmitis: 107 Consecutive Cases
Bernard H. Doft, MD
Pittsburgh, PA
Karl Olsen, MD, Robert Bergren, MD, Pamela Rath, MD, William Conrad, MD,
Avni Vyas, MD, Shalini Yalamanchi, MD, Judy Liu, MD
Purpose: To determine if there has been a change in the etiology and outcome of
endophthalmitis we assessed every new case presenting in the three years between
1/1/2010 and 12/31/2013. Endophthalmitis was considered present if our clinical suspicion
was strong enough that an initial therapeutic procedure (either TAP or PPV (along w/
injection of antimicrobials) was performed.
Methods: One hundred seven consecutive patients were included in this retrospective
study. Visual acuity was initially measured as LogMAR. For 34 patients final visions were
obtained as Snellen from an outside referring doctor, and converted to logMAR.
Results: Mean age was 71.8 years, and mean duration of f/u 201 days The inciting event
was cataract extraction (CE) in 52 (48.6%), intravitreal injection (IVI) in 35 (32.7%), filtering
surgery [FILTER] in 4 (3.7%), corneal graft [PK] in 2 (1.9%), strabismus surgery [STRAB] in
1 (.9%), penetrating trauma [TRAU] in 3 (2.8%) and endogenous (ENDOG) in 10 (9.4%).
Cultures were positive in 57 patients (53.27%), and the organisms were G+ other in 20
(35%), G+ coagulase negative in 33 (58%), Gram Neg in 1 (2%), and fungal in 3 (5%). Initial
intravitreal antimicrobials included vancomycin in 105 (98.1% ), along with either amikacin in
44 eyes (41.1%) or ceftazidime in 59 (55.1%). Voriconazole was administered in 5 eyes (4.7%).
Mean initial and final visual acuity [VA] was 20/1165 and 20/145 for all patients; 20/960 and
20/94 for CE, 20/1450 and 20/1175 for IVI; 20/1200 and 20/175 for ENDOG; 20/2825 and
20/850 for FILTER; 20/4475 and 20/315 for PK; and 20/475 and 20/500 for TRAU patients.
Forty-five percent of all patients, 60% of CE, 31% of IVI and 14% of ENDOG with final follow
up retained vision better than 20/60.
The initial procedure (all TAP) was performed in-office in 80 cases (74.8%), and in the OR
(all but 1 PPV) in 26 cases (24.3%). The mean time from inciting event to initial procedure
was 48.5 days (excluding ENDOG), for CE 10 days, IVI 7 days, FILTER 964 days, PK 17days,
STRAB in 1 case 7 days, and TRAU 5 days.
Conclusions: IVI is now the cause of approximately 1/3 of new cases of
endophthalmitis. Of interest in 43% of our cases the IVI was performed by a general
ophthalmologist and only referred to us only after endophthalmitis developed. About 3/4
of all cases can be managed as an outpatient with in-office TAP, though this will depend on
presenting acuity and inciting cause.
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The Retina Society
F E L LOWS HIP RE S EAR CH AWARD
Optical Coherence Tomography Drusen Volume and Retinal
Pigment Epithelium Abnormal Thinning Volume Predict
2-Year Progression of Age-Related Macular Degeneration
Francisco A. Folgar, MD
Durham, NC
Eric L. Yuan, BSE, Monica Sevilla, MS, Stephanie J. Chiu, BSE, Emily Y. Chew, MD,
Sina Farsiu, PhD, Cynthia A. Toth, MD
Purpose: To analyze the value of novel measures of retinal pigment epithelium (RPE)
plus drusen complex (RPEDC) volume to predict 2-year disease progression, including
choroidal neovascularization (CNV) or central geographic atrophy (CGA), in eyes with
intermediate age-related macular degeneration (AMD).
Methods: High-density spectral domain optical coherence tomography (SDOCT)
macular volumes were obtained in 314 AMD and 122 non-AMD subjects enrolled in the
prospective observational Age Related Eye Disease Study 2 Ancillary SDOCT Study
(A2ASDOCT). Semi-automated RPEDC segmentation within a 5-mm diameter macular field
with proprietary software and manual correction generated volumes of RPEDC, RPEDC
abnormal thickening (Drusen), and RPEDC abnormal thinning (RAT) in 265 AMD and 115
controls (one eye per subject). Volume changes from baseline to year 2 and hazard ratios
(HR) with 95% confidence intervals (CI) for advanced AMD were calculated.
Results: Mean (standard deviation) baseline RPEDC volume was 0.69 (0.21) mm3 for
AMD eyes and increased to 0.72 (0.46) mm3 at year 2 (p=0.011). Drusen volume increased
from 0.08 (0.16) mm3 to 0.10 (0.23) mm3 (p-3 mm3 to 1.8 (4.7) x10-3 mm3 (p3 increase
(HR 1.22, CI 1.10-1.35, p-3 mm3 increase (HR 1.27, CI 1.16-1.40, p3, Drusen was 0.38 (1.4) x10-4
mm3, and RAT was 3.0 (8.5) x10-4 mm3. Non-AMD volumes differed significantly from
AMD eyes and showed no significant change at year 2.
Conclusions: Macular Drusen and RAT volumes increased significantly in AMD eyes
over 2 years. These quantitative SDOCT biomarkers predict 2-year volume change and
AMD progression, and they are useful biomarkers for future clinical trials.
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85
J. D ONA L D M . G ASS AWARD
In Memoriam of the Art of Scleral Buckling
Philadelphia, PA
Purpose: In memoriam of the art of scleral buckling.
Methods: An historic review of retinal detachment surgery.
Results: From the initial description of the Helmholtz ophthalmoscope, the repair of
retinal detachments has been based upon the principle of: Find the hole, treat the hole and
close the hole. The skill set of finding the retinal defect, documenting the location of retinal
breaks, planning the type of scleral buckle procedure necessary for the closing of the
defects, and then flattening of the detachment often with external drainage of subretinal
fluid was learned over many years of training and experience. The technique of indirect
ophthalmoscopy with scleral depression, drainage of subretinal fluid and the placement of
just the right buckle became an art form rather that a rote surgical procedure. Today that
skill set is being lost. The repair of retinal detachments is now an intraocular procedure
which requires a new set of skills.
Conclusions: While the end result of retinal detachment surgery is the flattening of
the retina with restoration of vision, there is less and less controversy concerning the use of
vitreous surgery as a primary method for the repair of most retinal detachments. The result
is the loss of the experience necessary to learn when and how to perform scleral buckling
surgery. For that we now pay tribute.
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friday, September 12 | 12:45 pm
A Value-Based Medicine® Analysis of Genetic Testing for
Neovascular Age-Related Macular Degeneration—Patient
Value Gain and Financial Return-on-Investment
Plymouth Meeting, PA
Melissa M. Brown, MD, MN, MBA
Purpose: Controversy exists regarding genetic testing for the development of
neovascular age-related macular degeneration (NVAMD). The authors thus undertook
a Value-Based Medicine, patient preference-based, comparative effectiveness and costeffectiveness analysis of genetic testing for NVAMD in the United States.
Methods: A 12-year, combined-eye model, average cost-utility analysis was performed
to assess genetic testing for Category 3 AMD patients at age 65 to enable early-treatment
ranibizumab therapy (baseline vision 20/40-20/80) over late-treatment ranibizumab
therapy (baseline vision <20/160) for NVAMD in the MARINA Study. The base case
assumed genetic testing yields a 19.2% increase in early-treatment ranibizumab therapy
cases, half the 38.5% of Category 3 AMD patients not phenotypically predicted to develop
neovascular AMD over 10 years. Patient and financial value (2012 U.S. real dollar) outcomes
were discounted at 3% annually.
Results: Genetic testing-enabled, early-treatment ranibizumab therapy per treated
patient conferred mean 20/40-1 vision, a 0.845 QALY gain (14.1% quality-of-life gain),
versus mean 20/160+2 late-treatment vision, a 0.250 QALY gain (4.2% quality-of-life gain).
The net early-treatment over late-treatment gain was 0.595 QALY (10.0% quality-of-life
gain). The cost per patient for genetic testing/closer monitoring was $2,205, or $2.082
billion for the 944,400 estimated new Category 3 AMD patients annually. Genetic testing/
monitoring costs per early-treatment patient totaled $66,180. Incremental cost-savings
per early-treatment patient included: (-$40,914) direct non-ophthalmic medical costs,
(-$172,443) caregiver costs, and (-$14,098) employments costs, totaling (-$227,455). Total
societal costs were (-$160,583).
Assuming genetic testing-enabled a 19.2% increment in early-treatment ranibizumab
therapy, the societal cost-utility ratio (CUR) was (-$269,878)/QALY and third party insurer
CUR was $43,636. Genetic screening was cost-effective, using WHO criteria, when it
enabled a minimum, incremental 6,648 (4.1%) of 161,754 annual NVAMD patients to receive
early-treatment ranibizumab therapy. The base-case, 19.2% early-treatment, ranibizumab
therapy annual cohort returned $5.00 billion to society over 12 years, a 240% financial
return-on-investment (ROI) referent to genetic screening/monitoring costs.
Conclusions: Genetic screening for NVAMD is cost-effective if it enables an
incremental 4.1% of NVAMD patients to receive early-treatment ranibizumab therapy.
A 19.2% annual, screening-enabled, early-treatment cohort returns a net annual $5.0 billion
to society.
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friday, September 12 | 12:54 PM
Detection Rate of New Choroidal Neovascularization in Eyes
with Age-Related Macular Degeneraion at Visits Prompted
by Home Monitoring Device, Symptoms and Standard Care
Baltimore, MD
for the AREDS2 - HOME Study Group
Purpose: To report the rate at which new choroidal neovascularization (CNV) is
detected at routine office visits, office visits prompted by symptoms, and office visits
prompted by use of a home monitoring device in eyes with high risk of age-related macular
degeneration (AMD) progression within the HOME Study.
Methods: 1520 AMD patients were randomly assigned to standard care (SC) or standard
care plus home monitoring with the ForeseeHome device (FSH) with telemonitoring. All
participants were instructed to perform regular vision checks and to promptly return to
their investigator upon recognizing symptoms. Participants assigned to the FSH also were
requested to return promptly if device testing alerted change. Visits prompted by new
symptoms or FSH, and any routine visit at which signs of CNV were suspected required
protocol refraction and visual acuity (VA) determination, fundus photographs, fluorescein
angiography and OCT.
Results: The detection rate of CNV during the average follow-up period of 1.4 years
(range 0-32 months) was 14 CNV events/1949 routine visits or 0.72% (95% CI: 0.3%-1.1%)
in the SC arm; and 14 CNV events/1927 routine visits or 0.73% (95% CI: 0.4%-1.1%;) in
the FSH arm. Median VA loss was ~8 letters at CNV diagnosis in each group. Detection
of new CNV was identified in 17 CNV events/65 visits or 26% (95% CI: 15.5%-36.8%) of
symptom prompted visits in the SC arm and 37 CNV/318 visits or 11.6% (95% CI: 8.1%-15.2%)
in symptom or device prompted visits in the FSH arm. Median vision loss among CNV
eyes detected by symptoms in the SC arm was 11.5 letters as compared to 3 letters when
detected by symptoms or device alerts in the FSH arm (P=0.03).
Conclusions: Routine visits to monitor at risk AMD patients rarely (<1%) identified
CNV; whereas home monitoring with the FSH and symptom recognition resulted in a
substantial increase in the detection rate of CNV (RR= 16.0, 95% CI: 8.8, 29.3). Moreover,
visual acuity was significantly better at CNV diagnosis among eyes monitored with both SC
and the home device when compared to eyes monitored with SC alone.
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The Retina Society
Concentration of Vitamins C, Vitamin E, Zinc and Copper in
Dietary Supplements
Charles C. Barr, MD
Louisville, KY
Edward Apenbrinck MD, Xinmin Yin, Pawel Lorkiewicz PhD, Xiang Zhang PhD
Purpose: Vitamin and minerals contained in AREDS 2 preparations are considered
“dietary supplements” by the FDA, but in 2012 an estimated 70% of manufacturers
were considered noncompliant with “good manufacturing practices”. We tested the
concentration of vitamins C and E and minerals zinc and copper in National and Local
brands of dietary supplements recommended for patients at risk for macular degeneration.
Methods: We purchased AREDS #2 formula preparations from local stores; Occuvite
Preservision, I-Caps, Walgreens and Kroger brands were analyzed. Gas chromatography
mass spectrometry method was developed to separate Vitamin C and E, and then Vitamin
C and E were identified by mass spectrum matching followed by retention time matching.
Zinc and Copper were analyzed using atomic absorption spectroscopy.
Results: Results of our analysis are shown in the Table below
I-Caps
Occuvite
Walgreen
Kroger
Label Meas Label MeasLabel MeasLabel Meas Vit C
Vit E 250 257
Zinc Copper 250 292
250 260 250 255
7
5 64 60 67 60 57 60 57
30 37 40 48 40 46 40 46
2 2 2 2 2 2 2 2
Conclusions: All the dietary supplements we analyzed had relatively accurate
labeling of the concentrations of Vitamin C, E, Zinc and Copper, and manufacturers of
these products seem to be following “good manufacturing practices”. Physicians may
recommend generic brands with some confidence. We did not test for bioavailability of the
different substances.
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89
Combined Complement Factor H (CFH) and Age-Related
Maculopathy Susceptibility 2 (ARMS2) Risk Predicts
Response to AMD Nutritional Prophylaxis: A New Analysis
of AREDS Data
Carl C. Awh, MD
Nashville, TN
Brent Zanke, MD, PhD
Purpose: To investigate our published projections of the separate effects of CFH
and ARMS2 genetic risk on the response to components of the AREDS formulation, we
performed an outcomes analysis of AREDS patients based upon combined CFH and
ARMS2 risk. We propose guidelines for genotype-directed nutritional therapy of AMD
based upon actual outcomes in AREDS.
Methods: A retrospective, case-control study of prospectively acquired data from
AREDS. Analysis was restricted to white patients with available DNA and moderate
(AREDS 3) AMD in at least one eye (989). The incidence and timing of progression to
advanced AMD (AREDS Category 4A or 4B) as a function of treatment subgroup and CFH/
ARMS2 genotype status were determined. Four CFH/ARMS2 groups were defined to allow
sufficient numbers for statistical analysis and a rational distribution of genetic risk.
Cox proportionate regression analysis was used to estimate time to progression to
advanced AMD in each of the 4 genotype groups as a function of AREDS treatment
category.
Results: Genotype frequencies for CFH homozygous risk (C2), heterozygous (C1) and
homozygous non-risk (C0) were 36.3%, 51.6% and 12.1% respectively. ARMS2 homozygous
risk genotypes (A2) occurred in 14.3%, heterozygous (A1) in 44.2% and homozygous
non-risk (A0) in 41.6%. To simplify analysis we dichotomized genotype status at CFH
as either C2 or C1/C0 and at ARMS2 as either A0 or A1/A2 based on allele frequencies,
thereby defining 4 genotype groups: C01/A12 (350), C01/A0 (280), C2/A0 (131) and C2/
A12(228).
For C01/A12 individuals the odds of AMD progression at 7 years was minimized by
treatment with zinc, with a hazard ratio (HR) compared to placebo of 0.51 (p=0.0093). C01/
A0 patients had lowest progression (HR = 0.38, p=0.032) if treated with antioxidants. C2A0
patients had increased progression if treated with zinc (HR = 3.0, p = 0.023) or the AREDS
formulation (HR = 2.8, p = 0.029). For C2/A12 patients, no treatment was better than
placebo.
Conclusions: Combined CFH/ARMS2 status should be used to select the optimal
nutritional treatment for individuals with moderate AMD.
90
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The Retina Society
Preliminary Results of Phase I Study with AAV2-sFLT01
as Gene Therapy for Treatment of Exudative Age-Related
Macular Degeneration
Boston, MA
Peter Campochiaro, MD, Pravin Dugel, MD, Shalesh Kaushal, MD, Peter Kaiser, MD,
Jason Slakter, MD, John Connelly, PhD
Purpose: To report preliminary results of Phase I study with AAV2-sFLT01 as Gene
Therapy for the treatment of exudative AMD.
Methods: This clinical study is designed to primarily evaluate safety and tolerability and
to secondarily assess the biological activity of a single intravitreal administration of AAV2sFLT01 in patients with advanced neovascular AMD. The study is divided in 2 parts: Part 1, 4
different doses of the study drug has been studied in 4 separate groups of patients; Part 2,
the highest safe and well tolerated dose was studied in 7 additional patients.
The primary outcome is safety and tolerability of intravitreally administered AAV2-sFLT01
at one year. Secondary outcomes include changes in visual acuity and central foveal
thickness. Patients are asked to participate in an Extended Follow-Up program for up to an
additional 4 years to collect the long-term safety information as well as information about
the potential long-term treatment effects of the study drug.
Results: A total of 19 patients were randomized and treated. From the ongoing safety
monitoring, neither dose-limiting toxicity (as per protocol definition) nor unexpected safety
signals following administration of any dose level was observed.
Patient observations from a preliminary review of the OCT by an independent reading
center suggesting an effect of the gene therapy will be presented at the meeting.
Conclusions: AAV2-sFLT01, an intravitreally administered Gene Therapy for the
treatment of exudative AMD, appears safe, well tolerated and shows encouraging signals of
biological activity.
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91
Comparison of Distance and Near Vision in the Better-seeing
Eye vs. Both Eyes in Neovascular Age-Related Macular
Degeneration
Baltimore, MD
Lisa Chen, Voraporn Chaikitmongkol, MD, Adam Wenick, MD, PhD, Susan Bressler, MD
Purpose: To determine how distance visual acuity or near vision (reading acuity, reading
speed, critical print size) of the better-seeing eye alone compares with both eyes open in
patients with choroidal neovascularization (CNV) from age-related macular degeneration
(AMD).
Methods: Participants with unilateral or bilateral CNV from AMD and visual acuity
of at least 20/200 with habitual correction in at least one eye with CNV were identified
prospectively from three university-based retina specialists (NMB, ASW, SBB) and enrolled
after signing documentation of an informed consent process approved by a Johns Hopkins
University Institutional Review Board. Distance visual acuity was measured with habitual
distance correction using 3 different ETDRS Charts for the right eye alone, left eye alone,
and both eyes open. Near vision was measured with habitual near correction with the
right eye alone, left eye alone, and both eyes open using 3 different MNRead charts at
40 cm for reading acuity (smallest print size attempted in logMAR + [total word errors x
.01]), maximum reading speed (mean of 3 fastest reading speeds out of 90% of subject’s
maximum reading speed).
Results: Among 41 participants enrolled, 32 had a better-seeing distance visual acuity
eye (an eye with visual acuity letter score >5 letters better than the fellow eye when both
eyes were better than 20/100, or >10 letters better than the fellow eye when both eyes
were 20/100 to 20/200). Among these 32, only 1 participant (3%, 95% confidence interval
[CI]: 0% to 16%) had better visual acuity with both eyes open than with the better-seeing
eye alone and only 2 participants (6%, 95% CI: 1% to 21%) had worse visual acuity with both
eyes open than with the better-seeing eye alone. In contrast, 6 participants (19%, 95% CI:
7% to 36%) had a higher maximum reading speed using MNRead charts with both eyes
open than with the better-seeing eye alone while 7 participants (22%, 95% CI: 9% to 40%)
had a worse maximum reading speed with both eyes open than with the better-seeing eye.
Conclusions: These results among patients with CNV from AMD suggest, despite
some limitations, reading with both eyes open sometimes is better and sometimes is worse
than reading with the better-seeing eye alone, while distance visual acuity with both eyes
open usually is the same as the better-seeing eye alone.
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The Retina Society
Baseline Retinal Pigment Epithelial Elevation (RPEE) Size
and Intra-Retinal Fluid (IRF) Status Effect on Visual Acuity
(VA) Outcomes in the VIEW 1 and VIEW 2
Chirag Shah, MD, MPH
Boston, MA
On behalf of VIEW 1 and VIEW 2 Study Investigators
Purpose: To determine the effect of baseline (BL) RPEE Size and IRF status on VA
outcomes in the VIEW1 and 2 studies in neovascular AMD (NVAMD) patients.
Methods: 2457 subjects with NVAMD were randomized to: ranibizumab 0.5mg every 4
weeks (Rq4), intravitreal aflibercept (IAI) 2mg every 4 weeks (2q4), 0.5mg every 4 weeks
(0.5q4; not included in this analysis), and 2mg every 8 weeks following 3 initial monthly
injections (2q8). Analysis accounted for slight differences in VIEW 1 and 2 determination
of an RPEE; the RPEE height/size was defined as the sum of width and height. Based on
BL IRF status (absent/present) and RPEE size (0, median, >median), best-corrected visual
acuity (BCVA) outcomes were evaluated in the combined treatment group. Differences in
the methods for determining RPEE size and IRF within each study were accounted for in
this analysis.
Results: There were 1593 patients with available data for which BL IRF status (present/
absent) and 3 groups of RPEE size (RPEE = 0, RPEE median) were determined. At BL,
older age was associated with IRF and BCVA was higher in eyes without IRF. Within each
IRF status level, baseline VA was slightly dependent on the size of the RPEE. An analysis
adjusted for BL evaluations suggested in patients with IRF absent at BL, change in BCVA
from BL at week 52 were: 13.3, 10.9, and 7.5 letters and in without IRF at BL 8.8, 8.6 and
6.4 letters, for groups 1, 2 and 3, respectively. Data suggest BL presence of IRF had a
worsening effect on change in BCVA and change in BCVA decreased with increasing size
of RPEE irrespective of IRF status. The most common ocular AE’s in intravitreal aflibercept
injection group were conjunctival hemorrhage, eye pain, cataract, vitreous detachment,
vitreous floaters, and increased intraocular pressure.
Conclusions: Visual acuity outcomes at week 52 were dependent on both IRF status
and RPEE/PED size at baseline. The presence of IRF and larger RPEE/PED’s at baseline
were associated with worse VA outcomes at week 52 in VIEW 1 and 2 NVAMD patients.
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Toward a Lean Intravitreal Injection Clinic: Implementation
of the Rapid Access Vitreal Injection Guide (RAVI-Guide)
Dennis P. Han, MD
Milwaukee, WI
Ravi Singh, MD
Purpose: We report herein our preliminary experience incorporating the Rapid Access
Vitreal Injection Guide (RAVI-Guide) into intravitreal injection procedures and assessing its
acceptability by practitioners.
Methods: The RAVI-Guide allows intravitreal injection to be done in a single stage
procedure. It functions as a hand-held tension-free lid speculum and measuring device
that can clear the eyelids and lashes from the surgical field of the injection, identify an
injection site 3.5 mm posterior to the limbus, and simultaneously allow the opposite hand
to perform the injection. It can also be used to apply additional antisepsis immediately
prior to injection and to tamponade the injection site immediately afterward. It provides
vitreal access precisely when, where, and for the duration needed, following the “Just-InTime” Lean principle. The RAVI-Guide is being implemented during an intravitreal injection
clinic at the Medical College of Wisconsin and in clinical practice in Kansas City. A postprocedural survey is being used to gauge physician and patient acceptance of the device.
Results: Preliminary findings indicate a favorable acceptance rate, with a portion of
retina specialists at each of the two retina practices wanting to adopt the device for routine
use, and with a large majority of patients giving favorable feedback to the physicians using
the device. At the time of this submission, no adverse events have occurred in an estimated
100 consecutive uses. In a 3.5 hour, 21 patient injection clinic, the RAVI-Guide was
associated with an opportunity for increasing physician-patient face-to-face counseling
time by about 45-60 seconds per patient, or for adding 15-20 minutes of new physician
availability within that session.
Conclusions: Use of the RAVI-Guide showed acceptance levels by physicians and
patients sufficient to justify further introduction into clinical use. The RAVI-Guide appears
capable of facilitating Lean principles and increasing physician availability or physicianpatient interaction in many retina practices.
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The Retina Society
Cost Accounting and Prescribing Patterns of Bevacizumab
Before and After Enforcement of Patient-Specific
Prescription Rules
Baltimore, MD
Purpose: To perform a cost accounting of utilizing bevacizumab for retinal care before
and after enforcement of patient-specific prescription rules (PSPs), and to review the
prescribing patterns of bevacizumab during the same time period.
Methods: Cost accounting of materials and personnel necessary for utilizing
bevacizumab in a retinal practice. Review of prescribing patterns of bevacizumab,
ranibizumab, and aflibercept in the time bridging new enforcement of PSPs in Maryland.
Results: New enforcement of PSPs in Maryland began in November 2012. Cost of
materials including drug ($27.00), shipping/storage ($1.50), and personnel ($3.20) was
calculated to be $31.70. After PSP enforcement additional personnel time ($3.20) was
required for prescribing and handling. Drug “waste” cost of $2.71 was calculated from
observed utilization of 92.8% i.e. 92.8% of all doses could be delivered to the specific
patient on the labeled drug. Total increase in cost was $5.91, a 18.6% increase.
Prescribing patterns 1 year following enforcement of PSPs demonstrated a 36% decrease in
utilization of bevacizumab, a 4% increase in ranibizumab, and a 13% increase in aflibercept.
Conclusions: Enforcement of patient-specific prescriptions for bevacizumab results in
a modest increase in cost. Prescribing patterns during the same time period demonstrated
a dramatic decrease in utilization of bevacizumab in our study. Prescribing patterns may be
altered by factors other than cost.
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95
Influence of Vitreomacular Interface on Anti-VEGF Therapy
using Treat and Extend treatment protocol for Neovascular
Samuel K. S. Houston III, MD
Philadelphia, PA
Nadim Rayess, MD, Michael Cohen, MD, Allen Ho, MD, Carl Regillo, MD
Purpose: The purpose of this study is to determine the influence of the vitreomacular
interface (VMI) on treatment outcomes in patients with neovascular age-related macular
degeneration (nAMD) who are treated with anti-vascular endothelial growth factor (antiVEGF) agents using a treat and extend protocol.
Methods: This was a retrospective, consecutive case series of patients diagnosed with
new-onset nAMD who were treated with anti-VEGF agents with a minimum of one year
of follow-up at Mid Atlantic Retina and the Wills Eye Hospital Retina Service from 2009
to 2013. Following IRB approval, patient records were reviewed for age, gender, visual
comorbidities, visual acuity (VA), anti-VEGF treatment history, and central retinal thickness
(CRT), signs of exudative control, and VMI characteristics determined by spectral domain
optical coherence tomography (SD-OCT). For analysis, patients were divided into 2 groups:
Group 1 had no signs of vitreomacular adhesion (non-VMA) and Group 2 had vitreomacular
adhesion (VMA).
Results: A total of 204 eyes of 181 patients (116 female, 65 male) were analyzed with
153 eyes (75%) in Group 1 and 51 (25%) in Group 2. Baseline mean VA in Group 1 was 0.824
(Snellen equivalent 20/133) with a mean CRT of 350.5 microns. Baseline mean VA in Group
2 was 0.862 (Snellen equivalent 20/145) with a mean CRT of 371.8 microns. Mean VA in
Group 1 was 0.617 (20/83) and 0.504 (20/64) at years 1 and 2, respectively (P <0.01 for
both years). Mean VA in Group 2 was 0.607 (20/81) (P<0.01) and 0.630 (20/85) at years
1 and 2, respectively (P <0.01 for both years). In Group 1, the CRT was 289.71 microns and
267 microns at years 1 and 2, respectively (P <0.01 for both years). In Group 2, the mean
CRT was 305.3 microns and 289.24 microns at years 1 and 2, respectively (P <0.01 for both
years). The mean total number of injections at year 1 for Group 1 was 7.4 compared with
8.4 for Group 2 (P = 0.001). The mean longest extension between injections in the Group
1 was 11.8 weeks compared to 10.1 weeks in Group 2 (P=0.005). For year 2, the respective
mean total number of injections was 5.5 versus 6.7 for the two groups (P=0.027). Finally,
the mean longest extension between injections for Group 1 was 14.1 weeks compared to 12
weeks for Group 2 (P=0.041).
Conclusions: The vitreomacular interface appears to have a significant influence on
anti-VEGF treatment intervals but not visual acuity or exudative control outcomes. Eyes
with VMA on SD-OCT at baseline may require more intensive treatment with decreased
ability to extend treatment intervals.
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The Retina Society
A Systematic Review (Meta-Analysis) of Pro re nata (PRN)
versus Treat and Extend Anti-Vascular Endothelial Growth
Factor (Anti-VEGF) Regimens for Neovascular Age-Related
Macular Degeneration (AMD)
David S. Chin Yee, MD
St. Louis, MO
Thomas Eck, MD, Rajendra Apte, MD, PhD
Purpose: Multiple studies have evaluated PRN and Treat and Extend regimens with
anti-Vegf agents for NVAMD. Good visual outcomes have been reported with either
regimen. However, there is currently no randomized control trial that has reported a direct
comparison between the two treatment modalities; as such we performed a comprehensive
meta-analysis to compare the available literature for efficacy outcomes associated with
both approaches.
Methods: We conducted an exhaustive, systematic review of studies that evaluated the
efficacy of PRN or Treat and Extend regimen for NVAMD by searching CENTRAL, Cochrane
Library, EMBASE, and PUBMED up to November 2013. Included studies were selected
based on study duration of no less than 12 months, availability of outcome data, treatment
protocol for PRN groups following PRONTO criteria and all studies with treat and extend
protocols following the previously reported "inject and extend" regimen. The outcome data
was pooled, and we used Gregori et al conversion from Snellen to ETDRS letter scores to
analyze visual acuity outcomes.
Results: Literature search yielded 1046 peer reviewed articles meeting our initial
search criteria. After further review of the articles by two independent reviewers, 7 studies
meeting treat and extend protocol and 65 studies meeting PRN protocol were included.
The mean improvement in VA in the PRN group was 5.4 ETDRS letters compared to 9.8
ETDRS letters in the Treat and extend group. In the PRN group, an average of 5.6 injections
were received at 1 year compared to 7.6 in the Treat and extend group. CRT improved on
average by 113.5 microns in the PRN group compared to 79.3 microns in the Treat and
extend group. Each outcome of these outcomes were statistically significant. Superiority
of Treat and Extend regimen to PRN treatment in a 12-month period was suggested in this
extensive meta-analysis despite greater interval improvement in CRT in the PRN studies.
Conclusions: This systematic review demonstrated superiority of the Treat and
Extend regimen to PRN treatment in a 12-month period. Randomized clinical trials are
warranted to confirm these findings and further analysis can also be done to compare treat
and extend regimen to monthly therapy.
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97
Long-Term Treatment Outcomes for Neovascular AgeRelated Macular Degeneration using a "Treat and Extend"
Regimen
Nadim Rayess, MD
Philadelphia, PA
Steven Houston III, MD, Arunan Sivalingam, MD, Allen Ho, MD, Carl Regillo, MD
Purpose: To determine long-term treatment outcomes after 2 to 3 years of ranibizumab
or bevacizumab therapy using a “treat and extend” regimen for patients with neovascular
age-related macular degeneration (nAMD).
Methods: Retrospective consecutive case series of 120 eyes of 113 patients who were
diagnosed with treatment naïve nAMD and were treated with either ranibizumab or
bevacizumab for a minimum of 2 years using a “treat and extend” regimen. Patients were
initially treated with monthly anti-vascular endothelial growth factor (anti-VEGF) injections
until there were no signs of choroidal neovascularization (CNV) activity, and were then
extended by intervals of 1-2 weeks as long as no CNVM activity was noted on examination.
Records were reviewed for age, gender, visual acuity, anti-VEGF treatment history and
spectral-domain optical coherence tomography (SD-OCT) was used to document central
retinal thickness (CRT) and CNV activity.
Results: The mean follow-up period was 2.54 years. At baseline, mean Snellen visual
acuity was 20/112 and improved to 20/66 after 1 year of treatment (P<0.001). Mean Snellen
visual acuity remained stable at both 2 years (20/69; P<0.001) and 3 years follow-up
(20/65; P<0.001). At baseline, mean central retinal thickness (CRT) was 326µm and
decreased to 279µm following 1 year of treatment (P<0.001). Mean CRT remained stable
at 2 years (276µm; P<0.001) and 3 years follow up (276µm; P<0.001). Patients received on
average 7.6 injections during the first year of treatment, and over years 2 and 3 received
5.7 and 5.8 injections, respectively. At final follow-up, 93.3% of eyes lost < 3 Snellen lines
and 29.2% of eyes gained >3 Snellen lines. Finally, the average longest duration extended
between injections during year 1 was 11.2 weeks, and for years 2 and 3 were 13.8 weeks and
13.9 weeks, respectively. Conclusions: The “treat and extend” regimen is effective at both achieving and
maintaining visual and anatomical improvements in patients with neovascular AMD for up
to 3 years of anti-VEGF treatment.
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The Retina Society
Bioactive Lysophospholipids Generated by Hepatic Lipase
Degradation of Lipoproteins Activate Complement via the
Classical Pathway
New York, NY
Wanchao Ma, MS, David Paik, MD
Purpose: To determine bioactivity of lysophospholipids generated by degradation of
the lipoproteins VLDL and LDL with hepatic lipase (HL), an enzyme whose genetic locus is
associated with the development of AMD.
Methods: VLDL and LDL were treated with HL and cholesterol esterase (CE) after
immobilization on plates, and complement activation studies were performed with diluted
human serum. C3 fixation, a marker for complement activation, was determined with a
monoclonal anti-human C3d antibody. Enzymatic properties of HL and CE were assayed
with triglyceride and phosphatidylcholine substrates for triglyceride hydrolase and
phospholipase A activities. ARPE-19 cells were employed for viability studies.
Results: HL degradation of human lipoproteins LDL or VLDL results in the formation of
modified lipoproteins that can activate the complement pathway. Complement activation
is dose and time-dependent upon HL and occurs via the classical pathway. Enzymatic
studies suggest that the phospholipase A1 activity of HL generates complement-activating
lysophospholipids. C-reactive protein (CRP), known to simultaneously interact with
complement C1 and CFH, further enhances HL-induced complement activation. The
lysophospholipid 1-palmitoyl-sn-glycero-3-phosphocholine can be directly cytotoxic to
ARPE-19 cells.
Conclusions: HL degradation of subretinal lipoproteins, known to accumulate in
the outer retina and in drusen, can lead to the formation of bioactive lysophospholipids
that can trigger complement activation and induce RPE cellular dysfunction. Given the
known risk associations for AMD with HL, CRP, and CFH, this study elucidates a possible
damage pathway for AMD in genetically predisposed individuals, that HL activity may
lead to accumulation of lysophospholipids to initiate complement activation, with CFH
dysregulation exacerbating the effects of this process.
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99
Controlled Extended Release of Ranibizumab from Novel
Ocular Drug Delivery System
Chicago, IL
Christian R. Osswald, BS, William F. Mieler, MD
Purpose: We developed a controlled, extended release ocular drug delivery system
that can release anti-VEGF. Our system consists of poly(lactic-co-glycolic acid) (PLGA)
microspheres suspended within an injectable, thermo-responsive hydrogel that is fully
biocompatible. We have characterized the release of ranibizumab and a model protein,
ovalbumin, from microspheres alone and suspended within hydrogel.
Methods: Ranibizumab and ovalbumin were radiolabeled with iodine-125 and
encapsulated in PLGA 75:25 microspheres, created using a double-emulsion, solvent
evaporation technique. Polyethylene glycol, sucrose, bovine serum albumin, and Mg(OH2)
were incorporated into the microspheres as cryoprotectants, competitive protein for
polymer-water interfaces, and to buffer against the acidic degradation products of PLGA,
respectively. After the double-emulsion process, the microspheres were washed to remove
residual surfactant and solvent. Once lyophilized, microspheres were suspended within a
poly(N-isopropylacrylamide)-based thermo-responsive hydrogel. Encapsulation efficiency
(EE) was defined as the percent-drug within the microspheres relative to initial loading.
Release profiles were measured at 37°C under mild agitation with samples collected at 3, 7,
24, 48, 96, and 168 hours and then weekly. Cumulative release was calculated as a percent
of encapsulated drug. Initial burst (IB) was defined as amount released within the first 24
hours.
Results: Microsphere mean diameter was 7.7±5 m. EE was 21.8±3.9% for ovalbumin
and 92.7±1.65% for ranibizumab. Release for both ovalbumin and ranibizumab occurred in
a pulsatile manner, with release of ovalbumin beyond 17 weeks. By week 5, 34.55±0.95%
of ovalbumin and 53.70±2.16% of ranibizumab had released. Suspending microspheres
within thermo-responsive hydrogel significantly reduced the IB for both ovalbumin and
ranibizumab from 20.2±0.01% to 5.6±0.59% (p=1.610-5) and from 50.3±2.1% to 20±2.5%
(p=7.310-4), respectively, without altering subsequent release. Comparing release
characteristics at 5 weeks, 14.25±0.63% for ovalbumin and 30.50±3.22% for ranibizumab
from microspheres suspended in the hydrogel had released.
Conclusions: Our drug delivery system has a high EE rate for ranibizumab with
prolonged release. Suspending microspheres in our hydrogel reduces IB so that more
drug can be released over time as well as allowed for localization of the microspheres for
delivery to the target site. The proposed delivery system may be a promising treatment
option for delivery of anti-VEGF and may greatly improve current bolus injection therapies.
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The Retina Society
Macular Morphology and Visual Acuity in the Second Year
of the Comparison of Age-Related Macular Degeneration
Treatments Trials (CATT)
Sumit Sharma, MD
Durham, NC
Cynthia A. Toth, MD, Ebenezer Daniel, MBBS, PhD, Juan E. Grunwald, MD,
Maureen G. Maguire, PhD, Gui-Shuang Ying, PhD, Daniel F. Martin, MD,
Glenn J. Jaffe, MD
Purpose: To evaluate the morphologic features on fundus photography (FP) and optical
coherence tomography (OCT) associated with visual acuity in the second year of the
Comparison of Age-Related Macular Degeneration (AMD) Treatments Trials (CATT).
Methods: Eligibility criteria required evidence on fluorescein angiography and
OCT of choroidal neovascularization (CNV) secondary to AMD and visual acuity (VA)
between 20/25 and 20/320 in the study eye. Treatment was assigned randomly to
either ranibizumab or bevacizumab and to 3 different dosing regimens for over a 2-year
period. Spectral domain OCT scans from the 2 year visit were analyzed to determine the
morphologic features associated with visual acuity. A linear regression model was used to
provide estimates of mean VA adjusted for all significant morphologic features.
Results: Among 1185 CATT participants, 993 (84%) had fluid on OCT at baseline and
2-year follow up data. At 2 years, the mean VA (letters) of eyes varied substantially by
the type of subfoveal pathology on FP: 70.6 for no pathology, 74.1 for fluid only, 73.3 for
CNV or pigment epithelial (RPE) detachment, 68.4 for non-geographic atrophy, 62.9 for
geographic atrophy (GA), hemorrhage, RPE tear, or blocked fluorescence and 62.9 for scar
(p<0.0001). Eyes with subretinal fluid (SRF) in the foveal center on OCT had better mean
VA than eyes with no fluid (70.9 vs. 67.0 letters, p=0.006). Eyes with intraretinal fluid (IRF)
in the foveal center had worse mean VA than eyes without any IRF (59.9 vs. 70.9 letters,
p<0.0001). Eyes with retinal thickness <120 microns had worse VA compared to eyes with
retinal thickness 120 to 212 microns and retinal thickness >212 microns (59.4 vs. 71.3 vs. 70.3
letters, p<0.0001). Greater subretinal tissue complex thickness (p=0.03) and greater CNV
lesion area (p<0.0001) were associated with worse VA.
Conclusions: The associations between VA and morphologic features previously
identified through year 1 were maintained or strengthened during year 2. Eyes with foveal
IRF, abnormally thin retina, and those developing subfoveal GA or scar had the worst VA.
SRF was associated with better VA while greater thickness of the subretinal tissue complex
was associated with worse VA.
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101
Morphological Biomarkers Associated with Visual Acuity
Gain and Loss in Eyes with Neovascular Age-Related
Macular Degeneration Treated with Dual Antagonism of
an Anti-PDGF Aptamer, E0030 (1.5 mg), and an Anti-VEGF
agent, Ranibizumab (0.5 mg)
Glenn J. Jaffe, MD
Durham, NC
Purpose: Poor visual acuity (VA) in eyes given anti-VEGF therapy is typically associated
with CNV growth, development of subretinal fibrosis and geographic atrophy. In pre-clinical
models, dual targeting of platelet-derived growth factor (PDGF) and VEGF induces
neovascular tissue regression. PDGF is also a known mediator of fibrosis. We hypothesized
that PDGF/VEGF dual antagonism would induce neovascular tissue regression, and
decrease subretinal fibrosis and RPE atrophy, and thereby improve VA outcome in eyes
with neovascular AMD (NVAMD). Herein, we determined the association of changes
in morphological tissue biomarkers, with VA change from baseline in a large phase 2b,
controlled NVAMD trial investigating combination therapy (anti-PDGF/anti-VEGF) vs.
monotherapy (anti-VEGF).
Methods: Combination therapy (anti-PDGF/anti-VEGF) or monotherapy (anti-VEGF)
was administered for 24 weeks to 449 eyes of enrolled subjects. Optical coherence
tomographic (OCT), fundus photographic (FP) and fluorescein angiographic (FA) images
were obtained and VA was measured at pre-specified intervals. Images were graded in a
masked fashion to detemine subretinal hyper-reflective material (SHRM) by OCT, lesion
area by FA, subretinal fibrosis by FP, and RPE atrophy by FP.
Results: At 24 weeks, the mean VA improvement was 62% greater from baseline in the
combination arm vs the monotherapy arm and 37% of eyes vs. 29% gained >3-ETDRS lines
respectively; in eyes that gained > 3 letters, and treated with combination vs monotherapy,
SHRM resolved in 53.8% vs. 38.1% respectively. 9% of eyes given combination therapy
vs. 21.5 % of eyes given monotherapy lost VA (1-ETDRS); growth of neovascularization
in this group was 15% vs. 42.5% respectively. 21% of eyes given combination therapy vs.
51% of eyes given monotherapy with VA loss (0-ETDRS Letter loss) developed subretinal
fibrosis. RPE atrophy developed in 15.8% vs. 20.8% of eyes given combination therapy vs.
monotherapy.
Conclusions: Enhanced VA outcome with dual antagonism of PDGF/VEGF is
associated with resolution of SHRM. PDGF antagonism may also improve longer-term visual
prognosis by inhibiting formation of subretinal fibrosis, reducing neovascular tissue growth.
Confirmatory phase 3 trials with a sample size of approximately 1900 patients are currently
underway.
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The Retina Society
Interim Results from a Phase 2 Study of Squalamine Lactate
Ophthalmic Solution 0.2% in the Treatment of Neovascular
Rockville Center, NY
Thomas A. Ciulla, MD, Michael J. Elman, MD, Roger Vogel, MD, Jason S. Slakter, MD,
Peter K. Kaiser, MD, Irach B. Taraporewala, PhD, Samuel Backenroth
Purpose: To determine if topical Squalamine Lactate ophthalmic solution 0.2% BID
administered in combination with Ranibizumab PRN can safely improve visual outcomes
and reduce treatment frequency of Ranibizumab compared to Ranibizumab PRN
monotherapy in patients with treatment naïve neovascular AMD.
Methods: Phase 2, prospective, randomized, double-masked, placebo-controlled,
multicenter study in treatment naïve patients with CNV due to AMD measuring  12 disc
areas, OCT central subfield thickness 300 microns with subretinal fluid or cystoid macular
edema, any lesion composition, and BCVA of 20/40 to 20/320. Diabetics without diabetic
retinopathy were included. All patients received Ranibizumab at baseline and then were
randomized 1:1 to either topical Squalamine Lactate 0.2%BID (combination group) or
placebo vehicle solution BID (monotherapy group). Patients were followed monthly for 9
months. Retreatment with Ranibizumab (PRN criteria) was performed if OCT demonstrated
cystoid macular edema, intraretinal or subretinal fluid, or significant RPE elevation. Safety
analysis was also performed.
Results: A total of 142 patients were enrolled. This pre-specified, interim analysis was
performed when >50% (n=62) of the planned 120 enrollment had completed the 9 month
study. Mean baseline BCVA was 59.8 letters (~20/63 Snellen). Mean total lesion size on
FA was 8.5 mm2 or 3.4 disc area equivalent with 33/62 (53.2%) having some classic CNV
component and the remainder occult only lesions. At the end of study visit (week 38), the
mean change in BCVA in the squalamine combination group (n=29) was +10.4 letters vs
+6.3 letters in the Ranibizumab PRN monotherapy group (n=33), a 65% relative benefit
of topical squalamine. Three line or more improvement in vision was seen in 48.3% in the
combination group vs 21.2% in the monotherapy group. Four line or more gain was seen
in 27.6% vs 6.1% in the monotherapy group, and ≥5 line gain was seen in 17.2% vs 3% in the
monotherapy group. There was no difference in frequency of Ranibizumab retreatment
between the groups, with a mean of 6.2 and 6.4 injections administered in the squalamine
combination and Ranibizumab monotherapy arms, respectively. No safety issues were
identified. Additional demographic and subgroup outcome analyses will be presented.
Conclusion: Topical squalamine lactate 0.2% BID used with Ranibizumab administered
PRN demonstrated marked improvements over Ranibizumab monotherapy in mean gain
in visual acuity and percentage of patients gaining  3 lines, 4 lines, and 5 lines of
vision. Squalamine topical combination therapy with anti-VEGF injections was comparable
to reported visual improvements using an anti-VEGF/anti-PDGF intravitreal combination
approach but with fewer injections.
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103
Vitrectomy Induced Cataracts May Well Be Prevented
New York, NY
Shlomit Schaal, MD, Martin O'Toole, MD, Andrea Gobin, MD
Objective: To report the ability of a biocompatible photopolymerizable gel to
prevent cataract formation after vitrectomy surgery.
Methods: A biocompatible photopolymerizable gel was developed to seal off the
crystalline lens against oxygen diffusion to avoid cataract formation after vitrectomy. It’s
capability to prevent cataract formation in vitro and in vivo was tested. A composite
hydrogel was formulated to meet the following preset criteria: viscoelasticity; spreadability;
smoothness; ability to polymerize in situ; optical clarity; cohesiveness to remain adherent
to lens capsule; iso-osmolarity; biocompatibility; oxygen impermeability; refractive index
close to lens; surface energy >40 dyne/cm to avoid protein and cell adhesion; elastic
modulus >40 N/m2 to preserve lens accommodation, and biodurability. The gel was tested
on ex-vivo porcine lenses for its ability to prevent cataract formation. The gel was also
tested in vivo by coating porcine lenses during live animal 25-gauge vitrectomy surgery
with gas/fluid exchange. Six month follow up was performed using slit lamp examination
and electroretinograms to compare between the groups of vitrecomized uncoated lenses
control eyes with vitrectomized hydrogel coated lenses study eyes.
Results: The custom-designed and specifically engineered gel was composed of several
components to provide all the necessary properties for maintenance of a relatively hypoxic
state near the crystalline lens while being optically transparent and isotonic to the vitreous.
Ninety different permutations of the ingredients were tested for their conformity to the
required criteria. The optimum results were obtained by mixing 100 mg/mL PEG (6000 Da)
with 10 mg/mL of HA (viscosity 5200 mP.sec) and photoinitiating under green LED source
with Irgacure 2959 that was dissolved at 0.1 g/mL in 70% EtOH and added to PEG-polymer
solutions to complex with the acrylate groups on the PEG molecules in a 1.2/1 ratio. The
resultant clear (265-800 nm) gel had perfect spreadability, leveling, coverage, durability
and cohesiveness with a thermally stable (25-37 °C) refractive index of 1.33, surface energy
of 66 dyne/cm, and elastic modulus of 41.4 N/m2. Gel resisted protein and cell adhesion,
and reduced oxygen diffusion by 34 times. The biogel also proved to be biocompatible
with porcine lenses in the ex vivo studies and significantly delayed the development of
lenticular opacities without any apparent side effects. In vivo, the gel proved to be inert,
non-toxic, and non-inflammatory and was able to significantly prevent cataract formation
after surgery. Videos clearly demonstrated the significant difference between control eye
and the study in every pig.
Conclusion: New technology of intra-operative injection of spreadable gels to coat
the crystalline lens during vitrectomy surgery is currently emerging for post vitrectomy
cataract prevention. Formulated biogels can limit oxygen diffusion to crystalline lens. This
novel technology eliminates tedious head-down positioning and cataract formation after
vitrectomy surgery.
104
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The Retina Society
Macular Edema from Retinal Vein Occlusion (CRAVE):
Results of a Prospective Multicenter Randomized Clinical
Trial
Gaurav K. Shah, MD
St. Louis, MO
Rithwick Rajagopal, MD, PhD, Kevin Blinder, MD, Harpreet Walia, MD,
Amol Kolkarni, MD, Sapna Gangaputra, MD, Mike Altaweel, MD
Purpose: Intravitreal injection of vascular endothelial growth factor antagonists has
become first line treatment for macular edema from retinal vein occlusions, but differences
between agents have not yet been systematically studied. We performed the CompaRison
of Anti-Vascular Endothelial Growth Factor Therapy in Macular Edema from Retinal VEin
Occlusion (CRAVE)trial to compare efficacy of monthly intravitreal injections of 0.5 mg
ranibizumab with 1.25 mg bevacizumab for treatment of macular edema from retinal
vascular occlusion.
Design: Prospective, randomized, multicenter clinical trial with OCT analysis performed
independently by the Wisconsin Reading Center.
Participants: A total of 98 naïve patients with macular edema from ischemic and
nonischemic central and branch retinal vein occlusions.
Methods: Eligible patients were randomized in a 1:1 manner to receive either monthly
treatment with 0.5 mg ranibizumab or 1.25 mg bevacizumab. The primary outcome
measure was change in central macular thickness at 6 months compared to baseline.
Secondary outcomes included change in best-corrected visual acuity and change in area of
fluorescein leakage on angiogram at 6 months compared to baseline.
Results: Ninety-eight eyes from 98 patients across 9 institutions were randomized to
treatments. At baseline, mean central foveal thickness (± standard error of the mean) was
521.1 ± 28.9 microns in the bevacizumab group and 503.6 ± 23.7 microns in the ranibizumab
group (P=0.64). Both groups of patients experienced significant reductions in central
foveal thickness at 6 months (bevacizumab, -214.1 ± 42.3 microns; ranibizumab, -239.6 ±
37.9 microns), with no significant difference between treatments (P=0.66). Baseline visual
acuity was similar in both groups (bevacizumab, 0.76 ±0.06 logMAR; ranibizumab, 0.73 ±
0.07 logMAR). There were similar effects on change in visual acuity at 6 months between
drugs, with a 0.33 ± 0.07 logMAR change in the bevacizumab group and a 0.34 ± 0.06
logMAR change in the ranibizumab group (p=0.38). No drug-related adverse events
occurred in either group throughout the protocol.
Conclusions: In the treatment of macular edema from retinal vein occlusion, we find
equivalent effects of bevacizumab and ranibizumab in reducing macular thickness and
improving visual acuity at 6 months. Sustained equivalence of efficacy between these
drugs will be evaluated after 1 year of treatment with both agents, at the conclusion of
this study.
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105
Barnes Foundation
saturDAY
106
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The Retina Society
saturday, September 13 | 8:00 Am
Evidence that Macular Degeneration is Not Simply a Disease
of the Posterior Pole
Pittsburgh, PA
S.V. Sadda, MD, G. Bencic, MD, E. Chew, MD, Z. Vatavuk, MD, V. Jurisic Friberg, MD,
R. Danis, MD, et al.
Purpose: Age-Related Macular Degeneration historically was characterized as a disease
of the posterior pole. We imaged the peripheral retina in hundreds of AMD patients and in
many controls to determine the frequency of occurrence and extent of peripheral retinal
changes in these cohorts.
Methods: In an AREDS II ancillary investigation, the OPERA Study (Optos PERipheral
retinA), wide angle imaging was performed at several sites on 442 eyes of particpants
to document their peripheral retinal findings. These images were overlain with a custom
grid to divide each image into zones: Zone 1 (area between arcades), Zone 3 (peripheral
to arcades), and Zone 2 (region between 1 and 3). At a separate European site (Zagreb,
Croatia) 150 subjects with AMD and 150 age matched controls were similarly imaged.
Wide-field flurescein angiography was obtained in the AMD eyes at this site as well. Trained
readers documented morphological abnormalities found within each zone including
drusen size and number, hypo- and hyperpigmentation, cobblestone degeneration, and
the presence of reticular pigment degeneration. Comparisons between AMD subjects and
controls were made for the Croatian site.
Results: In AREDS II subjects, reticular pigment degeneration was found in Zone 2 in
26.5% of eyes and in superior Zone 3 in 31.7% of eyes. Drusen were present in Zone 2 in 75%
of eyes, and in Zone 3 in 56% of gradable eyes. Reticular drusen were present in 15%, and
1% of eyes in the same regions. Cobblestone degeneration was seen in Zone 3 superior in
6.8% of eyes.
In Croatia, any peripheral reticular pigmentation degeneration (PREP) was found in 41% of
AMD eyes and 15% of control eyes (P<0.05). The extent of this degeneration in total clockhours was significantly greater in AMD eyes vs control eyes p=0.0001). PREP was more
easily seen on FA than on color images. With respect to wet versus dry AMD eyes, PREP
did not occur more frequently in Wet AMD. Paving stone degeneration was found in 18%
and 3% of AMD versus control eyes respectively. The presence of any peripheral drusen as
seen on color images occurred in 189 of AMD subjects versus 108 of controls (P=0.0001).
Conclusions: The retinal periphery is affected with degenerative changes such as
drusen, paving stone degeneration, and reticular retinal pigmentation more commonly
in AMD eyes compared to controls. AMD does not appear to be a disease solely of the
posterior pole. DNA analysis of our subjects is forthcoming and may link the phenotypic
changes that we describe to the genetic make-up of our subjects.
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Diagnosis of Cognitive Impairment and Alzheimer’s Disease
using Integrated Assessments of Retina Structure and
Function
Kansas City, MO
Jeffrey Burns, MD, Peter Koulen, PhD, Nelson Sabates, MD, Gary Galliimore, COMT
Purpose: Early diagnosis of Alzheimer’s Disease (AD) and mild cognitive impairment
are extremely difficult due to the complete lack of accepted detection methods and the
difficulty to screen for early disease reliably and unambiguously. Since the retina is both
functionally as well as developmentally part of the brain, there is good rationale to expect
structural and functional changes in the retina similar to the rest of the brain. Our study
builds on previous clinical evidence that changes in the structure and function of the retina
occur in AD patients.
Methods: Patients were prospectively assessed neurologically by mean mini mental
state exam scores and standardized dementia rating scales for early stage cognitive
impairment and mild to moderate AD when compared to age-matched controls. Spectral
domain optical coherence tomography (SD-OCT) was used to assess the integrity of the
neural retina. Micoperimetry was used to assess the functional integrity of the retina. This
study was IRB approved.
Results: By identifying a unique combination of structural parameters and combining
them with a distinct array of functional measures, both the areas of needed sensitivity
and of needed power of discrimination between early stage cognitive impairment, AD and
other diseases were successfully addressed. As both sets of parameters were acquired
simultaneously, the logistical problem of temporal and spatial registration of findings does
not play a role. The complementary assessment of retina structure and function indicated
a high predictive value for clinical diagnosis and monitoring of disease progression and
therapy success.
Conclusions: The study indicates that integrating Spectral Domain Optical Coherence
Tomography with microperimetry generates a matrix of patient-specific parameters that
produce a unique and AD-specific “fingerprint” of structural and functional changes in
the retina enabling diagnosis without invasive or subjective measures and provides also
and more importantly diagnosis of early stage cognitive impairment. Advancing these
diagnostic methods will facilitate and enable independent strategies for the prevention or
early treatment of AD in order to avoid irreparable late-stage damage.
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Incidence of Sustained Ocular Hypertension Using
Prepackaged Versus Freshly-prepared Intravitreal
Bevacizumab Injections for the Treatment of Neovascular
Jason Hsu, MD
Philadelphia, PA
Philip Storey, MD, MPH, Vincent Ho, MD, Steven Yeh, MD, Benjamin Leiby, PhD,
Mitchell Fineman, MD, et al
Purpose: To compare the incidence of sustained ocular hypertension (OHT) following
intravitreal injections of prepackaged versus freshly-prepared bevacizumab monotherapy
for the treatment of neovascular age-related macular degeneration (AMD).
Methods: A retrospective, comparative case series was performed of 1216 patients
with neovascular AMD treated with intravitreal bevacizumab (IVB) monotherapy at two
retina practices using different preparations of bevacizumab between January 1, 2009 and
December 31, 2011 were reviewed. Data recorded included demographics, ocular diagnoses,
lens status, number of bevacizumab injections, and intraocular pressure (IOP) at each visit.
Results: A total of 740 eyes in 634 patients were included and 14 eyes (0.81% incidence
per eye-year) developed sustained OHT. For eyes without preexisting glaucoma, 7 of 298
eyes (1.11% incidence per eye-year) injected with prepackaged bevacizumab developed
sustained OHT compared to 3 of 361 eyes (0.32% incidence per eye-year) injected with
freshly-prepared bevacizumab, a difference that was not statistically significant (incidence
rate ratio: 3.43; 95% confidence interval: 0.68-17.30; p=0.14). Regardless of bevacizumab
preparation, increasing number of injections was associated with significantly higher
incidence of sustained OHT for eyes without preexisting glaucoma: 3 of 457 (0.66%) for
eyes receiving 1-10 injections compared to 7 of 202 (3.5%) for eyes receiving 11+ injections
(p=0.011). For eyes with preexisting glaucoma, 3 of 41 eyes (3.52% incidence per eye-year)
injected with prepackaged bevacizumab developed sustained OHT compared to 1 of
40 eyes (1.12% incidence per eye-year) injected with freshly-prepared bevacizumab,
a difference that was also not statistically significant (incidence rate ratio: 3.14; 95%
confidence interval: 0.33-29.88; p=0.32). Regardless of bevacizumab preparation, incidence
of sustained OHT was significantly higher for eyes with preexisting glaucoma (4 of 81 eyes;
2.29% incidence per eye-year) compared to eyes without preexisting glaucoma (10 of 659
eyes; 0.64% incidence per eye-year) (incidence rate ratio: 3.58; 95% confidence interval:
1.09-11.81; p=0.036).
Conclusions: Incidence of sustained OHT following intravitreal bevacizumab is low
with no statistically significant difference between prepackaged and freshly-prepared
injections. Regardless of bevacizumab preparation, increasing number of injections as well
as a history of preexisting glaucoma was associated with significantly higher incidence of
sustained OHT.
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One Year Results of a Phase 1 Study of the Safety and
Tolerability of Combination Therapy Using Sustained
Release Intravitreal Triamcinolone Acetonide and
Ranibizumab for Subfoveal Neovascular Age-Related
Jennifer I. Lim, MD
Chicago, IL
Marcia Niec, BS, Vernon Wong, MD
Purpose: To investigate safety and evidence of efficacy of IBI-20089, an intravitreal,
injectable liquid sustained drug delivery system formulated with triamcinolone acetonide
(TA) in combination with ranibizumab for choroidal neovascularization (CNV) secondary to
age-related macular degeneration (AMD).
Methods: Patients received a single intravitreal injection of IBI-20089 containing either
6.9 mg (25 ul) TA (Cohort 1) or 13.8 mg (50 ul) TA (Cohort 2) followed one week later by an
intravitreal injection of 0.5 mg ranibizumab. A sequential cohort dosing scheme was used.
Patients were seen monthly and underwent best corrected visual acuity testing, slit lamp
biomicroscopy, dilated ophthalmoscopy, fundus photos and optical coherence tomography
(OCT). Patients received pro re nata (PRN) monthly dosing of ranibizumab.
Results: Ten patients ranged in age from 59 to 81 years old (mean 73.4 years). Six
patients had received prior treatment with ranibizumab (range 4 to 16 injections; median
9) and 4 were treatment naÏve. Mean baseline OCT CST was 406 u (median 324 u) in
Cohort 1 and 291 u (median 286 u) in Cohort 2. All patients completed one year follow-up.
All patients showed a substantial drop in OCT CST as early as one week following therapy.
No serious related adverse events occurred. Ocular adverse events included mild elevation
of intraocular pressure (IOP) in 8 patients and cataract progression in 3 of the 5 phakic
patients. At one year, 30 of a total 120 (25 %) possible PRN re-Rx’s had been given.
Combination therapy resulted in a median number of 3.5 re-treatments at and including
month 12.
Conclusions: Combination therapy using IBI-20089 and ranibizumab was welltolerated and resulted in a lower rate of ranibizumab retreatments. Transient IOP elevation
and cataract progression occurred.
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Systematic Review of Safety Across the Phase 2 and 3
Clinical Trials of Intravitreal Aflibercept Injection
David S. Boyer, MD
Los Angeles, CA
Purpose: To systematically review safety including intraocular inflammation (IOI),
hypertension (HTN), and adjudicated Antiplatelet Trialists’ Collaboration (APTC)
events from randomized trials of intravitreal aflibercept injection (IAI) for 4 indications:
neovascular age-related macular degeneration (AMD), macular edema following central
retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO), and diabetic macular
edema (DME).
Methods: Patients were included from 8 phase 2/3 trials across 4 diseases: wet AMD
(CLEAR-IT 2 [52 weeks], VIEW 1, and VIEW 2 [96 weeks]); CRVO (COPERNICUS [100
weeks], GALILEO [76 weeks]); BRVO (VIBRANT [24 weeks]); DME (DA VINCI, VIVID, and
VISTA [52 weeks]). Data were analyzed in terms of number of events/person-years at risk
(PYR). Rates were calculated as events per 100 PYR. Different time periods across the trials
were evaluated to account for dosing regimen and comparator variability.
Results: Over 4000 patients contributed over 5400 PYR. At baseline, age ranged from
22-99 years and the majority were female (~60%) in the AMD studies. For the remaining
studies, the proportion of females ranged from 38%-46%. The incidence of HTN varied
from 10 per 100 PYR in wet AMD to 47.8 per 100 PYR in BRVO. The rates of all other
events studied were low. There were no meaningful differences between rates for IAI and
comparators or between fixed and alternative dosing. The IOI rates were 1.96 (IAI) and 3.07
(RBZ) in wet AMD, 1.134 (IAI) and 2.79 (sham) in CRVO, 2.38 (IAI) and 1.11 (laser) in DME,
and 0 (IAI and laser) in BRVO. The overall rates of HTN for the controls were 14.5 per 100
PYR vs. 12.7 for IAI. For adjudicated APTC events, the highest rates were observed in DME
and the lowest in CRVO. The overall rates were both 1.9 per 100 PYR in the controls and IAI,
respectively.
Conclusions: Data from phase 2/3 trials of IAI demonstrate that rates of selected
ocular and systemic adverse events were low for both fixed and alternative IAI dosing
regimens and were similar to controls. Compared to the controls studied, IAI was generally
well tolerated in patients in these AMD, CRVO, DME, and BRVO trials.
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Intravitreal Aflibercept Decreases the Volume of
Vascularized PEDs Better than Frequent Retreatment
with Intravitreal Bevacizumab or Ranibizumab
Miami, FL
Mariana Rossi Thorell, MD, Giovanni Gregori, PhD, William Feuer, MS
Purpose: To evaluate the effects of switching from bevacizumab or ranibizumab to
aflibercept in eyes with neovascular AMD requiring frequent retreatment every 4 to 6
weeks.
Methods: A retrospective review was performed on patients with neovascular AMD
undergoing anti-VEGF therapy for at least one year with persistent or recurrent macular
fluid requiring retreatment every 4 to 6 weeks with intravitreal bevacizumab or ranibizumab
prior to the switch to intravitreal aflibercept. Patients were followed for at least 6 months
after the switch. All patients were treated using a treat-and-extend strategy, and the
treatment interval immediately after the switch was the same as the interval immediately
before the switch. Best-corrected visual acuity (BCVA), number of injections, and SDOCT
imaging measurements were collected.
Results: A total of 72 eyes of 64 patients with neovascular AMD met the inclusion
criteria. The mean duration of anti-VEGF therapy prior to the first aflibercept injection
was 44.5 months (range 13.8-104.7). The mean number of total injections was 30.5 for the
entire treatment period prior to the switch and 9.9 for the 12 months prior to the switch.
The average number of anti-VEGF injections was reduced by 0.58 during the 6 months
after the first aflibercept injection compared with the 6 months prior to the first aflibercept
injection (p<0.001). BCVA increased by 0.5 letters during the 6 months after the switch
to aflibercept, which was not statistically different from the 1.0 letter increase during the
6 months before the switch to aflibercept (p=0.75). Central retinal thickness (CRT) did
improve from 257.4 microns to 239.7 microns during the 6 months after the switch to
aflibercept (p<0.001). Seventy of the 72 eyes had vascularized retinal pigment epithelial
detachments (PEDs). When compared with the change in PED cube-root volume 6 months
before the switch (+0.02 mm), the change in PED cube-root volume 6 months after the
switch to aflibercept (-0.07 mm) was statistically significant (p=0.007).
Conclusions: The volume of vascularized PEDs, the number of injections, and the
CRT decreased significantly following the switch to aflibercept in eyes undergoing frequent
reinjection using a treat-and-extend treatment strategy.
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One-year Results from the ROLL Trial: Aflibercept for
Patients with Recalcitrant PEDs Related to Wet Age-Related
Nashville, TN
John Kitchens, MD, Sarah Hines
Purpose: This report describes the one-year results from the ROLL trial. The subjects
in ROLL are participating in a two-year, open-label, prospective trial using aflibercept for
persistent pigment epithelial detachments (PEDs) due to wet AMD. All ROLL subjects
previously completed a two-year, prospective trial of monthly ranibizumab prior to directly
enrolling into the current study. Resolution of the PED, timing of treatments, safety, and
efficacy is evaluated.
Methods: ROLL is an on-going prospective, unmasked, three-center trial that evaluates
the conversion of the subjects from high-dose ranibiuzmab (1.0mg or 2.0mg) to standarddose aflibercept (2.0mg) in patients with a PED related to AMD. Upon entry into ROLL,
patients received three monthly doses of aflibercept followed by on-label, bi-monthly
treatment and the potential of monthly treatment if the PED or sub/intraretinal fluid on
OCT was persistent or there was a 5 letter ETDRS loss from a previous visit. This reports
includes the Nashville, TN and Lexington, KY sites.
Results: Sixteen patients had one-year data and were included in this analysis. During
the first year, there were 80 potential PRN injections. A total of 5 injections (6.3%) were
skipped in 3 patients. The remaining 13 patients received monthly aflibercept during the
first 12 months of ROLL. At the 12 month timepoint, the mean ETDRS letter change +1.5 and
the median letter change was +0.5 letters. One subject had a single episode of bilateral
vitritis and vision loss following bilateral aflibercept injections. This resolved with topical
therapy and the subject elected to continue treatment with aflibercept in the study. This
subject has not had a recurrent episode of vitritis.
Conclusions: A majority of subjects in ROLL have maintained vision and have needed
monthly treatment following conversion from high-dose ranibizumab to standard-dose
aflibercept. Less than bimonthly treatment appears to be necessary to maintain vision in
this subset of patients with vascularized PEDs in the setting of wet AMD.
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Type 3 Neovascularization: Evolution, Association with
Pigment Epithelial Detachment, and Response to Therapy
as Revealed by Spectral-Domain Optical Coherence
Tomography
Aaron Nagiel, MD, PhD
Los Angeles, CA
K. Bailey Freund, MD, Richard F. Spaide, MD, Jesse J. Jung, MD, Kavita Bhavsar, MD,
Giuseppe Querques, MD, PhD, David Sarraf, MD
Purpose: To demonstrate the maturation and treatment response of Type 3
neovascularization in eyes with age-related macular degeneration (AMD) using spectraldomain optical coherence tomography (OCT).
Methods: We retrospectively analyzed 30 eyes with Type 3 neovascularization and
AMD for which spectral-domain OCT images were obtained over an extended period of
follow-up. Eyes with coexistent Type 1 and Type 2 neovascularization were excluded from
the study.
Results: In 16 eyes, spectral-domain OCT imaging captured the development of early
Type 3 neovascularization from punctate hyper-reflective foci at the outer nuclear layer/
outer plexiform layer junction. The more mature Type 3 lesions appeared as round hyperreflective complexes emanating from the deep capillary plexus and associated with outer
retinal disruption and adjacent cystoid macular edema. In addition, 27/30 (90%) Type 3
lesions were associated with an underlying retinal pigment epithelial (RPE) detachment,
of which 17 (63%) were drusenoid, 6 (22%) were serous, and 4 (15%) were mixed. In all 10
cases associated with sub-RPE fluid, the Type 3 vessels appeared to leak fluid into the PED
cavity, creating serous PEDs as large as 925 microns in maximal height. Treatment with
intravitreal anti-vascular endothelial growth factor (VEGF) agents led to prompt involution
of the lesion and resorption of the intraretinal and sub-RPE fluid typically after 1 or 2
injections. Following treatment, 47% of cases exhibited focal outer retinal and RPE atrophy.
Conclusions: In some eyes with AMD, Type 3 neovascularization originates from the
deep capillary plexus and matures into a vascular complex adherent to the RPE. The lesions
leak fluid into the retina and in some cases beneath the RPE, creating a serous pigment
epithelial detachment. In contrast to Type 1 neovascularization, the Type 3 vessels and their
associated fluid are highly responsive to intravitreal anti-VEGF therapy, often requiring only
1 or 2 injections. Regression of the lesion often reveals photoreceptor and RPE atrophy at
the former site of Type 3 vessels.
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Gap Between BCVA and Low-luminance VA at Baseline
Predicts Treatment Response to Ranibizumab at Year 2 of
the HARBOR Study
Ronald Frenkel, MD
Beachwood, OH
Lawrence Singerman, MD, Howard Shapiro, PhD, Ivo Stoilov, MD
Purpose: This subanalysis of the HARBOR study (NCT00891735) explored the effect
of baseline low luminance visual acuity (LLVA) score on BCVA response to ranibizumab
treatment in patients with subfoveal wet age-related macular degeneration (AMD)
(n=1097).
Methods: Patients were randomized 1:1:1:1 to receive intravitreal ranibizumab 0.5 mg
or 2.0 mg monthly or PRN after 3 monthly loading doses. LLVA was measured by placing
a 2.0-log-unit neutral density filter in front of the study eye and having the participant
read the normally illuminated ETDRS chart. Pearson correlation was used to explore the
relationship between LLVA and BCVA at baseline and over 24 months of treatment (months
[M] 3, 6, 9, 12, 15, 18, 21, and 24).
Results: Mean baseline LLVA was similar across treatment groups (28.2 to 29.3 letters)
and was significantly correlated with baseline BCVA (PP or = 33 letters at baseline gained,
on average, only 2.4 letters in BCVA at M24.
Conclusions: LLVA and BCVA scores demonstrated a robust response to ranibizumab
treatment. The mean change in LLVA from baseline at M24 was greater than the mean
change in BCVA from baseline at M24, suggesting that BCVA measurements underestimate
the effect of treatment on LLVA. While baseline LLVA itself was not associated with a
differential treatment effect, the BCVA-LLVA gap was prognostic for treatment response,
with a wider BCVA-LLVA gap predicting lower BCVA gains, on average, over 24 months of
treatment. Therefore, a smaller BCVA-LLVA gap may be a manifestation of milder retinal
impairment and a predictor of greater capacity for visual function improvement with
ranibizumab therapy.
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saturday, SeptemBer 13 | 9:05 Am
Ocular Coloboma Classification and Examination of
Ultrasound as a Supplementary Measure of Prognosis
Miami, FL
Vincent D. Venincasa, BS, Yasha S. Modi, MD, Hassan A. Aziz, MD, Wei Shi, MS,
Purpose: Congenital ocular coloboma is a condition characterized by missing ocular
tissue in one or more locations since birth. Complications of colobomata include increased
risk of retinal detachment and impaired visual acuity. Currently, colobomatous eyes
are classified based on location of the defect and associated structural abnormalities
(i.e. microphthalmos, microcornia, retrobulbar cysts). In a large patient population, this
classification is reviewed using ultrasound measurements as a supplementary measure
of prognosis.
Methods: This study is a consecutive, non-comparative case series. Medical records
were reviewed from 1976 to 2013 at the Bascom Palmer Eye Institute to identify patients
that had documented coloboma by echography. Patients with morning glory syndrome
were excluded. The study included 66 patients of all ages with at least 1 coloboma for a
total of 91 colobomatous eyes. The data was analyzed statistically using Chi-square test,
student t-test, and Pearson’s correlation.
Results: Bilateral colobomata were present in 25 of 66 patients (37.9%). Retinal
detachment (RD) was present in 26 of 91 (29%) eyes; 3 patients had bilateral RDs (4.5%).
RD was present in 12 of 21 (57%) eyes with coloboma and microphthalmos, representing
an increased risk compared to those without structural abnormalities (p = 0.036). The
presence of a retrobulbar cyst (RC) had no effect on RD risk (p = 0.873): 6 of 20 (30%)
eyes with an RC had an RD while 20 of 71 (28%) eyes without an RC had an RD. The
presence of structural abnormalities (microphthalmos, microcornia or both) was associated
with worse visual acuity (VA) at last follow-up compared to those without structural
abnormality (p = 0.047). RC had no effect on VA (p = 0.92). Coloboma depth (n = 9,
p = 0.83) and coloboma depth to axial length ratio (n = 9, p = 0.72) had no effect on RD
risk, and no effect on VA at last follow-up (p = 0.68, p = 0.99, respectively).
Conclusions: The results of the current study suggest that microphthalmos with
coloboma, but not retrobulbar cyst, is associated with an increased incidence of RD and
worse VA. Visual acuity outcomes are often dependent on the extent of the coloboma and
associated complications. Further analysis is required to support or refute the utility of US
as a supplementary measure of prognosis.
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Acute Macular Neuroretinopathy Following Non-ocular
Trauma: A New Proposal Regarding Pathogenesis
Mark W. Johnson, MD
Ann Arbor, MI
Nicholas D. Chinskey, MD
Purpose: To describe the clinical characteristics and clinical course of acute macular
neuroretinopathy (AMN) following non-ocular trauma and propose a plausible pathogenic
mechanism for this uncommon disorder.
Methods: We retrospectively reviewed medical records of five patients who developed
symptoms and fundus findings suggestive of AMN following trauma to the face or
chest. Imaging studies including optical coherence tomography (OCT), infrared imaging,
fluorescein angiography (FA) and indocyanine green angiography (ICGA) were evaluated.
Multifocal electroretinography (mfERG) was available for a single patient.
Results: All five patients were identified as having AMN based on reddish-brown
macular lesions with corresponding scotomas. In each case, the visual symptoms started
immediately after non-ocular trauma. One patient had partial resolution of symptoms by
six months while the other four had persistent scotomas at last follow-up (ranging from
10 months to 5 years after trauma). There was no leakage of fluid by either FA or ICGA.
OCT imaging within days of the trauma demonstrated focal areas of hyperreflectivity
in the outer plexiform and outer nuclear layers. OCT performed at later time points
showed thinning of the outer nuclear layer and loss of the ellipsoid and outer segment
layers. mfERG demonstrated focal reduction of signal limited to the area corresponding
to the wedge shaped defects. The results of each imaging study were similar to those of
published cases of AMN linked to other causative agents.
Conclusions: The imaging characteristics and clinical courses of our five patients
with AMN following non-ocular trauma were comparable to published cases caused by
other known risk factors. We believe that acute ischemic injury caused by trauma-induced
catecholamine release and involving the deep retinal capillary plexus is the pathogenic
mechanism that most plausibly explains both the time course and clinical features of
traumatic AMN.
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Validation of the Accuracy and Precision of Out-of-Office
Testing for Retinal Disease: New Developments and ClinicoPathologic Correlations
Palo Alto, CA
Seung-Young Yu, MD, Pravin Dugel, MD, David Myung, MD, PhD, Lisa He, MD, MS,
Brian Toy, MD, Robert Chang, MD, et al
Purpose: To assess the feasibility and accuracy of a smartphone-based electronic
method of visual acuity (VA) testing for remote monitoring and clinical research, and to
evaluate its test-retest reliability and concordance in patients with normal vision, as well
ARMD. To assess clinicopathologic correlations in patients testing out of office between
patterns of vision testing and anatomic results. To introduce new modalities including out
of office photography enabled from within an out of office testing app linked to the vision
testing app.
Methods: Visual Acuity was measured with the smartphone-based electronic visual
acuity (SEVA) testing algorithm and both ETDRS distance chart and LEA numbers near
vision chart, on one eye of each of 80 normal and 40 age-related macular degeneration
(AMD) patients (n=120). Reliability and concordance were calculated using the BlandAltman limits of agreement, the coefficient of repeatability (COR), and the intraclass
correlation coefficient (ICC). Results were also compared with in office vision testing and
OCT on another cohort of patients under active anti-VEGF therapy. Finally clincial results
for obtaining color fundus photographs with a smart phone out of the office using this app.
Results: For the SEVA testing, test-retest reliability was high (ICCs=0.976 of all patients,
0.912 of normal subjects, 0.956 of AMD; 95% limits of agreement ± 0.20 logMAR). SEVA
and near VA with LEA numbers chart were highly correlated (r2=0.762 of initial test in
SEVA; r2=0.789 of repeated test in SEVA). SEVA and distance VA by ETDRS were highly
correlated (r2=0.837 of initial test in SEVA; r2=0.859 of repeated test in SEVA). There
were no differences between VA with SEVA and distance VA with the ETDRS chart in
both groups. The most consistent correlation between out of office testing and disease
status was baseline instability which typically preceded declines in vision associated
with worsening oct status. Representative fundus photographs of reasonable quality
demonstrating retinal pathology were able to be taken, and transmitted from physician to
physician from within the app and stored for remote interpretation in a linked database.
Conclusions: Smartphone-based electronic VA testing using the SEVA application
has high test-retest reliability and is in good concordance with ETDRS distance visual
acuity and standard near vision testing. These results can enhance the monitoring and
determination of optimal treatment regimens for patients on anti-VEGF therapy. Additional
functionalities include obtaining fundus photos from within the app using a low cost
adapter that couples an aspheric lens to the phone.
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Anatomic and Functional Outcomes of Symptomatic VitreoFoveal Adhesion. A Pilot Study from the Pan American
Collaborative Retina Study Group
Lihteh Wu, MD
San Jose, Costa RIca
Mauricio Maia, MD, Maria H. Berrocal, MD, J. Fernando Arevalo, MD,
Marta Figueroa, MD, Federico Graue, MD, Roberto Gallego, MD, et al
Purpose: To describe the functional and anatomic outcomes of eyes with symptomatic
vitreo-foveal adhesion (VFA).
Methods: Retrospective multicenter study of 100 eyes with symptomatic VFA and
spectral domain optical coherence tomography (SD-OCT) findings consistent with VFA. All
eyes were graded according to SD-OCT findings. Grade 1 was defined as incomplete cortical
vitreous separation with foveal attachment. Grade 2 was defined as Grade 1 plus intraretinal
cysts or clefts. Grade 3 was defined as Grade 2 plus a foveal detachment. All patients were
followed for at least 6 months.
Results: There were 32 male and 68 female patients with a mean age of 67.4 ± 11.2
years old. Patients were followed for a mean of 20.9 ± 18.2 months. The mean duration of
symptoms was 12.2 ± 24.2 weeks. At baseline the central macular thickness (CMT) was 352
± 124 µm and the mean VFA was 490 ± 457 µm. Also at baseline, 40 eyes had Grade 1, 49
eyes had Grade 2 and 11 eyes had Grade 3. At the last follow-up, the mean CMT was 321 ±
106 µm. After a mean of 8.2 ± 7.8 months, 36 eyes had spontaneous resolution of the VFA
(25 had normalization of the foveal anatomy, 5 eyes developed a lamellar macular hole and
6 eyes developed a full thickness macular hole). In the remaining 64 eyes, the mean VFA size
decreased to 419 ± 402 µm. At the last follow-up, 30 eyes had Grade 1, 29 eyes had Grade 2
and 5 eyes had Grade 3. The best corrected visual acuity improved from 0.40 ± 0.31 logMAR
at baseline to 0.36 ± 0.34 logMAR.
Conclusions: VFA spontaneously resolved in 36% (36/100) of eyes. An unfavorable
anatomic outcome occurred in 30.6% (11/36) of eyes with spontaneous resolution of its VFA.
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Vitreomacular Traction: Clinical Course and Outcomes
Managed by Initial Observation
Miami, FL
Jonathan H. Tzu, MD, Vishak J. John, MD, William E. Smiddy, MD, Adam Carver, MD,
Robert Leonard, MD, Homayoun Tabandeh, MD, et al
Purpose: The purpose of this study is to investigate the clinical course and outcomes of
patients with vitreomacular traction (VMT) and managed initially by observation.
Methods: The current study is a case series of patients with a diagnosis of vitreomacular
traction based on clinical symptoms and findings on spectral domain optical coherence
tomography (SD-OCT) between the years of 2005 and 2013. VMT was graded based on the
degree of distortion of the foveal contour. Grade 1 is incomplete cortical vitreous separation
with attachment at the fovea and visible distortion, Grade 2 is Grade 1 with any intraretinal
cysts or clefts, and Grade 3 is Grade 2 findings with subretinal fluid beneath the fovea.
Follow-up including visual acuity, changes in SD-OCT findings, and timing of the release of
VMT as seen on SD-OCT were recorded.
Results: VMT by SD-OCT from 5 retina clinics was identified in 196 eyes of 160 patients.
Mean age was 73 years and mean time of follow up was 28.4 months. Baseline VMT grading
was the following: Grade 1 - 78 eyes (40%), Grade 2 - 101 eyes (52%), and Grade 3 - 17
eyes (10%). By the last follow-up, spontaneous release of VMT occurred in 65 (33%) of
eyes. Spontaneous release of VMT occurred at a mean of 16.0 months from initial visit and
median of 10.0 months. At baseline, mean logMAR best corrected visual acuity (BCVA)
was 0.27 (20/37) [range 20/20 to 20/200], and at last follow up was 0.26 (20/36) [range
20/20 to 20/400]. Pars plana vitrectomy (PPV) was performed in 8 eyes (4.1%) [6 for
macular hole, 2 for increased VMT] and BCVA outcomes were 20/60 in 6 of 8 eyes.
Conclusions: In the current study, patients generally had a favorable clinical course
when managed by initial observation. Spontaneous release of VMT occurred in 33% of
patients, and PPV was performed in 4.1% of patients by last follow-up.
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Variations and Racial Differences in the Pattern of
Hydroxychloroquine Retinopathy
Palo Alto, CA
Ronald B. Melle, MD
Purpose: Severe hydroxychloroquine (HCQ) toxicity is classically described as a
parafoveal bull’s eye maculopathy. However, there are other patterns of damage and
associations that retina specialists should recognize, lest toxicity be missed or attributed to
incorrect disease.
Methods: Patients from the Byers Eye Institute (Stanford) and Kaiser Permanente
Northern California were studied. The Kaiser patients were part of a large database of
nearly 3500 chronic HCQ users. Clinical measures included 10-2 and other visual fields,
SD-OCT, and sometimes fundus autofluorescence (FAF) and mfERG. Toxicity was judged
by ring scotoma and retinal degeneration that could not reasonably be explained by other
disease patterns, along with high risk HCQ exposure relative to daily dosage and duration
of use.
Results: Out of our population of toxic cases in both institutions (close to 200),
we found that roughly 10% showed the development of ring damage well beyond the
parafovea (10-15° eccentricity). Some cases progressed from parafoveal damage outward,
or vice versa, but many had normal OCT structure in the central macula. Furthermore, 90%
of these patients were of Asian origin (including Filipino and Indian), and most others were
Black or Hispanic. Confirmation of the extent of damage required 30-2 fields, wide-angle
photography or FAF, and wide or eccentric SD-OCT cross-sections. Several patients were
initially thought to have a periccentral retinal dystrophy.
Conclusions: There are few disorders that produce pericentral retinal degeneration,
and diseases like pericentral RP or MIDD are too rare to account for the number of cases
we have seen, nor would they account for the striking predominance of Asian eyes.
Furthermore, all of these patients had long HCQ exposure that was fully consistent with
toxic retinopathy. We suspect that genetic differences or melanization can modify the
regional predilection of this drug. It is important that HCQ screening of Asian patients
include not only the central macula, but the region beyond the arcades.
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Choroidal Flecks in Stargardt's Disease Shown by High
Definition Optical Coherence Tomography Imaging Correlate
with Disease Severity
Louisville, KY
Niloofar Piri, MD, Brooke Nesmith, MD, JD
Purpose: To report for the first time the presence of choroidal flecks in Stargardt’s
disease and to investigate the relationship between number of flecks and disease severity.
Methods: Six hundred fifty-seven macular high definition optical coherence tomography
(HD-OCT) scans of patients with Stargardt’s disease were reviewed and evaluated for
presence and number of retinal/choroidal flecks, demographics, central macular thickness
(CMT), visual acuity, and disease duration. A search using PubMed and Google was
performed for published HD-OCT images in Stargardt’s disease, which were then reviewed
for the presence of choroidal flecks.
Results: Choroidal flecks were present in all eyes in the different layers. The mean
number of flecks in each retinal and choroidal layer, in decreasing frequency, were as
follows: Sattler’s 78.61 ± 30.28, Bruch’s membrane/RPE complex 62.38 ± 10.12, outer retina
19.23 ± 7.58, choriocapillaris 12.53 ± 6.35, inner retina 5.23 ± 3.00, and Haller’s 3.23 ± 2.35.
There was an inverse correlation between the number of flecks in Sattler’s layer and Bruch’s
membrane/RPE complex with CMT and visual acuity. Choroidal flecks were identified in
21/23 (91%) of HD-OCT images in Stargardt’s disease in the literature.
Conclusions: Choroidal flecks in Stargardt’s disease, prominent at the level of Sattler’s
layer and the Bruch’s membrane/RPE complex, correlate inversely with visual acuity and
degree of retinal atrophy.
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R AYMON D R . MA RG HE RIO AWA RD
Iron Rescue of Deferoxamine Toxicity in Human Retinal
Pigment Epithelial (RPE) Cells
John B. Miller, MD
Boston, MA
Haijiang Lin, MD, PhD, Evangelos S. Gragoudas, MD, Joan W. Miller, MD,
Demetrios G. Vavvas, MD, PhD
Purpose: Deferoxamine (DFX) is an iron chelator commonly used to treat iron overload
in patients requiring regular blood transfusions. Several ocular complications have been
reported, while in vitro studies have confirmed its toxicity in hepatic, cortical brain cells,
and bovine RPE cells. Our study is the first to examine DFX’s toxicity in an established
human RPE cell line (ARPE19) and whether apoptosis, necrosis, or mineral chelation
mediates toxicity.
Methods: MTT assays and TUNEL staining assessed ARPE19 cell survival. Inhibitors
of necroptosis (Nec-1) and apoptosis (z-Vad), ZnCl2, and FeCl3 were added to our cell
cultures.
Results: DFX toxicity to ARPE19 cells was confirmed by an MTT assay, and verified by
TUNEL staining. No toxicity was observed at 24 hours, but decreased cell survival began
at day 2 and progressed through day 5. There was no significant difference in cell survival
between 0.2, 0.4, and 0.8 mg/mL of DFX. While investigating the role of necroptosis and
apoptosis, we found that neither Nec-1 nor Z-Vad improved cell survival at days 2 and 3.
Before examining whether the chelation of minerals could reduce DFX’s toxicity, we first
checked for direct toxicity of iron and zinc. Zinc alone showed a dose dependent response
with high doses (0.04, 0.08, and 0.16M) demonstrating significant toxicity while lower
doses (10, 20, 40 uM) had no effect on cell survival. Iron alone showed no toxicity at
concentrations of 0.05, 0.1, and 0.2 M.
The addition of zinc to DFX treated RPE cells did not improve cell survival. However, iron
was able to rescue DFX toxicity when used at ratios of 1:1 and 2:1 (Fe:DFX). A favorable
effect was also noted when iron was premixed with DFX two hours before adding to cell
cultures. However, a two day delay in the addition of iron to DFX treated cells was unable
to prevent toxicity.
Conclusions: We are the first to confirm DFX toxicity in a human RPE cell line. DFX
toxicity appears to be time dependent. We found no role for necroptosis or apoptosis in
cell death. However, chelation with iron at specific concentrations rescues RPE cells from
DFX toxicity.
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CHA R L E S L . S CHE P EN S L EC TUR E
Development of Treatments for Retinal/Choroidal Vascular
Diseases
Baltimore, MD
Purpose: The pathway for development of new treatments for retinal/choroidal vascular
diseases is well-established and validated. The purpose is to present the pathway and
illustrate how it is used.
Methods: The first step is development of an animal model that mimics key aspects
of the disease process and is feasible and practical to use. It is then necessary to develop
candidate targets, a process that often involves piecing together bits of circumstantial
evidence often from patients with the disease process. It is then necessary to develop a
specific antagonist to the candidate target and if possible, a knockout of the gene that
codes for the target. The next step is to use the specific antagonist and/or knockout in
the animal model to determine if the candidate target is critical for development of the
disease phenotype. After choosing a route of administration and formulation, safety and
biodistribution must be established. The design of early phase clinical trials is an art,
because while the major goal is to test safety, it is advantageous to test for an efficacy
signal. Mid-phase proof-of-concept clinical trials are critical to make a go/no go decision
and to inform design of registration trials. Successful registration trials validate the target
and validate the animal model that was used in preclinical trials.
Results: Once a target is validated, new strategies to neutralize the target more
completely and for longer periods are tested in the validated model bringing the process
full circle. The circle is repeated many times to optimize neutralization of the validated
target and to try to identify new targets. When good animal models are not available, it is
sometimes necessary to truncate the circle and use patients with the disease as the model
provided there is good safety data for the specific antagonist and there are good efficacy
outcome measures.
Conclusions: Many examples to illustrate these points will be provided.
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saturday, SeptemBer 13 | 1:30 Pm
Initial Treatment and Outcomes of Unilateral and Bilateral
Retinoblastoma in a Midwestern University Pediatric
Oncology Center 1999 – 2013
Cincinnati, OH
Zélia M. Corrêa, MD, PhD, James I. Geller, MD, Todd A. Abruzzo, MD,
John C. Breneman, MD
Purpose: To describe baseline clinical features, initial management, and outcomes of
patients with retinoblastoma encountered in our center between 1/1/1999 and 12/31/2013.
Methods: Retrospective analysis of 108 patients evaluated and managed at our center
during their initial treatment period.
Results: The 108 patients (56 males, 52 females) had a median age at diagnosis of 13.2
months. 65 were unilateral and 43 were bilateral at initial diagnosis. Two of the patients
categorized initially as having unilateral involvement developed retinoblastoma in their
second eye during follow-up. Patients with bilateral retinoblastoma were substantially
younger (median age at diagnosis 7.1 months) than those with unilateral disease (median
age 23.0 months). 19 of 106 patients had a positive family history of retinoblastoma (18 of
the 45 bilateral cases, 1 of 61 unilateral cases); 2 patients were adopted. The International
Classification of Intraocular Retinoblastoma (ICIR) group of the affected eye in the 65
patients with unilateral retinoblastoma was 0 [retinoma] in 1, A in 2, B in 5, C in 6, D in
9, and E in 40. Initial management of these patients consisted of observation [retinoma
case], enucleation in 44, intravenous (iv) chemotherapy in 8, ophthalmic artery infusion
chemotherapy in 7, and focal treatment in 3. The ICIR group of the patients in the bilateral
cases was A/A in 4, B/A in 5, B/B in 6, C/A in 1, C/B in 1, C/C in 2, D/A in 1, D/B in 3,
D/D in 1, E/A in 3, E/B in 7, E/C in 3, E/D in 6 and E/E in two. The patients with bilateral
retinoblastoma were treated initially by IV chemotherapy in 30, enucleation of the worse
eye and IV chemotherapy for the better eye in 8, focal treatments for both eyes in 6, and
enucleation of the worse eye and focal treatments for the better eye in 1. Only 2 patients
have died, one of metastasis and the other of an undefined progressive neuromuscular
disease.
Conclusions: Enucleation was the most common initial treatment for unilateral
retinoblastoma and IV chemotherapy the most common initial treatment for bilateral
retinoblastoma in our Midwestern pediatric oncology center during the past decade.
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Clinical Characteristics of Uveal Melanoma in Patients with
Germline BAP1 Mutations
Mrinali Patel, MD
New York, NY
Margaret M. DeAngelis, PhD, Katie Mayne, BS, Anne Marie Lane, MPH,
Evangelos S. Gragoudas, MD, Ivana K. Kim, MD
Purpose: BAP1 (BRCA1 associated protein 1/ubiquitin carboxy-terminal hydrolase) is
thought to be a tumor suppressor gene with cell cycle regulation activity. Patients with
aggressive uveal melanomas and metastatic uveal melanoma exhibit a high rate of BAP1
mutations in the primary tumor. To date, the role of germline BAP1 mutations on the uveal
melanoma phenotype has not been characterized.
Methods: We sequenced the BAP1 gene from blood samples of 507 patients with uveal
melanoma. Each BAP1 mutation identified was characterized as missense (synonymous
or nonsynonymous), frameshift insertion, frameshift deletion, or nonsense. Previously
validated computational tools (PolyPhen and SIFT (Sorting Intolerant from Tolerant)
analyses) were employed to predict whether nonsynonymous missense mutations were
likely to be damaging to protein function, and whether synonymous mutations were
likely to induce splice site changes. These BAP1 mutations were then correlated to clinical
characteristics of the uveal melanoma.
Results: Of 507 blood samples analyzed, 25 (4.9%) exhibited BAP1 mutations. Of these,
computational analyses predicted that 8 (1.6%) were likely to result in damaged BAP1
protein (2 nonsynonymous missense mutations, 3 insertions, 1 insertion / deletion, and 2
nonsense mutations). Seven of these 8 mutations were novel. The 8 patients bearing these
mutations (“germline BAP1 mutation” group) were compared to the 499 other patients
(“control” group). Patients with germline BAP1 mutations exhibited larger tumor diameters
(15.9mm vs. 12.3mm, p=0.0047), higher rate of ciliary body involvement (75% vs. 21.9%,
p=0.0023), and higher rate of metastases (71% vs. 17.8%, p=0.0031) compared to controls.
There was a trend toward increased likelihood of other co-existing cancers (37.5% vs.
20.2%, p=0.2132) and of family history of cancer (100% vs. 70.3%, p=0.1132) in patients
with germline BAP1 mutations, though these did not reach significance. Patients with
germline BAP1 mutations and controls exhibited no differences in age at diagnosis, gender,
presenting visual acuity, distance of the tumor from the optic nerve or from the fovea, iris
involvement, extrascleral extension, or tumor pigmentation.
Conclusions: Germline BAP1 mutations, though infrequent, are associated with
larger tumors, ciliary body involvement, and increased risk of metastasis, suggesting that
germline BAP1 mutations may portend a poor prognosis in uveal melanoma.
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Ranibizumab in Combination with Proton Beam Irradiation
for Choroidal Melanoma: Interim Results
Ivana K. Kim, MD
Boston, MA
Anne Marie Lane, MPH, Evangelos S. Gragoudas, MD
Purpose: To investigate the safety and tolerability of the anti-VEGF compound,
ranibizumab, in combination with proton beam irradiation for the treatment of choroidal
melanoma
Methods: Forty patients with choroidal melanoma who were to receive proton
irradiation for large tumors (>15mm in diameter and/or >5 mm in height) or smaller tumors
(15mm in diameter and 5 mm in height) located within 2 disc diameters of the optic nerve
and/or macula were enrolled in this open-label study. Participants received ranibizumab
0.5 mg or 1 mg at the time of tantalum ring placement and every 2 months thereafter for
the study duration of 24 months. Outcome measures included the incidence of ocular and
non-ocular adverse events, the proportion of patients with final visual acuity better than
20/200, and other measures of ocular morbidity related to radiation complications.
Results: Fifteen patients were enrolled in the large tumor group and 25 patients in the
small tumor group. Twenty-nine patients have completed the month 12 follow-up (12 large,
17 small) and 16 patients have completed the month 24 follow-up (7 large, 9 small). No
serious ocular or systemic adverse events related to the study drug were observed. At 12
months, 67% of patients in the large tumor group and 100% of patients in the small tumor
group had visual acuity 20/200. At 24 months, 86% of the large tumor patients and 100%
of the small tumor patients had visual acuity 20/200. In those patients with small tumors,
the proportion with visual acuity 20/40 was 92% at baseline, 94% at month 12 and 89% at
month 24. The median central retinal thickness in the small tumor group was 276 microns
at baseline, 247 microns at month 12, and 241 microns at month 24. By month 24, 36% of
patients in the small tumor group had some clinical findings of radiation maculopathy.
Amongst the patients with large tumors, none developed neovascular glaucoma. One
enucleation was performed at patient request.
Conclusions: Ranibizumab in combination with proton beam irradiation for choroidal
melanoma appears safe and well-tolerated. In this small pilot study, high rates of visual
acuity retention were observed at 2 years. Continued follow-up and comparisons to
historical controls are ongoing.
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Treatment of Radiation-Induced Maculopathy
Chicago, IL
Kavitha Sivaraman, MD, Eric Feinstein, MD, Clement C. Chow, MD
Purpose: Radiation maculopathy (RM) is the most common cause of severe vision
loss following brachytherapy treatment of uveal melanoma. To date, no proven long-term
therapy for RM exists. This study compares the treatment efficacy of bevacizumab to
alternating therapy with bevacizumab and intravitreal triamcinolone (IVTA).
Methods: This was a retrospective case series of patients who underwent I-125
brachytherapy for uveal melanoma and were treated for RM by one surgeon, WFM, from
February 2009 to May 2013. Radiation maculopathy was defined as macular edema
with associated findings of exudation and capillary bed disruption. Outcome measures
were changes in logMar visual acuity (VA) and central foveal thickness (CFT) between
bevacizumab group and IVTA group on a monthly basis and between monotherapy group
(bevacizumab) and alternating therapy group (bevacizumab and IVTA) at 6 months.
Results: Sixty-two patients underwent I-125 brachytherapy and 8 developed RM. Four
additional patients were referred to WFM for treatment of RM (total N=12). Five patients
received bevacizumab monotherapy and 7 received alternating therapy after failing an
initial bevacizumab monotherapy trial. The mean age was 63 years (39-79); all were
Caucasians. Average tumor basal diameter was 10.6 mm; height 5 mm. Mean apex dose was
88.6 Gray. Patients developed RM at a mean of 22 months following brachytherapy. The
mean change in VA was 0.12 LogMar in both the bevacizumab and IVTA groups (p=0.49);
the mean reduction in CFT was 68 67.6 microns in the bevacizumab compared to 200 199.8
microns in the IVTA group (p=0.048). At 6 months, the monotherapy group had a 0.34
LogMar change in VA compare to 0.067 in the alternating therapy group (p=0.17). Mean
reduction in CFT was 174.4 microns in the monotherapy group compared to 1510.7 microns
in the alternating therapy group (p=0.38). Adverse events included increased intraocular
pressure controlled on topical glaucoma agents and posterior subcapsular cataracts.
Conclusions: The use of IVTA resulted in a statistically significant reduction in CFT
without corresponding change in VA. Alternating therapy did not lead to a statistically
significant improvement in VA or CFT compared to monotherapy. However, the results
are confounded by a selection bias as patients in the alternating therapy group had failed
initial bevacizumab monotherapy. Alternating bevacizumab and IVTA may be beneficial in
recalcitrant cases of RM.
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Retinal Metastasis from Systemic Cancer in Eight Cases
Philadelphia, PA
Jeffrey F. McMahon, BS, Hatice T. Atalay, MD, Murat Hasanreisoglu, MD,
Purpose: Metastatic tumors to the retina are exceedingly rare. In this presentation we
describe clinical features and outcomes of 8 consecutive patients.
Methods: Retrospective case series.
Results: Over a 40-year period, 8 patients with retinal metastasis were identified.
Seven patients had previous history of systemic cancer including cutaneous melanoma
(n=3), breast cancer (n=2), esophageal cancer (n=1), and lung cancer (n=1). In one case,
cutaneous melanoma was discovered following ocular diagnosis. The mean interval
from primary cancer diagnosis to retinal metastasis was 68 months (median 40 months,
range 0 - 214 months). Initial misdiagnosis as infectious or inflammatory retinitis (n=5),
hemangioma (n=1), choroidal neovascular membrane (n=1), or nerve fiber layer infarction
(n=1) for a mean interval of 5 months (median 5 months, range 0.25-11 months) was
recorded. At presentation, the mean patient age was 63 years (median 59 years, range
45-85 years) and all were Caucasian. Visual acuity was 20/40-20/60 (n=4) or 20/400light perception (n=3). The tumor was unilateral (n=7), involving the macula (n=3) and
mean distance to the foveola was 5 mm (median 4.6, range 0-13 mm). In one case, dense
vitreous blood precluded fundus visualization. The mean tumor basal dimension was 7.7
mm (median 9, range 1.5-12 mm) and mean thickness was 2.4 mm (median 2, range 1-5.6
mm). The tumor appeared white (n=2), yellow (n=4), brown (n=1), or combination (n=1).
The metastasis was located in the inner retina (n=5) or full-thickness retina (n=3), and with
vitreous seeds (n=3), vitreous hemorrhage (n=2), subretinal fluid (n=4), and intraretinal
exudation (n=1). Fluorescein angiography disclosed early retinal hypofluorescence and late
hyperfluorescence with staining. Fine needle aspiration biopsy confirmed the diagnosis
(n=4). Treatment included plaque radiotherapy (n=1) for localized disease or enucleation
(n=3) for extensive vitreous seeding (n=2) or pain (n=1). In 4 pre-terminal patients,
observed was preferred. Metastasis-related death occurred in 5 patients within 1 month in
each case. Of the remaining 3 patients, 2 were alive at 4 and 17 months and one was lost to
follow up.
Conclusions: Retinal metastases are rare, simulate retinitis, and are associated with
poor patient survival.
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Tumors of the Non Pigmented Epithelium of the Ciliary
Body. The Zimmerman Classification Revisited
Philadelphia, PA
Carol L. Shields, MD, Ralph C. Eagle Jr., MD, Kyle Ferguson, MD, and Swathi Kaliki, MD
Purpose: In 1970, Dr. Lorenz Zimmerman delivered the Norman McAlister Gregg Lecture
entitled “The remarkable polymorphism of tumors of the ciliary epithelium”. Therein, he
proposed a classification of these tumors that included congenital lesions (mainly ciliary
body medulloepithelioma) and acquired lesions (mainly adenoma and adenocarcinoma).
The classification was based on histopathologic observations without detailed clinical
information. The purpose of this presentation is to provide further clinical information on
these tumors of the nonpigmented ciliary body epithelium (NPCE).
Methods: Review of personal experience and published literature on tumors of the
NPCE.
Results: Since 1970, there were 43 cases of ciliary body medulloepithelioma, 13 cases
of adenoma/adenocarcinoma, one case of pleomorphic adenocarcinoma and one case
of Fuch’s adenoma of the NPCE seen by the authors. The patients underwent complete
ocular examination with detailed drawings, photography, ultrasound biomicroscopy
and anterior segment optical coherence tomography when available. Our clinical and
histopathologic observations, combined with a literature review, revealed new observations
regarding tumors of the NPCE. Regarding medulloepithelioma, we have learned of
the common associated features of neovascular glaucoma, retrolenticular neoplastic
cyclitic membrane, intralesional cysts, response to surgical resection, radiotherapy, and
association with Dicer-1 mutation, which is an autosomal dominant trait localized to
14q32.13. Patients with DICER-1 mutation are at risk for cancers of the cervix, colon, brain,
testes, ovaries, kidney, thyroid, muscle, synovium, and lung. It was found that 2 of our
patients with ciliary body medulloepithelioma had findings of this syndrome. Regarding
adenoma/adenocarcinoma, improved management with surgical resection (sparing
globe) can be achieved. Pleomorphic adenocarcinoma is a highly malignant variation of
adenocarcinoma of the NPCE. Fuchs adenoma, also termed coronal adenoma, is commonly
found histopathologically, despite its rare clinical visualization, and should be added to the
Zimmerman classification.
Conclusions: Since Zimmerman’s report on histopathologic features of tumors of the
NPCE, there have been numerous publications and further observations, by the authors
and others, on the clinical features and management of these intriguing neoplasms of the
NPCE.
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Cytological Characteristics of Uveal Melanoma
Carlos A. Medina, MD
Bay Village, OH
Charles V. Biscotti, Nakul Singh, Arun D. Singh
Purpose: To report on the cytological characteristics of choroidal melanoma.
Methods: All patients with clinical diagnosis of choroidal melanoma from May 2009 to
July 2012 who underwent prognostication FNAB were included. In this prospective, single
center study of consecutive patients, clinical and diagnostic cytological characteristics of
were analyzed.
Results: A total of 141 FNAB samples of 141 patients. Fifty-three percent of the patients
were male and the average age for all patients was 60 years. Transcorneal (7), transcleral
(69) and transvitreal (63) approaches were used (Table 1).
Of 141 samples, 129 adequate samples where obtained (91 % true positive). These included
121 samples that were positive for melanoma and 8 samples that contained atypical
cells consistent with melanoma. Twelve samples were inadequate (7 unsatisfactory for
interpretation, 2 negative for melanoma, and 3 non-diagnostic atypical cells). Average
tumor height was 6.3mm for adequate samples and 3.3 mm for inadequate samples
(p=0.0001). Median tumor height was 5 and 2.8mm for adequate and inadequate saples
respectively. Sample adequacy was varied significantly (p=0.029) by FNAB approach
(100% transcorneal, 97% transcleral, and 84% transvitreal). Spindle cells were observed in
98% of the samples (63% mixed and 25% spindle only) where as only epithelioid cells were
observed in 2% samples). Melanin was present in 80% of samples (Table 2). Tumor nuclear
grade (atypia) increased with tumor height and by tumor locations (least atypia with iris
tumors).
Conclusions: Cytological features such as spindle cells and melanin which where
present in 98% and 80% of samples respectively are important diagnostic features. Iris
melanoma has bland features as compared to ciliary and choroidal melanoma. Thinner
tumors (less than 3 mm in height) are likely to yield inadequate diagnostic FNAB sample.
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Micro-incisional Vitrectomy Surgery (MIVS) Enables Laser
Tumor Ablation and Fine Needle Aspiration Biopsy (FNAB)
Potentially Avoiding Radiotherapy in Small Uveal Malignant
Melanoma
Timothy G. Murray, MD, MBA, FACS
Miami, FL
Victor Villegas, MD, Aaron Gold, OD, Andrea Wildner, Jennifer Thomson, et al
Purpose: To report the outcomes of a novel treatment strategy targeted to small
ocular malignant melanoma. Primary micro-incisional vitrectomy surgery is utilized to
obtain tissue for molecular genomic analysis coupled with definitive ablation of the tumor
including endolaser, membrane peeling and intravitreal triamcinolone acetonide injection.
This approach enables treatment potentially avoiding radiotherapy in the management of
small ocular melanoma based on molecular genomic risk stratification.
Methods: A consecutive clinical case series of 50 patients with small uveal melanoma
presenting with increasing tumor size and/or increasing exudative retinal detachment
(focal) treated with microincisional pars plana vitrectomy (MIVS) utilzing 23/25 gauge
surgery, membrane peeling, endolaser tumor ablation, 25 gauge multipass fine needle
aspiration biopsy (FNAB/molecular genomics) and intravitreal triamcinolone acetonide.
Molecular genomics were determined for Class 1a/b or Class 2. All patients were evaluated
with pre-surgical widefield photography, sd OCT, echography and ophthalmological
examination and then serially followed at 1, 3, 6, 12, 18 and 24 months. All patients were
followed at 3 to 6 month intervals for metastatic development with an independent medical
oncologist.
Results: Fifty patients presented at a mean age of 65 years (39-86 years). Presenting
BCVA was 20/80. All patients had subretinal fluid (50/50, 100%) while 32 patients had
increasing tumor size (32/50, 64%). Mean pre-treatment tumor apical height was 1.9 mm
(1.2 -2.9 mm). Mean followup was 14 months (6 - 30 months) and BCVA improved to 20/30.
Molecular genomics classification was obtained in 49/50 patients (98%) and was class
2 in only 2 patients (2/50, 4%) One patient developed late post-operative progressive
retinal detachment (1/50, 2%) while one patient developed vitreous hemorrhage (1/50,
2%). No cases of choroidal detachment, hypotony or endophthalmitis occurred. No patient
developed ocular/orbital tumor dissemination, no patient developed metastatic disease and
no patient died during the study window (0/50, 0%).
Conclusions: MIVS pars plana vitrectomy coupled with membrane peeling, endolaser
tumor ablation, FNAB and intravitreal triamcinolone acetonide achieved definitive
molecular genomic analysis coupled with primary tumor ablation in all patients with small
malignant melanoma. This surgical approach enabled the ocular oncologist to deliver
focal tumor ablation while minimize the need for primary radiation treatment. All tumors
were controlled, no tumor dissemination was noted, and no patient developed metastatic
disease in this unique patient cohort. This treatment strategy incorporates advances in both
vitreo-retinal surgical management (MIVS) and uveal melanoma molecular tumor genomics
to achieve tumor control, improved visual function and anatomy for patients with small
malignant uveal melanoma.
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The American Brachytherapy Society (ABS) Consenus
Guidelines for Plaque Brachytherapy of Uveal Melanoma and
Retinoblastoma
Paul T. Finger, MD, FACS
New York, NY
The American Brachytherapy Society — Ophthalmic Oncology Task Force
Purpose: To present the 2014 American Brachytherapy Society Guidelines for Plaque
Brachytherapy of Choroidal Melanoma and Retinoblastoma.
Methods: In a two-year effort, an international, multicenter ophthalmic oncology task
force was assembled to include radiation oncologists, medical physicists and ophthalmic
oncologists. Tasked with producing consensus guidelines for ophthalmic plaque
brachytherapy, the committee included 47 eye cancer specialists from 10 countries. Each
was surveyed as to their current knowledge, practices and quality assurance guidelines.
Their responses were graded by levels of consensus, formed into a manuscript subject to
multiple levels of internal and external peer-review. This resulted in collaborative guidelines
based eye cancer specific world-wide clinical knowledge of the literature and experience.
Results: Consensus was reached that ophthalmic plaque radiation therapy is best
performed in subspecialty brachytherapy centers. Further, quality assurance, methods
of plaque construction and dosimetry should be consistent with the 2012 joint published
guidelines of the American Association for Physicists in Medicine (AAPM) and ABS.
Implantation of plaque sources should be performed by subspecialty trained surgeons.
Though there existed select restrictions related to tumor size and location, the committee
agreed that almost all uveal melanomas of the iris, ciliary body and choroid could be
treated with plaque brachytherapy. However, melanomas with gross orbital extension
> 5 mm, blind painful eyes and those with no light perception vision were unsuitable for
plaque brachytherapy. In contrast, only select retinoblastomas were eligible for primary
plaque brachytherapy. Radionuclide sources currently include assemblies of gold shells with
low-energy photon seeds (iodine-125, palladium-103, cesium-131), or solid ruthenium-106 or
strontium-90 beta-emitting plaques. Prescription doses, dose rates, treatment durations
and clinical methods were described. Subjects in need of future study are defined.
Conclusions: Plaque brachytherapy is an effective, eye and vision-sparing method
to treat patients with intraocular tumors. Practitioners are encouraged to use the 2012
American Association of Physicists in Medicine guidelines for plaque construction,
dosimetry and quality assurance. However, the 2014 consensus American Brachytherapy
Society guidelines for clinical plaque brachytherapy are presented to enhance your
practice.
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Ruthenium Eye Plaques for Uveal Melanoma: Long-term
Clinical Outcome
Arun D. Singh, MD
Cleveland, OH
Gaurav Marwaha, MD, Carlos Medina, MD, Mihir Naik, DO, Matt Ward, MD,
Alan Wilkinson, PhD
Purpose: We have previously reported a dosimetric advantage for Ruthenium 106
(Ru106) versus COMS Iodine 125 (I125) in select patients with small-medium size uveal
melanoma (UM). Here we examine the long-term disease control rates and toxicities for
patients treated with Ru106 plaques.
Methods: Forty-seven patients with primary UM treated with Ru106 eye plaque
brachytherapy from 2005-2009. Bebig “Plaque Simulator” software was used for both
Ru106 and I125 treatment-planning. Dose distributions were calculated for a prescription of
85 Gray (Gy) to the tumor apex. Patients were selected for Ru106 based on reduced dose
to vision critical structures (optic disc and macula) and followed clinically per institutional
protocol for local control (LC), disease free survival (DFS), and overall survival (OS), as
well as for radiation retinopathy and optic neuropathy (ON). Kaplan-Meier analyses were
performed for LC, DFS, OS, and toxicity rates. Univariate analyses with log-rank test and
Cox multivariate analyses were performed to identify factors predicting for DFS and visual
toxicities.
Results: Median follow-up was 58.9 months. Median age of patients was 64.3 years
(range : 26.3-91.1 years). Median apical height of tumors was 3.0 mm (1.5-5.2mm) and
median basal diameter was 10.0 mm (R: 4.5-17.0 mm). Globe preservation was achieved in
96% of patients. 2 patients underwent enucleation and 1 patient had repeat brachytherapy
for local recurrence. 5-year LC was 89% (95% CI: 78.7%-99.1%) with no failures reported
after 24.9 months. 15 patients developed radiation retinopathy, with a 5 year rate of 34%;
and, 4 patients developed radiation ON, with a 5 year rate of 14.3%. Distance (11.61mm vs.
>11.61mm; p=0.008) and dose (5.81 Gy vs. >5.82 Gy; p=0.001) to the optic disc and distance
(11.76mm vs. >11.76mm; p=0.001) and dose (7.93 Gy vs. >7.94 Gy; p=0.007) to the macula
predicted the development of radiation retinopathy or ON.
Conclusions: In the largest reported series for UM patients treated with Ru106 in the
United States, excellent long-term local control was achieved (89%). Toxicities were less
frequent than those reported in I125 series. Use of Ru106 in selected patient population
provides excellent long-term clinical outcomes with reduced local toxicity.
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Long-Term Visual Prognosis After Proton Irradiation of Uveal
Melanomas in Patients at High Risk of Vision Loss
Boston, MA
Anne Marie Lane, MPH, Ivana K. Kim, MD
Purpose: We previously evaluated patients with tumors of any size located within 1
disc diameter (dd) of the optic nerve to determine ocular outcomes after proton beam
therapy. However, the effects of tumor size and location on long-term visual function were
not assessed. We evaluated patients at high risk of visual loss (small and medium tumors
located near the optic nerve and large tumors) to determine long-term visual prognosis
after proton therapy.
Methods: Ninety-four patients with small or medium tumors (>5 mm in height and/
or >15 mm in basal diameter) were included in the analysis. All patients selected for
inclusion had pre-treatment visual acuity (VA) of 20/200 or better in the affected eye
(median VA was 20/40) and at least 5 years of follow-up after treatment. Two endpoints
were evaluated: vision retention of 20/200 or better and vision of counting fingers (CF) or
better. Rates of vision loss were calculated using the Kaplan-Meier method.
Results: Vision remained 20/200 or better in 37% of patients with large tumors 5 years
after radiation therapy and 64% had vision of counting fingers or better. Visual acuity of
20/200 or better was observed in 35% of patients with small and medium tumors located
near the disc, and 77% had visual acuity of CF at 5 years. Large tumors located near the
optic nerve fared poorly, with 14% having vision of 20/200 or better.
Conclusions: Ten years after proton therapy, patients with high risk characteristics
for vision loss maintained VA of CF or better in 45% of patients with large tumors and 59%
of patients with tumors near the optic nerve. Even in the group of patients at greatest risk
(large tumors within 1 disc diameter of the optic nerve) the 10 year rate was 25%.
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Genotype- phenotype Correlation of Patients with Wnt
Pathway Mutations Associated with Familial Exudative
Vitreoretinopathy: A Basis for Genetically Tailored
Management
Royal Oak, MI
Eric Nudleman, MD, PhD, Ahmed Alfaran, MD, Ankoor R. Shah, MD,
Antonio Capone Jr., MD, Michael T. Trese, MD
Purpose: Mutations in four genes in the Wnt Signaling pathway are known to be
associated with Familial Exudative Vitreoretinopathy (FEVR). These include the secreted
ligand Norrin (NDP), its receptor Frizzled-4 (FZD4), the co-receptor low-density lipoprotein
receptor-related protein 5 (LRP5), and the chaperone protein tetraspanin-12 (TSPAN12).
The severity of FEVR varies tremendously within the same family and even between the
eyes of the same person. We sought to determine the phenotypes associated with specific
mutations in an effort to understand the functional significance of the genetic loci involved
in order to direct and improve management of these patients and their families.
Methods: This is a retrospective chart review of all FEVR patients within our practice
with known mutations in NDP, FZD4, TSPAN12 and LRP5. Presenting stage of FEVR and
visual acuity were recorded. The locus of each mutation was compared to other mutations
at the same residue, within the same exon, and with published mutations. The mutations
in NDP and FZD4 were mapped on available structural data to identify key domains and 3
dimensional analysis was performed.
Results: One hundred and thirty eyes from sixty-five patients were included in the study.
Twenty-seven separate mutations in NDP, thirty-three in FZD4, two in TSPAN12, and two in
LRP5 were identified. Seventy-eight percent of patients with mutations in NDP presented
with bilateral stage 5 disease. Structural analysis of these mutations mapped to the pocket
responsible for binding to FZD4. These mutations included residues in all three NDP exons,
with greatest severity noted in the cysteine-knot mutations. Forty-three percent of patients
with mutations in FZD4 presented with bilateral stage 5 eyes. Among them were nine
patients with mutations in the cysteine-rich domain which has been shown to be required
for binding to Norrin. Twenty-three percent of patients with mutations in FZD4 had stage 1
or stage 2 disease and did not require surgery. Mutations in TSPAN12 and LRP5 resulted in
mild disease with only one eye requiring surgery.
Conclusions: The highest proportion of patients with advanced FEVR had mutations
in the binding interface between Norrin and FZD4. Mutations elsewhere in these genes,
or in the LRP5 and TSPAN12 coreceptors, resulted in less severe pathology. The tertiary
analysis confirms the importance of Norrin:FZD4 binding in the development and
maintenance of retinal vasculature. Furthermore, other Wnt ligands capable of binding
the FZD4 receptor are not able to preserve normal angiogenesis and angiomaintenance
in the eye. These data provide insight into the molecular and structural basis of the FEVR
phenotype and correlate disease severity and progression to genetic alterations. From this
data a more tailored approach to patient management is possible.
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Retinal Nerve Fiber Dysfunction in Retinal Degenerations
Ann Arbor, MI
Thiran Jayasundera, MD, Naheed W. Khan, PhD, Kevin Tozer, MD, Kari R. Branham MS,
Timothy Steffins, CRA
Purpose: To report specific retinal dystrophies and degenerations that have nerve fiber
layer (NFL) swelling, presumed axoplasmic stasis, and optic nervehead alterations from the
NFL swelling.
Methods: Only retinal dystrophy patients who have mutation proven retinal diseases
were analyzed, and control OCTs for NFL imaging were obtained from volunteers who had
normal vision and no history of eye disease. Standardized electroretinograms, Goldmann
visual fields, fundus photography, and Spectralis retinal and optic nervehead OCTs were
performed on patients. Nerve fiber thickness was measured at the peripapillary, edge of
disc, and three diameter measurements were obtained at the cribiform plate using standard
software applications. Retinal disease groups were compared to each other and normal
controls.
Results: Nerve fiber thickness correlated with specific diseases e.g., RP ciliopathies
(Usher and RPGR N= 10) are showing thicker NFL and swelling (greater diameters) at the
cribiform plate compared to normal controls (N=10) (average different 300um). Inspection
of 30 ciliopathy RP OCTs that had clinical scans of macula and optic nervehead confirmed
NFL thickening consistent with the above findings; and will be rescanned allowing protocol
measurements, and will be presented.
Conclusions: Ordinarily, the retinal NFL is not considered to be important in retinal
degeneration since it involves neurons that are two synapses distal to the photoreceptors.
With the advent of good quality OCT images, retinal detail can be visualized that is not
available on clinical examination. In surveying the status of the NFL on OCT in a large
number of retinal dystrophies, it became apparent that specific dystrophy patients had
thicker NFLs, and a pattern emerged that specific retinal dystrophies more commonly had
thicker NFLs, that typically extends into the anterior optic nervehead. Measurements of the
cribiform plate-optic nerve diameter were greater than normal in most of the NFL thicken
NFL patients. Compression of the swollen NFL at the cribiform plate could conceivably
contribute to the severity in the visual field loss in these patients.
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Comparison of Circulating MicroRNAs in Aqueous and
Vitreous as Putative Novel Diagnostic Biomarkers for
Diabetic Retinopathy
Sacramento, CA
Amar Patel, MD, Allan Hunter, MD, Leonard Hjelmeland, PhD, Zeljka McBride, PhD
Purpose: To compare the microRNA profiles in aqueous and vitreous and explore the
differences of microRNA species in normal vs. diabetic retinopathy patients as potential
biomarkers.
Methods: Blood, aqueous and vitreous samples were collected from surgical specimens
of 10 controls (macular pucker or macular hole patients) and 20 patients with diabetes (10
patients with Type 2 diabetes with retinopathy, 5 with Type 1 diabetes and 5 with Type 2
diabetes without retinopathy). MicroRNAs were isolated from aqueous and vitreous using
QIAgen microRNeasy kit, quantified on BioAnalyzer, labeled with FlashTag kit and profiled
on Affymetrix GeneChip miRNA 2.0 microarrays. Data analysis was done using GeneSpring
and IPA- Ingenuity Pathway Analysis software.
Results: Comparison of circulatory microRNA population of aqueous and vitreous
humor showed that out of total of 847 miRNA probes on the Affymetrix GeneChip miRNA
2.0, 25 were common for both aqueous and vitreous samples, and an additional 11 being
unique for aqueous, and 7 unique for vitreous. The most abundant common microRNAs
are members of the families hsa miR-218, regulation of vascular patterning and vascular
guidance cues, hsa-miR-193, differentiation of telocytes, stromal cells between blood
vessels and neurons, with a role in intercellular signaling, and miR-let-7, regulation of
retinal Muller glia dedifferentiation and retinal regeneration in teleosts. Our data suggests
that there is a set of circulatory microRNAs which might have differential abundance in
diabetic retinopathy patients compared to controls. TGF-beta pathway is the common
target for microRNAs upregulated in aqueous and vitreous. We identified potential diabetic
pre-retinopathy biomarker miR-20b, whose loss was established in plasma of diabetic
patients, can be detected only in vitreous of diabetic pre-retinopathy patients, and not
in diabetics with retinopathy. On the other hand, established diabetic plasma biomarker
miR-126, which is lost in diabetic patient’s plasma, is not present in aqueous or vitreous.
Conclusions: Comparative profiling of circulatory microRNAs shows that these
molecular species are present in aqueous and vitreous fluids. A small number of circulatory
microRNAs have shown differential presence in normal vs. diabetic retinopathy, offering
promise for further study on use of ocular fluids for further diagnostic or therapeutic
purposes.
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Vision Improvement After Retreatment with an Oral
Synthetic cis-Retinoid (QLT091001) in Subjects with
Inherited Retinal Disease caused by Mutations in RPE65
or LRAT
Baltimore, MD
RET IRD 02 Study Group
Purpose: To assess the visual outcomes and safety of retreatment with QLT091001,
an oral cis-retinoid prodrug, in subjects with inherited retinal disease (IRD) caused by
mutations in RPE65 or LRAT.
Methods: In a multi-center open-label Phase Ib clinical trial, subjects with Leber
Congenital Amaurosis (LCA) or Retinitis Pigmentosa (RP) caused by mutations in LRAT
or RPE65 received up to three 7-day courses of QLT091001 (10, 40 or 60 mg/m2) at
intervals ranging from 1 to 13 months. Enrollment was limited to these IRD subjects who
had received one treatment with QLT091001 in an earlier study. Goldmann visual field
(GVF) and best-corrected visual acuity (BCVA) were assessed at baseline and 7, 14, 30 and
60 days after each treatment course, then bimonthly until the next treatment course. Visual
field response was defined as an increase in GVF retinal area from baseline of at least 20%
in at least 1 eye at 2 consecutive visits within 6 months from the start of any QLT091001
treatment course. Visual acuity response was defined as a BCVA increase from baseline of
at least 5 ETDRS letters in at least 1 eye at 2 consecutive visits within 6 months from the
start of any QLT091001 treatment course. Electroretinograms, OCT retinal architecture,
complete ophthalmic and physical examinations, electrocardiograms and laboratory blood
work were completed to assess safety.
Results: Twenty-seven subjects (7-57 years old) with IRD due to LRAT (N=12) or RPE65
(N=15) mutations were enrolled. Of 71 treatment courses administered, most (approximately
80%) used the 40 mg/m2 dose. Follow-up assessments are ongoing. Preliminary results
in the 27 subjects show that 19 subjects (70%) had a visual field response, and 19 subjects
(70%) had a visual acuity response. For the subset of 15 subjects with RPE65 mutations,
11 subjects (73%) had a visual field response and 8 subjects (53%) had a visual acuity
response. For the subset of 12 subjects with LRAT mutations, 8 subjects (67%) had a
visual field response and 11 subjects (92%) had a visual acuity response. Headache, fatigue,
erythema, photophobia, nausea, flushing and vomiting were reported and reversible
elevations in triglyceride, LDL, cholesterol, AST and ALT levels and reduction in HDL were
recorded. One serious adverse drug reaction (intracranial hypertension) occurred in the
study and was resolved.
Conclusions: Oral retinoid QLT091001 led to improvements in visual function in the
majority of subjects treated in this population with IRD due to mutations in either RPE65
or LRAT. Adverse events were transient and/or reversible.
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Safety and Technical Aspects of Subretinal Injection for
Delivery of Cell and Gene Therapy
Los Angeles, CA
Ian Constable, MD, Mark Blumenkranz, MD
Purpose: To report on the long-term safety profile and the technical aspects of
subretinal injection for the delivery of cell and gene therapy. The subretinal space has
long been recognized as an attractive target for the delivery of cell and gene based
therapeutics. Rigorous safety data compiled from recent early stage clinical trials studying
delivery of relatively low volume (@150µl) injection into the subretinal space may yield
insights into the evolving technical aspects of this procedure.
Methods: Subretinal injection protocols from three ongoing clinical trials are compared.
These trials involve the delivery of therapeutic agents into the subretinal space, one a gene
therapy study using an AAV.sFLT construct designed to induce the RPE to produce and
secrete a naturally occurring anti-VEGF protein into the subretinal space of eyes with active
exudative AMD; the others are cell based therapy studies using human embrj140
yonic stem cell derived RPE in suspension for eyes with atrophic macular degeneration
and Stargardt’s macular dystrophy. Technical issues and long term safety data relating
specifically to the subretinal injection are reviewed.
Results: Combined data report on over 25 eyes with subretinal injections in patients
ranging in age from 40-93 years old. Follow-up ranged from 6-32 months. No cases of
retinal detachment, macular hole or significant immune reactions were observed.
Surgical control of bleb volume and location was satisfactory. Bioavailability can be
influenced by the polymeric composition of injection instrumentation as well as handling of
dead space.
Conclusions: The subretinal space is an attractive target for delivery of cell and gene
based therapeutic agents. Data reported herein suggest that subretinal injection appears
safe and precise. Evolving technique and instrumentation coupled with image guidance
may enhance safety and efficacy of subretinal injection.
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Ultra-Widefield Imaging with Autofluorescence and
Indocyanine Green Angiography in Central Serous
Chorioretinopathy
Claudine E. Pang, MD
New York, NY
Vinnie P. Shah, David Sarraf, K. Bailey Freund
Purpose: To describe the spectrum of ultra-widefield autofluorescence (AF) and
indocyanine green (ICG) angiographic findings in central serous chorioretinopathy (CSC).
Methods: Retrospective analysis of ultra-widefield AF and ICG angiographic images
was performed in eyes with CSC and correlated with clinical findings and spectral-domain
optical coherence tomography (SD-OCT) imaging.
Results: Sixty-five eyes of 37 patients with CSC were imaged using ultra-widefield
AF and 24 of these eyes were imaged using ultra-widefield ICG angiography. In 37 (57%)
eyes, a variety of altered AF patterns extended beyond the posterior 50 degrees of retina
including gravitational fluid tracts. Hyper-AF corresponded to areas of subretinal fluid
(SRF) on SD-OCT and was found to persist in 44 (70%) eyes for up to 8 years despite
resolution of SRF. These areas corresponded to outer retinal atrophy with viable retinal
pigment epithelium (RPE) on SD-OCT and may be explained by the unmasking of normal
background RPE AF. Ultra-widefield ICG angiography revealed dilated choroidal vessels
and choroidal hyperpermeability in areas corresponding to altered AF on ultra-widefield AF
in all 24 eyes. In 20 (83.3%) of these eyes, the dilated vessels were observed in association
with 1 or more congested vortex veins ampullas, suggesting that outflow congestion may
be a contributing factor to the pathogenesis of CSC.
Conclusions: Ultra-widefield AF and ICG angiography imaging in patients with
CSC revealed more widespread disease than evident on clinical examination or standard
field imaging and may be useful for identifying peripheral areas of previous or ongoing
subretinal fluid and choroidal hyperpermeability that can assist in the diagnosis of CSC,
surveillance of recurrent disease and treatment of active disease.
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Inner Retina and Vascular Imaging in Macular Telangiectasia
Using Adaptive Optics
Judy E. Kim, MD
Milwaukee, WI
Drew H. Scoles, BS, Barbara A. Blodi, MD, Christopher S. Langlo, BS,
Kimberly E. Stepien, MD, David V. Weinberg, MD, Joseph Carroll, PhD,
Alfredo Dubra, PhD
Purpose: While macular telangiectasia (Mac Tel) type 2 is characterized by vascular
changes seen on fluorescein angiogram, adaptive optics technology allows non-invasive
imaging of these structures at cellular resolution even without the use of fluorescein
dye. We sought to characterize inner retina and vascular changes in MacTel type 2 using
multimodal imaging.
Methods: Six subjects, average age 59 years, diagnosed with MacTel type 2 at various
stages were imaged in one or both eyes using confocal and non-confocal split-detection
adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral domain optical
coherence tomography (SD-OCT). Vascular perfusion maps were generated as the standard
deviation of split-detection AOSLO image sequences.
Results: In addition to photoreceptor abnormalities, substantial vascular changes
were observed in the inner retinal layers of MacTel patients. Split-detector AOSLO
vascular images and perfusion maps revealed abnormally enlarged and tortuous vessels
in all subjects and microaneurysms in three subjects over the central 3° around fixation.
Numerous microcysts were imaged in all subjects, ranging in size from 2 to 100 m. Splitdetector AOSLO also visualized fibrotic-like structures on the inner retinal surface and
sharply demarcated the cavitations noted with SD-OCT.
Conclusions: The combination of multiple AOSLO imaging techniques with SD-OCT
is useful for non-invasive study of the micro-pathology in MacTel. Split-detection AOSLO
reveals microcyst-like structures, vascular abnormalities, photoreceptor inner segments,
and microaneurysms, all of which could be useful as biomarkers of disease activity and
progression.
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Outer Retinal Tubulation in Advanced Age-Related Macular
Degeneration: Optical Coherence Tomographic Findings
Correlate with Histology
Karen B. Schaal, MD
New York, NY
K. Bailey Freund, MD, Katie M. Litts, BS, Jeffrey D. Messinger, DC,
Christine A. Curcio, PhD
Purpose: To correlate optical coherence tomography (OCT) and histology of outer
retinal tubulation (ORT) secondary to advanced age-related macular degeneration (AMD)
in patients and post-mortem specimens.
Methods: High-resolution OCT raster scans of 43 eyes (34 patients) manifesting
ORT secondary to advanced AMD were correlated with high-resolution histological
sections through the fovea and superior perifovea of donor eyes (13 atrophic AMD and 40
neovascular AMD) preserved 4 hours after death.
Results: ORT seen on OCT correlated with the histologic finding of tubular structures
comprised largely of cones lacking outer segments (OS) and, in some cases, lacking
inner segments (IS). A luminal border was delimited by an external limiting membrane
(ELM) formed by photoreceptors and Müller cells. ORT was observed in closed and
open configurations distinguishable from cysts and photoreceptor islands on both OCT
and histology. Hyper-reflective luminal material seen on OCT represents retinal pigment
epithelium (RPE) and non-RPE cells trapped within the ORT structure. ORT histologic and
OCT findings corresponded in regard to composition, location, shape, and stages in ORT
formation.
Conclusions: Histologic correlation gives a better understanding of ORT formation
and composition relevant to interpretation of the IS/OS junction in SD-OCT. The defining
features of ORT are location in the outer nuclear layer (ONL), an ELM border, and a hyperreflective band on OCT, differentiating it from cysts, and dysmorphic or absent RPE. The
reflectivity of ORT luminal walls on OCT does not seem to require an OS, or an IS-OS
junction, indicating an independent reflectivity source, possibly mitochondria, in the IS.
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Feasibility of Dynamic Optical Coherence Tomography
and Infrared Imaging
Edwin H. Ryan, MD
Minneapolis, MN
Purpose: To review the characteristics of confocal scanning laser ophthalmoscopy
(cSLO) and spectral domain optical coherence tomography (SD-OCT) that make dynamic
tracking and video analysis of tissues (mainly vitreous) following saccades feasible using
these modalities.
Methods: The SD-OCT uses simultaneous confocal scanning laser ophthalmoscopy
(c-SLO) and spectral domain optical coherence tomography (SD-OCT). The c-SLO image is
generated with an 820 nanometer laser, and is 30 x 30 degrees. The speed of acquisition is
such that the 30-degree view is refreshed 9 times per second. SD-OCT runs simultaneously
using an 870 nanometer laser. The SD-OCT acquisition speed is 40,000 A-scans per second
with a scanning depth of 1.8 microns. B-scan acquisition speed for a 30-degree scan width
is 48 B-scans per second in the high speed mode. Both the CSLO and SD-OCT images are
presented real time on a screen during image capture. While being scanned with SD-OCT
for a variety of clinical entities, patients were asked to perform a saccade, then re-fixate.
The vitreous was thus set in motion and the motion could be visualized with both infrared
imaging and SD-OCT, and captured as a movie file.
Results: Patients with vitreous hemorrhage and vitreous opacification were imaged
after saccades, and movement of the opacities was easily seen. In addition, the degree
and severity of shadowing could be estimated relative to normal. Patients with a variety of
conditions including vitreomacular traction, macular hole, evolving vitreous detachment
and others were imaged. In one patient, an open macular hole was not visualized with highdensity scans of the macula, but was seen with dynamic OCT and confirmed at surgery.
Other examples of dynamic infrared and OCT will be shown.
Conclusions: The rapid speed of acquisition allows for observation of tissues in
motion, at a refresh rate fast enough that a movie can be created. 24 frames/sec is
standard for movie theater projectors, and the highest speed OCT is twice this fast.
This rapid acquisition speed for SD-OCT allows it to be used much like dynamic ocular
B-scan ultrasound, albeit with a much greater resolution. The acquisition rate for infrared
was slower (9 frames/sec), but visualization of motion and shadowing from vitreous
hemorrhage and opacities was easily achieved.
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Quantitative Dynamics of Retina Microvascular
Disease Revealed by Adaptive Optics Scanning Light
Ophthalmoscopy
New York, NY
Moataz Razeen, MD, Alexander Gan, MD, Nishit Shah, MD, Alexander Pinhas, MS,
Toco Y. Chui, PhD, Rishard Weitz, BEng, MBA et al
Purpose: Adaptive Optics Scanning Light Ophthalmoscopy (AOSLO), combined with
fluorescein angiography (FA) or motion contrast imaging techniques, is able to reveal
dynamic cellular details of human retinal microvasculature in diseased as well as healthy
eyes. We used AOSLO to study configuration and metrics of microaneurysms (MA), foveal
avascular zones (FAZ), parafoveal capillary bed densities, and capillary lumen dimensions in
eyes with retinal vasculopathies to see how they differ from normal controls.
Methods: AOSLO imaging included simultaneous reflectance (790 nm) and
fluorescence (488 nm) 1.75°, 15 Hz image sequences which were montaged to create 6°
square microvascular maps centered on the fovea. AOSLO FA maps were skeletonized and
divided into regions of interest (ROIs). AOSLO offset pinhole reflectance images were used
to measure lumen diameter (µm) of capillaries forming the FAZ. Attribute quantification
of the FAZ included area (mm2), effective diameter (mm), perimeter (mm) and tortuosity
index (TI). Microneurysm characteristics were defined qualitatively using static and
dynamic imaging modes and sizes were measured with a custom algorithm.
Results: Fifty normal and diseased eyes were imaged. FAZ parameters were largest for
CRVO eyes followed by SCR, DR, and Controls. Tortuosity Index however was highest for
DR eyes, followed by SCR, CRVO, and Controls. FAZ capillary lumen diameter was greater
for diabetic subjects compared to controls.
CRVO fellow eyes revealed subclinical evidence of capillary dropout near the FAZ with
decreased vessel length and density compared to control eyes.
Microaneurysms were classifiable into of 6 configurations which progressed in size- focal
bulge, sacular, fusiform mixed, irregular and pedunculated. While there was no particular
preponderance due to disease type, sacular was most common overall, and MA sizes in
BRVO eyes were generally greater.
Conclusions: AO SLO imaging and analysis methodology appears capable of studying
the complexities of retinal vascular diseases quantitatively and serially. This approach may
help refine evaluation of pathological mechanisms and therapeutic interventions using
sensitive numerical data instead of impressions derived from conventional clinical imaging
technologies.
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Rapid Grading of Fundus Photos for Diabetic Retinopathy
Using Crowdsourcing: External Validation
Christopher Brady, MD
Philadelphia, PA
Andrea C. Villanti, MPH, PhD, Jennifer L. Pearson, MPH, PhD, Thomas Kirchner, PhD,
Omesh P. Gupta, MD, MBA, Chirag P. Shah, MD, MPH, Julia A. Haller, MD
Purpose: To refine and externally validate a novel method for fundus photo grading.
Methods: A crowd-sourcing interface for fundus photo classification developed for
Amazon Mechanical Turk (AMT), including annotated training images was refined based on
user feedback. In Phase 1, nineteen expert-graded images were posted for categorization
into 4 severity categories by anonymous workers (AWs), with 10 repetitions per photo.
Three sequential batches were posted with iterative refinements to the interface. In Phase
2, 400 images from the MESSIDOR public dataset of non-mydriatic fundus photos were
posted using the refined interface from Phase 1, asking graders to categorize the images as
normal or abnormal. The main outcome measure was proportion of images with matching
consensus AW and expert/gold-standard score.
Results: Across 190 grading instances in Phase I, AW consensus accuracy in 4-category
grading increased to a maximum of 52.6% from 26.3%. AW accuracy at categorizing the
images as normal vs. abnormal increased to 100% from a baseline of 89.5%. Throughout,
100% sensitivity for normal vs. abnormal was maintained. Maximum specificity was
85.7%. Across 4000 grading instances in Phase 2, AWs had an overall accuracy of 68.5%.
Excluding the first two MESSIDOR disease categories, level 1 (<5 microaneurysms (MA))
and level 2 (<15 MA or <5 hemorrhages), accuracy increased to 80.9% with a sensitivity
of 92.4% and specificity of 78.0%. Four out of 53 cases (7.5%) of level 3 (15 MA or 5
hemorrhages or neovascularization) retinopathy were missed.
Conclusions: With minimal training, the AMT workforce can rapidly and correctly
categorize fundus photos of diabetic patients as normal or abnormal when a moderate
to severe amount of disease is present. Further refinement is required for AWs to identify
subtle disease, and correctly categorize the level of disease. That worker accuracy was
preserved using a different dataset than that with which the interface was developed is a
critical validation. Images were interpreted for a total cost of $1.10 per eye. Crowdsourcing
may offer a novel and inexpensive means to reduce the skilled grader burden and increase
screening for diabetic retinopathy in resource-poor settings.
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Selective Immediate Sequential Bilateral Pediatric
Vitreoretinal Surgery
Royal Oak, MI
Josh Robinson, MD, Kim Drenser, MD, PhD, Michael Trese, MD
Purpose: To report on a series 6 children (12 eyes) who underwent immediate sequential
bilateral surgery (ISBS). In addition, we sought to assess how widespread the practice of
selective ISBS was among retinal specialists with a special interest in pediatric vitreoretinal
surgery.
Methods: Retrospective chart review, consecutive case series. In addition, a survey of
the Association of Pediatric Retinal Surgeons was conducted to assess the pervasiveness of
selective ISBS in this clinician population.
Results: Same-day consecutive bilateral surgical intervention was performed without
incident. Indications for immediate sequential bilateral surgery in this series included
the need for general anesthesia in the presence of bilateral visually significant posterior
segment pathology (all 6 children), travel for surgery/follow-up care representing a
significant hardship for the family (n = 3 children), and health of the patient limiting surgery
to one surgical encounter in the interest of minimizing systemic risk (n = 3 children). Survey
of the Association of Pediatric Retinal Surgeons indicated that the practice of ISBS in
selected cases is wide-spread.
Conclusions: ISBS is gaining in popularity broadly in ophthalmology, representing
approximately 50% of cataract cases in Finland and widely employed in the United States
for strabismus surgery, ocular adnexal/oculoplastics surgery, LASIK/refractive surgery, for
intravitreal injections, as well as bilateral ruptured globe repair. Cost and convenience issues
aside, the risk of ISBS may be justified when weighed against systemic risk considerations.
This series underscores the feasibility of ISBS in selected cases from global patient care
perspective. Survey of pediatric retinal specialists, indicates that the practice of selective
ISBS is common among pediatric retinal specialists.
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Identification of the Fovea and Diagnosis of Zone by
Fluorescein Angiography in Patients with the Diagnosis of
Retinopathy of Prematurity (ROP)
R.V. Paul Chan, MD
New York, NY
Samir N. Patel, BS, Michael A. Klufas, MD, Karyn E. Jonas, BSN, RN, Susan Ostmo, MPH,
Maria Ana Martinez-Castellanos, MD, Audina M. Berrocal, MD, Michael F. Chiang, MD
Purpose: To examine the utility of fluorescein angiography (FA) in identification of the
fovea and the diagnosis of Zone in patients with the diagnosis of retinopathy of prematurity
(ROP).
Methods: Thirty-two sets (16 color fundus photographs; 16 color fundus photographs
paired with the corresponding FA) of wide-angle retinal images obtained from 16 eyes
of eight infants with ROP were compiled on a secure web site. 10 ophthalmologists (3
pediatric ophthalmologists; 7 vitreoretinal surgeons), with experience in ROP diagnosis
and management, interpreted each image set, provided a diagnosis of Zone, and identified
the fovea. Sensitivity and specificity of Zone diagnosis (I, II, III) was calculated using a
consensus diagnosis, which was determined from assessment of the color fundus images
by three independent readers along with the clinical diagnosis on ophthalmoscopic
examination, as the reference standard. Intergrader agreement of fovea identification was
determined by calculating the mean distance from the center of the optic nerve to the
subject’s marked fovea response.
Results: For 3 of 16 eyes (19%), there was a significant difference in intergrader
agreement of fovea identification between the color fundus photograph and FA. Mean(SD)
sensitivity and specificity for detection of Zone I by the subjects when interpreting the
color fundus images alone was 0.40(0.28) and 1(0), respectively. When interpreting
the color fundus image and FA image set, the mean(SD) sensitivity and specificity was
0.55(0.36) and 1(0), respectively. Subjects agreed with the consensus diagnosis of Zone I
in 38 of 80 responses (48%) using the color fundus images alone and in 59 of 80 responses
(74%) when shown the color fundus image and FA image set. In cases with a consensus
diagnosis of Zone II, subjects agreed with the consensus diagnosis in 76 of 80 responses
(95%) using the color fundus images alone, and in 74 of 80 responses (93%) when shown
the color fundus image and corresponding FA.
Conclusions: There was no statistically significant difference in identification of the
fovea using FA as compared to color fundus photograph alone. Using FA in conjunction
with color fundus images may potentially improve identification of Zone I by experienced
ROP examiners.
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Vascular Endothelial Growth Factor (VEGF) Receptor
Activates and Interacts with the Erythropoietin Receptor to
Cause Pathologic Angiogenesis
Salt Lake City, UT
Haibo Wang, MD, PhD, Zhihong Yang, PhD, Yanchao Jiang, MS
Purpose: Erythropoietin (EPO), used for anemia of prematurity and experimentally as
a neuroprotective agent in diabetes and prematurity, has been reported associated with
pathologic intravitreal neovascularization (IVNV) in conditions associated with elevated
vascular endothelial growth factor (VEGF). We sought to understand the role of EPO in
VEGF-induced pathologic angiogenesis.
Methods: We studied a rat model of oxygen-induced retinopathy (OIR), representative
of human retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR),
and compared it to room-air raised pups of the same developmental ages (RA). In the
OIR model, newborn pups and dams were placed into a controlled oxygen environment,
which increased Müller cell-produced VEGF and caused IVNV at postnatal day (p)18. EPO,
EPO receptor (EPOR), phosphorylated (p-)EPOR and p-VEGF receptor 2 (p-VEGFR2)
were measured using western blot. Co-labeling of lectin-stained retinal endothelial cells
and p-VEGFR2 or p-EPOR was semiquantified by densitometry of retinal sections from
the OIR model. Human retinal microvascular endothelial cells (hRMVECs) stimulated with
EPO, VEGF or control were measured for p-VEGFR2, p-EPOR, p-STAT3 and for proliferation
following siRNA knockdown of EPOR, VEGFR2, or STAT3 compared to control siRNA.
Results: Compared to RA, retinal EPOR, but not EPO, increased in p18 OIR retinas
(p<0.001). p-EPOR was greater in p18 OIR retinas compared to RA and co-localized with
lectin-stained IVNV. In hRMVECs, VEGF up regulated and activated EPOR. Lentiviraldelivered shRNAs that knocked down Müller cell-expressed VEGF (vs. control luciferase
shRNA) reduced IVNV and also p-VEGFR2 or p-EPOR colocalization with lectin-stained
endothelium in the OIR model. VEGF-induced p-VEGFR2 caused an interaction between
p-VEGFR2 and p-EPOR in hRMVECs, and knockdown of EPOR or VEGFR2 with siRNAs
inhibited VEGF-induced EPOR-VEGFR2 interaction and hRMVEC proliferation (p<0.05)
mediated through STAT3.
Conclusions: Our results support the hypothesis that VEGF mediates pathologic
angiogenesis by activating EPOR that causes an interaction between p-EPOR and
p-VEGFR2, which overactivates STAT3 and causes angiogenesis. This pathway may suggest
a role for EPOR signaling in severe ROP and PDR.
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Newborn Eye Screen Testing: Evaluation of Retinal
Hemorrhages, Localization, and Timing of Resolution
Palo Alto, CA
Natalia Fijalkowski, BA, D.R. Fredrick, MD, Jennifer Jones, RN
Purpose: The Newborn Eye Screen Testing (NEST) program at Stanford University
School of Medicine is a multiyear, prospective study determining the incidence and type
of ocular pathology present in newborn infants for the purpose of evaluating whether
early identification and appropriate referral and treatment can reduce the incidence of
amblyopia by age 5 years.
Methods: All newborn infants at Lucille Packard Children's Hospital at Stanford
University School of Medicine greater than 35 weeks post-menstrual age are offered
ophthalmologic screening 24-72 hours after birth. These studies can include wide-angle
digital fiberoptic photographic screening, intraocular pressure assessment, automated
refraction, and optical coherence tomography. The dominant technological assessment is
photographic and the goal is to achieve at least 15 images: one external of the facies, one
of each iris, and five 130 degree views of each fundus, as well as a high magnification 80
degree view of the optic nerve in each eye. Data from each patient is evaluated by a skilled
grader and entered into the Research Electronic Data Capture (REDCap) Database where
it is stored in a HIPAA-compliant fashion. Infants are graded as either normal or abnormal,
and disease pathologies are noted for each abnormal.
Results: In the 8 month period from July 18, 2013 – March 16, 2014, a total of 452 infants
were offered screening, and 170 infants were enrolled (37.6% enrollment rate). Retinal
hemorrhages were noted to occur in 18.2% (n=31) of patients. The right eye was affected
in 21 patients and the left eye in 29 patients: 1quad (n=1 OD, n=5 OS), 2 quad (n=2 OU), 3
quad (n=1 OU), 4 quad (n=17 OD, n=20 OS), macula (n=16 OD, n=23 OS), fovea (n=2 OU),
white-centered subretinal hemorrhage (n=16 OD, n=18 OS), subretinal hemorrhage (n=2 OD,
n=6 OS), and intraretinal hemorrhage (n=3 OD, n=5 OS). In 27 of 31 patients, hemorrhages
resolved by 4 weeks, with pending following up on the remaining 4.
Conclusions: The incidence of retinal hemorrhages in newborn infants is 18.2% in
a prospective consecutive series of healthy term infants. Hemorrhages were more likely
diffuse (4 quadrants), bilateral, white-centered subretinal hemorrhages. Long-term
follow-up is planned to evaluate the potential for amblyopia.
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BENJAMIN FRANKLIN National Memorial
SUNDAY
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151
Sunday, SeptemBer 14 | 8:00 am
Canadian Assessment of Real-world Efficacy and Safety of
Dexamethasone Intravitreal Implant (0.7 mg) in Patients
with Macular Edema
David A. L. Maberley, MD
Vancouver, BC, Canada
Darryl C. Baptiste, PhD, MBA
Purpose: To evaluate the real-world use, efficacy and safety of dexamethasone
intravitreal implant (DEX implant) 0.7 mg in patients with macular edema.
Methods: Patients receiving 1 intravitreal injection(s) of DEX implant for treatment of
macular edema (ME) secondary to retinal disease, and having 3 months of follow-up after
the first DEX implant injection, were identified from medical records for December 2010 to
December 2012 from 10 Canadian retinal practices. Primary efficacy and safety outcomes
included peak mean change from baseline in visual acuity, central retinal thickness (CRT)
and intraocular pressure (IOP) over 2-26 weeks after the last available DEX implant
injection.
Results: One hundred-one patient charts yielded data on 120 eyes diagnosed with DME
(n=34), uveitis (n=23), BRVO (n=19), CRVO (n=11), post-surgery (n=13), or other indications
(n=20). Patients were predominantly elderly (60.9 years), male (65.3%) and hypertensive
(55.4%). Study eyes were mostly pseudophakic (60.8%) having ME 12 months (73.3%).
Baseline mean (±SE) VA, CRT, and IOP were 0.63 (0.3) LogMAR, 474.4 (±18.2) µm and 14.4
(±0.4) mmHg, respectively. During study follow-up, 1.7 (±0.1) DEX implant injections were
administered per eye with a re-injection interval ranging between 2.3–5.0 months. The
mean(±SE) peak change following DEX implant treatment in terms of VA lines, CRT and
IOP was +1.4 (±0.3; PPP=0.9762), respectively. IOP-lowering medication and/or glaucoma
surgery was required in 37.5% and 2.5% of study eyes. Cataract surgery occurred in 28.3%
(13/46) of phakic DEX implant-treated eyes.
Conclusions: DEX implant treatment(s) alone or in combination with other
treatments/procedures resulted in anatomical and functional improvements in eyes with
longstanding ME.
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A Pilot Study of Intravitreal Aflibercept for the Treatment
of Chronic Central Serous Chorioretinopathy: The CONTAIN
Study
John D. Pitcher III, MD
Philadelphia, PA
Andre Witkin, MD, F. Char Decroos, MD, Allen C. Ho, MD
Purpose: To evaluate the tolerability of intravitreal aflibercept injection as a treatment
for eyes with chronic central serous chorioretinopathy (CSCR).
Methods: This six-month prospective randomized pilot study included twelve patients
with chronic CSCR (persistent subfoveal fluid for at least 4-months duration). Patients
received either 6 monthly injections of aflibercept (group 1, n=6) or 3 monthly injections
and 1 injection two months later (group 2, n=6). All were followed with monthly BCVA and
EDI SD-OCT. The main outcome measure was the occurrence of adverse events. Other
outcome measures included mean change from baseline in ETDRS letter score, mean
change in foveal thickness on SD-OCT, mean change in choroidal thickness on EDI SD-OCT,
% of eyes with complete resolution of macular fluid on OCT, and % of eyes with absence of
leakage on FA.
Results: No patients experienced adverse events over the course of the study. All
patients were males aged 29 to 64 years old (median 55). Subfoveal fluid was present on
OCT for a median duration of 6 months (range 4-29) prior to treatment. Baseline BCVA
ranged from 20/25 to 20/160 (median 20/50), with a mean of 62 (sd=13) ETDRS letters.
Post-treatment BCVA ranged from 20/20 to 20/200 (median 20/40), with a mean of 64
(sd=16) ETDRS letters (p= 0.56).
Mean central macular thickness decreased from 400 µm (sd=104 µm) to 306 µm (sd=
94 µm) (p=0.03). Mean subfoveal fluid decreased from 159 µm (sd=93 µm) to 49 µm
(sd=68 µm) (p=0.02). Six of 12 patients (50%) had complete resolution of subfoveal fluid.
Mean choroidal thickness decreased from 307 µm (sd=72 µm) to 263 µm (sd=63 µm)
(p=0.0003). Leakage on FA resolved in eight of 12 patients (75%). There was no statistically
significant difference in visual (p>0.5) or anatomic outcomes (p>0.4) between group 1 and
group 2.
Conclusions: Intravitreal aflibercept was well tolerated over a six month treatment
course for chronic CSCR. No change was observed in visual acuity metrics. Anatomic
trends may suggest some morphologic activity, but randomized, controlled trials are
needed. There were no differences in outcomes between 6 monthly injections or 3 monthly
injections followed by an injection two months later.
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153
Mineralocorticoid Antagonist in the Treatment of Central
Serous Retinopathy
Kapil Kapoor, MD
Virginia Beach, VA
Alan L. Wagner, MD, FACS
Purpose: Central serous chorioretinopathy (CSR) is a sight-threatening condition
that has been associated with endogenous and exogenous glucocorticoids. Recently
overactivation of mineralocorticoid receptor pathways in choroidal vessels has been
implicated in the pathophysiology of CSR. The purpose of this study was to evaluate
mineralocorticoid receptor antagonists in the treatment of CSR.
Methods: A retrospective chart review was conducted of all patients at one center who
were diagnosed with CSR and were started on oral spironolactone or eplerenone with at
least six-week followup. All patients were initially started on spironolactone 50mg PO BID.
Results: Fifteen patients (13 male, 2 female) were included in the study. Mean age was
51.9 years (standard deviation = 11.7). Mean duration of followup on treatment was 12 weeks
(standard deviation = 4.0). Mean baseline BCVA was logMAR = .290 (Snellen 20/39) and
mean post-treatment BCVA was logMAR = .079 (Snellen 20/24) (p<0.05). Mean baseline
CMT on OCT was 267.0 microns and mean post-treatment CMT on OCT was 206.5 microns
(p<0.05). Five patients (33%) had previously failed other treatment (oral Depakote and/
or PDT). Twelve patients had significant resolution of subretinal fluid on initial followup on
spironolactone, and three patients with initial limited improvement were switched to either
spironolactone 50mg TID or eplerenone 50mg BID, with both having subsequent resolution
of subretinal fluid. Five patients (33%) experienced side effects that lead to dosage
reduction (dizziness = 2, blood pressure fluctuation = 2, gynecomastia = 1).
Conclusions: This data supports the use of oral mineralocorticoid receptor
antagonists in the treatment of CSR. There was statistically significant improvement in both
anatomic outcomes on OCT and functional outcomes on visual testing after treatment.
Monitoring for side effects is an important aspect of treatment that clinicians should be
aware of. Prospective randomized controlled trials are necessary to elucidate the precise
role of spironolactone in the treatment of CSR.
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Aflibercept for Recalcitrant Central Retinal Vein OcclusionAssociated Macular Edema Despite Prior Anti-VEGF Therapy
(The ARChiMEDES Trial)
Nashville, TN
Brandon Busbee, MD, Kenneth P. Moffat, MD, R. Trent Wallace, MD
Purpose: To evaluate the clinical effect of monthly aflibercept 2.0 mg in CRVO patients
with macular edema (ME) recalcitrant to other anti-VEGF therapy.
Methods: Prospective, open-label interventional study (Clinicaltrials.gov ID
NCT01857544). Patients with persistent ME associated with CRVO despite active monthly
treatment with ranibizumab or bevacizumab received monthly exams, OCT and intravitreal
aflibercept (IAI). Primary outcome measure was reduction in ME by SD-OCT at 6 mos.
Secondary outcome measures included change in ETDRS BCVA at 3 and 6 mos, extent of
reduction of ME, and adverse events (AE).
Results: To date, 7 patients have been enrolled and actively treated without any
serious AE. In all patients, reduction or elimination of ME was seen after one IAI and was
maintained for six months. ETDRS BCVA (baseline median 20/32) improved in all patients
by 3 mos (median 20/25) and 6 mos (median 20/25).
Conclusions: Monthly injection of aflibercept appears effective in reducing macular
edema and improving visual acuity in CRVO patients who respond incompletely to monthly
treatment with other intravitreal anti-VEGF agents.
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155
Effect of Aflibercept on Refractory Macular Edema
Associated with Central Retinal Vein Occlusion
Allen Chiang, MD
Philadelphia, PA
Alexander Juhn, BA, Samuel K. Houston, MD, James F. Vander, MD, Carl D. Regillo, MD
Purpose: To report short-term visual outcome and anatomical features of patients
who were switched from bevacizumab or ranibizumab to aflibercept for persistent and
refractory macular edema associated with central retinal vein occlusion (CRVO).
Methods: This was a retrospective, consecutive, non-comparative case series of 19
patients diagnosed with macular edema secondary to CRVO who were treated with antiVEGF agents (bevacizumab and ranibizumab), had persistent/refractory macular edema
and were switched to aflibercept treatment. Following IRB approval, patient records were
reviewed for age, gender, visual comorbidities, visual acuity (VA), anti-VEGF treatment
history, and spectral domain optical coherence tomography (SD-OCT) evaluation for
macular edema and central retinal thickness (CRT).
Results: The study included 19 patients (9 male, 10 female) with a mean age of 76 years
(range: 48 – 89). Mean visual acuity at CRVO diagnosis was logMAR 0.91 (20/163) with a
CRT of 568 microns. The average number of injections prior to switching to aflibercept was
11.7 injections (range: 2-40). 21.1% of patients gained 3 or more lines of visual acuity while
26.3% lost 3 or more lines of vision compared with baseline prior to switching therapy.
Mean number of months before switching to aflibercept was 20.8 months. Mean visual
acuity at switch to aflibercept was logMAR 1.01 (20/205) with mean CRT of 581.5 microns.
Mean follow-up from time of switch to last follow-up was 5.4 months. Mean number of
aflibercept injections was 4.1 with a final mean visual acuity of logMAR 0.86 (20/145) and
a CRT of 325.5 microns (P < 0.01). An additional 21.1% of patients had improvement of 3
or more lines of visual acuity, while no patients lost 3 or more lines of vision. Complete
resolution of macular edema, as determined by SD-OCT, occurred in 26% of patients with a
mean change in CRT of -256 microns.
Conclusions: Aflibercept appears to have a beneficial effect on anatomic and visual
acuity outcomes in a subset of patients with macular edema secondary to CRVO that is
refractory to treatment with bevacizumab or ranibizumab.
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REVOLUTIONARY: A Pilot Trial of Combination Peripheral
Scatter Laser and Ranibizumab for Macular Edema
Secondary to Branch Retinal Vein Occlusion
Ivan J. Suner, MD
Tampa, FL
Marc C. Peden, MD, Mark E. Hammer, MD
Purpose: To determine the efficacy, durability, and safety of combination peripheral
scatter laser and ranibizumab in patients with BRVO and macular edema associated with
peripheral retinal nonperfusion on ultrawide-field fluorescein angiography (UWFA).
Methods: A 12-month, randomized, controlled, prospective phase I/II study of 12
patients with BRVO and macular edema associated with peripheral nonperfusion on UWFA.
Patients were randomized to receive six monthly ranibizumab injections + UWFA-guided
peripheral scatter laser (n=6) or six monthly ranibizumab injections (n=6). They were
evaluated monthly for the subsequent six months and additional ranibizumab was given for
recurrences of macular edema.
Results: At 6 months, the treatment group patients had fewer recurrences warranting
retreatment (1/6 vs 6/6, p < 0.001). Mean change in final visual acuity and central foveal
thickness were not statistically significant between groups.
Conclusions: This pilot study suggests safety and durability of this combination
treatment regimen in patients with BRVO and macular edema associated with peripheral
nonperfusion on UWFA.
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157
Real World Vision Outcomes in RVO Treated with
Anti-VEGF injections — An Analysis of EMR Data From
a Large Integrated U.S. Health System
Chesterfield, MO
Hitesh Chandwani, PhD, Arghavan Almony, MD, Henry Ingraham, MD,
Steven J. Marks, MD, Ashley Cole, Joanna Campbell, PhD, Szliárd Kiss, MD
Purpose: Prior claims and registry data analysis have shown less frequent anti-vascular
endothelial growth factor (anti-VEGF) utilization in retinal diseases in clinical practice
compared with landmark randomized controlled trials (RCTs). The purpose of this study
is to examine vision outcomes in retinal vein occlusion (RVO) patients managed with
intravitreal anti-VEGF therapy in clinical practice.
Methods: Electronic medical records of patients with either branch retinal vein
occlusion (BRVO) or central retinal vein occlusion (CRVO) in an integrated health system
in the United States were analyzed. Patient eyes were included if treated with intravitreal
ranibizumab or bevacizumab from Jan 2007 to May 2013, with corrected visual acuity
(CVA) from 20/40 - 20/400 at index treatment (baseline), 12 months follow-up, and at least
one additional CVA reading between 60 and 419 days from baseline. Snellen visual acuities
were converted to the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale using
a published algorithm. Missing CVA data were imputed using the last observation carried
forward (LOCF) approach. Outcomes assessed included number of anti-VEGF injections,
change in CVA from baseline, and proportions of eyes gaining or losing 2 or 3 lines from
baseline at 3, 6 and 12 months. Analyses were performed on observed data and data
imputed by LOCF.
Results: Fifty-seven eyes met the inclusion criteria with mean (SD) BCVA of 54.9 (13.9)
letters at baseline. At 12 months, the mean number of anti-VEGF injections was 4.5; mean
change in CVA was 9.4 letters with proportions of eyes gaining 2 and 3 lines of 49.1% and
35.1% respectively, by LOCF. The proportions of eyes losing 2 and 3 lines were 12.3% (for
both). Outcomes in the observed population were slightly better than the LOCF group with
mean CVA improvement of 11.2 letters at 12 months.
Conclusions: Prior studies show less frequent RVO patient monitoring and antiVEGF injections in clinical practice than landmark RCTs. This study links less frequent
injections to less visual acuity gain in clinical practice than reported in RCTs like CRUISE
and BRAVO. Additional research is needed to assess other potential factors that may result
in underutilization of anti-VEGF injections for RVO patients.
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Two or More Dexamethasone Intravitreal Implants Used
Alone versus with Adjunctive Therapy in Patients with
Macular Edema Secondary to Retinal Vein Occlusion
Daniel B. Roth, MD
New Brunswick, NJ
Antonio Capone Jr., MD, Michael A. Singer, MD, Pravin U. Dugel, MD,
Richard F. Dreyer, MD, David G. Dodwell, MD, John G. Walt, MBA, et al
Purpose: To evaluate the efficacy and safety of 2 or more dexamethasone intravitreal
implants (DEX implants) used as monotherapy versus with adjunctive retinal vein occlusion
(RVO) treatments in patients with macular edema related to branch or central RVO.
Methods: A multicenter (26 sites), retrospective chart review of 289 RVO patients
treated with 2 or more DEX implants was conducted (SHASTA study). Data collected
from the time of the first DEX implant (baseline) to 3–6 months after the last DEX implant
included best-corrected visual acuity (BCVA), central retinal thickness (CRT) by optical
coherence tomography, DEX implant and other RVO treatments and procedures, adverse
events, intraocular pressure (IOP), and cataract and glaucoma surgeries. The present
subgroup analysis evaluated results in patients treated during the study period with DEX
implant alone versus DEX implant and additional RVO treatments.
Results: Mean duration of macular edema was 18.4 months; most patients (86.5%)
had received previous RVO treatments before DEX implant. During the study period, DEX
implant was used as monotherapy in 84 (29.1%) patients and in combination with other
RVO treatments in 205 (70.9%) patients. Mean number of DEX implant injections was 3.1
vs 3.3 in monotherapy vs combination therapy groups (P= 0.344); mean interval between
DEX implant injections was 151 vs 177 days (PP=0.048). No DEX monotherapy patients
underwent glaucoma incisional surgery.
Conclusions: Treatment with 2 or more DEX implants was safe and effective in the
treatment of RVO-associated macular edema, both when used alone and when used in
combination with other RVO treatments. Improvements in BCVA and CRT were generally
similar in the subgroups of patients treated with DEX implant monotherapy versus DEX
implant in combination therapy.
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Long Term Effects of Combination Therapy Using
Anti-Vascular Endothelial Growth Factor Agents (Anti-VEGF)
and Dexamethasone Intravitreal Implant (DEX Implant) for
Retinal Vein Occlusions (RVO)
San Antonio, TX
Darren Bell, MD, Paul Woods, Jason Epolita, Trevor Kreitz
Purpose: To analyze long term effects of combination therapy using anti-VEGF agents
and Dexamethasone Intravitreal (DEX) Implant for RVO.
Methods: A prospective IRB approved study examining patients who received multiple
cycles of combination therapy. Patients were included who had 3 or more DEX Implant
or those who were followed for greater than 15 months. Primary endpoints was duration
between anti-VEGF injections. Secondary endpoints were best corrected visual acuity, 15
letter gainers, reduction of OCT thickness and percent of patients who were dry on OCT.
Safety endpoints were increased intraocular pressure and cataract surgery.
Results: Fifty-five patients met criteria for inclusion in the analysis. The mean fluid-free
interval was 152 days for patients who had recurrent edema. The number of cycles ranged
from 1 to 11. There was no statistically significant difference in cycle length over the course
of the trial (P=NS). Mean best-corrected visual acuity improved 11 letters over the course
of the study. Thirty eight percent of patients (21 of 55) gained 15 letters of vision over the
course of the study. The mean change in OCT thickness was 202um. 84% (46 of 55) of
patients were considered dry (OCT < 290) at some point over the course of the study.
Forty two percent (23 of 55) of patients had an IOP reading of 23 or greater and 12 patients
(22%) had an IOP reading of 30 or greater during the trial. 21 of 38 (55%) eyes of patient
who were phakic at the start of the study required cataract surgery during the course of
the trial.
Conclusions: Combination therapy provides a highly predictable method of treating
patients with retinal vein occlusion. It provides increases in vision without monthly
injections.
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52-Week Results of the VIBRANT Study of Intravitreal
Aflibercept Injection in Macular Edema Secondary to Branch
Retinal Vein Occlusion
Julia A. Haller, MD
Philadelphia, PA
Purpose: The VIBRANT study was conducted to compare the efficacy and safety of
intravitreal aflibercept injection (IAI) with laser grid photocoagulation for the treatment of
macular edema secondary to branch retinal vein occlusion (BRVO).
Methods: VIBRANT was a double-masked, phase 3 trial that randomized 183 treatmentnaïve eyes with unilateral macular edema secondary to BRVO to receive either IAI 2 mg
every 4 weeks or grid laser from baseline to week 20. From week 24 onward, eyes in the
IAI group received IAI 2 mg every 8 weeks and if they required rescue could receive laser at
week 36; eyes in the laser group that required rescue could receive IAI 2 mg every 8 weeks
after 3 initial monthly doses. The primary efficacy endpoint was the proportion of eyes that
gained 15 letters in best-corrected visual acuity (BCVA) from baseline at week 24.
Results: The proportion of eyes that gained >15 letters from baseline to week 24
was 53% and 27% (P<.001) in the IAI and laser groups, respectively. The corresponding
mean improvement in BCVA from baseline to week 24 was 17.0 and 6.9 letters (P<.0001),
respectively. The mean reduction in CRT from baseline to week 24 was 280.5 and 128.8
mm (P<.0001) in the IAI and laser groups, respectively. The most common ocular adverse
events in IAI eyes were conjunctival hemorrhage (19.8%) and eye pain (4.4%). Traumatic
cataract in an IAI eye was the only ocular serious adverse event (SAE) that occurred over
the first 24 weeks of study. The incidence of non-ocular SAEs was 8.8% and 9.8% in the IAI
and laser groups, respectively. One death due to pneumonia and one Anti-Platelet Trialists'
Collaboration-defined event of non-fatal stroke occurred during the first 24 weeks of study,
both in patients in the laser group. The 52-week results will be presented.
Conclusions: Monthly intravitreal aflibercept injections provided significantly greater
visual benefit and reduction in CRT at 24 weeks than grid laser photocoagulation in eyes
with macular edema secondary to BRVO.
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161
Multimodal Imaging Analysis of Deep Capillary Plexus
Ischemia in Central Retinal Vein Occlusion
Ehsan Rahimy, MD
Philadelphia, PA
David Sarraf, MD, Allen Ho, MD
Purpose: To describe the findings of ischemia within the deep capillary plexus in
eyes with central retinal vein occlusion (CRVO) using multimodal imaging, including near
infrared (NIR) and spectral domain optical coherence tomography (SD-OCT) analysis.
Methods: A large database search of patients diagnosed with CRVO was performed
and analysis with NIR and SD-OCT imaging was used to identify eyes demonstrating
paracentral acute middle maculopathy (PAMM), an indicator of associated ischemia of the
deep capillary plexus.
Results: Twenty-five of 484 patients (5.2%) diagnosed with CRVO demonstrated
evidence of concurrent PAMM lesions. All patients showed nonischemic CRVO with
fluorescein angiography (FA), and hyper-reflective plaque-like lesions at the level of the
inner nuclear layer consistent with PAMM with SD-OCT analysis. Corresponding dark grey
lesions with NIR and perivenular deep retinal whitening with color fundus photography
were also noted, but there was no FA correlate to these lesions. These PAMM lesions
indicating ischemia of the deep capillary plexus resolved into areas of INL atrophy and
affected patients noted persistent paracentral scotomas.
Conclusions: Deep capillary plexus ischemia is a significant association of
nonischemic CRVO associated with persistent paracentral scotoma and identified best
with NIR and SD-OCT imaging. This series is the largest to date to describe deep capillary
ischemia and PAMM, and the first to associate this SD-OCT finding with nonischemic CRVO.
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Early Visual Acuity Improvement in RVO Patients Treated
with Ranibizumab in the SHORE Study
W. Lloyd Clark, MD
West Columbia, SC
Pin-wen Wang, PhD, Gary Sternberg, MD, MBA
Purpose: To analyze the time to first clinically significant improvement in best-corrected
visual acuity (BCVA) outcomes in patients with branch or central retinal vein occlusion
(RVO) enrolled in the 15-month, phase IV, randomized SHORE study (N=202). Baseline
demographics and characteristics predictive of early clinically significant VA improvement
were also evaluated.
Methods: From Month (M) 0-6, patients received 7 monthly ranibizumab 0.5 mg
injections. Between M7 and M14, patients continued to receive monthly ranibizumab
injections until the first month at which pre-specified VA and SD-OCT stability criteria
were met. Patients were then randomized 1:1 to continue ranibizumab monthly or switch to
ranibizumab PRN. Approximately 80% of those randomized were randomized by M8; 15%
of patients were not randomized (i.e., discontinued prior to randomization or never met
stability criteria through M14), and continued to receive monthly injections throughout the
study. Kaplan-Meier analyses were conducted to estimate time to first clinically significant
improvement in BCVA defined as gain of > or = 15 letters from baseline or Snellen
equivalent of 20/40 or better. Baseline demographics and characteristics were explored as
predictors of early VA improvement.
Results: 50.5% of all patients achieved 20/40 or better vision at M1, and 70-79% of
patients achieved 20/40 or better vision between M4-15. The median time to achieve 20/40
or better vision was 59 days (excluding 22 patients [10.9%] with 20/40 or better vision at
M0). Baseline factors associated with early improvement to 20/40 or better vision included
larger total macular volume (>9.99 mm3), higher BCVA (>50 letters), and presence of
subretinal fluid. For > or = 15 letters gainers, 39.0% of patients gained > or = 15 letters from
baseline at M1, and 61-71% of patients gained > or = 15 letters between M4-15. The median
time to > or = 15-letter gain from baseline was 63 days. Baseline factors associated with an
early gain of > or = 15-letters included lower BCVA (50 letters) and male gender.
Conclusions: Rapid improvements in VA to 20/40 or better and gain of > or =
15-letters were seen in BRVO and CRVO patients within a median of ~2 months of initiating
ranibizumab therapy. Understanding baseline characteristics that are predictive of early VA
response to ranibizumab treatment may allow retina specialists to better characterize their
RVO patients in clinical practice.
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Real World Vision Outcomes in DME Treated with
Anti-VEGF Injections — An Analysis of EMR Data from
a Large Integrated U.S. Health System
Szilárd Kiss, MD
New York, NY
Joanna Campbell, Arghavan Almony, Herbert Ingraham, Steven Marks, Ashley Cole,
Hitesh Chandwani, Nancy Holekamp
Purpose: Prior claims and registry analyses have demonstrated less frequent antivascular endothelial growth factor (anti-VEGF) utilization in a variety of retinal diseases in
clinical practice compared with landmark randomized controlled trials (RCTs). The purpose
of this study is to further examine real-world visual acuity (VA) outcomes following the use
of anti-VEGFs in the treatment of diabetic macular edema (DME).
Methods: This retrospective analysis of electronic medical records from an integrated
health system in the United States included eyes of DME patients receiving treatment with
intravitreal ranibizumab or bevacizumab from Jan 2007 to May 2013, with best corrected
VA (BCVA) from 20/40 - 20/320 at index treatment (baseline), 12 months follow-up, and
at least one additional BCVA reading after day 60. Snellen VAs were converted to the Early
Treatment of Diabetic Retinopathy Study (ETDRS) scale using a published algorithm. The
number of anti-VEGF injections, change in BCVA from baseline, and proportions of eyes
improving or losing 2 or 3 lines from baseline were assessed at 6 and 12 months. Analyses
were performed on observed data and data imputed by LOCF.
Results: Ninety-four eyes met the inclusion criteria with mean (SD) BCVA of 56.1 (11.9)
letters at baseline. Fifty-four eyes had consistent follow-up at least quarterly. At 12 months,
the mean numbers of anti-VEGF injections was 2.6 and mean change in CVA was 3.7 letters.
Numbers of eyes gaining 2 and 3 lines were 25(26.6%) and 21(22.3%) by LOCF; while
13(13.8%) and 10(10.6%) eyes lost 2 and 3 lines, respectively. BCVA change from baseline
was similar using observed and LOCF measures.
Conclusions: In this large health care system retrospective analysis, frequency of
intravitreal injections and subsequent visual acuity improvement in clinical practice are
lower than that reported in landmark RCTs. Prior studies have demonstrated less frequent
DME patient monitoring and anti-VEGF injections in clinical practice than in landmark
RCTs. This study links less frequent anti-VEGF injections to less VA improvement in clinical
practice than reported in pivotal RCTs like RISE/RIDE. Additional research is needed to
assess potential factors that may affect injection frequency and visual outcomes in a clinical
population with DME.
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Automated Identification and Quantification of Fluorescein
Leakage in Patients with Diabetic Macular Edema
Thiran Jayasundera, MD
Ann Arbor, MI
Amani Al-Tarouti, MD, MS, Dong Wei, PhD, Christopher Ranella, BSE,
Nathan Patel, BS, Thomas Gardner, MD, MS, Grant Comer, MD, MS, et al
Purpose: To determine the accuracy of a machine learning method of quantitative image
analysis for fluorescein angiography (FA) that demonstrates clinical utility in identifying and
following treatment efficacy of fluorescein leakage in diabetic macular edema (DME).
Methods: This study examined FA images from a prospective observational study
of patients with DME at the University of Michigan. For each set of FA images, regions
of fluorescein leakage were outlined by two retina specialists independently using an
interactive stylus display by assessing early phase (25-30 seconds) and late phase (7
minutes) images. The machine learning method then trained a pixel-wise classifier with
the FA images outlined by one of the two specialists using a supervised machine learning
algorithm. The feature vector describing each pixel comprised texture information derived
from wavelet transformation of the late phase image, and fluorescein kinetics information
obtained by subtracting normalized and registered early and late phase images.
Results: Ten of the sixty FA sets were analyzed in this proof-of-concept study. A
correlation coefficient of 0.81 (p2) was similar to the variation between each of the
specialists and the algorithm (mean differences of 0.65 and 5.11 mm2). In this alpha
prototype, the Dice coefficient which measures retinal region overlap found a marginally
lower overlap of the leakage regions identified by the method and outlined by either
specialist (51%), than the overlap of leakage regions outlined by both specialists (67%).
Conclusions: The machine learning method quantifying fluorescein leakage highly
correlates with that of retinal specialist subjective assessment. The significant intergrader variation found reflects the variation seen in subjective assessment of FA by retina
specialists. An automated computer vision algorithm has the potential to be superior for
detecting fluorescein leakage when leakage is defined as progressive enlargement of
hyperfluorescence. Such a method can be used as an endpoint for clinical trials, assist
in identifying retinal areas for treatment with focal laser, and monitoring response to
treatments.
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Intravitreal Aflibercept for Diabetic Macular Edema:
24-Month Results from VISTA-DME and VIVID-DME
David M. Brown, MD
Houston, TX
Purpose: To compare the efficacy and safety of intravitreal aflibercept injection (IAI)
with macular laser photocoagulation for the treatment of diabetic macular edema (DME).
Methods: VISTA-DME and VIVID-DME were two similarly designed, double-masked,
phase 3 trials that randomized and treated 461 and 402 DME patients, respectively, to
receive either IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks (2q8, following 5 initial
monthly doses), or laser. The primary efficacy endpoint was the mean change from baseline
in best corrected visual acuity (BCVA) at week 52.
Results: The mean BCVA gain from baseline to week 52 in the 2q4 and 2q8 groups vs
the laser group was 12.5 and 10.7 vs 0.2 letters (P<.0001) in VISTA-DME, and 10.5 and 10.7 vs
1.2 letters (P<.0001) in VIVID-DME, respectively. The corresponding proportion of patients
who gained 15 letters from baseline at week 52 was 41.6% and 31.1% vs 7.8% (P<.0001)
in VISTA-DME, and 32.4% and 33.3% vs 9.1% (P<.0001) in VIVID-DME, respectively. After
two years, the mean BCVA gain from baseline to week 96 in the 2q4 and 2q8 groups vs
the laser group was 11.5 and 11.1 vs 0.9 letters (P<.0001) in VISTA-DME. The most frequent
ocular adverse events (AEs) in VISTA-DME (24 months) and VIVID-DME (12 months) were
conjunctival hemorrhage, eye pain, and vitreous floaters. The overall incidence of ocular
and non-ocular AEs and serious AEs, including the Anti-Platelet Trialists’ Collaboration
(APTC)-defined arterial thromboembolic events, was similar across treatment groups in
VISTA-DME (24 months) and VIVID-DME (12 months). Two-year results of both studies will
be presented.
Conclusions: In both VISTA-DME and VIVID-DME, IAI demonstrated significant
superiority in visual endpoints over laser at week 52, with similar efficacy in the 2q4
and 2q8 groups. In VISTA-DME, BCVA gains from baseline with both IAI regimens were
sustained at week 100, compared with laser. IAI was generally well tolerated with no overall
difference between treatment groups in serious systemic AEs, including APTC events.
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Evaluation of Rescue Treatment with Intravitreal Aflibercept
Injection (IAI) in Patients with Diabetic Macular Edema
(DME) Receiving Laser in the VISTA-DME and VIVID-DME
Studies
Dennis Marcus, MD
Augusta, GA
Purpose: To evaluate the use of IAI rescue treatment and outcomes in patients
randomized to laser control.
Methods: VISTA-DME and VIVID-DME were two double-masked, phase 3 trials that
randomized 466 and 406 DME patients, respectively, to receive either IAI 2mg every 4
weeks (2q4), IAI 2mg every 8 weeks (2q8, following 5 initial monthly doses), or laser.
Rescue was available to patients beginning at week 24 if pre-defined rescue criteria were
met; qualifying patients in the laser group received IAI 2mg every 8 weeks (following
5 monthly doses). For the primary efficacy endpoint, mean change from baseline in
best-corrected visual acuity (BCVA) at week 52, the analysis was conducted using last
observation carried forward (LOCF); excluding measurements obtained after initiation of
rescue. Another analysis was performed which included measurements after initiation of
rescue (aLOCF).
Results: Mean BCVA gain from baseline to week 52 (LOCF) in the 2q4, 2q8 and laser
group was 12.5, 10.7 and 0.2 letters (PP, 48 (31.2%) and 32 (24.1%) of laser patients received
rescue in VISTA-DME and VIVID-DME, respectively. When data after rescue were included
(aLOCF), mean BCVA change from baseline at Week 52 in the laser group was 4.2 and 3.5
letters in VISTA-DME and VIVID-DME, respectively. For rescued patients in the laser group,
mean BCVA change through week 52 from the time rescue was initiated was 18.6 and 12.4
letters in VISTA-DME and VIVID-DME, respectively. When vision loss prior to rescue is
considered, these patients did not achieve the same magnitude of vision gain as the overall
population. The most frequent ocular serious adverse event was vitreous hemorrhage.
Conclusions: A considerable proportion of patients randomized to laser required
rescue in both studies. Patients receiving rescue in the laser arm gained, on average, 3-4
lines of vision, however due to visual acuity loss that occurred before rescue was given,
these patients did not achieve vision outcomes from baseline to Week 52 similar to those
patients treated with IAI from baseline. Early treatment with IAI is therefore recommended
in patients with DME.
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Intravitreal Aflibercept in the VISTA-DME and VIVID-DME
Studies: Subgroup Analysis by Baseline Demographics and
Systemic Disease Characteristics
Charles C. Wykoff, MD, PhD
Houston, TX
Purpose: The efficacy of intravitreal aflibercept injection (IAI) in comparison to macular
laser photocoagulation was evaluated in subgroups of diabetic macular edema (DME)
patients by race and baseline hemoglobin A1c (HbA1c) levels.
Methods: VISTA-DME and VIVID-DME, two parallel phase 3 trials, evaluated the efficacy
and safety of IAI for treatment of DME. These trials randomized 872 patients with DME
to receive either IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks following 5 initial
monthly doses (2q8), or laser. The primary efficacy endpoint was the mean change in bestcorrected visual acuity (BCVA) from baseline at week 52. An exploratory analysis examined
BCVA from baseline through week 52 in subgroups of DME patients by race and systemic
diabetic control at baseline as represented by HbA1c 8% and >8%.
Results: Of the VISTA-DME and VIVID-DME patients, 81.8% were White, 6.1% were Black,
and 10.3% were Asian. The mean change in BCVA from baseline to week 52 in the 2q4 and
2q8 groups vs the laser group was +11.9 and +10.7 vs +0.6 letters (PP.0206) in Blacks, and
+8.8 and +10.6 vs -0.4 letters (P8%, respectively. The mean change in BCVA from baseline
to week 52 in the 2q4 and 2q8 groups vs the laser group was +12.3 and +10.9 vs +1.1 letters
(PP8%, respectively.
Conclusions: These findings suggest that the improvements in vision achieved with
IAI 2q4 and 2q8 were significantly greater than laser and consistent among subgroups of
patients with differing race and variable systemic disease control at baseline (HbA1c 8%
and >8%).
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Anti-VEGF Therapy for Diabetic Macular Edema (DME):
Comparison of Year 1 Results from Prospective, Randomized,
Controlled Clinical Trials
Allen C. Ho, MD
Philadelphia, PA
Na Lu, PhD, Ivo Stoilov, MD
Purpose: Comparing 1-year results across ranibizumab, bevacizumab, and aflibercept
trials for the treatment of DME is challenging because RISE/RIDE 1-year data have not been
reported, and mean baseline VA (bVA) across trials ranges from 55-63 letters, suggesting
that VA gains may be influenced by a ceiling effect. The purpose of this exploratory analysis
was to evaluate patients with similar baseline characteristics in order to compare 1-year VA
outcomes across key anti-VEGF trials in DME.
Methods: Study designs, primary endpoints, inclusion/exclusion criteria, baseline
characteristics, and VA outcomes were compared for DRCR.net Protocol-I, RISE/RIDE,
BOLT, and VIVID/VISTA. Inclusion criteria were comparable except for bVA at enrollment:
Protocol-I enrolled patients with bVA up to 20/32 (Snellen equivalent), whereas the other
studies capped vision at 20/40. To compare across trials, a Protocol-I subgroup analysis
was conducted, only including study eyes with bVA of 20/40 (n=581, 68%).
Results: Mean duration of diabetes (years) at baseline ranged from 14.1 (VIVID)-18.4
(Protocol-I). VIVID had the highest percentage of Asian patients (20%). Only 1.5% of
patients in VIVID/VISTA had mild PDR vs 25-28% in RISE/RIDE. Across studies, most of
the BCVA gains occurred during the first year of treatment. Patients gained, on average,
+10-12 letters from baseline at year 1 in RISE/RIDE, which was similar to mean BCVA gains
achieved at year 1 in VIVID/VISTA (+11-13 letters), and higher than BOLT (+5.6 letters). In
the Protocol-I subanalysis, bVA was ~57 letters (comparable to RIDE/RISE, VIVID/VISTA,
BOLT). Mean BCVA gains from baseline were +11.7 and +11.5 letters (prompt vs deferred
laser, respectively), and were greater than in the all-comers population (+9 letters). Among
subgroup patients, 43% (prompt) and 34% (deferred) gained > or = 15 letters from baseline,
which was similar to RISE/RIDE and VIVID/VISTA findings.
Conclusions: When adjusted for bVA, BCVA gains from baseline appeared to be
comparable across studies between ranibizumab and aflibercept given monthly or lessthan-monthly, and were slightly less with bevacizumab. Comparatively smaller VA gains in
the Protocol-I general population could be related to a ceiling effect on vision gains due
to better-seeing eyes at enrollment. Findings should be interpreted with caution given the
limitations of cross-trial comparisons.
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Intravitreal Ranibizumab for Diabetic Macular Edema with
Prompt vs. Deferred Laser Treatment: 5-year Randomized
Trial Results
Portland, OR
for the Diabetic Retinopathy Clinical Research Network
Purpose: To report 5-year results from a previously reported multicenter randomized
clinical trial evaluating intravitreal 0.5-mg ranibizumab with prompt versus deferred (for
>24 weeks) focal/grid laser treatment for diabetic macular edema (DME).
Methods: One hundred eighty-seven participants were randomized to the prompt
laser group and 124 of these participants completed the 5-year visit while 188 participants
were randomized to the deferred laser group, and 111 completed the 5-year visit. Initial
visual acuity for all participants was 20/32 to 20/320 and all had DME involving the fovea.
Ranibizumab injections were given every four weeks until no longer improving (otherwise,
investigator discretion) and participants received the prompt or deferred focal/grid laser
treatment based on random assignment.
Results: The mean change in visual acuity letter score from baseline through the 5-year
visit was +7.2 letters in the prompt laser group compared with +9.8 letters in the deferred
laser group (mean difference -2.6 letters, 95% confidence interval -5.5 to +0.4 letters,
P = 0.09). From baseline through 5 years, 56% in the deferred group avoided laser, while
the median number of injections was 13 versus 17 in the prompt and deferral group
respectively. No differences in safety were noted between the two groups.
Conclusions: Most eyes with DME involving the fovea with vision impairment initiating
ranibizumab with prompt or deferred laser can maintain vision gains obtained by the first
year through 5 years with minimal treatment after 3 years. Five-year results also suggest
that focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better than
deferring laser treatment for 24 weeks. While eyes in the laser deferred group may require
more injections over 5 years to achieve the results observed in this study, this group also
may require fewer laser treatments.
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Open-Label Extension of the Phase III RIDE and RISE Trials —
Characteristics of DME Patients Associated with Treatment
Frequency
Carl D. Regillo, MD
Philadelphia, PA
Beiying Ding, PhD, Ivo Stoilov, MD
Purpose: To investigate patient characteristics associated with treatment frequency
during the RIDE and RISE open-label extension (OLE).
Methods: Summary statistics for the RIDE and RISE core studies were generated, including baseline characteristics and treatment responses. These were analyzed by number of
ranibizumab 0.5 mg injections per year during the OLE (0, >0–3, >3–7 and >7) Relationship
with injection frequency as a continuous variable was explored graphically. For selected
treatment response variables, analysis was also conducted by randomized treatment group
of the core studies.
Results: Month 36 of the RIDE and RISE studies was completed by 582 of 759 patients;
500 (85.9%) were enrolled in the OLE. Distribution of number of injections per follow-up
year was: 0 (n=121); >0–3 (n=132); >3–7 (n=159); >7 (n=88); with a mean 3.8 annualized
injections given during the extension. Compared to patients receiving >7 injections, patients
who received no retreatment had at baseline of the core studies a shorter duration of
diabetes (by 2 years), a shorter time from diagnosis of DME (by ~10 months), better vision
(58.4 vs. 54.3 letters) and less edema (440.5 mm vs. 525.5mm). More patients in the
untreated group had OCT thickness less than or equal to 250 mm at month 36 compared to
those receiving >7 injections (95% vs. 56.8%), and also received fewer macular rescue laser
treatments through month 36 (0.9 vs. 2.3). Diabetes retinopathy severity scores at baseline
and at months 24 and 36 were lower in the untreated group. The most frequently treated
patients (>7 injections per year) tended to have the least favorable disease characteristics
or treatment response during the core study for most variables explored.
Conclusions: This exploratory analysis revealed that following a period of monthly
treatment with ranibizumab 0.5 mg, a meaningful proportion of DME patients can maintain
vision and retinal anatomy with no or very few injections. In these patients, ranibizumab
therapy appears to have been initiated early, with higher baseline visual acuity and less
advanced DR. These data suggest that with early diagnosis and treatment, DME patients
may achieve disease remission and maintain vision gains without the need for ongoing
intravitreal injections.
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Repeated Ranibizumab Injections and Incidence of
Sustained IOP Elevation or Initiation of Ocular Hypotensive
Treatment in Eyes with Diabetic Macular Edema
Seema Garg, MD, PhD
Chapel Hill, NC
for the Diabetic Retinopathy Clinical Research Network
Purpose: To assess the risk of persistent intraocular pressure (IOP) elevation in eyes
with center-involved diabetic macular edema (DME) receiving repeated ranibizumab
injections laser through 3 years, compared with eyes receiving focal/grid laser alone.
Methods: In a phase III clinical trial conducted by the Diabetic Retinopathy Clinical
Research Network (DRCR.net), eyes with baseline center-involved DME and IOP 24 mmHg
were randomly assigned to sham+prompt laser (N = 260) or 0.5 mg ranibizumab+prompt
or deferred laser (N = 322). Pre-dilation IOP was assessed every 4 weeks through 1-year,
and every 16 weeks through 3-year visits. Cumulative probability of persistent IOP elevation
(defined as IOP 22 mmHg and 6 mmHg increase from baseline at 2 consecutive visits) or
initiation of ocular hypotensive therapy (medication or procedure), was calculated using
the Kaplan–Meier method. Data were censored if ocular or systemic steroids were received,
vitrectomy was performed, or an eye developed IOP elevation due to neovascularization,
ghost cell glaucoma or endophthalmitis. Sham eye data were censored if any vascular
endothelial growth factor inhibitor was received.
Results: Mean baseline IOP was 16±3 mmHg in both groups. Four and 5% of sham and
ranibizumab eyes, respectively, had baseline IOP of 22 to 24 mmHg. In each group, 3% had
a history of glaucoma or used IOP-lowering medicine prior to randomization. On average,
8 and 13 intravitreal injections were performed in the ranibizumab group through year 1
and 3 respectively. The cumulative probability of sustained IOP elevation or need for ocular
hypotensive therapy in ranibizumab vs. sham group was 5.5% versus 2.3% by 1 year and
9.4% vs. 3.3% by 3 years (hazard ratio = 2.9, 99% CI: 0.9 to 9.7, P = 0.02).
Conclusions: These data suggest that eyes with center-involved DME and no prior
glaucoma, treated with 0.5 mg ranibizumab intravitreal injections as in this DRCR.net study,
have a small increase in risk of sustained IOP elevation or need for ocular hypotensive
treatment. However, the absolute increase in percentage of affected people is small and the
magnitude of risk for actual loss of vision function remains unknown.
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Long-term Efficacy and Safety of Dexamethasone
Intravitreal Implant for Treatment of Diabetic Macular
Edema in Phakic and Pseudophakic Eyes
Victor H. Gonzalez, MD
Edinburg, TX
For the MEAD Study Group
Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant
(DEX implant) 0.7 mg and 0.35 mg in the treatment of diabetic macular edema (DME) in
phakic and pseudophakic eyes.
Methods: In a 3-year, randomized, multicenter, masked, sham-controlled, phase III
clinical study (MEAD study), patients were randomly assigned to study eye treatment
with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure. Patients who met
retreatment eligibility criteria could be retreated no more often than every 6 months.
The primary endpoint was achievement of 15-letter improvement in BCVA from baseline
at study end in the intent-to-treat population with last-observation-carried-forward for
missing values. Safety measures included adverse events and intraocular pressure (IOP).
Subgroup analysis evaluated results based on lens status in the study eye at baseline
(phakic or pseudophakic).
Results: Baseline lens status was phakic in 773 (73.8%) patients and pseudophakic in
275 (26.2%) patients. The percentage of patients with 15-letter improvement in BCVA at
study end (DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively)
was 21.9%, 19.3%, and 12.4% among baseline phakic patients (P 0.035, DEX implant 0.7
and 0.35 mg vs sham) and 23.3%, 15.9%, and 10.9% among baseline pseudophakic patients
(P =0.024, DEX implant 0.7 mg vs sham). Mean average reduction in CRT from baseline
(area-under-the-curve approach) was greater with DEX implant 0.7 and 0.35 mg than sham
in both baseline phakic patients (–104.9, –104.8, and –38.3 µm, P <0.001) and baseline
pseudophakic patients (–131.8, –117.1, and –50.8 µm, P <0.001). Rates of cataract-related
adverse events in baseline phakic patients were 67.9%, 64.1%, and 20.4%.
Conclusions: DEX implant 0.7 mg and 0.35 mg provided clinically significant
improvement in BCVA and reduction in CRT in phakic as well as pseudophakic eyes. BCVA
improvement was confounded by cataract development in phakic eyes, but after cataract
extraction and given time to recover, BCVA improvement was similar in baseline phakic and
pseudophakic eyes.
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Effect of Doxycycline versus Placebo on Retinal Function
and Diabetic Retinopathy Progression in Patients with
Severe Nonproliferative or Non-High-Risk Proliferative
Diabetic Retinopathy: A Randomized Trial
Hershey, PA
Gregory R. Jackson, PhD, David A. Quillen, MD, Michael Larsen, MD, DMSc,
Ronald Klein, MD, MPH, Jason Liao, PhD, Stig Holfort, MD, PhD, et al
Purpose: To investigate, in a proof-of-concept clinical trial, whether low-dose oral
doxycycline can (1) slow the deterioration of, or improve, retinal function or (2) induce
regression or slow the progression of diabetic retinopathy in patients with severe
nonproliferative diabetic retinopathy (NPDR) or non-high-risk proliferative diabetic
retinopathy (PDR), and to determine the potential usefulness of visual function end points
to expedite the feasibility of conducting proof-of-concept clinical trials in patients with
diabetic retinopathy.
Methods: Randomized, double-masked 24-month proof-of-concept clinical trial. Thirty
patients with 1 or more eyes with severe NDPR or PDR less than Early Treatment Diabetic
Retinopathy Study (ETDRS)-defined high-risk PDR were randomized to receive 50 mg
of doxycycline monohydrate or placebo daily for 24 months. Outcome measures include
change at 24 months compared with baseline in functional factors (frequency doubling
perimetry [FDP], Humphrey photopic Swedish Interactive Thresholding Algorithm 24-2
testing, contrast sensitivity, dark adaptation, visual acuity, and quality of life) and anatomic
factors (ETDRS diabetic retinopathy severity level, area of retinal thickening, central
macular thickness, macular volume, and retinal vessel diameters).
Results: From baseline to month 24, mean FDP foveal sensitivity decreased in the
placebo group (-1.9 dB) and increased in the doxycycline group (+1.8 dB) (p=.02). A higher
mean FDP foveal sensitivity in the doxycycline group compared with the placebo group
was detected at 6 months (p=.04), and this significant difference persisted at 12 and 24
months. A difference between the groups was not detected with respect to the other visual
function outcomes and all anatomic outcomes assessed.
Conclusions: To our knowledge, this is the first observation suggesting a link
between a low-dose oral anti-inflammatory agent and subclinical improvement in inner
retinal function. Oral doxycycline may be a promising therapeutic strategy targeting the
inflammatory component of diabetic retinopathy. Further, study results suggest that FDP,
which primarily measures inner retinal function, is responsive to intervention and may
be a useful clinical trial end point for proof-of-concept studies in patients with diabetic
retinopathy.
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Topical Nepafenac to Manage Non-central Diabetic Macular
Edema
Lakeland, FL
on behalf of the Diabetic Retinopathy Clinical Research Network
Purpose: To assess if the topical NSAID, nepafenac 0.1%, administered 3 times per
day for one year in eyes with good visual acuity and non-central DME can reduce retinal
volume as measured on spectral domain optical coherence tomography (OCT) images
when compared with placebo. Secondary outcomes include prevention of central DME and
assessment of safety.
Methods: A randomized clinical trial was conducted by the Diabetic Retinopathy
Clinical Research Network. After a 30-60-day run-in phase using artificial tears to monitor
compliance, eyes with non-central involved DME and visual acuity 20/32 or better were
randomly assigned to nepafenac (N= 61) or placebo (nepafenac vehicle, N= 64) 3 times/
day for 12 months. Other DME treatment during study was allowed if OCT central subfield
increased above gender- and OCT machine-specific mean thickness from normal eyes+ 2
SD provided there was at least a 10% increase in thickness from entry. Primary outcome
was the change in mean retinal volume at 12 months adjusted for baseline volume.
Results: Median participant age was 60 years, with 41% women and 66% were White.
The majority of participants (84% in nepafenac and 69% in placebo) had diabetes mellitus
for 10 years or more. History of previous DME treatment was reported in 49% and 44%
of study eyes in the nepafenac and placebo groups respectively. Thirty-four percent and
17% of nepafenac and placebo eyes were pseudophakic at baseline. The 12-month visit
was completed by 93% and 94% of participants in the nepafenac and placebo groups
respectively. OCT and VA were performed at 4, 8 and 12 months. The primary outcome
results of this clinical trial will be presented at the meeting as well as secondary outcomes
including visual acuity and other treatments administered to manage DME.
Conclusions: Final conclusions based on the results presented will be included at the
meeting.
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Italian Market
POSTERS
Poster session is not eligible for CME credit
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POSTER 1
Fellow Eye Comparison of Area of Geographic Atrophy (GA)
in Patients Undergoing Long-Term Anti-VEGF Therapy for
Nvamd in One Eye
Michelle Carle, MD
Los Angeles, CA
Thomas G. Chu, MD, PhD, Homayoun Tabandeh, MD, Firas Rahhal, MD,
David S Boyer, MD
Purpose: To evaluate area of geographic atrophy (GA) using Fundus Auto-Fluorescence
(FAF) in both eyes of patients undergoing long-term anti-VEGF therapy for nvAMD in one
eye.
Methods: Clinical case series. Inclusion criteria: Patients undergoing antiVEGF therapy
for nvAMD in one eye for a duration of 4 or more years. Exclusion criteria: nvAMD and other
retinal diseases in the fellow eye, media opacity obscuring acquisition of Autofluorescence.
Previous treatment with PDT and steroid were acceptable. Area of GA was measured using
Fundus Auto-Fluorescence (FAF) (Heidelberg Spectralis HRA) performed under BluePeak
Blue Laser Autofluorescence. Automated measurements of the GA area was performed by
a photographer and verified by a physician. (Figure 1)
Results: Twenty-four eyes of 12 patients were evaluated. Anti-VEGF agents included
ranibizumab, bevacizumab, and aflibercept. The average number of antiVEGF injections for
each eye was 35 (range 11-55), and the average duration of treatment was 6 year (range:
4-8 years) (Table 1). The average area of GA was 2.613mm2 (range 0.46-7.456mm2) in the
treated eyes and 0.449mm2 (range 0-3.135mm2) in the untreated fellow eyes (excluding
the outlier of 65.289mm2). The BCVA ranged 20/20 to 20/175 (median 20/70) in the
treated eyes and 20/20 – CF (median 20/30), and for the untreated eye was. Nine of the 12
pairs of eyes had a greater area of GA in the treated eye.
Conclusions: Progression of GA over years is noticeable significant cause of vision
loss in patients with nvAMD undergoing anti-VEGF therapy. The current study indicates
more extensive GA in eyes with nvAMD undergoing long-term anti-VEGF therapy
compared with the fellow eyes with non-neovascular AMD not receiving any treatment.
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Poster #2
Squalamine Lactate Then and Now: A Review of IV
and Topical Formulation Data and Comparison of
Pharmacokinetics
Indianapolis, IN
Purpose: Squalamine Lactate is a small molecule inhibitor of multiple growth factors
including VEGF and PDGF via a unique intracellular mechanism of action. The drug had
previously been evaluated using an intravenous formulation in clinical phase II studies, with
demonstrated activity in exudative AMD, but was discontinued due to the pharmacokinetic
deficiency of the IV administration and infusion site reactions. Utilizing recent advances
in topical formulation technology, the molecule was formulated for topical delivery and
increased residence time in posterior ocular tissues.
Methods: This poster will review the prior clinical studies, present relevant
pharmacokinetics of the topical formulation, and present current clinical study design and
status.
Results: Preclinical animal models demonstrate drug concentrations in posterior
ocular tissues comparable to those seen in the previous intravenous formulation. Thus, in
the current clinical trials, there is potential to overcome the pharmacokinetic deficiency
of the intravenous formulation by non invasive delivery to consistently replenish drug
concentrations in posterior ocular tissues.
Conclusions: Several clinical studies are currently underway to evaluate the safety
and efficacy of topical Squalamine Lactate drops in indications including exudative
macular degeneration, branch and central retinal vein occlusion, and proliferative diabetic
retinopathy.
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Poster #3
Induced Pluripotent Stem (iPS) Cell-Derived RPE Transplants
Induce Immune Response in Pigs
Elliott H. Sohn, MD
Iowa City, IA
Chunhua Jiao, MD, Robert Mullins, PhD, Edwin Stone, MD, PhD, Budd Tucker, PhD
Purpose: Stem cell strategies focused on replacement of RPE cells for the treatment
of geographic atrophy are under intense investigation. Although the eye has long been
considered immune privileged, a limited number of large animal studies focused on the
post-transplant immune response have been performed. The purpose of this study was to
determine if allogenic iPS cell-derived RPE cells delivered to the subretinal space of the pig
would survive and fail to induce an immune response in non-diseased eyes.
Methods: 250,000 iPSC-derived RPE cells, generated from GFP-positive outbred
domestic swine, were injected subretinally into 12-week-old vitrectomized Yucatan mini
swine (a subset of eyes received BSS vehicle control only). Eyes were enucleated at 3
weeks post-op, fixed in 4% paraformaldehyde, cryosectioned and immunostained with
antibodies targeted against GFP, ZO1, IgG, macrophages (BA4D5), CD45, GFAP, nestin,
Ki67, and PCNA. Vitreous samples extracted at the time of vitrectomy and again at post-op
week 3 were assayed for cytokine levels using a swine cytokine Quantibody array kit
(RayBiotech, Inc). Data were analyzed using Student’s t-test and one-way ANOVA followed
by Fisher’s LSD test.
Results: GFP-positive cells expressing the RPE marker ZO-1 were identified in the
subretinal space at 3 weeks post-injection along with IgG positive cells. Accompanying
GFP-negative cells positive for CD45 and macrophage markers were also identified. All
cells were negative for GFAP as well as the cell cycle markers nestin, Ki67, and PCNA. At
post-op week 3, vitreous TGF-beta1 levels were elevated in the iPSC-RPE group compared
to BSS controls and native vitreous. IL-12 levels were greater in post-op week 3 compared
to native vitreous but not post-op week 3 BSS controls.
Conclusions: Subretinal injection of allogenic iPS-RPE cells into wild-type mini-pigs
can induce an immune response. These findings suggest that immunologically matched or
autogenic donor cells may be required for clinical RPE cell replacement.
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179
Poster #4
Retinal Drusen in the Morbidly Obese
Katherine Whalen, MD
Danville, PA
G. Craig Wood, MD, Christopher D. Still, DO, Tamara Vrabec, MD
Purpose: To describe prevalence and characteristics of retinal drusen among morbidly
obese and determine if age, gender, eye color, BMI or other systemic co-morbidities
(diabetes mellitus, sleep apnea, hyperlipidemia, hypertension, high sensitivity C-reactive
protein and smoking) are associated.
Methods: Ninety-four morbidly obese patients with BMI>40 kg/m2 or BMI>35 kg/m2
and at least 2 significant co-morbidities were included in this prospective, non-controlled
study. Digital fundus images were graded for presence and size of drusen. The Wisconsin
Age-Related Maculopathy Grading System was used to grade the images. Values for
number and size of drusen were assigned based on each patient's more affected eye.
Results: The 94 patients included 27 males and 67 females and had a mean age of 49
years (range=29-71). Ninety two of 94 were Caucasian (98%). The mean BMI was 48 kg/
m2 (SD=9.4), with 38% (n=36) having a BMI>50 kg/m2 and 7% (n=7) having a BMI>60 kg/
m2. Eighty patients (85%) had macular drusen. All had small drusen (125 u). An additional
4 patients had large extramacular drusen. Twenty-six percent had 1-10 drusen, 18% had
11-20 and 39% had >20 drusen (including 9 with >100 drusen). More males had >20 drusen
compared to females (59% versus 34%, p=0.026). Though not significant, the percent with
>20 drusen was higher in those with diabetes as compared to those without diabetes (51%
versus 33%, p=0.081). The associations between drusen and blue eye color, age, BMI or
systemic co-morbidities were not significant.
Conclusions: The prevalence of any macular drusen in the morbidly obese is similar
to that reported for Caucasians 18-54 years. However, the total number of drusen per eye
and the number of medium and large drusen are greater. Drusen are more prevalent among
morbidly obese males. No other systemic associations were identified.
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Poster #5
Practice Preference Survey: Anti-VEGF in the Treatment of
Diabetic Eye Disease
Mary Champion, MD
Roeland Park, KS
Johnny Tang, MD
Purpose: Retina specialists in North America were surveyed regarding their use of
intravitreal anti-vascular endothelial growth factor (anti-VEGF) for conditions in diabetic
eye disease such as diabetic macular edema (DME), proliferative diabetic retinopathy
(PDR), and neovascular glaucoma (NVG).
Methods: In February of 2014, a survey was emailed to 1,681 retinal specialists
identified through the American Society of Retina Specialists directory. The survey queried
indications for anti-VEGF use in diabetic eye disease, criteria for switching anti-VEGF
agents for DME treatment, endpoint for DME treatment, and preference of anti-VEGF agent
for DME treatment. Participants were not required to answer all questions. The REDCap
software tool (V5.7.7) was used to email surveys and track responses.
Results: There were 272 participants (16.3%) out of 1,668 deliverable email survey
invitations. 50.0% (± 6.1%) routinely used anti-VEGF for PDR surgery, 93.4% (± 3.0%) used
anti-VEGF for NVG in conjunction with PRP, and 94.8% (± 2.7%) incorporated focal/grid
laser with anti-VEGF for treatment of DME. For patients requiring cataract surgery, 77.9%
(± 5.0%) of participants treated patients who have DME, and 28.3% (± 5.5%) treated patient
who have non-centered DME. For non-centered DME (assuming no significant retinopathy),
most participants (57.0% ± 6.0%) used a follow-up interval of six months.
Bevacizumab was the most popular first line agent for DME (58.1% ± 6.0%), followed by
ranibizumab (38.5% ± 5.9%), and aflibercept (3.3% ± 2.2%). 90.1% (± 3.6%) of participants
switched anti-VEGF agents for various reasons during treatment of DME. The most
common treatment endpoint for anti-VEGF injections for DME was resolution of edema by
OCT or clinical exam (68.4% ± 5.6%), although 32.4% (± 5.7%) of participants indicated that
they treat and extend with no definite endpoint.
Conclusions: Most participants used anti-VEGF for NVG and in conjunction with
focal/grid laser for DME. There was variation in the usage of anti-VEGF for PDR surgery
and for treatment of DME prior to cataract surgery. Participants had various treatment
endpoints for anti-VEGF in DME, and many switched anti-VEGF agents during treatment
of DME for different reasons. The lack of consensus underscores the need for randomized
clinical trials to guide treatment algorithms.
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Poster #6
Comprehensive Analysis of Retinal Function and Structure in
Proliferative Diabetic Retinopathy
Ann Arbor, MI
Grace E. Boynton, BS, Maxwell S. Stem, MD, Leon Kwark, MS, Sina Farsiu, PhD,
Gregory R. Jackson, PhD
Purpose: To identify changes in retinal function and structure in persons with
proliferative diabetic retinopathy (PDR), including effects of panretinal photocoagulation
(PRP). We hypothesized the presence of inner retinal dysfunction in untreated PDR and
additional impairment of photoreceptor function following PRP.
Methods: This cross-sectional study examined 30 adults who had received PRP for
PDR, 15 with untreated PDR, and 15 healthy age-matched controls. Participants underwent
contrast sensitivity testing and frequency doubling perimetry (FDP) to assess inner retinal
function, and photostress recovery time and dark adaptation to evaluate outer retinal
function. Spectral domain OCT scans were semi-automatically segmented.
Results: Patients with PDR had significant reduction of FDP mean deviation (MD) in
after PRP (MD ± SD: -8.20 ± 5.76 dB, p=0.000) and before treatment (-5.48 ± 4.48 dB,
p=0.000) relative to controls (1.07 ± 2.50 dB). Reduced log contrast sensitivity compared
with controls (1.80 ± 0.14) was also observed in treated (1.42 ± 0.17, p=0.000) and untreated
(1.56 ± 0.20, p= 0.001) patients with PDR. Compared to controls, patients treated with PRP
had increased photostress recovery time (151.02 ± 104.43 sec vs 70.64 ± 47.14 sec, p=0.001)
and dark adaptation speed (12.80 ± 5.15 min vs 9.74 ± 2.56 min, p=0.022). Treatment-naïve
patients had equivalent photostress recovery time (p=0.633) and dark adaptation speed
(p=0.437) relative to controls.
PRP-treated patients had diffusely thickened nerve fiber layers (p=0.022), thinned
combined ganglion cell and inner plexiform (GCL+IPL) layers in central ETDRS regions,
diffusely thinned inner segment/outer segment (ISOS) layers (p=.018), and diffusely
thinned retinal pigment epithelia (RPE) (p=.005) versus controls. Untreated patients with
PDR had thinned GCL+IPL layers in central ETDRS regions, diffusely thickened combined
outer plexiform and outer nuclear layers (OPL+ONL) (p=.006), and diffusely thinned RPE
layers (p=.036) compared to controls.
Conclusions: Patients with PDR exhibit inner retinal dysfunction, as evidenced by
reduced contrast sensitivity and FDP performance. Untreated and treated patients with
PDR exhibit alterations in both inner and outer retinal structure, with progressive changes
in outer retinal structure after PRP treatment. Distinguishing the effects of PDR and PRP on
retinal function may guide the development of restorative vision therapies for patients with
advanced diabetic retinopathy.
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Poster #7
Comparison of the Outer Retina in Diabetics and Its
Correlation With Visual Acuity Using Four Different OCT
Machines
Veronica Kon Graversen, MD
Raleigh, NC
Maurice B. Landers III, MD, Elle Alexander, MS, Eric Powers, MS
Purpose: To determine the relationship of retinal thickness measurements and outer
retina integrity (ORI) with visual acuity in patients with diabetic macular edema by
comparing four commercially available spectral domain (SD) OCT instruments.
Methods: Case-control study. All participants underwent a complete ophthalmological
evaluation prior to the scans. OCT imaging with Cirrus, Optovue, Nidek and Spectralis
devices were obtained during the same visit. The scans were centered on the fovea.
Central retinal thickness (CRT) and ORI were calculated, analyzed and compared using
(SigmaScan Pro version 5.0; Systat software Inc., Point Richmond, Calif, USA). The main
outcome measure was to observe diagnostic accuracy and sensitivity between outer retina
abnormalities in diabetic macular edema detected by OCT and their association with visual
acuity.
Results: Thirty eyes with clinically significant diabetic macular edema were studied. The
patients had a mean age of 51 years and average logMAR visual acuity of 0.54. Outer retina
abnormalities were visible on all the scanning devices in all patients. Further results will be
disclosed at the meeting regarding.
Conclusions: There are variations in CRT values in patients with DME, likely due to
different segmentation algorithms. There are also variations in ORI among the different
devices, with some of them providing more detail of the outer retina structures. Sensitivity
and specificity of several OCT devices are similar to detect irregularities of the ORI that are
associated with visual acuity in patients with diabetic macular edema.
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183
Poster #8
Macular Hole and Mid-Peripheral Retinoschisis in Alport
Syndrome
Justin Baynham, MD
Portland, OR
Mark Pennesi, MD, PhD, Christina Flaxel, MD
Purpose: To describe the imaging findings of two patients with macular holes secondary
to Alport syndrome.
Methods: Optical coherence tomography (OCT) and additional imaging modalities of
two patients with full thickness macular holes were examined.
Results: Patient 1. Forty-six year-old male with Alport syndrome. Vision was 20/40
OD and 20/60 OS. Slit lamp examination revealed subepithelial corneal clouding OU.
Mid-peripheral yellow flecks were noted in the retina OU. A blunted foveal light reflex with
surrounding retinal thinning was noted OD. A full-thickness macular hole (FTMH) was noted
OS. No lenticonus was noted.
OCT images taken 8 months prior showed inner retinal thinning without a FTMH at the
fovea OU. By the time of examination, a FTMH OS had developed. FAF appeared normal.
Photopic mfERG revealed subnormal amplitudes and normal implicit times of the central
macular cone responses.
Patient 2. Sixty-one year-old male with Alport syndrome. Vision was 20/150 OD and 20/30
OS. Slit lamp examination revealed subepithelial corneal clouding OU. A large FTMH with a
cuff of subretinal fluid was noted OD. A blunted foveal light reflex with surrounding retinal
thinning was noted OS. A vitelliform lesion was noted temporal to the macula OS. No
lenticonus was noted.
OCT images revealed a large FTMH with everted edges OD. Retinoschisis-like changes
were noted in the temporal macula OD. Thinning of the inner retina at the fovea was noted
OS. Retinoschisis-like changes in the retinal ganglion cell, inner nuclear, and outer nuclear
layers were noted in the mid-peripheral retina OS. The FTMH was noted to have enlarged
significantly over the course of 4 months.
Conclusions: To our knowledge, vitelliform lesions have been reported only once and
mid-peripheral retinoschisis has never been reported with Alport syndrome. Macular holes
are rare complications of Alport syndrome. Attempts to explain the pathogenesis of these
holes have focused on Bruch’s membrane (BM) and the internal limiting membrane of the
retina known to contain type IV collagen. The retinoschisis-like changes involving multiple
retinal layers may suggest additional areas are involved. Alternatively, the schisis cavities
may represent accumulation of intraretinal fluid due to abnormal BM permeability.
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Poster #9
Influence of Risk Alleles Associated with Age-Related
Macular Degeneration on Recessive Stargardt Disease
Phenotypes
Robert Sisk, MD
Cincinnati, OH
Robert Hufnagal, MD, PhD, Brent Zanke, MD, PhD, Megan Kingdon, RN, BSN, CCRC,
Zubair Ahmed, PhD
Purpose: Autosomal recessive Stargardt disease (STGD1) may present with varying
degrees of lipofuscin accumulation, photoreceptor dysfunction, and macular degeneration.
This phenotypic variability, familial disconcordance, and inconsistency in reports describing
pathogenicity of specific alleles all suggest STGD1 phenotypes are inadequately explained
by ABCA4 genotypes alone. Digenic interactions have been described with other rim
proteins. We hypothesize that genes associated with age-related macular degeneration
(AMD) may influence the age of presentation and severity of macular degeneration in
STGD1.
Methods: IRB-approved, prospective genetic evaluation using Macula Risk™ NXG
platform and corresponding retrospective records review of patients with genetically
confirmed STGD1. ELOVL4, RDS, and PROM1 mutations were excluded. All patients
underwent phenotypic evaluation that included funduscopy, spectral domain optical
coherence tomography, fundus autofluorescence, and/or full field electroretinography
(ffERG). CFH, CFI, C3, C2, CFB, LIPC, ABCA1, CETP, Col8A1, APOE, TIMP3, and ARMS2
alleles were graded per AMD risk classifications and assigned a risk score. Results from
STGD1 patients were then compared with age-matched controls without STGD1 and with
patients from the AREDS 2 trial.
Results: Twenty patients with STGD1 (5 male) presented at a mean age of 23 (range 9 to
55 years) with mean VA of 20/83 (range 20/20 to 20/400) and were followed a median of
4.5 years. At presentation, 13 (65%) had visible lipofuscin flecks, 12 (60%) had atrophy, and
3 (15%) had severe reduction in ffERG waveforms. Interim analysis of 17 patients revealed
mean risk score was elevated at 62%. There was no observed association between age at
presentation, severity of macular degeneration, or Gass grouping with the risk score. All
patients had moderate to high-risk CFH, C2, CFB, ABCA1, Col8A1, APOE, and TIMP3 alleles.
Results from the final analysis will be presented at the meeting.
Conclusions: STGD1 may exhibit significant phenotypic variability that may be
modulated by genes that influence AMD phenotypes. Current risk stratification schemes
for AMD can probably not be applied to STGD1. Further subgroup analysis may warrant a
larger trial for validation of multigenic interactions.
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185
Poster #10
Genetic Interaction Mapping of Age-Related Macular
Degeneration Susceptibility Genes and their Expression in
Human Vitreous
Lee Kiang, MD, PhD
Ann Arbor, MI
Jillian T. Huang, MS, David N. Zacks, MD, PhD, Thiran Jayasundera, MD, FRCSC,
Jeffrey M. Sundstrom, MD, PhD
Purpose: Although many genes have been associated with Age-Related Macular
Degeneration (AMD), the underlying molecular mechanisms and pathways are unknown.
Smoking is the strongest modifiable risk factor for the disease. We hypothesized that
analysis of protein-protein interactions among known AMD-associated genes and smokingassociated genes would identify common genes through which they interact, which could
reveal novel pathogenetic pathways for AMD. We predicted that these gene products
would be present in human vitreous. Expression or post-translational modification of these
proteins may correlate with disease progression.
Methods: Literature review identified genes associated with AMD and those over
expressed in plasma of smokers. First-degree genetic interactions were identified by
creation of a gene interaction map in silico. Presence of known AMD risk factor gene
products and the novel intermediate genes suggested by our in silico analysis in human
vitreous was confirmed by literature review and by mass spectroscopy of human vitreous
samples obtained from the University of Michigan Vitreous Biorepository.
Results: First-degree genetic interaction mapping of the AMD risk factors ABCA4,
APOE, HTRA1/ARMS2, C2, CFB, C3, CETP, CFH, CFI, COL8A1, FBLN5, FRK, COL10A1,
LIPC, TIMP3 and VEGFA revealed primary interacting genes, namely: ALB, EFEMP2,
GRB2, ITGAM, LRP1, CFP, THBS1, EP300, UBC, KDR, HNF4A, C5, MASP1, C4B, ONECUT1.
Genes upregulated in smoking, LRRN3, CLDND1, MUC1, GOPC and LEF1, interacted with
AMD-associated genes via ABL1, SMAD3, GRB2, EP300, HNF4A, ONECUT1 and UBC.
Literature review revealed that 7 of 16 established AMD-associated genes and 5 of 15
inferred candidate genes were previously identified in human vitreous. This reflects a
compilation of 8 studies. Application of an optimized unbiased proteomics assay with
a false discovery rate of <1:1000 revealed gene products of 8 of the 16 established AMD
susceptibility genes, and identified 9 of 15 of the inferred candidate gene products,
including GRB2, which links the AMD risk factors to smoking.
Conclusions: Identification of primary interacting genes between well-known AMD
risk factors revealed novel candidate genes in AMD pathogenesis that were confirmed in
vitreous samples. Future studies examining the relationship among vitreous expression
profiles, smoking, and disease progression will help to clarify which factors are most
relevant to the pathophysiology of AMD.
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The Retina Society
Poster #11
Retinal Astrocytoma: Diagnosis by Multimodality Imaging
Ekaterina Semenova, MD, PhD
New York, NY
Sabah Shah, MD, Lucia DePablo, MD, Paul T. Finger, MD, FACS
Purpose: To cross characterize retinal astrocytomas using modern diagnostic imaging.
Methods: We evaluated color fundus photography, fluorescein angiography (FA), high
resolution spectra spectral domain optical coherence tomography (SD-OCT), fundus
autofluorescence (FAF) images and ultrasonography (USG) in 10 patients with retinal
astrocytoma. Images were analyzed and characteristic tumor features were recorded.
Results: Six patients were female, 4 male and their mean age was 41.3 years (range: age
9-76 years). Two had tuberous sclerosis. One had bilateral multifocal astrocytomas. The
patients mean visual acuity was 20/20 (range 20/16-20/160). Eight patients were followed
for a mean 33 months (maximal follow-up for 76 months).
Seven tumors were located near or touching the optic disc. The rest were in the posterior
pole. Color fundus photography revealed white to yellow tumors; 6 were opaque and 4
translucent. Fluorescein angiography initially revealed discrete intrinsic tumor vessels in
7 cases. All demonstrated late diffuse tumor hyperfluorescence. FAF (n=5/10) revealed
hyperautofluorescence in 2 tumors and hypoautofluoresence in 3. SD-OCT was performed
in all cases and revealed vitreous tumor seeding in 6 as well as 1 tumor with adjacent
subretinal fluid. Multiple small cysts were visualized in the tumor stroma. USG was
performed (n=8/10) and revealed moderate to high internal tumor reflectivity and posterior
orbital shadowing in 4. Overall, mean tumor thickness was measured at 1.4mm (range
1.0-1.6).
Conclusions: Multimodality imaging of retinal astrocytomas was performed and
contrasted. Fundus imaging revealed tumor color, that was mostly an opaque white to
yellow and opaque. SD-OCT offered the best resolution of internal astrocytoma structures
and subretinal fluid. Flourescein angiography revealed intrinsic vasculaturity and USG
could be used for tumor measurement. With 33 mean months of observation, all astrocytic
hamartomas were non-progressive.
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187
Poster #12
Automated Choroidal Thickness Map Generation Using
Image Segmentation Analysis
Sabin Dang, MD
Detroit, MI
Satyesh Rana, BS, Ankur Mehta, MD, Asheesh Tewari, MD
Purpose: Advances in imaging technology allow for in vivo investigations of choroidal
pathology, however these technologies require manual tracing of choroidal-scleral
boundaries to perform measurements. Such manual tracing makes it difficult to perform
large analyses and develop clinical applications. In this study we developed a novel image
segmentation analysis to automatically generate choroidal thickness maps using available
OCT hardware and tested how well these maps compare to those generated by manual
image segmentation.
Methods: Ten images from 5 normal subjects and 5 subjects with dry macular
degeneration were selected from our Zeiss Cirrus image database. Our image segmentation
algorithm was applied to these images and provided points corresponding to the RPE
and choroidal-scleral interface. Additionally, a blinded grader manually traced these same
boundaries. The resulting choroidal thickness measurements from both methods were
compared. Finally, we employed a support vector machine (SVM) to ascertain if clinically
relevant data could be extracted from the pattern of choroidal thickness as assessed by our
algorithm.
Results: Mean choroidal thickness for the dry AMD group was measured to be
138.53±33 by the manual grader and 147.41±33 by our image segmentation algorithm
(p 2 = 0.99). Moreover, the SVM analysis accurately diagnosed dry AMD via pattern analysis
in 80% of images analyzed by our algorithm.
Conclusions: Several manufacturers are working towards OCT systems that can
provide automated choroidal thickness data. However, many practicing retina specialist
have already invested in imaging equipment capable of visualizing the choroid. Our proofof-concept study demonstrates that clinically relevant choroidal thickness mapping can be
obtained without the expense of new OCT systems.
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The Retina Society
Poster #13
Microaneurysm (MA) Wall Hyperreflectivity on Adaptive
Optics Scanning Laser Ophthalmoscopy (AOSLO) Imaging is
Associated with Worse Vision and MA Persistence over Time
in Diabetic Eyes
Jennifer K. Sun, MD
Boston, MA
Jan Lammer, MD, Paolo S. Silva, MD, Lloyd Paul Aiello, MD, PhD
Purpose: To characterize the association of MA wall hyperreflectivity on AOSLO imaging
with visual acuity and MA turnover in eyes of diabetic patients.
Methods: MAs in eyes with diabetic retinopathy were imaged by AOSLO utilizing
confocal and pinole aperture offset techniques. Dewarping, averaging and automatic
registration of all images were performed with customized Matlab software. AOSLO images
were graded for wall hyperreflectivity (WH), size, and perfusion pattern. All eyes underwent
spectral domain optical coherence tomography (SDOCT), and the substack of 5 B-scans
centered on each MA was graded for structural characteristics including disorganization
of the retinal inner layers (DRIL). Demographic information including best corrected visual
acuity (VA) was obtained from the customized electronic medical record.
Results: Imaging was performed for 109 MAs from 30 eyes (29 subjects: mean±SD age
46±13yrs, DM duration 26±10yrs, 62% male). WH was more frequent in MAs visible on 30°
photographs (93% vs 60%, p=0.0007), more likely to have lumen clots (68% vs 17%,p>20%
(91% vs 25%, p=0.003) over time. In contrast, MAs with WH at follow-up were significantly
less likely to have decreased in size than those without (0% vs 71%, p=0.02).
Conclusions: These preliminary results suggest that MA wall hyperreflectivity on
AOSLO imaging is correlated with both functional and anatomic ophthalmic outcomes.
Future studies may determine whether this AOSLO parameter is a reliable biomarker for
visual loss or regression of vascular lesions in the diabetic eye.
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189
Poster #14
Intraocular Inflammation Following Aflibercept Injection
Howard F. Fine, MD, MHSc
New Brunswick, NJ
Daniel B. Roth, MD, Sumit P. Shah, MD, H. Matthew Wheatley, MD
Purpose: To report the characteristics and frequency of intraocular inflammation
following intravitreal aflibercept injection.
Methods: A retrospective review was performed of consecutive patients who received
intravitreal aflibercept in a group retinal practice from November 2011 through June 2013.
Results: There were 28 cases of intraocular inflammation following a total of 5905
aflibercept injections among 1660 patients. The mean baseline acuity was 20/57 which
decreased to 20/179 at diagnosis (p<0.0001), but recovered to 20/59 at month 1, 20/57
at month 3, and 20/52 at month 6 (p=NS). Vitreous culture and injection of antibiotics
was performed in 8 cases, all were culture negative; the remainder received only topical
corticosteroids.
Conclusions: The frequency of inflammation following aflibercept was 0.47% per
injection. Visual acuity and inflammation returned to baseline within 1 month in most cases
with topical corticosteroids.
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Poster #15
Intravitreal Aflibercept for Treatment of Radiation
Retinopathy
James Singer, DO
Wyoming, MI
Liliya Shevchenko, DO, Thomas Aaberg Jr, MD
Purpose: To report the results of aflibercept for radiation-related ophthalmic
complications.
Methods: A retrospective chart review of 21 patients who received aflibercept for
radiation-related complications from July 2012 to October 2013 was conducted. 19 patients
underwent treatment for radiation retinopathy-associated cystoid macular edema (CME)
and 2 patients for radiation-induced anterior segment neovascularization. All patients
received a series of 2 initial monthly intravitreal aflibercept injections followed by a
treat and extend protocol. The following data was recorded and analyzed: visual acuity,
central subfield thickness measured by optical coherence tomography, presence of
neovascularization, intraocular pressure, lapse time from initial radiation insult, number of
injections, complications encountered, and prior treatments.
Results: On average, patients received injections every 5.4 weeks over a mean follow up
period of 10.2 months (range 5-13). In those patients treated for radiation-associated CME
(n=19), the mean best-corrected visual acuity improved from 20/121 at baseline to 20/96
at the last follow-up, but this improvement was not statistically significant (p=0.085). The
mean central subfield thickness decreased from 425µm at baseline to 300µm at the last
follow-up (p=0.001). Six patients had failed prior treatment(s) for radiation retinopathy.
Anterior segment neovascularization temporarily regressed for two patients at which point
panretinal photocoagulation was performed. No serious systemic or ocular side effects
were observed.
Conclusions: Intravitreal aflibercept appears to promote resolution of CME and
anterior segment neovascularization in patients with radiation retinopathy, yielding
improved anatomical outcomes. While patients with CME also experienced a trend towards
improved visual acuity, this finding was not statistically significant. These data suggest
intravitreal aflibercept represents a viable treatment option for radiation-related ophthalmic
complications, even in certain recalcitrant cases which have failed other modalities. Larger
studies are indicated to affirm these findings and to further establish the effect of this
medication on visual outcomes.
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191
Poster #16
Visual and Anatomical Improvement Following
Dexamethasone Intravitreal Implant in Eyes with Anti-VEGF
Resistant Macular Edema due to Retinal Vein Occlusion
Great Neck, NY
Khurram Chaudhary, MD
Purpose: To report six cases of visual and anatomical improvement following
dexamethasone intravitreal implant (DEX) in patients with anti-VEGF resistant macular
edema due to retinal vein occlusion.
Methods: The medical records of six patients with anti-VEGF resistant macular edema
due to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) were
retrospectively reviewed. Included patients were treated with one or more intravitreal
anti-VEGF injections with minimal improvement or worsening in macular edema and visual
acuity that showed marked improvement following intravitreal treatments with DEX.
Results: We identified six patients with retinal vein occlusion who presented with
macular edema that was resistant to treatment with anti-VEGF agents and improved with
subsequent injection of DEX implant. Three patients had a CRVO and three patients had
a BRVO. The median number of anti-VEGF injections prior to DEX was 11.5 (Range, 1 to
15). The median initial foveal thickness was 518um (Range, 290um to 983um). The median
foveal thickness following anti-VEGF injections was 675um (Range, 514um to 821um). After
treatment, median final foveal thickness (following one DEX implant) was 273um (Range,
248um to 381um). The median initial visual acuity was 20/155 (Range, 20/100 to 20/400).
The median visual acuity following anti-VEGF injections was 20/123 (Range, 20/60 to
20/250). After one DEX injection, median visual acuity improved to 20/55 (Range, 20/25 to
20/80).
Conclusions: Macular edema from retinal vein occlusions that are not responsive to
anti-VEGF medications may improve significantly when treated with DEX. Early use of DEX
in eyes that do not respond well to initial anti-VEGF therapy should be considered.
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Poster #17
Efficacy and Tolerability of Bilateral DEX Implant for the
Treatment of Non-Infectious Posterior Uveitis and Macular
Edema Secondary to Retinal Vein Occlusion
Steven J. Ryder, MD
New York, NY
Swetangi Bhaleeya, MD, Szilárd Kiss, MD, Thomas Albini, MD
Purpose: To report our experience with bilateral placement of dexamethasone 0.7 mg
sustained-release intravitreal implant (DEX Implant) in the management of macular edema
secondary to retinal vein occlusion or inflammation in in the setting of noninfectious
posterior uveitis.
Methods: A retrospective chart review of patients treated with bilateral DEX implants
was performed. Demographic data, complete ophthalmic examinations including signs of
inflammation, visual acuity, fundus photography, fluorescein angiography, optical coherence
tomography, and tolerability of the implants were assessed.
Results: Twenty-two eyes of 11 patients (9 female) treated with a total of 31 DEX
implants were included. The mean follow-up for all eyes was 24.4 months (range 1-28
months). 6 eyes received 2 and 1 eye received 4 implants during the follow-up period. 10 of
11 patients received bilateral DEX implants due to active non-infectious uveitis: 7 patients
had bilateral idiopathic posterior uveitis, 1 had sarcoidosis associated bilateral panuveitis,
1 patient had polyarteritis nodosa associated posterior inflammation, and 1 patient had
active Vogt-Koyanagi-Harada syndrome. None of the patients had bilateral injections on
the same day. The mean interval between injection of the initial eye and the injection of the
second eye was 24.36 days (range 2 to 71 days). All 20 uveitis eyes demonstrated clinical
and angiographic evidence of decreased inflammation following DEX injection. 6 patients
required re-injection for recurrence of inflammation (mean interval between 1st and repeat
injection was 6.33 ± 2.43 months). The 11th patient in the series presented with bilateral
CRVO. The interval between the DEX implant in the initial eye and the subsequent DEX the
in fellow eye was 40.76 months (reflecting the interval between the CRVOs). 7 of 22 eyes
(31.8%) were pseudophakic at the time of initial DEX injection; no eyes underwent cataract
extraction during the follow-up period. No serious ocular or systemic adverse effects were
noted during the follow-up period. On average, the visual acuity improved from 20/43.8
(logMAR 0.34 ± 0.43) to 20/36.4 (logMAR 0.26 ± 0.41) [p=0.23]. During the follow-up
period, the mean intraocular pressure (IOP) increased from 14.13 ± 3.13 mm Hg to 15.10 ±
3.64 mm Hg (p=0.19). 5 eyes (23.8%) required initiation of IOP lowering medications. No
patients required glaucoma laser or filtering procedure during the follow-up.
Conclusions: Bilateral DEX implants appear to be well tolerated and an effective
treatment option in the setting of posterior non-infectious uveitis and retinal vein occlusion.
The efficacy and safety profile of bilateral implants appears to be similar to that seen in the
pivotal DEX clinical trials, where only one eye of each patient was included.
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193
Poster #18
Inpatient Ophthalmology Consultation for Fungemia:
Prevalence of Ocular Involvement and Necessity of
Funduscopic Screening
Murtaza Adam, MD
Philadelphia, PA
Megan M. Nichols, BA, Sina Vahedi, BA, Robert E. Fintelmann, MD,
Jeremy D. Keenan, MD, Sunir J. Garg, MD, et al
Purpose: Recently published data suggest routine ophthalmic consultation for
asymptomatic, verbal patients with positive fungal blood cultures may be an inefficient
use of resources as the risk of ocular involvement was less than 1%. To determine the
generalizability of these findings, we examined the prevalence of and current microbial
profile of fungal chorioretinitis and endophthalmitis among patients with positive fungal
blood cultures who received ophthalmologic consultation at a tertiary care medical center.
Methods: Inpatient ophthalmology consults from Thomas Jefferson University Hospital
(TJUH) between January 1, 2006 and December 31, 2012 were retrospectively reviewed and
cross referenced to a microbiologic database of positive fungal blood cultures for study
inclusion. Clinical data was obtained from records held by the microbiology laboratory and
TJUH inpatient records. Patients were deemed to have ocular fungal involvement if they
had evidence of chorioretinitis or endophthalmitis on dilated fundus examination.
Results: Of the 215 consults requested to rule out ocular involvement following
positive fungal blood cultures over a 6 year period, 11 patients (5.2%, 95% CI 2.6-9.0%)
were diagnosed with fungal chorioretinitis or endophthalmitis. Of these 11 patients, 4 were
unable to communicate, 5 were symptomatic, and 2 were asymptomatic. An additional 11
patients (5.2%) had non-specific fundus lesions considered to be inconsistent with ocular
fungal involvement. Of the remaining 193 patients, 4 (2.1%) had visual symptoms without
visible retinal pathology. The most common fungal species identified in decreasing order
of frequency were Candida albicans (N=78), Candida glabrata (N=56), and Candida
parapsilosis (N=40).
Conclusions: Our study found a low rate of disseminated ocular involvement in
patients with positive fungal cultures referred for ophthalmologic consultation. However,
over half of the affected patients were asymptomatic or unable to communicate, which
supports the current practice of routine ophthalmic examinations for patients with
fungemia.
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Poster #19
White Dot Syndromes, How to Diagnose and Treat Tropical
Cases: Diffuse Unilateral Subacute Neuroretinitis (DUSN )
and Punctacte Outer Macular Toxoplasmosis
Londrina, PR
Purpose: Describe clinical features, follow up and treatment of these interesting cases
of tropical white dots, DUSN and Atypical Macular Toxoplasmosis called as Punctate Outer
Toxoplasmosis.
Methods: Case Series of 20 cases of inflammatory white dots were analyzed with a
complete ophthalmological exam, retinography and OCT.
Results: Most of the patients were children or young adults; all the DUSN patients
had afferent pupillary defect, nerve fiber layer atrophy on OCT. Some retinal reflex could
mimic a worm on retinography or biomicroscopy. Long term follow up of 3 cases of outer
toxoplasmosis showed recurrences with macular scarring. Some lesions of toxoplasmosis
cases were in inner retina on OCT.
Conclusions: DUSN especially in initial stages and puntacte outer toxoplasmosis can
mimic each other. However, carefully ocular examination and OCT can help to differentiate
each other, and both are treatable diseases.
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195
Poster #20
Endophthalmitis Caused by Streptococcal Species: Clinical
Settings, Microbiology, Management, and Outcomes
Ajay E. Kuriyan, MD, MS
Miami, FL
Harry W. Flynn Jr., MD, William E. Smiddy, MD, Audina M. Berrocal, MD,
Thomas A. Albini, MD, Darlene Miller, MD
Purpose: To report the clinical settings, antibiotic susceptibilities, and outcomes of
endophthalmitis caused by Streptococcus species.
Methods: Single-center, retrospective, observational case series evaluating all patients
with culture-positive endophthalmitis caused by Streptococcus species between January 1,
2000 and December 31, 2011.
Results: Study criteria were met by 63 patients. The most common clinical settings were
bleb-associated (17, 27%), post-intravitreal injection (16, 25%), and post-cataract surgery
(13 21%). The isolates were S. viridans (47, 71%), S. pneumoniae (13, 21%), and ?-hemolytic
Streptococci (5, 8%). Sixty (95%) of 63 isolates were susceptible to vancomycin, 47 (98%)
of 48 to ceftriaxone (third generation cephalosporin), and 57 (93%) of 61 to levofloxacin
(third generation fluoroquinolone). Between the first and second half of the study period,
the minimal inhibitory concentration (MIC) of antibiotics required to inhibit 90% of isolates
increased by 1.5-fold for ceftriaxone and 2-fold for levofloxacin, and remained the same for
vancomycin. Initial treatment was vitreous tap (49, 78%) or pars plana vitrectomy (14, 22%);
all received intravitreal antibiotics. Visual acuity outcomes were variable; best corrected
visual acuity (BCVA) was ?20/400 in 16 (25%) patients and
Conclusions: Streptococcus isolates generally had high susceptibility rates. However,
three isolates in the current study were vancomycin non-susceptible, which has not been
reported in previously published casesof endophthalmitis caused by Streptooccus. There
were higher MICs required to inhibit 90% of isolates in vitro in the second half of the
study period compared to the first half, for ceftriaxone and levofloxacin. Despite prompt
treatment, the majority of patients had poor outcomes.
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Poster #21
Killer Cell Immunoglobulin-like Receptor (KIR) Genes, HLA
Genes, and Parasite Serotypes Among Individuals Infected
with Toxoplasma Gondii
David C. Reed, MD
Philadelphia, PA
Gary Holland, MD, Christian Sanfilippo, MD, Fei Yu, PhD, Patrick Coady, MD,
Ying Qian, MD, et al, and the North American Ocular Toxoplasmosis Study Group
Purpose: Toxoplasma gondii is a common protozoan parasite that can cause
retinochoroiditis in a minority of those infected. Killer cell immunoglobulin-like receptor
(KIR) genes control the effector function of natural killer cells, which are involved in the
early immune response against Toxoplasma gondii infection. Human leukocyte antigens
(HLA) serve as ligands for KIR. Our purpose was to identify genetic risk factors for
developing toxoplasmic retinochoroiditis: parasite (serotype/genotype), host (KIR and HLA
genotype), as well as interactions between parasite serotype and host KIR/HLA.
Methods: We characterized the KIR and HLA genotypes and T. gondii serotype of
123 immunocompetent adults from six clinical sites with serologic evidence of T. gondii
infection. All subjects underwent ophthalmic examination to determine the presence of
toxoplasmic retinochoroiditis. The KIR and HLA genotypes of patients with and without
toxoplasmic retinochoroiditis were compared, and interactions with T. gondii serotype were
measured.
Results: Type II toxoplasmosis was more common in white Caucasians (9/33; 27%)
than in Hispanics (12/88; 14%). Type II toxoplasmosis was also more common in the
Northeast (5/24; 21%) than in California (16/99; 16%). Type I/III toxoplamosis was more
common in California Hispanics with toxoplasmic retinochoroiditis (9/29; 31%) than those
without (10/51; 20%). Nonreactive serotypes were more common in California Hispanics
without retinochoroiditis (23/51; 45%) than those with retinochoroiditis (8/29; 27.6%).
There were no significant associations between individual KIR genes and toxoplasmic
retinochoroiditis. Four HLA genotypes showed statistically significant differences between
the retinochoroiditis and control groups: ligand HLA-C1, and antigens HLA-A68, -B39,
and -C6. Among Hispanics, an interaction between the functional KIR2DL1/HLA-C2 pair
and type II serotype was found to be protective against retinochoroiditis. In contrast, an
interaction between the functional KIR3DL1/HLA-Aw4 was found to increase susceptibility
to retinochoroiditis.
Conclusions: Our data supports a role for T. gondii serotype, and suggests an
interaction between serotype and host KIR genes and HLA genes in susceptibility to
clinically apparent toxoplasmic retinochoroiditis.
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197
Poster #22
Histopathology of Streptococcus Mitis/Oralis
Endophthalmitis After Intravitreal Injection with
Bevacizumab; A Report of 7 Patients
Miami, FL
Jared L. Matthews, MD, Roger A. Goldberg, MD, MBA, Harry W. Flynn Jr., MD
Purpose: To report the histopathologic findings of a series of patients from an outbreak
of Streptococcal endophthalmitis after intravitreal injection of bevacizumab prepared by a
single compounding pharmacy.
Methods: Design: Case series.
Participants: Seven surgical specimens (5 enucleated globes and 2 evisceration
specimens) from 7 patients with endophthalmitis after intravitreal injection of bevacizumab.
Retrospective case series, including clinical data and histopathologic specimens examined
by light microscopy.
Results: Main Outcome Measures: Review of clinical data included baseline visual acuity,
clinical intervention, and time elapsed from injection to loss of globe. Histopathologic
specimens were reviewed for pathologic changes at all tissue levels.
Seven of 12 total patients (4 women, 3 men; mean age, 77.7 years) from an outbreak of
Streptococcus mitis/oralis endophthalmitis after bevacizumab injection ultimately sustained
loss of the affected globe, with an average of 139.1 days elapsed between injection and
globe loss. Mean time from injection to presentation was 2.86 days (range, 1e6), and all
patients were initially treated with vitreous tap and injection. Although histologic review of
surgical specimens disclosed a wide range of pathologic tissue changes, recurring patterns
of tissue damage were evident. All 5 enucleated globes displayed retinal detachment,
fibrous proliferation with cyclitic membrane formation, rubeosis iridis, and secondary angle
closure. All 7 specimens displayed persistent choroidal inflammation, in 1 case 208 days
after injection. Six of 7 specimens had foci of retinal necrosis. Although vitreous cultures
were positive in all cases, no organisms were identified by light microscopy in any of the 7
specimens.
Conclusions: S. mitis/oralis endophthalmitis is a devastating complication of
intravitreal injection with bevacizumab with a high rate of globe loss (7 of 12 patients,
58.3%) and a wide variety of severe pathologic tissue changes. Although no organisms
were identified in the examined tissues, persistent inflammation was present in all cases,
and fibrous proliferation resulted in cyclitic membrane formation and retinal detachment in
all enucleated globes. These findings suggest that potential globe-salvaging interventions
must address a pattern of changes involving persistent, chronic inflammation and
fibrovascular proliferation as key components.
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Poster #23
Streptococcalmitis Endophthalmitis Presenting as Occlusive
Vasculitis Following Intravitreal Injection of Ranibizumab
Alan J. Ruby, MD
Royal Oak, MI
George A. Williams MD
Purpose: To report on the wide field fluorescein angiographic findings of a patient
presenting with streptococcal mitis endophthalmitis eighteen hours following intraviteal
injection of ranimizumab.
Methods: Wide field fluorescein angiography was used to evaluate a patient who
presented with decreased vision of hand motion and findings suggestive of an occlusive
vasculitis less than one day following intravitreal injection. No significant findings
suggesting an inflammatory condition were noted at the time of presentation.
Results: Wide field angiography showed a diffuse vasculitis involving both the
veins and arteries. There was complete non perfusion of the major vessels distal to the
macula and three disc diameters from the optic nerve head in the remaining nine clock
hours. Large intraretinal hemorrhages were seen inferiorly, superiorly and temporally as
well as smaller hemorrhages in the macula. No vitritis was noted and only rare anterior
chamber pigmented cells were seen. The patient was taken to surgery where a pars plans
vitrectomy with injection of intraviteal antibiotics was performed for a presumed diagnosis
of endophthalmitis. Cultures grew out many strep mitis sensitive to vancomycin. The
patient returned to surgery one week following initial vitrectomy for a repeat vitrectomy ,
laser and silicone oil in hopes of preventing anterior segment neovascularization and the
development of PVR. One week later the patient remains with an attached retina, clear
media and vision of counting fingers.
Conclusions: We report the first documented case of streptococcal mitis
endophthalmitis following intravitreal injection presenting with diffuse occlusive vasculitis
documented with wide field angiography and no significant ocular inflammation Strep mitis
is an uncommon pathogen as a cause of post injection endophthalmitis. The bacteria can
secrete a substance which can result in diffuse platelet aggregation and vascular occlusion.
Clinicians should be aware of this unusual presentation of post injection endophthalmitis
demonstrating widespread occlusive vasculitis with poor vision in the absence of significant
inflammation .
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199
Poster #24
Endophthalmitis Rates and Clinical Features Following
Intravitreal Anti-Vascular Endothelial Growth Factor
Injections for Diabetic Eye Disease Versus Neovascular AgeRelated Macular Degeneration and Retinal Vein Occlusion
Eric Chen, MD
Houston, TX
Nadim Reyess, MD, Ehsan Rahimy, MD, Chirag Shah, MD, MPH, Jeremy Wolfe, MD,
Jason Hsu, MD
Purpose: To determine whether patients receiving intravitreal anti-vascular endothelial
growth factor (VEGF) therapy for diabetic eye disease have a greater incidence of
endophthalmitis compared to patients receiving injections for neovascular age-related
macular degeneration (AMD) or retinal vein occlusion (RVO).
Methods: Retrospective, multicenter, observational, case series of patients who received
intravitreal anti-VEGF injections (bevacizumab, ranibizumab, or aflibercept) for the
diagnosis of neovascular AMD, branch RVO, central RVO, diabetic macular edema (DME)
or proliferative diabetic retinopathy (PDR). Patient records were reviewed for age, gender,
affected eye, indication for receiving intravitreal injections, visual acuity, diagnoses, isolated
organisms and sensitivities, number of injections received, procedures performed, and
complete ophthalmic examination of both eyes.
Results: A total of 152 cases of endophthalmitis following 379,609 intravitreal antiVEGF injections (1/2317) were identified. 130 cases of endophthalmitis occurred out of
319,156 injections for neovascular AMD (1/2455), 14 cases occurred out of 25,286 injections
for DME/PDR (1/1580), and 8 cases occurred out of 35,167 injections (1/4395) for RVO.
Chi-square analysis (Stata 12, College Station, Tx) comparing patients with DME/PDR to
patients with neovascular AMD found no difference in rates of endophthalmitis (P=0.273),
as did patients with neovascular AMD compared to those with RVO (P=0.105). Conversely,
endophthalmitis rates were significantly higher for patients receiving intravitreal injections
for DME/PDR than RVO (P=0.038).
Conclusions: Endophthalmitis following intravitreal injections is a rare complication.
In this study, patients with neovascular AMD and DME/PDR had similar endophthalmitis
rates which can be attributed to the older population group in neovascular AMD patients
offsetting the impact of diabetes on the immunity of DME patients. Conversely, patients
with diabetic eye disease and RVO represent patient populations of similar age groups,
with diabetes being the only major contributor towards decreased immunity. Therefore,
patients with diabetic eye disease may be more susceptible to developing endophthalmitis
following intravitreal injections than patients with RVO.
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Poster #25
Uses of the Word “Macula” in Written English,
1400 – Present
Naples, FL
Christopher Leffler, MD, MPH
Purpose: We reviewed various uses of the word “macula” in written English. “Macula”
is commonly used by retina specialists and the lay public, but the word has a rich history
that may be under appreciated. Newer databases, encompassing millions of historical
documents, provide powerful tools to explore various and changing uses of words through
time.
Methods: We searched “macula” in multiple databases, including the Early English
Books Online Text Creation Partnership, which includes over 40,000 texts during 14751700; America’s Historical Newspapers, which includes over 1,000 American newspapers
from 1690 until the early 20th century; the Gale Cengage collections; the Google n-gram
database, which calculates the annual frequencies of 1- to 5-word phrases (n-grams), based
on approximately 6% of books ever published; and others.
Results: The Google n-gram database shows a marked increase in the frequencies of
both “macula” and “macula lutea” following the introduction of the ophthalmoscope in
1850.
“Macula” has been used: as a non-medical “spot” or “stain”, literal or figurative, including
in astronomy and in Shakespeare; as a medical skin lesion, occasionally with a following
descriptive adjective, such as a color ("macula alba"); as a corneal lesion, including the
earliest identified use in English, circa 1400; and to describe the center of the retina.
Francesco Buzzi described a yellow color in the posterior pole (“retina tinta di un color
giallo”) in 1782, but did not use the word “macula”. “Macula lutea” was published by Samuel
Thomas von Sömmering by 1799, and subsequently used in 1818 by James Wardrop, which
appears to be the first known use in English. The definition of the macula evolved during
the 1970s, as illustrated by the sequential editions of the Gass atlas: the original (1970)
edition did not specifically define the size or boundaries of the macula, but the second
(1977) and subsequent editions defined the macula as equivalent to the central retina.
Conclusions: “Macula” has been used in multiple contexts in written English. Modern
databases provide powerful tools to explore historical uses of this word, which may be
under appreciated by contemporary retina specialists.
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201
Poster #26
Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis
(Irvan) Syndrome: A Case Report
Bogota, DC, Colombia
Flor Edith Gómez, MD, Ricardo Infante, MD, Marcela Valencia, MD
Purpose: To describe a bilateral case of idiopathic retinal vasculitis, aneuryms and
neuroretinitis (IRVAN) syndrome that was treated with laser photocoagulation and followed
for 18 years.
Methods: Case report. We reviewed the records of a patient with IRVAN syndrome
between 1985 and 2013. This report describes clinical and angiographic characteristics, and
the evolution of the condition after treatment with focal laser on the aneurysms.
Results: A total of two sessions of laser in the right eye and three sessions in the left eye
were made, which improved macular exudation and achieved stabilization or improvement
of visual acuity. There were no complications.
Conclusions: We report a case of IRVAN syndrome and its evolution, documented by
fluorescein angiography and optical coherence tomography (OCT), in a 18-year follow-up.
Visual and anatomical results achieved with focal laser in this case were higher than other
treatments described for IRVAN syndrome.
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Poster #27
Cystoid Macular Edema After Cataract Surgery in Eyes with
Previous Vitrectomy for Epiretinal Membrane Removal
Tanuj Banker, MD
Washington, DC
James Osher MD, Kristen Migdley BS, Michael Lai MD
Purpose: To determine the incidence of CME after cataract extraction and posterior
chamber intraocular lens placement (CE/PCIOL) in eyes that have undergone small gauge
pars plana vitrectomy (PPV) with epiretinal membrane peel (MP).
Methods: Retrospective consecutive interventional case series of eyes that underwent
PPV for ERM removal and subsequent CE/PCIOL from 2010 to 2012. All PPVs were
done using 23g or 25g systems by 17 surgeons from the Retina Group of Washington.
Exclusion criteria included pre-existing macular disease, postoperative retinal detachment,
previous PPV, follow-up less than three months, and combined PPV/CE/PCIOL. CME was
documented by clinical exam, and confirmed with Spectral Domain Optical Coherence
Tomography (SD-OCT) and fluorescein angiography (FA). Primary outcome measure was
the incidence of CME post CE/PCIOL. Secondary outcome measures included visual acuity
(VA) assessment, changes in macular thickness on SD-OCT, and risk factors associated with
development of CME.
Results: Eighty-one eyes with a mean age of 65.16 +/- 11.7 years were followed for
a mean time of 579 days. The mean VA was 20/60 (logMAR 0.48 ± .24) pre-MP, 20/80
(logMAR 0.59 ± .39) prior to CE/PCIOL, and improving to 20/30 (logMAR 0.21 ± .19) post
CE/PCIOL (p < 0.01). The mean central macular thickness (CMT) was 396.30µ ± 84.1µ
pre-MP, decreasing to 334.1µ ± 71.25µ post-MP (p<0.01), and to 341.41µ ± 99.2µ post CE/
PCIOL (p<0.02). Post CE/PCIOL, 21.0% of eyes (n=17) had CME documented by clinical
exam and confirmed with OCT and FA. CMT was 385.67µ ± 129.95µ for eyes with CME vs.
317.40µ ± 69.97µ for eyes without CME (p<.04). Post CE/PCIOL, the mean VA was 20/40
(logMAR 0.29± .20) for eyes with CME vs. 20/30 (logMAR 0.17± .17) (p<.03). 59.3% (n=48)
of MPs included intraoperative internal limiting membrane peeling (ILM) peeling. Eyes with
ILM peeling had a higher rate of CME (31.25%) vs. (7.69%) for eyes without peeling (p<.02). Conclusions: CME develops frequently after cataract surgery in eyes that have
undergone previous PPV for ERM removal. Peeling of the ILM may be associated with
higher rates of CME. Eyes undergoing CE/PCIOL after PPV/MP require careful monitoring
with SD-OCT to rule out postoperative CME.
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Poster #28
Silicone Oil Behavior: Emulsified Imaging (15 Cases) and
“Non-Emulsified” Extracted Analysis
Yale L. Fisher, MD
Delray Beach, FL
Jesse T. McCann, MD, PhD, Suqin Yu, MD
Purpose: The purpose of this project was to confirm the presence of emulsified silicone
oil, via multimodal imaging, in 15 cases that have undergone vitreoretinal tamponade,
and to report on the electron microscopic imaging and polymeric analysis of extracted,
“non-emulsified” oil.
Methods: High resolution optical coherence tomography, ultrasound imaging and
adaptive optics were utilized to image silicone oil droplets within the vitreous, retina and
optic nerve of 15 patients following attempted extraction of emulsified oil. In 2 additional
patients, extracted “non-emulsified” silicone oil was also examined by cryo-electron
microscopy and polymeric chemical analysis.
Results: In all 15 eyes with emulsified silicone oil, droplets could be detected by at least
one imaging technique. Dissemination of nano- and micro-sized bubbles of silicone oil
was visible within the vitreous, retina and optic nerve. Appearance differed by each of the
imaging techniques. Extracted silicone oil from “non-emulsified” cases was analyzed by
electron microscopy and revealed micro-emulsification. Results of the polymeric analysis
will be presented.
Conclusions: Intraocular silicone oil droplets emulsify and disseminate throughout
the ocular structures in nano- and micro-sized bubbles that can be imaged in vivo by
multimodal techniques. Oil droplet residues persist in the ocular tissues following extraction
attempts. In vitro cryo-electron microscopy is suggestive of early possible dissemination
even prior to clinical observation. The equilibration of silicone oil with lipid-soluble
components in the eye is consistent with phase-equilibrium behavior.
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Poster #29
Evaluation of an Adhesive Biopolymer for the Treatment
of Retinal Detachment in Rabbit Eyes to Evaluate the Safety
and Efficacy of a Newly Developed Biopolymer for the
Treatment of Rhegmatogenous Retinal Detachment
Los Angeles, CA
Purpose: To evaluate the safety and efficacy of a newly developed biopolymer for the
treatment of rhegmatogenous retinal detachment on rabbit eyes.
Methods: Pars plana vitrectomy with posterior vitreous detachment followed by
induction of a retinal tear and retinal detachment was performed in 6 rabbits. One eye was
operated on for each rabbit and the fellow eye was used as control. Group A consisted
of 4 rabbits that were treated with the bioplolymer to seal the retinal tear after retinal
re-attachment and laser retinopexy was performed. Group B consisted of two rabbits that
were treated with SF6 as the tamponading agent. Funduscopic examination was carried
out in both groups at day 1, 7, 14 and 21. B-scan evaluation of the retina was performed at
day 7, 14 and 21. Eyes of group A were enucleated on 14th and 21st postoperative day for
histological evaluation.
Results: The funduscopic examination showed that the retina was reattached in all eyes.
Histological examination revealed that the biopolymer adhered tightly to the retina and
there was no inflammatory change at the application sites.
Conclusions: This study confirms that the new adhesive biopolymer, which
demonstrated absence of any functional and anatomical retinal toxicity on previous studies
conducted on mice, adheres and seals retinal tears effectively without any inflammatory
reaction on retinal detachment in rabbit eyes.
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205
Poster #30
Outcomes of Diabetic Vitrectomy in a County Hospital
Population
Annal Dhananjayan Meleth, MD, MS
Marietta, GA
Usha Pinninti, MD, Cindy Hwang, MD, Mediha Ahmad, BS, Golnaz Javey, MD,
Jaafar El-Annan, MD, et al.
Purpose: To determine the visual outcomes and factors influencing these following
diabetic vitrectomy.
Methods: Retrospective chart review of diabetic vitrectomy performed at a single
county hospital from June 2010 to January 2013. Data collected included systemic, ocular,
and surgical variables: Age, Sex, Race, Diabetes duration, Insulin dependence, A1c, Renal
status, Neuropathy, Coronary artery disease, Cerebrovascular accident, blood pressure,
Cholesterol, Body Mass Index, Pre-operative diagnosis, Pre-operative and post-op visual
acuity, vitrectomy gauge, tamponade agent, # of iatrogenic breaks, and # of surgeries.
Statistical comparisons between categorical variables were performed and a logistic
regression model was fit with improvement in visual acuity as the dependent variable.
Results: 249 eyes of 168 patients (77.5% Hispanic) were included. Mean HbA1c at
baseline was 8.7%, Mean BMI was 30.5. The primary indication for vitrectomy was tractional
retinal detachment (65.7%). Vision improved following diabetic vitrectomy in 74.7%.
Patients with non-clearing vitreous hemorrhages (NCVH) were less likely to lose vision (OR
0.29, 95% CI 0.0-0.53, p<0.01). Similarly, patients requiring a single surgery were also less
likely to have worsening of vision (OR 0.55, 95% CI 0.08-0.56, p<0.01). Type of tamponade,
and number of iatrogenic breaks were not significantly associated with likelihood for
improvement in vision. The average presenting visual acuity was Count Fingers. The
proportion of patients achieving better than 20/63 visual acuity at their final post-operative
visit was 57% among patients with NCVH, and 20% among patients with TRDs. The overall
rate of LP vision or less was 21.5%.
Conclusions: Visual outcomes for diabetic vitrectomy are generally good. The
probability of visual improvement is much higher in patients presenting with NCVH. In the
study population, tractional retinal detachment at presentation and the requirement for
multiple vitrectomies leads to poorer visual outcomes.
206
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The Retina Society
Poster #31
Combined DSEK and Transconjunctival Pars Plana
Vitrectomy
Saad Shaikh, MD
Orlando, FL
Mona Sane, MD, Naazli Shaikh, MD
Purpose: To describe surgical technique and limitations for combined DSEK and
transconjunctival pars plana vitrectomy in patients with bullous keratopathy and
concomitant vitreoretinal pathology.
Methods: Retrospective non-comparative case series. Three cases underwent combined
DSEK for bullous keratopathy and pars plana 23 gauge vitrectomy for preexisting
vitreoretinal pathology. Methods and surgical technique are described.
Results: None of the patients had intraoperative or postoperative complications.
Anatomic and visual outcomes of combined DSEK and vitrectomy were excellent.
Conclusions: Combined DSEK and small gauge vitrectomy may be considered in
patients with corneal decompensation and posterior segment pathology amenable to
surgical management. Limitations to technique and patient selection should be noted. The
combined minimally invasive techniques allow for rapid anatomical recovery and return of
function and visual acuity in a single sitting in selected patients.
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207
Poster #32
A Systematic Review and Meta-Analysis Comparing
Same-Day vs. Delayed Vitrectomy Clinical Outcomes for
Intravitreal Retained Lens Fragments After Age-Related
Cataract Surgery
Elizabeth A. Vanner, PhD
Stony Brook, NY
Michael W. Stewart, MD
Purpose: Perform a systematic review and meta-analysis comparing the risk difference
(RD) of clinical outcomes for same-day (SD-PPV) vs. delayed pars plana vitrectomy
(DEL-PPV).
Methods: Searched MEDLINE (English, 1/1/85 to 07/16/2013) and article reference lists,
for patients with crystalline retained lens fragments (RLF) and discussion of SD-PPV vs.
DEL-PPV. For meta-analysis, articles needed the number of patients receiving SD-PPV and
DEL-PPV and the number in each group who experienced one or more of the outcomes:
not good visual acuity (VAng20/200), retinal detachment, increased intraocular pressure,
intraocular infection/inflammation, cystoid macular edema, and corneal edema.
Results: Of 304 articles identified, 23 provided data for the meta-analysis. Results were
mixed.
(1) With all studies included in the meta-analysis, neither vitrectomy time produced better
outcomes. For VAng, RD=10.3% (positive RDs indicated better outcomes for SD-PPV), 95%
confidence interval (CI)=(-0.4% to 21.0%), p=0.059. For VAB, RD= -0.3% (negative RDs
indicated better outcomes for DEL-PPV), 95%CI=(-10.7% to10.1%), p=0.953.
(2) Studies that only included SD-PPVs performed immediately after cataract surgery (no
long waits, no inter-facility patient transport, and no cataract surgeons attempting RLF
removal) indicated better outcomes with immediate SD-PPV compared to all DEL-PPVs.
For VAng, RD=16.2%, 95%CI=(0.8% to 31.5%), p=0.039. For VAB, RD=8.5%; 95%CI=(0.8%
to16.2%), p=0.030.
(3) Results comparing immediate SD-PPV and prompt DEL-PPV (3-7, 3-14, or 7-14 days
post-cataract surgery) were mixed: 23 results favored SD-PPV and 12 favored DEL-PPV.
Only 1 result (of 35, 2.9% - less than the expected Type I error rate of 5%) was statistically
significant. For VAng, RDs ranged from -19.9% to 6.5%, and for VAB, RDs ranged from
-6.9% to 7.4%. This supports a preliminary hypothesis that prompt DEL-PPV and immediate
SD-PPV may produce similar outcomes.
Conclusions: Perhaps SD-PPV should be limited to facilities at which a vitreoretinal
surgeon is immediately available. Otherwise, when RLFs occur, as long as the cataract
surgeon refers the patient to a vitreoretinal surgeon in time for a prompt DEL-PPV, results
support current cataract surgery practice patterns and locations, but don’t support interfacility transport for a SD-PPV. A multi-centre, randomized controlled trial could test a
non-inferiority hypothesis comparing immediate SD-PPV and prompt DEL-PPV outcomes.
208
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The Retina Society
Poster #33
Postmarketing Surveillance Survey of Adverse Events of
Ocriplasmin
Sumit P. Shah, MD
Norwalk, CT
Karen Jeng, MPH, Howard F. Fine, MD, MHSc, Harold M. Wheatley, MD,
Daniel B. Roth, MD
Purpose: To study the postmarketing safety profile of ocriplasmin as experienced by
retinal physicians in the United States.
Methods: Two thousand four hundred sixty-five (2465) retinal physicians were
surveyed via the web based SurveyMonkey® software regarding their frequency of use of
ocriplasmin and incidence of ocular adverse events.
Results: There were 270 respondents (11.0%) who reported treating 1056 eyes
with ocriplasmin; 91.5% of respondents were male and 8.5% were female. Geographic
distribution of respondents was: Northeast (32.1%), South (24.4%), Midwest (24.4%), and
West coast (19.1%). Practice type distribution included: retina group practice (49.4%),
multispecialty group practice (23.2%), full time academic practice (16.2%), solo private
practice (10.7%).
The incidence of adverse events were as follows: acute decline in Va 179 (16.95%),
development of submacular fluid or serous RD 108 (10.23%), dyschromatopsia 96
(9.09%), progression of VMT to macular hole 92 (8.71%), development of RRD 28 (2.65%),
development of retinal tear 21 (1.99%), development of afferent pupillary defect 19 (1.80%),
ERG abnormalities 6 (0.57%), crystalline lens instability 4 (0.38%), and vasculitis 3 (0.28%).
15.9% of physicians who experienced an adverse event reported their incident to the Food
and Drug Administration and 84.1% did not.
Conclusions: Although the incidence of many ocular adverse events reported in this
study are comparable to those reported in the phase III registration trials, additional phase
IV safety studies are warranted to better understand the pathophysiology of ocular adverse
events of ocriplasmin.
|
209
Poster #34
Comparing Retina Quality Performance Measures Publicly
Reported by Ophthalmic Organizations
Monica Michelotti, MD
Ann Arbor, MI
Jennifer Weizer, MD, Simon P. Kelly, FRCSEd, FRCOphth, FEBO,
Bill Aylward, FRCOphth, Declan Flanagan, FRCOphth, Mark W. Johnson, MD, et al
Purpose: There is increasing global interest in evaluating health care quality by
measuring clinical and patientreported outcomes in all specialties, and in publishing these
outcomes for the medical field and lay public. Several ophthalmic provider groups now
publicly report performance, but the metrics used differ. Critical analysis of currently used
metrics can improve the usefulness of reported outcomes.
Methods: An online search for quality, especially outcomes, data for international
ophthalmic institutions was performed; results were compared with published outcomes
and performance data for retinal surgery. The World Association of Eye Hospitals provided
additional unpublished hospitalspecific measures. Data were available from Aravind Eye
Hospital, Cole Eye Institute, University of Michigan W.K. Kellogg Eye Center, Massachusetts
Eye and Ear Infirmary, Moorfields Eye Hospital, Singapore National Eye Center, and St Erik’s
Eye Hospital.
Results: The number of retinal metrics measured by institutions varied from two to
twenty-nine. Postoperative retinal reattachment rates ranged from 80% to 98% (n=5), with
some institutions separating cases based on complexity (n=3) and others combining all
cases (n=2). The number of specific complications rported varied significantly (n = 3 range
=0 - 13). The incidence of endophthalmitis after intravitreal injection ranged from 0% to
0.04% (n=4). Two hospitals reported visual improvement rates after retinal surgery and one
reported visual improvement rates after injections for macular degeneration. Outcomes for
macular hole surgery included anatomic closure, vision improvement ? 3 ETDRS lines, and
average visual improvement. Unique measures included success of retinopexy at 6 months
(laser 90%, cryotherapy 95%), and visual improvement in diabetic vitrectomy for tractional
retinal detachments (mean 11.9 ETDRS letters).
Conclusions: Published outcomes and quality of care data in ophthalmology varies
by institution, and therefore understanding and identifying metrics that all might agree
upon is crucial. It is necessary to identify case mix in order to appropriately interpret data
in a useful manner. Comparing outcomes by international ophthalmic institutions will help
benchmark services in the timely quest to improve quality and safety in healthcare.
210
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The Retina Society
special thanks
special thanks to our GOLD PATRONS AND PATRONs
for their level of support
T
he Retina Society sincerely thanks our corporate supporters at every level
for their contributions to our meeting. In addition, we are deeply grateful
for their ongoing commitment to provide innovative and sophisticated
equipment, pharmaceuticals, and services for the care of patients with vitreoretinal
diseases. We acknowledge our debt to their excellence, and are delighted to
have such talent in the development of new vitreoretinal treatments.
gold patrons
Genentech
BOOTH #20 — Grant
Regeneron Pharmaceuticals, Inc.
BOOTH #7 — Meade
patrons
Alcon
BOOTH #21 — Grant
Allergan
BOOTH #18 — Grant
ThromboGenics
BOOTH #16 — Meade
This CME activity is supported by an educational grant from
RetinaLink LLC
|
211
Exhibitors
Alcon — PATRON
BOOTH #21 — Grant
Elsevier
TABLE #4 — Grant
6201 South Freeway
Ft. Worth, TX 76134-2099
CONTACT: Janet Burk
[email protected]
817.551.8776
1600 JFK Blvd, Suite 1800
Philadelphia, PA 19103
CONTACT: Kimberly Pollock
[email protected]
215.239.3722
www.elsevierhealth.com
Alimera Sciences
BOOTH #2 — Meade
6120 Windward Parkway, Suite 290
Alpharetta, GA 30005
CONTACT: Elizabeth VanDeBogart
[email protected]
678.527.1307
alimerasciences.com
Allergan — PATRON
BOOTH #18 — Grant
Genentech — GOLD PATRON
BOOTH #20— Grant
1 DNA Way, MS 313B
South San Francisco, CA 94080
CONTACT: Sue Garcia
[email protected]
650.238.8040
www.gene.com
Heidelberg Engineering
BOOTH #3 — Meade
2525 Duont Drive
Irvine, CA 92612
CONTACT: Harry Davis
[email protected]
714.246.5135
1808 Aston Avenue, Suite 130
Carlsbad, CA 92008
CONTACT: Deanne Redick
[email protected]
760.536.7100
www.heidelbergengineering.com
Bausch + Lomb
BOOTH #10 — Meade
Insight Instruments, Inc.
BOOTH #12 — Meade
700 Route 202/206 North
Bridgewater Township, NJ 08807
CONTACT: Brenda Dugue
[email protected]
908.541.3254
www.bausch.com
2580 SE Willoughby Blvd.
Stuart, FL 34994
CONTACT: Jade Gold
[email protected]
772.678.5699
insightinstruments.com
Carl Zeiss Meditec
BOOTH #9 — Meade
Janssen Pharmaceutical of J&J
BOOTH #17 — Grant
5160 Hacienda Drive
Dublin, CA 94568
CONTACT: Philina Abbott
[email protected]
925.557.4429
www.meditec.zeiss.com
1400 McKeane
Springhouse, PA 19007
CONTACT: Susan Orr
[email protected]
817.300.8366
www.janssen.com
Dutch Ophthalmic USA
BOOTH #4 — Meade
Lippincott Williams & Wilkins |
Wolters Kluwer Health
TABLE #2 — Grant
10 Continental Drive, Bldg. 1
Exeter, NH 03833
CONTACT: Laura Jendrick
[email protected]
800.753.8824
www.DORC.NL
212
Two Commerce Square
2001 Market Street
Philadelphia, PA 19103
CONTACT: Joey-Rose Jester
[email protected]
215.521.8300
www.lww.com
|
The Retina Society
Exhibitors
Notal Vision
BOOTH #15 — Meade
4500 Southgate Place, Ste. 400
Chantilly, VA 20151
CONTACT: Jodi Wiener
[email protected]
888.910.2020
www.foreseehome.com
Oculus Surgical, Inc
BOOTH #1 — Meade
562 NW Mercantile Place, Suite 104
Port St. Lucie, FL 34986
CONTACT: Len Kendrigan
[email protected]
772.236.2622
www.oculussurgical. com
OMIC
TABLE #1 — Grant
655 Beach Street
San Francisco, CA 94109
CONTACT: Deena Mader
[email protected]
415.202.4628
www.omic.com
Optos, Inc
BOOTH #13 — Meade
67 Forest Street
Marlborough, MA 01752
CONTACT: Judy Reger
[email protected]
800.854.3039
optos.com
Optovue, Inc
BOOTH #5 — Meade
2800 Bayview Drive
Fremont, CA 94538
CONTACT: Mary Anne Ereso
[email protected]
510.623.8868
www.optovue.com
Pine Pharmaceutical
BOOTH #8 — Meade
5110 Main Street
Williamsville, NY 14221
CONTACT: Douglas Mooradian
[email protected]
716.531.1750
www.pinepharmaceuticals.com
Quantel Medical
BOOTH #6 — Meade
601 Haggerty Lane
Bozeman, MT 59715
CONTACT: Paula Hook
[email protected]
877.782.6835
www.quantel-medical.com
Regeneron Pharmaceuticals,
Inc. — GOLD PATRON
BOOTH #7 — Meade
777 Old Saw Mill River Road
Tarrytown, NY 10591
CONTACT: Jason Montanez
[email protected]
914.847.3317
www.regeneron.com
Retina Today
TABLE #3 — Grant
1008 Upper Gulph Road
Wayne, PA 19087
CONTACT: Alan Guralnick
[email protected]
484.581.1832
retinatoday.com
Retinal Physician
TABLE #5 — Grant
323 Norristown Road, Ste 200
Ambler, PA 19002
CONTACT: Michelle Kieffer
[email protected]
215.779.3746
www.retinalphysician.com
ThromboGenics — PATRON
BOOTH #16 — Meade
1370 India Street, Suite 200
San Diego, CA 92101
CONTACT: Patrick Brauer
[email protected]
619.269.3000
Topcon Medical Systems
BOOTH #11 — Meade
111 Bauer Drive
Oakland, NJ 07436
CONTACT: Christina Peccini
[email protected]
201.599.5050
www.topconmedical.com
|
213
Robert Indiana’s iconic LOVE statue
214
|
The Retina Society
Authors Index
Rahimy, Ehsan...................... 162
Adam, Murtaza ...................194
Garg, Seema ......................... 172
Adelman, Ron ................. 45, 68
Garg, Sunir J. ..........................83
Rath, Pamela P. ..................... 44
Agarwal, Anita ....................... 45
Gonzalez, Victor H. ............. 173
Rayess, Nadim ........................98
Augsburger, James J.......... 125
Gragoudas, Evangelos S. . 135
Recchia, Franco M. ......44, 155
Awh, Carl C. ............................ 90
Greven, Margaret A. .............76
Reed, David C. ...................... 197
Bagheri, Nika ..........................82
Haller, Julia A. ........................ 161
Regillo, Carl D. ....................... 171
Banker, Tanuj ........................203
Han, Dennis P. ........................ 94
Ripandelli, Guido ....................71
Barile, Gaetano R. .........44, 99
Hartnett, Mary Elizabeth.. 149
Rodriguez, Alvaro .............. 202
Barr, Charles C. .......................89
Heckenlively, John R. ......... 137
Rosen, Richard B. ................ 145
Baumal, Caroline R........ 45, 75
Heier, Jeffrey S. .......................91
Rosenfeld, Philip J. .............. 112
Baynham, Justin ................. 184
Ho, Allen C. ............................ 169
Roth, Daniel B. ...................... 159
Berrocal, Audina M. ..... 44, 116
Holekamp, Nancy M. .......... 158
Ruby, Alan J. ......................... 199
Berrocal, Maria H. .......... 45, 65
Houston, Samuel K. S. ........ 96
Ryan, Edwin H. ............ 44, 144
Blumenkranz, Mark S. ......... 118
Hsu, Jason ..............................109
Ryder, Steven J. .................. 193
Boyer, David S. ....................... 111
Hubschman, Jean-Pierre .205
Sabates, Felix N. .................108
Brady, Christopher ..............146
Iezzi, Raymond....................... 45
Sarraf, David ..................... 44, 81
Bressler, Neil M. ......................92
Jaffe, Glenn J. .......................102
Schaal, Karen B. ................. .143
Bressler, Susan B. ..................88
Jayasundera, Thiran ........... 165
Schaal, Shlomit .............44, 122
Brown, David M. ................... 166
Johnson, Mark W. ..........44, 117
Scholl, Hendrik P. ............... 139
Brown, Gary C. .......................87
Joondeph, Brian C. .............. 80
Schwartz, Stephen G. .44, 201
Brucker, Alexander J. ... 35, 86
Kang-Mieler, Jennifer J. ... 100
Schwartz, Steven D. ......... 140
Busbee, Brandon G. ............ 113
Kapoor, Kapil ........................ 154
Scott, Ingrid U. ..................... 174
Campbell, J. Peter ................ 45
Khurana, Rahul N................... 70
Semenova, Ekaterina ......... 187
Campochiaro, Peter A. .31, 124
Kiang, Lee............................... 186
Shah, Chirag ............................93
Capone Jr., Antonio ........... 147
Kim, Ivana K. ......................... 127
Shah, Gaurav K. ....................105
Carle, Michelle ...................... 177
Kim, Judy E. .......................... 142
Shah, Sumit P. ......................209
Casella, Antonio M. .......44, 95
Kiss, Szilárd ...........................164
Shaikh, Saad ......................... 207
Champion, Mary .................. 181
Kon Graversen, Veronica .. 183
Sharma, Sumit .......................101
Chan, R.V. Paul ..................... 148
Kuriyan, Ajay E. .................... 196
Shields, Carol L. ........... 44, 129
Chen, Eric ............................ 200
Li, Helen K. .............................. 44
Shields, Jerry A. ........... 45, 130
Chiang, Allen ......................... 156
Lim, Jennifer I. .......................110
Singer, James ........................ 191
Chin Yee, David S. .................97
Lima, Luiz..........................44, 66
Singer, Michael A..................160
Ciulla, Thomas A. ................ 178
Maberley, David ................... 152
Singh, Arun D. ...................... 134
Clark, W. Lloyd ..................... 163
Marcus, Dennis ..................... 167
Sisk, Robert A. ...............44, 185
D'Amico, Donald J. ...............79
Marmor, Michael F. ........44, 121
Sjaarda, Raymond N. ...........95
Dang, Sabin ........................... 188
Medina, Carlos A................... 131
Sohn, Elliott H. ...................... 179
Deramo, Vincent A. ............ 192
Meleth, Annal D. ................206
Stewart, Jay M. ...................... 44
Doft, Bernard H. .................... 84
Michelotti, Monica ...............210
Stoller, Glenn L. ....................103
Drenser, Kimberly A. .......... 136
Mieler, William F. ...........45, 128
Storey, Philip............................73
Dubovy, Sander ................... 198
Miller, John B. ............... 39, 123
Sun, Jennifer K. .................... 189
Eagle, Ralph C. .......................27
Morse, Lawrence S. ............ 138
Suner, Ivan J. ......................... 157
Ehlers, Justis P. .......................74
Moshfeghi, Darius M. ..........150
Tabandeh, Homayoun...........72
Fine, Howard F. ....................190
Murray, Timothy G. ............. 132
Tezel, Tongalp H. .................104
Finger, Paul T. ....................... 133
Nagiel, Aaron ......................... 114
Thompson, John T. .............. 69
Fisher, Yale L. .......................204
Ober, Michael D. .....................77
Vajzovic, Lejla......................... 45
Flaxel, Christina J. ............... 170
Packo, Kirk H. .................. 45, 67
Vanner, Elizabeth A. ..........208
Flynn, Jr., Harry W. .......29, 120
Palestine, Alan G. ................. 44
Walia, Harpreet S. .................63
Folgar, Francisco A. ..... 38, 85
Pang, Claudine E. ................. 141
Weng, Christina...............45, 64
Frenkel, Ronald ..................... 115
Patel, Mrinali .......................... 126
Whalen, Katherine ..............180
Friberg, Thomas R. ............. 107
Pitcher III, John D. ............... 153
Wu, Lihteh ............................... 119
Friedman, Scott M. ............. 175
Prenner, Jonathan..................78
Wykoff, Charles C. .............. 168
Gardner, Thomas W. ........... 182
Pulido, Jose S. ....................... 45
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215
PARIS
The Retina Society annual Scientific Meeting
Mark your caLendar
October 7 – 1 1, 2 0 1 5
Le grand intercontinental Hotel
Paris, France
T he R e t in a S oc ie t y
Design: Barbara Lande
The Retina Society
P HI LA D E LP HIA , P ENN SY LVANIA
2 014

SatuRday, SePtemBeR 13

Transcription

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