PEDIATRIC OPHTHALMOLOGY Pediatric Ophthalmology 2011: A Child’s View from Here…and There 2011

Transcription

Subspecialty Day
2011
Orlando
October 21 – 22
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Pediatric Ophthalmology 2011:
A Child’s View from Here…and There
Pediatric
Ophthalmology 2011
A Child’s View From
Here . . . and There
Program Directors
George S Ellis Jr MD, David B Granet MD, Ken K Nischal MBBS
In conjunction with the Section on Ophthalmology of the American Academy of Pediatrics
Orange County Convention Center
Orlando, Florida
Saturday, October 22, 2011
Presented by:
The American Academy of Ophthalmology
Pediatric Ophthalmology 2011
Planning Group
George S Ellis Jr MD
Program Director
David B Granet MD
Program Director
Ken K Nischal MBBS
Program Director
Former Program Directors
2009
Donny W Suh MD FAAP
Kenneth W Wright MD
Subspecialty Day Advisory Committee
William F Mieler MD
Associate Secretary
Donald L Budenz MD MPH
Daniel S Durrie MD
Robert S Feder MD
Leah Levi MBBS
R Michael Siatkowski MD
Jonathan B Rubenstein MD
Secretary for Annual Meeting
Staff
Melanie R Rafaty CMP, Director, Scientific
Meetings
Ann L’Estrange, Scientific Meetings
Coordinator
Debra Rosencrance CMP CAE,
Vice President, Meetings & Exhibits
Patricia Heinicke Jr, Editor
Mark Ong, Designer
Gina Comaduran, Cover Design
©2011 American Academy of Ophthalmology. All rights reserved. No portion may be reproduced without express written consent of the American Academy of Ophthalmology.
ii
2011 Subspecialty Day | Pediatric Ophthalmology
Dear Colleague:
On behalf of the American Academy of Ophthalmology and the Section on Ophthalmology of the
American Academy of Pediatrics, it is our pleasure to welcome you to Orlando and to Pediatric
Ophthalmology 2011: A Child’s View From Here . . . and There.
Expertise does not reside in just one region of the world. Consequently, we have drawn not only on
colleagues in disciplines throughout ophthalmology but also on specialists from around the globe.
We are certain this group will be creative in their presentations and that the discussion will be lively!
In fact, the format is interactive, with time for significant audience participation.
The outstanding faculty of internationally regarded experts will provide up-to-date and pertinent
information on a variety of pediatric ophthalmology and strabismus topics. We are excited and
honored to have brought in Helen Mintz-Hittner MD to discuss innovative new treatments for
ROP—a timely, even controversial, topic.
In addition, the Section on Ophthalmology of the American Academy of Pediatrics (AAP) is proud
to present experts on the effects of anesthesia and radiation on children. When is enough enough?
Further, the discussion on health care change by the head of the AAP Washington office will be
important to us all.
As cochairs of the Pediatric Ophthalmology Subspecialty Day Program Planning Group, we know
this Pediatric Subspecialty Day will provide practical information that clinicians and subspecialists
can use in their practices.
Again, we welcome you Pediatric Ophthalmology 2011: A Child’s View From Here . . . and There;
we hope you find it educational and enjoyable.
Sincerely,
George S Ellis Jr MD Program Director
David B Granet MD
Program Director
Kanwal K Nischal MBBS
Program Director
PS: In an effort to put together innovative and interesting Subspecialty Day meetings in the future,
we request that you assist us by completing the evaluation form. We carefully review all comments to
better understand your needs, so please indicate the strengths and shortcomings of today’s program.
Pediatric Ophthalmology 2011 Contents
Program Directors’ Welcome Letter ii
CME Credit iv
Faculty Listing v
Program Schedule ix
Section I:
Will This Change My Practice? 1
Section II:
Oh, No! 8
Section III:
Oh, No! Part 2: What Do We Do Now? 15
Section IV:
New Techniques for Children 16
Surgery by Surgeons Update 22
Section V:
Pediatric Ophthalmology Conundrums 23
Keynote Lecture 28
Section VI:
Challenging Dogma (and Other Good Questions) 31
Section VII:
Challenging Dogma (and Other Good Questions), Part II 44
Section VIII:
Have You Thought About . . . 49
Section IX:
How Do You Handle Strabismus When . . . 57
Faculty Financial Disclosure 65
Presenter Index 68
iii
iv
CME Credit
Academy’s CME Mission Statement
Attendance Verification for CME Reporting
The purpose of the American Academy of Ophthalmology’s
Continuing Medical Education (CME) program is to present ophthalmologists with the highest quality lifelong learning
opportunities that promote improvement and change in physician practices, performance or competence, thus enabling such
physicians to maintain or improve the competence and professional performance needed to provide the best possible eye care
for their patients.
Before processing your requests for CME credit, the Academy
must verify your attendance at Subspecialty Day and/or the 2011
Annual Meeting. In order to be verified for CME or auditing
purposes, you must either:
2011 Pediatric Ophthalmology Subspecialty Day
Meeting Learning Objectives
Upon completion of this activity, participants should be able to:
• Evaluate new disease entities, practices and treatment that
may change practice
• Plan the surgical treatment of complex strabismus
problems
• Assess the relative merits and disadvantages of some therapies in a balanced way
• Discuss ocular manifestations of various systemic diseases
and explore new developments in the treatment
• Present various pediatric neuro-ophthalmology cases and
discuss the latest diagnostic and treatment options
Meeting Target Audience
The intended target audience for this program is pediatric ophthalmologists, comprehensive ophthalmologists, medical professionals, visual physiologists and orthoptists who are involved in
maintaining high quality health care for the pediatric and strabismus populations.
CME Credit
The American Academy of Ophthalmology is accredited by the
Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The American Academy of Ophthalmology designates this
live activity for a maximum of 7 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with
the extent of their participation in the activity.
Scientific Integrity and Disclosure of Relevant
Financial Interest
The American Academy of Ophthalmology is committed to
ensuring that all continuing medical education (CME) information is based on the application of research findings and the
implementation of evidence-based medicine. It seeks to promote
balance, objectivity and absence of commercial bias in its content. All persons in a position to control the content of this activity must disclose any relevant financial interest. The Academy
has mechanisms in place to resolve all conflicts of interest prior
to an educational activity being delivered to the learners.
• Register in advance, receive materials in the mail and turn
in the Final Program and/or Subspecialty Day Syllabus
exchange voucher(s) onsite;
• Register in advance and pick up your badge onsite if materials did not arrive before you traveled to the meeting;
• Register onsite; or
• Use your ExpoCard at the meeting.
CME Credit Reporting
Level 2, Lobby B; Academy Resource Center, Hall A4,
Booth 1359
Attendees whose attendance has been verified (see above) at the
2011 Annual Meeting can claim their CME credit online during
the meeting. Registrants will receive an e-mail during the meeting
with the link and instructions on how to claim credit.
Onsite, you may report credits earned during Subspecialty Day
and/or the Annual Meeting at the CME Credit Reporting booth.
Academy Members: The CME credit reporting receipt is not
a CME transcript. CME transcripts that include 2011 Annual
Meeting credits entered onsite will be available to Academy
members on the Academy’s website beginning Nov. 16, 2011.
NOTE: CME credits must be reported by Jan. 18, 2012.
After the 2011 Annual Meeting, credits can be claimed at
www.aao.org.
The Academy transcript cannot list individual course attendance. It will list only the overall credits spent in educational
activities at Subspecialty Day and/or the Annual Meeting.
Nonmembers: The Academy will provide nonmembers with
verification of credits earned and reported for a single Academysponsored CME activity, but it does not provide CME credit
transcripts. To obtain a printed record of your credits, you must
report your CME credits onsite at the CME Credit Reporting
booths.
Proof of Attendance
The following types of attendance verification will be available
during the 2011 Annual Meeting and Subspecialty Day for those
who need it for reimbursement or hospital privileges, or for nonmembers who need it to report CME credit:
• CME credit reporting/proof-of-attendance letters
• Onsite Registration Form
• Instruction Course Verification Form
Visit the Academy’s website for detailed CME reporting
information.
Faculty
No photo
available
Steven M Archer MD
Mark Del Monte JD
Ann Arbor, MI
Associate Professor of Ophthalmology
University of Michigan
Washington, DC
Director, Department of Federal Affairs
American Academy of Pediatrics
New Orleans, LA
No photo
available
Michael J Callahan MD
Monte A Del Monte MD
Boston, MA
Ann Arbor, MI
Skillman Professor of Pediatric
Ophthalmology
University of Michigan
Director of Pediatric Ophthalmology and
Adult Strabismus
W K Kellogg Eye Center
Brian J Forbes MD PhD
Wallingford, PA
Assistant Professor of Ophthalmology
Children’s Hospital of Philadelphia
University of Pennsylvania School of
Medicine
David K Coats MD
Houston, TX
Professor of Ophthalmology and
Pediatrics
Baylor College of Medicine
Department Chief
Pediatric Ophthalmology
Texas Children’s Hospital
Sharon F Freedman MD
Sean P Donahue MD PhD
Nashville, TN
Professor of Ophthalmology, Neurology,
and Pediatrics
Vanderbilt University Medical Center
Chief of Pediatric Ophthalmology
Vanderbilt Children’s Hospital
Durham, NC
Professor Of Ophthalmology and
Pediatrics
Duke Eye Center
v
vi
Faculty Listing
David B Granet MD
Mark E Jacobson MD
Sylvia R Kodsi MD
La Jolla, CA
Anne Ratner Professor of
Ophthalmology and Pediatrics
University of California, San Diego
Strabismus
Ratner & Shiley Eye Centers
Univeristy of California, San Diego
Santa Rosa, CA
New York, NY
Co-chief, Pediatric Ophthalmology and
Strabismus
North Shore - Long Island Jewish Health
Systems
Associate Professor
Hofstra North Shore-LIJ School of
Medicine
Ramesh Kekunnaya MD FRCS
Hyderabad, AP, India
Associate Professor, Pediatric
Ophthalmology
L V Prasad Eye Institute
Richard W Hertle MD
Burton J Kushner MD
Akron, OH
Chief of Ophthalmology
Children’s Vision Center
Akron Children’s Hospital
Professor of Surgery (Ophthalmology)
Northeastern Ohio Universities College
of Medicine
Madison, WI
John W and Helen Doolittle Professor of
Ophthalmology
Department of Ophthalmology and
Visual Sciences
University of Wisconsin, Madison
Don O Kikkawa MD
La Jolla, CA
Professor Of Ophthalmology
Chief, Division of Ophthalmic Plastic
and Reconstructive Surgery
Department of Ophthalmology
University of California, San Diego
Constance S Houck MD
Boston, MA
G Robert LaRoche MD
Halifax, NS, Canada
Professor of Ophthalmology
Dalhousie University
Faculty Listing
vii
Thomas C Lee MD
David A Plager MD
Los Angeles, CA
University of Southern California
Director, Retina Institute
Childrens Hospital Los Angeles
Pittsburgh, PA
Director, Children’s Hospital of
Pittsburgh UPMC, Pittsburgh
Indianapolis, IN
Indiana University Medical Center
Strabismus
Indiana University Medical Center
Paolo Nucci MD
Helen A Mintz-Hittner MD FACS
Houston, TX
Professor of Ophthalmology and Visual
Sciences
University of Texas Health Science
Center at Houston Medical School
Milano, Italy
Professor of Ophthalmoogy
University of Milan
Director
San Giuseppe Eye Clinic
Jean E Ramsey MD MPH
Boston, MA
and Pediatrics
Boston University School of Medicine
Council, Vice-chair
American Academy of Ophthalmology
No photo
available
No photo
available
Scott E Olitsky MD
Daniel S Mojon MD
St Gallen, Switzerland
Kansas City, MO
Chief of Ophthalmology
Children’s Mercy Hospitals and Clinics
University of Missouri, Kansas City,
School of Medicine
Shira L Robbins MD
La Jolla, CA
viii
Faculty Listing
Daniel J Salchow MD
Jane C Sowden PhD
M Edward Wilson Jr MD
New Haven, CT
Assistant Professor
Department of Ophthalmology & Visual
Science and Department of Pediatrics
Yale University School of Medicine
London, United Kingdom
Charleston, SC
Professor and Chairman of
Ophthalmology
Storm Eye Institute
Medical University of South Carolina
Elias I Traboulsi MD
Nicoline Schalij-Delfos MD
Cleveland, OH
Cleveland Clinic Lerner College of
Medicine
Voorschoten, Netherlands
Terri L Young MD
Durham, NC
Professor of Ophthalmology, Pediatrics,
and Medicine
Duke University
Professor of Neuroscience
Duke - National University of Singapore
No photo
available
Eduardo D Silva MD
Figueira Da Foz, Portugal
Assistant Professor of Ophthalmology
University of Coimbra, Portugal
MD, PhD
IBILI, School of Medicine, Coimbra,
Portugal
Abhay Raghukant Vasavada
MBBS FRCS
Ahmedabad, Gujarat, India
Raghudeep Eye Clinic
Director
Iladevi Cataract & IOL Research Centre
Gerald W Zaidman MD FACS
Valhalla, NY
Director of Ophthalmology
Westchester Medical Center
New York Medical College
ix
Pediatric Ophthalmology 2011:
A Child’s View From Here . . . and There
Saturday, October 22, 2011
6:30 AM
REGISTRATION/MATERIAL PICKUP/CONTINENTAL BREAKFAST
8:00 AM
Welcome and Opening Remarks
Section I: Will This Change My Practice?
Moderator: David B Granet MD*
8:05 AM
Video: Minimally Invasive Strabismus Surgery
Daniel S Mojon MD
1
8:09 AM
Propranolol for Capillary Hemangiomas: Can I Use This All the Time?
David A Plager MD*
3
8:17 AM
Dynamic Retinoscopy
Burton J Kushner MD
5
8:25 AM
Anesthetic Neurotoxicity: Are We Poisoning Children’s Brains?
6
8:37 AM
Panel Discussion
Section II: Oh, No!
Moderator: Kanwal K Nischal MBBS*
8:48 AM
Video: Rupture of Muscle During Strabismus Surgery
David B Granet MD*
8
8:51 AM
When to Order What!
Sylvia R Kodsi MD
9
8:59 AM
The Good, the Bad, and the Ugly: Nonaccidental Injury
11
9:07 AM
“Skew You”
Sean P Donahue MD PhD*
13
9:15 AM
Panel Discussion
Section III: Oh, No! Part 2: What Do We Do Now?
Moderator: George S Ellis Jr MD*
9:30 AM
AAP Federal Affairs Update
Mark Del Monte JD
15
9:42 AM
Questions and Answers
9:47 AM REFRESHMENT BREAK and ANNUAL MEETING EXHIBITS
Section IV: New Techniques for Children
10:17 AM
Video: Goniotomy in an Aniridic Patient
Kanwal K Nischal MBBS*
16
10:20 AM
Descemet-Stripping Automated Endothelial Keratoplasty/Deep Lamellar
Endothelial Keratoplasty: What Are They? Are They Good for Kids?
Gerald W Zaidman MD FACS* 17
10:28 AM
Endoscopic Vitreoretinal Surgery
Thomas C Lee MD
18
10:36 AM
Intracameral Medications for Every Intraocular Surgery?
Is This Safe for Kids?
M Edward Wilson Jr MD*
19
* Indicates that the presenter has financial interest.
No asterisk indicates that the presenter has no financial interest.
George S Ellis Jr MD*
x
Program Schedule
10:44 AM
Fundus Autofluorescence in Pediatric Ophthalmology
10:52 AM
Panel Discussion
11:07 AM
Surgery by Surgeons Update
Section V: Pediatric Ophthalmology Conundrums
11:12 AM
Elias I Traboulsi MD*
20
22
COMETs CLAMP ATOM: The Myopia Studies—
Can We Affect Refractive Outcome?
Terri L Young MD*
23
11:20 AM
Iris Clip Lenses for Aphakia
24
11:28 AM
Should We Be Using Mitomycin So Readily in Pediatric Glaucoma Surgery?
Sharon F Freedman MD*
25
11:36 AM
Do Adjustable Sutures Enhance Outcomes?
Paolo Nucci MD*
26
11:44 AM
Congenital Corneal Opacifications: Time for a Re-think?
Kanwal K Nischal MBBS*
27
11:52 AM
Panel Discussion
Keynote Lecture
12:07 PM
Avastin for ROP
12:27 PM
12:32 PM
LUNCH and ANNUAL MEETING EXHIBITS
Section VI: Challenging Dogma (and Other Good Questions)
1:47 PM
Video: Cataract Surgery for Marfan Syndrome
Daniel J Salchow MD
31
1:50 PM
Why Don’t We Operate to Eliminate Lower-Power Hyperopic Spectacles
in Accommodative Estotropia?
Scott E Olitsky MD
32
1:58 PM
Is the Pediatric Eye Disease Investigator Group Wrong About . . . ?
Steven M Archer MD
33
2:06 PM
Eye Drops for Nystagmus? Really?
Richard W Hertle MD
35
2:14 PM
Do Study Design and Methodology Affect Pediatric Cataract Outcomes?
Ramesh Kekunnaya MD FRCS 39
2:22 PM
Panel Discussion
Section VII: Challenging Dogma (and Other Good Questions) — Part II
2:37 PM
The Ciliopathies: What Are They?
Eduardo D Silva MD*
44
2:45 PM
Retinal Repair by Transplantation of Photoreceptor Precursors
Jane C Sowden PhD
46
2:57 PM
Radiation Exposure to Children From Medical Imaging: Is There a Problem? Michael J Callahan MD
3:09 PM
3:21 PM REFRESHMENT BREAK and ANNUAL MEETING EXHIBITS
Helen A Mintz-Hittner MD
FACS28
47
Program Schedule
xi
Section VIII: Have You Thought About . . .
3:51 PM
Video: Fishtail Sign in Posterior Lenticonus
MBBS FRCS*
49
3:54 PM
Current Management Strategies for Blepharokeratoconjunctivitis
Mark E Jacobson MD
50
4:02 PM
Evaluation of the Non-seeing Infant
Shira L Robbins MD*
53
4:10 PM
Update on Oculoplastics
Don O Kikkawa MD
55
4:18 PM
Managing Psychosocial Effects of Strabismus
Daniel S Mojon MD
56
4:26 PM
Panel Discussion
Section IX: How Do You Handle Strabismus When . . .
4:41 PM
The Patient Has Thyroid Ophthalmopathy
David B Granet MD*
57
4:49 PM
There Is a CN VI Palsy
G Robert LaRoche MD
59
4:57 PM
The Patient Has Adult-Onset CN III Palsy
David K Coats MD
61
5:05 PM
You Are Faced With Partially Accommodative Esotropia ±
High Accommodative Convergence-to-Accommodation Ratio
62
5:13 PM
Panel Discussion
5:28 PM
Closing Remarks
5:30 PM
Adjourn
George S Ellis Jr MD*
1
Video: Minimally Invasive Strabismus Surgery
Daniel S Mojon MD
B. Instead of one large opening, there are several keyhole cuts where main surgical steps (usually suturing) are performed.
C. For some surgical procedures, you need to create
tunnels between the cuts.
D. Openings placed far away from limbus
E. Junction of cuts allows one to convert to usual, large
limbal opening.
F. Perimuscular tissue dissection is reduced to absolute minimum, which still allows one to displace or
anchor muscles.
G. Openings are all covered postoperatively by eyelids,
minimizing visibility of surgery and patient discomfort.
1. Opening remains covered by the lids after surgery.
H. Reduction of frequency of corneal complications,
for example dellen formation
I. Minimal tissue disruption facilitates reoperations.
2. Minimal postoperative discomfort
3. Difficult in young patients (prominent Tenon tissue), old patients (inelastic conjunctiva), and for
repeat surgery (scarring)
J. Transconjunctival suturing (TRASU)9 and marginal
dissection (MADI)10 allow further reduction of tissue disruption and operating time.
Disclosure: Daniel Mojon has no relevant financial relationships.
I. Frequently Used Conjunctival Access Techniques for
Strabismus Surgery
A. Limbal
approach1
1. Permits full visualization of the operated muscle
2. Patients have considerable postoperative discomfort.
3. Interpalpebral conjunctiva is red for weeks.
4. Prone for corneal dellen formation and Tenon
prolapse
5. Large anatomical disruption between the muscle
and perimuscular tissue
B. Fornix approach2
4. Moderate anatomical disruption between the
muscle and perimuscular tissue
5. Need for an assistant surgeon to displace the
opening over operated muscle
C. Minimally invasive strabismus surgery (MISS)3-4
1. Permits performance of most types of strabismus
surgeries (rectus muscle recessions, resections,
plications, reoperations, retroequatorial myopexias, transpositions, and oblique muscle recessions
and plications)
2. Minimal postoperative discomfort
3. Minimal anatomical disruption between muscle
and perimuscular tissue
4. No need for assistant surgeon for most techniques
5. However, adjustable sutures are difficult with
MISS.
6. Increased risk for scleral perforation for inexperienced surgeons
7. Rather long learning curve
II. MISS in More Detail3-16
III. Tips for Starting With MISS4,14
A. Surgeons switching from magnifying glasses to operating microscope should perform several procedures
with own technique with microscope before starting
with MISS.
B. Start with primary horizontal rectus muscle displacements of 4 mm or less.
C. Use a corneal traction suture.
D. Use plications instead of resections (more demanding through small cuts); dose-response relationship
will not change.
E. Ideal patient age between 14 and 40 years; abundant Tenon tissue makes surgery difficult in very
young patients, reduced elasticity of the conjunctiva
increases risk of a conjunctival tear in very old
patients.
F. Before starting with MISS visit an already skilled
surgeon; the author always welcomes colleagues in
his operating theater.
IV. Instruments for MISS4,14
A. Use small instruments in order to minimize risk of
conjunctival tearing.
B. Clamp a serrefine to the eyelid speculum to avoid
corneal rubbing of a traction suture.
C. Use spatulas of different sizes to visualize tissue
through the cuts.
A. Best performed with operating microscope
2
D. Use a bipolar, coaxial diathermy tip.
E. Use only blunt scissors to minimize risks.
F. Use a blunt cannula to safely displace needles
through tunnels.
References
1. Harms H. Über Muskelvorlagerung. Klin Monatsbl Augenheilk.
1949; 115:319-324.
2. Parks MP. Fornix incision for horizontal rectus muscle surgery. Am
J Ophthalmol. 1968; 65:907-915.
3. Gobin MH, Bierlaagh JJM. Chirurgie horizontale et cycloverticale
simultaneé du strabisme. Anvers Belgium: Centrum voor Strabologie; 1994.
4. Mojon DS. Minimally invasive strabismus surgery. In: Fine HI,
Mojon DS, eds. Minimally Invasive Ophthalmic Surgery. Heidelberg: Springer; 2009.
5. Mojon DS. Minimally invasive strabismus surgery. Br J Ophthalmol. 2009; 93:843-844.
6. Mojon DS. Comparison of a new, minimally invasive strabismus
surgery technique with the usual limbal approach for rectus muscle
recession and plication. Br J Ophthalmol. 2007; 91:76-82.
7. Kushner BJ. Comparison of a new, minimally invasive strabismus surgery technique with the usual limbal approach for rectus
muscle recession and plication [comment]. Br J Ophthalmol. 2007;
91(1):5.
8. Pellanda N, Mojon DS. Minimally invasive strabismus surgery
technique in horizontal rectus muscle surgery for esotropia. Ophthalmologica 2010; 224:67-71.
9. Mojon DS. A new transconjunctival muscle reinsertion technique
for minimally invasive strabismus surgery. J Pediatr Ophthalmol
Strabismus. 2010; 47:292-296.
10. Mojon DS. A modified technique for rectus muscle plication in
minimally invasive strabismus surgery. Ophthalmologica 2009;
224:236-242.
11. Mojon DS. Minimally invasive strabismus surgery for rectus muscle
posterior fixation. Ophthalmologica 2009; 223:111-115.
12. Mojon DS. Minimally invasive strabismus surgery (MISS) for rectus
muscle transpositions. Br J Ophthalmol. 2009; 93:747-753.
13. Mojon DS. Minimally invasive strabismus surgery for horizontal
rectus muscle reoperations. Br J Ophthalmol. 2008; 92: 16481652.
14. Mojon DS. Minimally invasive strabismus surgery (MISS) for inferior obliquus recession. Graefes Arch Clin Exp Ophthalmol. 2009;
247:261-265.
15. Kaup M, Mojon-Azzi SM, Kunz A, Mojon DS. Intraoperative conversion rate to a large, limbal opening in minimally invasive strabismus surgery (MISS). Graefes Arch Clin Exp Ophthalmol. E-pub
ahead of print 24 May 2011.
16. Mojon DS. Minimally invasive strabismus surgery [review]. Expert
Rev Ophthalmol. 2010; 5:811-820.
3
Propranolol for Capillary Hemangiomas: Can I Use
This All the Time?
David A Plager MD
Introduction
The serendipitous finding that propranolol has a salutary effect
on the growth of infantile hemangiomas has led to an explosion
of interest in this drug for treatment of this common tumor in
infants. Several articles in the refereed medical literature describing its use have appeared in the brief time since that initial publication. Although it appears to be revolutionizing the treatment
paradigm for such vision-threatening adnexal tumors, the indications, dosage, optimal treatment duration, and relative risks of
treatment remain controversial or at least unknown.
Background
Prior to the discovery of the usefulness of propranolol for treating infantile hemangioma, the most common treatments available included systemic or intralesional injection of steroids,
excisional surgery, and in especially difficult cases, more toxic
drugs such as vincristine, cyclophosphamide, or alpha interferon.
The side effects of those medications are common, well known,
and significant. In contrast, the long-standing safety profile and
well-tolerated nature of propranolol when used for other (cardiac) indications has led to its enthusiastic embrace as a potential
cornerstone of treatment for hemangioma.
Pharmacology
Propranolol is a nonselective beta-blocker with effects on many
target tissues, including the heart, lungs, and in gluconeogenesis.
Its effects on hemangioma growth are thought to result from
a combination of 3 mechanisms: Blockade of beta-2 receptors
in capillary endothelial cells leads to vasoconstriction. Blockage of beta-1 receptors is thought enhance apoptosis. The third
mechanism is thought to be the reduction in vascular endothelial
growth factor (VEGF) levels caused by beta-blockers leading to
decreased angiogenesis.
Its current principle uses in children include treatment of
cardiac arrhythmias, some congenital heart defects, and for
migraine prophylaxis.
as a result of illness or intentional or prolonged fast. However,
there have been a small handful of reported symptomatic events
requiring emergency room evaluation in otherwise healthy
infants with reportedly normal oral intake. Symptoms of hypoglycemia with which the child’s caretakers must be made aware
include early signs of shakiness, sweating, and anxiety, which
can lead to lethargy, lack of responsiveness, and seizure. These
symptoms respond rapidly to normalization of blood sugar level.
Summary
For many physicians, including this author, propranolol has
become the treatment of choice for vision-threatening infantile
hemangiomas that require systemic treatment. However, other
treatment options including intralesional injection of steroid and
surgical resection may be preferred for an individual patient.
Clinical examples are shown of small astigmatism-inducing eyelid hemangiomas that will respond to 1 or 2 injections of steroid.
This treatment may be preferable to subjecting the same infant to
multiple months of a 3 times/day systemic medication.
Similarly, some well-circumscribed eyelid tumors with normal
overlying skin will have an immediate, dramatic, and permanent
response to surgical resection. For carefully selected cases, this
outpatient surgical procedure may be preferable to a protracted
course of systemic therapy.
Prospective trials of propranolol treatment are under way, but
in the meantime, clinicians can be comfortable that propranolol
has been shown to be very safe and effective in many infants with
vision-threatening hemangiomas. Careful attention to potential
side effects, especially hypoglycemia, and comanagement with
physicians experienced in the care of young infants will optimize
the safety for these young patients.
Indiana University Propranolol Treatment Algorithm
I.Premedication
A. Physical exam with baseline vital signs
B. Is the hemangioma segmental and over 5 cm?
Side Effects of Propranolol
Propranolol has a long and well-documented safety profile as
noted by Love and Sikka:4 “With 40 years of extensive clinical
experience, not one documented case of death or serious cardiovascular morbidity as a direct result of a beta-blocker exposure
is to be found in an English language review for children under 6
years of age.” However, there are many potential side effects.
• Most significant side effects: hypotension, bradycardia,
hypoglycemia
• Miscellaneous side effects: bronchospasm, sleep disturbance, GI disturbance (diarrhea), rash
Hypoglycemia is probably the clinically most important side
effect. The vast majority of case reports of symptomatic hypoglycemia have involved infants whose oral intake has been reduced
1. If yes, MRI/MRA of head and neck and echo
must be done to rule out PHACE syndrome and
any contraindication for propranolol.
2. PHACE screening done
3. No contraindications for propranolol on MRI/
MRA or echo
Figure 1.
C. Baseline EKG
4
II. Medication Administration
A. Propranolol preparation: 20 mg/5 cc or 40 mg/5 cc
B. Dosing schedule
1. 0.5 mg/kg/d divided into t.i.d. x 2-3 days
4. 2.0 mg/kg/d divided into t.i.d. x 2-3 days (final
dose)
III.Monitoring
Blood pressure/ heart rate taken 24 hours after any
dosage change including the initial administration (see
example below). If abnormal then decrease dose and
see cardiology.
A. Day 1: Start medication.
B. Day 2: Check blood pressure and heart rate.
C. Day 4: Check blood pressure and heart rate.
Reference and Selected Readings
1. Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi
F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of
infancy. N Engl J Med. 2008; 358(24):2649-2651.
2. Haider KM, Plager DA, Neely DE, Eikenberry J, Haggstrom A.
Outpatient treatment of periocular capillary hemangiomas with
propranolol. J AAPOS. 2010:251-256.
3. Holland KE, Frieden IJ, Frommelt PC, et al. Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma.
Arch Dermatol. 2010; 146:775-778.
4. Love JN, Sikka N. Are 1-2 tablets dangerous? Beta-blocker exposure in toddlers. J Emerg Med. 2004; 26:309-314.
5. Love JN, Howell JM, Klein-Schwartz W, et al. Lack of toxicity
from pediatric beta-blocker exposures. Hum Exp Toxicol. 2006;
25:341-346.
6. Missoi TG, Lueder GT, Gilbertson K, Bayliss SJ. Oral propranolol
for treatment of periocular infantile hemangiomas. Arch Ophthalmol. 2011; 129(7):899-903.
7. Propranolol versus prednisolone for treatment of symptomatic
hemangiomas. http://clinicaltrials.gov/ct2/show/NCT00967226.
8. Propranolol in capillary hemangiomas. http://clinicaltrials.gov/ct2/
show/NCT00744185.
5
Dynamic Retinoscopy
Burton J Kushner MD
I.Technique
A. Dry retinoscopy as patient shifts fixation to target
just below retinoscope light 1-3
B. End point
1. Normal: Brisk change to neutrality
2.Abnormal
a. Sluggish change to neutrality
b. Persistent with motion
II.Utility
A. Accommodative insufficiency 4
1. Neurologic impairment
2. Down syndrome5
B. Determining whether to correct moderate hyperopia
if orthophoric in preverbal children
1. Orthophoric but normal and full accommodation: No glasses
2. Orthophoric but not fully accommodating: Prescribe glasses
a. Will become ET without glasses
b. Or will be bilateral refractive amblyope
References
1. Guyton DL, O’Connor GM. Dynamic retinoscopy. Curr Opin
Ophthalmol. 1991; 2:78-80.
2. del Pilar Cacho M, Garcia-Munoz A, Garcia-Bernabeu JR, Lopez
A. Comparison between MEM and Nott dynamic retinoscopy.
Optom Vis Sci. 1999; 76:650-655.
3. Hunter DG. Dynamic retinoscopy: the missing data. Surv Ophthalmol. 2001; 46:269-274.
4. Eskridge JB. Clinical objective assessment of the accommodative
response. J Am Optom Assoc. 1989; 60:272-275.
5. Haugen OH, Hovding G. Strabismus and binocular function in
children with Down syndrome: a population-based, longitudinal
study. Acta Ophthalmol Scand. 2001; 79:133-139.
6
Anesthetic Neurotoxicity: Are We Poisoning
Children’s Brains?
Introduction
Every year millions of preterm and newborn infants undergo
general anesthesia for a variety of surgical procedures and imaging studies. The landmark studies of Anand and Hickey demonstrated more than 20 years ago that general anesthesia in infants
ameliorates the surgical stress response and can lead to decreased
morbidity and mortality perioperatively. However, recent
research in immature animal models has revealed general anesthetic-induced neurotoxicity and thus has raised questions about
the long-term safety of general anesthesia in human babies. All of
this research has led to a concern that general anesthetics given
to young, vulnerable children may be deleterious to their neurologic growth and development.
Background
Anesthetic agents that function as N-methyl-D-aspartate
(NMDA) antagonists (eg, ketamine and nitrous oxide) and anesthetic agents that function as gamma amino butyric acid (GABA)
agonists (eg, volatile anesthetics, midazolam, thiopental, and
propofol) have been shown to cause neuroapoptosis in immature
mice, rats, guinea pigs, and rhesus monkeys. It is important to
recognize that neuroapoptosis is part of the normal pruning of
redundant neurons during mammalian development and is a
natural process as the brain differentiates into specific functions.
However, the neuroapoptosis seen in the animal experiments
was excessive and led to developmental impairments when the
animals were allowed to mature. In all of these animal species,
there is a specific period of vulnerability to neuroapoptosis that
corresponds to the animal’s period of rapid brain growth. It is
unclear when this vulnerable time would be for human infants,
but neurodevelopmental studies would suggest that the period of
rapid human brain growth occurs from 28 weeks postconception
to 24 months of age.
Most of the animal experiments to date have involved relatively large doses of anesthetic agents per body weight (although
the minimum doses needed to keep the animals anesthetized)
and have exposed the animals for at least 4 hours. It is unknown
whether 4 hours of anesthesia in an animal with a natural life
span of 2 years would be comparable to 4 hours of anesthesia in a human with a life span of greater than 80 years. It is
also impossible to replicate in animal experiments the careful monitoring that human infants receive during anesthesia,
leading some researchers to speculate that at least some of the
neurotoxicity seen in the animals may be due to poor anesthetic
conditions.
A recent series of epidemiologic studies has linked exposure
to anesthesia at a young age in humans with learning disabilities. Robert Wilder and his colleagues in Minnesota examined a
cohort of over 5000 children and found an association between
2 or more anesthetics before the age of 4 and the cumulative
development of learning deficits by age 18 (see Figure 1). Similar
findings were seen in a study examining Medicare records in
New York state.
However, a study of monozygotic twins from the Netherlands
revealed that the intellectual attainments were similar between
the anesthesia-exposed and nonexposed twin, leading these
researchers to conclude that exposure to anesthesia was not a
cause of learning deficits. In most association studies it is impossible to separate the confounders, ie, the effects of surgery and
the morbidity that is associated with the need for surgery, from
the effects of the exposure to anesthesia. A very recent study
compared 2689 Danish adolescents (15-16 year olds) who had
undergone inguinal hernia repair in infancy with a matched
cohort of more than 15,000 adolescents who had not had surgery in infancy and found no difference in academic performance
when adjusting for known confounders, including gender, birth
weight, congenital anomalies, and academic achievement of both
parents.
In response to these emerging concerns, in 2010 the FDA and
the International Anesthesia Research Society (IARS) entered
into a public-private partnership initially called SAFEKIDS
(Safety of Key Inhaled and Intravenous Drugs in Pediatrics)
to provide research support to investigators in this area. This
partnership has subsequently expanded and evolved and is now
called SmartTots (Strategies for Mitigating Anesthesia-Related
Neuro-Toxicity in Tots; see www.smarttots.org). With funding
from the FDA and other government agencies, several ongoing international and national studies are currently enrolling
patients, including the PANDA and GAS studies. The PANDA
study is assembling a cohort of U.S. children who underwent
inguinal herniorrhaphy before age 3 and matching them with an
unexposed sibling for extensive neurologic and developmental
testing. The GAS trial is a multinational, randomized controlled
trial of preterm and term infants undergoing inguinal herniorrhaphy utilizing either a spinal or general anesthetic and comparing the neurodevelopmental outcomes of each cohort at ages 2
and 5.
Conclusions
Although there are several recent epidemiologic studies that
suggest an association between anesthesia exposure and developmental issues in humans, no study to date has been able to
demonstrate a causal link. Because of the many concerning animal studies, however, the neurobehavioral effects of sedative and
anesthetic agents are being extensively studied at the moment
and this is a high priority for the FDA and the anesthesia community. Until further data are available, it may be prudent to
consider delaying purely elective surgeries until children are older
than 2.
References and Selected Readings
Reviews
1. Creeley CE, Olney JW. The young: neuroapoptosis induced by
anesthetics and what to do about it. Anesth Analg. 2010; 110:442448.
7
2. Jevtovic-Todorovic V, Olney JW. PRO: Anesthesia-induced developmental neuroapoptosis: status of the evidence. Anesth Analg.
2008; 106:1659-1663.
15. Slikker W Jr, Zou X, Hotchkiss CE, et al. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci. 2007;
98:145-158.
3. Loepke AW. Developmental neurotoxicity of sedatives and anesthetics: a concern for neonatal and pediatric critical care medicine?
Pediatr Crit Care Med. 2010; 11:217-226.
16. Straiko MM, Young C, Cattano D, et al. Lithium protects against
anesthesia-induced developmental neuroapoptosis. Anesthesiology
2009; 110:862-868.
4. Loepke AW, Soriano SG. An assessment of the effects of general
anesthetics on developing brain structure and neurocognitive function. Anesth Analg. 2008; 106:1681-1707.
17. Stratmann G, May LD, Sall JW, et al. Effect of hypercarbia and
isoflurane on brain cell death and neurocognitive dysfunction in
7-day-old rats. Anesthesiology 2009; 110:849-861.
5. Rappaport B, Mellon RD, Simone A, Woodcock J. Defining safe
use of anesthesia in children. N Engl J Med. 2011; 364:1387-1390.
18. Stratmann G, Sall JW, May LD, et al. Isoflurane differentially
affects neurogenesis and long-term neurocognitive function in
60-day-old and 7-day-old rats. Anesthesiology 2009; 110:834-848.
Animal Studies
6. Bercker S, Bert B, Bittigau P, et al. Neurodegeneration in newborn
rats following propofol and sevoflurane anesthesia. Neurotox Res.
2009; 16:140-147.
7. Head BP, Patel HH, Niesman IR, Drummond JC, Roth DM, Patel
PM. Inhibition of p75 neurotrophin receptor attenuates isofluranemediated neuronal apoptosis in the neonatal central nervous system. Anesthesiology 2009; 110:813-825.
8. Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999; 283:70-74.
9. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure
to common anesthetic agents causes widespread neurodegeneration
in the developing rat brain and persistent learning deficits. J Neurosci. 2003; 23:876-882.
10. Loepke AW, Istaphanous GK, McAuliffe JJ III, et al. The effects of
neonatal isoflurane exposure in mice on brain cell viability, adult
behavior, learning, and memory. Anesth Analg. 2009; 108:90-104.
11. Lunardi N, Ori C, Erisir A, Jevtovic-Todorovic V. General anesthesia causes long-lasting disturbances in the ultrastructural properties
of developing synapses in young rats. Neurotox Res. 2010; 17:179188.
19. Yon JH, Carter LB, Reiter RJ, Jevtovic-Todorovic V. Melatonin
reduces the severity of anesthesia-induced apoptotic neurodegeneration in the developing rat brain. Neurobiol Dis. 2006; 21:522-530.
20. Young C, Jevtovic-Todorovic V, Qin YQ, et al. Potential of ketamine and midazolam, individually or in combination, to induce
apoptotic neurodegeneration in the infant mouse brain. Br J Pharmacol. 2005; 146:189-197.
Human Studies
21. Bartels M, Althoff RR, Boomsma DI. Anesthesia and cognitive performance in children: no evidence for a causal relationship. Twin
Res Hum Genet. 2009; 12:246-253.
22. DiMaggio C, Sun LS, Kakavouli A, Byrne MW, Li G. A retrospective cohort study of the association of anesthesia and hernia repair
surgery with behavioral and developmental disorders in young children. J Neurosurg Anesthesiol. 2009; 21:286-291.
23. Hansen TG, Pedersen JK, Henneberg SW, et al. Academic performance in adolescence after inguinal hernia repair in infancy: a
nationwide cohort study. Anesthesiology 2011; 114:1076-1085.
24. Kalkman CJ, Peelen L, Moons KG, et al. Behavior and development
in children and age at the time of first anesthetic exposure. Anesthesiology 2009; 110:805-812.
12. Ma D, Williamson P, Januszewski A, et al. Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain.
Anesthesiology 2007; 106:746-753.
25. Sprung J, Flick RP, Wilder RT, et al. Anesthesia for cesarean delivery and learning disabilities in a population-based birth cohort.
13. Rizzi S, Ori C, Jevtovic-Todorovic V. Timing versus duration:
determinants of anesthesia-induced developmental apoptosis in the
young mammalian brain. Ann N Y Acad Sci. 2010; 1199:43-51.
26. Wilder RT, Flick RP, Sprung J, et al. Early exposure to anesthesia
and learning disabilities in a population-based birth cohort. Anesthesiology 2009; 110:796-804.
14. Sanders RD, Xu J, Shu Y, et al. Dexmedetomidine attenuates
isoflurane-induced neurocognitive impairment in neonatal rats.
8
Section II: Oh, No!
Video: Rupture of Muscle During Strabismus Surgery
David B Granet MD
N otes
Section II: Oh, No!
9
When to Order What!
The Child With Nystagmus
Sylvia R Kodsi MD
I. Nystagmus in Childhood: Differentiate by Age of
Onset
A. Congenital: Before 3 months of age
B. Acquired: After 3 months of age
II. Congenital Nystagmus Subtypes: Differentiate by Eye
Exam and Electroretinogram (ERG)
A. Motor nystagmus: Good vision
B. Sensory nystagmus: Poor vision
III. Characteristics of Congenital Motor Nystagmus
A. Onset within 3 months of age
B. Usually horizontal
C. Good vision
D. No ocular or CNS abnormalities
E.Bilateral
F. Dampened by convergence and may be associated
with esotropia
G. May have a null point
H. May have a family history
I. Paradoxical inversion of optokinetic nystagmus
response
J. Normal ERG
IV. Characteristics of Congenital Sensory Nystagmus
A. Poor vision
B.Bilateral
C. Usually horizontal
D. Onset by 3 months of age
E. Cause of bilateral loss of vision may or may not be
readily apparent by eye examination.
A. Cataracts: Family history, chromosomal studies
B. Corneal opacities: Peters anomaly or herpes simplex
virus
C. Aniridia: PAX6, WT1 genetic testing
D. Albinism: Hermansky-Pudlak syndrome
E. Optic nerve hypoplasia: MRI of brain and endocrine evaluation
F. Optic nerve colobomas: MRI of brain
G. Chorioretinal scars in the macula: toxoplasmosis,
cytomegalic virus and lymphocytic choriomeningitis
virus titers
A. Leber congenital amaurosis: Absent rod and cone
response
B. Congenital stationary night blindness: Absent rod
response
C. Achromatopsia (complete and incomplete): Absent
cone response
D. Blue cone monochromats: Partial cone response at
short wavelengths
VII. Importance of Identifying Etiology of Congenital Sensory Nystagmus in Children With a Normal Eye Exam
A. Gene therapy: Identification of patients with Leber
congenital amaurosis RPE 65 gene mutation, which
is the only subtype of patients that is eligible for
gene therapy at the present time
B. In vitro fertilization and preimplantation testing for
future pregnancies
VIII. Acquired Nystagmus Characteristics
A. Occurs after 3 months of age
B. May or may not have oscillopsia
C. Always requires MRI to rule out a structural lesion
V. Etiology of Sensory Nystagmus Visible on Eye
Examination
VI. Etiology of Sensory Nystagmus With Normal Eye
Exam: Need ERG
H. Optic atrophy: MRI
IX. Main Etiologies of Acquired Nystagmus in Children
A. Spasm nutans-head nodding and torticollis, diagnosis of exclusion
B. Chiasmal or suprachiasmal glioma or mass
C. Pinealoma: Convergence retraction nystagmus
D. Craniopharyngioma: Seesaw nystagmus
E. Opsoclonus: Postinfectious or paraneoplastic sign of
neuroblastoma
F. Arnold-Chiari malformation: Esotropia and downbeat nystagmus
X. Latent Nystagmus
A. Although thought to be congenital, it is often not
seen until early childhood.
B. Occurs in children with poor fusion from strabismus or poor vision
C. When one eye is occluded, a jerk nystagmus occurs
in both eyes with a fast phase toward the uncovered
eye.
D. Binocular vision is better than monocular vision.
10
Section II: Oh, No!
E. “Fogging with +6.00 lens” should be used to check
vision monocularly.
F. This type of nystagmus does not require any further
workup.
XI.Conclusion
A. Importance of identifying congenital vs. acquired
nystagmus in children
B. If congenital nystagmus is present, identify the cause
by either eye exam or ERG studies.
C. Acquired nystagmus in children always requires
imaging studies.
4. McLeod R, Boyer K, Karrison Y, et al for the Toxoplasmosis Study
Group. Outcome of treatment for congenital toxoplasmosis, 19812004: The National Collaborative Chicago-Based, Congenital
Toxoplasmosis Study. Clin Infect Dis. 2006; 42:1383-1394.
5. Garcia-Fillion P, Epport K, Nelson M, et al. Neuroradiographic,
endocrinology and ophthalmic correlates of adverse developmental
outcomes in children with optic nerve hypoplasia: a prospective
study. Pediatrics 2008; 121:653-659.
6. Traboulsi EI, Ellison J, Sears J, et al. Aniridia with preserved visual
function: a report of four cases with no mutations in PAX6. Am J
Ophthalmol. 2008; 145(4):760-764.
7. Robinson DO, Howarth RJ, Williamson KA, et al. Genetic analysis
of chromosome 11p13 and the PAX6 gene in a series of 125 cases
referred with aniridia. Am J Med Genet A. 2008; 146A:558-569.
Selected Readings
8. Sawada M, Sato M, Hikoya A, et al. A case of aniridia with unilateral Peters anomaly. J AAPOS. 2011; 15(1):104-106.
1. Drack AV, Johnston R, Stone EM. Which Leber congenital amaurosis patients are eligible for gene therapy trials? J AAPOS. 2009;
13:463-465.
9. Yu JT, Culican SM, Tychsen L. Aircardi-like chorioretinitis and
maldevelopment of the corpus callosum in congenital lymphocytic
choriomeningitis virus. J AAPOS. 2006;10(1):58-60.
2. Chung DC, Traboulis EI. Leber congenital amaurosis: clinical correlations with genotypes, gene therapy trials update, and future
directions. J AAPOS. 2009; 13:587-592.
10. Hanna NN, Eickholt K, Agamanolis D, et al. Atypical Peters plus
syndrome with new associations. J AAPOS. 2010; 14(2):181-183.
3. Mets MB, Barton LL, Khan AS, et al. Lymphocytic choriomeningitis virus: an underdiagnosed cause of congenital chorioretinitis. Am
J Ophthalmol. 2000; 130(2):209-215.
11. Tsilou ET, Rubin BI, Reed GF, et al. Milder ocular findings in
Hermansky-Pudlak syndrome type 3 compared with HermanskyPudlak syndrome type 1. Ophthalmology 2004; 111:1599-1603.
Section II: Oh, No!
11
The Good, The Bad, and The Ugly:
Nonaccidental Injury
Abusive Head Trauma (The Shaken Baby Syndrome)
Homicide is the leading cause of injury and death in infancy;
80% of infant homicides are thought to represent infant child
abuse, and each year some 2000 children in the United die as
a result of child abuse. The majority of these deaths are caused
by inflicted neurotrauma, which results from violent, nonaccidental shaking, blunt impact to the head, or both. Historically,
the injuries resulting from repetitive unrestrained head and neck
movements from shaking were termed the “whiplash shaken
infant syndrome,” “shaken baby syndrome,” and now the more
comprehensive term “abusive head trauma.”3
Clinical findings in affected infants include subdural hemorrhage, hypoxic-ischemic brain injury, retinal hemorrhages,
skeletal injuries, and cutaneous or other injuries. Unlike most
other forms of ocular trauma, there are usually minimal external
ocular signs of injury and no evidence of direct blows to the eye.
Skeletal fractures are found in 30%-70% of injured children, and
retinal hemorrhages are seen in approximately 80%.4,5 Victims
of abusive head trauma are generally less than 3 years of age, and
the majority are infants.
Acute Ophthalmic Findings in Abusive Head Trauma
Autopsy and in vivo studies of the acute ocular findings in
infants and toddlers less than 3 years with nonaccidental head
injury from abusive head trauma have described a consistent
clinical picture. These characteristic ophthalmic findings include
intraocular hemorrhage with a reported frequency of 50%100%, with most papers reporting approximately 80%.4,5
Retinal hemorrhage occurs at all levels of the retina, including
blot, flame-shaped, and preretinal hemorrhage as well as vitreous
hemorrhage. Retinal hemorrhages can be few in number, exclusively intraretinal, and confined to the posterior pole, although
often they are too numerous to count, present at all layers, and
extend to the ora serrata. Dense preretinal or vitreous hemorrhages may obscure underlying retinal hemorrhage. Retinoschisis
may occur, most often in the macular area but also peripherally.
Ophthalmoscopically there is a dense central hemorrhage surrounded by a pale, elevated retinal fold in a circular shape. These
lesions, seen both histopathologically and clinically, have also
been called “hemorrhagic macula cysts” and “perimacular circular folds”6 and have a unique and characteristic appearance seen
only rarely in other types of head trauma.7
Late Ophthalmic Findings in Abusive Head Trauma
In contrast to the dramatic and relatively specific acute findings,
late changes associated with abusive head trauma are neither
consistent nor specific to abusive head trauma. Permanent visual
impairment is frequent, and central visual impairment related to
the hypoxic ischemic brain injury from abusive head trauma and
optic atrophy is the most common cause of long-term reduced
vision.
Abusive Head Trauma Prevention
The Shaken Baby Syndrome Prevention & Awareness Program
was developed in 1998 in Upstate New York by Dr. Mark Dias
MD, pediatric neurosurgeon. Since the inception of the SBS
program, upstate New York has reduced the incidence of infant
abusive head injuries by nearly 50%. The results of this research
project were published in the Journal of Pediatrics in April 2005.
In 2005, the upstate New York program expanded into pediatric
offices and has shown an additional 10% decrease in infant abusive head injuries. Over the last several years, the body of robust,
scientific research on infant crying, shaken baby syndrome/
abusive head trauma (SBS/AHT) and the Period of PURPLE Crying program has grown significantly. Period of PURPLE Crying
programs have grown extensively throughout North America
over the past few years, with 49 of 50 U.S. States and 8 of 10
Canadian provinces having implemented the program at some
level, as shown in Figure 1.
The Role of the Ophthalmologist in the Diagnosis
and Management of Abusive Head Trauma
The primary role of the ophthalmologist in the care of these
young children is to provide complete evaluation of the intraocular hemorrhages. Ophthalmic consultation allows complete
assessment and documentation of the eye findings, frequently
with retinal photography, an essential component of the diagnosis of abusive head trauma. In addition to establishing the
diagnosis, examination provides prognostic information related
to the eye findings. Physicians who treat infants and children
are mandated to report suspected child abuse to child welfare
agencies for investigation, and ophthalmologists who encounter
children with ophthalmic manifestations of abuse need to ensure
that the proper steps are taken to protect their patients from further harm.
12
Section II: Oh, No!
Figure 1. PURPLE implementation map.
References
1. Brenner RA, Overpeck MD, Trumble AC, DerSimonian R,
Berendes H. Deaths attributable to injuries in infants, United States,
1983-1991. Pediatrics 1999; 103:968-974.
2. Overpeck RA, Brenner AC, Trumble LB, Trifilette LB, Berendes
HW. Risk factors for infant homicide in the US. New Engl J Med.
1998; 339:1211-1216.
3. Caffey J. The whiplash shaken infant syndrome: manual shaking by
the extremities with whiplash-induced intracranial and intraocular
bleedings, linked with residual permanent brain damage and mental
retardation. Pediatrics 1974; 54:396-403.
4. Levin, AV, Christian CW. The eye examination in the evaluation of
child abuse. Pediatrics 2010; 126(2):376-380.
5. Kivlin JD, Simons KB, Laxoritz A, Ruttum MS. Shaken baby syndrome. Ophthalmology 2000; 107:1246-1254.
6. Greenwald MJ, Weiss A, Oesterle CS, Friendly DS. Traumatic retinoschisis in battered babies. Ophthalmology 1986; 93:618-625.
7. Gaynon M, Koh K, Marmor M, Frankel LR. Retinal folds in the
shaken baby syndrome. Am J Ophthalmol. 1988; 106:423-425.
8. Dias M, Smith, D, deGuehery K, Mazur P, Li V, Shaffer M. Preventing abusive head trauma among infants and young children: a
hospital-based, parent education program. Pediatrics 2005; 115:4
e470-e477.
9. Barr R, Rivara F, Barr M, et al. Effectiveness of educational materials designed to change knowledge and behaviors regarding crying
and shaken-baby syndrome of newborns: a randomized, controlled
trials. Pediatrics 2009; 123(3):972-980.
Section II: Oh, No!
13
“Skew You”
Skew Deviation
I.Definition
6. Head tilt right
A. Vertical ocular deviation
a. Stimulates right anterior and posterior canals
B. Can be comitant or incomitant
b. Inhibits left anterior and posterior canals
C. Typically associated with ocular torsion
c. Right eye incyclotorters activated
D. Often associated with abnormal head tilt
d. Left eye excyclotorters activated
E. Pathology in brain stem
e. Compensatory counter-rolling occurs
F. Can mimic oblique muscle palsy
f. Gain is less than 1
G. Etiology typically infarction, demyelination, trauma
II.Background
A. Ocular counter-rolling reflex
7. Head tilt left
a. Stimulates left anterior and posterior
b. Inhibits right anterior/posterior canals
1. Mediated by otoliths and semicircular canals
c. Left eye incyclotorted
2. Semicircular canals project to vestibular nuclei
and then to extraocular subnuclei (respond to
acceleration, phasic)
d. Right eye excyclotorted
3. Otolithic projections less well known but probably similar (respond to position, tonic)
B. Semicircular canal projections
1. Horizontal to horizontal recti
2. Anterior canal
a. Excitatory to ipsilateral superior rectus (SR)
and contralateral inferior oblique (IO)
b. Inhibitory to ipsilateral inferior rectus (IR)
and contralateral superior oblique (SO)
C. Skew deviation is a perturbation of these projections.1
1. Caused by lesions of the prenuclear vestibular
ocular reflex pathways
2. Ocular tilt reaction
a. Excitatory to ipsilateral SO and contralateral
IR
b. Inhibitory to ipsilateral IO and contralateral
SR
4. Head pitch forward
a. Excites both anterior canals
b. Inhibits both posterior canals
c. Elevators stimulated, depressors inhibited
d. Eyes move up
a. Excites both posterior canals
b. Inhibits both posterior canals
c. Depressors stimulated, elevators inhibited
d. Eyes move down
b. Vertical strabismus head tilt
c. Paradoxical ocular torsion
d. Torsion and tilt in same direction
3. Can be comitant or incomitant and can mimic
oblique muscle palsy depending on relative
involvement of each pathway
4. Distinguishing feature is torsion as it is in the
opposite direction for oblique palsy.
III. Localizing Skew Deviation9
A. Caudal brainstem lesions
1. Typically caudal pons and medulla
2. Hypertropic eye contralateral to lesion
3. Lesion on side of lower eye for lower lesions
5. Head pitch backward
a. Type of skew deviation
3. Posterior canal
B. Rostral brainstem lesions
1. Typically upper pons and midbrain
2. Hypertropic eye ipsilateral to lesion
3. Lesion on side of higher eye for higher lesions
C. All cases are associated with torsion and head tilt
toward lower-most eye.
14
Section II: Oh, No!
IV. Naming Skew Deviation
A. Neurologists typically name based upon hypotropic
eye.
B. Strabismus specialists in neuro-ophthalmology
name based upon which eye is higher: “left over
right skew”
A. Asymmetric lesions to the otolithic pathways corresponding to those of a particular semicircular canal
pathway produce an incomitant skew deviation that
can mimic an oblique muscle palsy.
B. Lesions most affecting contralateral posterior canal
pathways can mimic a superior oblique palsy (ie,
lesion on side of hypotropic eye).6
C. Lesions most affecting anterior canal pathways on
ipislateral side can mimic an inferior oblique palsy
(ie, lesion on side of hypotropic eye).2
D. Key feature is ocular torsion.
1. Skew deviation has hypertropic eye incyclotorted
or hypotropic eye excyclotored.
2. Superior oblique palsy has hypertropic eye
excyclotorted.
3. Inferior oblique palsy has hypotropic eye
incyclotorted.
E. Difference in vertical deviation from upright to
supine may also be helpful.7,8
VI. Treatment of Skew Deviation10
A. Await spontaneous resolution.
B. Prism for small angle deviation
C. Surgery must correct vertical and torsion.
D. Consider using synoptophore in surgical
evaluation.
1. Assess if torsion significant.
2. Determine potential stereopsis.
1. If torsion not significant (ie, fuse vertical in free
space)
a. Vertical rectus recession if large
b. Horizontal rectus recession/resection
V. Distinguishing Skew Deviation From Oblique Muscle
Palsy: Background
E. Surgical options
2. If no fusion in free space
a. Consider horizontal transposition of vertical
rectus
b. Consider oblique surgery
VII. Skew as a Mechanism in Childhood Strabismus
A. Primarily theoretical
B. Several papers postulate an association.3-5
References
1. Brodsky MC, Donahue SP, Vaphiades M, Bandt. Skew deviation
revisited. Surv Ophthalmology. 2006; 51:105-128.
2. Donahue SP, Lavin PJ, Mohney B, Hamed L. Skew deviation and
inferior oblique palsy. Am J Ophthalmol. 2001; 132:751-756.
3. Donahue SP, Brodsky MC. Posterior canal predominance in bilateral skew deviation. Br J Ophthalmol. 2001; 85:1395.
4. Brodsky MC, Donahue SP. Primary oblique muscle overaction: the
brain throws a wild pitch. Arch Ophthalmol. 2001; 119:1307-1314.
5. Donahue SP, Itharat P. A-pattern strabismus with overdepression
in adduction: a special type of bilateral skew deviation? J AAPOS.
2010; 14:42-46.
6. Donahue SP, Lavin PJ, Hamed LM. Tonic ocular tilt reaction simulating a superior oblique palsy: diagnostic confusion with the 3-step
test. Arch Ophthalmol. 1999; 117:347-352.
7. Parulekar MV, Dai S, Buncic JR, Wong AM. Head position-dependent changes in ocular torsion and vertical misalignment in skew
deviation. Arch Opthalmol. 2008; 126:899-905.
8. Wong AM. Understanding skew deviation and new clinical test to
differentiate it from trochlear nerve palsy. J AAPOS. 2010; 14:6167.
9. Brandt T, Dieterich M. Skew deviation with ocular torsion: a vestibular brainstem sign of topographic diagnostic value. Ann Neurol.
1993; 33:528-534.
10. Siatkowski RM, Sanke RF, Farris BK. Surgical management of
skew deviation. J Neuroophthalmol. 2003; 23:136-141.
Section III: Oh, No! Part 2: What Do We Do Now?
AAP Federal Affairs Update
Mark Del Monte JD
N otes
15
16
Video: Goniotomy in an Aniridic Patient
Goniotomy for aniridic patients is challenging, as there is no protection for the lens due to an absent iris. This video demonstrates
the angle anomaly seen in aniridia that may benefit from angle
surgery. The use of prophylactic goniotomy in aniridia has not
gained favor, but in those cases with early onset glaucoma where
the pathophysiology of glaucoma is likely due to an anomalously
developed angle (similar to that seen in primary congenital glaucoma) this procedure may still be considered as an option.
17
Descemet-Stripping Automated Endothelial
Keratoplasty / Deep Lamellar Endothelial Keratoplasty:
What Are They? Are They Good for Kids?
I. History of Corneal Transplant Surgery: PKP vs.
Selective Corneal Transplant
VI.Results
II. Historical Overview of Corneal Transplant Surgery in
Children
III. Indications for Pediatric Corneal Transplant Surgery
1. Peters anomaly, sclerocornea, dermoids: 65%70%
2. Dystrophies (congenital hereditary endothelial
dystrophy [CHED], congenital hereditary stromal dystrophy, posterior polymorphous corneal
dystrophy): 15%
3. Congenital glaucoma: 15%
B. Acquired nontraumatic: 20%
1. Keratoconus: 50%
2. Bacterial infections: 20% (contact lens wearers,
rosacea)
3. Herpes simplex virus: 14%
4. Failed grafts: 7%
C. Traumatic: 10%
IV. Development of Endothelial Keratoplasty
A. Melles, 2000; Terry, 2003; Gorovoy, 2005-6
B. Terminology and technique
1. Excellent, with high success rate in routine cases;
50% endothelial cell loss after 5 years
2. Results more problematic in patients with glaucoma/shunts/filters
A. Congenital: 65%-70%
A.Adults
1. Deep lamellar endothelial keratoplasty (DLEK)
2. Descemet-stripping automated endothelial keratoplasty (DSAEK), Descemet-stripping endothelial keratoplasty (DSEK)
3. Descemet membrane endothelial keratoplasty
(DMEK)
V. Pediatric Corneal Diseases That Might Require
Endothelial Keratoplasty
A. Endothelial decompensation
1. CHED: 17 cases in literature
2. Congenital glaucoma: 0 cases
3. Failed grafts: 0 cases
B. Children: Limited data
VII.Conclusions
A. An operation with good potential in a very select
group of children
B. Steep learning curve
C. Very little short- or long-term data in children
References and Selected Readings
1. Melles GR, Lander F, van Dooren BT, Pels E, Beekhuis WH. Preliminary clinical results of posterior lamellar keratoplasty through
a sclerocorneal pocket incision. Ophthalmology 2000; 107:18501856.
2. Terry MA, Ousley PG. Replacing the endothelium without corneal
surface incisions or sutures: the first United States clinical series
using the deep lamellar endothelial keratoplasty procedure. Ophthalmology 2003; 110:755-764.
3. Gorovoy MS. Descemet’s stripping automated endothelial keratoplasty. Cornea 2006; 25:886-889.
4. Zaidman GW, Flanagan JK, Furey CC. Long term visual prognosis
in children after corneal transplant surgery for Peters anomaly Type
I. Am J Ophthalmol. 2007; 144:104-108.
5. Lee WB, Jacobs DS, Musch DC, Kaufman SC, Reinhart WJ, Shtein
RM. Descemet’s stripping endothelial keratoplasty: safety and
outcomes: a report by the American Academy of Ophthalmology.
Ophthalmology 2009; 116:818-830.
6. Pineda R, Jain V, Shome D, Hunter DC, Natarajan S. Descemet’s
stripping endothelial keratoplasty: is it an option for congenital
hereditary endothelial dystrophy? Int Ophthalmol. 2010; 30:307310.
7. Mittal V, Mittal R, Sangwan VS. Successful Descemet stripping
endothelial keratoplasty in congenital hereditary endothelial dystrophy. Cornea 2011; 30:354-356.
8. Price MO, Fairchild KM, Price DA, Price FW. Descemet stripping
endothelial keratoplasty: five-year graft survival and endothelial cell
loss. Ophthalmology 2011; 118:725-729.
9. Busin M, Beltz J, Scorcia V. Descemet-stripping automated endothelial keratoplasty for congenital hereditary endothelial dystrophy.
Arch Ophthalmol. E-pub ahead of print 9 May 2011.
18
Endoscopic Vitreoretinal Surgery
Thomas C Lee MD
N otes
19
Intracameral Medications for Every Intraocular
Surgery? Is This Safe for Kids?
M Edward Wilson MD, Rupal H Trivedi MD MSCR
Every pediatric eye surgeon has dreamed of the day when topical medications after surgery can be eliminated. Many parents
struggle to comply with the surgeon’s instructions for preoperative and postoperative topical drops. We have all seen children
with persistent inflammation, cell deposits on the surface of the
IOL, and posterior synechia of the pupil. These complications
are more often seen in situations where the parents have not been
consistent in the application of postoperative medications.
As part of his Binkhorst Lecture in 2000, Robert Osher
stated: “One of the major changes in ocular surgery I expect to
see in my lifetime is the obsolescence of topical drops.” Since
then, intracameral medications have been studied, in adults, for
pupil dilation, infection prophylaxis, and control of postoperative inflammation. Questions remain, however. Are these medications safe for children? Do they add value to the topical regime
we all use for children? Can intracameral medications replace
topical applications, or can they at least reduce the consequences
of parental noncompliance?
After surgery we still instruct the parents of our pediatric
patients in the proper method and frequency of antibiotic and
steroid drop application. However, at surgery, we are exploring every possible way to promote healing and prevent infection
without having to rely on the compliance of the parents postoperatively. Can we achieve “no drops” pediatric cataract surgery?
Will we see effective healing and the same low incidence of
infection in noncompliant families as we do in those who comply with 4 weeks of multidose daily drops?1-7 Perhaps we can.
Herein we will focus discussion on the safety and effectiveness of
intracameral mydriatics, antibiotics, and triamcinolone for pediatric intraocular surgery.
References
1. Lundberg B, Behndig A. Separate and additive mydriatic effects of
lidocaine hydrochloride, phenylephrine, and cyclopentolate after
intracameral injection. J Cataract Refract Surg. 2008; 34:280-283.
2. Myers WG, Shugar JK. Optimizing the intracameral dilation regimen for cataract surgery: prospective randomized comparison of 2
solutions. J Cataract Refract Surg. 2009; 35:273-276.
3. Gills JP, Gills P. Effect of intracameral triamcinolone to control
inflammation following cataract surgery. J Cataract Refract Surg.
2005; 31:1670-1671.
4. Dixit NV, Shah SK, Vasavada V, et al. Outcomes of cataract surgery and intraocular lens implantation with and without intracameral triamcinolone in pediatric eyes. J Cataract Refract Surg. 2010;
36:1494-1498.
5. Cleary CA, Lanigan B, O’Keeffe M. Intracameral triamcinolone
acetonide after pediatric cataract surgery. J Cataract Refract Surg.
2010; 36:1676-1681.
6. Barry P, Seal DV, Gettinby G, Lees F, Peterson M, Revie CW;
ESCRS Endophthalmitis Study Group. ESCRS study of prophylaxis
of postoperative endophthalmitis after cataract surgery: preliminary
report of principal results from a European multicenter study. J
Cataract Refract Surg. 2006; 32:407-410.
7. Espiritu CR, Caparas VL, Bolinao JG. Safety of prophylactic intracameral moxifloxacin 0.5% ophthalmic solution in cataract surgery
patients. J Cataract Refract Surg. 2007; 33:63-68.
20
Fundus Autofluorescence in Pediatric Ophthalmology
Introduction
FAF in Children
Fundus autofluorescence (FAF) imaging utilizes the fluorescent
properties of lipofuscin to study the health and viability of the
retinal pigment epithelium / photoreceptor complex. Lipofuscin
is a heterogeneous fluorescent waste material that accumulates
with age in some active postmitotic cells such as cardiac myocytes, select neurons, and the retinal pigment epithelium (RPE).1
RPE lipofuscin can be visualized in vivo using FAF imaging, and
its patterns of distribution, accumulation, or absence can be
characteristic of a variety of inherited or age-related retinal disorders.2 This presentation will review examples of FAF in selected
inherited childhood retinal disorders and its usefulness in the
diagnosis and follow-up of patients.
Because lipofuscin accumulates with aging, levels of autofluorescence may be low in very young children.
Physiology
Lipofuscin is derived from phagocytosed photoreceptor outer
segments and normally accumulates in the RPE.3 RPE lipofuscin
differs from that of other cells in that it is mainly derived from
chemically modified residues of incompletely digested photoreceptor outer segments. It is composed of a mixture of lipids, proteins, and different fluorescent compounds, the main fluorophore
of which is a derivative of vitamin A (retinoids). Formation of
RPE lipofuscin fluorophores is almost completely dependent on a
normal visual cycle, and the absence of retinal (both all-trans and
11-cis) for example in RPE65- knockout mice drastically reduces
its formation. Hence normal FAF reflects the anatomic integrity
of RPE and photoreceptors, normal outer segment turnover, and
normal vitamin A metabolism.4
FAF Imaging Technology
Fundus autofluorescence (FAF) is recorded with a confocal scanning laser ophthalmoscope. The distribution of lipofuscin in
fundus RPE using FAF was described by von Ruckmann et al.5
In the normal fundus in subjects over the age of 15 years, they
found diffuse autofluorescence with the retinal blood vessels
and optic disc appearing as negative shadows. In patients with
long-standing retinal atrophy, they observed absent autofluorescence that corresponded spatially to the atrophy but present
fluorescence in adjacent regions of surviving retina. FAF can be
visualized with other cameras such as the Topcon TRC 50IX
fundus camera. The highest degrees of fundus AF are detected
in normal individuals at 7 degrees from the fovea and the lowest
degrees are at the fovea. Physiologically reduced FAF is observed
in the absence of RPE cells (eg, at the optic disc) or may be due
to absorption of the incident short wavelength light by melanin,
macular pigment, and the retinal vessels. Reduced FAF in retinal
diseases may be due to a number of factors, including photoreceptor and/or RPE cell loss, disrupted phagocytosis, or disruption of the retinoid cycle.4
Stargardt Disease
In Stargardt disease there are high levels of lipofuscin in the RPE.
This results in high levels of autofluorescence on FAF imaging.
As the disease progresses, patchy areas of loss of FAF are visualized and correspond to loss of retinal sensitivity reflecting photoreceptor cell death.6
Bestrophinopathies
In the bestrophinopathies, including Best disease, there is
increased autofluorescence in the fovea and in extrafoveal lesions
as a result of the accumulation of larger-than-normal levels of
lipofuscin in the RPE.2, 7 A diffuse increase in FAF is detected due
to the generalized accumulation of lipofuscin in RPE cells.
Leber Congenital Amaurosis
FAF may be preserved in the presence of severe photoreceptor
dysfunction, as shown by undetectable full-field ERGs,4 and
indicates structurally intact photoreceptors and preservation
of the photoreceptor/RPE complex. In patients with CEP290
(NPHP5) and NPHP6 mutations, there is diffuse loss of FAF
except in the foveal region, in which there is a preserved disc of
FAF that corresponds to overlying remaining functioning cones;
all rods and underlying RPE have degenerated.8 Patients with
RPE65 mutations have reduced or severely reduced levels of FAF
as a result of the severely reduced levels of retinoids.
Retinitis Pigmentosa
More than half of retinitis pigmentosa (RP) patients have an
abnormally high-density parafoveal FAF ring (AF ring).9 This
AF ring represents the border between functional and dysfunctional retina.10 Aizawa et al showed that that the size of AF ring
decreased with the progression of RP. This was accompanied by
a shortening of the length of the inner segment/outer segment
line, a decrease in retinal sensitivity, and a worsening of BCVA.11
Fundus Albipunctatus
In fundus albipunctatus there are areas of increased AF of the
RPE that correspond to the ophthalmoscopically visible lesions
and RPE lesions on OCT images; in retinitis punctata albescens,
in addition to the white lesions there is an enhanced AF ring in
a parafoveal location.12 Mutations in RDH5 lead to a defect in
oxidation of 11-cis-retinol into 11-cis-retinal. In the absence of
this conversion, there is presumed storage of a retinoid, likely in
an esterified form, within RPE cells. RLBP1 encodes the protein
CRALBP, located within RPE and Müller cells, which binds
21
to the vitamin A derivatives 11-cis-retinol and 11-cis-retinal.
Impaired function of this protein could lead to the accumulation of a retinoid compound(s) within RPE cells, hence increased
FAF.
5. von Ruckmann A, Fitzke FW, Bird AC. Distribution of fundus
autofluorescence with a scanning laser ophthalmoscope. Br J Ophthalmol. 1995; 79:407-412.
Conclusions
7. Lois N, Halfyard AS, Bird AC, Fitzke FW. Quantitative evaluation
of fundus autofluorescence imaged “in vivo” in eyes with retinal
disease. Br J Ophthalmol. 2000; 84:741-745.
Because of its ability to detect lipofuscin mainly at the RPE level,
FAF is a useful method to assist in the diagnosis and progression
of a wide variety of inherited and acquired retinal diseases even
at stages in which fundus changes are not clearly evident on routine ophthalmoscopy. Normal or near-normal FAF may reflect
the presence of structurally intact photoreceptors and preserved
photoreceptor/RPE complex. Hence FAF imaging findings may
have implications for gene and other therapies of inherited retinal disorders.
References
1. Sparrow JR, Boulton M. RPE lipofuscin and its role in retinal
pathobiology. Exp Eye Res. 2005; 80:595-606.
2. Spaide R. Autofluorescence from the outer retina and subretinal
space: hypothesis and review. Retina 2008; 28:5-35.
3. Kennedy CJ, Rakoczy PE, Constable IJ. Lipofuscin of the retinal
pigment epithelium: a review. Eye 1995;9(pt 6):763-771.
4. Scholl HP, Chong NH, Robson AG, Holder GE, Moore AT, Bird
AC. Fundus autofluorescence in patients with Leber congenital
amaurosis. Invest Ophthalmol Vis Sci. 2004; 45:2747-2752.
6. Sunness JS, Steiner JN. Retinal function and loss of autofluorescence in Stargardt disease. Retina 2008; 28:794-800.
8. Cideciyan AV, Rachel RA, Aleman TS, et al. Cone photoreceptors are the main targets for gene therapy of NPHP5 (IQCB1) or
NPHP6 (CEP290) blindness: generation of an all-cone Nphp6
hypomorph mouse that mimics the human retinal ciliopathy. Hum
Mol Genetics. 2011; 20:1411-1423.
9. Popovic P, Jarc-Vidmar M, Hawlina M. Abnormal fundus autofluorescence in relation to retinal function in patients with retinitis
pigmentosa. Graefes Arch Clin Exp Ophthalmol. 2005; 243:10181027.
10. Robson AG, Saihan Z, Jenkins SA, et al. Functional characterisation and serial imaging of abnormal fundus autofluorescence in
patients with retinitis pigmentosa and normal visual acuity. Br J
Ophthalmol. 2006; 90:472-479.
11. Aizawa S, Mitamura Y, Hagiwara A, Sugawara T, Yamamoto S.
Changes of fundus autofluorescence, photoreceptor inner and outer
segment junction line, and visual function in patients with retinitis
pigmentosa. Clin Experiment Ophthalmol. 2010;38:597-604.
12. Genead MA, Fishman GA, Lindeman M. Spectral-domain optical
coherence tomography and fundus autofluorescence characteristics
in patients with fundus albipunctatus and retinitis punctata albescens. Ophthalmic Genet. 2010; 31:66-72.
22
Surgery by Surgeons
2011 Surgery by Surgeons Update
With this year’s passage of legislation in Kentucky that allows
optometrists to perform laser surgery, the American Academy
of Ophthalmology’s partnership with ophthalmic subspecialty
and state societies on the Surgery by Surgeons campaign becomes
even more important in protecting quality patient eye care across
the country.
In 2009-2010, the Eye M.D.s serving on the Academy’s Secretariat for State Affairs collaborated with the leadership of many
state ophthalmology societies on legislative battles in which
optometry continued to push for expanded scope of practice.
Leadership of subspecialty societies provided essential support
in some of these battles. Success was reached with surgery provisions removed and/or bills defeated in Idaho, Maine, Mississippi, Nebraska, South Carolina, Texas, Washington and West
Virginia.
In 2011, the stakes were raised with the disappointing outcome in Kentucky. The Kentucky legislation also includes the
creation of an independent optometric board; no other board or
state agency has the authority to question what constitutes the
practice of optometry. The Secretariat for State Affairs continues
to work diligently with state society leaders in South Carolina,
Nebraska, Tennessee and Texas to ensure that a Kentucky outcome is not repeated. For example, following the passage of legislation in Kentucky, fundraising material by organized optometry in Tennessee made it clear that they would like to replicate
optometry’s outcome in Kentucky and have begun discussions
with state legislators.
The Surgical Scope Fund (SSF) is a critical tool of the Surgery
by Surgeons campaign to protect patient quality of care. The
Academy relies not only on the financial contributions via the
SSF by individual Eye M.D.s but also on the contributions made
by ophthalmic state, subspecialty and specialized interest societies. The American Association for Pediatric Ophthalmology &
Strabismus (AAPOS) contributed to the SSF in 2010 and 2011,
and the Academy counts on its continued support.
The results in Kentucky should be viewed as a failure neither
of the SSF nor of the Academy’s Secretariat for State Affairs,
which geared up immediately to strategize with Kentucky Academy physician leadership. In a period of fifteen days, with no
advanced warning, optometry was able to introduce and pass a
bill in the Kentucky state legislature and secure its passage into
law. But a SSF disbursement actually assisted with critical media
buys and powerful public messaging favoring ophthalmology
and quality patient eye care for the citizens of Kentucky. This
should be a lesson to each Eye M.D. in the country about the
importance of contributions to your state eyePAC and to the
SSF.
Leaders of AAPOS are part of the Academy’s Ophthalmology Advocacy Leadership Group (OALG), which has met for
the past four years in the Washington DC area to provide critical
input and to discuss and collaborate on the Academy’s advocacy agenda. The AAPOS and AAP-Section on Ophthalmology
remain crucial partners to the Academy in its ongoing federal
and state advocacy initiatives. As 2011 Congressional Advocacy
Day (CAD) partners, the two pediatric societies ensured a strong
presence of pediatric specialists to support ophthalmology’s
priorities as over 350 Eye M.D.s had scheduled CAD visits to
members of Congress in conjunction with the Academy’s 2011
Mid-Year Forum in Washington DC.
At the state level, the Academy’s Surgery by Surgeons campaign has demonstrated a proven track record. Kentucky was an
outlier; the Academy’s SSF has helped 31 state ophthalmology
societies reject optometric surgery language.
Help us help you protect our patients and quality eye care.
The Academy’s SSF remains a critical tool in the Surgery by Surgeons campaign. The Academy’s SSF Committee works hard on
your behalf to ensure the ongoing strength and viability of the
SSF.
Thomas Graul MD (Nebraska): Chair
Arezio Amirikia MD (Michigan)
Kenneth P Cheng MD (Pennsylvania)
Bryan S Lee MD PhD (Maryland): Consultant
Richard G Shugarman MD (Florida)
Stephanie J Marioneaux MD (Virginia)
Bryan S Sires MD PhD (Washington)
Andrew Tharp MD (Indiana)
Ex-officio members:
Cynthia A Bradford MD
Daniel J Briceland MD
The SSF is our collective fund to ensure that optometry does
not legislate the right to perform surgery. Do not forget about
Congress, where ophthalmology’s influence is expressed through
OPHTHPAC. Just as a strong state presence is needed, so do we
need to remain strong in the federal arena. While OPHTHPAC
is the third largest medical PAC, a mere 15% of the Academy’s
membership contribute.
The Kentucky legislation is not in the best interests of patient
safety and quality patient care. Ophthalmology needs the active
support of every member—and this includes contributions to the
Surgical Scope Fund, state eye PACs and OPHTHPAC.
Please respond to your SSF Committee and OPHTHPAC
Committee colleagues when they call on you and your subspecialty society to contribute. There are some decisions that require
thought, but donating $500 to the SSF and OPHTHPAC is the
easy answer for you and your patients. Do it today. Do it now.
COMETs CLAMP ATOM: The Myopia Studies—
Can We Affect Refractive Outcomes?
Terri L Young MD
Myopia (nearsightedness) is a potentially blinding eye condition
and the most common human eye disorder. With its increasing prevalence and earlier age of onset in recent birth cohorts,
myopia now affects almost 33% of adults in the United States,
and epidemic proportions of 85% to 90% of adults in Asian cities. The prevalence of myopia in Western population 7-year-old
children is less than 5%, compared to 29% in Asian children. In
addition to the direct economic and social burdens of myopia,
associated ocular complications may lead to substantial visual
loss. This presentation summarizes the current literature regarding myopia epidemiology, genetics, animal model studies, risk
factors, and clinical treatments.
23
24
Iris Clip Lenses for Aphakia
Lens dislocation can be found in children with hereditary ectopia
lentis, Marfan syndrome, or homocystinuria, or after trauma.
The absence of sufficient capsular support after removal of
the lens interferes with in-the-bag fixation of an IOL, making
IOL implantation in these cases a challenge, especially in children. The choice of lens design is open to debate, and no large,
prospective, randomized clinical trials are available. In 2003
Wagoner et al performed an ophthalmic technology assessment
(OTA) to evaluate options for IOL implantation in the absence
of capsular support. They reviewed scientific literature published
up to March 2002 and concluded that open-loop anterior chamber, scleral sutured posterior chamber (PC), and iris-sutured
posterior chamber IOLs could all be used safely and effectively,
without one being superior to the other.1 Reported complications were corneal edema, secondary glaucoma, IOL dislocation, cystoid macular edema (CME), suture erosion, and retinal
detachment.
More recently other techniques have been introduced such as
a capsular tension ring with PC-IOL in the capsular bag, sutured
to the sclera,2,3 and endoscopic guided PC-IOL implantation in
the sulcus during pars plana vitrectomy.4
In 1978, the Artisan aphakia IOL (Ophtec, Groningen), a
one-piece PMMA anterior chamber iris-fixated lens, designed by
JG Worst, was introduced in the Netherlands. Since then, this
lens has been used to correct aphakia, originally in adults but
later also in children. Sminia et al5,6 published about the use of
this lens in children with bilateral cataract, traumatic cataract,
and lens dislocation. Nowadays, the Artisan IOL is only used in
children with insufficient capsular support. The lens has a body
of 5.0 mm and an overall diameter of 8.5 mm. For small eyes
a pediatric design is available with a body of 4.4 mm and an
overall diameter of 6.5 or 7.5 mm. The anterior chamber depth
should be at least 3.3 mm, which is normally no problem in these
children.
studies have been undertaken but follow-up is still short. Other
possible causes of concern are IOL dislocation by erosion of the
claws through the iris, prolonged postoperative inflammation,
chronic anterior uveitis, cystoid macular edema, and iris atrophy. Dislocation of the lens is rare, since the design of the claws
was adapted in the mid-1980s, but it can be seen after blunt
trauma to the eye. However, repositioning is easy to perform.
Other complications do not occur more frequently compared to
PC-IOLs.
Advantages of implantation of an iris clip lens are that the
implantation technique is straightforward and easy to acquire
and there is no need for angle support, pupil fixation, or transscleral sutures. For post-traumatic aniridia an Artisan iris
reconstruction lens is available.8 Furthermore, the IOL can be
exchanged easily in case of substantial refractive errors when
the eye is full grown. So, in conclusion, iris clip lenses are a good
alternative for implantation in eyes of children without support
of the capsular bag.
Surgical Technique
5. Sminia ML, Odenthal MT, Wenniger-Prick LJ, Gortzak-Moorstein
N, Völker-Dieben HJ. Traumatic pediatric cataract: a decade of
follow-up after Artisan® aphakia intraocular lens implantation.
J AAPOS. 2007; 11(6):555-558.
After removal of the crystalline lens and the capsular bag, constriction of the pupil is obtained with carbacholine 0.1 mg/ml or
acetylcholine 10 mg/ml. A viscoelastic is used to fill the anterior
chamber and protect the corneal endothelium. The Artisan is
inserted through a 5-mm incision, and the claws are attached to
the iris by enclavation of peripheral iris tissue. To prevent pupillary block glaucoma, a peripheral iridectomy is obligatory.
Concerns and Advantages
One of the concerns is the possible long-term negative effect
on the corneal endothelial cell density. Small case studies with
follow-up varying from 8 months to 10 years have shown no
significant difference compared to control eyes.6,7 Prospective
References
1. Wagoner MD, Cox TA, Ariyasu RG, Jacobs DS, Karp CL. Intraocular lens implantation in the absence of capsular bag support: a
report by the AAO. Ophthalmology 2003; 110(4):840-859.
2. Konradsen T, Kugelberg M, Zetterström C. Visual outcomes and
complications in surgery for ectopia lentis in children. J Cataract
Refract Surg. 2007; 33(5):819-824.
3. Vasavada V, Vasavada VA, Hoffman RO, Spencer TS, Kumar RV,
Crandall AS. Intraoperative performance and postoperative outcomes of endocapsular ring implantation in pediatric eyes. J Cataract Refract Surg. 2008; 34(9):1499-1508.
4. Olsen TW, Pribila JT. Pars plana vitrectomy with endoscopicguided sutured posterior chamber intraocular lens implantation in
children and adults. Am J Ophthalmol. 2001; 151(2):287-296e2.
6. Sminia ML, Odenthal MT, Prick LJ, Mourits MP, Völker-Dieben
HJ. Long-term follow-up of the corneal endothelium after aphakic
iris-fixated IOL implantation for bilateral cataract in children.
J Cataract Refract Surg. 2011; 37:886-872.
7. Lifshitz T, Levy J, Klemperer I. Artisan aphakic intraocular lens in
children with subluxated crystalline lenses. J Cataract Refract Surg.
2004; 30:1977-1981.
8. Sminia ML, Odenthal MT, Gortzak-Moorstein N, Wenniger-Prick
LJ, Völker-Dieben HJ. Implantation of the Artisan® iris reconstruction intraocular lens in 5 children with aphakia and partial aniridia
caused by perforating ocular trauma. J AAPOS. 2007; 11:268-272.
25
Should We Be Using Mitomycin So Readily in Pediatric
Glaucoma Surgery?
I. The Problem: Poor Success of Filtration Surgery in
Children
A.Background
1. The candidates: Refractory pediatric glaucoma
a. Primary congenital/infantile glaucoma after
failed angle surgery
b. Aphakic/pseudophakic glaucoma (angle surgery failed first?)
c. Juvenile open-angle glaucoma (selected cases)
d. Other secondary glaucomas (selected cases)
a. Poor success in “plain” trabeculectomy in
children?
b. 5-fluorouracil and irradiation for pediatric
filtration surgery
c. Other filtration surgery: “Combined” trabeculectomy-otomy
d. Alternatives to filtration surgery: Glaucoma
drainage devices, cycloablation
3. Mitomycin: Why it “works”
a. Chemotherapeutic agent
b. Inhibitor of cell (fibroblast) proliferation
B. Mitomycin and adult glaucoma surgery
1. The early days – high hopes
a. Improved trabeculectomy success in adults
b. Better than the competition (5-fluorouracil)
2. Sobering truths
a. Infections: Blebitis, endophthalmitis
b. Leaks, early and late
3. “Optimal” dosing; best kept secret
a.Concentration
b. Time of exposure
c. Exposure location and methods
II. Mitomycin and Pediatric Glaucoma Surgery
A.Trabeculectomy
1. Improved “success”
a. Reality of infections and leaks
b. Failures over time despite drug
c. Selection of suitable candidates
2. Mitomycin-less trabeculectomy
2. Sobering facts
3. Modified techniques
a. Fornix incisions
b. Exposure to drug
c. Will they improve safety/success?
B. Glaucoma drainage implant surgery
1. Role for mitomycin?
2. Improved success, or paradoxical effect?
3. Other risks
III.Conclusions
A. Mitomycin provides a useful tool in pediatric glaucoma surgery.
B. There is no “free lunch.”
C. Long-term follow-up needed.
D. Bevacizumab – the “next” mitomycin?
Selected Readings
1. Freedman SF. Medical and surgical treatments for childhood glaucoma. In: Allingham RR, Shields MB, eds. Shield’s Textbook of
Glaucoma, 6th ed. Philadelphia: Lippicott Williams & Wilkins;
2010.
2. Mandal AK, Matalia JH, Nutheti R, Krishnaiah S. Combined trabeculotomy and trabeculectomy in advanced primary developmental glaucoma with corneal diameter of 14 mm or more. Eye 2006;
20(2):135-143.
3. Tanimoto SA, Brandt JD. Options in pediatric glaucoma after angle
surgery has failed. Curr Opin Ophthalmol. 2006; 17(2):132-137.
4. Pakravan M, Homayoon N, Shahin Y, Ali Reza BR. Trabeculectomy with mitomycin C versus Ahmed glaucoma implant with
mitomycin C for treatment of pediatric aphakic glaucoma. J Glaucoma. 2007; 16(7):631-636.
5. Mahdy RA. Adjunctive use of bevacizumab versus mitomycin C
with Ahmed valve implantation in treatment of pediatric glaucoma.
J Glaucoma. E-pub ahead of print 16 Aug 2010.
6. Al-Mobarak F, Khan A. Two-year survival of Ahmed valve implantation in the first 2 years of life with and without intraoperative
mitomycin-C. Ophthalmology 2009; 116(10):1862-1865.
26
Do Adjustable Sutures Enhance Outcomes?
Paolo Nucci MD, Massimiliano Serafino MD, Matteo Sacchi MD
Not all strabismus surgeons use adjustable sutures (AS). To tell
the truth, the attitude toward AS seems to be fideistic: some surgeons use them in almost all situations, while some are reluctant
even when there is a strong evidence that AS could obtain better
results.
Our attempt, apparently reactionary and “against the current
thinking,” is to give voice to the group of surgeons not keen to
do this surgery. We interviewed 33 surgeons reluctant to perform
the AS technique, and we collected the reasons they asserted to
justify their aversion to AS.
I. “Sincerely, I am not comfortable in operating awake
patients.”
Corollary: Strabismus surgeons are often people not as
used to finely move forceps and scissors as the majority
of ophthalmic surgeons, and they can treat muscles and
tissues quite aggressively. Topical or local anesthesia
creates anxiety for these surgeons and does not warrant
complete comfort for the patient.
II. “Dealing with a sixth cranial nerve palsy there is not
much to adjust; I have no risk for overcorrecting the
condition.”
Some surgeons prefer to maximally recess the antagonist, medial rectus, and consider resection of a paretic
muscle unpredictable. Lastly, they are convinced that
transposition surgery takes effect only few days after
the procedure . . . so . . . !
III. “Inferior rectus recession, the most needed surgery for
Graves ophthalmopathy, tends to increase in effect
with time.”
Strabismus surgeons believe there is no reason to strive
to obtain the alignment intraoperatively (or the day
after) if muscle function will change weeks or months
after the operation.
IV. “How reliable is cover test evaluation in the OR?”
Do surgeons’ and patients’ expectation to quickly complete the maneuvers concur with a truly accurate measurement? Is quality of vision after ocular manipulation
always enough to disclose fine misalignment? These are
questions related to the reliability of finely adjusting the
eye position.
V. “AS have good effect only if you can restore the normal binocular vision (NBV); there is no reason to opt
for this surgery in conditions in which NBV cannot be
restored.”
In other words, we trust in stereopsis restoration to be
sure our surgery obtained the best possible result.
VI. “AS are effective only with topical anesthesia.”
The idea behind this exception is that even local subtenon anesthesia could affect muscle movement and
induce unpredictable results when the drug effect fades.
VII. “No prospective, randomized, double-blind studies
show that the long-term results of strabismus surgery
are better using AS.”
As a matter of fact, a recent Cochrane study did not
find any randomized controlled trials comparing
adjustable to non-AS for strabismus surgery.
27
Congenital Corneal Opacification: Time for a Re-think?
Traditionally, congenital corneal opacification has been considered in terms of various etiologies and these have often been
remembered by the following mnemonic:
S: Sclerocornea
T: Trauma
U: Ulcer
M: Metabolic
P: Peters anomaly
E: Endothelial dystrophy
D: Dermoid
Although this is helpful, it doesn’t help us formulate a plan or
speculate on prognosis for a child with congenital corneal opacities. Over 12 years this author has seen over 200 children with
congenital corneal opacification, and it has become apparent
that there is a pattern that lends itself to a clinically more practical classification.1
Corneal opacities may be considered as being primary or secondary:
• Primary corneal problem
– Corneal dystrophy (eg, congenital hereditary endothelial dystrophy, posterior polymorphous dystrophy,
congenital X-linked endothelial dystrophy)
– Corneal dermoid
– Isolated sclerocornea: Termed CNA1 or CNA2. This is
not associated with total corneal opacification.2
• Secondary corneal problem
–Congenital
* Primary intraocular problem (eg, affecting the lens,
trabecular meshwork, or iris)
* Primary systemic problem (eg, metabolic)
– Acquired (eg, infection, trauma, inflammation)
It is no coincidence that primary corneal problems do better
in the published literature with corneal transplantation than do
secondary ones.3
Now let us look at the secondary corneal problems in greater
detail.
Secondary Corneal Problems
Lens
These can be termed kerato-irido-lenticular dysgenesis (KILD):
• Lens fails to separate from cornea (aka Peters anomaly
type II)
– Developmental (eg, as seen in Dyl mouse4)
– Mechanical. Clues to this include:
* Lens epithelium discernible on ultrasound biomicroscopy
* Evidence of persistent pupillary type membrane(s)
* Intact iris stromal architecture
• Lens separates but fails to form thereafter.
• Lens fails to form (primary aphakia; eg, as seen in aph
mouse5)
• Due to persistent hyperplastic primary vitreous, lens is literally pushed forward.
Trabecular meshwork
Infantile glaucoma causes corneal opacity that reverses if IOP is
controlled quickly enough.
Iris
• Iridocorneal adhesions (aka Peters type I)
• Iris anomalies (eg, Axenfeld Rieger anomaly/syndrome;
aniridia)
It is well known that if at the time of surgery the lens is
removed due to keratolenticular adhesions (ie, due to KILD
above), then the chances of graft survival are reduced. Similarly
if there is no lens (ie, primary aphakia), the chances of successful
corneal transplant are reduced significantly. Under these conditions it becomes important to consider alternatives such as optical iridectomy if possible.
This approach should not be surprising; we would never consider a corneal graft for a child presenting with hazy corneas due
to infantile glaucoma since the primary problem is not the cornea
but the pressure in the eye.
Similarly, we need to change our approach to corneal opacification and determine the primary disease before acting on a
treatment algorithm.
The one exception to this is where there are only iridocorneal
adhesions causing opacities in the cornea. Here there is published
evidence that good results can be attained but only if the sole
abnormality is iridocorneal adhesion and not abnormal iris with
iridotrabecular anomalies.6
References
1. Nischal KK. Congenital corneal opacities: a surgical approach to
nomenclature and classification. Eye 2007; 21(10):1326-1337.
2. Nischal KK, Naor J, Jay V, MacKeen LD, Rootman DS. Clinicopathological correlation of congenital corneal opacification using
ultrasound biomicroscopy. Br J Ophthalmol. 2002; 86(1):62-69.
3. Javadi MA, Baradaran-Rafii AR, Zamani M, et al. Penetrating keratoplasty in young children with congenital hereditary endothelial
dystrophy. Cornea 2003; 22(5):420-423.
4. Sanyal S, Hawkins RK. Dysgenetic lens (dyl)Fa new gene in the
mouse. Invest Ophthalmol Vis Sci. 1979; 18(60):642-645.
5. Blixt A , Mahlapuu M, Aitola M, Pelto-Huikko M, Enerback S,
Carlsson P. A forkhead gene, FoxE3, is essential for lens epithelial
proliferation and closure of the lens vesicle. Genes Dev. 2000;
14:245-254.
6 Zaidman GW, Flanagan JK, Furey CC. Long-term visual prognosis
in children after corneal transplant surgery for Peters anomaly type
I. Am J Ophthalmol. 2007; 144(1):104-108.
28
Keynote Lecture
Avastin for ROP
I. Off-Label Use of Bevacizumab (Avastin) for ROP:
Efficacy = Benefit
3. Rescue therapy using bevacizumab following
laser in advanced Stage 3+ and 4a can be very
effective, although the ideal time for treatment (ETROP)2 has been missed and the infant
already has been subjected to the natural consequences of and random complications of laser
therapy, unnecessarily.
4. Combination therapy using bevacizumab with
laser for plus disease and extraretinal fibrovascular proliferation as conventional Stage 3 ROP
or as aggressive posterior ROP does not increase
efficacy.
Decreasing VEGF does not require this
2-pronged offensive: ablative laser therapy is not
additive to bevacizumab (as anti-EPO is additive
to anti-VEGF). Laser destroys the natural retinal
barrier and allows bevacizumab to escape more
A. Timing is critical for antivascular endothelial
growth factor (VEGF) for ROP.1
1. Pre-emptive strikes using bevacizumab in Stages
1 and 2 are not appropriate:
A severe retinal dystrophy will likely occur if
anti-VEGF therapy is given before the appearance of plus disease, usually before 31 weeks
postmenstrual age.
2. Rescue attempts using bevacizumab in Stages 4b
and 5 are not appropriate:
An accelerated tractional retinal detachment may
well occur by contraction of dense vasoproliferative membranes, usually after 44 weeks postmenstrual age.
Figure 1. Pathogenesis and therapy for ROP:
Postmenstrual ages of Phase I (cessation of
normal vessel growth) and Phase II (initiation
of neovascularization) in relation to the development of retinopathy of prematurity stages.
Reprinted with permission from the New England Journal of Medicine. Mintz-Hittner HA,
Kennedy KA, Chuang AZ. Efficacy of intravitreal bevacizumab for Stage 3+ retinopathy of
prematurity. NEJM 2011; 364(7):603-615.
Keynote Lecture
freely. This may make it necessary to repeat bevacizumab injections before inner retinal vascularization has been completed more frequently than
use of bevacizumab alone, and thereby exposes
the infant to higher systemic levels of this antiVEGF therapy.
5. Monotherapy using bevacizumab (without laser)
for plus disease and extraretinal fibrovascular
proliferation as conventional Stage 3 ROP or as
aggressive posterior ROP is recommended.
The regression of extraretinal fibrovascular proliferation and the continued vascularization of
the peripheral retina subsequent to bevacizumab
monotherapy have been documented by several
case reports, case series, a prospective, randomized, multicenter clinical trial,1 human histopathology,3 and rat histopathology.4,5 The BEATROP clinical trial 6-month results have been
published; however, 1- through 5-year results
will be forthcoming:
a. Long-term ocular structural data (fundus
photographs, fluorescein angiograms, and
OCTs) will be evaluated by masked examiners with potentially lasered areas cropped.
precursors had reached at the time of preterm
birth, not necessarily to the ora serrata. (If thick
fibrovascular membranes have formed, some
peripheral laser may be required to prevent late
tractional retinal detachment.)
II. The Worrisome Unknown: Toxicity = Risk
A. A developmental evaluation will also be performed
by masked examiners including motor, language,
and other neurologic functions to identify any evidence of central nervous system toxicity6-8 in survivors of the BEAT-ROP clinical trial.
B. Additional organ systems will also be evaluated in
survivors of the BEAT-ROP clinical trial to identify
other organ system damage, especially effects of
abnormal pulmonary vascularization,9 that may
occur as a result of bevacizumab therapy.
C. The importance of limiting the dose of bevacizumab
(perhaps identifying a larger molecular weight drug
that will exit the eye less readily) and of being vigilant for any signs of toxicity cannot be over emphasized.
III. Future Trials
A. Any prospective, randomized, multicenter clinical
trials must randomize infants, rather than eyes,
in order to clearly separate efficacy and toxicity.
Bevacizumab definitely gets out of the eye to some
extent, especially in association with leakage from
fragile neovascular vessels. Thus, bevacizumab
injection in one eye will affect the ROP in the fellow
eye. Also, VEGF circulates in the blood, so recurrence in one eye may stimulate recurrence in the fellow eye.
B. When randomizing eyes, rather than infants, reaction to extensive laser, especially following treatment for zone I disease, may cause deprivation
amblyopia by creating vitreous reaction (which can
be observed by slitlamp examination) or may cause
structural amblyopia by creating macular edema (as
shown by OCT) compared to the fellow eye.
C. Additionally, when randomizing eyes, rather than
infants, (1) all infants are being exposed to any
potential ocular and systemic toxicity of bevacizumab, (2) all infants are at risk for the possible
consequences of laser in one eye (decreased field,
anisometropic amblyopia due to myopia, etc.), and
(3) all infants are at risk for the potential infrequent
complications of laser in one eye: corneal and lenticular opacities, ie, leukomas and cataracts, angleclosure glaucoma, hemorrhage in the anterior or
posterior segments of the eye, decreased pressure
(phthisis), etc.
D. Determination of a minimally required dose is
essential. Thus, pharmacokinetics of all utilized
bevacizumab (and/or other anti-VEGF drugs) doses
should be planned. Comparison of VEGF levels
(and levels of other angiogenic factors) following
laser and different doses of bevacizumab should
be included in the study design. Documentation of
b. Long-term ocular functional data will be
obtained by independent masked examiners. These data will report ocular outcomes
including visual acuity (isolated and linear),
contrast sensitivity, color vision, depth perception, visual field, refraction, and presence
or absence of strabismus.
B. Appearance of the retina following bevacizumab
therapy
1. With regression following bevacizumab, retinal
vessels advance to the location that the endothelial precursors had reached at the time of preterm
birth, not necessarily to the ora serrata. At this
location, a ridge of variable thickness is usually
seen.
2. Often, in the most immature infants (gestational age 22 to 26 weeks), the peripheral retina
remains avascular and never differentiates with
thickening of the retina. Thus, the peripheral
avascular retina is not hypoxic, VEGF is not
increased, and ablative laser is not usually
required. (High myopia and tractional elements
may generate peripheral pathology later if present.)
3. With recurrence following bevacizumab, plus
disease returns and extraretinal fibrovascular
proliferation is seen again (1) from the original
location of extraretinal fibrovascular proliferation and (2) from the advancing edge as an
increasingly thick ridge—“two lines of recurrence.”
4. When recurrence is recognized early, re-treatment with bevacizumab is possible—retinal vessels advance to the location that the endothelial
29
30
Keynote Lecture
the retinal appearance photographically and with
OCTs prior to and at predetermined times following
treatment should be included in the trial design. The
relationship of each dose to efficacy and the time of
recurrence—number of recurrences associated with
each dose (%) and the postmenstrual age at which
recurrence is noted (weeks)—are both important to
develop clinical guidelines for postinjection followup examinations. (Large numbers of infants will be
required for these trials.)
E. Determination of efficacy of bevacizumab (compared to laser) for zone II is warranted. The BEATROP clinical trial did not enroll enough infants
to answer the question of bevacizumab efficacy
for zone II ROP because recurrences are so infrequent in zone II. (Large numbers of infants will be
required for these trials.)
F. Keep vigilant for very long-term toxicity. (Large
number of infants—in national or international registry—will be required to identify any related toxicity definitively.)
IV.Conclusion
Because of severe zone I cases and imperfect results
following laser surgery, further investigation of this
less destructive, less labor intensive, readily available
therapy is warranted.
References
1. Mintz-Hittner HA, Kennedy KA, Chuang AZ. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J
Med. 2011; 364(7):603-615.
2. Early Treatment for Retinopathy of Prematurity Cooperative
Group. Revised indications for the treatment of retinopathy of prematurity. Arch Ophthalmol. 2003; 121(12):1684-1694.
3. Kong L, Mintz-Hittner HA, Penland RL, Kretzer FL, Chevez-Barrios P. Intravitreal bevacizumab as anti-vascular endothelial growth
factor therapy for retinopathy of prematurity: a morphologic study.
Arch Ophthalmol. 2008; 126:1161-1163.
4. Geisen P, Peterson LJ, Martiniuk D, Uppal A, Saito Y, Hartnett
ME. Neutralizing antibody to VEGF reduces intravitreous neovascularization and may not interfere with ongoing intraretinal vascularization in a rat model of retinopathy of prematurity. Mol Vis.
2008; 14(2):345-357.
5. Budd S, Byfield G, Martiniuk D, Geisen P, Hartnett ME. Reduction
in endothelial tip cell filopodia corresponds to reduced intravitreous
but not intraretinal vascularization in a model of ROP. Exp Eye
Res. 2009; 89(5):718-727.
6. Ogunshola OO, Antic A, Donoghue MJ, et al. Paracrine and
autocrine functions of neuronal vascular endothelial growth factor (VEGF) in the central nervous system. J Biol Chem. 2002;
277:11410-11415.
7. Sun Y, Jin K, Xie L, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest.
2003; 111:1843-1851.
8. Nishijima K, Ng YS, Zhong L, et al. Vascular endothelial growth
factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J
Pathol. 2007; 171:53-67.
9. Voelkel NF, Vandivier RW, Tuder RM. Vascular endothelial
growth factor in the lung. Am J Physiol Lung Cell Mol Physiol.
2006; 290(2):L209-L221.
Video: Cataract Surgery for Marfan Syndrome
Daniel J Salchow MD
The surgical treatment of a child with Marfan syndrome and
lens subluxation is discussed using the edited surgical video of
the case. The surgeon may be challenged in several ways, including (1) removal of the unstable lens, (2) treatment of vitreous
prolapse, and (3) fixation of an IOL without capsular support.
These and other aspects of the surgery are discussed, and different options are presented.
31
32
Why Don’t We Operate to Eliminate Lower-Power
Hyperopic Spectacles in Accommodative Esotropia?
Scott E Olitsky MD
I. What causes accommodative esotropia?
V. Surgery to Eliminate the Need for Spectacles
A. The history of acceptance (or lack thereof)
A.Accommodation
B. Accommodative convergence
1. Stages of acceptance
C. Accommodative convergence-to-accommodation
ratio (AC/A)
2. Current state of the art
D. Fusional divergence
E. Esotropia occurs when the stimulus to cross outweighs the control to prevent it.
II. What is the natural history of accommodative
esotropia?
A. Level of hyperopia
B. AC/A ratio
C. Previous strabismus (fusional divergence)
D. Changes in hyperopia
E. Changes in AC/A ratio
III. The Child With Accommodative Esotropia and
Normal or Low Levels of Hyperopia
A. Normal AC/A ratio
B. High AC/A ratio
IV. Why would we consider surgery to eliminate glasses in
these children?
A. Limited desire to wear glasses
B. Minimal benefit in visual acuity
C. Potential increase in amount of time eyes are aligned
D. Eliminate diplopia in some children when not wearing glasses
E. Eliminate the need for glasses in an active population
B. Types of refractive surgery
1.Corneal
2.Lens
3.Strabismus?
VI. Potential Options for the Child With Normal or Low
Levels of Hyperopia and Accommodative Esotropia
A. High AC/A ratio
1. Strabismus surgery for excess esotropia at near
2.Medication
3.Observation
B. Normal AC/A ratio
1. Strabismus surgery
2. Refractive surgery
a. Full correction of hyperopia
b. Partial correction of hyperopia to maintain
alignment
33
Is the Pediatric Eye Disease Investigator Group
Wrong About . . . ?
Amblyopia Treatments Are All Equal
Steven M Archer MD
I. Comparative PEDIG Amblyopia Treatment Studies
A. ATS1: Daily atropine and patch 6 hours/day are
equal.
B. ATS2A: Patch 6 hours/day and full-time are equal.
C. ATS2B: Patch 2 hours/day and 6 hours/day are
equal.
E. ATS6: Patch with near and distance activities are
equal.
a. “Success” is final acuity ≥ 20/30 or ≥ 3 lines
improvement
b. Mean starting acuity is 20/68 (range: 20/4020/100)
F. ATS8: Atropine with and without optical penalization are equal.
G. ATS9: Weekend atropine and patch 2 hours/day are
equal.
H. ATS10: Bangerter foil and patch 2 hours/day are
equal.
II. Why is the result always “equal?”
A. These are studies of “prescribed treatment.”
1. If compliance is poor, all groups may actually get
similar treatment.
2. Consistent with “intention to treat” analysis,
open to question
B. Study design factors
a. Statistical power calculations give some limits.
b. Noninferiority design; design errors favor
equivalence.
c. Equivalence design (two one-sided tests—
TOST)
2. PEDIG study design is always meticulous, but
could it be biased to favor an “equal” result?
1. Atropine evangelists propose the study.
2. Those who propose the study help design the
study.
B. Design the study to achieve the desired result
1. Minimize disadvantage of atropine being slow
a. Make this a relatively long (6-month) study
ii. Does 20/70 → 20/30 meet expectations for
6 months of treatment?
1. Difference in final acuity
a. 0.034 logMAR
b. 95% CI, 0.005-0.064
2. “Success” (final acuity ≥ 20/30; improvement ≥ 3
lines)
a. Patching: 164/208 (79%)
b. Atropine: 144/194 (74%)
c.
P = .29 (not actually reported)
3. Improvement ≥ 3 lines
a. Patching: 146/208 (70%)
b. Atropine: 116/194 (60%)
c.
A. Motivation behind the study
i. Is 20/40 → 20/30 a success? (One patient
in the atropine group actually started at
20/30.)
c.
P ≈ .03 (not actually reported)
III. Anatomy of an “Equal” Result: ATS1
C. Results reported honestly but analysis reported
selectively
1. Not possible to prove the null hypothesis—
“absence of proof is not proof of absence.”
2. Less effective treatment looks equal if you set the
bar low enough.
D. ATS4: Weekend atropine and daily atropine are
equal.
b. Give atropine a chance to catch up by allowing decreased/discontinued treatment if early
“success” (for about one-fourth of patients;
this may have actually been a trial of 5 weeks
of patching compared to 15 weeks or 6
months of atropine.)
4. Final acuity ≥ 20/30
a. Patching: 132/208 (63%)
b. Atropine: 103/194 (53%)
c.
5. Final acuity ≥ 20/25
a. Patching: 85/208 (41%)
b. Atropine: 56/194 (29%)
c.
34
6. Parental questionnaire scores
D. Spin the conclusion
1. Primary outcome: 6-month visual acuity in
amblyopic eye
a. Result: Visual acuity at the final 6-month
exam is significantly better in the patching
group than the atropine group.
b. PEDIG description: “Atropine and patching
produce improvement of similar magnitude. . . . [T]he difference in mean visual acuity between groups was small . . . and clinically inconsequential.”
2. Secondary outcome: 6-month “success”
a. Result: The difference in “success” rates is not
statistically significant; however, patching is
significantly better with regard to each component of “success” (acuity ≥ 20/30 and ≥ 3
lines improvement).
b. PEDIG description: “The difference between
groups in the percentage of patients meeting
our criteria for successful treatment . . . was
also small.”
3. Other factors: Speed of improvement
a. Result: Visual acuity in the atropine group is
worse at 5 weeks and never catches up to the
patching group, even after 6 months. This,
in spite of the fact that treatment may have
been reduced or discontinued in more of the
patched patients well before the 6-month conclusion of the study.
b. PEDIG description: “Improvement in the
atropine group lagged behind that in the
patching group. It is possible that if our primary outcome had occurred at a time point
longer than 6 months, the atropine group
might have shown further improvement,
perhaps achieving the same proportion of
patients with 20/30 or better amblyopic eye
acuity as found in the patching group.”
IV. Is PEDIG wrong about atropine vs. patching?
B. Atropine is effective, but for any treatment duration
up to at least 6 months, it is significantly less effective than patching. Is the difference really “clinically
inconsequential”?
a. Worse on all 3 subscales for patching vs. atropine
b.
P = .002, P < .001, P < .001 (the only comparative amblyopic eye results with reported
P-values)
A. 5 weeks of patching ≅ 15 weeks of atropine.
1. If each patient’s 6-month vision is only one-third
line better with patching, as the authors imply,
that may be of little importance.
2. Alternatively, if one-third of patients are a full
line better at 6 months with patching, that
sounds more substantive.
C. In the long run, when investigators can prescribe
subsequent treatment in whatever manner they
choose, the initial 6 months of treatment has little
bearing on the outcome at 2 or 10 years.
Selected Readings
1. Pediatric Eye Disease Investigator Group. A randomized trial of
atropine vs. patching for treatment of moderate amblyopia in children. Arch Ophthalmol. 2002; 120:268-278.
prescribed patching regimens for treatment of severe amblyopia in
children. Ophthalmology 2003; 110:2075-2087.
patching regimens for treatment of moderate amblyopia in children.
Arch Ophthalmol. 2003; 121:603-611.
atropine regimens for treatment of moderate amblyopia in children.
Ophthalmology 2004; 111:2076-2085.
5. Pediatric Eye Disease Investigator Group. A randomized trial of near
versus distance activities while patching for amblyopia in children
aged 3 to less than 7 years. Ophthalmology 2008; 115:2071-2078.
6. Pediatric Eye Disease Investigator Group. Pharmacologic plus optical penalization treatment for amblyopia: results of a randomized
trial. Arch Ophthalmol. 2009; 127:22-30.
7. Pediatric Eye Disease Investigator Group. Patching vs atropine to
treat amblyopia in children aged 7 to 12 years: a randomized trial.
Arch Ophthalmol. 2008; 126:1634-1642.
8. Repka MX, Kraker RT, Beck RW, et al. Treatment of severe
amblyopia with atropine: results from two randomized clinical trials. J AAPOS. 2009; 13:258-263.
9. Pediatric Eye Disease Investigator Group. A randomized trial comparing Bangerter filters and patching for the treatment of moderate
amblyopia in children. Ophthalmology 2010; 117:998-1004.
10. Pediatric Eye Disease Investigator Group. Two-year follow-up of a
6-month randomized trial of atropine vs patching for treatment of
moderate amblyopia in children. Arch Ophthalmol. 2005; 123:149157.
atropine vs patching for treatment of moderate amblyopia: followup at age 10 years. Arch Ophthalmol. 2008; 126:1039-1044.
35
Eye Drops for Nystagmus? Really?
Richard W Hertle MD
Introduction
Nystagmus comes from the Greek word nystagmos, “to nod,”
“drowsiness,” and from nystazein, “to doze”; probably akin to
Lithuanian snusti, also “to doze.” It is a rhythmic, involuntary
oscillation of one or both eyes. Using the information obtained
from a complete history, physical examination, and radiographic
and eye movement recordings, over 40 types of nystagmus can
be distinguished. Some forms of nystagmus are physiologic,
whereas others are pathologic. Although the nystagmus is typically described by its more easily observable fast (jerk) phase, the
salient clinical and pathologic feature is the presence of a slow
phase in one or both directions. Thus, clinical descriptions of
nystagmus are usually based on the direction of the fast phase
and are termed horizontal, vertical, or torsional, or any combination of these. The nystagmus may be conjugate or dysconjugate.
The nystagmus may be predominantly pendular or jerky, the former referring to equal velocity to-and-fro movement of the eyes,
and the latter referring to the eyes moving faster in one direction
and slower in the other. Involuntary ocular oscillations containing only fast phases are “saccadic oscillations and intrusions”
and not nystagmus. It is well documented that these differences
may be difficult, if not impossible, to differentiate clinically and
can only be accomplished with eye movement recordings. Recent
advances in eye movement recording technology have increased
its application in infants and children who have clinical disturbances of the ocular motor system.
We define the ocular motor condition infantile nystagmus
syndrome according to the National Eye Institute collaborative
Classification of Eye Movement Abnormalities and Strabismus
(CEMAS; see Table 1). Estimations of incidence of the most
common form of nystagmus (infantile nystagmus syndrome,
INS) vary from 1 in 500 to 1 in 6000. Other clinical characteristics include increased intensity with fixation and decreased with
sleep or inattention, variable intensity in some position of gaze
(a null position), changing direction in different positions of gaze
(about a neutral position), decreased intensity (damping) with
convergence, anomalous head posturing, strabismus, and the
increased incidence of significant refractive errors. INS can occur
in association with congenital or acquired defects in the visual
sensory system (eg, albinism, achromatopsia, and congenital
cataracts).
The visual symptoms are inversely proportional to the frequency (and speed) of the oscillation in patients with nystagmus.
Visual sensitivity for both pattern and movement detection is
reduced because of these eye movements. The object of regard
spends little time in the foveal area, and image movement, often
in excess of 80 degrees/second, causes blur, oscillopsia, diplopia,
and vertigo. These symptoms begin at retinal slip velocities of
greater than 4 degrees/second. Abolishing or reducing the nystagmus frequency would ameliorate these symptoms. Ideally, the
Table 1. A Classification of Eye Movement Abnormalities
and Strabismus (CEMAS): Report of a National Eye
Institute–Sponsored Workshop
1. Peripheral vestibular imbalance
Meniere, drug toxicity
2. Central vistibular imbalance
Downbeat, upbeat, drug toxicity
3. Instability of vestibular mechanisms
Periodic alternating nystagmus
4. Disorders of visual fixation
Vision loss, see-saw nystagmus, drug toxicity
5. Disorders of gaze holding
Gaze evoked, acquired pendular, drug toxicity
6. Acquired pendular nystagmus
Central myelin, oculopalatal, Whipple, drug toxicity
7. Saccadic intrusions and oscillations
Square wave jerks, macrosaccadic oscillations, opsoclonus
8. Miscellaneous eye movements
Superior oblique myokymia, ocular motor neuromyotonia
9. Infantile nystagmus syndrome
“Congenital,” “motor,” “sensory,” idiopathic, nystagmus
blockage
10. Fusion maldevelopment nystagmus syndrome
Latent, manifest latent, nystagmus blockage
11. Spasmus nutans syndrome
Without optic pathway glioma, with optic pathway glioma
treatment of nystagmus should be directed against the pathophysiological brain mechanism responsible for the ocular oscillation. In the absence of directly affecting neurological function,
secondary ameliorative therapies treat the eyes directly (ie, prism
glasses, contact lenses, occlusion, botulinum toxin and anesthetic
injections, and eye muscle surgery).
Treatments
Infantile nystagmus may respond to surgical, medical, and optical treatments.
36
Table 2. Incidence of Operation Types
Operation Type (100 Patients)
Percent
Operation 1: Horizontal head posture alone
Horizontal rectus recess and resect or recess and tenotomy + reattach
22
Operation 2: Chin down head posture (± strabismus)
Superior rectus recess 5.0 mm + inferior oblique myectomy
16
Operation 3: Strabismus alone
Primary position deviation using at least 2 recti each eye
15
Operation 4: Horizontal head posture + strabismus
Fixing eye straightens head + nonfixing eye straightens eyes
10
Operation 5: Chin up head posture (± strabismus)
Inferior rectus recess 5.0 mm + superior oblique tenectomy 5.0 mm
10
Operation 6: No head posture, strabismus, or vergence damping
9
Horizontal rectus tenotomy + reattach
Operation 7: Multiplanar head posture (± strabismus)
Transposition of recti + combinations of oblique or recti recess
7
Operation 8: Vergence damping alone (artificial divergence)
Medical rectus recess 3.0 mm + lateral rectus tenotomy + reattach
6
Operation 9: Torsional head posture alone
Horizontal transposition of vertical recti 1 tendon width
5
Table 3. Medical Treatment of Nystagmus
Nystagmus Type
Treatment
Infantile nystagmus syndrome
Fresnell prisms, orthoptics, memantine, acetazolamide, gabapentin, baclofen, biofeedback,
acupuncture
Acquired pendular nystagmus
Fresnell prisms, orthoptics, gabapentin, baclofen, clonazepam, cannibis, alcohol, carbamazipine,
5-hydroxytryptophan, scopolamine, memantine, Botox
Peripheral vestibular
Positional exercises, betahistine, cinnarizine, acetazolamide
Downbeat
3,4 Diaminopyridine, clonazepam, gabapentin
Upbeat
Baclofen, clonazepam, gabapentin
Periodic alternating
Baclofen, Botox
Seesaw
Baclofen
Saccadic intrusions/oscillations
Baclofen, propranolol, clonazepam
Superior oblique myokymia
Carbamazepine, propranolol, timolol,
Opsoclonus
Corticosteroids, propranolol, clonazepam, baclofen
Ocular motor neuromyotonia
Carbamazepine
Voluntary ocular flutter
Prism, orthoptics
Chronic internuclear ophthalmoplegia
Prism, orthoptics
Topical Medications
In 1979, Dell’Osso and Flynn recorded eye movements of 3
patients before and after surgery for INS. In addition to shifting the nystagmus null, they observed broadening of the null
region and an overall reduction of nystagmus intensity at all gaze
angles. This led them to speculate that the surgery caused “nonlinear changes in ocular motor plant dynamics (i.e., changes in
the characteristics of the muscles, tendons, Tenon’s capsule, fatty
and scar tissue interactions) as a result of the surgical changing of the points of insertion and methods of attachment of the
muscles to the globe.” Bosone et al found similar results. Subsequently, Dell’Osso et al and Hertle et al showed that eye muscle
tenotomy and reattachment (T&R) alone had salutary effects on
nystagmus amplitude and velocity in dogs with nystagmus and
in 2 human trials in patients with INS. A hypothesis evolved that
T&R damaged proprioceptive structures in the eye muscle tendon at its insertion on the globe (enthesis) that favorably affected
the nystagmus oscillation. Enthesial neurons recently identified
and studied by Hertle et al and Buttner-Ennever et al have been
shown to have proprioceptive anatomy and physiology. They
probably provide feedback that assists with alignment and stabilization of the eyes. It has been also shown over the last 10 years
that surgical disruption of the enthesis (and associated enthesial
neuroanatomy) in patients with INS results in long-standing
beneficial effects on nystagmus and visual function. The neurological hypothesis for the “improvement” in the nystagmus is
that there is a reduction of small-signal gain of the ocular motor
plant by interfering with enthesial, neural proprioceptive tension
control. Enthesial nerves are probably palisade type nontwitch
motoneurons and are likely involved in modulating the gain of
sensory feedback from the eye muscles analogous to the gamma
motoneurons, which control the gain of proprioceptive feedback
in skeletal muscles.
In general, the membrane potential of these neurons that are
not transmitting signals is called their resting potential and is typically between -60 and -80 mV. In all neurons, the resting potential depends on the ionic gradients that exist across the plasma
membrane. In general, mammalian neurons have an extracellular
Na+ concentration of 150 millimolar (mM) and a K+ concentration of 5 mM. In the cytosol, the Na+ concentration is 15 mM
and the K+ concentration is 150 mM. The gradients are maintained by sodium-potassium pumps in the plasma membrane.
These ion pumps use the energy of ATP hydrolysis to actively
transport Na+ out of the cell and K+ into the cell. Gradients of K+
and Na+ across the plasma membrane represent potential energy.
Converting this chemical potential to electrical potential involves
ion channels, pores formed by clusters of specialized proteins
that span the membrane. Acid-sensing ion channels (ASIC) form
a subset of voltage-independent cation channels that predominantly conduct Na+ ions, and were identified at the molecular
level a little more than a decade ago. ASICs form effective proton
sensors in both central and peripheral sensory neurons.
Carbonic anhydrase (CA) may play an important role in the
neurochemical functioning of these enthesial ending’s membrane
potential as it does in other sensory systems. Hansson’s enzyme
histochemical method for the demonstration of carbonic anhydrase has found numerous carbonic anhydrase positive neurons
in the trigeminal and geniculate ganglia as well as in the mescencephalic trigeminal nucleus. There is evidence that CA partici-
37
pates in the response of sensory stretch receptors of the trigeminal nerve and its nerve endings. CA inhibition has been shown
to attenuate the steady-state inhibitory response of laryngeal
receptors to airway CO2 and to completely block the inhibition
of pulmonary stretch receptor activity caused by airway CO2. A
functioning CA system may be involved in facilitating enthesial
neuronal feedback to central ocular motor areas continuing to
enhance the developmentally disturbed circuit, resulting in the
ocular oscillation of INS. A CA inhibitor (CAI) may interfere
with the sodium-potassium ATPase membrane bound system,
thus interrupting enthesial neurophysiology (analogous to surgery), creating a damped circuit resulting in improvement in the
ocular oscillation and subsequent enhanced visual function.
Case Report
Sixty-seven-year-old white male with INS known to PI and no
medical or surgical treatment for INS other than prism spectacles
was prescribed topical CAI as part of associated eye condition.
Eye movement recordings and subsequent calculation of his
NAFX as a function of gaze was accomplished prior to and after
beginning his topical CAI and compared to no treatment, contact lenses, and convergence (all known to affect the nystagmus
waveform and associated NAFX). The data from that single
anecdotal case is presented below. The data show an improvement of NAFX and “predicted” acuities across all gaze angles
after topical administration of a topical CAI. The curves represent NAFX as a function of gaze, the best NAFX is seen across
gaze with convergence (Figure 1, top dashed line), followed by
topical CAI only, contacts only and least with no convergence,
contacts or CAI from top to bottom.
Topical Brinzolamide Ophthalmic Suspension vs.
Placebo in the Treatment of Infantile Nystagmus
Syndrome
This study is currently recruiting participants. Verified on March
2011 by Akron Children’s Hospital. Study NCT01312402.
Information provided by Akron Children’s Hospital, First
Received on January 21, 2011. Last Updated on March 9, 2011.
Brief summary
This study is a prospective, single crossover, double-masked,
controlled clinical trial that will use topical brinzolamide (Azopt)
ophthalmic medication to try to improve the nystagmus and
visual consequences of nystagmus in patients with infantile nystagmus syndrome (INS). Subjects will undergo a clinical exam,
questionnaire, and eye movement recordings on Day 1 and then
receive either topical Azopt or placebo 3 times a day in both
eyes for Days 2, 3, and 4, followed on the morning of Day 5 by
a repeat clinical exam, questionnaire, and eye movement recordings. After at least 1 week, this protocol is repeated with the
crossover regimen being taken by the subject. One week after
all medications are discontinued, another clinical exam is done
before study discharge. The hypothesis is that nystagmus and
associated visual symptoms will be improved while on the Azopt
compared to the placebo. There will be a total of 5 visits over a
1-2 month period. For more information on the current study,
visit http://clinicaltrials.gov/ct2/show/NCT00967226.
38
Figure 1. Abbreviations: Poly indicates polynomial fit curve; positive gaze angle, gaze right; negative gaze angle,
gaze left, LFD, patient PFD; Conv, convergence; PD, prism diopters.
39
Do Study Design and Methodology Affect Pediatric
Cataract Outcomes?
Ramesh Kekunnaya FRCS, Sumit Monga FRCS
The advances in technology and refinements in surgical techniques over the past two decades have catapulted pediatric cataract surgery into a new era. This has led to vastly improved surgical and functional outcomes. Various innovative studies have
contributed to the current understanding and evolution of surgical techniques that have helped to partly overcome the challenges
of pediatric cataract management.1 However, pediatric cataract
surgery has been associated with many complex issues that have
been debated in literature.1 We believe that possibly the information on key aspects of pediatric cataract surgery may have been
influenced by study methodologies and surgical techniques that
have been reported in the literature.
Surgical Technique
Pediatric cataract surgery has evolved from the procedure of
discission and aspiration in 1930s, lensectomy in the 1970s, and
extracapsular cataract extraction in 1980s to the present surgical
technique of anterior continuous capsulorrhexis with phacoaspiration of lens matter with primary posterior capsulorrhexis
with limited anterior vitrectomy.2
The use of mechanized vitrectomy instrumentation to selectively perform a primary posterior capsulectomy and vitrectomy combined with IOL implantation resulted in decreasing
the scourge of visual axis opacification and has led to fewer
reoperations in younger children.1,2 In the literature, the rate of
posterior capsular or visual axis opacification (PCO or VAO) is
up to 100% when the posterior capsule remains intact.3 There
is a strong relationship between age and incidence of PCO or
VAO.1-3 The rate of membrane formation is high in young children, reflecting greater tissue reactivity of lens epithelial cells
(LECs).1 When primary posterior capsulectomy (PPC) is not
combined with anterior vitrectomy, the incidence of posterior
capsule closure is up to 60%.3 The main reason for the occurrence of VAO after performing a posterior continuous curvilinear capsulorrhexis could be the increased LEC activity and also
the presence of an intact anterior vitreous face, which acts as a
scaffold for LEC migration.3 Reported rates of VAO after vitrectomy are less than 6%.3 The importance of anterior vitrectomy
in pediatric surgery is emphasized in cataract surgery in patients
younger than 7 years by several authors.3 In a study, the technique of optic capture through the posterior capsulorrhexis has
been shown to prevent PCO.2,3 However, Vasavada et al found
that optic capture without anterior vitrectomy did not always
ensure a clear visual axis.3 Eyes with an obscured visual axis had
reticular fibrosis of the anterior vitreous face in the first 2 months
after surgery.3 Hence, vitreous opacification could be a primary
response of the anterior vitreous face when it occurs with the
IOL optic rather than a secondary scaffold response caused by
proliferating LECs, inflammatory cells, and exudate deposits.
As per the current understanding, one can make the following recommendations. In children younger than 5 years, PPC
with anterior vitrectomy is advisable. PPC without anterior
vitrectomy may be considered in children between 5 years and 7
years. If the child is cooperative, Nd:YAG capsulotomy may be
the other option. In older children, maintaining intact posterior
capsule is debatable, as we see more and more PCO formation.
There are no clear-cut data available on this issue. Personally we
favor PPC until 10 years of age.
Primary IOL Implantation in Children
IOLs are being used increasingly for the optical correction of
aphakia in infants following cataract surgery. In children older
than 2 years of age, primary IOL implantation of a foldable
acrylic IOL is the current standard of care.2 There is growing evidence in the literature to support the use of primary IOL implantation in children less than 2 years of age.4-12 While the surgical
technique has mostly remained similar for all studies, the study
methodology was variable. Most of the reports are retrospective, noncomparative series,7-9,12 while others have compared the
outcomes of primary IOL implantation with the group receiving
contact lens for visual rehabilitation.5,11 The number of patients
in these series failed to provide the statistical power necessary to
adequately assess the outcomes of IOL implantation. Four studies, depicted in Table 1, are prospective,4,5,10,11 and only one is a
randomized trial comparing outcomes in the IOL with outcomes
in a contact lens (CL) group.16 The reporting of results in the retrospective and nonrandomized studies could have been marred
by fallacies of inadequate sample size and lack of standardized
protocols.
The primary outcome measure in the majority of these studies
has been the complication rate and overall safety profile of IOLs
in young children.4,6-8,10,12 VAO has been the most frequent
complication in all studies, but its incidence rate has differed
between them. One glaring explanation could be the variable
follow-up, as posterior capsular opacification (PCO) can have a
delayed onset. Particularly, the use of acrylic foldable IOLs has
been implicated with delayed and milder variety of PCO.2,3 At
the start of the decade, many studies had some cases in which
polymethyl-methacrylate (PMMA) IOLs were implanted.
Research has conclusively established that IOL material and
design has a direct influence on PCO rates.1 Acrylic foldable
IOLs have been documented with lesser PCO rates and less severity of PCO compared to PMMA and silicone foldable IOLs.2,3
This trend has been corroborated by demonstrating increased
biocompatibility and improved IOL design of acrylic foldable
IOLs. Further, placement in-the-bag has been shown to be associated with lesser postoperative inflammation and PCO rates.
Table 1 reveals that the information on type of fixation of IOLs,
either in sulcus or bag, either has been missed or the exact number of cases with each type of fixation has not been mentioned.
Moreover, the presence of associated ocular anomalies, like persistent fetal vasculature, in almost half of the studies could have
influenced the VAO rates.6-9 Hence, the differential reporting of
visual axis opacification and reoperation rates in various studies could partly be explained by the above-mentioned factors. It
is worth noting that in the recent study by the Infant Aphakia
Treatment Study (IATS) group, in spite of meticulous surgical
protocols based on current knowledge, the reoperation rates in
the IOL group were reasonably high.11 Possibly there are some
40
Table 1. Studies on Primary IOL Implantation in Children Less Than 2 Years of Age: Methodology
Coexisting
Laterality Ocular /
of
Systemic
Cataract Pathology
N
(No.
of
eyes)
Age
Group
(Weeks)
Mean
Follow-up
(months)
Prospective,
nonrandomized
UL
Excluded
11
2-22
Lambert SR,
20015
Prospective,
nonrandomized
UL
Excluded
12
Plager D et al,
20026
Retrospective,
comparative
UL, BL
Included
Trivedi RH7,
2004
Retrospective
UL, BL
Lundvall A,
20068
Retrospective
Ashworth JL9,
2007
Authors,
Year of
Publication
Type of
Study
Type of
IOL
IOL Power Type of
Calculation IOL
Formula
Fixation
Lambert SR
et al, 19994
13 ± 6
PMMA (5) /
AcrySof (6)
Holladay
SRK II or I
Bag
3-22
-
PMMA (6) /
AcrySof (6)
Holladay I or
SRK II
Bag
15
3-20
NA
AcrySof
3-piece
SRK II or
SRK-T
Bag
Included
29
0.8-43.2
33.4 ± 16.1
AcrySof
single piece
Holladay
Bag (86.2%) /
Sulcus
(13.6%)
UL
Included
28
1-40
36
HSM-PMMA,
AcrySof
NA
Bag
Retrospective
UL, BL
Included
25
1-51
44.36
NA
SRK-T
NA
Ram J et al,
200710
Prospective,
nonrandomized
UL, BL
Excluded
45
3-104
18 ± 9.3
HSM-PMMA
NA
Bag, Sulcus
IATS, 201011
Prospective,
randomized,
comparative
UL
Excluded
57
4-24
12
AcrySof
Holladay I
Bag (93%) /
Sulcus (7%)
Gupta A et al,
201112
Retrospective,
noncomparative
UL, BL
Excluded
120
1-23
months
8.856 ±
7.73
PMMA (30)/
AcrySof (90)
SRK II
Bag, Sulcus
Abbreviations: UL indicates unilateral; BL, bilateral.
undetermined factors, particularly in infants, which may lead to
visual axis opacification.
An attempt has been made to document the visual outcomes
of primary IOL implantation in monocular aphakia in infancy,
first by a pilot study5 and then by a randomized clinical trial by
the IATS group.11 The results of the latter study, at 1 year of
age, showed that there was no significant difference between
the median visual acuity in the treated eyes with IOL and the
CL group after cataract surgery during the first 6 months of life.
This was in contrast to the pilot study, where visual outcomes in
the IOL group were found to be better than the CL group. The
authors of the study reason that the discrepancy could probably
be explained by the fact that the subjects in the pilot study were
comparatively older at time of evaluation of grating visual acuity and that all children could not be assessed for visual acuity.
Moreover, in the IATS, standardized protocols for testing visual
acuity, by a masked examiner, were followed for testing all the
included subjects.
Hence, although IOL implantation has the advantage of
providing at least a partial optical correction at all times, this
advantage must be balanced against the reported high complication rate in the eyes of infants undergoing such surgery. The
partial optical correction will be particularly useful in children in
developing countries where contact lenses are expensive, and all
of us agree that it needs to be replaced frequently. The safety profile and better visual outcomes of primary IOL in young children
needs to validated by randomized controlled trials, spread across
different countries.
IOL Power Calculation and Myopic Shift
Other issues that have received attention in the literature are the
need for accuracy in postoperative target refraction and a trend
of emmetropization of refractive errors.
The need for pediatric IOL calculation formulae has been felt
for a long time, primarily because all available formulas were
derived from considerations regarding the adult eye.13 Unlike
adults, pediatric eyes undergo rapid growth and significant
refractive changes in the early years. Moreover, in most pediatric cases, the desired postoperative refraction is different from
plano. All these factors add to the complexity of the IOL power
calculations in children.13
Various IOL formulae designed for adult eyes are being used
to predict IOL power in pediatric eyes, which have shown varying degrees of accuracy.14,15 Neely et al found that the SRK II
regression formula gave the least amount of variability, whereas
the Hoffer Q gave the greatest amount, particularly among the
youngest group of children with axial length (AL) < 19 mm.14 In
a recent study, Nihalini et al concluded for eyes with significant
deviation in prediction error (> 0.5 D) that there was usually an
undercorrection, except with Hoffer Q, which was almost as
likely to overcorrect as undercorrect.15 This may be explained by
the higher proportion of short eyes in their series (AL < 22 mm;
69 eyes), and because Hoffer Q was formulated for shorter eyes.
A potential source of error in IOL power selection in children is inaccuracy of AL and/or keratometry power measurements. Most studies have used either applanation or immersion
technique for AL calculation under general anesthesia.13-15
41
Table 2. Studies on Primary IOL Implantation in Children Less Than 2 Years of Age: Results
Authors, Year of Publication
Outcome Measures
Conclusion
Reoperation Rates
Lambert SR et al, 19994
Adverse events, myopic shift
Increased adverse events, large
myopic shift
72%
Lambert SR, 20015
Grating visual acuity at conclusion
of study
Improved visual outcome
compared to CL
83%
Plager D et al, 20026
Complication rate
VAO rate = 80%; higher
reoperation rates
80%
Trivedi RH, 20047
Visual axis opacification (VAO)
VAO rate = 37.9%, greater VAO
with associated ocular anomalies
37.9%
Lundvall A, 20068
Complications and visual results
VAO rate = 67%; better visual
outcomes in BL cases compared to
UL cases
70%
Ashworth JL, 20079
Refractive outcome
Satisfactory mean refractive
outcomes, but wide range of errors
-
Ram J et al, 200710
Safety profile of IOLs
VAO rate = 13.3%; no major
refractive surprises
28%
IATS, 201011
Grating visual acuity at 1 year of
age, adverse events
Similar visual outcome in IOL
and CL; VAO rate 72%; higher
reoperation rates in IOL group
63%
Gupta A et al, 201112
Safety profile of IOLs
VAO rate = 6.7%; adverse
events comparable in age group
< 6 months and beyond
NA
Abbreviations: CL indicates contact lens; UL, unilateral; BL, bilateral.
Applanation technique is thought to artificially reduce the AL
and can contribute to the significant amount of additional error,
especially for high-powered IOLs. Additionally, most studies
except one15 failed to mention whether they tried to minimize the
interobserver variability, by deploying single observers for biometry and refractive error measurements.
With the trend toward implanting IOLs in infants with
shorter ALs (see Table 1), there is a felt need to understand the
accuracy and the differences between prediction formulas at the
lower extremes of AL and higher keratometry values. While in
a few studies the age stratification of younger children was not
done, in others an attempt was made to dichotomize children
according to the age at the time of surgery.13-15 As most of the
ocular growth occurs during the first 2 years of life, most studies
have taken the same as the cutoff for grouping children. In two
major studies, the number of eyes in < 2 year age group constituted about one-fifth of the total, the percentages being 22.7% in
the study by Neely et al14 and 16.2% in the study by Nihalini B
R et al.15 In other studies, the cutoff for “younger children” varies between 12 months, 18 months, and 36 months.18 This disparity and the smaller number of cases limits our understanding
about refractive outcomes in the younger, especially the infantile,
age group. However, these studies concur that there is a greater
variability of refractive outcomes following cataract surgery in
younger children compared to older children. In the work by
Eibschitz et al,16 an analytical comparison of predicted implant
power using in the pediatric range of AL and keratometry values
was performed. Significant differences in IOL power prediction
were found among the Hoffer Q, Holladay I, and SRK II formulas. This explains the higher degree of prediction error that was
documented in the age group < 2 years in 2 recent studies.
It has been reported there is a trend toward larger postoperative prediction errors in younger children, compared to adults.13
The refractive outcome of pediatric patients depends on the
assumed anterior chamber depth (ACD), effective lens position
of the IOL, and the effects of axial displacement of the IOL. The
effect is even more pronounced in pediatric eyes, as these short
eyes require higher-power IOLs. The standardized assumptions
about ACD and vaulting characteristics of an IOL within the bag
may not be accurate for pediatric eyes owing to shallow anterior
chambers and the particular postoperative dynamics of posterior
capsule contraction, vitreous pressure, haptic angulation, effects
of primary posterior capsulotomy and vitrectomy on lens position, and, later, the sometimes significant reproliferation of lens
material. So it is imperative that studies evaluating IOL calculation formulae in children should include information on these
parameters so as facilitate better comparison between them.
It has been documented that axial elongation of the globe in
a pseudophakic eye leads to myopic shift, akin to what happens
in normally developing eyes.13 Younger children are more prone
to have larger and more unpredictable myopic shifts. Further, the
myopic shifts have been shown to be variable, and no consistent
correlations with preoperative axial length or IOL power have
been found.13,14
One basic discrepancy in the reporting of myopic shifts in
various studies has been the variable timing of the initial refraction and the length of the follow-up period. The initial refraction
may vary from 2 weeks to 12 weeks, and the mean follow-up has
ranged from 1 to 7 years.17 This has led to disagreement on the
amount of myopic shift in different, largely retrospective studies.
Further, the heterogeneity of study groups in terms of age groups
and number of eyes included may be a determining factor.
42
It has been reported that pseudophakic eyes have tendency
to grow longer than the fellow phakic eyes.13,17 Interestingly,
in pseudophakic eyes, apart from the normal process of axial
elongation with age, there can possibly be factors like secondary
glaucoma or amblyopic visual deprivation that could influence
the amount of myopic shift. Further, there could be other undetermined reasons, including genetic factors, that could contribute
to the myopic shift. In the study by Greiner et al, the axial elongation in pseudophakic eyes was reduced in comparison to the
phakic eye.18 It was worth noting that all eyes in this study had
sulcus fixation of IOLs, compared to in-the-bag implantation
in most other studies. However, the exact mechanism of sulcus
fixation contributing to the myopic shift needs to be evaluated.
Further, an interesting proposition was made by Nischal et al,
who wondered whether the reduction of peripheral visual input
by anterior capsular fibrosis in pseudophakic eyes might explain
the refractive and axial length change following pediatric cataract surgery.17 It is possible that with improved understanding of
IOL power calculation and prediction of postoperative refraction
in younger children, improved results may be achieved in future
studies.
Glaucoma
Secondary glaucoma is one of the most vexing problems after
congenital cataract surgery. It can emerge years later and can
jeopardize vision. Some earlier studies had studied children
and eyes with a coexistence of conditions associated with cataracts that will also develop glaucoma, such as Lowe syndrome,
aniridia, and trauma.19 However, more useful information could
be attained only after studying “uncomplicated” cases of surgical
aphakia.
There is a wide variation in the reported incidence of glaucoma after congenital cataract extraction. It ranges between 6%
and 58.7% of children, depending on the population studied and
the length of follow-up.19 Initial reports by Chandler, Phelps,
and Arafat drew attention to this problem.20 Magnusson et al
studied Swedish children born with cataracts and found a 12%
incidence of aphakic glaucoma (mean follow-up: 9.6 years).21
This figure is probably more reliable since the study was conducted within the confines of a fixed geographic location with
centralized data collection. In the IATS, preliminary results
showed that glaucoma developed in 5% of eyes in the CL group
and in 12% of eyes in the IOL group.11 But the follow-up was
too short to derive a true incidence.
Various factors have been postulated to influence the risk
of developing postoperative glaucoma, such as age at detection
of cataract, age at cataract surgery, cataract surgery procedure,
primary IOL implantation, significant postoperative uveitis, and
microphthalmia.19,22 However, such information is available
from reports of selected individual case series, which may be subject to bias and confounding. The data, procured from the British
Congenital Cataract Study, was an attempt to derive results from
population-based research.23 Its finding suggested that detection
of cataract was the only significant factor associated with the
development of glaucoma after surgery for congenital cataract.
It is imperative to believe that early detection of cataract would
directly translate to early age of cataract surgery.
Literature review points out to a bimodal pattern of onset
for aphakic glaucoma.19,22 The first onset peak is noticed within
the first weeks to months following cataract surgery. This earlyonset glaucoma is frequently associated with pupillary block,
shallowing of the anterior chamber, and angle closure. It is well
known that smaller eyes and eyes with reduced corneal diameter
are more prone to develop angle closure in the postoperative
period.22,23 However, the unavailability of data about preoperative gonioscopic findings in cases undergoing pediatric cataract
extraction limits our understanding about the pre-existing state
of the angle and its predisposition to insult in the postoperative
period. Residual lens material contributes to the development of
glaucoma by forming Elschnig pearls that may cause pupillary
block and induce inflammatory adhesions in the angle and at the
pupil edge, which can cause pupillary block and angle closure.
It has been observed that sulcus-fixation of the IOL is a risk factor for the development of pupillary block.19,22 But it is notable
that most studies reporting the incidence of glaucoma following
pediatric primary IOL implantation have failed to specify the
differentiation of in-the-bag vs. sulcus fixation.22,23 The possible
mechanism of glaucoma can occur due to the pupillary block,
leading to extensive synechial closure or the forward displacement of iris tissue by the haptics of a sulcus-fixated IOL, causing
crowding of structures in the angle.
The onset of delayed-onset open-angle glaucoma may occur
years following the cataract. Because of the late onset occurring
5 or more years following the cataract surgery, it is not likely
that inflammation, use of postoperative corticosteroids, or any
other portion of the cataract surgery is the cause of this problem.
Asrani et al, in a meta-analysis of 377 eyes with primary lens
implantation, found only 1 eye with open-angle glaucoma.24
They have suggested that when a primary IOL is used, there is
a reduced incidence of delayed-onset glaucoma. However, it is
worth noting that implants are infrequently placed in eyes with
microcornea and the surgery in this series was relatively delayed
(mean age at surgery: 5.06 years). Hence, two important risk
factors, microcornea and early age of surgery, which could have
influenced the results otherwise, were conspicuous by their
absence.
Although it is clear that pediatric cataract surgery places the
eye at risk for glaucoma, the exact mechanism remains elusive.
The volume of the lens and its dynamic role in accommodation
are more prominent in younger eyes. Surgical removal of the lens
early in life can alter normal development of the filtration angle.
Morphologic studies of developing eyes of children have shown
that the angle recess of the iridocorneal angle is expected to move
toward the periphery, exposing the scleral spur and the ciliary body band.25 It has been speculated that the absence of the
lens early in life alters or causes an arrest in development of the
filtration angle, or it may be a lack of accommodation and pull of
the ciliary muscles on the trabecular meshwork that in some way
permits the meshwork to become compact and dysfunctional.25
It may be that some chemical substance may diffuse from the
posterior eye into the anterior chamber and change the facility of
outflow of the eyes. Clearly, there are some undetermined genetic
and mechanical factors that may contribute to the development
of glaucoma after pediatric cataract surgery.
On the one hand, early cataract surgery has been advocated
to prevent amblyopia, and on the other hand, the possibility of a
higher complication rate after early cataract surgery looms large.
This leads to the dilemma, for which there are no clear answers.
At present, the clinician may be best advised to do a balancing
act of performing early cataract surgery, avoiding the neonatal
period, followed by a careful surveillance to detect postoperative
glaucoma. The latter must continue for the long term. Probably
future prospective studies, in which children would be randomized to cataract surgery at different ages within the critical
period, would enlighten us about the issue of optimum timing.
In summary, pediatric cataract surgical outcome is affected
by multiple factors. Among them, surgical technique, IOL power
calculation, postoperative myopic shift, and occurrence of glaucoma play major roles in the final visual outcome. There is a
need to study these factors in a robust way to find out possible
answers to many issues, which are still not clear. When we offer
surgery for these children, all these factors have to be incorporated in our decision making, keeping central the best interest of
the child.
References
1. Lambert SR, Drack AV. Infantile cataracts. Surv Ophthalmol.
1996; 40:427-458.
2. Forbes BJ, Guo S. Update on surgical management of pediatric
cataract. J Pediatr Ophthalmol Strabismus. 2006; 43(3):143-151.
3. Vasavada AR, Praveen MR, Tassignon MJ, et al. Posterior capsule
management in congenital cataract surgery. J Cataract Refract Surg.
2011; 37:173-193.
4. Lambert SR, Buckley EG, Plager DA, Medow NB, Wilson ME. Unilateral intraocular lens implantation during the first six months of
life. J AAPOS. 1999; 3:344-349.
5. Lambert SR, Lynn M, Drews-Botsch C, et al. A comparison of grating acuity, strabismus and reoperation outcomes among children
with aphakia and pseudophakia after unilateral cataract surgery
during the first six months of life. J AAPOS. 2001; 5:70-75.
6. Plager DA, Yang S, Neely D, Sprunger D, Sondhi N. Complications
in the first year following cataract surgery with and without IOL in
infants and older children. J AAPOS. 2002; 6:9-14.
7. Trivedi RH, Wilson ME Jr, Bartholomew LR, Lal G, Peterseim
MM. Opacification of the visual axis after cataract surgery and
single acrylic intraocular lens implantation in the first year of life.
J AAPOS. 2004; 8:156-164.
43
12. Gupta A, Kekunnaya R, Ramappa M, Vaddavalli PK . Safety
profile of primary intraocular lens implantation in children below 2
years of age. Br J Ophthalmol. 2011; 95:477-480.
13. Eibschitz-Tsimhoni M, Archer SM, Del Monte MA. Intraocular
lens power calculation in children. Surv Ophthalmol. 2007; 52:474482.
14. Neely DE, Plager DA, Borger SM, Golub RL. Accuracy of intraocular lens calculations in infants and children undergoing cataract
surgery. J AAPOS. 2005; 9:160-165.
15. Nihalani BR, VanderVeen DK. Comparison of intraocular lens
power calculation formulae in pediatric eyes. Ophthalmology 2010;
117:1493-1499.
16. Eibschitz-Tsimhoni M, Tsimhoni O, Archer SM, Del Monte MA.
Effect of axial length and keratometry measurement error on intraocular lens implant power prediction formulas in pediatric patients.
J AAPOS. 2008; 12:173-176.
17. Nischal KK, Solebo L, Russell-Eggitt I. Paediatric IOL implantation
and postoperative refractive state: what role do study methodology
and surgical technique play? Br J Ophthalmol. 2010; 94(5):529531.
18. Griener ED, Dahan E, Lambert SR. Effect of age at time of cataract
surgery on subsequent axial length growth in infant eyes. J Cataract
Refract Surg. 1999; 25:1209-1213.
19. Russell-Eggitt I, Zamiri P. Review of aphakic glaucoma after surgery for congenital cataract. J Cataract Refract Surg. 1997; 23:664668.
20. Phelps CD, Arafat NI. Open-angle glaucoma following surgery for
congenital cataracts. Arch Ophthalmol. 1977; 95:1985-1987.
21. Magnusson G, Abrahamsson M, Sjostrand J. Glaucoma following
cataract surgery: an 18-year longitudinal follow-up. Acta Opthalmol Scand. 2000; 78:65-70.
22. Rabiah P. Frequency and predictors of glaucoma after pediatric
cataract surgery. Am J Ophthalmol. 2004; 137:30-37.
8. Lundvall A, Zetterstrom C. Primary intraocular lens implantation
in infants: complications and visual results. J Cataract Refract Surg.
2006; 32:1672-1677.
23. Chak M, Rahi JS. Incidence of and factors associated with glaucoma after surgery for congenital cataract: findings from the British
Congenital Cataract Study. Ophthalmology 2008; 115:1013-1018.
9. Ashworth JL, Maino AP, Biswas S, et al. Refractive outcomes after
primary intraocular lens implantation in infants. Br J Ophthalmol.
2007; 91:596-599.
24. Asrani SG, Wilensky JT. Glaucoma after congenital cataract surgery. Ophthalmology 1995; 102(4):863-867.
10. Ram J, Brar GS, Kaushik S, et al. Primary intraocular lens implantation in the first two years of life: safety profile and visual results.
Indian J Ophthalmol. 2007; 55(3):185-189.
11. The Infant Aphakia Treatment Study Group. A randomized clinical trial comparing contact lens with intraocular lens correction
of monocular aphakia during infancy. Arch Ophthalmol. 2010;
128(7):810-818.
25. Mori M, Keech RV, Scott WE. Glaucoma and ocular hypertension
in pediatric patients with cataracts. J AAPOS. 1997; 1:98-101.
44
Section VII: Challenging Dogma — Part II
The Ciliopathies: What Are They?
Eduardo José Gil Duarte Silva MD
Ciliopathies are a recently defined group of rare genetic disorders
characterized by dysfunction of a hair-like cellular organelle—
the primary cilium. Cilia are microtubule-based structures found
on almost all vertebrate cells. They originate from a basal body,
a modified centrosome, which is the organelle that forms the
spindle poles during mitosis. The cilium-centrosome complex
represents nature’s universal system for cellular interaction, cellular detection, and management of external signals.
Primary cilium-related dysfunction can either affect a single
tissue or organ, or lead to a full-blown syndromic spectrum of
ciliopathy-related manifestations with simultaneous involvement
of several organs. The retina is a good example of a single-tissue
ciliopathy. Primary cilium dysfunction frequently affects photoreceptors (ciliated retinal cells) and causes retinal degeneration.
Mutations in retina-specific ciliary genes lead to isolated nonsyndromic retinitis pigmentosa (RP). These mutations include the
most common form of X-linked retinitis pigmentosa, linked to
the RPGR gene, or subtypes of autosomal recessive Leber congenital amaurosis (LCA) linked to NPHP6/CEP290 and LCA5/
lebercilin.
The retinitis pigmentosa phenotype is a common feature of
syndromic ciliopathies. These include Usher syndrome (RP plus
sensory-neural deafness with/without vestibular involvement),
Bardet-Biedl syndrome (BBS), MORM (Mental retardation,
truncal Obesity, Retinal dystrophy and Micropenis), Alström
syndrome, Senior-Loken syndrome (SLS), Joubert syndrome–
related diseases (JSRD), Jeune syndrome, and Meckel-Gruber
syndrome (MKS).
Most syndromic ciliopathies are inherited in an autosomal
recessive fashion. However, more complex inherited mechanisms
(triallelism, modifier effect) have been described. Allelic variability, defined as different mutations in the same gene giving
rise to different clinical presentations or syndromes, is common
among syndromic ciliopathies. It is well established that NPHP6/
CEP290 mutations may cause a pure retinal phenotype (isolated
LCA) to the lethal multisystemic MKS.
The cardinal features of Bardet-Biedl syndrome (BBS) are
retinal dystrophy (RD), obesity, polydactyly, hypogonadism,
cognitive impairment, and renal failure. Secondary clinical features such as anosmia, diabetes, cardiac anomalies, liver fibrosis,
brachydactyly, and Hirschprung disease may also be present.
Different types of retinal dystrophy have been reported in BBS.
These are mainly a rod-cone dystrophy or a cone-rod dystrophy;
however, a choroidal dystrophy and a global severe retinal dystrophy have also been described.
BBS is a genetically heterogeneous condition with 16 genes
identified to date. These account for about 80% of the cases. All
BBS genes have been related to cilium biogenesis and/or function.
BBS1 and BBS10 are the two most common culprits. Interestingly, several BBS genes are implicated in other ciliopathies:
BBS13 is MKS1 (Meckel Gruber syndrome 1) and BBS14 is the
CEP290/NPHP6 gene associated with LCA, JS, and MKS. In
contrast, retinal-specific splice variants of BBS3 and BBS8 have
been identified and mutations in these transcripts cause nonsyndromic RP.
Alström syndrome manifestations include RP in early childhood, hearing disability, and metabolic defects leading to hyperinsulinemia, type II diabetes mellitus, and obesity in childhood.
However, these patients lack polydactyly and cognitive impairment, commonly seen in BBS.
Senior-Loken syndrome is a combination of nephronophthisis
(NPH) and retinal degeneration. NPH is characterized by normal
kidney size, tubulointerstitial nephritis, and a loss of corticomedullary differentiation leading to cyst formation. The first
symptoms are often polyuria and polydipsia caused by a defect in
urinary concentration. Three forms of NPH can be distinguished
based on end-stage of renal failure: infantile, juvenile, and earlyadulthood. The occurrence of the retinal dystrophy is higher
in the juvenile form of NPH. To date, 11 genes (named NPHP
1e11) are known to be causative of SLS.
Joubert syndrome is a combination of cognitive impairment,
ataxia, tachypnea, and eye movement abnormalities. Cerebellar
vermis hypoplasia is a pathognomonic finding on MRI named
molar tooth sign. Multiple other features can be associated with
this midbrain-hindbrain malformation, leading to the denomination of Joubert syndrome–related disorders (JSRD). The
retinal phenotype includes macular colobomas and a rod-cone
dystrophy.
Within the spectrum of syndromic ciliopathies, MeckelGruber syndrome represents the most severe end of the disease
spectrum, leading to prenatal or perinatal mortality. It is characterized by occipital encephalocele, kidney cystic dysplasia,
hepatic ductal proliferation, liver fibrosis, and polydactyly. Seven
genes have been found to be implicated in MKS: MKS1, 2 and 3,
CEP290, NPHP3, RPGRIP1L, and CC2D2A.
Retinal degeneration due to primary cilium structure disruption has been put under the spotlight through the multispecies
ciliopathy studies that have enabled the identification and dissection of the signaling pathways involving the connecting cilium.
The retinitis pigmentosa phenotype secondary to dysfunction
of the primary cilium can be associated with several other clinical
manifestations (syndromic RP) and impacts on clinical practice.
It is important to be aware of the target organs for ciliopathies
defining well-known and new overlapping syndromes. Therefore, a child with RP/CRD should be assessed for associated features such as obesity, kidney impairment, polydactyly (asking for
removal of extra digits during childhood), cognitive impairment,
tested for anosmia and diabetes, and checked for bone changes,
as the diagnosis of a ciliopathy will influence follow-up.
Identification of ciliopathy genes has improved both our
biological understanding of these conditions and genetic counseling. The challenge is to dissect the mechanisms that underlie this
retinal degeneration subgroup. Pharmacological therapy aimed
at preventing connecting cilium dysfunction is still hypothetical.
Understanding the mechanisms underlying biogenesis and function of the photoreceptor connecting cilium is essential to identifying therapeutic strategies.
Selected Readings
1. Coppieters F, Lefever S, Leroy BP, DeBaere E. CEP290, a gene with
many faces: mutation overview and presentation of CEP290base.
Hum Mutat. 2010;31(10):1097-1108.
2. Gascue C, Katsanis N, Badano JL. Cystic diseases of the kidney:
ciliary dysfunction and cystogenic mechanisms. Pediatr Nephrol.
2011; 26(8):1181-1195.
3. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med.
2011; 364:1533-1543.
4. Mockel A, Perdomo Y, Stutzmann F, Letsch J, Marion V, Dollfus
H. Retinal dystrophy in Bardet-Biedl syndrome and related syndromic ciliopathies. Prog Retin Eye Res. 2011; 30:258-274.
5. Muller J, Stoetzel C, Vincent MC, et al. Identification of 28 novel
mutations in the Bardet–Biedl syndrome genes: the burden of
private mutations in an extensively heterogeneous disease. Hum
Genet. 2010; 127: 583-593.
6. Parisi MA. Clinical and molecular features of Joubert syndrome
and related disorders. Am J Med Genet C Semin Med Genet. 2009;
151C(4):326-340.
45
46
Retinal Repair by Transplantation of
Photoreceptor Precursors
Stem Cell Therapy for Retinal Disease: Future Prospects for the Clinic
Jane C Sowden PhD
Funding: Supported by grants from the Medical Research Council UK, Fight for Sight, the Macula Vision Research Foundation,
the Ulverscoft Foundation, the NIHR Biomedical Research
Centre for Ophthalmology. JCS is supported by Great Ormond
Street Hospital Children’s Charity.
Summary
New treatments are needed for retinal diseases involving the
death of photoreceptor cells. Remarkable progress is being made
in the research laboratory toward the development of novel stem
cell strategies for retinal repair. I will review recent advances
in generating new retinal neurons from pluripotent stem cells
in vitro and describe our work demonstrating the feasibility of
photoreceptor transplantation in animal models. Challenges for
the development of clinical cell-replacement therapies for retinal
disease will be discussed.
Selected Readings
1. Sowden JC, Ali RR. Stem cell therapy for blindness: new developments and implications for the future. Expert Rev Ophthalmol.
2011; 6(1):1-3.
2. MacLaren RE, Pearson RA, et al. Retinal repair by transplantation
of photoreceptor precursors. Nature 2006; 444:203-207.
3. Lakowski J, Baron M, et al. Cone and rod photoreceptor transplantation in models of the childhood retinopathy Leber congenital
amaurosis using flow-sorted Crx-positive donor cells. Hum Mol
Genetics. 2010; 19:4545-4559.
47
Radiation Exposure to Children from Medical Imaging:
Is There a Problem?
Michael Callahan MD, Marilyn Goske MD
Introduction
Computerized tomography (CT) has been recognized as one of
the major scientific advances in patient care. This remarkable
technology enables the radiologist to diagnose medical disease
and life-threatening illness faster and more precisely, obviating the need for emergency and exploratory surgeries. Pediatric
patients have been shown to be triaged more appropriately and
faster in the emergency room while lowering the cost of patient
care. Yet it has been shown that children are often imaged using
adult technique, resulting in radiation doses that are higher than
necessary. This presentation will focus on the challenges in discussions of radiation and will discuss educational interventions
that can be used to promote safe care.
Reasons for Increased Attention in the Use of
Ionizing Radiation in Imaging in Children
Both the scientific and the lay press have paid increasing attention to the use of radiation in medical imaging, particularly in
children, for several reasons: The number of CT scans in children has risen dramatically in the United States. CT scans can
be performed in less than a second.1 Many of the newer scanners (“helical scanners”) allow acquisition of a volume of data
that can be “reconstructed” in many different scan planes. The
number of CT scans in the United States has risen from 3 million
in 1980 to 62 million in 2006,2 with 4-7 million of these scans
performed annually in children.3 While the radiation dose from
a single CT scan is usually relatively low, some studies suggest
that the radiation dose to pediatric patients may be higher than is
necessary.4 The dose from a single CT scan is significantly higher
than x-rays. Compared to one day of background radiation, for
example, a single-view chest x-ray is similar to one day of background radiation, while a head CT is similar to up to 8 months
of background radiation.5
Children are more vulnerable to changes from
radiation.
Children are more susceptible than adults to changes in their cells
from a given dose of radiation. The primary risks to children
from a CT scan are the slight increased risk in developing cancer
and changes to their genes over their lifetime. Children’s cells are
growing rapidly. This puts them at greater risk to many types of
cell injury. The organs of a child’s body that are more susceptible
to changes from radiation are the lens of the eye, bone marrow,
thyroid, breast and the ovaries and testes. (Strategies to decrease
dose to the lens of the eye include angling the gantry to exclude
the lens in brain CT and lead shielding.) Children have more
remaining years of life during which radiation-induced cancer
could develop. If a child’s cells change as a result of a radiation
exposure, it may take 10, 20, or even 30 years for the cancer to
develop. Finally, we know from phantom or simulation studies
that if a child has a CT scan using an adult technique, the child’s
dose is greater. Since children have less subcutaneous tissues,
their core doses are significantly greater than an adult’s dose
when incorrect “adult-sized” techniques are used.
Potential risk is a complex topic to discuss with
families.
Discussion of risk from ionizing radiation used in medical imaging is complex, as it relates to population statistics, assessing risk
compared to benefit, and the fact that cancer occurs in about
40% of all people in the United States over the course of their
lifetime. The risk of developing a fatal cancer is about 20% over
the course of a lifetime in the United States. Therefore, separating
out the number of cases that arose from a specific medical radiation event is extremely challenging.
Comparison of Imaging Tests to Background
Radiation
•
•
•
•
•
•
•
Natural background radiation: 3 mSv/yr
Airline passenger (cross-country): 0.04 mSv
Chest x-ray (single view): up to 0.01 mSv
Chest x-ray (2 view): up to .1 mSv
Head CT: up to 2 mSv
Chest CT: up to 3 mSv
Abdominal CT: up to 5 mSv
Use of Alternate Imaging Strategies That Do Not
Use Ionizing Radiation
When considering any medical imaging, evaluating the benefit
to the patient relative to any potential risks from performing the
study is first and foremost. Alternate strategies may include clinical follow-up or other consultation ultrasound and MR that do
not use ionizing radiation. However, there are some instances
when CT is the only test that provides the specific information.
CT of the lung for suspected metastatic disease is an example of
this situation.
The Image Gently Campaign
Image Gently is an education and awareness campaign to promote radiation protection for children worldwide.5 Sponsored
by the Alliance for Radiation Safety in Pediatric Imaging, a consortium of more than 55 groups that represents over 700,000
health care professionals, the campaign hopes to change practice
locally . Our website, www.imagegently.org, provides additional
information.
References
1. Brenner DJ, Hall EJ. Computed tomography: an increasing source
of radiation exposure. J Engl J Med. 2007; 357(22):2277-2284.
2.IMV 2006 CT Marketing Summary Report. Des Plains, IL: IMV
Medical Information Division; 2006.
48
3. National Cancer Institute. Radiation Risks and Pediatric Computed
Tomography (CT): A Guide for Health Care Providers. 2009.
Available at www.cancer.gov/cancertopics/causes/radiation-riskspediatric-CT. Accessed August 8, 2011.
4. Hollingsworth C, Frush DP, Cross M, Lucaya J. Helical CT of the
body: a survey of techniques used for pediatric patients. AJR Am J
Roentgenol. 2003; 180:401-406.
5. Goske MJ; Alliance for Radiation Safety in Pediatric Imaging steering committee. The Image Gently campaign: working together to
change practice. AJR Am J Roentgenol. 2008; 109:273-274.
Video: Fishtail Sign in Posterior Lenticonus
Pre-existing Posterior Capsule Defect
Abhay Raghukant Vasavada MBBS FRCS
This video will highlight the diagnostic signs of a pre-existing
posterior capsule defect (PPCD). A significant proportion of
infants and small children with congenital cataracts have a PPCD
in the posterior capsule. In classic cases, the PPCD is hidden
behind a seemingly routine pediatric cataract in an undilated
pupil. The defect looks like a total, white cataract. Preoperative evaluation of such a cataract under maximum dilatation is
mandatory to unveil the important diagnostic signs. PPCDs have
a visible demarcation by their thick margins, mainly as a result
of capsule fibrosis. When the globe is moved with forceps the
degenerated vitreous with white granules moves like a fishtail,
which is pathognomonic of a PPCD. Specific staining of the vitreous reveals calcium accumulation in the chalky white granules
around the defect. Often, it is possible to identify the thick margins of the PPCD despite the “total” cataract. The cataract may
not be uniformly white on dilatation, the density of whiteness
being greatest in the center, with the periphery being semitransparent.
49
50
Current Management Strategies for
Blepharokeratoconjunctivitis
Mark E Jacobson MD
I. Blepharokeratoconjunctivitis is an eyelid margin disease with secondary conjunctivitis or corneal involvement.
A. Divided into anterior and posterior disease
C. Once hot, wring out washcloth in hot water.
D. Wrap washcloth around hot gel pack and check on
wrist to ensure it is not too hot.
E. Place on eyes until cooled (8-plus minutes).
1. Anterior disease includes inflamed eyelids with
debris and/or telangiectic vessels around cilia.
F. Once removed, children will have a red flush (raccoon mask).
2. Posterior disease includes inflammation and/or
glandular debris around the meibomian orifices.
G. Ingenuity and parent persistence are required.
B. Not uncommon, 2 large centers found it accounted
for 12%-15% of their referrals.1,2
C. Mean age of symptoms at age 4 and mean age of
referral for treatment at age 6 (range: 7 months to
16 years).1-3
D. Symptoms noted
1. Conjunctival erythema
2. Lid margin erythema
3. Eyelash anomalies
a.Blepharitis
b.Madarosis
c.Styes
4.Epiphora
5.Photophobia
6. Recurrent chalazion1,3,4
1. Parent/child sing favorite songs during compress.
2. Listen to music or a book or tape.
3. Parent read from a “chapter book” (ie, no pictures).
4. Compress one eye at a time while watching
favorite video (often the best way, especially if
treating a chalazion and doing this 4 to 6 times a
day).
5. Do in the bathtub.
H. Do every night at bedtime for 6-8 weeks until
follow-up appointment. Watch skin for chapping or
drying and apply facial moisturizer if noted.
IV. Flaxseed Oil
A. Dosage varies by weight: About 1 teaspoon per 33
pounds up to a maximum of 1 tablespoon if 100plus pounds.
B. Flaxseed oil (α linolenic acid) is dietary source of
omega-3 essential fatty acids.
C. Two studies in women with omega-3 dietary supplement
E. Clinical findings
1. As noted in D above.
2. Meibomian gland dysfunction
3. Corneal/limbal changes
a. Mild punctuate epithelial erosions to limbal
phylctenules
b. More severe: Corneal opacity, corneal scarring, or vascularization1-4
1. Improved dry eye symptoms
2. Changed the meibomian glands secreted lipid
profile5,6
D. My personal experience mimics that reported by
Kronemyer.7 Regular dietary intake of flaxseed oil
thins and clears the meibomian gland secretions
over time.
E. Adding flaxseed oil to child’s diet:
II. My Treatment of Blepharokeratoconjunctivitis
Treatment regimen may vary, but all include 2 mainstays:
A. Hot compresses
B. Flaxseed oil
1. Mix in smoothie or yogurt.
2. Mix in already cooked food to mask flavor
and texture (parental experimentation). Note:
Cooking flaxseed oil breaks down its nutritional
benefit.
3. Mix in old-fashioned peanut butter if child likes
and will eat it.
III. Hot Compress
Method and duration most important:
A. Use washcloth and small soft hot/cold gel pack.
B. Preheat gel pack in hot water.
a. Measure and pour off peanut oil on top and
replace with equal amount of flax seed oil.
b. A PB&J sandwich daily provides intake.
c. Note: You must refrigerate this peanut butter,
as the flaxseed oil will become rancid.
4. If improvement noted, discuss continuing flaxseed oil.
5. Taper the hot compresses to once or twice a
week, depending on how clear and thin the oil is.
V. Getting Parents to Buy Into Regimen
A. Explanation and understanding of purpose
B. Demonstration by digitally expressing the meibomian gland content and showing parent and child.
1. Description of normal oil as thin clear olive oil.
2. Showing thick, white, often wax-like substance
that was expressed allows parent to understand:
a. The need for prolonged hot compress to melt
wax.
b. The need for adding the gland’s dietary fuel to
help it make new clear oil.
C. This treatment of blepharokeratoconjunctivitis by
clearing out the meibomian glands (although done
in a different manner) by Beauchamp et al in 1981
in his Case 1 was shown effective. The reference citings, however, only focus on Case 2 with its use of
erythromycin.8
VI. Additional Arms of Treatment: Steroid Use
B. No improvement or desire to follow current controlled study literature
1. Discussion centers on continuing present regimen
and adding antibiotic.
2. Erythromycin or doxycycline dependent on age
and state of dentition.
3. Erythromycin is given 15-25 mg/kg 2 times a
day for 6 to 8 weeks (in literature may be longer).2,4,9,10
4.Follow-up
1. My concern is exasperation with increased
release of antigenic toxins with hot compresses.
2. Generally use an antibiotic-steroid combination
drop 3 to 4 times a day for 2 weeks then at bedtime after compress for 2 more weeks.
3. Literature notes desire to use least amount in
dosage and concentration through a tapering
regimen.1-3,9
4. For most cases steroid use is avoided because it
quickly masks symptoms and parents discontinue the real treatment of heat and flaxseed oil.
B. When steroids are not used, always forewarn parents of “storm before the quiet,” noting that eyes
will often look worse right after hot compress and
release of toxin-filled debris.
C. Erythromycin ointment at bedtime
1. Use with mild punctate epithelial erosions or
other surface irritation.
2. Use in cases of blepharitis.
VII.Follow-up
A. See patient back in 6-8 weeks.
1. On initial visit always note to parent that
this regimen does not always work and if no
improvement noted may need systemic antibiotics.
2. Review clinical signs and symptoms with parent
and patient.
3. Perform re-expression of the meibomian gland, if
possible.
a. Signs and symptoms improved: Discontinue
antibiotics, continue flaxseed oil, taper compresses, and review in 6- 8 weeks.
b. No change is noted: The oral course is
repeated and recheck in 6-8 weeks.
VIII.Conclusion
A. Over the past several years, systemic antibiotics
have rarely been needed.
A. Limited to perilimbal vessels or corneal infiltrates
51
1. Occasionally a mild steroid like fluorometholone
is needed for a short 2 times a day course while a
nightly regimen of hot compress is reinstituted.2
2. Occasionally patient will have relapse when
flaxseed oil/compresses have been discontinued.
Reinstating both usually clears the eye.
B. Mainstay of treatment in my mind is omega-3/flaxseed oil.
1. Essential need in developing infants is demonstrated by inclusion in baby formulas and recent
studies.11,12
2. Young children have no less need in their development but with lack of omega-3 included in
packaged processed food the need for external
supplements becomes apparent.
References
1. Gupta N, Dhawan A, Beri S, D’Souza P. Clinical spectrum of pediatric blepharokeratoconjunctivitis. J AAPOS. 2010; 14:527-529.
2. Hammersmith KM, Cohen EJ, Blake TD, Laigson PR, Rapuano CJ.
Blepharokeratoconjunctivitis in children. Arch Ophthalmol. 2005;
123:1667-1670.
3. Jones SM, Weinsttein JM, Cumberland P, Klein N, Nischal KK.
Visual outcome and corneal changes in children with chronic blepharokeratoconjunctivitis. Ophthalmology 2007; 114:2271-2280.
4. Wong IBY, Nischal KK. Managing a child with an external ocular
disease. J AAPOS. 2010; 14:68-77.
5. Miljanovic B, Trivedi KA, Dana MR, et al. Relation between
dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women. Am J Clin Nutr. 2005; 82:887-893.
52
6. Sullivan BD, Cermak JM, Sullivan RM, et al. Correlations between
nutrient intake and the polar lipid profiles of meibomian gland
secretions in women with Sjogrens syndrome. Adv Exp Med Biol.
2002; 506:441-447.
7. Kronemyer B. Dry eye successfully treated with oral flaxseed
oil. Ocul Surg News (Europe/Asia-Pacific edition). November
2000. Available at: www.osnsupersite.com/view.asp?rID=14973.
Accessed August 10, 2011.
8. Beauchamp GR, Gillette TE, Friendly DS. Phlyctenular keratoconjunctivitis. J Pediatr Ophthalmol Strabismus. 1981; 18:22-28.
9. Viswalingam M, Rauz S, Morlet N, Dart JK. Blepharokeratoconjunctivitis in children: diagnosis and treatment. Br J Ophthalmol.
2005; 89:400-403.
10. Meisler DM, Raizman MB, Traboulsi EI. Oral rosacea in childhood. Am J Ophthalmol. 2004; 137:138-144.
11. Uauy-Dagach R, Men P. Nutritional role of omega-3 fatty acids
during the perinatal period. Clin Perinatol. 1955; 22:157-175.
12. Birch EE, Carlson SE, Hoffman DR, et al. The DIAMOND (DHA
Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation
of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr. 2010; 91:848-859.
53
Evaluation of the Non-seeing Infant
Shira L Robbins MD
I. Identifying Poor Visual Behavior
A. What is normal?
B. Cerebral immaturity, foveal immaturity and lack of
ciliary body control lead to hazy and intermittent
vision, better in dim light.
C. This typical poor newborn vision prevents sensory
overload until the neurologic system is more mature.
D. Visual acuity greatly improves several months after
birth.
E. Eye movement coordination develops by 3-4
months.
F. Fine depth perception develops at 3-5 months
(requires good eye movement coordination and
adequate retinal nerve cell maturity).
II. Medical History (Development /Systemic Disease)
1. Visual behavior (Recognition, Navigation,
Response to Light and Dark)
2. Optokinetic nystagmus
3. Pupillary response
4. Presence of nystagmus
5. Sensorimotor if possible
6.Slitlamp
7. Dilated retina
8. Cycloplegic retinoscopy
V. Additional Testing
A. Preferential looking
B. Vestibulo-ocular reflex
C. Unequal nystagmus test
III. Family History (Ocular and Systemic)
D. Visual evoked potential
IV. Physical Examination
E.Electroretinogram
F.MRI
A. Exam style
1. Talk to the infant before touching.
G.EEG
2. Watch infant’s body response—not just eyes/
visual response.
H. Eye movement recordings
3. No abrupt hand movements near or on infant as
no visual cues to warn patient
I. Pediatric neurology consult
J. Metabolic workup
B. Parts of the physical exam
K. Genetic workup
VI. Diagnosis: Ocular, Cerebral, or Both
Figure 1. Reprinted with kind
permission from the author and
Springer Science+Business Media:
Pediatric Neuro-Ophthalmology,
The Apparently Blind Infant.
2010, 2, Brodsky MC, Fig 1.1.
54
VII.Treatment
A. Philosophy of treatment: Patient is a baby/child first
who happens to be non-seeing.
B. Medical: Diagnosis, prognosis
C. Psychiatric counseling
1. Grieving process of parents
2. Eventual grieving process of patient
3.Advocacy
4.Accommodations
D.Educational
1. Braille learning readiness, similar to reading or
kindergarten readiness: Braille learners need fine
motor skills, tactile sensitivity, ability to recognize small shapes, identify difference between
rough and smooth, follow a line with their finger
across a page.
2. Formal non-sighted education includes listening
skills, orientation and mobility, daily living skills,
art, physical education, and music, among others.
3. Developmental associations
E. Communication assistance: Vision is not main communication or learning mode. Sign language and
Braille can be positively framed as learning a foreign
language. Braille can lead to faster reading efficiency
instead of magnifying small portions of a page with
assistive devices.
F. Local community resources
G. Global resources
Selected Readings
1. Brodsky, Michael C. The apparently blind infant. In: Brodsky MC.
Pediatric Neuro-Ophthalmology, 2nd ed. New York: Springer;
2010:2.
2. Casteels I. Clinical investigation of bilateral poor vision from birth.
In: Taylor D, Hoyt CS, eds. Pediatric Ophthalmology and Strabismus, 3rd ed. Edinburgh: Elsevier Saunders; 2005:1011-1014.
3. Moller MA, Skolnick RD. Working with visually impaired children and their families. In: Wright KW, Spiegel PH, eds. Pediatric
Ophthalmology and Strabismus, 2nd ed. New York: Springer;
2003:538-545.
4. Robbins SL, Christian W, Hertle R, Granet DB. Vision testing in
children. Ophthalmol Clin North Am. 2003:253-267.
5. Maurer D, Maurer C. The World of the Newborn. New York:
Basic Books; 1988:105-133.
a. Delay gross motor → need to teach jumping,
hopping, and running
b. Delay body image
Additional Resource for Parents
c. Delay sensory integration → need increased
sensory exploration, especially tactile, and
encourage to use any vision patient has
6. National Association for Parents of the Visually Impaired (NAPVI),
www.spedex.com/napvi/.
d. Decreased imaginative play → can be healthy
to be around sighted peers to encourage this
55
Update on Oculoplastics
Don O Kikkawa MD
Eyelid/Face
The developing child undergoes dramatic transformation that
includes both volumetric and 3-dimensional growth. Many
anomalies that affect the pediatric populations arrest development, leading to deformity and functional deficit.
It is well recognized that one’s facial volume is full as a child
and that with growth, certain areas of the face lose volume. Identical twin studies have shown that, in general, the heavier twin
appears to be older in age until a certain age is reached (middle
age). At that point, the heavier twin appears younger. Loss of
facial volume is a noticeable characteristic in advanced age. The
trend in aesthetic rejuvenation is volume replenishment.
This concept has been translated to the pediatric population.
Craniofacial anomalies—in particular, clefting syndromes—lead
to characteristic deficiencies in bone and soft tissue. Much of the
previous reconstructive efforts have focused on rebuilding of the
facial skeleton, lacking emphasis on soft tissues. Examples will
be shown where use of soft tissue augmentation leads to fully
restored facial volume.
Vascular tumors continue to be a management challenge.
Pharmacologic advances, such as propranolol use for capillary
hemangioma, are proving to be first-line therapy. Surgical excision, however, remains an option for recalcitrant cases.
Orbital
The relationship of exophthalmos and ocular motility is nowhere
better examined than in thyroid eye disease (TED). In TED,
ocular motility may be limited due to tight restricted muscles.
This relationship worsens when the eye is proptotic because this
further worsens the situation by putting the already tight muscle
on stretch. In such cases orbital decompression can dramatically
improve ocular motility. In TED patients with large angle deviation, orbital decompression should be considered in preparation
for strabismus surgery.
Restriction of ocular motility can also be found in previously
operated eyes due to adhesions between the muscles and surrounding orbital tissues. The ability to alter the tissue biology of
wound healing is often essential to optimizing the outcomes in
difficult reoperations. The use of antimetabolite therapy intraoperatively and in the clinic setting can be very useful to prevent
further scarring in these difficult cases.
Lacrimal
Small incision or endoscopic procedures are favored in lacrimal
surgery because of faster healing times and minimized scarring.
Endoscopic lacrimal procedures in the pediatric population are
often challenging due to the size of the instrumentation and the
nasal passage in children. In addition, permanent bypass tubes
can be problematic in both children and adults. In the properly
selected child, however, permanent bypass tubes are well tolerated and effective.
Selected Readings
1. Guyuron B, Rowe DJ, Weinfeld AB, Eshraghi Y, Fathi A, Iamphongsai S. Factors contributing to the facial aging of identical
twins. Plast Reconstr Surg. 2009; 123(4):1321-1331.
2. Korn BS, Kikkawa DO, Cohen SR, Hartstein M, Annunziata CC.
Treatment of lower eyelid malposition with dermis fat grafting.
Ophthalmology 2008; 115(4):744-751.
3. Gomi CF, Yang SW, Granet DB, Kikkawa DO, Langham KA,
Banuelos LR, Levi L. Change in proptosis following extraocular
muscle surgery: effects of muscle recession in thyroid-associated
orbitopathy. J AAPOS. 2007; 11(4):377-380.
4. Komínek P, Cervenka S, Matousek P, Pniak T, Zeleník K. Conjunctivocystorhinostomy with Jones tube: is it the surgery for children?
Graefes Arch Clin Exp Ophthalmol. 2010; 248(9):1339-1343.
56
Managing Psychosocial Effects of Strabismus
Daniel S Mojon MD
Strabismus is a visible facial abnormality that has been shown to
be associated with many adverse psychosocial consequences in
adults.1-10 Adults often experience difficulties finding an employment6-9 and problems finding a partner.10 In children, it has been
demonstrated that visible differences in general11 and also strabismus have a negative impact on how they are perceived.11-15
Even a negative social bias of teachers against schoolchildren
with strabismus has been reported.12
Unfortunately, an increasing number of health care insurances try to refuse reimbursement for strabismus surgery procedures despite the large body of literature showing that visible
strabismus, even if there is no prospect for binocular vision, cannot be judged to be cosmetic.1-15,17-18
In children, surgery should be performed before negative attitudes toward strabismus emerge. Until recently, it was unclear
when such an attitude emerges.13-14 A recent study looking at
which children are invited by peers to birthday parties showed
that a negative attitude emerges at approximately 6 years.15
Children older than 6 years selected children with strabismus significantly less frequently than those with aligned eyes. Although
until 6 years no preference for children with straight eyes was
shown, a large percentage of children between 4 and 6 years
of age already noted that something was strange with the eyes.
The results show that corrective surgery for strabismus without
prospects for binocular vision should be performed before the
age of 6 years, when negative social attitudes may arise. The differences in the perception of strabismus between age groups can
be explained by studies on the development of children in the
recognition of facial features. These studies show that children
older than 6 years of age mostly process faces holistically, like
adults. Children younger than 4 years use part-based processing,
meaning that faces are categorized in terms of piecemeal characteristics. Therefore, younger children may not be able to realize
that two eyes are not straight.16
What is the role of glasses on the perception of visible strabismus in children? A high percentage of children with strabismus
wear glasses. Can glasses distract from visible strabismus? The
results of studies about this topic are controversial. Terry and
Stockton17 report that glasses have a negative effect; Walline
et al18 report that they make children look smarter and more
honest.
3. Satterfield D, Keltner JL, Morrison TL. Psychosocial aspects of strabismus study. Arch Ophthalmol. 1993; 111:1100-1105.
4. Burke JP, Leach CM, Davis H. Psychosocial implications of strabismus surgery in adults. J Pediatr Ophthalmol Strabismus. 1997;
34:159-164.
5. Beauchamp GR, Black BC, Coats DK, et al. The management of
strabismus in adults: III. The effects on disability. J AAPOS. 2005;
9:455-459.
6. Olitsky SE, Sudesh S, Graziano A, Hamblen J, Brooks SE, Shaha
SH. The negative psychosocial impact of strabismus in adults.
J AAPOS. 1999; 3:209-211.
7. Coats DK, Paysse EA, Towler AJ, Dipboye RL. Impact of large
angle horizontal strabismus on ability to obtain employment. Ophthalmology 2000; 107:402-405.
8. Mojon-Azzi SM, Mojon DS. Strabismus and employment: the opinion of headhunters. Acta Ophthalmol. 2009; 87:784-788.
9. Goff MJ, Suhr AW, Ward JA, Croley JK, O’Hara MA. Effect of
adult strabismus on ratings of official US Army photographs.
J AAPOS. 2006; 10:400-403.
10. Mojon-Azzi SM, Potnik W, Mojon DS. Opinions of dating agents
about strabismic subjects’ ability to find a partner. Br J Ophthalmol. 2008; 92:765-769.
11. Harper DC. Children’s attitudes to physical differences among
youth from Western and non-Western cultures. Cleft Palate Craniofac J. 1995; 32:114-119.
12. Uretmen O, Egrilmez S, Kose S, Pamukcu K, Akkin C, Palamar M.
Negative social bias against children with strabismus. Acta Ophthalmol Scand. 2003; 81:138-142.
13. Paysse EA, Steele EA, McCreery KM, Wilhelmus KR, Coats DK.
Age of the emergence of negative attitudes toward strabismus.
J AAPOS. 2001; 5:361-366.
14. Johns HA, Manny RE, Fern KD, Hu YS. The effect of strabismus
on a young child’s selection of a playmate. Ophthalmic Physiol
Opt. 2005; 25:400-407.
15. Mojon-Azzi SM, Kunz A, Mojon DS. Strabismus and discrimination in children: are children with strabismus invited to fewer birthday parties? Br J Ophthalmol. 2011; 95: 473-476.
16. Pellicano E, Rhodes G. Holistic processing of faces in preschool
children and adults. Psychol Sci. 2003; 14:618-622.
References
17. Terry RL, Stockton LA. Eyeglasses and children’s schemata. J Soc
Psychol. 1993; 133:425-438.
1. Menon V, Saha J, Tandon R, Mehta M, Khokhar S. Study of the
psychosocial aspects of strabismus. J Pediatr Ophthalmol Strabismus. 2002; 39: 203-208.
18. Walline JJ, Sinnott L, Johnson ED, Ticak A, Jones SL, Jones LA.
What do kids think about kids in eyeglasses? Ophthalmic Physiol
Opt. 2008; 28:218-224.
2. Jackson S, Harrad RA, Morris M, Rumsey N. The psychosocial
benefits of corrective surgery for adults with strabismus. Br J Ophthalmol. 2006; 90:883-888.
57
The Patient Has Thyroid Ophthalmopathy
Battle of the Bulge: Experience of the UCSD Thyroid Eye Center
David B Granet MD
I. Thyroid Eye Center
In 1997 UCSD Multidisciplinary Thyroid Eye Center
formed, combining Oculoplastics, Strabismus Specialist, Neuro-ophthalmologist, Fellows and Residents.
The center improves care via improved communication,
coordinated care, making treatment easier for patient
and improving process/compliance, and research.
5. Medial and/or inferior rectus
6. Adjunct to orbital decompression
7. Type II patients with large muscles or strabismus
in primary gaze undergoing decompression
II. Graves Hyperthyroid
C. Botulinum toxin A role in restrictive strabismus
1. IOP effects, preop, intraoperative
2. Dose 5-15 units per muscle
A. Almost all have some eye signs.\
3. Multiple injections per muscle
B. Half are clinically evident.
4. IOP in injection patients
5. Decrease in IOP on upgaze
III. Thyroid Eye Disease: Clinical Spectrum of Disease
A. Type I: Fat infiltration
6. Primary gaze IOP also dropped
B. Type II: Extraocular muscle involvement
7. Sustained after 3 months
IV. Overall Approach: Five-Step Plan
D. Strabismus surgery
A. Medical treatment
1. Primary position and reading position
B. Botox / prism if needed
2. Our guidelines
C. Orbit (unless neuropathy)
a. Undercorrect vertical: Aim for below primary
D. Strabismus repair
b. Assymmetric surgery, recessions
E. Lid repair
c. Use tendon shifts
V. Medical RX
Lubricants, topical decongestants/anti-histamines/
plugs, prisms, steroids (oral, IV, retrobulbar), Botulinum toxin, XRT (ORGO study)
VI. What have we learned?
A. Depression study; 2 groups
1. Severe/moderate eye signs vs. Mild/none
2. POMS survey (profile of Mood States)
3. Significant depression compared to non-ophthalmic Graves
4. More associated with disfigurement than
diplopia
5. Psychological burden should be considered in
planning treatment and prompt referral to mental health professionals.
B. Orbital decompression (bony)
1. Diplopia new onset: 10%
2. Botulinum toxin A as an adjunct to decompression
3. Intramuscular injection under direct visualization
4. 10 to 15 units Botulinum A toxin
3. EOM surgery
a. Defer until stabilizes after decompression
b. Usually requires inferior rectus, medial rectus
recession on adjustable
c. ± Botulinum toxin
d. Don’t forget lid issues
VII. Thyroid Strabismus Patterns: AAPOS 2005
A. 45%: Inferior rectus OA pattern
B. 22.5%: Superior rectus OA pattern
C. 22%: Inferior oblique OA pattern
D. 9.68%: Superior oblique OA pattern
VIII. Patient Education
A. Use of adjustable sutures
B. Delay adjustment
C. Approach oblique muscles
D.
Other center approaches . . .
1. May worsen proptosis
2. May worsen lid position
58
E. Lower lid retraction repair
1. AAO 2003
2. For patients that go through the entire process,
33 months until finished from Dx, 9 months
from start to finish for repair, RAI and thyroid
orbitopathy
3. RAI and thyroid eye disease
59
There Is a Cranial VI “Palsy”
G Robert LaRoche MD
I. First: Sort out if it is a paresis or paralysis.
To help in the differential diagnosis of a paralysis vs.
possible residual function of the lateral rectus, details
of history can be useful and essential diagnostic maneuvers are essential.
A.Cause
C. Loss of fusional ability (brain injury): Free space
and/or haploscope
D. Patient expectations
1. Neurosurgery vs. closed head trauma
1. Field of single binocular vision
2. Vascular insufficiency vs. progressive tumorrelated compression
2. Number of surgeries
3. Motility vs. visual ultimate expectations
B. Chronicity and delays
1. Cause (see above)
2. Stability of maximum angle: without any recovery
3. Spread of commitance
III. Third: Setting Up a Plan
C. Full orthoptic assessment
1.Motility
1. Improve ocular rotation
2. Balance yokes
3. Anticipate problems
B. Paresis = Recess-resect (RR); can be asymmetrical or
large numbers
a. Measures of the estotropia (ET): Lateral
incommitancy, etc.
C. Contracture = Release (Botox and timing vs. recession)
b. Secondary deviations: Hess, Lees, Harms
screens
D. Paralysis = Transposition(s)
E. Other cranial nerves = Other muscles, other eye
F. Larger field of binocular single vision = Balance
yokes
2.Fusion
a. Confirm potential
b. Eliminate motility barriers (eg, torsions – haploscope)
A. Three principles of Buckley
3. Single binocular field
a. Patient friendly
b. Preop: Assessment, patient education, setting
goals
c. Postop: Results, planning
D. Essential diagnostic tests
1. Saccades by clinical optokinetic nystagmus or
velocity recordings (essential): Limited by clinical
experience, contractures, equipment
2. Generated forces: Requires patient cooperation
++
3. Forced ductions
a. Useful in cases of small saccades amplitude
b. Important to rule out contractures
II. Second: Complicating Factors
B. Other cranial nerve involvement (eg, CN IV): Will
require additional surgical consideration (eg, IV in
head trauma cases and hypertropia)
A. Medial rectus contracture (with or without conjunctival shrinkage): Will demand a different surgical
approach
1. Weaken contralateral agonist (medial rectus
[MR])
2. . . . Weaken contralateral antagonist (lateral rectus [LR])
3. Posterior fixation in small primary position
deviations
G. Good results in general
IV. The Interventions: Timing and Type
A. Botox and contracture: Prevention vs. treatment
B. 6-12 months of absolute stability. Unless . . .
C.RR
1. Complete recovery and residual ET = RR
2. More often partial recovery = More resection
3. Large chronic angle but good function = Large
RR
a. Watch for resulting lateral incommitancy
b. Conjunctival recession
60
D.Transpositions
1. Full tendon: Knapp with or without Foster
sutures
2. Partial tendon:
C.Overcorrection
1. Most cases, short lived . . . adjustable ?
2. Reported with MR recession/Botox when no
contracture
a. Preserve one-half of vascular supply from the
muscles
3. Restriction of antagonist (MR) rotation (exotropia in opposite gaze)
b. Hummelsheim with or without Foster sutures
c.Hummelsheim-Kaufmann
4. Avoid excessive MR recession. Instead: Posterior
fixation of contralateral agonist
5. Occurs with late recovery of the LR (hasty surgery)
3. In all = Watch for tight inferior rectus and resulting hypotropia (HoT)
E. Prisms, and additional surgeries
D. Vertical deviation
1. Inferior rectus and Lockwood complex are too
tight
2. Surgery on bigger vertical or missed contralateral
CN IV
2. Undiagnosed CN IV or partial/partially recovered CN III
3. Surgery: Residual ET or increase binocular field
– contralateral MR
3. Asymmetrical full transposition
4. Importance of technique: Forced and spring balance tests
5. Possible advantage of some form of adjustable . . . .
1. Prisms: Small residual horizontal or vertical
a.Recession
b. Retro-equatorial myopexy (posterior fixation)
i.Scleral
ii.Pulleys
V.Complications
Selected Readings
1. Rare if only 2 muscles operated
1. Rosenbaum A, Santiago A. Selected transposition procedures. In:
Rosenbaum AL, Santiago AP, eds. Clinical Strabismus Management: Principles and Surgical Techniques. Philadelphia: WB Saunders; 1999:476-489.
2. Advantage of Botox on the homo-lateral antagonist MR
2. Coats D, Olitsky S. Transposition procedures. In: Strabismus Surgery and Its Complications. Springer; 2007:131-139.
3. Advantage of partial transposition with MR surgery
3. Roth A, Speeg-Shatz C. Paralytic strabismus. In: Eye Muscle Surgery: Basic Data. Swetts & Zeitlinger; 2001:337-353.
A. Anterior segment ischemia
B.Undercorrection
1. With misdiagnosis of complete paralysis
2. In untreated contracture of the homo-lateral
antagonist (MR)
3. In partial transposition . . . role of Foster sutures/
Kaufmann technique
4. Buckley E. General principles in the treatment of paralytic strabismus (The Richard G Scobee Lecture). Am Orthoptic J. 2008;
58:49-58.
5. Walsh L, LaRoche R. Abduction paralysis with hypotropia: signs
of weakness of a contralateral superior oblique. Strabismus 2001;
9(4):231-238.
The Patient Has Adult-Onset CN III Palsy
David K Coats MD
I.Abstract
The treatment of a severe paresis or palsy of the third
cranial nerve with onset after visual maturation is
complex. Patients are almost always motivated to have
surgical correction and frequently, if not usually, have
unrealistic expectations as to their prognosis. This
talk will provide an overview of 3 key components of
the management of an adult with a third cranial nerve
palsy: (1) the complex decision to recommend surgery
or not, (2) surgical treatment options and expectations,
(3) long-term follow-up needs.
III. Surgical Treatment Options
A. Is this patient a surgical candidate?
1. Attitude and expectations of the patient
2. Concurrent problems
1. Alignment objectives
2.Diplopia
3. Corneal exposure
4. Residual ptosis
5. Other potential complications
6. Timing of ptosis surgery
1. Large recess/resect operation
2. Transposition procedures
3. Mechanical fixation
B. Anticipated outcome
1. Residual strabismus
2. Duction limitations
3. Abnormal head posture
4. Residual ptosis
IV. Long-term Follow-up Needs
B. Preoperative patient discussion
II. Approach to the Patient Prior to Surgery (Assuming
Etiology Is Known and Spontaneous Resolution Is Not
Anticipated)
A. Traditional muscle surgery
A.Strabismus
1. Progressive recurrence possible
2. Additional surgery may be warranted.
B. Anterior segment
1. Corneal exposure concerns
2. Protection of the cornea
61
62
You Are Faced With Partially Accommodative
Esotropia ± High Accommodative Convergence-toAccommodation Radio
I. Treatment of Accommodative Esotropia (ET)
Full hypermetropic correction as soon as possible:
A. To straighten eyes by relaxing the overconvergence
caused by accommodating
B. Delay can result in loss of binocular potential.
C. Child must wear optical correction full time.
D. Atropine relaxation: Short course of cycloplegia
(atropine 1% O.U. x 7 days) if patient does not
accept hypermetropic glasses
1. Eyes straightened to within 8 prism diopters (PD)
at distance and near
2. Binocular vision and stereo present
1. Good compliance with glasses
2. Residual esotropia of more than 10 PD for distance or near (with bifocal)
3. No fusion or stereopsis with glasses
A. Bilateral medial rectus (MR) recession: procedure of
choice
B. Controversy: Surgical dose
C. Standard surgery: Surgical tables
D. Residual deviation at distance after full hypermetropic correction
E. Result: Undercorrection (42%-65%)
F. Augmented surgery: Increase amount of surgery
2. Wright: Average of Ncc (near with correction)
and Nsc (near without correction); or average of
Nsc and Dcc (distance with correction) if AC/A
ratio high
3. Kushner, West and Repka: Use near deviation
with correction
III. New Surgical Protocol
A. New surgical protocol for augmented surgery based
on the average of Ncc and Dsc (distance deviation
without correction). Used by author from 1985 to
the present.
2. < Dsc: To reduce likelihood of overcorrection
that cannot be treated with glasses reduction
B. Patients operated by MADM
C. Inclusion criteria
1. Residual ET > 12 PD after full hypermetropia
correction
2. Surgery after 6 months of age
3. Postop follow-up for at least 6 months
4. No associated palsy
5. A/ V pattern, IO surgery, Down syndrome,
developmental delay included
V.Results
A. 107 patients operated from July 1987 to Dec. 2008
B. 58 (55.2%) males, 49 females (44.8%)
C. Age at time of surgery: 4.77 years (0.64-15.9
years)
D. Duration of symptoms: 2.4 years (1 to 178 months)
E. 12.6% Medicaid, 87.3% private insurance
1. Parks: Add 1 mm to recession of each MR if high
accommodative convergence-to-accommodation
(AC/A) ratio
A. Retrospective review
II. Surgical Dose Controversial
1. > Ncc: Prefer overcorrection, so can treat with
decrease plus/remove glasses
F. After 2 to 4 weeks, surgery indicated if:
IV.Methods
E. Continue full correction if:
B. Rationale—Must correct:
VI. Preop Characteristics
A. Hyperopia: +4.29 (+0.5 to +8.75)
B. Stereopsis: 55% none, 38% gross, 12% refined
C. 100% distance glasses, 35% bifocals
D. Near deviation without correction: 46.5 PD
E. Distance deviation without correction: 38.0 PD
F. Near deviation with correction: 35.0 PD
G. Distance deviation with correction: 28 PD
H. Mean target angle: 38 PD
I. AC/A ratio: 8.9 (48.5% ≥ 10)
VII. Operative Details
A. Bilateral medial rectus recession
B. Mean 4.9 mm in each eye (3.25-6.75)
63
Table 1.
Author (Year)
Success
Criteria
Success
Overcorrection
No. of
Subjects
Target Angle
Jotterbrand, Isenbert (1988)
ET ≤ 10
65%
15%
20
Avg. of Dcc, Dsc
Multicenter Prism Adapt (1990)
ET/XT ≤ 8
83%
3.3%
61
Full prism adapted near angle
Wright (1993)
ET/XT ≤ 10
88%
12%
40
Avg. of Nsc, Ncc
West, Repka (1994)
ET/XT ≤ 10
80%
8%
25
Ncc + Aug (AC/A > 10)
Kushner (2001)
ET < 10
86%
4.5%
22
Ncc + Aug
Del Monte, Leo (2010)
ET ≤ 10
91.5%
3.4%
107
Avg. of Ncc, Dsc
Abbreviations: ET indicates esotropia; Dcc, distance deviation with correction; Dsc, distance deviation without correction; XT, exotropia; Nsc, near deviation without correction; Ncc, near deviation with correction.
C. 2 supra-placement (for A-pattern), 1 infra-placement (for V-pattern)
D. 29.5% associated inferior oblique surgeries
VIII. Treatment Success: 2 Months Postop (Without Manipulation of Glasses), N = 92
XI. Discussion (See Table 1)
XII.Summary
A. Full hyperopic correction for fully refractive accommodative ET; bifocals for high AC/A
B. Use new surgical protocol for augmented surgery
for to treat partially accommodative esotropia.
Physiologic target angle based on the average of Ncc
and Dsc.
C. Restores binocular vision
D. Allows reduction or elimination of glasses or bifocals in selected patients
A. Alignment at near and distance:
1. Success if ET ≤ 10
2. Any XT considered failure
B. Ortho: 62%
C. ET ≤ 10: 33%
D. ET > 10: 3%
E. Safe, with low overcorrection/reoperation rates
E. XT: 2%
F. Stereo: 10% nil, 17.5% gross, 62.5% refined
F. Greater success than any other published surgical
protocol
IX. Results at 2 Months Postop
Success in subgroup (18 patients; 17%): Good alignment and good visual acuities without glasses at distance and near!
A. Mean spherical equivalent: +2.95 (range: +0.75 to
+4.25, unaided visual acuity 20/25 or better)
B. Mean target angle: 30.25 PD (15 to 42.5 PD)
C. Mean preop near deviation without correction: 41.8
(28 to 52.5 PD)
X. Treatment Success 2 years Postop
A. 88 patients
B. 54% no glasses, 38% distance glasses, 8.0% bifocals (average +1.36)
C. Stable alignment
1. Near deviation: 96% ortho/ ET ≤ 10
2. Distance deviation: 94% ortho/ ET ≤ 10
D. 94% success
Selected Readings
1. Wright KW, Bruce-Lyle L. Augmented surgery for esotropia associated with high hypermetropia. J Pediatr Ophthalmol Strabismus.
1993; 30(3):167-170.
2. West CE, Repka MX. A comparison of surgical techniques for the
treatment of acquired esotropia with increased accommodative convergence/accommodation ratio. J Pediatr Ophthalmol Strabismus.
1994; 31(4):232-237.
3. Kushner BJ, Preslan MW, Morton GV. Treatment of partly accommodative esotropia with a high accommodative convergenceaccommodation ratio. Arch Ophthalmol. 1987; 105(6):815-818.
4. Kushner BJ. Fifteen-year outcome of surgery for the near angle in
patients with accommodative esotropia and a high accommodative
convergence to accommodation ratio. Arch Ophthalmol. 2001;
119(8):1150-1153.
5. Jotterand VH, Isenberg SJ. Enhancing surgery for acquired esotropia. Ophthalmic Surg. 1988; 19(4):263-266.
65
Financial Disclosure
The Academy’s Board of Trustees has determined that a financial relationship should not restrict expert scientific, clinical, or
nonclinical presentation or publication, provided that appropriate disclosure of such relationship is made. As an Accreditation
Council for Continuing Medical Education (ACCME) accredited
provider of CME, the Academy seeks to ensure balance, independence, objectivity, and scientific rigor in all individual or jointly
sponsored CME activities.
All contributors to Academy educational activities must disclose any and all financial relationships (defined below) to the
Academy annually. The ACCME requires the Academy to disclose the following to participants prior to the activity:
• any known financial relationships a meeting presenter,
author, contributor, or reviewer has reported with any
manufacturers of commercial products or providers of
commercial services within the past 12 months
• any meeting presenter, author, contributor, or reviewer
(hereafter referred to as “the Contributor”) who report
they have no known financial relationships to disclose
For purposes of this disclosure, a known financial relationship is defined as any financial gain or expectancy of financial
gain brought to the Contributor or the Contributor’s family,
business partners, or employer by:
• direct or indirect commission;
• ownership of stock in the producing company;
• stock options and/or warrants in the producing company,
even if they have not been exercised or they are not currently exercisable;
• financial support or funding from third parties, including
research support from government agencies (e.g., NIH),
device manufacturers, and/or pharmaceutical companies;
or
• involvement in any for-profit corporation where the Contributor or the Contributor’s family is a director or recipient of a grant from said entity, including consultant fees,
honoraria, and funded travel.
The term “family” as used above shall mean a spouse, domestic partner, parent, child or spouse of a child, or a brother, sister,
or spouse of a brother or sister, of the Contributor.
Category
CodeDescription
Consultant / Advisor
C
Consultant fee, paid advisory
boards or fees for attending a
meeting (for the past one year)
Employee
E
Employed by a commercial
entity
Lecture fees
L
Lecture fees (honoraria), travel
fees or reimbursements when
speaking at the invitation of a
commercial entity (for the past
one year)
Equity owner
O
Equity ownership/stock options
of publicly or privately traded
firms (excluding mutual funds)
with manufacturers of commercial ophthalmic products or
commercial ophthalmic services
Patents / Royalty
P
Patents and/or royalties that
might be viewed as creating a
potential conflict of interest
Grant support
S
Grant support for the past one
year (all sources) and all sources
used for this project if this form
is an update for a specific talk
or manuscript with no time
limitation
66
2011 Pediatric Ophthalmology Planning Group
Financial Disclosures
Alcon Laboratories, Inc.: L
David B Granet MD
Alcon Laboratories: C
Ken K Nischal MBBS
Bausch + Lomb: C
AAO Staff
Ann L’Estrange
None
Melanie Rafaty
None
Debra Rosencrance
None
Faculty Financial Disclosure
Steven M Archer MD
Ramesh Kekunnaya MD FRCS
Shira L Robbins MD
None
None
Michael J Callahan MD
Don O Kikkawa MD
Allergan, Inc.: C
Department of Health and Human
Services: L
None
None
David K Coats MD
Sylvia R Kodsi MD
None
None
Mark Del Monte JD
Burton J Kushner MD
None
None
G Robert LaRoche MD
None
None
Thomas C Lee MD
Diopsys Corp.: C,
SureSight Vision Screening: C
None
None
None
Pfizer, Inc.: C
David B Granet MD
Daniel S Mojon MD
None
None
Eduardo D Silva MD
Genzyme: L
Jane C Sowden PhD
None
Genzyme: C,L
Oxford Biomedica: C
MBBS FRCS
M Edward Wilson Jr MD
Paolo Nucci MD
Alcon Laboratories, Inc.: C,S
Bausch + Lomb Surgical: C
Springer Book Publishers: P
Alcon Laboratories, Inc.: C,L
Serono: L
Richard W Hertle MD
Scott E Olitsky MD
None
None
David A Plager MD
None
Alcon Laboratories, Inc.: C
Bausch + Lomb Surgical: C
None
None
Bausch + Lomb: C
Alcon Laboratories: C
Mark E Jacobson MD
Daniel J Salchow MD
None
Terri L Young MD
National Eye Institute: S
Alcon Laboratories, Inc.: S
67
68
Presenter Index
Archer, Steven M 33
Callahan, Michael J 47
Coats, David K 61
Del Monte, Mark 15
Del Monte, Monte A 62
Donahue*, Sean P 13
Forbes, Brian J 11
Freedman*, Sharon F 25
Granet*, David B 8, 57
Hertle, Richard W 35
Houck, Constance S 6
Jacobson, Mark 50
Kekunnaya, Ramesh 39
Kikkawa, Don O 55
Kodsi, Sylvia R 9
Kushner, Burton J 5
LaRoche, G Robert 59
Lee, Thomas C 18
Mintz-Hittner, Helen A 28
Mojon, Daniel S 1, 56
Nischal*, Kanwal K 16, 27
Nucci*, Paolo 26
Olitsky, Scott E 32
Plager*, David A 3
Ramsey, Jean E 22
Robbins*, Shira L Rob 53
Salchow, Daniel J 31
Schalij-Delfos, Nicoline 24
Silva*, Eduardo D 44
Sowden, Jane C 46
Traboulsi*, Elias I 20
Vasavada*, Abhay Raghukant 49
Wilson*, M Edward 19
Young*, Terri L 23
Zaidman*, Gerald W 17

PEDIATRIC OPHTHALMOLOGY Pediatric Ophthalmology 2011: A Child’s View from Here…and There 2011

Transcription

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