Session 312 Glaucoma Surgery I

Transcription

ARVO 2016 Annual Meeting Abstracts
312 Glaucoma Surgery I
Tuesday, May 03, 2016 8:30 AM–10:15 AM
Exhibit/Poster Hall Poster Session
Program #/Board # Range: 2923–2956/A0272–A0305
Organizing Section: Glaucoma
Program Number: 2923 Poster Board Number: A0272
Presentation Time: 8:30 AM–10:15 AM
Cell adhesion and protein adsorption studies of 3D printed
photopolymers
Richard M. Lee1, 2, Maryam Alband2, Matthew Penny2,
Stephen T. Hilton2, Steve Brocchini1, 2, Peng T. Khaw1. 1National
Institute for Health Research (NIHR) Biomedical Research Centre at
Moorfields Eye Hospital NHS Foundation Trust and UCL Institute
of Ophthalmology, London, United Kingdom; 2UCL School of
Pharmacy, London, United Kingdom.
Purpose: 3D printing technology has the potential to develop
personalised ophthalmic devices or organs with improved cost
effectiveness and productivity. Limited experimental data exists
as to the biocompatibility response of 3D printed photopolymers.
We performed cell adhesion and protein adsorption studies of 3D
printed photopolymers and materials used in current ophthalmic
devices (Silicone, Polytetrafluoroethylene (PTFE) and Poly (methyl
methacrylate) (PMMA)).
Methods: Poly(ethylene glycol) diacrylate (PEGDA) (Sigma,
MO, USA) and proprietary photopolymer (‘Clear’ and ‘Flexible’
resin, FormLabs, MA, USA) sample discs (n=6, 5mm diameter)
were developed using a high-resolution, desktop stereo-lithography
(SLA) 3D printer (Form 1+, Formlabs). Materials used in current
ophthalmic devices (Silicone, PTFE, PMMA) were punched out with
similar dimensions to the 3D printed discs. Protein adsorption was
quantified using fetal calf serum (Invitrogen, CA, USA) with a micro
bicinchoninic acid (Micro BCA, ThermoFisher, MA, USA) protein
assay kit and direct assessment of fluorescein-conjugated bovine
serum albumin (FITC-BSA, Sigma) adsorption. Discs were seeded
with monocytes and incubated for 24 hours at 37oC. Quantification
of cell metabolism and cytotoxicity were performed using Alamar
Blue and Live/Dead (ThermoFisher) assay kits respectively. Readings
were recorded using a plate reader (Fluostar Optima, BMG Labtech,
Buckinghamshire, UK). Data were compared using a two-tailed
unpaired t-Test.
Results: 3D printed photopolymers demonstrated similar cell
adhesion and protein adsorption compared to materials used in
current ophthalmic devices. There were no statistically significant
differences in measurements observed between 3D printed materials
(P>0.05).
Conclusions: 3D printed photopolymer material demonstrated a
similar biocompatibility response to currently used materials and may
allow for the development of customisable ophthalmic devices or
organs.
Commercial Relationships: Richard M. Lee, None;
Maryam Alband, None; Matthew Penny, None; Stephen T. Hilton,
None; Steve Brocchini, None; Peng T. Khaw, None
Support: National Institute for Health Research Biomedical
Research Centre
Conjunctival tissue proteome demonstrates abnormal expression
of wound response proteins in glaucoma patients
Hannu M. Uusitalo1, 2, Antti Jylhä1, Janika Nättinen1, 3,
Anu Vaajanen2, Miihkali Härkönen2, Matti Nykter3, Lei Zhou4,
Roger W. Beuerman1, 4. 1Ophthalmology, SILK, PPM, University of
Tampere, Tampere, Finland; 2Tays Eye Center, Tampere University
Hospital, Tampere, Finland; 3BioMediTech, University of Tampere,
Tampere, Finland; 4SERI, Singapore, Singapore.
Purpose: Medically uncontrolled glaucoma is usually treated
surgically. Postoperative scarring and fibrosis often occur as adverse
outcomes requiring additional treatment and cause surgical failure.
Using a novel proteomic analysis conjunctival health was evaluated
in conjunctival specimens of glaucoma patients at the time of
operation and compared to healthy conjunctiva.
Methods: Conjunctival tissues (1×2-5mm) were collected from 34
glaucoma patients undergoing glaucoma surgery after long-term
(2-21 years) use of topical antiglaucoma medication. Conjunctival
tissues of 8 strabismus surgery patients were used as controls.
Proteins derived from conjunctival tissues were analyzed for
library generation using UniProtKB/SwissProt database. Relative
quantification of protein expression levels in 4 μg of each biopsy
sample was done by NanoLC-MSTripleTOF using SWATH
acquisition. Statistical and MS data analysis were performed with
extensive software by Sciex and David Bioinformatics.
Results: A protein identification library consisting of >1800 proteins
(FDR 1 %) was established. In total >1550 proteins were identified
and quantified in each sample. GO analysis of the conjunctiva
proteome revealed 85 wound response associated proteins of which
48 were differentially expressed (p≤0.05) between glaucoma and
control patients. A number of proteins were under-expressed in
glaucoma, such as complement factors (≥1.5 fold), fibrinogens (≥2
fold) and serpinase family proteins (≥1.6 fold). Known tear fluid
function-related proteins such as lysozyme decreased 2-fold and a
plasma protein clusterin was up regulated 1.5-fold in conjunctival
tissue from glaucoma patients.
Conclusions: Proteomic analysis of conjunctiva demonstrates protein
profile of >1800 proteins and offers a powerful tool to further analyze
processes like inflammation and wound healing in glaucoma patients
who may be at risk from chronic use of glaucoma medications. It
will also give an opportunity to further analyze the role of pathogenic
mechanisms leading to failure in glaucoma surgery and to develop
novel therapies for glaucoma patients.
Commercial Relationships: Hannu M. Uusitalo; Antti Jylhä,
None; Janika Nättinen, None; Anu Vaajanen, None;
Miihkali Härkönen, None; Matti Nykter, None; Lei Zhou, None;
Roger W. Beuerman, None
Support: The Finnish funding agency of innovation grant
66/31/2012, Elsemay Björn Fund, Competitive Research Funding of
the Tampere University Hospital 9S071
Collagen VIII and XI as Biomarkers for Post-operative
Conjunctival Fibrosis
Tina T. Wong2, 3, Li Zhen Toh2, Stephanie Chu2, Jocelyn Chua1,
Li Fong Seet2, 3. 1Singapore National Eye Centre, Singapore National
Eye Centre, Singapore, Singapore; 2Ocular Therapeutics and Drug
Delivery, Singapore Eye Research Institute, Singapore, Singapore;
3
Duke NUS Medical School, Singapore, Singapore.
Purpose: Collagen, in particular collagen I, is the major extracellular
matrix responsible for the development and persistence of fibrosis.
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to access the versions of record.
The study aims to identify other collagen genes that may significantly
define subconjunctival fibrosis following experimental glaucoma
filtration surgery.
Methods: Subconjunctival scarring was induced using a mouse
model of glaucoma filtration surgery (GFS). The early and late
phases of wound healing were analyzed by RNA sequencing
(RNA-seq). The top ten highest expressed collagen genes in the
late phase were validated by quantitative polymerase chain reaction
(qPCR). Immunoblotting and immunolocalization were performed
to verify and determine the expression profiles of the top three
highest expressed collagen genes. Mouse and human conjunctival
fibroblasts were treated with TGF-β2 to determine the inducibility of
the collagen transcripts. Conjunctival tissues, collected from 20 and
15 patients requiring initial and repeat GFS respectively were also
analyzed by qPCR.
Results: RNA-seq identified Col8a1 (70-fold), Col11a1 (40-fold)
and Col8a2 (20-fold) as the three most highy expressed collagen
genes in the late phase conjunctival transcriptome. These collagens
were also induced at the protein level in late phase tissues. Type VIII
collagen co-localized with type I collagen in fibrous structures and
in ACTA-2-positive pericytes, appearing to fill gaps where type I
collagen was low. Type XI collagen showed little co-localization with
both collagens but was associated with the presence of macrophages.
TGF-β2 induced the top ten collagen genes in both mouse and human
conjunctival fibroblasts. Conjunctival tissues from eyes undergoing
repeat trabeculectomy surgery expressed 3.60-fold and 2.78-fold
increase in type VIII and I collagen transcripts respectively compared
to conjunctival tissues from primary trabeculectomy.
Conclusions: The high induction and unique expression profiles of
types VIII and XI collagen suggest that together with collagen I, form
a group of collagen biomarkers for the evaluation of fibrosis in the
mouse model of GFS and post trabeculectomies.
Commercial Relationships: Tina T. Wong, None; Li Zhen Toh,
None; Stephanie Chu, None; Jocelyn Chua, None; Li Fong Seet,
None
Support: NMRC/TCR/008/2013
Utility of purified collagenase (Xiaflex®) as a possible aid in
glaucoma surgery: A pilot study
Robert A. Honkanen1, Kevin Kaplowitz1, Edward Yung1,
Alan G. Fong1, Jonathan P. Wright2. 1Ophthalmology, SUNY
Stony Brook, Stony Brook, NY; 2School of Medicine, Stony Brook
University, Stony Brook, NY.
Purpose: Trabeculectomy ab externo (Trab) remains one of the
most commonly performed surgeries targeted at lowering intraocular
pressure (IOP). Post-operative episcleral fibrosis over the scleral
flap is a common cause of failure. Modulation of wound healing
with mitomycin C remains the current gold standard for inhibiting
post-operative scarring, and has been shown to extend bleb survival
to 30 days post-operatively in rabbits. We hypothesize that the use
of a purified collagenase Xiaflex® (Endo Pharmaceutical, {Dublin,
Ireland}) given perioperatively may extend the life of glaucoma
filtering surgery and re-establish filtration post-operatively in a rabbit
model of glaucoma filtering surgery.
Methods: 13 eyes of New Zealand White rabbits underwent limbalbased Trab without the use of antifibrotic agents by the same surgeon
(RH). Purified collagenase was delivered peri-operatively and
post-operatively by subconjunctival injections of 12.5 µl volumes at
varying concentrations. Post-operative filtration was assessed using
Moorfield grading of the bleb on examination and photographs, IOP
measurements via TonoPen®, fluorescein transmission through the
bleb, and ultrasound biomicroscopy (UBM). Clinical bleb failure
was defined as increase in IOP to baseline or failure of fluorescein
transmission. Eyes undergoing surgery without the administration of
collagenase were used as controls.
Results: Four eyes underwent both peri-operative and post-operative
injections of Xiaflex, with improved survival time by IOP and
fluorescein transmission compared to controls. Three of the four eyes
demonstrated clinical bleb survival beyond 30 days post-operatively.
Two of five eyes that underwent only post-operative injections
demonstrated an improved survival time compared to controls.
Four eyes in the control group demonstrated clinical bleb failure
between 11 and 14 days. Adverse events included subconjunctival
hemorrhage, eyelid ecchymosis, corneal ectasia and pannus, and
conjunctival breakdown. Moorfield grading and UBM was found to
be of limited value.
Conclusions: This pilot study preliminarily demonstrates that Xiaflex
can extend the life of glaucoma filtering surgeries. Best results
were obtained with peri-operative and post-operative injections of
the medication. Further work must be done to optimize dosage and
develop a delivery protocol prior to a formal efficacy study.
Commercial Relationships: Robert A. Honkanen;
Kevin Kaplowitz, None; Edward Yung, None; Alan G. Fong,
None; Jonathan P. Wright, None
Support: Unrestricted Investigator Initiated Research Award from
Endo Pharmaceuticals
Novel MRTF/SRF inhibitors prevent conjunctival scarring after
glaucoma filtration surgery: An ex vivo and in vivo study
Cynthia Yu-Wai-Man3, Richard M. Lee3, Scott Larsen1,
Richard Neubig2, Peng T. Khaw3. 1Vahlteich Medicinal Chemistry
Core, College of Pharmacy, University of Michigan, MI; 2Department
of Pharmacology and Toxicology, Michigan State University, MI;
3
National Institute for Health Research (NIHR) Biomedical Research
Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL
Institute of Ophthalmology, London, United Kingdom.
Purpose: Post-surgical scarring remains the main cause of failure of
glaucoma filtration surgery and current antimetabolites carry the risk
of potentially blinding complications. There is increasing evidence
that the Myocardin-related transcription factor/Serum response
factor (MRTF/SRF) pathway plays a pivotal role in myofibroblast
activation. We thus hypothesised that inhibiting the MRTF/SRF
pathway would reduce scarring in an aggressive rabbit model of
conjunctival fibrosis.
Methods: Ex vivo segments of rabbit conjunctiva were cultured in
100μM MRTF inhibitor 1 or PBS control and imaged for tissue area
changes over 30 days. We validated our results using a randomised,
prospective, masked-observer study of 24 New Zealand White female
rabbits undergoing glaucoma filtration surgery. The animals received
either intraoperative 0.2mg/ml mitomycin-C (MMC) [N=6] or
postoperative subconjunctival injections of 100μM MRTF inhibitor
1 [N=6] or 100μM MRTF inhibitor 2 [N=6] or PBS [N=6]. Bleb
morphology and intraocular pressure were recorded over 30 days.
Tissue sections were immunohistochemically graded on day 30. We
analysed our results using Kaplan-Meier curve Log-rank test and
Student’s t-test.
Results: Ex vivo conjunctival tissue contraction was significantly
reduced by 35%(day 6), 39%(day 15), 48%(day 21) and 68%(day
30) with inhibitor 1 compared to PBS (Fig 1). In vivo, bleb survival
was significantly improved with inhibitor 1 (p=0.01) and inhibitor
2 (p=0.0005) compared to PBS (Fig 2). The mean day of bleb
failure was 28.8 (range=24-30) for MMC, 28.5 (range=24-30) for
inhibitor 2, 24.5 (range=15-30) for inhibitor 1, and 14 (range=12-18)
for PBS. IOP also remained significantly lower with inhibitor 1
(p=0.027) and inhibitor 2 (p=0.0005) compared to PBS. MMC
treatment led to thin avascular blebs with destruction of the epithelial
layer. MRTF inhibitors however were not toxic and significantly
reduced conjunctival scarring using H&E, picrosirius red, Gomori’s
trichrome, and alpha-smooth muscle actin staining (p<0.05).
Conclusions: Novel MRTF inhibitors significantly improved bleb
survival and prevented conjunctival scarring. MRTF inhibitor 2 had
more potent anti-scarring effects than inhibitor 1. They were safe
for subconjunctival delivery and less destructive to local tissue than
MMC. MRTF inhibitors show potential as a novel class of antifibrotic agents in glaucoma filtration surgery.
Commercial Relationships: Cynthia Yu-Wai-Man;
Richard M. Lee, None; Scott Larsen, None; Richard Neubig,
None; Peng T. Khaw, None
Support: The National Institute for Health Research (NIHR)
Biomedical Research Centre at Moorfields Eye Hospital NHS
Foundation Trust and UCL Institute of Ophthalmology, the Medical
Research Council, the Special Trustees of Moorfields Eye Hospital,
the Freemasons Grand Charity, the Michael and Ilse Katz Foundation,
the Helen Hamlyn Trust, and Fight for Sight (UK).
Effects of rho-associated protein kinase inhibitor Y-27632 on
scarring formation after glaucoma filtration surgery
Hideaki Okumichi, Wakana Iwata, Satoshi Okimoto, Ji-Ae Ko,
Yoshiaki Kiuchi. Department of Ophthalmology and Visual Science,
Institute of Biomedical and Health Sciences, Hiroshima University,
Hiroshima, Japan.
Purpose: Glaucoma filtration surgery usually fails because of post
surgical scarring, a process in which fibroblasts play a prominent
role. To elucidate the effects of rho-associated protein kinase (ROCK)
inhibitor Y-27632 in post surgical scarring (fibrosis), we have now
investigated the molecular mechanism with human tenon fibroblasts.
Methods: Human tenon fibroblasts were cultured with Y-27632 or
various antiglaucoma drugs for indicated periods. After cultivation,
we have prepared total RNA and protein samples from tenon
fibroblasts. Using multiple RT-PCR array, we examined the factors
respond to Y-27632. And, we have studied the expression of factor(s)
of relating scarring formation using RT-PCR, immunoblot and
immunofluorescence analysis. Also, we have examined the threedimensional collagen gels cultivation for gel contraction by various
antiglaucoma drugs.
Results: Collagen gel contraction by tenon fibroblasts was blocked
in the presence of Y-27632. In multiple RT-PCR array using fibrosisrelated genes, the expression of MMP-3 was down-regulated in tenon
fibroblasts by additional Y-27632. Furthermore, immunoblot and
immunoflurorescence analysis revealed that the expression of fibrosis
markers was down-regulated in the presence of Y-27632.
Conclusions: These results suggest that the ROCK inhibitor
Y-27632 may block scarring formation with interaction MMP-3 after
glaucoma surgery. And, it will be possible that ROCK inhibitors
and MMP-3 may have potential to be developed for treatment of
glaucoma and other ocular diseases.
Commercial Relationships: Hideaki Okumichi, None;
Wakana Iwata, None; Satoshi Okimoto, None; Ji-Ae Ko, None;
Yoshiaki Kiuchi, None
Effects of ripasudil (K-115), a Rho kinase inhibitor, on the
activation of human conjunctival fibroblasts
Akiko Futakuchi, Toshihiro Inoue, Tomokazu Fujimoto,
Miyuki M. Inoue, Hidenobu Tanihara. Ophthalmology, Kumamoto
University Hospital, Chuo-ku, Kumamoto city, Japan.
Purpose: Ripasudil, a selective Rho kinase inhibitor, is an
ophthalmic solution which was approved in Japan for the twice-daily
treatment of glaucoma and ocular hypertension in 2014. The purpose
of this study is to assess the effects of ripasudil on the activation of
human conjunctival fibroblasts.
Methods: Human conjunctival fibroblasts were pretreated with or
without different concentrations of ripasudil (25 and 50 μM) for
1 hour and subsequently stimulated with 5 ng/ml TGF-β2 for 48
hours. The effects of ripasudil on α-smooth muscle actin (α-SMA)
expression and extracellular matrix (ECM) expression were analyzed
by Western blot analysis. Contractile activity was evaluated by
collagen gel contraction assay. Cell viability and cytotoxicity were
assessed using WST-8 assay and Hoechst 33342/propidium iodide
(PI) dual staining, respectively. The human monocytic cell line
THP-1 were differentiated into M1- and M2-like macrophages, and
fibroblasts were treated with conditioned medium derived from these
macrophages in the presence or in the absence of 50 μM ripasudil to
quantify the α-SMA expression level.
Results: TGF-β2-treated fibroblasts showed a significant increase
(p < 0.0001), 38 ± 4-fold in the expression of α-SMA compared
with controls without TGF-β2 stimulation. When fibroblasts were
pretreated with ripasudil before TGF-β2 stimulation, α-SMA
expression was significantly decreased in a dose-dependent manner
(25 and 50 μM, respectively, p < 0.01). Ripasudil pretreatment
significantly attenuated TGF-β2-induced fibronectin expression (p
< 0.0001). Ripasudil pretreatment significantly attenuated TGF-β2induced collagen gel contraction (p < 0.0001). TGF-β2 increased
the proliferation of fibroblasts (p < 0.0001), and the effect was
significantly attenuated by ripasudil (p < 0.0001). Ripasudil did not
cause any cellular toxicity at the tested doses. Conditioned medium
from M2-like macrophages induced a significant increase (p < 0.001),
3.4 ± 0.7-fold in the expression of α-SMA, and ripasudil suppressed
this upregulated expression (p < 0.01).
Conclusions: Ripasudil attenuated the activation of human
conjunctival fibroblasts. Our results suggest that ripasudil might have
a therapeutic potential in the prevention of excessive scarring after
glaucoma filtration surgery.
Commercial Relationships: Akiko Futakuchi; Toshihiro Inoue,
None; Tomokazu Fujimoto, None; Miyuki M. Inoue, None;
Hidenobu Tanihara, Alcon Japan (S), MSD (C), Pfizer Japan (S),
Kowa (C), Santen Pharmaceutical (S), Senju Pharmaceutical (S)
Support: Kowa Company, Ltd., Nagoya, Japan.
Anti-fibrotic effect of a multilayered nanoparticle system for
delivery of siSPARC in a mouse model of experimental glaucoma
surgery
Yang Fei Tan1, 2, Li Fong Seet2, Li Zhen Toh2, Subbu Venkatraman1,
Tina T. Wong2, 1. 1Nanyang Technological University, Singapore,
Singapore; 2Singapore Eye Research Institute, Singapore, Singapore.
Purpose: Post-operative scarring following glaucoma filtration
surgery is the major obstacle for any long-term surgical success.
Therapeutic application of siRNAs is challenging due to
sustainability of gene silencing and limits its potential effect. The
secreted protein, acidic and rich in cysteine (SPARC) is a protein
involved in extracellular matrix (ECM) production and organisation.
The purpose of the study is to investigate the sustainability in siRNA
silencing by using of a multilayered nanoparticle system for siSPARC
in the prevention of fibrosis in a mouse model of conjunctival
scarring.
Methods: Double SPARC siRNA layered layer by layer
nanoparticles was fabricated with hydroxyapatite (HA) as
the core and poly-L-arginine (ARG) as protective layers
(HA|ARG|siRNA|ARG|siRNA|ARG). Modified glaucoma filtration
surgeries were performed on 50 mice. At the end of each surgery,
mice were injected with either siSPARC-loaded nanoparticles (n=50)
or with nanoparticles loaded with scrambled siRNA (n=50). The
mice were sacrificed on days 7 and 14, and the conjunctival tissues
harvested. qPCR was performed on the tissues to quantify SPARC
and collagen I expression. Western blot analysis was also performed
on day 7.
Results: Knock down of SPARC was observed and maintained at
34.25% (P= 0.046) on Day 7 and 36.79% (P = 0.049) on Day 14.
Collagen expression was reduced by 47.05% (P = 0.0031) on day
7 and 29.52% (P = 0.047) on Day 14. Both SPARC and collagen I
protein expression was decreased on Day 7.
Conclusions: A multi-layered nanoparticle system provides
prolonged siSPARC knock down and a reduction in postoperative
fibrosis following experimental glaucoma surgery. Delivery of siRNA
using a nanoparticles platform is a promising method for developing
sustained siRNA therapeutics for treatment of fibrosis.
Commercial Relationships: Yang Fei Tan, None; Li Fong Seet,
None; Li Zhen Toh, None; Subbu Venkatraman, None;
Tina T. Wong, None
The antiproliferative effect of bevacizumab on human tenon
fibroblasts is presumably not through VEGF inhibition
Charlotte Fischer, Viktoria Mans, Nicolas Feltgen, Hans Hoerauf,
Christian van Oterendorp. Ophthalmology, University medicine
Goettingen, Germany, Goettingen, Germany.
Purpose: Bevacizumab has previously been shown to reduce
proliferation and myofibroblast transdifferentiation of human
tenon fibroblasts (hTF). Data from previous publications suggest a
direct toxic effect of bevacizumab. We have investigated whether
bevacizumab acts on hTF via inhibition of VEGF or rather through a
non-antigen dependent effect.
Methods: Primary cultures of hFT were treated with bevacizumab
(2.5 to 10 mg/ml), ranibizumab (2,5mg/ml) or aflibercept (5mg/
ml to 10mg/ml) for 24h. Proliferation was quantified by cell counts
and staining for viable and dead cells (LIVE/DEAD ® cell imaging
kit, Life Technologies). Immunostainings and western blot were
performed for detection of intracellular IgG. Bevacizumab-Antibody
and its solvent buffer were separated by membrane filtering
(Amicon® Ultra-30k, Merck Millipore).
Results: Bevacizumab significantly inhibited cell proliferation
in concentrations of 5mg/ml and 10mg/ml (1,2±0,8 (mean and
SEM) and 0,001±0,0005 cells/mm2, respectively), in comparison to
untreated controls (32,4±2,3 cells/mm2; p<0,0001), whereas 10mg/
ml aflibercept (53,4±4,8 cells/mm2) and 2,5mg/ml ranibizumab
(35,4±2,8 cells/mm2) did not decrease proliferation. Staining for dead
cells showed a significant increase 24h after incubation with 5mg/
ml bevacizumab (21,1±2,5 cells/mm2) compared to untreated cells
(4,3±0,7 cells/mm2; p<0,0001), or aflibercept (4,7±2,0 cells/mm2)
or ranibizumab (4,6±0,8cells/mm2) treated cells in concentrations
bioequivalent to 5mg/ml bevacizumab. Exposure of hTF with either
the bevacizumab solvent buffer without protein or the pure antibody
in PBS did not inhibit cell proliferation, however, the number of
dead cells was increased with the solvent buffer (16,3±3,4 vs 4,6±0,9
cells/mm2; p=0,0085). IgG was detected in intracellular vesicles after
incubation with bevacizumab in a dose depended manner. The same
was observed with pure bevacizumab antibody in PBS as well as
aflibercept but without the antiproliferative and cell death inducing
effect.
Conclusions: Bevacizumab, but not aflibercept or ranibizumab at
equivalent concentration, inhibits cell proliferation and promotes
cell death in hTF. This suggests a non-VEGF-dependent effect of
bevacizumab, which might, in part, be mediated by its solvent buffer.
Commercial Relationships: Charlotte Fischer, None;
Viktoria Mans, None; Nicolas Feltgen, None; Hans Hoerauf,
None; Christian van Oterendorp, None
Lipid nanoemulsion associated with paclitaxel as a new
antiscarring agent in experimental glaucoma surgery
Vital P. Costa1, Marcelo Occhiutto1, Fatima R. Freitas2,
Patricia Picciarelli2, Raul Maranhao2. 1Ophthalmology, University of
Campinas, Sao Paulo, Brazil; 2INCOR, University of Sao Paulo, Sao
Paulo, Brazil.
Purpose: To investigate the effects of paclitaxel associated to lipid
nanoemulsions (LDE-PTX) upon postoperative scarring in rabbits
undergoing trabeculectomy.
Methods: Thirty-four New Zealand rabbits that underwent
trabeculectomy were allocated to 4 groups: LDE-PTX/SC (n=9),
treated with one intraoperative subconjunctival injection of LDEPTX(1.5 mg); LDE-PTX/IV (n=9), treated with LDE-PTX (4mg/
kg/day intravenously) at the end of the surgery and once a week
for 3 weeks; MMC(n=9), treated with intraoperative 0.4 mg/
mL mitomycin-C for 3 minutes; and control group (CTL, n=7),
without treatment. Bleb characteristics, anterior chamber depth and
intraocular pressure were evaluated over 4 weeks by a maskedobserver. Bleb failure was defined when a flat, scarred, vascularized
bleb was observed in association with a deep anterior chamber.
Animals were sacrificed on day 28. Histologic analyses were
performed to assess the amount of scarring and toxicity to the
conjunctiva and ciliary body.
Results: Groups were similar with respect to intraocular pressure and
anterior chamber depth during the 28-day observation period. LDEPTX/SC,LDE-PTX/IVand MMCgroups showed greater bleb height
than controls on days 14 and 21 (p<0.01). The median survival times
were 14, 21, 28 and 28 days for the CTL, LDE-PTX/IV, LDE-PTX/
SC and MMC groups, respectively. LDE-PTX/SC, LDE-PTX/IV
and MMC showed significantly longer bleb survival times than CTL
(p<0.001). There were no significant differences in survival times
among the 3 treatment groups (p>0.05). LDE-PTX/SC,LDE-PTX/
IV and MMC were equally effective in reducing fibrosis (p<0.001),
number of blood vessels (p<0.001) and chronic inflammatory cells
(p<0.001) at the surgical site. However, LDE-PTX/SC and LDEPTX/IV treatments had lower conjunctival and ciliary body toxicity
(p<0.001) compared to MMC.
Conclusions: Both LDE-PTX/SC and LDE-PTX/IV were effective
in reducing the scarring process following trabeculectomy to the
same extent as mitomycin C, but with considerably less toxicity
to the conjunctiva and ciliary body. The novel preparation in both
administration routes may offer promising results for wound healing
modulation in the surgical treatment of glaucoma.
Commercial Relationships: Vital P. Costa, New World Medical
(F), Genom (F), Merck (F), Alcon (F), Solx (F), Merck (C),
Alcon (C); Marcelo Occhiutto, None; Fatima R. Freitas, None;
Patricia Picciarelli, None; Raul Maranhao, None
Effects of gelatin hydrogel containing transforming growth
factor-β antibody in a canine filtration surgery model
Michiko Miki1, Shota Kojima1, Tetsuya Sugiyama2, Denan Jin3,
Shinji Takai3, Ryohsuke Kohmoto1, Mari Ueki1, Tsunehiko Ikeda1.
1
ophthalmology, Osaka Medical College, Takatsuki-city, Japan;
2
Nakano Eye Clinic, Kyoto, Japan; 3Pharmacology, Osaka Medical
College, Takatsuki, Japan.
Purpose: A phase-III study (CAT-152 0102 Trabeculectomy Study
Group; Ophthalmology, 2007) of a subconjunctival two-time
injection of transforming growth factor-β2 (TGF-β2) antibody
failed to find any significant effects on preventing the progression of
fibrosis after trabeculectomy. In this present study, we investigated
the effect of a controlled release of TGF-β antibody in a canine model
of glaucoma filtration surgery using gelatin hydrogel (GH).
Methods: Glaucoma surgery models were made in 10 beagles
according to our previous report (Kojima et al.; IOVS, 2011),
and the eyes being divided into the following three groups: 1)
subconjunctival implantation of TGF-β antibody-loaded GH (GHgroup eyes, n=7), 2) subconjunctival implantation of GH alone
(Control-group eyes, n=7), and 3) subconjunctival injection of TGF-β
antibody (Injection-group eyes, n=6). Intraocular pressure (IOP) and
bleb features were then assessed in each eye at 2-weeks and 4-weeks
postoperative, followed by histological evaluation.
Results: No significant decrease in IOP was found in the Injectiongroup eyes, but IOP was significantly reduced at 4-weeks
postoperative in the other two groups (p<0.05) and IOP in the
GH-group eyes was significantly lower compared with Controlgroup eyes. In the Injection-group eyes, the bleb score at 4-weeks
postoperative was significantly lower than the other two groups. The
numbers of fibroblasts, proliferative-cell nuclear antigen-positive
cells, mast cells, and TGF-β antibody-positive cells were significantly
lower in the GH groups than in the control group.
Conclusions: The findings in this study suggest that compared with
subconjunctival injection, implantation of TGF-β antibody-loaded
GH maintains IOP reduction and bleb formation by suppressing
conjunctival scarring due to proliferation of fibroblasts for a longer
time via a sustained release of TGF-β antibody from GH.
Commercial Relationships: Michiko Miki, None; Shota Kojima,
None; Tetsuya Sugiyama, None; Denan Jin, None; Shinji Takai,
None; Ryohsuke Kohmoto, None; Mari Ueki, None;
Tsunehiko Ikeda, None
Effect of Uveitis Activity on Surgical Outcomes in Uveitic
Glaucoma
Hye Jin Kwon1, 2, William L. Tao1, Lyndell L. Lim1, 2,
Jonathan G. Crowston1, 2, Jonathan Ruddle1, 2, George Y. Kong1, 2.
1
Department of Ophthalmology, Royal Victorian Eye and Ear
Hospital, East Melbourne, VIC, Australia; 2Department of
Ophthalmology, Centre for Eye Research, East Melbourne, VIC,
Australia.
Purpose: Surgical treatment in managing uveitic glaucoma is often
difficult due to its complex balance between inflammation and
intraocular pressure control. We have conducted a retrospective
study to examine surgical outcomes of trabeculectomy and glaucoma
drainage implant (GDI) surgery in uveitic glaucoma. In particular,
we examined the effect of uveitic activity at the time of surgery or
following surgery on surgical outcomes.
Methods: Retrospective chart review of 82 consecutive cases with
uveitic glaucoma who underwent either trabeculectomy or GDI
surgery between 2006 and 2014 at Royal Victorian Eye and Ear
Hospital. Primary outcome measures were based on conesnsus
definition from World Glaucoma Association.
Results: 54 eyes underwent trabeculectomies and 28 eyes underwent
GDI surgery, of which 12 were primary GDIs. Mean age of patients
was 50 ±2.35 (8-85) years. Follow up duration was 25.1±2.33 (3-125)
months.
37% trabeculectomies and 57.1% GDIs had anterior uveitis. 65.9%
trabeculectomies and 34.1% GDIs were steroid responders. All
trabeculectomies were performed with an antimetabolite. In GDIs,
21 had Baerveldt tubes and 7 had Molteno tubes. At final follow
up, similar Qualified Success rate was observed in trabeculectomies
(64.8%) and in GDIs (64.2%). No significant difference was observed
between Primary and secondary GDIs (58.3 vs 68.8%, p= 0.70). A
higher rate of Absoulte Success was achieved in trabeculectomies
(48.1% trabs vs 21.4% GDIs, p=0.03). 35.2% of trabeculectomies
and 3.5% of GDIs had active uveitis at the time of surgery(p<0.01).
Uveitic activity at the time of surgery was not associated with
increased risk of failure in our trabeculectomy group (p=0.91).
Overall, uveitis flare up was observed in 43.9% of all cases following
surgery. In trabeculectomies, there was a trend for decreased success
rate in those who had uveitis flare up. 60% of those with flare up
compared to 85.7% of those without flare up achieved Qualified
Success, although not reaching statistical significance (p=0.16).
Similar but lesser trend was also observed in GDIs, 54.5% with flare
up compared to 71.4% without flare up achieved Qualified Success
(p=0.64).
Conclusions: No significant difference in success rate between
trabeculectomies and GDIs in management of uveitic glaucoma in
this series. Good control of post operative uveitis activity should
be considered to ensure success of glaucoma surgery for uveitic
glaucoma.
Commercial Relationships: Hye Jin Kwon; William L. Tao,
None; Lyndell L. Lim, None; Jonathan G. Crowston, None;
Jonathan Ruddle, None; George Y. Kong, None
Subconjunctival injection vs surgical sponge application of
mitomycin-C (MMC) during trabeculectomy in a county clinic
Mallika Doss1, 2, Alice Z. Chuang1, Lauren Blieden1, 2. 1Ruiz
Department of Ophthalmology and Visual Science, The University of
Texas Health Science Center (UTHealth) McGovern Medical School,
Houston, TX; 2Robert Cizik Eye Clinic, Houston, TX.
Purpose: Evaluate short-term bleb failure and complication rates
using subconjunctival injection or conventional sponge application of
MMC.
Methods: Patients who underwent trabeculectomy with MMC
between 2010 and 2014 at the Lyndon B. Johnson Hospital were
included in this matched case-control study. A participant was
assigned to the injection group if MMC was delivered by injection
and was matched with a patient where MMC was delivered by
sponge. Eyes were matched based on patient age (±5 years) and
race. Eyes were excluded if there was concomitant surgery or prior
scarring. If both eyes underwent injection, only one eye was included
in the study. Bleb failure was defined as hypotony or restarting
IOP-lowering medications. Because the injection method was first
employed in 2013, only 6 month data was available and recorded.
Results: Thirteen eyes in each study group were included. Baseline
characteristics were similar, including mean treated IOP which was
24.6 mmHg (±9.2) and 24.3 mmHg (±9.8) for injection and sponge
group, respectively. Ten (77%) eyes in the injection group versus 6
(46%) eyes in the sponge group underwent argon laser suture lysis.
Two patients in each group required early bleb needling. Neither
group had major intraoperative or postoperative complications nor
underwent a second glaucoma surgery during the study timeframe.
At 6 months, IOP reductions were similar [11.2 mmHg (±9.3) for
injection and 11.9 mmHg (±12.0) for sponge]. Eight (62%) eyes in
the injection group versus 5 (38%) of eyes in the sponge group were
on IOP-lowering medications by 6 months after surgery (Table 1).
The mean number of medications in the injection group was 1.5
while it was 2 in the sponge group.
Conclusions: In a county clinic setting, MMC delivery via
subconjunctival injection has a similar complication rate to sponge
delivery at 6 months, but a larger percentage of eyes in the study
group were restarted on IOP-lowering medications. However, there
may be a selection bias toward success in the sponge group because
they may not have been selected if they had early failure. A larger
study is required to further look into this surgical technique.
Table 1. Demographics, Ocular Baseline Characteristics, and
Outcomes
Commercial Relationships: Mallika Doss, None; Alice Z. Chuang;
Lauren Blieden, None
Support: National Eye Institute Vision Core Grant P30EY010608,
a Challenge Grant to The University of Texas Health Science Center
(UTHealth) McGovern Medical School from Research to Prevent
Blindness, and the Hermann Eye Fund
Comparison of intraoperative injection of Mitomycin (MMC)
versus conventional sponge-applied MMC during double site
phaco-trabeculectomy
Vivek Pullutipadath Sasikumar1, Shani Reich2, Manju Pillai1,
Avika Kanathia1, Shanthi Priya1, Prathiba S1, Janet Serle2. 1Aravind
Eye Center, India, India; 2Ophthalmology, Icahn School of Medicine
of Mount Sinai Hospital, New York, NY.
Purpose: To study the safety and efficacy of intraoperative injection
of Mitomycin (MMC) versus conventional sponge-applied MMC
during double site phaco-trabeculectomy (PT) in a cohort of patients
from Southern India
Methods: POAG and PXFG patients were prospectively randomized
to intra-op injection of 0.1ml of 0.1 mg/ml MMC or 2 sponges
soaked in 0.4 mg/ml MMC applied for 2 minutes. Demographics,
visual acuity (VA), intraocular pressure (IOP), number of glaucoma
medications, post-op complications, interventions, additional surgery
were collected at baseline, post-op: day 1, week 2, month 1, 3, and 6.
Mean, T-test, or chi-square tests were performed. The surgeries were
performed by multiple surgeons in a single center.
Results: 71 eyes were included: 36 injection group, and 35 sponge
group. Pre-op IOP, number of glaucoma medications (2.3±0.4), and
VA (6/24) was similar (p >0.418) between groups. Pre-operative IOP
(mean mmHg±SD) was 22.8±7.0 in the injection group and 21.6±6.0
in the sponge group. At 6 months, IOP was decreased (P <0.001)
in both groups to 13.3±2.6 (36.3%) in the injection and 16.3±3.4
(20.1%) in the sponge group and was lower (P <0.0001) in the
injection group than in the sponge group. All patients in the injection
group achieved complete or qualified surgical success at 6 months,
defined as IOP<21 with or without medication and no complications,
whereas only 42.8% of the patients in the sponge group had complete
or qualified surgical success (P <0.001). 8% of patients in the
injection group and 25% of patients in sponge group required one
of more glaucoma medications postop (p = 0.05). Post-op vision
was similar (p=.554) in both groups, and improved (p<.001) from
baseline. Complications included two cases of hyphema and one case
of endophthalmitis which all occurred in the sponge group.
Conclusions: Subconjunctival injection of MMC during PT was safe
and more effective than conventional sponge application of MMC
with greater IOP reduction and more patients with surgical success.
Longer follow-up of a larger cohort is needed to further characterize
the efficacy and safety of this modality.
Commercial Relationships: Vivek Pullutipadath Sasikumar;
Shani Reich, None; Manju Pillai, None; Avika Kanathia, None;
Shanthi Priya, None; Prathiba S, None; Janet Serle, nicox (F),
allergan (F), aerie (C), ono (C)
Support: This study was supported in part by The Fund for
Ophthalmic Knowledge, New York, NY and an unrestricted grant
from Research to Prevent Blindness Inc, New York, NY
Clinical Trial: Institutional Review Board, IRB201400155
Does type of postoperative anti-glaucoma drug affect
morphological changes of filtering bleb after trabeculectomy? –
Utilizing the data from the Collaborative Bleb-Related Infection
Incidence and Treatment Study
Yuji Yamamoto1, Kazuhiko Mori1, Isao Yokota2, Yoko Ikeda1,
Morio Ueno1, Kojiro Imai1, Haruna Yoshikawa1, Satoshi Teramukai2,
Shigeru Kinoshita1, Chie Sotozono1. 1Ophthalmology, Kyoto
Prefectural University of Medicine, Kyoto, Japan; 2Biostatistics,
Kyoto Prefectural University of Medicine, Kyoto, Japan.
Purpose: Various factors affect the morphological changes of
filtering blebs post trabeculectomy (TLE). The purpose of this
present study was to investigate whether the type of postoperative
anti-glaucoma medication (anti-GM) affects the changes of bleb
morphology utilizing data from the Collaborative Bleb-Related
Infection Incidence and Treatment Study (CBIITS), a multicenter
prospective cohort study conducted by the Japan Glaucoma Society
(Yamamoto et al., Ophthalmology 2014).
Methods: This study involved 51 glaucoma patients (32 males and
19 females, mean age: 64.8) out of 1098 cases from the CBIITS
data sets. They were prescribed either prostaglandin analogues (PG
Group) or β blockers (β-blocker Group) over a less-than 6-month
time period. Patients with no bleb shape information, whose bleb had
become smaller than the scleral flap size at 6-months post TLE, or
who had undergone needling in less-than 6-months post TLE were
excluded from the study. Bleb morphology was evaluated by the bleb
characteristics of width (W) and depth (D). Bleb shape was described
at 6-month intervals throughout the 5-year follow-up period, and
each characteristic was compared between the two groups. Time to
bleb failure was defined as the time from TLE until bleb failure, i.e.,
blebs became smaller than the scleral flap size (W and D) or had
undergone needling. Cox proportional hazards regression model was
used to examine the effects of the type of postoperative anti-GM after
adjustment for sex, age, those combined with phacoemulsification
and intraocular lens implantation or not, and those with a fornixbased flap or with a limbal-based flap.
Results: Of the 1098 cases, 33 cases were PG Group and 18 cases
were β-blocker Group. The failure-free advantage in favor of the
PG Group was not significant in the characteristic of W (p=0.16,
hazard-ratio (HR): 0.52; 95%CI: 0.21-1.32; median follow-up time:
42 months], and D [p=0.12, HR: 0.50; 95% CI: 0.20-1.20; median
follow-up time: 36 months]. However, the failure-free period of the
PG Group was longer than those of the β-blocker Group during the
5-year follow-up period.
Conclusions: The findings of this observational study show that the
use of PG following TLE may maintain filtering blebs better than
β-blocker.
Commercial Relationships: Yuji Yamamoto; Kazuhiko Mori,
None; Isao Yokota, None; Yoko Ikeda, None; Morio Ueno, None;
Kojiro Imai, None; Haruna Yoshikawa, None; Satoshi Teramukai,
None; Shigeru Kinoshita, None; Chie Sotozono, None
Safety and Efficacy of Trabeculectomy with Mitomycin C
Injection
Sze H. Wong1, Scott M. Walsman2, 1, Albert S. Khouri1. 1Institute of
Ophthalmology and Visual Science, Rutgers New Jersey Medical
School, Newark, NJ; 2Hudson Eye Physicians and Surgeons, Jersey
City, NJ.
Purpose: Trabeculectomy is traditionally performed with the
placement of mitomycin-C (MMC) soaked sponges subconjunctivally
to prevent fibrosis; however, the use of injected MMC has become
popular. We evaluated the safety and efficacy of injecting MMC in
trabeculectomy.
Methods: We performed a retrospective chart review on
trabeculectomies with MMC injection performed by one surgeon
(SMW). MMC 0.4 mg/mL was first diluted 50:50 with 2% lidocaine,
then 0.2 mL of the mixture (equivalent to 40 μg MMC) was injected
subconjunctivally in the beginning of surgery prior to subconjunctival
space dissection and scleral flap creation. Inclusion criteria were age
18 to 100 years and uncontrolled intraocular pressure (IOP) despite
maximum tolerated medical therapy. Exclusion criteria were no
light perception vision, pregnant or nursing women, uveitis, superior
conjunctival scarring, and previous trabeculectomy or tube shunt
surgery in the same eye. Student T-tests between different time points
and ethnicities were performed. Kaplan-Meier curve for absolute
success was generated.
Results: A total of 66 eyes were reviewed. Average follow-up time
was 15.9±9.4 months. Significant IOP lowering was observed at all
postoperative time points, as shown in Graph 1 (P<0.01). Number
of glaucoma medications decreased from 3.6±0.5 preoperatively
to 0.1±0.4 at last follow-up (P<0.01). Visual acuity remained
unchanged at 0.4±0.4 logMAR (P=0.48). Postoperative failure
was defined as IOP ≤5 mmHg or >21 mmHg in two consecutive
visits, IOP not reduced by 20% from preoperative IOP in two
consecutive visits, reoperation for glaucoma, or loss of light
perception vision. Cumulative probability of failure during 2 years
of follow-up was 12.5%. Postoperative complications are listed in
Table 1. African American eyes (n=29) had undergone significantly
more 5-fluorouracil injections (P<0.01), laser suture lysis
procedures (P<0.01), and longer topical steroid duration (P<0.04)
postoperatively, compared with Caucasian eyes (n=20).
Conclusions: Injecting 40 μg of MMC in trabeculectomy appeared
effective, and the complication rate was comparable to MMC sponge
historic data. Additional treatments were needed to prevent bleb
failure in African American eyes. A prospective study with longer
follow-up is needed to compare the outcomes of MMC injection
versus MMC-soaked sponges in trabeculectomy.
between the two groups (p >0.05). Few complications were found
in both groups, no significance difference was found between them
(p>0.05). Both groups required less antiglaucomatous medications,
the difference was statistically significant between pre and post
surgery medications (p<0.05) but there was no difference in the
comparison between both groups (p>0.05).
Conclusions: Non-penetrating deep sclerectomy proved to be safe
and an effective technique in open-angle glaucoma patients and the
control of IOP was comparable with the trabeculectomy. Long term
follow-up is needed to confirm our results.
Commercial Relationships: David Berrones Medina;
Alberto Hernández-Vargas, None; JESUS JIMENEZ-ARROYO,
None; Armando Castillejos- Chévez, None; Jesus JiménezRoman, None
Commercial Relationships: Sze H. Wong, None;
Scott M. Walsman, None; Albert S. Khouri, None
Non-penetrating deep sclerectomy versus trabeculectomy for
open angle glaucoma in Mexican population
David Berrones Medina, Alberto Hernández-Vargas,
JESUS JIMENEZ-ARROYO, Armando Castillejos- Chévez,
Jesus Jiménez-Roman. Ophthalmology, Asociación para Evitar la
Ceguera en Mexico, Mexico City, Mexico.
Purpose: To compare the safety and effectiveness of non-penetrating
deep sclerectomy (NPDS) surgery and conventional trabeculectomy
in patients with open angle glaucoma and their complications.
Methods: Case series, prospective and longitudinal study of patients
with medically uncontrolled open-angle glaucoma who underwent
glaucoma surgery. They were divided in 2 groups, one treated with
conventional trabeculectomy and the other with non-penetrating deep
sclerectomy, each group with 13 eyes. We compared in both groups
preoperative and postoperative intraocular pressure (IOP) at the first
day, first month, six months and one year, best-corrected visual acuity
(BCVA), visual field mean deviation, number of antiglaucomatous
medications, and complication rates. The follow-up was one year
after surgery. Data were analyzed with IBM SPSS® statistics v.21.
Results: We included 26 eyes of twenty patients, 13 male (50%)
and 13 female (50%). The mean age of the trabeculectomy group
was 59 years (SD 11.01) and 62.84 years (SD 14.78) in the NPSD
group; twenty four patients (92%) had primary open-angle glaucoma
and two patients (8%) had secondary open-angle glaucoma. The
mean BCVA for the trabeculectomy group was 0.16 logMAR, and
0.40 logMAR for the NPDS group. The preoperative IOP for the
trabeculectomy group was 15.69 mmHg (SD 2.87) and 17.69 mmHg
(SD 6.77) for the NPDS; the postoperative IOP at the first month
was 11.76 mmHg (SD 1.76) in the trabeculectomy group and 11.18
mmHg (SD 2.78) in the NPDS group; at six months was 13.23 mmHg
(SD 3.72) in the trabeculectomy group and 13.46 mmHg (SD 2.93)
in the NPDS group; at one postoperative year, the IOP was 14.30
mmHg (SD 2.75) in the trabeculectomy group and 14.23 mmHg (SD
2.94) in NPDS group. No significance difference was found over time
Attaining intraocular pressure of 10 mmHg or less: a comparison
of tube and trabeculectomy surgery in eyes with pseudophakic
glaucoma and initial glaucoma surgery
Alissa Meyer, Khalil Harbie, Cooper Rodgers, Nicole Rosenberg,
Mark B. Sherwood. Ophthalmology, University of Florida,
Gainesville, FL.
Purpose: Patients with advanced glaucoma can need IOP’s below
the normal range to prevent further glaucomatous progression.
Trabeculectomy surgery with anti-fibrotic supplementation and
glaucoma drainage device (GDD) surgery have been the common
surgical methods to lower IOP when medication is insufficient. The
TVT study1 suggested similar mean IOP’s in the low teen level with
both techniques. However, for patients that require very low IOP’s
(10 or less) it is unclear which surgical procedure is more likely to be
successful.
Methods: A retrospective, single-center review of 60 pseudophakic
patients with a diagnosis of POAG, Pseudoexfoliation or Pigmentary
glaucoma, undergoing either a GDD implant or a trabeculectomy
with adjunctive antifibrosis therapy as an initial glaucoma procedure
(n=28 for GDD and n=32 for trab). Patient demographics,
preoperative and postoperative IOP’s, visual acuities, ocular
medications, complications, and need for additional surgeries were
recorded.
Results: Demographically, there was no significant difference
between the groups for age, gender and diagnoses but there were
more African Americans in the Tube group (39% versus 13%).
Mean IOP’s at 1, 3, and 4 years post-op were 13.1 (SD=5.4), 12.6
(SD=5.7), 13.5 (SD=6.4) mmHg, and 8.9 (SD=5.0), 7.3 (SD=3.6), 6.9
(SD=3.9) mmHg for the drainage implant and trabeculectomy groups
respectively. The IOP’s were statistically different at all these timepoints (p<0.05). The number of patients with a mean IOP 10 mmHg
or less at 2 years was 5/19 (26.3%), for the GDD patients and 15/23
(65.2%), for trabeculectomy patients (p=0.028). At 3 years worsening
of visual acuity (2 lines Snellen or more) occurred in 4/16 patients
in the GDD group, with 4/16 improving 2 lines or more. 3/21 in the
Trabeculectomy group worsened, with 2/21 improving. There were
no significant differences between the two procedures for decrease of
visual acuity at 1, 2, 3 or 4 years.
Conclusions: Trabeculectomy gives lower mean IOP and is more
likely to provide a pressure of 10 or less than GDD’s in pseudophakic
primary glaucoma patients with no differences noted in visual acuity.
1. Gedde, S. J., Schiffman, J. C., Feuer, W. J., et al. (2012). Treatment
outcomes in the Tube Versus Trabeculectomy (TVT) study after five
years of follow-up. Am J Ophthalmology, 153(5), 789–803.
Commercial Relationships: Alissa Meyer; Khalil Harbie,
None; Cooper Rodgers, None; Nicole Rosenberg, None;
Mark B. Sherwood, None
Changes in Cup-to-Disc Ratio Following Trabeculectomy
Cassie N. Confait, Omolola Idowu, Meghan Moroux. Ophthalmology,
University of Mississippi Medical Center, Madison, MS.
Purpose: To evaluate the changes in cup-to-disc area ratio as seen
on confocal scanning laser ophthalmoscopy (CSLO) following
trabeculectomy in patients with primary open angle glaucoma and to
determine the correlation of post-operative intraocular pressure with
any changes in cup-to-disc ratio observed.
Methods: Individual patient records for all patients that underwent
trabeculectomy at the University of Mississippi Medical Center
between 2007 and 2014 were reviewed in a retrospective chart review
series. Pre-operative and post-operative intraocular pressure (IOP)
and cup-to-disc area ratio (C:D) measurements obtained by CSLO
were reviewed. The study eyes were divided into three groups based
on IOP at 12 months status-post trabeculecotmy (Group 1 = 0-10
mmHg, Group 2 = 11-15 mmHg, and Group 3 = >15 mmHg). For
each group, the pre-operative and post-operative C:D, as measured
by CSLO, were then compared to determine any relative change. A
reversal of C:D was defined as any negative change in C:D postoperatively as compared to pre-operative measurements.
Results: Of 479 eyes that underwent trabeculectomy at the
University of Mississippi Medical center between 2007 and 2014, 36
eyes (35 patients) were included in the study. The majority of patients
excluded were for failure of follow-up or for absence of CSLO data
within specified pre-operative and post-operative range. At 12 months
status-post trabeculecotmy, 25% of eyes (n=9) had an IOP of <10
mmHg, 44.4% (n=16) had an IOP of 11-15 mmHg, and 30.6% (n=11)
had an IOP of >15 mmHg. There was found to be no statistically
significant difference in pre-operative C:D between the 3 groups.
The mean pre-operative and mean post-operative C:D for each group
were then compared in order to determine the relative change (Figure
1). It was determined that C:D reversal occurred in 88.9% of patients
in Group 1, 43.75% of patients in Group 2, and 27.27% of patients in
Group 3.
Conclusions: The results of this study reveal that lower postoperative IOP is associated with an increased likelihood of C:D
reversal. It was determined that obtaining a post-operative IOP of
<10 mmHg led to mean reversal of C:D. Additionally, patients with a
post-operative IOP of 10-15 experienced a mean stabilization of C:D
while those with IOP >15 had continued increase in C:D indicating
continued glaucoma damage.
Commercial Relationships: Cassie N. Confait, None;
Omolola Idowu, None; Meghan Moroux, None
Aberrometric changes induced by trabeculectomy performed in
an Argentinian teaching hospital
Pablo R. Ruisenor Vazquez, Javier F. Casiraghi. Glaucoma Section,
Ophthalmology Division, Hospital de Clínicas, University of Buenos
Aires, Capital Federal, Argentina.
Purpose: Trabeculectomy involves the placement of traction sutures
and fixation of the conjunctival filtering bleb to the superior cornea,
which could induce changes in corneal shape. The purpose of this
work was to evaluate the refractive and aberrometric effect of
trabeculectomy in glaucoma patients.
Methods: Retrospective chart review of glaucoma patients who
underwent fornix-based trabeculectomy between January and
November 2015 at the Glaucoma Section of our hospital. Patients
were evaluated with iTrace aberrometer (Tracey Technologies,
Houston, TX) one week before and 3 months after surgery. Data is
shown as mean±SD and statistical significance was set at p<0.05.
Results: Data from 21 patients (11 female, 53±9 years) was
analyzed. At the preoperative evaluation, mean spherical equivalent
was -0.25±2.23 D, refractive cylinder was -1.68±0.94 D, refractive
cylinder axis was 75±53°, average keratometry was 43.05±2.00 D,
corneal astigmatism was 1.39±0.76D, steepest corneal meridian was
100±53°, refractive higher-order aberrations were 0.170±0.038 μm,
coma was 0.102±0.029 μm and spherical aberration was 0.003±0.059
μm. A statistically significant change at 3 months after surgery was
observed only in refractive cylinder axis (31±51°), steepest corneal
meridian (-52±59°) and higher-order aberrations (0.150±0.138 μm).
Conclusions: The trabeculectomy filtering bleb seems to exert a
flattening effect on the superior cornea, leading to a shift in the
astigmatism axis, but not in its magnitude, and an increase in higherorder aberrations. Such changes might contribute to the impaired
visual quality that some patients refer after successful glaucoma
surgery.
Commercial Relationships: Pablo R. Ruisenor Vazquez, None;
Javier F. Casiraghi, None
Toric intraocular lens in patients with glaucoma undergoing
phacoemulsification and trabeculectomy: two years follow-up
Yael Azses, Angela Garcés-Valencia, Carolina Prado Larrea,
Rafael Castañeda Diez, Jesus Jiménez-Roman. Asociación para evitar
la ceguera en México, Mexico city, Mexico.
Purpose:
To determine the visual acuity, residual astigmatism and control
of intraocular pressure of patients with glaucoma undergoing
phacoemulsification surgery with toric lens implantation and
trabeculectomy during a 2 year follow-up in our hospital.
Methods:
We conducted a prospective, longitudinal, interventional, comparative
case series study. We included 6 patients from March to November
2013 with diagnosis of glaucoma, cataract and astigmatism who
underwent phacoemulsification surgery with toric intraocular lens
implantation + trabeculectomy. All surgeries where performed by the
same surgeon. The main outcomes measured were residual refraction,
best corrected visual acuity, control of intraocular pressure (IOP) and
mean deviation in the visual field which were collected preoperative
and at one and two years after surgery.
Results:
We included 6 patients in our study. The mean age was 74 (± 5.13
SD). The average preoperative, one and two years follow-up logMAR
visual acuity was 0.99 (± 0.52 SD), 0.29 (± 0.11 SD) 0.44 (± 0.17
SD) respectively. We found a statistically significant improvement in
visual acuity during the first and second year (ANOVA p = 0.0054).
The average preoperative, one and two years follow-up intraocular
pressure was 19.17mmHg (± 8.7 SD),11.0 (± 1.78 SD),12.8 (± 2.4
SD) respectively, with a statistically significant difference between
pre and 2 years follow-up IOP (ANOVA p = 0.0017). The average
mean deviation of the preoperative, one and two years follow-up
visual field was -9.44 (± 4.5 SD), -3.6 (± 9.8 SD), -4.8 (± 10.06 SD)
respectively with no statistically significant difference (ANOVA p =
0.47). Average refractive preoperative, one and two year follow-up
astigmatism was -2.29 D (± 0.99 SD), - 1.0 (± 0.9 SD), -0.70 (± 0.57
SD) respectively with a statistically significant difference between
pre and 2 year follow-up astigmatism (p = 0.01 ANOVA).
Conclusions:
Patients with previous diagnosis of glaucoma and cataracts
undergoing toric IOL implantation had good results, decreasing
the refractive astigmatism with consequent improvement in visual
acuity in postoperative evaluations. Combined surgery achieved a
statistically significant decrease in intraocular pressure and showed
no progression of the disease. Further studies with a greater number
of patients are required to corroborate this findings.
Commercial Relationships: Yael Azses, None; Angela GarcésValencia, None; Carolina Prado Larrea; Rafael Castañeda Diez,
None; Jesus Jiménez-Roman, None
Long-term outcomes of trabeculectomy in contact lens wearers
Jose A. Paczka1, 2, Luz A. Giorgi-Sandoval2, 3,
Andrea Orozco-García4, 2. 1Institute of Ophthalmology and Visual
Sciences, University of Guadalajara, Guadalajara, Mexico; 2Research,
Unidad de Diagnostico Temprano del Glaucoma, Guadalajara,
Mexico; 3Research, Asistencia e Investigacion en Glaucoma,
Guadalajara, Mexico; 4Ophthalmology, Antiguo Hospital Civil de
Guadalajara, Guadalajara, Mexico.
Purpose: Contact lens wearing in patients in whom a filtering bleb
is present after trabeculectomy imposes potential risks regarding IOP
control and infection. The current aim of this report is to determine
safety and efficacy of trabeculectomy in a cohort of patients wearing
contact lenses on a long-term basis.
Methods: A retrospective review of complete medical records of patients
who underwent trabeculectomy and kept wearing contact lenses after
surgery for at least five years was done. Visual function (acuity and
visual field), IOP control and bleb appearance were considered major
outcome variables. Descriptive and comparative statistics were used,
having a P value of 0.05 or less as a significant one.
Results: Twenty three cases from 16 patients (6 males, 10
females; mean age of 59 ± 8.3 years) were included in the study.
A miscellaneous group of glaucomas was present: Primary openangle (65.2%), primary angle-closure (17.4%), steroid-induced
(8.7%), Axenfeld-Rieger syndrome (4.3%) and traumatic (4.3%).
Follow up after trabeculectomy was at least 5 years (9.3 ± 3.8) and
time of contact lens wearing started no later than four months after
surgery. Most eyes were supplemented with mitomycin C during
trabeculectomy (86.9%), had moderate glaucoma damage (mean
MD index, -8.12 ± 4.8 dB; mean vertical c/d ratio, 0.76 ± 0.22), high
myopia (74.9%) and remained stable regarding visual acuity (86.9%).
Mean pre-operative IOP (23.4 ± 5.3 mm Hg) was significantly higher
(P = 0.001) as compared to the mean IOP of the last post-operative
visit (15.4 ± 4.2 mm Hg). Bleb appearance was reported as aceptable
or good (78.3%), avascular (17.4%) or encapsulated (4.3%). A
few cases required cataract surgery (13%) or needling (17.4%). A
target IOP was achieved in 82.6% of the cases, needing glaucoma
medication in 7 cases. One case had a progression of visual field
damage. No other siginificant complication was reported in the postoperative follow up period.
Conclusions: According to our findings contact lens wearing seems
to be compatible with good outcomes after trabeculectomy in the
long-term although a judicious behaviour has to be used to care
for such patients due to potential hazards that can impact filtering
integrity and function.
Commercial Relationships: Jose A. Paczka, None; Luz A. GiorgiSandoval, None; Andrea Orozco-García, None
Risk of Surgical Failure in Patients with Hypotony after
Trabeculectomy
Carole H. Kim1, Victoria L. Tseng1, 2, Pablo Romero1, Fei Yu1, 3,
Joseph Caprioli1, Harrison Quarry1, Anne L. Coleman1, 2. 1Stein Eye
Institute, David Geffen School of Medicine at UCLA, Los Angeles,
CA; 2Department of Epidemiology, UCLA Fielding School of Public
Health, Los Angeles, CA; 3Department of Biostatistics, UCLA
Fielding School of Public Health, Los Angeles, CA.
Purpose: To compare risk of surgical failure in patients with or
without hypotony after trabeculectomy
Methods: We identified glaucoma patients at the Stein Eye
Institute who had a trabeculectomy between 1990 and 2014 with
hypotony defined as intraocular pressures (IOP) of ≤5 mmHg on ≥2
consecutive visits at least six weeks after surgery. Controls included
eyes without postoperative hypotony. Baseline characteristics that
were examined included demographics, glaucoma type, presence of
diabetes and hypertension, history of prior trabeculectomy, history of
cataract surgery, family history of glaucoma, number of IOP-lowering
medications, IOP, visual acuity (VA), number of sutures, laser suture
lysis, and surgeon. Surgical failure was defined as (1) need for
surgical bleb revision or additional glaucoma surgery or (2) loss of ≥2
lines of VA on ≥2 consecutive visits at least six weeks after surgery.
Cox proportional hazard regression was performed to compare time
between trabeculectomy and failure by each definition in eyes with
or without hypotony, while adjusting for baseline factors. Logistic
regression was performed to examine adjusted associations between
baseline characteristics and hypotony.
Results: We included 201 eyes with hypotony and 151 eyes without
hypotony. The majority of patients were female (n=214, 60.8%),
white (n=222, 66.1%), and diagnosed with primary open-angle
glaucoma (n=187, 53.1%). Mean age was 66.9 ± 13.9 years and mean
preoperative IOP was 19.5 ± 8.6 mmHg. There were no statistically
significant associations between hypotony and time to failure by
definition 1 (hazards ratio [HR]=1.04, 95% confidence interval
[CI]=0.54-1.98) or definition 2 (HR=1.33, 95% CI=0.72-2.45).
Baseline factors associated with postoperative hypotony included
race (odds ratio [OR]=0.41, 95% CI=0.17, 0.99 for black vs. white;
OR=0.41, 95% CI=0.17, 0.99 for other race vs. white), family
history of glaucoma (OR=0.55, 95% CI=0.32-0.92), laser suture
lysis (OR=0.45, 95% CI=0.27, 0.75), and surgeon (OR=3.48, 95%
CI=1.69, 7.20 for surgeon 3 vs. surgeon 1).
Conclusions: This study suggests that patients with hypotony
after trabeculectomy do not have increased risk of further surgical
intervention or vision loss compared to patients without hypotony.
Although numerical hypotony alone is often used as a criterion for
surgical failure in studies of trabeculectomy outcomes, it often does
not represent surgical failure in clinical practice.
Commercial Relationships: Carole H. Kim, None;
Victoria L. Tseng, None; Pablo Romero, None; Fei Yu,
None; Joseph Caprioli, New World Medical (F), National Eye
Institute, National Institutes of Health (F), Alcon (F), Research
to Prevent Blindness (F), Allergan (F); Harrison Quarry, None;
Anne L. Coleman
Support: Hintz Glaucoma Research Fund, Research to Prevent
Blindness Unrestricted Grant
Effect and Risk Factor for Failure of Trabeculectomy in the
Glaucoma Patients with Low Baseline Intraocular Pressure in the
Collaborative Bleb-Related Infection Incidence and Treatment
Study
Yosuke Miyoshi1, Hajime Sakata1, Yoshiaki Kiuchi1, Yosuke Sugimoto2,
Yumiko Murakami3, Tomomi Higashide4, Kazuhisa Sugiyama4.
1
Ophthalmology, Hiroahima University Hospital, Hiroshima, Japan;
2
Ophthalmology, Hiroshima Prefectural Hospital, Hiroshima, Japan;
3
Ophthalmology, Hiroshima Red Cross Hospital & Atomic-bomb
Survivors Hospital, Hiroshima, Japan; 4Ophthalmology, Kanazawa
University Hospital, Kanazawa, Japan.
Purpose: To evaluate the efficacy and safety of trabeculectomy for
glaucoma patients with low baseline intraocular pressure (IOP) who
were enrolled in the Collaborative Bleb-related Infection Incidence
and Treatment Study (CBIITS).
Methods: This is a multicenter, prospective, cohort study.
A total of 295 eyes in 295 patients with glaucoma who had
undergone trabeculectomy alone or trabeculectomy combined with
phacoemulsification with low baseline IOP (IOPs < 22 mmHg before
surgery) at 34 clinical centers were examined in this study.
The enrollment period was 2 years, and follow-up was conducted
every 6 months for up to 5 years. Outcomes were measured
at 6-month intervals. Two levels of success were defined by
achievement of the following IOP: (A) The patients that 20% of IOP
reduction were obtained, (B) the patients that 30% of IOP reduction
were obtained. The primary outcome was the qualified success rate
according to the defined criteria. The secondary outcomes included
IOP, risk factors for surgical failure, and surgical complications.
Results: Mean IOP and preoperative antiglaucoma medications
were significantly decreased from 16.7±2.7 to 11.6±4.0 mmHg (P
< 0.0001) and from 2.7±1.1 to 1.0±1.2 (P < 0.0001), respectively, 5
years after surgery. For criteria A and B, the qualified success rates
were 94.9% and 74.1% at 1 year, respectively, and 87.3% and 42.0%
at 5 years, respectively. The third or subsequent trabeculectomy
was less effective than the first and second trabeculectomies. The
needling procedure and laser suture lysis were associated with the
risk of failure. The rates of postoperative hyphema, shallow anterior
chamber, bleb leak, and choroidal detachment were 2.3%, 2.0%,
3.4%, and 2.0%, respectively, in our series.
Conclusions: Trabeculectomy with mitomycin C is an effective and
safe procedure for reducing IOP in the patients in the CBIITS even
if preoperative IOP was low. The number of previous glaucoma
surgeries, preoperative IOP, the needling procedure and laser suture
lysis after trabeculectomy influenced the success rate, as determined
by the target IOP.
Commercial Relationships: Yosuke Miyoshi, None;
Hajime Sakata, None; Yoshiaki Kiuchi, None; Yosuke Sugimoto,
None; Yumiko Murakami, None; Tomomi Higashide, None;
Kazuhisa Sugiyama, None
Early Postoperative Complications of the Ex-PRESS
Implantation versus Trabeculectomy: A Randomized Clinical
Trial
Shogo Arimura, Yuji Takihara, Seiji Miyake, Kentaro Iwasaki,
Makoto Gozawa, Takehiro Matsumura, Takeshi Tomomatsu,
Yoshihiro Takamura, Masaru Inatani. Ophthalmology, University of
Fukui, Fukui, Japan.
Purpose: We aimed to compare early postoperative complications
between trabeculectomy and Ex-PRESS implantation.
Methods: Enrolled patients with primary open-angle or exfoliative
glaucoma were randomly assigned to receive trabeculectomy
(trabeculectomy group) or Ex-PRESS implantation (Ex-PRESS
group) (FIGURE 1). Primary outcomes were early postoperative
complications, including postoperative anterior chamber
inflammation, frequencies of hyphema, flat anterior chamber,
choroidal detachment, hypotonic maculopathy, and visual acuity.
Secondary outcomes were open anterior chamber duration during
surgery, postoperative intraocular pressure, postoperative antiglaucoma medications, frequencies of laser suture lysis and bleb
needling, and the relationship between iris contact with the ExPRESS tube and anterior chamber depth in the Ex-PRESS group.
Results: Sixty-four patients were divided between the groups. The
Ex-PRESS group had significantly lower flare values between 7
days and 1 month after the surgery (P = 0.015, 0.035, and 0.023 at 7,
10, and 30 days after the surgery, respectively). Hyphema occurred
significantly more frequently in the trabeculectomy group (P =
0.0025). The duration of the open anterior chamber was significantly
shorter for the Ex-PRESS group (P = 0.0002). The eyes with iris
contact with the Ex-PRESS tube had significantly shallower anterior
chambers than did the eyes without iris contact (P = 0.013) (FIGURE
2). There were no significant differences between the two groups for
other outcomes.
Conclusions: The Ex-PRESS implantation prevented early
postoperative inflammation and hyphema in the anterior chamber and
shortened the duration of anterior chamber opening. Iris contact with
the Ex-PRESS tube occurred more frequently in eyes with open-angle
glaucoma and shallow anterior chambers.
than in the SM and M groups on POD 21(P = 0.03, ANOVA). No
other complications were observed in any of the groups.
Conclusions: We have demonstrated that the self-assembling peptide
gel is safe in the trabeculectomy in the short-term. However, further
investigation is needed on the long-term safety of this technique.
Commercial Relationships: Kenji Matsushita, Menicon Co.,
Ltd. (F); Rumi Kawashima, Menicon Co., Ltd. (F); Koji Uesugi,
Menicon Co., Ltd.; Haruka Okada; Hirokazu Sakaguchi, Menicon
Co., Ltd. (F); Kohji Nishida, Menicon Co., Ltd. (F)
Support: Public-Private innovation program
Commercial Relationships: Shogo Arimura; Yuji Takihara, None;
Seiji Miyake, None; Kentaro Iwasaki, None; Makoto Gozawa,
None; Takehiro Matsumura, None; Takeshi Tomomatsu, None;
Yoshihiro Takamura, None; Masaru Inatani, None
Support: This work was supported by the Japan Society for the
Promotion of Science KAKENHI; Grant Number 15K15630 in
Japan.
Clinical Trial: http://www.umin.ac.jp, 000008680
The evaluation of the safety of a self-assembling peptide gel as
a potential device for providing a clear operative field in the
trabeculectomy
Kenji Matsushita1, Rumi Kawashima1, Koji Uesugi1, 2,
Haruka Okada2, Hirokazu Sakaguchi1, Kohji Nishida1.
1
Ophthalmology, Osaka University Medical School, Suita, Japan;
2
Menicon Co., Ltd., Kasugai, Japan.
Purpose: We have developed a self-assembling peptide gel (SAPG)
as a potential device for providing a clear operative field in the ocular
surgery. SAPG can keep an operative field clear, blocking blood
coming in there. However it is still unknown whether SAPG is safe in
any ocular surgery. The aim of this study is to evaluate the safety of
SAPG applied in the trabeculectomy.
Methods: Nine healthy New Zealand white (NZW) rabbits
underwent a trabeculectomy on the right eye. Three rabbits of
them underwent the trabeculectomy using the SAPG. Following a
conjunctival incision, the SAPG was applied on the sclera. A sclera
flap was created through the SAPG, and the SAPG was subsequently
removed. And then they underwent usual trabeculectomy combined
with mitomycin C (MMC) (SM group). Other three rabbits
underwent usual trabeculectomy combined with MMC without
using the SAPG (M group). And other three rabbits underwent usual
trabeculectomy without the usage of MMC or SAPG (C group).
Examination with a slit-lamp microscopy (SL F7, Topcon co. ltd.,
Japan), a tonometer (TONOVET, iCare Finland Oy, Finland) and an
anterior segment Optical Coherent Tomography (SS-1000, Tomey
co. ltd, Japan) was performed on each eye pre-operatively and on the
post-operative day (POD) 1, 3, 7, 14, and 21. The statistical analysis
was performed with Origin.
Results: Intraocular pressure (IOP) was significantly lower in the SM
and M groups than in the C group on POD 21(P = 0.002, ANOVA).
The height of the bleb was also significantly reduced in the C group
Trabeculectomy in Both Eyes; the First-Operated Versus the
Second-Operated Eyes: A Comparative, Multicenter Study.
Kentaro Iwasaki1, Yoshihiro Takamura1, Takashi Nishida2,
Akira Sawada2, Keiichiro Iwao3, Ayano Shinmura5,
Shiho Kunimatsu-Sanuki4, Hidenobu Tanihara3, Kazuhisa Sugiyama5,
Toru Nakazawa4, Masaru Inatani1. 1ophthalmology, University of
Fukui, Fukui, Japan; 2University of Gifu, Gifu, Japan; 3University
of Kumamoto, Kumamoto, Japan; 4University of Tohoku, Tohoku,
Japan; 5University of Kanazawa, Kanazawa, Japan.
Purpose: Despite of the successful intraocular pressure (IOP)
reduction after trabeculectomy in one eye, trabeculectomy in the
other eye often results in surgical failure. We evaluated, when both
eyes are treated, whether the surgical outcome of trabeculectomy in
the second eye is worse than that in the first eye.
Methods: The retrospective, comparative studies were conducted for
patients who had undergone trabeculectomy in both eyes at 5 clinical
centers in Japan. Inclusion criteria are open-angle glaucoma; both
eyes operated by one surgeon. Exclusion criteria are patients with
one phakic and the other pseudophakic eyes before trabeculectomy;
patients with prior vitrectomy or prior filtering surgery; patients with
one fornix-based and the other limbus-based trabeculectomized eyes.
Surgical failure was defined as <20% reduction of the preoperative
IOP, reoperation, or loss of light perception vision, hypotony of <5
mmHg, or IOP >21 mmHg (criterion A), IOP >18 mmHg (criterion
B), or IOP >15 mmHg (criterion C).
Results: Eighty-eight patients satisfied the criteria. The probability
of success at 3 years in the first-operated eyes vs in the secondoperated eyes was 72.2% vs 60.6% for criterion A (P=0.12), 57.8%
vs 54.2% for criterion B (P=0.57) and 42.6% vs 41.6% for criterion
C (P=0.68), respectively. In the subgroup analysis of the patients
that had success in the first-operated eyes, the interval between
trabeculectomies was significantly longer when the second eyes
failed than when they were successful, exhibiting the mean interval
of 574 vs 175 days for criterion A (P=0.0023), 518 vs 150 days for
criterion B (P=0.0026) and 508 vs 142 days for criterion C (P=0.011),
respectively. The probability of success showed significantly worse
outcomes in the group of the interval >2 months than <2 months
(77.5% vs 91.9% for criterion A, P=0.013). The subgroup analysis
of the failed first-operated eyes showed no significant differences of
surgical intervals between the successful and failed second-operated
eyes.
Conclusions:
If the first-operated eyes are successful, the long interval between
the trabeculectomies results in surgical failure of the second eyes.
Because the long-term successful filtration exposes intraocular
antigens to the lymphocytes in the conjunctiva, systemic immune
reaction might occur, causing failure in the second-operated eyes.
Commercial Relationships: Kentaro Iwasaki, None;
Yoshihiro Takamura, None; Takashi Nishida, None;
Akira Sawada, None; Keiichiro Iwao, None; Ayano Shinmura,
None; Shiho Kunimatsu-Sanuki, None; Hidenobu Tanihara,
None; Kazuhisa Sugiyama, None; Toru Nakazawa, None;
Masaru Inatani, None
Hypotony Maculopathy after Trabeculectomy
Victoria L. Tseng1, 2, Anne L. Coleman1, 2, Pablo Romero1, Fei Yu1,
Kenneth W. Robertson-Brown1, Joseph Caprioli1. 1UCLA/Stein Eye
Institute, Los Angeles, CA; 2Epidemiology, UCLA Fielding School of
Public Health, Los Angeles, CA.
Purpose: To identify factors associated with hypotony maculopathy
after trabeculectomy.
Methods: A case control study was performed of glaucoma
patients at the Stein Eye Institute who had trabeculectomy between
1990 and 2014. Cases included eyes with postoperative hypotony
maculopathy, and controls included eyes with postoperative
numerical hypotony without maculopathy, defined as intraocular
pressure (IOP) ≤5 mmHg on 2 or more consecutive visits 6 weeks or
later after surgery. Preoperative characteristics that were evaluated
included demographics, glaucoma type, systemic comorbidities,
history of previous trabeculectomy, lens status, family history of
glaucoma, number of glaucoma medications, IOP, visual acuity,
visual field mean deviation (MD), number of sutures in the scleral
flap, postoperative laser suture lysis, and surgeon. Cox proportional
hazards regression was performed to assess the association between
each preoperative characteristic and time to hypotony maculopathy.
Results: The study population included 32 cases and 152 controls.
The majority of the population was diagnosed with primary open
angle glaucoma (n=99; 53.8%). Mean preoperative IOP was 17.9±7.0
mmHg (range 5.0-51.0 mmHg), and average MD was -11.9±7.9
dB (range -31.4 to 2.8 dB). Mean IOP at the time of hypotony
maculopathy was 4.1±2.9 mmHg (range 0.0-14.0 mmHg). There were
7/32 eyes (21.9%) with IOP >5 mmHg at the time of maculopathy.
All of these eyes had numerical hypotony prior to maculopathy,
with a mean duration between numerical hypotony and hypotony
maculopathy of 453.7±618.7 days, versus 990.0±842.8 days in eyes
with IOP ≤5 mmHg at the time of hypotony maculopathy (p=0.23).
Significant adjusted risk factors hypotony maculopathy included
number of medications (hazards ratio [HR]=0.39, 95% confidence
interval [CI]=0.18, 0.85 for ≥3 medications vs. <3 medications) and
number of sutures (HR=0.11, 95% CI=0.03, 0.50 for 3 vs. 2 sutures).
Conclusions: Potential factors associated with maculopathy after
trabeculectomy include number of medications prior to surgery and
number of sutures on the scleral flap. Having IOP >5 mmHg at the
time of maculopathy is potentially associated with shorter mean
duration between numerical hypotony and hypotony maculopathy.
We recommend further studies of the relationship between hypotony
maculopathy and posteropative IOP fluctuations and trends to gain
insight for clinical practice and prevention efforts.
Commercial Relationships: Victoria L. Tseng, None;
Anne L. Coleman, None; Pablo Romero, None; Fei Yu, None;
Kenneth W. Robertson-Brown, None; Joseph Caprioli, New World
Medical (F), Alcon (F), Allergan (F)
Support: UCLA Hintz Fund, Research to Prevent Blindness
unrestricted grant
Uveitis, Glaucoma, Hyphema Syndrome: A Referral-Based,
Retrospective Analysis
Trevor A. Smith, Albert Cheung, John C. Hart, Charity Chen.
Ophthalmology, Beaumont Health - Royal Oak, Royal Oak, MI.
Purpose: Uveitis–glaucoma–hyphema syndrome (UGH) is caused
by improper intraocular lens (IOL) positioning, which results in
mechanical trauma to uveal tissue. The purpose of this study was
to examine the effect that IOL implant type and position have in
patients who develop UGH. We performed a ten-year retrospective
chart review to determine if different IOL types and positions were
associated with varying degrees of UGH severity as well as varying
amounts of visual impairment.
Methods: We reviewed 249 patients who were referred to an anterior
segment surgeon for IOL reposition or exchange. Of these patients 56
eyes of 53 patients were documented to have UGH at presentation.
All eyes had IOL repositioning or exchange by a single surgeon
(JCH). The involved eyes were sorted based on the type and position
of the IOL. One-piece posterior chamber (PC) IOLs, three-piece
PC IOLs, and anterior chamber (AC) IOLs were compared. Initial
and final visual acuities; time from cataract surgery to diagnosis of
UGH; number of ophthalmologists seen prior to diagnosis of UGH;
and development of glaucoma, uveitis/CME, and hyphema/vitreous
hemorrhage were outcome measures.
Results: Patients who developed UGH caused by an AC IOL had
worse initial and final visual acuities and were more likely to develop
glaucoma or CME than any other group. This group also had the
longest time from cataract surgery to diagnosis of UGH (mean 6.7
years) and saw the greatest number of ophthalmologist prior to
diagnosis of UGH. One-piece PC IOLs were diagnosed with UGH
earlier than any other group (mean 4.4 years). Patients with either
one- or three-piece PC IOLs who developed UGH had similar initial
and final visual acuities as well as similar rates of development of
glaucoma and uveitis/CME. There was a considerable delay for
all groups from the time of cataract surgery until the diagnosis of
UGH despite being evaluated by multiple ophthalmologists. Eyes
were often treated for uveitis, glaucoma, or hyphema/VH without
recognition of underlying UGH.
Conclusions: Patients who had UGH caused by AC IOLs fared
worse than any other group. PC IOLs tended to act equivalently in
terms of time to diagnosis, development of glaucoma and uveitis/
CME, and final visual outcomes. Ophthalmologists should recognize
the signs of UGH earlier in order to decrease morbidity from this
sight threatening complication of cataract surgery.
Commercial Relationships: Trevor A. Smith; Albert Cheung,
None; John C. Hart, None; Charity Chen, None
Early post-operative wound leak after trabeculectomy with
mitomycin C with and without placement of bandage contact lens
Ingrid Chang, Karine D. Bojikian, Divakar Gupta, Philip P. Chen.
Ophthalmology, University of Washington, Seattle, WA.
Purpose: To assess whether placement of a bandage contact lens
(BCL) after fornix-based trabeculectomy with mitomycin C (MMC)
at the time of surgery affects early post-operative wound leak.
Methods: Retrospective chart review of all patients with glaucoma
who underwent fornix based trabeculectomy with MMC as a sole
procedure, at one institution (2 surgeons) from July 2007 to July
2014. An early wound leak was defined as one that developed within
the first post-operative month.
Results: 90 eyes in 90 patients were studied, with a mean age (±SD)
of 63.8± 16.0 years. There were 22 eyes (24%) identified with early
post-operative wound leak. Mean time to wound leak development
was 10.8 days, and average duration of wound leak was 3.4 weeks.
Out of the 22 eyes with wound leak, 12 patients had placement of a
BCL at the time of surgery and 10 patients did not have placement of
BCL (p=0.80). Eleven out of 52 eyes (21%) that had placement of a
BCL had post-operative wound leak compared to 10/38 eyes (26%)
without BCL (p=0.36). For those with a wound leak, 16 (72.7%) eyes
resolved with medical management alone (placement of BCL and
topical antibiotic drops), and 6 (27.3%) eyes required trabeculectomy
revision in the operating room. Rate of trabeculectomy revision for
wound leak was not different between the group with placement
of a BCL (4/14 eyes, 33%) versus those without a BCL (2/10 eyes,
20%, p=0.67). No significant differences were found in age, race,
sex, type of glaucoma, prior laser peripheral iridotomy, prior laser
trabeculoplasty, preoperative intraocular pressure, number of topical
medications, preoperative visual acuity, and central corneal thickness
between eyes with or without an early wound leak (p≥0.09).
Conclusions: Placement of a BCL after fornix-based trabeculectomy
with MMC did not decrease the risk of an early postoperative wound
leak, nor the rate of trabeculectomy revision for severe leak.
Commercial Relationships: Ingrid Chang, None;
Karine D. Bojikian, None; Divakar Gupta, None; Philip P. Chen,
None
The effect of trabeculectomy surgery on the central visual field
in patients with glaucoma and an established central visual field
defect using Micro-perimetry and Optical coherence tomography
Gokulan Ratnarajan1, 2, Jasleen K. Jolly2, 3, John Salmon2.
1
Ophthalmology, Queen Victoria Hospital, Chalfont St Peter, United
Kingdom; 2Oxford Eye Hospital, Oxford, United Kingdom; 3Nuffield
Laboratory of Ophthalmology, Oxford, United Kingdom.
Purpose: Trabeculectomy surgery is considered when more
conservative treatment options such as topical treatment or
laser have failed to prevent glaucoma progression and is a long
established and effective treatment. We investigated the functional
and structural effect of trabeculectomy surgery on patients with
advanced glaucomatous visual field loss threatening fixation using
microperimetry (MP) and optical coherence tomography (OCT).
Methods: Prospective, observational case series of thirty consecutive
patients listed for trabeculectomy surgery who had established visual
field defects within 10 degrees of fixation had 10-2 Maia MP and
optic disc Spectralis OCT pre-operatively, 1 month and 3 month
post-operatively. Fellow eyes were used as controls. The study was
approved by an ethics and R&D committee: 15/NW/0231.
Results: The mean and standard deviation in MP average threshold
values was 19.8 ± 6.8dB in the control eye vs 13.7 ± 5.2dB at
baseline, 20.0 ± 6.6dB vs 14.3 ± 5.4dB at 1 month and 19.5 ± 6.9dB
vs 13.9 ± 5.5dB at 3 months. A linear mixed model did not show
any significant difference following surgery at either timepoint in
either eye(p=0.94). The mean and standard deviation in OCT nerve
fibre layer thickness was 71 ± 19µm in the control eye vs 54 ± 12µm
at baseline, 71 ± 20µm vs 54 ± 12dB at 1 month and 67 ± 19µm
vs 55 ± 15µm at 3 months. A linear mixed model did not show any
significant difference following surgery at either timepoint in either
eye (p=0.98). Kappa agreement between OCT and microperimetry
classification of glaucomatous disease was 0.735 (95% confidence
interval 0.59 to 0.88), which represents a good agreement.
Conclusions: The results from this case series are encouraging in
that the central visual function is preserved in all the patients having
trabeculectomy and actually improved in 2 patients.
Whilst a larger sample size with longer follow-up is required to make
definitive conclusions, this case series should help guide glaucoma
surgeons who are contemplating trabeculectomy surgery on patients
with advanced glaucoma threatening fixation who are worried about
the risk of “wipe-out”.
MP in conjunction with OCT is a useful method to observe these
patients providing both structural and functional parameters.
Commercial Relationships: Gokulan Ratnarajan, None;
Jasleen K. Jolly, None; John Salmon, None
Clinical Trial: 15/NW/0231.
The effect of intraoperative application of chemically defined
bioadhesive powder for trabeculectomy in rabbit eyes
Yoshifumi Okamoto1, Sujin Hoshi1, Mikki Arai2, Genichiro Kishino1,
Fumiki Okamoto1, Tetsuro Oshika1. 1University of Tsukuba, Tsukuba,
Japan; 2Arai Eye Clinic, Fukuoka, Japan.
Purpose: A newly developed chemically defined bioadhesive (CDB)
which is made from dextran and poly lysine is used to prevent
postoperative tissue adhesion. CDB contains no animal-derived
ingredients made from antibiotic food additives and its safety has
been confirmed. The purpose of this study was to investigate the
effect of CDB powder to prevent postoperative tissue adhesion in
trabeculectomy.
Methods: Three rabbit eyes with α chymotrypsin induced
glaucoma underwent trabeculectomy. A 3x3 mm scleral flap
was made following fornix based conjunctival incision. CDB
powder was applied under the conjunctiva and scleral flap, and
was gelled by dripping the balanced salt solution. The scleral
flap and conjunctiva were closed with 10-0 nylon water-tightly.
No mitomycin-C (MMC) or other agents were used. Slit-lamp
examination, intraocular pressure (IOP) measurement, and
anterior segment optical coherence tomography (AS-OCT) were
carried out at 7 days, 1 and 2 months postoperatively.
Results: No significant inflammation and infection were observed in
all eyes with slit-lamp examination throughout the follow-up period.
IOP was significantly reduced by surgery during the study period.
AS-OCT imaging showed successful bleb formation up to 2 months
postoperatively in every operated eye.
Conclusions: The new CDB powder may be effective to inhibit
conjunctival and scleral adhesion after trabeculectomy without
MMC.
Commercial Relationships: Yoshifumi Okamoto, None;
Sujin Hoshi, None; Mikki Arai, None; Genichiro Kishino, None;
Fumiki Okamoto, None; Tetsuro Oshika, None
Second Trabeculectomy After Failure of The First
Trabeculectomy : Outcomes and Risk Factors for Failure
Pradtana Hirunpatravong, Reza Alizadeh, Pablo Romero,
Kouros Nouri-Mahdavi, Joseph Caprioli. Ophthalmology, Glaucoma
division, JSEI,UCLA, Los Angeles, CA.
Purpose: To evaluate long-term IOP tonometric outcomes of
a second trabeculectomy with MMC after failure of the first
trabeculectomy and risk factors for failure in patients with open-angle
glaucoma.
Methods: Patients with POAG, NTG, exfoliative or pigmentary
glaucoma 40 years or older of age at the time of a second
trabeculectomy were included. Threelevels of success were defined
: (A)IOP <18 mmHg and IOP reduction of 20%; (B)IOP <15 mmHg
and IOP reduction of 25%; and (C)IOP <12 and IOP reduction of
30%. The primary outcome was qualified Kaplan-Meier success
rate (with or without medications) according to the defined criteria
A, B, and C. Cox’s proportionalhazard regression analysis was used
to identify risk factors for failure. Secondary outcomes included
IOP and number of medications at 1,3 and 5 years aftersurgery,
postoperative complications, and need for further glaucoma surgery.
Results: A total 1of44 eyes(130 patients) with the success rates
(+SE) at the first, third and fifth years of follow-up for criteria A
were 72.3%(+3.8%), 61.0%(+4.4%)and 50.7(+4.9%); for criteria
B were 63.6 %(+4.1%), 49.9 %(+4.5%) and 43.0(+4.7%); for
criteria C were 47.3%(+4.3%), 31.2%(+4.2%) and 27.6%(+4.2%)
(Fig1). The mean IOP (mmHg+SD) decreased from 17.2(+5.3)
before surgery to 12.8(+5.0) at 1year, 11.9(+4.2) at 3 years and
12.1(+4.85) at 5 years (P i>0.001)(Fig2). The mean number of
medications decreased from 2.8(+1.0) preoperatively to 1.2(+1.4)
at 1year, 1.24(+1.4) at 3 years and 1.36(+1.4) at 5 years (P/
i>0.001)(Fig3). An interval between the first and the second
trabeculectomy that less than 3 years was associated with a
higher rate of failure in criteria A and B ;(HR =9.2; P = 0.02) and
(HR=2.8; P = 0.05) respectively. The interval of less than 2 years
was associated with a higher rate of
failure in criteria C (HR =2.3; P=0.04). The requirement for
postoperative laser suture lysis was associated with a higher rate of
failure for criteria A; the hazardratio (HR) was 2.1(P=0.04). Baseline
VA is a risk factor for failure in criteria B; (HR =1.4; P=0.06) and C;
(HR=1.5; P=0.04).
Conclusions: The long-term tonometric success rate and medication
reduction of repeat trabeculectomy with MMC support its juidicious
use in open-angleglaucoma patients. An interval between the first and
the second trabeculectomy < 3 years and requirement for laser suture
lysis are associated with a higher risk offailure.
Commercial Relationships: Pradtana Hirunpatravong, None;
Reza Alizadeh, None; Pablo Romero, None; Kouros NouriMahdavi, None; Joseph Caprioli, None
Alteration of lymphatic vessels after filtration surgery in mouse
Akira Matsuda, Yosuke Asada, Satoshi Iwamoto, Jobu Sugita.
Ophthalmology, Juntendo Univ School of Med, Tokyo, Japan.
Purpose: To clarify possible roles for lymphatic vessels for absorption
of aqueous humor after glaucoma filtration surgery, we investigated the
alteration of lymphatic vessels using mouse filtration surgery models.
Methods: Using BALB/c mouse, filtration surgery model was made by
incision of limbal conjunctiva, followed by the insertion of 33G needle
tip into the anterior chamber, and 11-0 nylon suture. The conjunctival
tissue was sampled chronologically after surgery and analyzed by
whole mount immunohistochemical staining using anti-mouse LYVE1
antibody. The expression of lymphatic growth factor genes (vegfc and
flt4, which encoding VEGFR3) were quantified by realtime PCR.
Results: LYVE-1 positive lymphatic vessels were observed
circumferentially around corneal limbus in naïve conjunctival tissue. The
LYVE-1 positive staining was disappeared in the filtering bleb at one
day after surgery. At 7 days after surgery, LYVE-1 positive lymphatic
vessels were observed from peripheral bleb region toward corneal limbus
with the sprout formations. Upregulation of vegfc (2.99 fold) and flt4
(2.44 fold) gene expression was observed at the bleb tissue 7 days after
filtration surgery compared to the naïve conjunctival tissue.
Conclusions: Our results suggested remodeling of lymphatic vessels
in mouse models of glaucoma filtration surgery.
Commercial Relationships: Akira Matsuda, None; Yosuke Asada,
None; Satoshi Iwamoto, None; Jobu Sugita, None

Session 312 Glaucoma Surgery I

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