1. health and fitness
2. disease
3. diabetes

ARVO 2014 Annual Meeting Abstracts
238 Diabetic Macular Edema Therapy
Monday, May 05, 2014 11:00 AM–12:45 PM
Exhibit/Poster Hall SA Poster Session
Program #/Board # Range: 1745–1792/A0182–A0229
Organizing Section: Retina
Contributing Section(s): Physiology/Pharmacology
Program Number: 1745 Poster Board Number: A0182
Presentation Time: 11:00 AM–12:45 PM
Differential systemic gene expression profile in patients with
diabetic macular edema: responders versus non-responders
Shwetha Mangalesh1, Supriya Dabir1, Debashish Das2, Jeyabalan
Nallathambi3, Naresh Yadav1, Rohit Shetty4. 1Retina, Narayana
Nethralaya, Bangalore, India; 2Stem Cell Biology, Narayana
Nethralaya, Bangalore, India; 3Genetic Research, Narayana
Nethralaya, Bangalore, India; 4Refractive, Narayana Nethralaya,
Bangalore, India.
Purpose: To identify signaling pathways involved in the
development of diabetic macular edema and assess the differential
systemic gene expression profile based on response to treatment.
Methods: A pilot, case control, prospective, observational series
where DME patients were treated with bevacizumab and sub
classified as treatment naïve, treatment responders and treatment nonresponders. RNA extraction followed by labelling, amplification and
hybridisation was done and microarray data analysed. Genes were
classified based on functional category and pathways.
Results: The total number of genes upregulated among all three
experimental groups were 5 whereas 105 genes were downregulated.
There were no common genes upregulated between the responders
and non-responders. There was only 1 gene upregulated between
the diabetic and diabetic responders post treatment. There were 19
genes upregulated and 8 genes downregulated in the inflammatory
pathway in group 2 vs group 1. There were no down regulated
genes detected in vascular angiogenesis and transcription group.
There were identical numbers of genes up and down regulated in
the inflammatory pathway. Seventeen genes were upreguated and
11 genes downregulated in receptor activity, that remained the
predominant group in the group classification.
Conclusions: This study provides an insight into the probable
signaling mechanisms for disease pathogenesis as well as
progression. This eventually would aid in developing or improvising
existing treatment modules with a rational approach towards
personalized medicine, in future addressing the differential responses
to treatment.This will herald the era of pharmacogenomics for
titrating individualized treatment.
Commercial Relationships: Shwetha Mangalesh, None; Supriya
Dabir, None; Debashish Das, None; Jeyabalan Nallathambi, None;
Naresh Yadav, None; Rohit Shetty, None
Program Number: 1746 Poster Board Number: A0183
Presentation Time: 11:00 AM–12:45 PM
Prospective Randomised Trial of Intravitreal Bevacizumab vs.
Triamcinolone for Patients with Diabetic Macular Edema at the
Time of Cataract Surgery (The DiMECAT Trial)
Lyndell L. Lim1, 2, Sukhpal S. Sandhu1, 2, Marios Constantinou1, Julie
Morrison1, Sanjeewa Wickremasinghe1, 2, Ryo Kawasaki1, 3, Salmaan
H. Qureshi1, 2. 1Centre for Eye Research Australia, University of
Melbourne, East Melbourne, VIC, Australia; 2Royal Victorian Eye
and Ear Hospital, Melbourne, VIC, Australia; 3Public Health and
Ophthalmic Epidemiology, Yamagata University, Yamagata, Japan.
Purpose: Cataract surgery in diabetic patients often results in poor
visual outcomes from the progression of diabetic retinopathy and
accelerated development of Diabetic Macular Edema (DME). This
study compares the final visual and anatomical outcomes after
the use of either intravitreal bevacizumab (BVB, AvastinTM), or
triamcinolone (TA, TriesenceTM) at the time of cataract surgery in
patients with DME.
Methods: Prospective randomized clinical trial of an intravitreal
injection of either 1.25mg of BVB or 4mg of TA at the time of
cataract surgery, and at subsequent review if required, in diabetics
with visually significant cataract and one of: i) refractory DME at
the time of surgery, ii) treated DME within the 12 months prior to
surgery, or iii) microaneurysms within the foveal avascular zone
not amenable to focal macular laser. End points were best-corrected
visual acuity, change in central macular thickness (CMT) on SD-OCT
from baseline, number of injections and ocular complications at 6
months post-operatively.
Results: To date, 47 patients have been recruited at the Royal
Victorian Eye and Ear Hospital, Melbourne, Australia, 31 of whom
have had surgery (17 in the TA group). At baseline, the BVB group
with 56±16 LogMAR letters and CMT of 366±108μm, was similar
to the TA group with 50±17 LogMAR letters and CMT 386±152μm
(p=0.28 and 0.69 respectively).
Ten TA and 7 BVB subjects have currently reached the 6-month time
point. At 6 months, both BVB and TA groups gained vision from
baseline (mean 26.2 letter gain in TA group, 17.4 letter gain in BVB,
p=0.40). However, only the TA group had a sustained reduction in
CMT that was significantly better than the BVB group (315mm TA
vs. 433mm, p=0.011).
The BVB group received an average of 4.2±1.6 injections over 6
months, compared to a total of 2 injections in the TA group. There
was one case of raised intraocular pressure (≥22mmHg) in the TA
group (10%).
Conclusions: When administered at the time of cataract surgery
in patients with DME, both TA and BVB result in improved visual
acuity at 6 months post operatively – however only TA resulted in a
sustained reduction in central macular thickness. Further follow up
will determine whether this translates into better long term visual
outcomes in the TA group.
Commercial Relationships: Lyndell L. Lim, None; Sukhpal S.
Sandhu, None; Marios Constantinou, None; Julie Morrison,
None; Sanjeewa Wickremasinghe, None; Ryo Kawasaki, None;
Salmaan H. Qureshi, None
Support: Royal Victorian Eye and Ear Hospital Research Grant
Clinical Trial: ACTRN12611000888965
Program Number: 1747 Poster Board Number: A0184
Presentation Time: 11:00 AM–12:45 PM
Initial Choroidal Thickness and Response to Treatment in
Diabetic Macular Edema
Nika Bagheri1, Nadim Rayess1, 2, Ehsan Rahimy1, 2, Alexander Juhn1, 2,
Jason Hsu1, 2. 1Retina Service, Wills Eye Hospital, Philadelphia, PA;
2
Mid Atlantic Retina, Plymouth Meeting, PA.
Purpose: To identify baseline anatomic characteristics on spectraldomain optical coherence tomography (SD-OCT) in treatment-naïve
patients with diabetic macular edema (DME) that may help predict
better response to intravitreal anti-vascular endothelial growth factor
(VEGF) therapy.
Methods: Retrospective, observational case series of treatment-naïve
patients (no prior injections or laser) diagnosed with DME who were
subsequently treated with ranibizumab or bevacizumab at the Retina
Service of Wills Eye Hospital (Philadelphia, PA). Pertinent clinical
data, including age, gender, baseline and follow-up visual acuity
(VA), biomicroscopic examination findings, injection history, and
length of follow-up were all recorded. Serial SD-OCT scans were
analyzed for internal structure and measurements were obtained for
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
subfoveal choroidal thickness (SFCT), foveal thickness (FT), and
central macular thickness (CMT). Statistical analysis was performed
using a paired two-tailed t-test.
Results: Nineteen eyes with DME met inclusion criteria. Initial
measurements were compared to those after 3 monthly injections
of ranibizumab/bevacizumab. In eyes with initial SFCT > 250 mm
(n=10), subsequent SFCT reduction observed was statistically
significant (p=0.002), but not in eyes with initial SFCT < 250 mm
(n=9, p=0.06). Mean change in logMAR VA showed a positive trend
towards improvement in both groups with greatest change in eyes
with thicker initial SFCT (< 250 mm: mean change -0.07, p=0.12; >
250 mm: mean change -0.10, p=0.08). In eyes with initial SFCT <
250 mm, the average FT decreased by 22% from 363.6 to 283.6 mm
(p=0.01), whereas CMT decreased by 19.7 % from 434.3 to 348.7
mm (p=0.02). In eyes with initial SFCT > 250mm, the average FT
decreased by 13.8% from 367.3 to 316.7 mm (p=0.06) and average
CMT decreased by 12.9% from 468.8 to 408.2 mm (p=0.03).
Conclusions: Quantifiable SD-OCT anatomic characteristics,
such as SFCT, appear to show promise in identifying eyes with
DME that may respond more favorably to intravitreal anti-VEGF
pharmacotherapy. In this study, eyes with thinner baseline SFCT
had greater reductions in FT and CMT after intravitreal anti-VEGF
injections.
Commercial Relationships: Nika Bagheri, None; Nadim Rayess,
None; Ehsan Rahimy, None; Alexander Juhn, None; Jason Hsu,
None
Program Number: 1748 Poster Board Number: A0185
Presentation Time: 11:00 AM–12:45 PM
Vascular changes in the macula of eyes with diabetic macular
edema treated with varying doses of ranibizumab
Liz J. Zapata, Yasir Sepah, Jose Maya, Mostafa S. Hanout,
Mohammad A. Sadiq, Salman Sarwar, Nithya Rajagopalan, Kathleen
E. Guinn, Quan Dong Nguyen, Diana V. Do. Ocular Imaging
Research and Reading Center, Stanley M. Truhlsen Eye Institute,
University of Nebraska Medical Center, Omaha, NE.
Purpose: The aim of this study is to assess the changes in vessel
diameter in the macula of patients with diabetic macular edema
(DME) treated with 2 different doses of ranibizumab (RBZ).
Methods: Fundus photos from 38 patients (38 eyes) enrolled in the
READ-3 study (comparison of 0.5mg vs. 2.0mg of RBZ for DME)
were analyzed. Photos were divided in two groups according to
treatment arms (Group A=0.5mg; Group B=2.0mg). All eyes received
6 monthly injections starting at the baseline visit. Macular retinal
arterial equivalent (MRAE) and macular retinal venular equivalent
(MRVE) were measured using Interactive Vessel Analysis (IVAN)
software centered on the fovea; the 2 largest venules and arterioles
one-half to one disc diameter from the fovea were measured.
Parametric tests (paired t-test, independent t-test) were performed to
compare the MRVE and MRAE between the two groups.
Results: 17 patients were included in group A; 21 in group B. The
mean age was 62 and 64 in group A and B, respectively. 10 patients
were male in group A; 13 males in group B. There was reduction in
both MRAE and MRVE at month 6 compared to baseline for both
doses of RBZ (table). The changes were statistically significant in
MRVE and demonstrated a trend towards significance in MRAE.
However, the changes (MRAE and MRVE) that occurred in group
A were similar to those in group B and did not demonstrate any
statistically significant differences (p=0.210 for MRAE and p=0.614
for MRVE).
Conclusions: Treatment of DME with RBZ appears to induce similar
reduction in MRVE and MRAE, regardless of dose. Such findings
with fovea-centered vascular grading imply that low and high dose
of RBZ may have similar effects on macular vasculature in eyes with
DME.
Commercial Relationships: Liz J. Zapata, None; Yasir Sepah,
None; Jose Maya, None; Mostafa S. Hanout, None; Mohammad
A. Sadiq, None; Salman Sarwar, None; Nithya Rajagopalan,
None; Kathleen E. Guinn, None; Quan Dong Nguyen, Genentech
(F), Regeneron (F); Diana V. Do, Genentech (F), Regeneron (F)
Support: JDRF International
Clinical Trial: NCT01077401
Program Number: 1749 Poster Board Number: A0186
Presentation Time: 11:00 AM–12:45 PM
Choroidal thickness before and after intravitreal anti-VEGF
therapy in patients with diabetic macular edema
Deepti Saini, Joanna Olson, Ingrid U. Scott, Esther M. Bowie.
Ophthalmology, Penn State Milton Hershey Medical Center, Hershey,
PA.
Purpose: o investigate if intravitreal anti-vascular endothelial growth
factor (anti-VEGF) therapy is associated with a change in choroidal
thickness in patients with diabetic macular edema (DME).
Methods: Prospective case series of patients treated at Penn State
Hershey Eye Center with intravitreal anti-VEGF therapy for DME.
Participants were consented according to IRB protocol. Exclusion
criteria include patients who received intravitreal anti-VEGF
injection(s), photocoagulation to the retina or vitrectomy within the
prior three months. Choroidal thickness measurement on spectral
domain optical coherence tomography (SDOCT) was performed
using enhanced depth imaging (EDI) at baseline and monthly by two
readers. The Cirrus linear measurement tool was used to measure
choroidal thickness from the outer edge of the hyperreflective retinal
pigment epithelium (RPE) to the inner sclera at 500 micron intervals
temporal and nasal to the fovea up to 3000 microns. Statistical
analysis was performed on the average thickness measurements from
the two readers using paired T-test.
Results: To date, 13 patients have been enrolled into the study. Of
these 13 patients, pre- and post-anti-VEGF SDOCT EDI results are
available for 7 eyes of 7 patients. Five of the 7 patients (71%) are
Caucasian and 6/7 (86%) are men. All of the patients have a history
of type 2 diabetes mellitus and all were treated with intravitreal
ranibuzumab 0.3mg. Among the 7 study eyes, for each of the 6
locations of choroidal thickness measurement except for at the fovea,
there was a decrease from baseline in the mean choroidal thickness
at 1 month post-injection (range of reduction in thickness: 2.5 to 48.5
microns).
Conclusions: Intravitreal anti-VEGF therapy may be associated
with a decrease in choroidal thickness in patients with DME. Larger
prospective studies with longer follow-up are warranted to investigate
the potential effects of anti-VEGF therapy on choroidal thickness in
patients with DME.
Commercial Relationships: Deepti Saini, None; Joanna Olson,
None; Ingrid U. Scott, None; Esther M. Bowie, None
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Program Number: 1750 Poster Board Number: A0187
Presentation Time: 11:00 AM–12:45 PM
Choroidal Thickness Measurement with Varying Frame Number
in Patients with Diabetic Macular Edema
William Best1, Ryan Man1, Jonathan E. Noonan1, Jing Xie1, Sukhpal
S. Sandhu1, Ecosse L. Lamoureux1, 2. 1Centre for Eye Research
Australia, Melbourne, VIC, Australia; 2Singapore Eye Research
Institute, Singapore, Singapore.
Purpose: Choroidal thickness(CT) measurement using Enhanced
Depth Imaging Optical Coherence Tomography(EDI-OCT) is
often performed with 100 frames per line to decrease the signal
to noise ratio. However, a high scan density can make it difficult
to image large areas due to the increased time required. This issue
may be compounded by diabetic macular edema(DME), where
reduced acuity may cause poor fixation and edema may obscure the
underlying choroid. Measurement of CT with a smaller number of
frames would reduce patient discomfort, test time and allow for larger
areas to be imaged. However, the accuracy of reduced frame scans
is unknown. We investigated the accuracy of CT measurements in
patients with DME with a reduced number of frames as compared to
the standard 100 frames.
Methods: Ten patients with DME(any severity), aged 54 to 74,
were recruited from laser and injection clinics in Victoria, Australia.
Consecutive images of the study eye were taken with 10, 25,
50 and 100 frames. The average value of sub-foveal choroidal
thickness for each scan density, manually measured three times
per image, was compared to the standard 100-frame image. Within
subject differences were assessed by repeated measures analysis of
variance (ANOVA) and Dunnett-adjusted pairwise comparisons,
while Pearson’s correlation coefficient was utilized to assess the
correlations between these measurements.
Results: Median (interquartile range [IQR]) best-corrected visual
acuity using the logarithm of the minimum angle of resolution
(logMAR) chart was 0.44 (0.3-0.6), and median duration of diabetes
was 13 years(IQR 5-18). Mean CT measurement was 249.9 ± 59um,
254.0 ± 56.0μm, 264.4 ± 69.6μm and 257.8 ± 66.6um for 10, 25,
50 and 100 averaged scans respectively. There was no significant
difference between the means (P>0.36 using ANOVA) and pairwise
comparisons showed no differences in thickness between 10, 25 and
50 scans vs. 100 scans (all P>0.05). Pearson’s correlation coefficient
showed high correlations between the standard 100 frames with
10 frames (correlation coefficient: 0.98), 25 frames (correlation
coefficient: 0.84) and 50 frames (correlation coefficient: 0.95).
Conclusions: Measurement of CT with 10 A-scans per line in
patients with DME is comparable to the standard 100 scans per line.
Our finding allows for shorter imaging times, which is helpful in
those with impaired fixation, and is likely to increase patient comfort.
Commercial Relationships: William Best, None; Ryan Man, None;
Jonathan E. Noonan, None; Jing Xie, None; Sukhpal S. Sandhu,
None; Ecosse L. Lamoureux, None
Program Number: 1751 Poster Board Number: A0188
Presentation Time: 11:00 AM–12:45 PM
Increased health care utilization among patients with diabetic
macular edema compared with diabetic patients without edema
Chris J. Wallick1, Ryan N. Hansen2, Joanna Campbell1, Jonathan
W. Kowalski1, Szilard Kiss3, Sean D. Sullivan2. 1Global Health
Outcomes Strategy and Research, Allergan, corona del mar, CA;
2
Pharmaceutical Outcomes Research and Policy Program, University
of Washington, Seattle, WA; 3Ophthalmology, Weill Cornell Medical
College, New York, NY.
Purpose: Diabetic macular edema (DME) serves not only as a
marker of progression and severity of diabetes but also in itself
adds to the increasing burden of medical care in diabetic patients.
However, the specific effect of having DME on health care utilization
among patients with diabetes remains unclear. The objective of the
present study was to examine health care utilization in a working-age
commercially insured cohort of patients with diabetes and to compare
resource utilization in diabetic patients with and without DME.
Methods: A retrospective cohort study was carried out using
enrollment and health care claims data from the Truven Marketscan
Commercial Claims and Encounters Database, a large database
of insured, working age adults in the US. We matched an incident
(2008-2011) DME patient group (n=24,326) 1:5 with a non-DME
diabetic patient cohort (n=122,710) on age, sex, region, and calendar
years with insurance coverage. Claims for relevant procedures and
visits to health care specialists were analyzed over 1- and 3- year
cohort periods.
Results: Health care resource utilization rates were significantly
higher in DME patients than diabetic control patients for every
category, including emergency, outpatient, inpatient and eye-care
related visits (see table). The mean total number of outpatient visits in
1-year was more than 10 days greater in DME cohort patients than in
non-DME patients (25.5 vs. 14.9 days). Among the DME cohort this
represents, on average, a visit to a healthcare provider more than once
every 2 weeks over the course of a year.
Conclusions: Health care utilization among diabetic patients with
macular edema was substantially greater when compared with
those patients without DME. This increased burden of medical
care was significant across all ophthalmic and non-ophthalmic
resource utilization measures. Since the standard-of-care for the
treatment of DME during the inclusion period of this study was laser
photocoagulation, the more recent emergence of repeated intravitreal
injections as a primary treatment modality for DME may likely add
to the already high health care utilization for these patients. Given
this considerable medical burden for patients with DME (25 visits per
year) it is important to consider intravitreal injection frequency when
making treatment decisions for this population.
Utilization of selected health care resources
Commercial Relationships: Chris J. Wallick, Allergan (E); Ryan
N. Hansen, None; Joanna Campbell, Allergan (E); Jonathan W.
Kowalski, Allergan (E); Szilard Kiss, Alimera (C), Allergan (C),
Allergan (F), Allergan (R), Genentech (C), Genentech (F), Genentech
(R), Regeneron (C), Regeneron (F), Regeneron (R); Sean D.
Sullivan, None
Program Number: 1752 Poster Board Number: A0189
Presentation Time: 11:00 AM–12:45 PM
Evolving Visual Results and Cost in Diabetic Macular Edema
Treatment
Richard M. Feist1, 2, Deepthi M. Reddy1, 2, Richard M. Feist1, 2, John
O. Mason1, 2, Martin L. Thomley1, 2, Michael A. Albert1, 2, Carrie E.
Huisingh2, Natalie Price1. 1Research, Retina Consultants of Alabama,
PC, Birmingham, AL; 2Ophthalmology, UAB, Birmingham, AL.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Purpose: To evaluate the effect on clinical practice of the
introduction of anti-vascular endothelial growth factor (anti-VEGF)
treatment for diabetic macular edema.
Methods: Two cohorts with clinically significant diabetic macular
edema were identified and studied retrospectively. One group
began treatment 10 years prior to identification while the other
began treatment 3 years prior to identification. Entry vision, final
vision, and treatments were tabulated for each group. Treatment
cost was calculated using current fee schedules for Medicare and
the predominant private insurance carrier for the state of treatment
(Alabama). A maximal and minimal cost model was built for both
payer type and by anti-VEGF drug.
Results: Treatment in the 10-year-old cohort consisted entirely of
laser photocoagulation while treatment in the 3-year-old cohort
consisted of a combination of laser photocoagulation and antiVEGF treatment. The 3 year cohort had fewer laser procedures (1.8
versus 2.4), better visual retention during 2 years of follow up (mean
logMAR of visual loss 0.05 p=.32 versus 0.22 p<.0001 at 2 years
follow up) and a higher mean treatment cost. Modeled treatment costs
ranged from 7% to over 200% higher in the 3 year cohort. Pricing
of the anti-VEGF medication was by far the strongest factor in cost
differences among various treatment models.
Conclusions: Pharmacotherapy with anti-VEGF agents offers better
visual prognosis for patients with clinically significant diabetic
macular edema. This improved prognosis may come with a higher
cost of treatment with drug costs composing most of the increase.
Commercial Relationships: Richard M. Feist, None; Deepthi M.
Reddy, None; Richard M. Feist, None; John O. Mason, None;
Martin L. Thomley, None; Michael A. Albert, None; Carrie E.
Huisingh, None; Natalie Price, None
Support: Research to Prevent Blindness Departmental Grant
Program Number: 1753 Poster Board Number: A0190
Presentation Time: 11:00 AM–12:45 PM
Comparison of the National Institute of Clinical Excellence
with the Royal College of Ophthalmologists guidelines on the
treatment of Diabetic Macular Oedema
Stylianos D. Georgoulas1, Dawn A. Sim2, Pearse A. Keane2,
Catherine A. Egan2. 1Moorfields Eye Hospital, London, United
Kingdom; 2Medical Retina, Moorfields Eye Hospital, London, United
Kingdom.
Purpose: The Royal College of Ophthalmologists (RCOPHTH)
and the National Institute of Clinical Excellence (NICE) in United
Kingdom recently released guidelines on the use of ranibizumab
in patients with diabetic macular oedema (DMO). NICE indicates
the use of ranibizumab when central macular thickness (CMT) is
≥400μm and the RCOPHTH suggests it when CMT ≥ 250μm and
visual acuity (VA) is 78-24 ETDRS letters. The purpose of the study
is to identify how many patients who were receiving macular laser
therapy would qualify for ranibizumab treatment under the current
RCOPHTH and the NICE guidelines.
Methods: Patients from a single-consultant’s clinic were identified
from the MEH laser database during the period August-February
2013. Patients who underwent macular laser (focal or grid) were
included. Data collected: a) VA on day of macular laser. b) OCT
macular thickness measurement of all 9 areas of the macula (as
identified by Heidelberg Spectralis OCT and Topcon 2000 software)
pre- and post- laser therapy.
Results: 103 eyes from 98 patients were included. The mean age
was 66.2 years (range 42-77 years old), 46.7% were male and
53.3% female. 28/103 eyes (27.2%) met the NICE criteria for
ranibizumab treatment with a mean CMT of 491 μm (range 400678). The remaining 75 eyes (72.8%), which did not meet the NICE
criteria, had a mean CMT of 299 μm (range 162-399 μm). With
the RCOPHTH criteria, 27/103 (26.2%) of eyes were eligible for
ranibizumab treatment. 86/103 eyes had CMT ≥ 250μm (mean
CMT of 374 μm, range 250-678 μm) and 30/103 eyes had ETDRS
VA between 78-24 letters. 19/103 eyes (18.4%) met both NICE
and RCOPHTH criteria, and 9/103 eyes (8.7%) met NICE but not
RCOPHTH criteria and 8/103 eyes (7.8 %) met RCOPHTH but not
NICE criteria.
Conclusions: This study indicates that, although the implementation
of the two different guidelines results in about the same percentage
of ranibizumab treatment eligibility for DMO and there is treatmentagreement in the majority of cases, there is a potential undertreatment risk for about 9% of the sample.
Commercial Relationships: Stylianos D. Georgoulas, None; Dawn
A. Sim, None; Pearse A. Keane, None; Catherine A. Egan, None
Program Number: 1754 Poster Board Number: A0191
Presentation Time: 11:00 AM–12:45 PM
Is Hyperbaric Oxygen Useful in the Treatment of Diabetic
Macular Edema?
Efrain Romo-Garcia1, 2, David Magana-Garcia1, Mariana
Gonzalez-Reyes1, Tania Nieblas-Aguilar1, Sergio Sital-Gastelum1.
1
Ophthalmology, Centro de Investigación y Docencia en Ciencias
de la Salud Universidad Autónoma de Sinaloa, Culiacan, Mexico;
2
Retina, Fundación BuenaVista IAP, Culiacan, Mexico.
Purpose: To compare the use of hyperbaric oxygen in conbination
with bevacizumab and bevacizumab alone when treating diabetic
macular edema.
Methods: In this pilot study, patients diagnosed with nonproliferative diabetic retinopathy and diabetic macular edema in
age range 40-85 years old were randomized into 2 groups. Control
group were treated with intravitreal bevacizumab and study group
in addition to intravitreal bevacizumab received hyperbaric oxygen
therapy.
A complete ophthalmological examination was perform at baseline,
1 week, 1 month and 3 months; FA and macular SD-OCT were
recorded at baseline and monthly.
Results: Data show that hyperbaric oxygen is an effective adjuvant
to bevacizumab in the treatment of diabetic macular edema. Both
groups show improvement of macular edema and visual acuity. The
group with combine theraphy showed better results when comparing
to control group. The reduction of the macular edema seems to last
longer in the study group as documented on FA and SD-OCT.
Conclusions: Our results suggest that the coadjuvant use of
hyperbaric oxygen in addition to the antiangiogenic effect of
intravitreal bevacizumab, could be beneficial in the treatment of
diabetic macular edema. Long-term follow up and better study
desings are needed for a better understanding of this combination
theraphy.
Commercial Relationships: Efrain Romo-Garcia, None; David
Magana-Garcia, None; Mariana Gonzalez-Reyes, None; Tania
Nieblas-Aguilar, None; Sergio Sital-Gastelum, None
Program Number: 1755 Poster Board Number: A0192
Presentation Time: 11:00 AM–12:45 PM
Efficacy of nepafenac ophthalmic solution in preventing macular
edema after cataract surgery in patients with diabetes
Kaori Sekimoto, Kensuke Haruyama, Tetsuri Sugimoto, Yuta Suzuki,
Shigehiko Kitano. Depertment of Ophthalmology, Diabetes Center,
Tokyo Medical Women, Tokyo, Japan.
Purpose: To evaluate whether topical nepafenac 0.1% solution alone
is as efficacious as is topical nepafenac plus betamethasone sodium
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
phosphate 0.1% solution in the outcomes of cataract surgery in
patients with diabetes.
Methods: Patients who had retinal thickening of less than 300 μm
were eligible to enter the study. They were scheduled to undergo
phacoemulsification cataract extraction with posterior chamber
intraocular lens implantation and were randomized to receive either
topical nepafenac 0.1% 3 times daily alone (nepafenac group:
n=22) or nepafenac 0.1% 3 times daily plus betamethasone sodium
phosphate 0.1% 4 times daily (nepafenac/steroid group: n=26) for
approximately six weeks postoperatively. Outcomes were measured
by observing best-corrected visual acuity, intraocular pressure,
flare in the anterior chamber, and change in macular thickness
using optical coherence tomography. The same method was used to
compare patients with non-proliferative retinopathy (NPDR).
Results: There was no significant difference in best-corrected visual
acuity, intraocular pressure, and flare between the nepafenac group
and the nepafenac/steroid group. At 4 weeks, the mean central
macular subfield thickness was 255.3 ±25.9 μm in the nepafenac
group and 271.7 ±32.5 μm in the nepafenac/steroid group. Up to 4
weeks, there was no significant difference in the macular thickness
between the nepafenac group and the nepafenac/steroid group. In
patients with NPDR, the increase in macular thicknesses was more
inhibited in the nepafenac group than the nepafenac/steroid group at
4 weeks.
Conclusions: This study suggests that topical nepafenac 0.1% alone
has effects equivalent to or greater than those of nepafenac 0.1% plus
betamethasone sodium phosphate 0.1% in the outcomes of cataract
surgery in patients with diabetic retinopathy.
Commercial Relationships: Kaori Sekimoto, None; Kensuke
Haruyama, None; Tetsuri Sugimoto, None; Yuta Suzuki, None;
Shigehiko Kitano, None
Clinical Trial: 2287
Program Number: 1756 Poster Board Number: A0193
Presentation Time: 11:00 AM–12:45 PM
Trial to Assess the Efficacy of Neuroprotective Drugs
Administered Topically to Prevent or Arrest Diabetic
Retinopathy (EUROCONDOR)
Sandrina Nunes. AIBILI, Coimbra, Portugal.
Purpose: Baseline data of the EUROCONDOR Project (ECFP7-278040) to assess neurovascular changes and the efficacy of
neuroprotective drugs administered topically to prevent or arrest
diabetic retinopathy (DR).
Methods: 450 type 2 diabetic patients, 194 with no DR (ETDRS
level < 20) and 256 with mild non-proliferative DR (NPDR – ETDRS
levels 20 or 35) were included in a 2-year interventional clinical
trial to assess functional abnormalities related to neurodegeneration
and the efficacy of neuroprotective drugs administered topically to
prevent or arrest DR. Patients were recruited in 11 clinical sites in
the European Vision Institute Clinical Research Network (EVICR.
net). The study started in February 2013 and recruitment was
completed in November 2013. Five visits are planned at months 0,
6, 12, 18 and 24, including best corrected visual acuity (BCVA),
multifocal electroretinography (mfERG), colour fundus photography
(CFP) for ETDRS classification and microaneurysm (MA) turnover
using RetmarkerDR®, and spectral domain optical coherence
tomography (SD-OCT). Centralised reading of mfERG, ETDRS, MA
turnover and SD-OCT is performed by the Coimbra Ophthlamology
Reading Centre (CORC). A normative database of 110 patients was
established to evaluate mfERG implicit time Z-scores. One eye per
patient is selected by the Reading Centre as the study eye.
Results: 450 patients were included (65.6% males) with ages ranging
from 45 to 75 years. The mean systolic and diastolic blood pressure
was, respectively, 135.1 ± 14.7 and 77.2 ± 10.1 mmHg. Eyes/patients
showed at baseline a mean number of MA of 0.7 ± 1.3 and a mean
BCVA of 83.7 ± 10.3 ETDRS letters. HbA1C was significantly
increased in NPDR patients (7.27 ± 1.05 % vs, 6.95 ± 0.86 %;
p=0.001). Comparing mean central subfield retinal thickness (RT)
with normal values, 2.8 % of the eyes/patients showed an abnormally
decreased RT and 1.4% an abnormally increased RT.
Conclusions: mfERG, RT and MA registered at baseline indicate
varying involvement of the different components of the neurovascular
unit. The results obtained in the baseline data analysis will contribute
to identify correlations between DR initial neurodegenerative and
microvascular changes.
Commercial Relationships: Sandrina Nunes, None
Support: EC-FP7-278040
Clinical Trial: NCT01726075
Program Number: 1757 Poster Board Number: A0194
Presentation Time: 11:00 AM–12:45 PM
A Phase 1b/2a Open-Label, Multiple-Ascending Dose Cohort
Study to Assess the Safety, Tolerability, Pilot Efficacy,
Pharmacokinetics and Pharmacodynamic Effects of 28-Day
Repeat Subcutaneous Doses of AKB-9778 in Subjects with
Diabetic Macular Edema
Mitchell G. Brigell1, Peter A. Campochiaro2, Raafay Sophie2, Michael
Tolentino3, Daniel Miller4, David Browning5, David S. Boyer6, Jeffrey
S. Heier7, Kevin Peters1. 1Aerpio Therapeutics, Cincinnati, OH;
2
Johns Hopkins Wilmer Eye Inst, Baltimore, MD; 3Ctr for Retina
And Macular Disease, Winter Haven, FL; 4Cincinnati Eye Institute,
Cincinnati, OH; 5Charlotte EENT Associates, Charlotte, NC; 6Retina
Vitreous Associates Medical Group, Los Angeles, CA; 7Ophthalmic
Consultants of Boston, Boston, MA.
Purpose: Although VEGF inhibitors have provided a significant
advance in treatment of clinically significant DME, many patients
remain inadequately treated. AKB-7998 activates the TIE2 pathway
to restore retinal vascular integrity in the presence of elevated ANG2
and VEGF levels. This study was designed to evaluate the safety and
efficacy of 28 day BID subcutaneous dosing of AKB-9778 in patients
with clinically significant DME.
Methods: Twenty-four DME patients with central retinal subfield
thickness (CRT) of > 325 μm and ETDRS acuity < 74 letters
participated in the study. Patients were included if they had not been
treated for DME in the study eye for > 28 days prior to baseline.
Cohorts of 6 patients each were treated with 5 mg, 15 mg, 22.5 mg
and 30 mg of AKB-9778 delivered subcutaneously BID for 28 days.
Patients were observed for an additional 56 days. Ophthalmic exams
including OCT and BCVA, physical exams, blood chemistry and
hematology were obtained weekly. Pharmacokinetic samples were
obtained at multiple time points post-dosing on Day 1 and Day 14.
Results: All dose levels of AKB-9778 were well tolerated. There
were no serious adverse effects or deaths and no changes in clinical
labs or hematology were observed. Subcutaneous injections were
well tolerated. A transient, generally asymptomatic reduction in blood
pressure was observed at the 22.5 and 30 mg doses. One patient
in each of these dose groups discontinued from the study after the
first dose due to vasovagal events. Pharmacokinetics showed dose
proportional increase in exposure with a tmax of 15 - 30 minutes and
a half-life of ~1 hour. The 5 mg dose did not improve visual acuity or
CRT. At doses of 15 mg or greater, after 1 month of treatment, 7/18
patients had reduction in CRT of > 50 μm and 12/18 patients gained 5
or more letters of visual acuity.
Conclusions: The present study shows that subcutaneous dosing
of AKB-9778 is safe and well tolerated through 28 days of dosing
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
at levels up to 30 mg BID. Reduction of DME and corresponding
increase of visual acuity were observed at doses of 15 mg and above.
The results suggest that TIE2 activation may be effective in the
treatment of DME.
Commercial Relationships: Mitchell G. Brigell, Aerpio
Therapeutics (E); Peter A. Campochiaro, Abbvie (C), Aerpio
Therapeutics (C), Aerpio Therapeutics (F), Alimera (C), Genentech
(C), Regeneron (C); Raafay Sophie, None; Michael Tolentino,
Aerpio Therapeutics (F), Bayer (C), Regeneron (C), Valient (C);
Daniel Miller, Aerpio (F); David Browning, Aerpio (F), Alimera
Sciences (C), Alimera Sciences (R); David S. Boyer, Aerpio
Therapeutics (F), Alcon (C), Alcon (R), Alimera Sciences (C),
Allergan (C), Allergan (R), Bausch and Lomb (C), Bayer (C),
Genentech (C), Genentech (R), Merck (C), Thrombogenics (C);
Jeffrey S. Heier, Aerpio Therapeutics (C), Aerpio Therapeutics (F),
Alcon (C), Allergan (C), Bausch and Lomb (C), Genentech (C),
Genentech (R), Genzyme (C), Lpath (C), Neovista (C), Neovista
(R), Novartis (C), Regeneron (C), Regeneron (R), Sanofi-Fovea (C);
Kevin Peters, Aerpio Therapeutics (E)
Clinical Trial: NCT01702441
Program Number: 1758 Poster Board Number: A0195
Presentation Time: 11:00 AM–12:45 PM
Demographics and Baseline Characteristics of the iDEAL
Study: A Randomized, Multi-center, Phase II Study of the safety,
Tolerability, and Bioactivity of Repeated Intravitreal Injections of
iCO-007 as Monotherapy or in Combination with Ranibizumab
or Laser Photocoagulation in the Treatment of Diabetic Macular
Edema with Involvement of the FoveAL Center
Yasir Sepah1, Diana V. Do1, David Callanan2, Victor H. Gonzalez3,
Lawrence Halperin4, Brian B. Berger5, Mostafa S. Hanout1, Peter
Hnik6, Quan Dong Nguyen1. 1Ocular Imaging Research and Reading
Center, Stanley M. Truhlsen Eye Institute. University of Nebraska
Medical Center, Omaha, NE; 2Texas Retina Associates, Arlingtoin,
TX; 3Valley Retina Institute, Harlingen, TX; 4Retina Group of
Florida, Ft Lauderdale, FL; 5Retina Research Center, Austin, TX;
6
iCo Therapeutics Inc., Vancouver, BC, Canada.
Purpose: iCo-007 is a 2nd generation anti-sense inhibitor targeting
C-raf kinase mRNA. C-raf kinase plays a key role in the MAP
kinase signaling pathway, involved in angiogenesis and vascular
permeability. The Phase I study demonstrated bioactivity of
intravitreal iCo-007 in a number of eyes with diffuse diabetic
macular edema (DME). The design, demographics, and baseline
characteristics of the iDEAL Study are described.
Methods: Subjects 18 years of age with ME secondary to type 1
or 2 diabetes across 28 sites in the US were enrolled in the Study.
Key inclusion criteria were 1) best corrected visual acuity (BCVA)
of ≤20/32 or ≥20/320; 2) central foveal thickness (CFT) of >250m
on time-domain OCT at baseline (BL); 3) non-proliferative diabetic
retinopathy (NPDR) or inactive PDR.
Patients were randomized to 4 groups in a 1:1:1:1 ratio. Groups I
and II receive 350mg and 700mg of iCo-007 at BL and month (M)
4, respectively. Group III receives 350mg of iCo-007 at BL and M4
with mandatory focal/grid laser treatment 7 days after BL iCo-007,
and optional laser at M4 + 7 days. Group IV receives ranibizumab
(0.5mg) at BL and M4 followed 14 days later (BL + 14 days and
M4 + 14 days) by iCo-007 350mg. Re-treatment at M8 (primary end
point) is optional for all groups based on predetermined retreatment
criteria.
Primary objective of the study is the change in VA from BL to M8.
Secondary objectives include VA change from BL to M12, changes in
FTh from BL to M8 and M12, along with safety and tolerability.
Results: The iDEAL study has finished enrollment with 187 subjects
randomized (185 treated). Mean age of subjects is 62.2; 102 males
(55.1%), 144 are Caucasians (77.8%). Mean BL VA/CFT were
57.5/426mm in group I, 59.5/450mm in group II, 61.1/422mm in group
III, and 61.2/412mm in group IV. Mean BL HbA1c was 7.5%, 7.8%,
7.7%, and 7.4% in groups I, II, III and IV, respectively. 34.1% of
study eyes were treatment naive.
Conclusions: Demographics of subjects in the iDEAL study are
consistent with those reported from other phase II/III studies for
DME. Therefore, safety and efficacy outcomes of the study may be
generalizable to other populations with DR and DME.
Commercial Relationships: Yasir Sepah, None; Diana V. Do,
Genentech (F), iCo Therapeutics (F), Regeneron (F); David
Callanan, Alcon (C), Allergan (C), Bausch and Lomb (C), Forsight
Inc. (I); Victor H. Gonzalez, Alcon (F), Alimera Sciences (F),
Allergan (F), Ampio (F), Bausch and Lomb (F), Bayer Inc. (F),
DRCR.net (F), Eyetech (F), Genentech Inc. (F), Iconic (F), Iconic
Pharmaceuticals (F), Ista Pharmaceuticals (F), Janix (F), Lpath (F),
Ophthotec (F), Pfizer (F), Quark (F), Regeneron (F), Thrombogenics
(F), Valeant (F); Lawrence Halperin, Covalent Medical (I); Brian B.
Berger, Acucela (F), Alcon labs (F), Alimera Sciences (F), Allergan
(F), ALLERGAN ADVISORY PANEL (C), Ampio Pharmaceuticals
(F), Comentis (F), DRCR.net (F), Genentech (F), Genera (F), Glaxo
Smith Kline (F), iCo Therapeutics (F), Lpath (F), Lux Biosciences
(F), MacuSight (F), Ophthotech (F), Pfizer Inc. (F), Santen Advisory
Board (C), Thrombogenics (F), XOMA (F); Mostafa S. Hanout,
None; Peter Hnik, iCo Therapeutics (E); Quan Dong Nguyen,
Genentech (F), iCo Therapeutics (F), Regeneron (F)
Support: Juvenile Diabetes Research Foundation
Clinical Trial: NCT01565148
Program Number: 1759 Poster Board Number: A0196
Presentation Time: 11:00 AM–12:45 PM
Visual Outcomes and Adverse Events in Diabetic Macular Edema
Treated with VEGF Inhibitors-A Systematic Review
Karim Diab1, Swati Chavda1, Nathan Gorfinkel1, William Hodge1,
2
, Brad Dishan3, Hargurinder Singh1, 2. 1Ophthalmology, Western
University, London, ON, Canada; 2Epidemiology & Biostatistics,
Western University, London, ON, Canada; 3Medical Library, St.
Joseph’s Health Care, London, ON, Canada.
Purpose: VEGF Inhibitors are being used as part of the standard of
care for diabetic macular edema. We did a systematic review to assess
the overall efficacy and side effects of these agents for this condition.
Methods: Relevant literature was obtained using an exhaustive
search from the Medline, Biosis, CINAHL, Cochrane and Web
of Science databases. Grey literature that consisted of lectures,
seminars and conferences was also retrieved. The results were then
inserted into EPPI, the systematic review program. Duplicates were
then removed using EPPI after a bibliographic record was made.
Literature was then passed through two levels of screening followed
by a data extraction level. Papers had to be included after each level
of screening in order for data to be extracted from them. EPPI records
whether a publication is included or excluded after each level of
screening.
Results: 24 studies treating 3992 eyes were retrieved. 83% of
studies recorded an improvement in mean macular thickness ranging
from an average of 16 to 194 microns. 93% of studies recorded an
improvement of central vision. 14 cases of endophthalmitis have been
reported (0.35%) and 39 cases of retinal detachment (0.98%). 105
cases of vitreous hemorrhage have been reported (2.6%)
Conclusions: VEGF inhibitor treatment for diabetic macular edema
shows consistently positive results with few side but potentially
serious effects.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Commercial Relationships: Karim Diab, None; Swati Chavda,
None; Nathan Gorfinkel, None; William Hodge, None; Brad
Dishan, None; Hargurinder Singh, None
Support: AMOSO Innovation 2011-2012 Fund (INN12-010)
Ontario, Canada
Program Number: 1760 Poster Board Number: A0197
Presentation Time: 11:00 AM–12:45 PM
Diabetic Macular Oedema and Intravitreal Bevacizumab
(Avastin)
Shiao Wei Wong, Pallavi Tyagi, Simon A. Hewick. Ophthalmology,
NHS, Inverness, United Kingdom.
Purpose: To determine the clinical effectiveness of intravitreal
bevacizumab (Avastin) in the treatment of patients with diabetic
macular oedema.
Methods: Data was collected retrospectively from August 2012 to
February 2013 in Raigmore Hospital, Inverness, Scotland. 19 patients
(24 eyes) with clinically significant diabetic macular oedema were
included in this study. Response to treatment was monitored by best
corrected visual acuity (BCVA) and OCT central retinal thickness
(CRT) monthly following treatment. Main outcome measure is any
change in BCVA .
Results: A total of 24 eyes of 19 patients received treatment for
diabetic macular oedema. Mean age at receiving first injection was
66 years (range 47 – 83 years). The average number of injections in
24 eyes was 3 (range 1-6 injections). Average duration of follow up
was 15 months (range 4 - 48 months). 12 eyes out of 24 eyes (50%)
showed improvement of vision at final follow up. 2 eyes (8.3%)
maintained vision at final follow up. 10 eyes (41.7%) showed worse
vision at final follow up. The OCT CRT was reduced in most patients
(90.9%) at final follow up but only 45.0% of these patients showed
improvement in vision at final follow up.
Conclusions: Our patients with diabetic macular oedema who
received Avastin intravitreal injection showed 50% visual response
rate to Avastin. OCT CRT was reduced in most patients but there
was not a correlation between OCT CRT and visual improvement.
Initial OCT CRT is not a useful predictor of visual gain. Ceiling was
effect seen in patients with poorer initial vision who are getting more
gain in vision than patients with better initial vision. Finally, the
subsequent visual response to Avastin can possibly be predicted from
visual response after the first 3 loading doses of Avastin.
Commercial Relationships: Shiao Wei Wong, None; Pallavi Tyagi,
None; Simon A. Hewick, None
Program Number: 1761 Poster Board Number: A0198
Presentation Time: 11:00 AM–12:45 PM
Changes in macular perfusion during antiangiogenic treatment of
diabetic macular edema
Sonja G. Prager1, Christian Simader1, Gabor G. Deak1, Jan
Lammer1, Bianca Gerendas1, Sebastian M. Waldstein1, Michael
Kundi2, Ursula Schmidt-Erfurth1. 1Ophthalmology, Medical
University Vienna, Vienna, Austria; 2Center of Public Health,
Medical University Vienna, Vienna, Austria.
Purpose: To investigate angiographic changes in retinal perfusion
during the course of treatment with repeated intravitreal ranibizumab
injections in patients with diabetic macular edema.
Methods: Subanalysis of biannually performed fluorescence
angiography (FA) in patients of the RESTORE study. Patients with
visual impairment due to diabetic macular edema were included
in this prospective, multicenter clinical trial and randomized to
3 treatment arms: 0.5 mg intravitreal ranibizumab monotherapy
(RT), 0.5 mg intravitreal ranibizumab combined with macular laser
(CT) or laser therapy only (LT). After a loading dose of 3 monthly
ranibizumab injections or baseline laser therapy respectively patients
were treated following predefined retreatment criteria (PRN).
Biannually acquired FA images were graded by certified readers of
the Vienna Reading Center: The innermost capillaries around the
fovea were outlined manually and the area was calculated defining
the foveal avascular zone (FAZ). Changes in size and formation of
the FAZ as well as capillary drop out at the macula were followed
over the period of treatment to assess treatment dependent effects on
macular perfusion within and between treatment arms.
Results: Three hundred forty five diabetic patients were included in
this clinical trial. At baseline, the FAZ configuration was severely
or completely destroyed in 17 % of patients (RT=18 %,, CT=17
%, LT=17%). A parafoveal capillary dropout was found in 3% of
patients (RT=3 %,, CT=3 %, LT=2%). After 12 months, the FAZ
configuration was severely or completely destroyed in 9% of patients
(RT=10 %,, CT=11 %, LT=5%) and parafoveal capillary dropout was
found in only 1% of patients (RT=1 %,, CT=1 %, LT=1%).
Conclusions: Within 12 months no progression of central
microangiopathy and non-perfusion was found in diabetic patients
receiving prolonged and repeated anti VEGF therapy.
Commercial Relationships: Sonja G. Prager, None; Christian
Simader, None; Gabor G. Deak, None; Jan Lammer, None;
Bianca Gerendas, None; Sebastian M. Waldstein, None; Michael
Kundi, None; Ursula Schmidt-Erfurth, Alcon (C), Allergan (C),
Bayer HealthCare (C), Boehringer (C), Novartis (C)
Clinical Trial: NCT00687804
Program Number: 1762 Poster Board Number: A0199
Presentation Time: 11:00 AM–12:45 PM
Intravitreous Bevacizumab and Standard Metabolic Control for
Diabetic Macular Edema – A Contrast Sensitivity Pilot Study.
Augusto Motta, Lisa Vasquez, Daniel A. Ferraz, Marcia S. Queiroz,
Maria Teresa B. Bonanomi, Walter Y. Takahashi. Ophtalmology (
Retina and Vitreous), University of Sao Paulo, São Paulo, Brazil.
Purpose: To evaluate the effects on contrast sensitivity (CS)
measuraments of intravitreal bevacizumab injections associated with
standard metabolic control in eyes with diabetic macular edema.
Methods: Prospective, randomized, masked and interventional
study. Forty-one eyes of 34 patients with type 2 DM, Glycate
hemoglobin (HbA1c) less than 11% and previously treated macular
edema three months before were randomized in two groups. The
baseline examination consisted of visual acuity (VA), CS using the
Pelli-Robson Charts, optical coherence tomography (OCT) and
angiofluoresceinography for all eyes. Group 1 ( 21 eyes) was treated
with intravitreal bevacizumab injection (1.25mg) at the weeks 0,6,12
and 18. Group 2 (20 eyes) received a sham injection at the weeks 0
and 6; and intravitreal bevacizumab injetion at the weeks 12 and 18.
The Mann-Whitney U and Wilcoxon tests were applied to compare
the differences between the two groups to categorical and continuous
variables, respectively. The null hypothesis were rejected for P-value
< 0.05.
Results: Reduction > 0.5% on average HbA1c levels in both groups
in the period of 24 weeks. The corresponding data: the baseline
was 8.28% ± 1.08 and 8.44% ± 1.20; and at week 24, 7.72% ±
0.99 and 7.66% ± 1.15 for groups 1 and 2 respectively. The mean
CS for groups 1 and 2 was at baseline respectively: 1.14±0.37 and
1.00±0.32 logCS (p=0.36). At week 12, respectively 1.30±0.24 and
1.13±0.30 logCS (p=0.11). At week 24, respectively 1.28±0.23 and
1.21±0.22 logCS (p=0.51). No statistically significant difference was
found between the two groups for VA, OCT or CS in the period of 6
months. Both groups improved substantially their VA, OCT and CS at
week 12 and 24 (p<0.05).
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Conclusions: The CS improvement demonstrated in both groups
can be attributed to better control of the blood glucose with glycated
hemoglobin (HbA1c) associated with intravitreal bevacizumab
injections. Two consecutive intravitreal bevacizumab injections
associated with standard metabolic control were comparable to two
consecutive sham injections associated with standard metabolic
control for macular structure and function in diabetic macular edema
Commercial Relationships: Augusto Motta, None; Lisa Vasquez,
None; Daniel A. Ferraz, None; Marcia S. Queiroz, None; Maria
Teresa B. Bonanomi, None; Walter Y. Takahashi, None
Program Number: 1763 Poster Board Number: A0200
Presentation Time: 11:00 AM–12:45 PM
Assessing pan-retinal cone function following ranibizumab
treatment for diabetic macular edema by recording the photopic
electroretinogram
Ammar M. Al-Sayegh1, Ambreen Tariq1, Aman Kirmani2, Samantha
Mann2, Christopher J. Hammond1, 2, Omar A. Mahroo1, 2.
1
Ophthalmology, King’s College London, London, United Kingdom;
2
Ophthalmology, St Thomas’ Hospital, London, United Kingdom.
Purpose: AntiVEGF agents have shown to be effective in treating
diabetic macular edema (DME). VEGF also has a maintenance role
in the normal retina, so there are theoretical concerns about possible
adverse ocular effects of inhibition. One study showed that switching
off VEGF expression in the adult mouse retina led to marked cone
photoreceptor dysfunction (Kurihara et al, J Clin Invest 2012). We
explored whether patients receiving intravitreal ranibizumab for
DME might have detectable changes in cone function after their
first dose or after three loading doses by recording the photopic
electroretinogram (ERG) at baseline and before each subsequent
dose.
Methods: Patients, who had no previous antiVEGF treatment, and
who were due to receive a course of ranibizumab treatment (three
injections approximately 4-6 weeks apart) for DME in one eye
were enrolled. Photopic 30 Hz flicker and flash full-field ERGs
(corresponding to the ISCEV standard photopic protocol) were
recorded from both eyes prior to their first treatment and at each
subsequent visit prior to treatment. Response parameters (amplitudes
and implicit times for flicker ERG and for flash a-waves and
b-waves) post-treatment were compared to baseline (paired t test).
Results: Post-treatment ERGs were available for 13 patients 4-6
weeks following their first injection. For these patients, posttreatment ERG parameters were no more than 10% different from
baseline in the treated eye, and were no more than 20% different
from baseline in the untreated eye. In the treated eye, none of the
comparisons were statistically significant; in the untreated eye
there was a significant increase in 30 Hz flicker amplitude (mean
increase 15%, p = 0.026). For 6 patients, post-treatment ERGs were
available 4-6 weeks following their third injection. Post-treatment
ERG parameters for these patients were no more than 10% different
from baseline for both treated and untreated eyes, and none of the
comparisons here reached statistical significance.
Conclusions: In this exploratory study, no significant change in
global cone function, as assessed from photopic ERG responses, was
detectable in the treated eyes of patients, and changes appeared to be
no greater than those seen in the untreated eyes.
Commercial Relationships: Ammar M. Al-Sayegh, None;
Ambreen Tariq, None; Aman Kirmani, Novartis (R); Samantha
Mann, Alimera (R), Novartis (R); Christopher J. Hammond, None;
Omar A. Mahroo, None
Support: Fight for Sight UK grant to OAM (Grant 1409/10)
Program Number: 1764 Poster Board Number: A0201
Presentation Time: 11:00 AM–12:45 PM
Intravitreal injection of bevacizumab for diabetic macula edema:
morphological and functional outcomes at 1 day after injection
Rieko Higashida, Yutaka Imamura, Atsushi Ishikawa, Yorihisa
Tsutsumi, Yoshikazu Ichikawa, Takeshi Wakakuri, Masahiro Ishida.
Ophthalmology, Teikyo University School of Medicine, Kawasaki,
Kanagawa, Japan.
Purpose: To evaluate and compare the visual and anatomical
outcomes in eyes with diabetic macular edema (DME) at 1 day and 1
week after injection of intravitreal bevacizumab.
Methods: A retrospective, consecutive case series identified 21
consecutive patients with DME undergoing intravitreal injection of
bevacizumab. Optical coherence tomography images were taken at
the day of injection and 1-day and 1 week after injection. Retinal
thickness at fovea and visual acuity were monitored before and after
injection.
Results: The mean age of patients was 65.1 years old (10 females).
Retinal thickness at fovea was 490 ± 169 mm before injection, and
was 442 ± 162 mm and 335 ± 148 mm at 1 day and 1 week after
injection. (Student t test, P=0.001 and 0.004, respectively) Visual
acuity (logMAR) was 0.616±0.344 before injection and 0.682±0.413
and 0.425±0.237 at 1 day and 1 week after injection. (P=0.567 and
0.063, respectively)
Conclusions: Resolution of intraretinal fluids was observed at 1
day postoperatively, however at least 1 week is needed so that large
amounts of fluids are absorbed in DME. Significant improvement
of vision was not observed at 1 day and 1 week after injection.
Intraretinal fluids seem to disappear more slowly in DME than those
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
in retinal vein occulusion after intravitreal injection of bevacizumab
(Ishikawa A, 2013 ARVO abstract).
Commercial Relationships: Rieko Higashida, None; Yutaka
Imamura, None; Atsushi Ishikawa, None; Yorihisa Tsutsumi,
None; Yoshikazu Ichikawa, None; Takeshi Wakakuri, None;
Masahiro Ishida, None
Program Number: 1765 Poster Board Number: A0202
Presentation Time: 11:00 AM–12:45 PM
Influence of ranibizumab on electrophysiological responses in
diabetic eyes with macular edema
Monica Loevestam-Adrian, Kristina Holm. Ophthalmology, Lund
University Hospital, Lund, Sweden.
Purpose: To evaluate the influence of ranibizumab on the multifocal
electroretinography (mfERG), full-field electroretinography (ffERG)
and Optical Coherence Tomography (OCT) in diabetic eyes (n=16)
with diabetic macular edema.
Methods: In 16 eyes (15 diabetic subjects), (age 63±12 years,
duration 17±12 years) with no or background diabetic retinopathy
(DR) and macular edema, and not previously treated, the change
in visual acuity (ETDRS letters), mfERG, ffERG and OCT was
analyzed, before and one month after three monthly injections with
ranibizumab.
Results: From baseline mean BCVA improved from 53±6 ETDRS
letters to 61±6 ETDRS letters (p=0.000) one month after the last
injection. The mean central retinal thickness reduced, from 404±117
to 286±54 m (p=0.000). There were no changes in neither mfERG
amplitudes or implicit time in any of the five rings measured, or in
the blue light amplitudes. There was a trend towards shorter implicit
time in 30Hz flicker, after treatment; 34.3±3.5 vs. 33.5±2.8 ms,
(p=0.07).
Conclusions: Though the central retinal thickness was reduced after
three injections with ranibizumab and the subjects gained a mean of
8 ETDRS letters, there was no change in amplitude or implicit time
in mfERG. A trend towards shorter implicit time in 30 Hz flicker was
seen.
Commercial Relationships: Monica Loevestam-Adrian, None;
Kristina Holm, None
Support: Novartis
Clinical Trial: 2011/590
Program Number: 1766 Poster Board Number: A0203
Presentation Time: 11:00 AM–12:45 PM
Retinal vascular changes in eyes with diabetic macular edema
treated with different doses of ranibizumab
Jose Maya, Yasir Sepah, Liz J. Zapata, Mostafa S. Hanout,
Mohammad A. Sadiq, Salman Sarwar, Kathleen E. Guinn, Nithya
Rajagopalan, Diana V. Do, Quan Dong Nguyen. Ocular Imaging
Research and Reading Center, Stanley M. Truhlsen Eye Institute,
Unviersity of Nebraska Medical Center, Omaha, NE.
Purpose: The aim of this study is to assess the changes in vessel
diameter in patients with diabetic macular edema (DME) treated with
2 different doses of ranibizumab (RBZ).
Methods: Fundus photos from 55 patients (55 eyes) enrolled in the
READ-3 study (comparison of 0.5mg VS 2.0mg of RBZ for DME)
were analyzed. Photos were divided into two groups according to the
treatment arm (Group A=0.5mg; Group B=2.0mg). All eyes received
6 monthly injections starting at baseline visit. Central retinal arterial
equivalent (CRAE) and central retinal venular equivalent (CRVE)
were measured using Interactive Vessel Analysis (IVAN) software,
½ disc diameter to 1 disc diameter from the margin of the optic disc,
in 6 largest venules and arterioles. Parametric tests (paired t-test,
independent t-test) were performed to compare the CRVE and CRAE
between the two groups.
Results: 26 patients were included in group A; 29 in group B. The
mean age was 63 and 65 in group A and B, respectively. 14 patients
were males in group A; 17 males in group B. There was reduction
in both CRAE and CRVE at month 6 compared to baseline for both
doses of RBZ (table). The changes were statistically significant in
CRVE and demonstrated a trend towards significance in CRAE.
However, inter-comparison did not demonstrate any statistically
significant differences between the two dose groups.
Conclusions: Treatment of DME with RBZ appears to induce similar
reduction in CRVE and CRAE regardless of the dose. Such findings
imply that low and high dose of RBZ may have similar effects on
retinal vasculature in eyes with DME.
Commercial Relationships: Jose Maya, None; Yasir Sepah, None;
Liz J. Zapata, None; Mostafa S. Hanout, None; Mohammad A.
Sadiq, None; Salman Sarwar, None; Kathleen E. Guinn, None;
Nithya Rajagopalan, None; Diana V. Do, Genentech (F), Regeneron
(F); Quan Dong Nguyen, Genentech (F), Regeneron (F)
Support: JDRF International
Clinical Trial: NCT01077401
Program Number: 1767 Poster Board Number: A0204
Presentation Time: 11:00 AM–12:45 PM
Are Improvements in Diabetic Retinopathy Severity Clinically
Meaningful? Insights from Studies of Intravitreal Ranibizumab
(RBZ) in Patients with Diabetic Macular Edema (DME)
Jason S. Ehrlich, Jiameng Zhang. Genentech, Inc, South San
Francisco, CA.
Purpose: Worsening of diabetic retinopathy (DR) severity, seen by
step changes in the Early Treatment Diabetic Retinopathy Study
(ETDRS) DR severity scale, is clinically important because even
a single step worsening implies a markedly increased risk for
proliferative DR and/or DME in the future. However, the clinical
relevance of DR improvement is not well understood because it
has not been commonly observed in controlled trials. We have
reported that intravitreal RBZ not only reduces the likelihood of
DR worsening, but also improves DR severity in many patients,
providing an opportunity to study the clinical significance of
improvement. We explored associations between DR improvement
and clinical outcomes using data from Phase III studies of DME
patients.
Methods: Twenty-four month outcomes from 468 RBZ-treated
patients in RIDE (NCT00473382) and RISE (NCT00473330) were
used; these were patients randomized to monthly 0.3mg or 0.5mg
RBZ who had baseline DR severity data. Best-corrected visual acuity
(BCVA) was assessed by ETDRS testing; contrast sensitivity (CS) by
a Pelli-Robson chart; central foveal thickness by optical coherence
tomography (OCT); and ETDRS DR severity levels by evaluation
of photos at a reading center. BCVA, CS, and OCT outcomes across
groups experiencing varying levels of change in DR severity were
displayed along with the incidence of DR-associated clinical events.
Durability of DR severity changes following cessation of RBZ
therapy was examined.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Results: At month 24, significant BCVA gain (≥15 ETDRS letters)
was more common in patients with 2 or ≥3-step DR improvement
compared to those with no change or 1 step DR improvement or
worsening (Table). Similarly, the magnitude of mean BCVA and
CS changes were greater with 2 or ≥3-step DR improvement, and
resolution of macular edema (OCT ≤250 um) was more common.
Conclusions: Patients with substantial DR improvement (2 or ≥3
steps) were more likely to show significant gains in vision, and also
trend to better mean improvements in BCVA, visual function, and
anatomic outcomes compared to those with either no change or
worsening in DR severity. Substantial improvement in DR severity is
thus a clinically important outcome.
Commercial Relationships: Jason S. Ehrlich, Genentech (E);
Jiameng Zhang, Genentech (E)
Clinical Trial: NCT00473382, NCT00473330
Program Number: 1768 Poster Board Number: A0205
Presentation Time: 11:00 AM–12:45 PM
Ranibizumab for diabetic macular edema refractory to multiple
prior treatments
Lauren Ciulla, Thomas A. Ciulla. Midwest Eye Institute,
Indianapolis, IN.
Purpose: Diabetic macular edema (DME) can be refractory to
multiple treatment modalities, such as laser photocoagulation,
intravitreal triamcinolone (TA), and intravitreal bevacizumab (BEV).
There have been anecdotal reports of ranibizumab (RAN) showing
efficacy when these other modalities provided limited benefit. This
study sought to investigate this observation further.
Methods: A retrospective chart review was conducted in DME
patients refractory to multiple prior treatments who were being
treated with 0.3 mg RAN every 4 to 6 weeks on average. Number
and type of prior treatments, Snellen visual acuity and OCT central
subfield thickness at each RAN injection were reviewed.
Results: 38 eyes of 24 patients with refractory DME were treated
with RAN. Prior to treatment with RAN, this group of eyes received
an average of 1.5 macular laser treatments, 0.5 TA, and 3.4 BEV. The
mean visual acuity prior to the initial RAN injection was 20/155 and
the mean CSFT was 438 um. There was a linear relationship between
the number of RAN injections and mean CSFT, improving with
nearly each RAN injection to 288 um by the sixth RAN injection (R2
= 0.86, P = 0.022). Visual acuity did not improve however.
Conclusions: RAN improves DME refractory to prior treatments
with laser photocoagulation, TA, and BEV. Visual acuity did not
improve; this could be due to photoreceptor dysfunction from chronic
DME, ischemia or both. Further study is warranted.
Commercial Relationships: Lauren Ciulla, None; Thomas A.
Ciulla, None
Program Number: 1769 Poster Board Number: A0206
Presentation Time: 11:00 AM–12:45 PM
Effects of the treatment with intravitreal injection of
Ranibizumab for Diabetic Macular Edema.Our Experience: 30
month Follow up
lucia comastri, Matias Iglicki, Juan Pablo Francos, Juan Manuel
Cortalezzi, Diego Bar, Carmen N. Demetrio, Mario J. Saravia, Jorge
Bar, Pablo Chiaradia, Marcelo Zas. RETINA, Hospital de Clincas,
Buenos Aires, Argentina.
Purpose: To present the effects of the treatment with intravitreal
injection of Ranibizumab (lucentis) for Diabetic Macular Edema:
Methods: The Study included 8 patients with diabetic macular edema
with or whiout previous Argon LASER and with or whitout previous
neovascularization.The diagnosis and monitoring of the treatment
were done by means of best correction visual acuity ( BCVA)
with ETDRS chart, symptoms, fluorescein angigraphy and optical
coherence tomography ( OCT) . The patients were monitored 7 and
30 days after the injection
Results: 30 days after the injection of ranibizumab (Lucentis)
0,05mg (0,5ml), BCVA had improved in 7 of 8 patients; they had
improved 3 lines at reading letters on the ETDRS chart. The OCT
showed an improvement in the retinal architecture in all patients:
the retinal thickness reduced an average of 60 micrometres and has
remained at that level up to the present (30 months follow-up).
Conclusions: One of the causes of diabetic macular edema is the
increase of the permeability of the hematoretinal barrier, the VEGF
is an important factor in this kind of increase. Thus, anti VEGF could
be a possible treatment for this pathology. Further follow-up of the
BCVA, OCT and symptoms is needed to decide whether retreatment
is required.
Commercial Relationships: lucia comastri, None; Matias Iglicki,
None; Juan Pablo Francos, None; Juan Manuel Cortalezzi, None;
Diego Bar, None; Carmen N. Demetrio, None; Mario J. Saravia,
None; Jorge Bar, None; Pablo Chiaradia, None; Marcelo Zas,
None
Program Number: 1770 Poster Board Number: A0207
Presentation Time: 11:00 AM–12:45 PM
Effect of intravitreal ranibizumab on retinal oxygen saturation in
diabetic macular edema – a pilot study
Christoph Mitsch, Katharina Kriechbaum, Katharina Kefer,
Magdalena Baratsits, Sonja G. Prager, Andreas Pollreisz,
Christoph D. Scholda, Ursula Schmidt-Erfurth. Ophthalmology and
Optometrics, Medical University of Vienna, Vienna, Austria.
Purpose: To determine the effect of intravitreal ranibizumab on the
oxygen saturation in retinal vasculature of patients with diabetic
macular edema (DME)
Methods: In 15 eyes of 15 consecutive patients with DME indicated
to receive intravitreal injections of 0.5ml ranibizumab, we performed
automatic retinal oximetry (Oxymap Inc., Reykjavik, Iceland) in the
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
treated and the non-treated eye 15 minutes prior to and 15 minutes
after intravitreal injection. The oxygen saturations in retinal arteries
and veins was determined. Vessel segments of first or second degree
were selected. The same segment was analysed before and after the
injection. Oximetry data were compared by paired two-tailed t-test.
The same examinations were performed in the untreated eye of the
same patients.
Results: Intravitreal administration of ranibizumab did not alter the
arterial hemoglobin saturation with oxygen (103.8 ± 9.7% prior to
the injection and 104.9 ± 25.4% after the procedure, p = 0.853). The
mean venous hemoglobin saturation with oxygen did not change
significantly after intra-vitreal injection (63.7 ± 9.6% to 59.6 ± 7.9%,
p = 0.168).
In untreated eyes, arterial hemoglobin saturation with oxygen did not
vary significantly (101.6 ± 5.2% prior to the injection of the other
eye and 101.1 ± 5.4% after the procedure, p = 0.763). Consistently,
the mean venous hemoglobin saturation with oxygen remained
unchanged (67.7 ± 6.3% to 66.0 ± 8.1%, p = 0.262).
Conclusions: Oxygen saturation in retinal vessels of DME eyes is
not altered significantly after intravitreal injection of ranibizumab.
Commercial Relationships: Christoph Mitsch, None; Katharina
Kriechbaum, None; Katharina Kefer, None; Magdalena Baratsits,
None; Sonja G. Prager, None; Andreas Pollreisz, None; Christoph
D. Scholda, None; Ursula Schmidt-Erfurth, Alcon (C), Bayer (C),
Böhringer (C), Novartis (C)
Program Number: 1771 Poster Board Number: A0208
Presentation Time: 11:00 AM–12:45 PM
The Course of Eyes with Vitrectomy Prior to Enrollment in a
Randomized Trial Evaluating Ranibizumab Plus Prompt or
Deferred Laser for Diabetic Macular Edema
Brian B. Berger. Retina Research Center, Austin, TX.
Purpose: To evaluate and compare the visual and optical coherence
tomography (OCT) outcomes in eyes with and without prior
vitrectomy receiving anti-Vascular Endothelial Growth Factor (antiVEGF) treatment for center involved diabetic macular edema (DME)
with reduced visual acuity
Methods: A post hoc exploratory evaluation was performed on eyes
in a Diabetic Retinopathy Clinical Research Network (DRCR.net)
study that received intravitreal ranibizumab plus prompt or deferred
laser for DME. Visual acuity (VA), OCT metrics, and number of
intravitreal injections and focal/grid laser treatments were compared
in eyes with previous vitrectomy (N = 25) and eyes without previous
vitrectomy (N = 335).
Results: At baseline, eyes with prior vitrectomy had worse VA,
thinner maculas, more advanced retinopathy, and more pseudophakia
than eyes without a history of vitrectomy. Analysis adjusted for these
covariates did not identify any differences between the vitrectomy
subgroups at each annual visit through 3 years for VA. At the 16 and
32 week visits, the adjusted mean decrease in OCT central subfield
thickness was greater for eyes without prior vitrectomy compared
with eyes with prior vitrectomy. However, after 1 year and through 3
years, a difference in thickness between the subgroups could not be
identified.
Conclusions: Early in the course of managing eyes with DME
and prior vitrectomy, the rate of anatomic, but not visual acuity,
improvement appears to be slower than eyes without vitrectomy, and
appears to require more monthly anti-VEGF treatments. However,
there is little evidence that eyes similar to those enrolled and
treated in this trial with center-involved DME and a history of prior
vitrectomy would have long term clinically important differences
with respect to visual acuity outcomes, OCT outcomes, or number of
injections compared with those without vitrectomy.
Commercial Relationships: Brian B. Berger, Alcon laboratories
(F), Allergan (C), Allergan (F), Ampio Pharmaceuticals (F),
Genentech (F), GlaxoSmithKline (F), iCo Therapeutics (F),
LpathIncorporated (F), Neovista (F), Santen (C), Thrombogenics (F),
Xoma (F)
Support: Supported through a cooperative agreement from the
National Eye Institute and the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, U.S.
Department of Health and Human Services EY14231, EY018817
Program Number: 1772 Poster Board Number: A0209
Presentation Time: 11:00 AM–12:45 PM
Intravitreal injections of ranibizumab with deferred laser grid
laser photocoagulation for the treatment of diabetic macular
edema with visual impairment: results at 1 year of LLOMD study
Agathe Cazet-Supervielle, Michèle Boissonnot, Sahbi Rouissi,
Nicolas Leveziel. Ophthalmology, Universital Hospital of Poitiers,
Poitiers, France.
Purpose: The diabetic macular edema (DME) is the most common
cause of central visual loss in diabetic patients. Intravitreal injections
(IVT) of ranibizumab have been approved for the treatment of DME.
However, around 10 ranibizumab IVTs are needed during the first
year of treatment with ranibizumab alone (RESOLVE study). In this
context, ranibizumab IVTs combined with macular laser may be
beneficial to reduce the number of IVT. The aim of this study was to
evaluate the efficacy of IVT associated with deferred laser grid for
diabetic macular edema. The primary endpoint was the number of
reinjections, the best-corrected visual acuity (BCVA) and the central
retinal thickness (CRT) measured at one year, of a strategy based on
intravitreal ranibizumab injection associated with laser treatment in
DME.
Methods: Prospective, monocentric open-label, uncontrolled phase
2 study.
15 eyes of 14 patients with BCVA ≤ 69 letters and CRT ≥ 310μ (OCT
Cirrus Zeiss) due to DME were enrolled between October 2011 and
October 2012.
Patients were treated with ranibizumab 0.5 mg given for 3 months
then with laser grid at month 4. During follow-up, a ranibizumab
injection was performed every 2 months in case of BCVA decreased
more than 5 letters.
Each patient in the study underwent VA measurement on the
Early Treatment Diabetic Retinopathy Study chart (ETDRS),
spectral domain-OCT, quality of life scale, glycated hemoglobin
(HbA1c) measurement, fluorescein angiography, and multifocal
electroretinogram at baseline and during their follow-up.
Results: The mean age of the subjects was 62 years old. At baseline,
their characteristics were (expressed as mean): duration of diabetes:
15 years, HbA1c: 7,4%, VA: 52 letters (20/100 snellen equivalent),
CRT: 475,6μ. From baseline at 12 months, there is a mean gain of
9,8 letters of BCVA (p = 0.013). The decrease in the average CRT is
55,3μ (p = 0.0425). 40% of patients didn’t require a new IVT at 12
months. No endophthalmitis cases occurred.
Conclusions: Adding macular grid to ranibizumab IVT appears
promising in the treatment of DME. It seems to reduce the number of
IVTs and consequently the economic burden of the treatment
Commercial Relationships: Agathe Cazet-Supervielle, None;
Michèle Boissonnot, None; Sahbi Rouissi, None; Nicolas Leveziel,
None
Clinical Trial: NCT01823965
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Program Number: 1773 Poster Board Number: A0210
Presentation Time: 11:00 AM–12:45 PM
Structural vs. Functional Changes in Diabetic Macular Oedema
Treated with Ranibizumab
James T. Brodie, Luke Membrey. Ophthalmology, Maidstone and
Tunbridge Wells NHS Trust, Maidstone, United Kingdom.
Purpose: Anti-VEGF therapies have emerged as a novel treatment
for diabetic macular oedema (DMO). Clinical trials investigating the
efficacy of treatment modalities for DMO typically use measurements
of macular thickness on ocular coherence tomography (OCT) to
assess therapeutic effect. Colour discrimination testing has been
shown to be highly sensitive and specific in identifying the presence
of clinically significant macular oedema. The purpose of this study
was to compare the structural changes seen on OCT imaging with
the functional changes on testing colour vision using the Cambridge
Colour Test ™ (CCT) in patients with DMO undergoing treatment
with Ranibizumab (Lucentis).
Methods: 14 patients (mean age = 61) initiating treatment with
Lucentis for DMO were recruited. Colour vision was assessed by
quantitatively measuring colour discrimination thresholds along the
protan, deutan, and tritan chromatic axes using the CCT at baseline
and 4 weeks post-injection. Visual acuity was measured using the
LogMAR chart and central macular thickness (CMT) using the
Topcon 3D OCT-2000.
Results: Tritan vector impairment was the most sensitive colour
discrimination measure to the presence of DMO with impairment
found in all treated eyes (n=19). Tritan discrimination was also the
most significantly impaired vector compared with protan and deutan
vectors. At baseline, there was a significant correlation between
impairment in tritan discrimination and reduction in BCVA (r=-0.46,
p=0.05). However, there was no significant correlation between CMT,
BCVA, and impairments in the other colour discrimination vectors.
The majority of treated eyes (15/19) had both reduced CMT and
improved BCVA. Colour discrimination along the protan and tritan
vectors was improved in more than half of treated eyes. Deutan
discrimination was the least improved vector. Although there was a
positive trend of improvements in CMT, BCVA, and protan and tritan
colour discrimination after treatment, the correlation between these
changes was not statistically significant.
Conclusions: Impairment in tritan colour discrimination thresholds
provides a sensitive indication of the presence of retinal thickening
and correlates strongly with reductions in visual acuity. These
preliminary findings also suggest that colour discrimination, as
measured by the CCT, may be a novel way to monitor the efficacy
of treatment in DMO in conjunction with BCVA and CMT
measurements.
Commercial Relationships: James T. Brodie, None; Luke
Membrey, None
Program Number: 1774 Poster Board Number: A0211
Presentation Time: 11:00 AM–12:45 PM
Impact of summer follow-up interruption on functional and
anatomical results over the course of Ranibizumab treatment for
Diabetic Macular Edema
ora levy, Franck Fajnkuchen, Benjamin Penaud, Gilles Chaine,
Audrey Giocanti-Auregan. Ophthalmology, APHP Hopital Avicenne,
Bobigny, France.
Purpose: Ranibizumab Intravitreal injections (IVT) improve Best
Corrected Visual Acuity (BCVA) and lower Central Foveal Thickness
(CFT) in Diabetic Macular Edema (DME). This treatment requires
a monthly follow-up. Nevertheless, a long period of follow-up
interruption can occur during summer break. The purpose of this
study was to evaluate whether this period actually impacts on BCVA
and CFT over the course of DME treatment.
Methods: We included in a retrospective fashion all patients with
DME over the course of Ranibizumab injections from April to
October 2013 with good anatomical and functional results after 3
initial IVT followed by a pro re nata strategy. We have included
all patients who were neither followed nor injected during at
least 7 consecutive weeks. 2 outcomes were assessed : BCVA
(ETDRS scale) and CFT on spectral domain OCT, (OPKO, Optos,
Dunfermline, Scotland) before and after the break.
Results: We have included 12 eyes of 11 patients (6 women, 5 men)
who stopped their follow-up for at least 7 weeks. Mean age was 61.8
years, mean duration of break was 12 weeks (from 7.1 to 26 weeks).
Patients underwent an average of 4 IVT and were treated for 5.7
months before the summer break. All patients came back to followup after the break. When the patients were back to follow-up, mean
decrease in BCVA was -3.6 letters (from +8 to -22 letters) and mean
increase in CFT was +209 microns (from -200mm to +920 mm).
Conclusions: 3 months of break in follow-up generally due to
summer holiday, does not seem to have irreversible consequences
on functional results in DME treatment. In this case series, the break
of follow-up has widely increased CFT while it did not significantly
impact BCVA. This fact underlines the weak correlation between
anatomical and functional results over the course of DME treatment.
Commercial Relationships: ora levy, None; Franck Fajnkuchen,
None; Benjamin Penaud, None; Gilles Chaine, None; Audrey
Giocanti-Auregan, None
Program Number: 1775 Poster Board Number: A0212
Presentation Time: 11:00 AM–12:45 PM
Aflibercept therapy for diabetic macular edema resistant to
ranibizumab and bevacizumab
Peter Karth, Darius M. Moshfeghi, Theodore Leng. Byers Eye
Institute, Stanford University, Department of Ophthalmology, Palo
Alto, CA.
Purpose: To evaluate the anatomic and visual acuity outcomes of
intravitreal aflibercept 2.0 mg in cases of diabetic macular edema
(DME) with persistent fluid on spectral domain optical coherence
tomography (SD-OCT) despite regular intravitreal injections (IVI) of
ranibizumab 0.5 mg and/or bevacizumab 1.25 mg.
Methods: In this retrospective interventional case series, DME
patients with persistent retinal fluid despite regular IVI therapy with
ranibizumab 0.5 mg and/or bevacizumab 1.25 mg were switched
to IVI aflibercept 2.0 mg. Collected data includes details of prior
treatments, best available visual acuity, central subfield thickness
(CST), and the area of thickest edema on registered SD-OCT before
and after aflibercept IVI.
Results: A total of 13 eyes with persistent DME were included.
All eyes had persistent fluid after at least 3 monthly ranibizumab or
bevacizumab IVIs (range 3-12). At 1 month after the first aflibercept
IVI, 77% (10/13 eyes) showed anatomic improvement although
none were fluid free; 23% (3/10 eyes) showed stable or worsening
edema. On average, CST decreased from 411 to 332 microns (19%;
p<0.023) after one aflibercept IVI. When measuring the thickest
point in the macula on registered SD-OCT, the thickness decreased
from 536 to 466 microns (13%; p<0.030) after one aflibercept IVI.
All eyes followed over multiple aflibercept injections showed further
improvement (3 eyes). Visual acuity improved in 3 of 10 eyes one
month after the first aflibercept IVI (p=0.61). Treatment was well
tolerated with no adverse events.
Conclusions: A majority of DME cases with persistent fluid on
SD-OCT despite regular ranibizumab 0.5 mg and/or bevacizumab
1.25 mg IVIs showed a positive anatomic response to aflibercept 2.0
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
mg. IVI aflibercept appears to be anatomically beneficial in cases of
DME with persistent fluid despite treatment with ranibizumab and/or
bevacizumab.
Commercial Relationships: Peter Karth, None; Darius M.
Moshfeghi, Convene (I), Genentech (E), Grand Legend Tech
(I), Oraya Theraputis (I), Realm Global (I), Synergetics (I),
Thrombogenics (I), VersaVision (I); Theodore Leng, None
Clinical Trial: NCT02000102
Program Number: 1776 Poster Board Number: A0213
Presentation Time: 11:00 AM–12:45 PM
Risk factors for refractory diabetic macular edema after subTenon capsule injection of triamcinolone injection
Yuta Kitamura, Toshiyuki Oshitari, Sakiko Nonomura, Miyuki Arai,
Eiju Sato, Yoko Takatsuna, Shuichi Yamamoto. Chiba University,
Chiba, Japan.
Purpose: To identify the risk factors for a recurrence and/or a
persistence of diabetic macular edema (DME) after sub-Tenon
capsule triamcinolone acetonide (STTA) injection.
Methods: All of the procedures conformed to the tenets of the
World Medical Association Declaration of Helsinki. The medical
records of 124 patients (124 eyes) treated by STTA were reviewed.
Seventy-four patients (59.7%; 42 men, 32 women) had a persistent
DME or a recurrence within a year. The age, sex, HbA1c, bestcorrected visual acuity (BCVA), central macular thickness (CMT),
insulin use, pioglitazone use, hypertension, serous retinal detachment
(SRD), diabetic nephropathy, pan-retinal photocoagulation (PRP),
microaneurysm photocoagulation (MAPC), subthreshold micropulse
diode laser photocoagulation (SMDLP), cataract surgery, and history
of vitrectomy were examined by logistic regression analysis.
Results: At the time of treatment, the mean age was 61.5±13.0 years,
mean HbA1c was 6.8±1.3%, mean BCVA was 0.6±0.4 logMAR
units, and mean CMT was 557.2±143.7um. Twenty-three patients
(31.1%) used insulin, 8 used pioglitazone (10.8%), 33 patients
(44.6%) had hypertension, and 29 patients (39.2%) had nephropathy.
Thirty-three patients (44.6%) underwent PRP and 15 patients
(20.3%) underwent cataract surgery. These factors were found not
to be risk factors. Thirty-five patients (47.3%) underwent MAPC
and 11 patients (14.9%) underwent SMDLP combined with STTA.
These procedures were determined to be significantly associated
with DME treated with STTA (P=0.0315, P=0.04, respectively).
However, 7 patients (9.5%) with a history of PPV were found to have
significantly fewer recurrences and/or persistent DME after STTA
(P=0.0464).
Conclusions: Patients who had combined MAPC and SMDLP had
significantly higher refractoriness to DME after STTA, but avitreous
may prevent the recurrence and/or persistent DME after STTA.
Commercial Relationships: Yuta Kitamura, None; Toshiyuki
Oshitari, None; Sakiko Nonomura, None; Miyuki Arai, None;
Eiju Sato, None; Yoko Takatsuna, None; Shuichi Yamamoto, None
Program Number: 1777 Poster Board Number: A0214
Presentation Time: 11:00 AM–12:45 PM
Intravitreal Dexamethasone Implant for the Treatment of
Macular Edema in Retinal Vascular Diseases in Saudi Arabia
Saeed T. Alshahrani1, J Fernando Arevalo1, 2. 1Vitro/Retinal, King
Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 2Retina
division, Wilmer Eye Institute, Johns Hopkins University School of
Medicine, Baltimore, MD.
Purpose: To study the efficacy and safety of an intravitreal implant
(sustained release of dexamethasone, Ozurdex®) for the treatment of
macular edema in retinal vascular diseases in Saudi Arabia
Methods: Retrospective non-consecutive study of patients with
macular edema secondary to central retinal vein occlusion, branch
retinal vein occlusion and diabetic retinopathy treated with a
dexamethasone implant of 0.7 mg. Follow-up visits were performed
at 1 month, 3 months and 6 months. Early Treatment Diabetic
Retinopathy Study (ETDRS) best corrected visual acuity, Goldmann
tonometry and macular thickness on spectral domain-optical
coherence tomography (SD-OCT) were registered.
Results: Fourteen eyes with macular edema of 14 patients were
included; 2 with branch retinal vein occlusion, 7 with central retinal
vein occlusion, and 5 with diabetic macular edema. Nine (64.2%)
eyes improved best-corrected visual acuity (BCVA). Four (28.5%)
eyes achieved 3 lines or more of BCVA gain, 5 (35.7%) eyes
showed improvement of BCVA of less than 3 lines (1 to 2 lines),
and 5 eyes (35.7%) remained stable at 1 month. Central macular
thickness (CMT) at base line (BL) had a mean of 637 mm (range:
310 to 950 mm). All cases showed anatomical response at 1 month
with a mean CMT of 272 mm (range: 140 to 460 mm). In 9 (64.2%)
eyes the macular edema resolved at month 1. Eleven (78.5%) eyes
showed recurrence of macular edema at month 3 with a mean CMT
of 493 mm (range: 157 to 1430 mm). At 6 months the CMT had
a mean of 522 mm (range: 94 to 1083 mm). All these differences
were statistically significant when compared to BL (p < 0.05). High
intraocular pressure (> 21 mm Hg) was observed after implantation
in 5 (35.7%) eyes but it was controlled with topical anti-glaucoma
medications. No other serious side effects were observed.
Conclusions: Our study showed the efficacy and safety of an
intravitreal dexamethasone implant in the treatment of macular
edema due to retinal vascular diseases. Functional and anatomical
efficacy was achieved at month 1. However, the effect lasted less than
3 months in most eyes, which is shorter than previously published.
Commercial Relationships: Saeed T. Alshahrani, None; J
Fernando Arevalo, ALCON LABORATORIES (C), IRIDIX (F),
KING KHALED EYE SPECIALIST HOSPITAL (S), NOVARTIS
PHARMACEUTICALS CORP (F), OPTOS (F), SECOND SIGHT
LLC (F), SPRINGER SBM LLC (P)
Program Number: 1778 Poster Board Number: A0215
Presentation Time: 11:00 AM–12:45 PM
Intravitreal dexamethasone implant for diabetic macular edema :
a retrospective study
Elsa Bensoussan, Pierre Gastaud, Stephanie A. Baillif. CHU NICE
ST ROCH, Nice, France.
Purpose: To evaluate the efficacy of dexamethasone 0.7mg
intravitreal implant in patient with chronic diabetic macular edema
(DME).
Methods: Seventeen patients charts were retrospectively reviewed.
Inclusion criteria comprised patients with recalcitrant DME. The
main outcome measures were best corrected visual acuity (BCVA),
mean central retinal thickness (CRT) and intraocular pressure (IOP).
Results: The patients mean age was 70,7 years. Seventy five percent
of the patients were pseudophakik. All the patients had received a
prior treatment for DME : 94% were treated with anti-VEGF therapy
and 35 % with laser photocoagulation. The pre injection mean CRT
was 481μm. It improved to 339μm at month 1 and to 337μm at
month 3. Mean preinjection BVCA was 0,6 logmar. Mean BCVA
was 0,5 logmar at month 1 and 0,4 logmar at month 3. Three patients
(18%) presented with an elevated IOP.
Conclusions: Intravitreal dexamethasone improved visual acuity and
macular thickness at month 1 and month 3 after injection in patients
with recalcitrant DME. Longer follow-up in necessary to state on its
beneficial effect in DME.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Commercial Relationships: Elsa Bensoussan, None; Pierre
Gastaud, None; Stephanie A. Baillif, None
Program Number: 1779 Poster Board Number: A0216
Presentation Time: 11:00 AM–12:45 PM
Long-term Efficacy and Safety of Dexamethasone Intravitreal
Implant in Phakic and Pseudophakic Eyes with Diabetic Macular
Edema
Young Hee Yoon1, David S. Boyer2, Rubens Belfort, Jr.3, Francesco
Bandello4, Raj K. Maturi5, Albert J. Augustin6, Xiao-Yan Li7, Harry
Cui7, Yehia Hashad7, Scott M. Whitcup7. 1Asan Medical Center,
Ophthalmology, Univ of Ulsan, College of Med, Seoul, Republic of
Korea; 2Retina-Vitreous Associates Medical Group, Los Angeles,
CA; 3Vision Institute, Federal University of São Paulo, São Paulo,
Brazil; 4Hospital San Raffaele, University Vita Salute, Milan,
Italy; 5Midwest Eye Institute, Indianapolis, IN; 6Ophthalmology,
Staedtisches Klinikum Karlsruhe, Karlsruhe, Germany; 7Allergan,
Inc., Irvine, CA.
Purpose: To evaluate the efficacy and safety of dexamethasone
intravitreal implant (Ozurdex, DEX implant) 0.7 mg and 0.35 mg
for treatment of diabetic macular edema (DME) in phakic and
pseudophakic eyes.
Methods: Subgroup analysis of pooled data from two 3-year,
randomized, multicenter, masked, sham-controlled, phase III clinical
trials with identical protocols. Patients (n=1048) were randomized
in a 1:1:1 ratio to treatment with DEX implant 0.7 mg, DEX implant
0.35 mg, or sham procedure in the study eye. Patients who met
retreatment eligibility criteria could be retreated no more often than
every 6 months. The primary endpoint for the United States FDA
was achievement of ≥15-letter improvement in BCVA from baseline
at study end in the intent-to-treat population with last-observationcarried-forward for missing values.
Results: Baseline lens status in the study eye was phakic in 773
(73.8%) patients and pseudophakic in 275 (26.2%) patients. The
percentage of patients with ≥15-letter improvement in BCVA from
baseline at study end in the DEX implant 0.7 mg, DEX implant 0.35
mg, and sham groups, respectively, was 22.2%, 18.4%, and 12.0%
overall (P≤0.018 for DEX implant 0.7 and 0.35 mg vs sham); 21.9%,
19.3%, and 12.4% among baseline phakic patients (P≤0.035 for DEX
implant 0.7 and 0.35 mg vs sham); and 23.3%, 15.9%, and 10.9%
among baseline pseudophakic patients (P=0.024 for DEX implant 0.7
mg vs sham). Mean average reduction in CRT from baseline during
the study (area-under-the-curve approach) was greater with DEX
implant 0.7 and 0.35 mg than sham in both baseline phakic patients
(–104.9, –104.8, and –38.3 mm; P<0.001) and baseline pseudophakic
patients (–131.8, –117.1, and –50.8 mm; P<0.001). Rates of cataractrelated adverse events in baseline phakic patients were 67.9%, 64.1%,
and 20.4%. Only 1 (0.3%) patient treated with DEX implant 0.7 mg
and 1 (0.3%) treated with DEX implant 0.35 mg underwent glaucoma
incisional surgery for steroid-induced intraocular pressure increases.
Conclusions: With an average of only 4–5 injections over 3 years,
DEX implant 0.7 mg and 0.35 mg provided clinically significant
improvement in BCVA and reduction in CRT in phakic as well as
pseudophakic eyes. The safety profile was favorable.
Commercial Relationships: Young Hee Yoon, Allergan, Inc. (C),
Allergan, Inc. (R); David S. Boyer, Allergan, Inc. (C), Allergan,
Inc. (F), Allergan, Inc. (R); Rubens Belfort, Jr., Allergan, Inc. (C),
Allergan, Inc. (F), Allergan, Inc. (R); Francesco Bandello, Allergan,
Inc. (C), Allergan, Inc. (R); Raj K. Maturi, Allergan, Inc. (C);
Albert J. Augustin, Allergan, Inc. (F), Allergan, Inc. (R); Xiao-Yan
Li, Allergan, Inc. (E); Harry Cui, Allergan, Inc. (E); Yehia Hashad,
Allergan, Inc. (E); Scott M. Whitcup, Allergan, Inc. (E)
Support: Allergan, Inc.
Clinical Trial: NCT00168337, NCT00168389
Program Number: 1780 Poster Board Number: A0217
Presentation Time: 11:00 AM–12:45 PM
Intravitreal Dexamethasone Implant (Ozurdex) as Primary
Treatment for Diabetic Macular Edema
Qi N. Cui, Jay M. Stewart. Department of Ophthalmology, University
of California, San Francisco, San Francisco, CA.
Purpose: Recently, the intravitreal dexamethasone implant Ozurdex
(Allergan, Inc.) 0.7mg has gained momentum as a possible option
for the management of persistent diabetic macular edema (DME). In
this case series, we evaluated the effectiveness of Ozurdex as primary
treatment for DME.
Methods: Six patients (3 M, 3 F; 7 eyes) affected by persistent DME
were selected. The average age was 69 ± 9 yrs (± SD; range 60–87)
and the duration of DME was 808 ± 586 days (range 83–1618) at the
time of initial Ozurdex injection. One patient received prior posterior
subtenon triamcinolone, one received intravitreal triamcinolone,
and 3 patients received prior focal and/or grid photocoagulation, all
without a significant effect upon the DME. None of the patients had
received previous treatment with anti-VEGF. Outcomes evaluated
included central macular thickness (CMT), BCVA, and IOP prior to
injection, and then at 1 & 3 months follow-up.
Results: Baseline CMT prior to injection was 425 ± 101μm. Of the
6 eyes with available OCT, a decrease in CMT was detected with
an average thickness of 310 ± 77μm (p < 0.05) at 1 month. The
improvement from baseline persisted at 3 months with an average
CMT of 319 ± 84μm (p < 0.05). The differences in CMT between
1 and 3 months were not significant. Mean BCVA (converted to
LogMAR) did not differ significantly between baseline (0.55 ± 0.35),
1 month (0.57 ± 0.41), and 3 months (0.51 ± 0.42; p = 0.741875).
In long-term follow-up, a trend towards improved visual acuity
was observed in all eyes. One patient required vitrectomy and
membrane peel for an ERM prior to observable visual improvement.
Two patients required repeated injections at 3 – 4 month intervals
for continued visual improvement. With an average follow-up of
492 ± 389 days (range 147–1210), no other ocular or systemic
complications were noted. All patients had normal IOP (14.6 ± 3.2
mmHg) prior to injection, IOPmax during follow-up was 24.9 ±
7.2 mmHg, and 3 patients/4 eyes required topical therapy for IOP
management. The only patient with a native lens at the time of
placement experienced cataract progression resulting in cataract
extraction 657 days post-injection.
Conclusions: In this small series, Ozurdex significantly decreased
CMT with a trend towards improved BCVA in long-term follow-up.
Duration of action appeared to be around 3 months. IOP elevation
was observed requiring medical management alone in a subset of
patients.
Commercial Relationships: Qi N. Cui, None; Jay M. Stewart,
None
Support: NIH-NEI EY002162 - Core Grant for Vision Research;
Research to Prevent Blindness Unrestricted Grant
Program Number: 1781 Poster Board Number: A0218
Presentation Time: 11:00 AM–12:45 PM
Effects of Ozurdex on intraocular pressure: a real- life clinical
practice study
Beatriz Jiménez Gómez, Alex Fonollosa, Joseba Artaraz, Ana Orive,
Sonia Valsero, Maria Elena Gonzalez-Montpetit, Jose A. Sanchez.
Cruces University Hospital, Ugao Miraballes, Spain.
Purpose: The Dexamethasone biodegradable implant Ozurdex
is approved by the US Food and Drug Administration and by the
European Medical Agency for the treatment of intermediate and
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
posterior uveitis and for the treatment of macular edema following
retinal vein occlusion. Use as off label drug for treating diabetic
macular edema has been reported, showing promising results. The
pivotal clinical trials HURON and GENEVA showed a low rate of
ocular hypertension after Ozurdex treatment. The aim of our study
was to assess the effects on intraocular pressure in a cohort of patients
from the real- life clinical practice.
Methods: Retrospective review of clinical records of patients treated
with Ozurdex in Hospital Universitario Cruces in a 6 month period.
The following variables were recorded: age, gender, diagnosis and
history of glaucoma; intraocular pressure, antihypertensive treatment
and macular thickness were recorded before injection and at 1st,
2nd, 4th and 6th months after the injection. Statistical tests: MannWhitney U test, Chi square test (with Fisher’s correction when
needed) and Wilcoxon test. The level of statistical significance was
set at p<0.05.
Results: The effects of 75 injections given to 67 patients (35 women,
52%, mean age 62) was evaluated. The diagnosis were: 14 (18.7%):
Central retinal Vein Occlusion, 25 (33.3%): Branch retinal Vein
Occlusion, 12 (16%): diabetic macular edema and 24 (32%): Uveitis.
Mean intraocular pressure before the injection was 15.9 mmHg and
at 1st, 2nd, 4th and 6th months after the injection: 18.80 (p=0.627),
18.84 (p=0.494), 17.02 (p=0.796) and 15.5 (p=0.829). Regarding
antihypertensive treatment, 30.7% were on drops before the injection
and 37.3% at 6th month. (p=0.118). We did not observe statistically
significant differences in intraocular pressure measurements at the
mentioned follow up visits between patients with and without history
of glaucoma. Mean macular thickness before injection was 483.46
microns; after injection, at 2nd month: 301 (p<0.001) and at 6 th
month 373 (p=0.023).
Conclusions: In the real -life clinical practice, Ozurdex shows an
excellent safety profile in terms of intraocular hypertension. Patients
with history of glaucoma may also show this profile, being Ozurdex a
good option to treat retinal diseases in these patients.
Commercial Relationships: Beatriz Jiménez Gómez, None; Alex
Fonollosa, None; Joseba Artaraz, None; Ana Orive, None; Sonia
Valsero, None; Maria Elena Gonzalez-Montpetit, None; Jose A.
Sanchez, None
Program Number: 1782 Poster Board Number: A0219
Presentation Time: 11:00 AM–12:45 PM
INTRAVITREAL DEXAMETHASONE IMPLANT IN EYES
WITH CHRONIC
REFRACTORY DIABETIC MACULAR OEDEMA
Juan Giralt, Socorro Alforja, Johannes Keller, Marta Latasiewicz,
Christian Fontecilla, Alfredo Adan Civera. Hospital Clinic,
Barcelona, Spain.
Purpose: To describe the changes in retinal thickness(RT) and visual
acuity over time in patients with clinically significant refractory
diffuse diabetic macular oedema (DME) after intravitreal implant of
dexamethason (OZURDEX) .
Methods: Retrospective, interventional nonrandomized case series
of patients that underwent intravitreal implant of dexamethasone for
chronic diabetic macular oedema refractory to previous treatment.
All patients had best corrected visual acuity, slit-lamp biomicroscopy,
intraocular pressure check and OCT at 1 week, 1, 3 and 6 months.
Results: We analize 33 eyes of 32 patients, 23 male and 9 female,
that underwent intravitreal implant of dexamethasone. All patients
had previously had treatment with either argon laser, anti-VEGF,
triamcinolone or a combination of these treatments. Retinal thickness
measured by OCTdecreased in all eyes. The reduction of edema was
maximal in the first month and tended to be stable for more than 3
months in some cases. We observed statistically significant decrease
in central macular thickness from baseline .496.6um to 294.7um
(P<0.0001) in the third month, and 356.9 (p=0.0015)um in the sixth
month. Visual acuity improved in some cases, but this improvement
over time was not significant.
Conclusions: Intravitreal implant of dexamethason appears to be
promising in the short term, for improving retinal thicknes more than
visual acuity in eyes whith chronic macular oedema unresponsive to
other treatments. Randomised controlled trials with longer follow up
are required to define optimum treatment regimens.
Commercial Relationships: Juan Giralt, None; Socorro Alforja,
None; Johannes Keller, None; Marta Latasiewicz, None; Christian
Fontecilla, None; Alfredo Adan Civera, None
Program Number: 1783 Poster Board Number: A0220
Presentation Time: 11:00 AM–12:45 PM
Long-term visual outcomes based on baseline vision in patients
with chronic diabetic macular edema (DME) treated with
fluocinolone acetonide (FAc)
Peter A. Campochiaro. Ophthalmology and Neuroscience, Johns
Hopkins Wilmer Eye Inst, Baltimore, MD.
Purpose: ILUVIEN® (intraocular, nonbioerodible, 0.2 μg/d FAc
implant) is approved in 7 European countries for the treatment of
chronic DME considered insufficiently responsive to available
therapies. Here we examine response among patients with chronic
DME in the Fluocinolone Acetonide in Diabetic Macular Edema
(FAME) study based on baseline vision.
Methods: The FAME study (2 randomized, multicenter, 36-month,
phase 3 trials under a single protocol) assessed efficacy and safety of
0.2 μg/d FAc and 0.5 μg/d FAc vs sham injection (control) in patients
with DME. These trial results indicated greatest benefit was seen
in patients with chronic DME (≥ 3 years at baseline). Patients with
chronic DME were analyzed for clinical benefit based on baseline
best corrected visual acuity (BCVA).
Results: At baseline, ≈ 43% of patients with chronic DME had
BCVA ≤ 20/100 (48/112 [42.9%] control and 90/209 [43.1%] 0.2
μg/d FAc-treated patients); ≈ 60% had BCVA ≤ 20/80 (63/112
[56.3%] and 124/209 [59.3%], respectively) and ≈ 80% had BCVA ≤
20/60 (90/112 [80.4%] and 161/209 [77.0%], respectively). Among
all patients with chronic DME, the proportion with ≥ 15-letter
improvement at month 36 was 13.4% for control and 34.0% for 0.2
μg/d FAc-treated patients, a treatment difference of 20.6%. Among
patients with chronic DME with baseline BCVA ≤ 20/60, 14.4% of
control and 38.5% of 0.2 μg/d FAc-treated patients experienced ≥
15-letter improvement (treatment difference, 24.1%). For those with
≤ 20/80 baseline vision, these values were 12.7% vs 42.7% (treatment
difference, 30%), and those with ≤ 20/100 had the greatest benefit,
12.5% vs 46.7% (treatment difference, 34.2%). At 36 months, mean
change in BCVA among those with ≤ 20/80 vision was +2.1 vs +10.7
letters for control and 0.2 μg/d FAc, respectively (P = .002). Among
those with ≤ 20/100 vision, mean change was +1.5 vs +12.2 letters,
respectively (P < .001).
Conclusions: Robust 36-month efficacy was noted in patients with
chronic DME treated with 0.2 μg/d FAc, with treatment difference
from sham being even more pronounced in patients with lower
baseline visual acuity. In the FAME trial, long-term sustained-release
corticosteroid therapy provided the greatest benefit in patients with
worst baseline disease.
Commercial Relationships: Peter A. Campochiaro, Aerpio (C),
Aerpio (F), Alimera (C), Allergan (F), Gene Signal (C), Genentech
(C), Genentech (F), Kala (C), Regeneron (C), Regeneron (F), Roche
(F)
Clinical Trial: NCT00344968
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Program Number: 1784 Poster Board Number: A0221
Presentation Time: 11:00 AM–12:45 PM
Changes in the cup-to-disc ratio in patients with diabetic macular
edema (DME) treated with fluocinolone acetonide (FAc) implants
Richard K. Parrish. Ophthal-Bascom Palmer Eye Inst, Miller Sch of
Med-Univ of Miami, Miami, FL.
Purpose: Elevated IOP is a common adverse event associated with
ocular corticosteroids. Because of concerns regarding glaucomatous
change associated with elevated IOP, patients in the Fluocinolone
Acetonide for Diabetic Macular Edema (FAME) study were assessed
for changes in the optic nerve head.
Methods: Patients in the randomized phase 3 FAME trials received
sham injection (control; n = 185), or active treatment with 0.2 μg/d
FAc (n = 376) or 0.5 μg/d FAc (n = 395) implants. The University
of Wisconsin Fundus Photograph Reading Center performed the
grading of the optic nerve head in the study eye using color digital
and Field One film images. Two independent graders trained in optic
nerve head evaluations performed measurements of the vertical cup
and disc to determine the effect of FAc. Images were analyzed at
baseline and month 36, or last observation in the absence of month 36
assessment.
Results: Baseline and post-baseline assessments were available in
169 control patients, 354 patients treated with 0.2 μg/d FAc, and 368
patients treated with 0.5 μg/d FAc. The mean change in vertical cupto-disc ratio was 0.005 for control, 0.016 for 0.2 μg/d FAc, and 0.014
for 0.5 μg/d FAc. The number of patients with a worsening (increase
from baseline > 0.1) in the vertical cup-to-disc ratio was 2 (1.2%)
for control, 12 (3.5%) for 0.2 μg/d FAc and 17 (4.7%) for 0.5 μg/d
FAc. A clinically meaningful change (increase from baseline of > 0.2)
occurred in 0 control patients, 4 patients (1.2%) receiving 0.2 μg/d
FAc, and 3 patients (0.8%) receiving 0.5 μg/d FAc. Confounding
factors, such as heavy use of panretinal photocoagulation or loss of
glycemic control, were noted in some of these patients.
Conclusions: A clinically meaningful worsening in the cup-to-disc
ratio was noted in a small proportion of patients treated with 0.2 μg/d
FAc implants, which may have been confounded by factors unrelated
to treatment. Overall the risk of glaucomatous change is low for these
patients, many of whom experienced significant visual benefit in the
study.
Commercial Relationships: Richard K. Parrish, Alimera Sciences,
Inc. (C)
Clinical Trial: NCT00344968
Program Number: 1785 Poster Board Number: A0222
Presentation Time: 11:00 AM–12:45 PM
Clinical applications of the SAVE grading protocol for diabetic
macular edema based on optical coherence tomography and
fluorescein angiography criteria
Vignesh Vetrivel1, Dawn A. Sim2, Pearse A. Keane2, Mirjam E.
Van Velthoven3, Javier Zarranz-Ventura4, Florian M. Heussen5,
Matthias Bolz6. 1Heatherwood and Wexham Park Hospitals NHS
Trust, Slough, United Kingdom; 2Moorfields Eye Hospital, London,
United Kingdom; 3Rotterdam Eye Hospital, Rotterdam, Netherlands;
4
Bristol Eye Hospital, Bristol, United Kingdom; 5Charite - University
Medicine Berlin, Berlin, Germany; 6Medical University of Vienna,
Vienna, Austria.
Purpose: To investigate the application of a new grading protocol for
clinically significant macular edema (DME).
Methods: A pilot study, which included patients who underwent
fluorescein angiography (FA) and optical coherence tomography
(OCT), and laser therapy for diabetic macular edema. Patients were
grouped according to their response to macular laser. A response
to treatment was defined as a reduction in OCT-derived central
macular thickness (CMT) of >20mm. FA and OCT images were
graded according to the following modified “SAVE” criteria: “S”
- Subretinal fluid (score: present=1, absent=0); “A” – The Area of
retinal thickening (score: greater than one disc diameter=1, less than
one disc diameter=0; “V” - Vitreomacular abnormalities (score:
present=1, absent=0); and “E” – the Etiology of DME (Score: the
presence of focal or diffuse leakage= 0 or 1 respectively, diabetic
macular ischemia=1, and retinal atrophy=1). The range of possible
modified SAVE scores was 0 to 6.
Results: 48 eyes from 48 patients were included. In all patients,
the modified SAVE score was correlated to change in CMT
measurements after macular laser therapy (r=-0.29, p=0.05). A
poor visual acuity prior to laser therapy was also associated with a
high modified SAVE score (r=0.56, p=0.002). The mean reduction
in CMT measurements of responders to macular laser (n=20) was
99.7±56.9mm, and the mean increase in CMT of non-responders
(n=28) was 65.1±80.7mm (p=0.0001). Responders to macular laser
had a lower modified SAVE score (mean=2.4, 95% CI=1.79 to 3.01),
compared to non-responders (mean=3.2, 95% CI=2.60 to 3.82)
(p=0.05).
Conclusions: We present a simplified version of the “SAVE”
grading protocol for diabetic macular edema, and assess it’s clinical
usefulness and potential application to patients undergoing macular
laser therapy for diabetic macular edema. We observed that the
modified SAVE score was associated with both responsiveness to
treatment and pre-morbid visual function.
Commercial Relationships: Vignesh Vetrivel, None; Dawn A.
Sim, None; Pearse A. Keane, None; Mirjam E. Van Velthoven,
None; Javier Zarranz-Ventura, None; Florian M. Heussen, None;
Matthias Bolz, None
Program Number: 1786 Poster Board Number: A0223
Presentation Time: 11:00 AM–12:45 PM
Complete retinal fluid resorption with low visual acuity in
patients with diabetic macular edema (DME) over the course of
ranibizumab treatment: Optical Coherence Tomography (OCT)
analysis
Benjamin Penaud, Audrey Giocanti-Auregan, Ora Levy, Gilles
Chaine, Franck Fajnkuchen. Avicenne hospital, Bobigny, France.
Purpose: Intravitreal ranibizumab injections in DME often leads
to resorption of edema. Nevertheless, complete resorption of DME
is weakly correlated with good visual acuity. The purpose of our
study was to investigate the anatomical OCT features of patients
treated with ranibizumab for DME with low visual acuity despite of
complete dry retina.
Methods: We included in a retrospective fashion all patients over
the course of ranibizumab treatment for DME at Avicenne Hospital
(Bobigny, France) from November 2011 to July 2013 with a dry
retina after treatment (central foveal thickness (CFT) ≤ 250 μm and
presence of foveal pit). We analyzed the characteristics of outer
retinal layers in spectral-domain OCT (Optos OCT SLO, Optos pls,
Dunfermline, Scotland) in case of low final visual acuity (bestcorrected visual acuity (BCVA) with dry retina < 5/10 after at least 3
injections).
Results: We included 40 patients. Complete retinal fluid resorption
was achieved for 24 patients (60%). Among these patients, half of
them (12 patients ie 30 % of our cohort) had low visual acuity (group
1) and 12 patients had good visual acuity ( group 2). Mean CFT was
713 μm in group 1 (G1) and 666μm (p = 0.64) in group 2 (G2). After
treatment, mean CFT in G1 was 165 μm against 174 μm (p = 0.6) in
G2. For all patients in G1, anatomical changes were noted on OCT
pictures after treatment: loss or thinning of ellipsoid band (n = 6),
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
atrophic cyst (n = 6), exudates (n = 3), epi retinal membrane (n =
2). At baseline, mean BVCA was 1.2/10 in G1, 2.4/10 in G2. After
treatment, mean BVCA was 2,7/10 in G1 and 7,1/10 in G2. Mean
improvement in BVCA was 1.5/10 in G1 and 4.7/10 in G2.
Conclusions: Insufficient improvement of BCVA after complete
retinal fluid resorption happened in about 30% of patients over the
course of ranibizumab treatment for DME, and was often associated
in our study with alterations of outer retinal layers in SD-OCT
imaging.
Commercial Relationships: Benjamin Penaud, None; Audrey
Giocanti-Auregan, None; Ora Levy, None; Gilles Chaine, None;
Franck Fajnkuchen, None
Program Number: 1787 Poster Board Number: A0224
Presentation Time: 11:00 AM–12:45 PM
Optical Coherence Tomography - guided Selective Focal Laser
Photocoagulation: A Novel Protocol for Diabetic Macular Edema
Joo Youn Shin1, Oh Woong Kwon2, 1, Suk Ho Byeon1. 1The Institute of
Vision Research, Department of Ophthalmology, Yonsei University
College of Medicine, Seoul, Republic of Korea; 2Nune Eye Hospital,
Seoul, Republic of Korea.
Purpose: To introduce optical coherence tomography (OCT)-guided
selective focal laser
photocoagulation (OCT-laser) as an alternative to modified Early
Treatment Diabetic Retinopathy Study (mETDRS) laser treatment for
diabetic macular edema (DME).
Methods: We analyzed outcomes in 47 consecutive eyes treated with
OCT- laser compared to matched 31 eyes treated with mETDRS.
Best-corrected visual acuity (BCVA) and retinal thickness(central
subfield thickness, maximum retinal thickness,) by OCT were
compared at baseline and 12 months after treatment between OCTlaser and mETDRS treatment groups. Degree of retinal damage by
fundus autofluorescence and OCT imaging were also compared.
Results: OCT-laser treatment resulted in significant improvements in
BCVA and retinal thickness from baseline at 12 months from the time
of therapy (change from baseline: +2.5 letter score, p=0.04; -45.56
μm in CST, p<0.001; -91.6 μm in MRT,p<0.001). There were also
no differences in changes of these parameters from baseline at 12
months between two groups (p=0.56, p=0.89, p=0.43, respectively).
Fundus autofluorescence (FAF) and OCT revealed minimal tissue
damage in OCT-laser-treated eyes, compared to eyes treated with
mETDRS(p<0.001).
Conclusions: OCT-laser is a safe and effective treatment for DME.
In an era of anti-VEGF therapy, this novel laser technique may be a
promising adjuvant modality for the treatment of DME.
Imaging processing of treatment plan for OCT-guided selective focal
laser photocoagulation.
Serial morphological changes on OCT after OCT-guided selective
focal laser photocoagulation.
Commercial Relationships: Joo Youn Shin, None; Oh Woong
Kwon, None; Suk Ho Byeon, None
Support: National Research Foundation of Korea (NRF) funded by
the Ministry of Education (2013R1A1A2007865)
Program Number: 1788 Poster Board Number: A0225
Presentation Time: 11:00 AM–12:45 PM
Foveal Disorganization of Retinal Inner Layers (DRIL) Predicts
Long Term Visual Acuity (VA) Outcomes in Eyes with Diabetic
Macular Edema
Jan Lammer1, 2, Michael Cheney1, Michael Lin3, Lloyd B. Aiello1,
Paolo S. Silva1, 4, Lloyd P. Aiello1, 4, Jennifer K. Sun1, 4. 1Beetham
Eye Institute, Joslin Diabetes Center, Boston, MA; 2Department of
Ophthalmology and Optometry, Medical University Vienna, Vienna,
Austria; 3Harvard Medical School, Boston, MA; 4Department of
Ophthalmology, Harvard Medical School, Boston, MA.
Purpose: To assess whether spectral domain optical coherence
tomography (SDOCT) parameters predict change in VA over 1 year
in eyes with center-involved diabetic macular edema (ciDME).
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Methods: ETDRS VA & Spectralis SDOCT imaging (20x20°, 49B
scans, 16 ART Mean, high res setting) were performed at baseline,
4 & 12 months. The central 1mm wide area of 7 B-scans centered
on the fovea was graded in masked fashion for presence & extent
of DRIL (inability to distinguish inner retinal layer boundaries on
SDOCT), hyperreflective foci, cysts, subretinal fluid, epiretinal
membranes, and external limiting membrane (ELM) or photoreceptor
ellipsoid zone (EZ) disruption.
Results: In 62 eyes of 52 patients, baseline mean±SD logmar VA was
0.25±0.22 and central subfield thickness (CST) 408±101mm. Mean
participant age was 63±11yrs, diabetes duration 23±13yrs, 50% were
male and 35% had type 1 DM. Worse VA at baseline was significantly
associated with greater DRIL extent (point estimate [95% CI]: 0.03
[0.008-0.05], p=0.01), increased CST (0.1 [0.04-0.16], p=0.003) and
ELM disruption (0.05 [0.003-0.09], p=0.04). Worse VA at 1yr was
similarly related to greater baseline DRIL extent (0.02 [0.002-0.03],
p=0.03) and increased baseline CST (0.05 [0.0005-0.1], p<0.05). VA
change over 1 yr was correlated with 4mo change in DRIL extent
(0.12 [0.22-0.02] p=0.03). An increase in DRIL of ≥200mm at 4mo
was associated with an average worsening of VA by ~1 line at 1yr
(n=7: 0.11±0.10 logmar VA change) whereas eyes with decreased
DRIL ≥200mm at 4mo had a mean increase in VA of >1 line (n=10:
-0.13±0.26). VA change at 1yr was also related to EZ disruption (0.05
[0.004-0.09], p=0.04) at 4mo. DRIL change from baseline to 4mo
remained related to VA at 1yr (p<0.05) after controlling for baseline
VA, 4mo change in CST or 4 mo change in EZ disruption.
Conclusions: In eyes with ciDME, both extent of baseline DRIL
and changes in DRIL over 4mo are related to worse VA at 1yr.
If confirmed in larger studies, change in DRIL may become an
important predictive biomarker of future VA outcomes in eyes with
DME.
Commercial Relationships: Jan Lammer, None; Michael Cheney,
None; Michael Lin, None; Lloyd B. Aiello, None; Paolo S. Silva,
None; Lloyd P. Aiello, None; Jennifer K. Sun, Optovue (F)
Support: Eleanor Chesterman Beatson Childcare Ambassador
Program Foundation Grant, JDRF 17-2011-359, Massachusetts Lions
Eye Research Fund, Inc.
Program Number: 1789 Poster Board Number: A0226
Presentation Time: 11:00 AM–12:45 PM
Efficacy of indocyanine green angiography-guided laser
photocoagulation for diabetic macular edema
Soichiro Kuwayama, Tsutomu Yasukawa, Aki Kato, Shuntaro Ogura,
Yoshida Munenori, Yuichiro Ogura. Ophthalmology, Nagoya City
Univ Med School, Nagoya, Japan.
Purpose: Diabetic macular edema (DME) is the major cause of
vision loss in patients with diabetic retinopathy. Focal DME is
treatable by microaneurysm-targeted laser photocoagulation (PHC),
while diffuse DME is often refractory to grid laser photocoagulation
performed without concrete targets. Previously, we reported that
indocyanine green angiography (IA) could detect responsible leaking
points even for diffuse DME more sensitively than fluorescein
angiography (FA) and that IA-guided PHC was effective for the
treatment of DME (ARVO 2012). The purpose of this study is to
evaluate long-term efficacy of IA-guided PHC for DME.
Methods: Eighteen eyes of 12 patients with diffuse DME diagnosed
conventionally on FA were enrolled. Mean age was 68.0 years.
The mean follow-up period was 18.4 months (range 12 to 24). FA
and IA were performed with Heidelberg Retina Angiogram 2. IAguided PHC was performed on the basis of middle or late phase IA.
Subtenon’s injection of triamcinolone acetonide (STTA) (20mg)
was additionally performed as needed. The best-collected visual
acuity (BCVA) was measured. The central retinal thickness (CRT)
and macular volume (MV) were measured periodically by optical
coherence tomography.
Results: Mean BCVA in the LogMAR unit was significantly
improved from 0.56±0.10 at baseline to 0.47±0.08 in month 6
(p<0.05) and 0.46±0.08 in month 12 (p<0.05). The mean CRT
was significantly decreased from 420±26.5 μm to 265±16.8 μm
(p<0.01) and 258±15.3 μm (p<0.01), respectively. Mean MV was
also significantly decreased from 13.4±0.34 mm3 to 11.4±0.26 mm3
(p<0.01) and 11.3±0.28 mm3 (p<0.01), respectively. In month 12, the
BCVA was improved by 0.3 or more LogMAR units in 3 eyes (17%),
stable in 14 eyes (78%), and worsened only in 1 eye (6%). STTA was
performed in 8 eyes (44%), one of which has undergone retreatment
of STTA. Additional PHC was performed only in 1 eye.
Conclusions: IA is useful to detect targets of PHC even for diffuse
DME. IA-guided PHC may be effective with lower recurrence rate
for the treatment of diffuse DME. Further study is needed to compare
other treatment modalities such as anti-vascular endothelial growth
factor therapy.
Commercial Relationships: Soichiro Kuwayama, None; Tsutomu
Yasukawa, None; Aki Kato, None; Shuntaro Ogura, None;
Yoshida Munenori, None; Yuichiro Ogura, None
Program Number: 1790 Poster Board Number: A0227
Presentation Time: 11:00 AM–12:45 PM
Predictive Factors for Visual Acuity Loss after Focal/Grid
Photocoagulation for Diabetic Macular Edema
Daniel Lee, Ryan K. Wong, James K. Kempton, John J. Huang.
Ophthalmology and Visual Science, Yale School of Medicine, New
Haven, CT.
Purpose: Macular edema accounts for the majority of vision
loss in those with diabetic retinopathy. Though focal/grid laser
photocoagulation remains the standard for treatment, many studies
are showing the benefit of other modalities, such as intravitreal
corticosteroids or anti-vascular endothelial growth factor (VEGF)
agents. With an array of treatment choices, it is at times difficult
to determine which modality to use. We aim to identify prognostic
factors for response to laser photocoagulation treatment of diabetic
macular edema (DME).
Methods: A retrospective chart review was conducted on patients
referred for DME to the West Haven Veteran’s Administration
Hospital from January 2010 to January 2013. Inclusion criteria
included: patients treated with focal/grid laser photocoagulation for
clinically significant macular edema. Exclusion criteria included:
lack of followup, previous vitrectomy, history of intraocular surgery
or previous treatment for DME within the previous 4 months prior to
treatment, or any concomitant ocular pathology know to also cause
macular edema (epiretinal membrane, vein occlusion, tractional
detachment).
Data was collected on the following at baseline: visual acuity, age,
renal function (eGFR), diabetic retinopathy stage, smoking status,
HbA1c, blood pressure, and BMI. Endpoints were visual acuity at 4
month followup and 1 year followup.
Results: 15/56 (27%) patients and 24 eyes qualified for the study.
Tables 1 and 2 demonstrate that worse renal function (eGRF) was a
predictive factor for vision loss (change of 0.1 logMAR) following
focal/grid laser photocoagulation at both the 4-month followup
(p=.04) and the 1-year followup (p=0.02). Baseline visual acuity, age,
diabetic retinopathy stage, smoking status, HbA1c, systolic blood
pressure, mean arterial blood pressure, and BMI were not predictive
of visual acuity worsening following treatment.
Conclusions: Though a larger study will need to validate our data,
the results suggest a possible predictive role of renal function for
treatment failure following focal/grid laser photocoagulation for
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
DME. Though laser photocoagulation still remains the proven
standard for treatment, this information could be useful in
determining which patients should forgo laser photocoagulation for
alternative treatments such as corticosteroids or anti-VEGF agents.
Table 2: One year follow-up
Commercial Relationships: Daniel Lee, None; Ryan K. Wong,
None; James K. Kempton, None; John J. Huang, Allergan (R)
Table 1: Four month follow-up
Program Number: 1791 Poster Board Number: A0228
Presentation Time: 11:00 AM–12:45 PM
Morphological parameters relevant for visual and anatomic
outcomes during anti-VEGF therapy of diabetic macular edema
in the RESTORE trial
Bianca Gerendas1, Christian Simader1, Gabor G. Deak1, Sonja G.
Prager1, Jan Lammer1, 3, Sebastian M. Waldstein1, Michael Kundi2,
Ursula Schmidt-Erfurth1. 1Department of Ophthalmology and
Optometry, Vienna Reading Center, Medical University of Vienna,
Vienna, Austria; 2Institute of Environmental Health, Center for
Public Health, Medical University of Vienna, Vienna, Austria; 3Joslin
Diabetes Center, Beetham Eye Institute, Boston, MA.
Purpose: Identification of relevant morphologic factors in
multimodal imaging during anti-VEGF therapy for diabetic macular
edema (DME) and prediction of visual and anatomical outcomes.
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2014 Annual Meeting Abstracts
Methods: In a subanalysis of a prospective randomized phase III
clinical trial, images of 345 patients with DME were systematically
analyzed. Patients were randomized to receive 0.5mg Ranibizumab
(RZ), 0.5mg Ranibizumab plus laser (RZ+L) or laser alone (L). After
an initial loading phase (LP) of 3 injections in the RZ(+L) arms and
one laser treatment at baseline (BL) in the (RZ+)L arms, patients
were treated as needed (PRN). After standardized image evaluation
at the Vienna Reading Center parameters of optical coherence
tomography (OCT), fluorescein angiography (FA) and color fundus
(CF) images were correlated with best corrected visual acuity
(BCVA).
Results: At BL mean BCVA was 64±10.5 letters (RZ: 65, RZ+L: 63,
L: 62); change in BCVA from BL to month 12 (M12) was 5.5±10.0
letters (RZ: 7.5, RZ+L: 7.7, L: 0.9). Mean central retinal thickness
(CRT) at BL was 418±121mm (RZ: 428mm, RZ+L: 417mm, L:
409mm); change in CRT from BL to M12 was 105±123mm (RZ:
126mm, RZ+L: 126mm, L: 59mm). An overall trend for correlation
between BCVA gain and CRT decrease was observed during the
LP but lost afterwards. IRC at BL were associated with a lower BL
BCVA in all arms but had no influence on BCVA values at M12;
however, patients with IRC at BL had a larger BCVA gain in RZ
which resulted in the same BCVA at M12 for groups with and
without IRC at BL. The same groups showed significantly (p=0.036)
different CRT values at M12: in the group with IRC at BL it was
317mm, in the group without IRC at BL it was 284mm. In RZ+L IRC
of ≤380mm in height were continuously associated with significantly
(p<0.001) better BCVA from BL to M12. SRF at BL was not
associated with a worse BCVA at BL. However, patients with SRF at
BL had a significantly (p=0.004) higher BCVA gain from BL to M12
in RZ which also resulted in higher final BCVA levels. No significant
impact on BCVA and anatomical outcomes was found for parameters
derived from FA and CF.
Conclusions: Morphologic evaluation of multimodal images may
allow predicting functional and anatomical response to anti-VEGF
therapy. In particular, active disease at BL (i.e. IRC and SRF) is
associated with higher BCVA gain, while CRT alone cannot predict
BCVA response.
Commercial Relationships: Bianca Gerendas, None; Christian
Simader, None; Gabor G. Deak, None; Sonja G. Prager, None;
Jan Lammer, None; Sebastian M. Waldstein, None; Michael
Kundi, None; Ursula Schmidt-Erfurth, Alcon (C), Bayer (C),
Boehringer Ingelheim (C), Novartis (C)
Clinical Trial: NCT00687804
therapy), and (2) non-responders. Thinning of the macular was
defined as a reduction of > 20mm in OCT-derived measurements.
Results: 44 eyes from 44 patients were included. The mean reduction
of CMT in the “responders” was 99.7±56.9mm, and the mean
increase of CMT in the “non-responders” 65.1±80.7mm (p=0.0001).
The mean pre-laser FAZ area of “non-responders” (0.38±0.23mm2)
was significantly larger than “responders” (0.29±0.19mm2)
(p=0.048). No association between FAZ size and TMT measurements
were observed.
Conclusions: We observed that eyes with a large FAZ area,
corresponding to early treatment diabetic retinopathy study (ETDRS)
grades of moderate to severe diabetic macular ischemia, did not
respond to macular laser therapy for diabetic macular edema,
irrespectively of pre-treatment retinal thickness measurements. FAZ
size may be a useful parameter for assessing the suitability of these
patients for alternative treatments for macular oedema.
Commercial Relationships: Zaman K. Durani, None; Dawn
A. Sim, Allergan (R), Fight for Sight Charity, UK (R); Pearse A.
Keane, Allergan (R), Fight For Sight UK (R); Marcus Fruttiger,
None; Adnan Tufail, Alcon (R), Allergan (R), Bayer (R), Heidelberg
Engineering (R), Novartis (R), Oculogics (R), Pfizer (R), Roche (R),
Thrombogenics (R); Catherine A. Egan, None
Program Number: 1792 Poster Board Number: A0229
Presentation Time: 11:00 AM–12:45 PM
The effects of macular ischemia to the response to laser therapy
for diabetic macular edema
Zaman K. Durani1, Dawn A. Sim1, 2, Pearse A. Keane1, 2, Marcus
Fruttiger1, 2, Adnan Tufail1, 2, Catherine A. Egan1, 2. 1Medical Retina,
NIHR Biomedical Research Centre for Ophthalmology, Moorfields
Eye Hospital NHS Foundation Trust, London, United Kingdom;
2
UCL Institute of Ophthalmology, London, United Kingdom.
Purpose: To investigate the effect of diabetic macular ischemia
(DMI) on the efficacy of macular laser therapy.
Methods: Consecutive patients who underwent fluorescein
angiography, optical coherence tomography, and laser therapy
for diabetic macular edema over a 6-month period were included.
Parameters quantified included the pre-laser foveal avascular zone
(FAZ) area, and the pre- and post- laser central (CMT) and total
macular thickness (TMT) measurements. Patients were divided into
2 groups; (1) responders (i.e. thinning of the macular post-laser
©2014, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].