Download ARVO 2016 Annual Meeting Abstracts 442 AMD Clinical Research 3

ARVO 2016 Annual Meeting Abstracts
442 AMD Clinical Research 3
Wednesday, May 04, 2016 11:00 AM–12:45 PM
Exhibit/Poster Hall Poster Session
Program #/Board # Range: 4963–4986/A0353–A0376
Organizing Section: Retina
Program Number: 4963 Poster Board Number: A0353
Presentation Time: 11:00 AM–12:45 PM
Clinical features and long-term progression of reticular
pseudodrusen in age-related macular degeneration: Findings
from a multi-center cohort
Joao Gil1, 4, João Pedro Marques1, 4, Ruth E. Hogg2, Chiara Rosina3,
Maria L. Cachulo1, 4, Ana Rita Santos4, Giovanni Staurenghi3,
Usha Chakravarthy2, Rufino M. Silva1, 4. 1Centro de Responsabilidade
Integrado de Oftalmologia, Centro Hospitalar e Universitário de
Coimbra, Coimbra, Portugal; 2Center for Experimental Medicine,
Belfast, Ireland; 3Eye Clinic, Department of Clinical Science Luigi
Sacco, Milan, Italy; 4Association for Innovation and Biomedical
Research on Light - AIBILI, Coimbra, Portugal.
Purpose: The importance of reticular pseudodrusen (RPD) as a
retinal phenotype associated with age-related macular degeneration
(AMD) but long follow-up data is still lacking. We conducted a
multicenter, longitudinal, observational, study to determine whether
RPD confer a long-term increased risk of progression to late AMD in
the second eye of patients with unilateral exudative-AMD (eAMD).
Methods: Fellow eyes of patients with unilateral eAMD were
recruited from 2 european centers and evaluated on the risk of
progression to late-AMD. A minimum follow-up of 5 years was
required, unless progression occurred first. Baseline retinal profile
of patients was evaluated using a multimodal imaging approach that
included color fundus photographs (CFP), fundus auto-fluorescence
(FAF), infra-red (IR), optical coherence tomography (OCT), and
red-free (RF) images. Baseline images were graded by two separate
centers. Main outcome measures were the incidence of choroidal
neovascularization (CNV) and geographic atrophy (GA).
Results: We recruited 88 patients (48 female) with a mean age
of 75.6 ± 7.1 years and a mean follow-up of 65.7 ± 20.9 months.
Baseline prevalence of RPD was 58% (n=51). There was no
statistically significant association of RPD with increased age
(p=0.29) or sex distribution (p=0.39). The most sensitive image
modality for RPD was IR (93%), followed by FAF (92%), OCT
(74%, RF (33%) and CFP (29%). After 5 years, 54.50% (n=48) of
the study eyes progressed to late-AMD. Of those, 81.25% (n=39)
developed CNV and 18.75% (n=9) geographic atrophy (GA). After
correcting for age and sex, the presence of RPD was significantly
associated with development of late-stage AMD (OR=2.55, p=0.03).
In a multivariate analysis using a model that included other known
risk markers – hypo and hyperpigmentation, intermediate drusen, and
large drusen - the association between RPD presence and increased
risk of progression was still observed but no longer reached statistical
significance (OR=2.35; p=0.089).
Conclusions: RPD are highly prevalent in the fellow eyes of patients
with unilateral AMD. Presence of RPD is associated with increased
long-term risk of progression, highlighting the importance of
comprehensive multimodal retinal imaging and careful monitoring of
at-risk patients.
Commercial Relationships: Joao Gil, None; João
Pedro Marques, None; Ruth E. Hogg, None; Chiara Rosina,
None; Maria L. Cachulo, None; Ana Rita Santos, None;
Giovanni Staurenghi, None; Usha Chakravarthy, None;
Rufino M. Silva, None
Program Number: 4964 Poster Board Number: A0354
Presentation Time: 11:00 AM–12:45 PM
De novo and recurrent polypoidal lesions are amenable to antiVEGF therapy
Gisela Velez1, 2. 1Central Massachusetts Retina and Uveitis Center,
Worcester, MA; 2Ophthalmology, University of Massachusetts
Medical School, Worcester, MA.
Purpose: Polypoidal choroidal vasculopathy (PCV) can present a
treatment challenge. We performed a retrospective review of patients
with PCV and describe our experience using anti-VEGF therapies
in the management of de novo and recurrent polypoidal lesions. Our
goal was to identify lesion characteristics which may predict response
to anti-VEF therapy.
Methods: Records of all patients with exudative age related
macular degeneration were reviewed. Eight patients (9 eyes) with
PCV were identified and confirmed by indocyanine green (ICG)
angiography (Spectralis, Heidelberg). De novo lesions were defined
as those diagnosed at the time of presentation, or new lesions in
previously treated patients without evidence of PCV at the time of
initial diagnosis. Successful treatment was defined as (1) complete
resolution of subretinal fluid (SRF) on SD-OCT (Cirrus 4000, Zeiss)
with (2) stabilization (1 line or less loss of vision) or improvement of
visual acuity (VA).
Results: Patients ragned in age from 50 to 86 years. Six patients were
caucasian, 2 hispanic/latino. Six eyes were treated with bevacizumab
(1.25mg) followed by aflibercept (2 mg), 1 eye with ranibizumab
(0.5mg) followed by aflibercept, and 2 eyes with aflibercept (2 mg).
One patient was treated with aflibercept (2 mg) in combination with
photodynamic therapy (PDT). Eight eyes had de novo polypoidal
lesions, 6 at the time or presentation and 2 developed after protracted
anti-VEGF therapy, possibly representing the result of vascular
remodeling. One eye presented with recurrent polypoidal lesions after
PDT therapy.
All 9 eyes had a partial or complete response to anti-VEGF therapy.
Median number of treatments in eyes successfully treated was 15,
ranging from 1 to 36. In 3/9 eyes treatment was unsuccessful- one
eye had a decrease of 2 lines of vision, two eyes had persistent SRF.
Eyes with persistent SRF represented lesions resulting from vascular
remodeling. Polypoidal lesions persisted despite SRF resolution in
most eyes, and resolved in 2/6 eyes with de novo lesions at the time
of initial presentation and 1/1 eyes with recurrent lesions.
Conclusions: Different subtypes of polypoidal lesions have different
patterns of response to anti-VEGF therapy. In our study, recurrent
lesions had the best response, while lesions that arose from vascular
remodeling were most resistant to treatment. Ultimately, however, all
subtypes can be successfully managed with anti-VEGF therapy.
Commercial Relationships: Gisela Velez, Regeneron (C),
Allergan (C)
Program Number: 4965 Poster Board Number: A0355
Presentation Time: 11:00 AM–12:45 PM
Intravitreal Aflibercept for Treatment-Resistant Neovascular
Age-related Macular Degeneration Patients: 3-Year Outcomes
Wijeyanthy Wijeyakumar1, 2, Meidong Zhu1, 2, Andrew A. Chang1, 2.
1
Sydney Institute of Vision Science, Sydney, NSW, Australia; 2Save
Sight Institute, The University of Sydney, Sydney, NSW, Australia.
Purpose: Long-term safety and efficacy of intravitreal aflibercept
on treatment-resistant neovascular age-related macular degeneration
(TR-nAMD) patients is unknown. We prospectively evaluate the
efficacy and safety of intravitreal aflibercept over 3-years.
Methods: Forty-nine TR-nAMD patients aged over 50 years were
treated with three monthly loading doses of intravitreal aflibercept
followed by injections every 8 weeks across 48-weeks. Subsequently,
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ARVO 2016 Annual Meeting Abstracts
a spectral-domain optical coherence tomography (SD-OCT) guided
“as-needed” regime was given for a further 2-years. Ophthalmic
examinations included best-corrected visual acuity (BCVA) assessed
in Early Treatment of Diabetic Retinopathy Study charts and central
macular thickness (CMT) measured by SD-OCT at each visit.
Changes in BCVA and CMT were analysed using paired t-test,
Pearson’s correlation and linear regression methods.
Results: Mean BCVA at baseline was 60.5±16.2 letters and this
improved significantly over the 1st year by 4.7±9.1 letters (p<0.001),
and maintained up to years-2 and 3 (changes of 0.8±9.2 letters,
p=0.573 and 1.1±10.0 letters, p=0.535), compared to baseline. Mean
CMT at baseline was 448.4±141.2μm, which reduced significantly
at years-1, 2, and 3 by 97.2±149.3µm, 144.0±149.7µm and
142.2±158.9µm, (p<0.001, for all), compared to baseline. BCVA
improvements correlated with CMT changes at week-24 only (r=-0.295, p=0.039). Mean number of injections and visits over
1st year were 7.0±0.0 and 13.0±0.0. Mean injection numbers
increased by 0.7±2.1, (p=0.031) and 1.5±3.1, (p=0.003) while visit
numbers decreased by -3.8±1.8 and -4.0±3.0, (all p<0.001) over
2nd and 3rd years compared to baseline. There were no significant
systemic and ocular safety issues found over 3-years of treatment.
Cardiovascular related severe adverse events were myocardial
infarction (1%), atrial fibrillation (2%), deep vein thrombosis (2%),
mini stroke (2%) and heart attack (2%). Ocular adverse events over
3-years of treatment in study eye were sub-macular haemorrhage
(2%) and intraocular pressures elevation >25mmHg (4%).
Conclusions: Aflibercept has been suggested to be effective in
anatomical improvement and maintaining vision in TR-nAMD
patients over 3-years. Vision improvement in first 24-weeks may
relate to the reduction in macular oedema. Intravitreal aflibercept
appears safe to use over 3-year treatment.
Commercial Relationships: Wijeyanthy Wijeyakumar, None;
Meidong Zhu, None; Andrew A. Chang, Novartis (R), Bayer (C),
Alcon (R), Alcon (C), Bayer (R), Bayer (F), Novartis (C)
Clinical Trial: ACTRN, ACTRN 12612000666820 and ACTRN
12612001310853
Program Number: 4966 Poster Board Number: A0356
Presentation Time: 11:00 AM–12:45 PM
Phenotype characteristics of patients with age-related macular
degeneration carrying a rare variant in the CFH gene
Eveline Kersten1, Maartje Geerlings1, Sascha Fauser2,
Anneke I. Den Hollander1, Carel C. Hoyng1. 1Ophthalmology,
Radboud university medical center, Nijmegen, Netherlands;
2
Ophthalmology, University Hospital of Cologne, Cologne, Germany.
Purpose: Several rare genetic variants in the complement factor H
(CFH) and its association with age-related macular degeneration
(AMD) have been described recently. However there is limited
literature on the phenotypes accompanying these variants. To help
ophthalmologists in their decision of doing additional genetic testing,
we aim to describe the phenotypical characteristics of patients with
AMD carrying a rare variant in the CFH gene.
Methods: We searched the clinical database of the Department
of Ophthalmology at the Radboud university medical center and
the European Genetic Database (EUGENDA) for subjects with a
variant in CFH. Whole exome sequencing and/or Sanger sequencing
was performed to detect variants in the CFH gene. We selected
cases carrying variants with protein changing coding regions and a
population frequency (MAF) of less than 1%. In total 54 subjects,
with 43 different CFH variants, were included in this study. Fundus
features were graded based on color fundus photographs of both
eyes, and if available also on other image modalities. The following
features were assessed: presence of drusen, type and number of
drusen, location of drusen, presence of pigmentary abnormalities,
geographic atrophy or signs of neovascularization.
Results: The mean age of first symptoms in these patients was 58
years (SD 13.0). There was a high degree of symmetry between
the eyes of patients carrying a rare variant in CFH. The drusen area
inside the ETDRS grid was very extensive, but in most cases also
peripheral (small hard) drusen were present, known as cuticular
drusen.
Conclusions: AMD patients carrying a rare genetic variant in the
CFH gene have a relatively early age of first symptoms, a high grade
of symmetry between the two eyes, an extensive drusen area and in
most cases also peripheral drusen. These characteristics could help
ophthalmologists to select patients for additional genetic testing more
efficiently.
Commercial Relationships: Eveline Kersten, None;
Maartje Geerlings, None; Sascha Fauser, None; Anneke I. Den
Hollander, None; Carel C. Hoyng, None
Support: This project has received funding from the European
Union’s Horizon 2020 research and innovation programme under
grant agreement No 634479.
Program Number: 4967 Poster Board Number: A0357
Presentation Time: 11:00 AM–12:45 PM
Prevalence of drusen and conversion to neovascular age-related
macular degeneration in the HARBOR study fellow eyes
Caroline R. Baumal1, Carlos Quezada Ruiz2, Shamika Gune2,
Pin-wen Wang2, Anne E. Fung2. 1Ophthal-Tufts Univ, New England
Eye Center, Boston, MA; 2Genentech, Inc., South San Francisco, CA.
Purpose: To evaluate the prevalence of drusen at baseline and
the conversion to neovascular age-related macular degeneration
(AMD) based on fluorescein angiography (FA) and spectral-domain
optical coherence tomography (SD-OCT) findings, in fellow eyes
of the HARBOR study population. Previously, The Age-Related
Eye Disease Study 2 (AREDS2) demonstrated that 35.5% (248 of
698 eyes) with bilateral large drusen and late AMD in one eye at
baseline progressed to neovascular AMD over a median of 4.9 years
of follow-up (The Age-Related Eye Disease Study 2 (AREDS2)
Research Group, et al. JAMA Ophthalmol. 2014;132:142-9).
Methods: This retrospective analysis of the 24-month, phase 3,
randomized, double-masked, active-treatment controlled HARBOR
study focused on the fellow eyes that had drusen (hard or soft) at
baseline without the presence of neovascular AMD, defined as no
neovascular AMD reported from history in the case report form,
absence of choroidal neovascularization (CNV) on baseline FA,
central subfield thickness (CST) <275 μm on baseline SD-OCT, and
no subretinal fluid (SRF), cystoid space, intraretinal fluid (IRF), or
pigment epithelial detachment (PED) on baseline SD-OCT. Fellow
eye conversion was defined as presence of CNV on FA and any
SD-OCT fluid defined as presence of SRF, cystoid space, IRF, PED,
or CST ≥275 μm at any post-baseline visits.
Results: In HARBOR, 352 fellow eyes had drusen without any
neovascular AMD at baseline. Of these, 28 (8%) eyes had hard
drusen and 324 (92%) eyes had soft drusen. At 24 months, eyes with
soft drusen had a higher rate of conversion to CNV than eyes with
hard drusen (18% vs 4%, respectively). While the proportion of eyes
with hard drusen at baseline was small, 86% of them developed
soft drusen by 24 months. Imaging case studies will be presented to
illustrate these findings.
Conclusions: In the HARBOR study, the majority of fellow eyes had
soft drusen at baseline. Many of those with hard drusen at baseline
converted to soft drusen over two years. Of fellow eyes with soft
drusen and no neovascular AMD at baseline, 18% converted to CNV
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ARVO 2016 Annual Meeting Abstracts
by 2 years. Such eyes should be carefully monitored for conversion to
exudative AMD.
Commercial Relationships: Caroline R. Baumal, None;
Carlos Quezada Ruiz, Genentech, Inc.; Shamika Gune, Genentech,
Inc.; Pin-wen Wang, Genentech, Inc.; Anne E. Fung, Genentech,
Inc.
Support: Genentech, Inc., South San Francisco, CA, provided
support for the study and participated in the study design; conducting
the study; and data collection, management, and interpretation
Clinical Trial: NCT00891735
Program Number: 4968 Poster Board Number: A0358
Presentation Time: 11:00 AM–12:45 PM
Association of COL8A1 rs139380413 polymorphism with dry
AMD in two Sardinian genetic isolates
Maria Silvana Galantuomo1, Maria Elena Galimi1, Ginevra Biino2,
Maria Pina Concas3, Roberta Farci1, Mario Pirastu3,
Maurizio Fossarello1. 1Ophthalmology, University of Cagliari, Quartu
Sant Elena, Italy; 2Institute of Molecular Genetics, National Research
Council of Italy, Pavia, Italy; 3Support OU, Institute of Genetic and
Biomedical Research, National Research Council of Italy, Sassari,
Italy.
Purpose: To ascertain the prevalence of age related macular
degeneration (AMD) and to examine the role of a polymorphism in
the candidate gene COL8A1 (collagen, type VIII, alpha 1) in two
Sardinian genetic isolates.
Methods: An epidemiologic survey was conducted in two Ogliastra
villages, in central eastern Sardinia, Baunei and Urzulei (n=2593).
Detailed questionaries were administered to obtain demographic
information, smoking history, alcohol intake, sunlight exposure,
medical history, medication use and diet. Participants underwent a
complete eye examination including OCT. We then evaluated those
subjects over 50 years old (n=1148) for the clinical signs of AMD,
that were assessed on colour fundus photographs using a modification
of the Wisconsin Age-related Maculopathy Grading System protocol.
Blood samples were taken for biochemical determinations and
DNA extraction. Subjects were genotyped using Illumina Human
Exome BeadChip array. A case control test for samples with related
individuals was performed on rs139380413 SNP (COL8A1 gene) in
169 subjects.
Results: AMD lesions were classified as dry (n=106), wet (n=11)
and mixed (n=4). Overall prevalence of AMD was 10.5%, with no
significant gender differences. We reconstructed the pedigrees of all
diseased subjects and observed that those affected by the dry form of
AMD (dAMD) better clustered in families. The case control test for
related individuals was performed on 73 cases with dAMD and 96
controls, and resulted in a significant association of the rs139380413
SNP with dAMD (p=0.037). We observed a frequency of the A allele
of 6.8% in cases and 2.6% in controls.
Conclusions: The rs139380413(A) allele is reported here for first
time to be differently distributed between dAMD patients and
controls. COL8A1 rs139380413 polymorphism is associated with
dAMD, suggesting that this gene may be a susceptibility gene locus
for dAMD in Sardinian population.
Commercial Relationships: Maria Silvana Galantuomo,
None; Maria Elena Galimi, None; Ginevra Biino, None; Maria
Pina Concas, None; Roberta Farci, None; Mario Pirastu, None;
Maurizio Fossarello, None
Program Number: 4969 Poster Board Number: A0359
Presentation Time: 11:00 AM–12:45 PM
Relationship between foveal ellipsoid zone integrity and central
visual function in age related macular degeneration
Noelia Pitrelli Vazquez1, Simon P. Harding1, 2, Heinrich Heimann2,
Paul C. Knox1. 1Eye and Vision Science, Institute of Ageing and
Chronic Disease, University of Liverpool, Liverpool, United
Kingdom; 2Royal Liverpool University Hospital, Liverpool, United
Kingdom.
Purpose: Lack of ellipsoid zone (EZ) hyper-reflectivity in high
resolution optical coherence tomography (OCT) has been associated
with poor retinal sensitivity at corresponding retinal loci measured
by microperimetry. We investigated the relationship between EZ
hyper-reflectivity over the foveal area and two measurements of
central visual function: shape discrimination hyperacuity (SDH) and
best corrected visual acuity (BCVA) in eyes at risk of developing late
age-related macular degeneration (AMD).
Methods: Patients attending hospital to receive treatment for
neovascular AMD (nAMD) to their first eye performed BCVA,
SDH and Heidelberg Spectralis OCT with their fellow eye (study
eye, SE), which was required to have no evidence of nAMD or
central geographic atrophy. EZ hyper-reflectivity was assessed in all
B-scans lines falling within the foveal area (1200µm in diameter)
and measured using the software provided calliper. The sums of the
lengths of each line where hyper-reflectivity was intact and abnormal
/absent were calculated and transformed into a percentage of the total.
A grade of “0” was given when the EZ was intact, “1” when <20% of
the EZ was abnormal/absent and 2 when >20% of abnormal/absent
EZ was present.
Results: Of 78 SEs [mean participant age 77±8 years (range 57 to
91); 49 females], 33 (42%) were graded as “0”. For these, mean
(95%CI) SDH and BCVA were: -0.62 (-0.68 to -0.57) and 0.06
(0.01 to 0.1) logMAR. For 17 eyes (22%) graded as “1” SDH and
BCVA were -0.59 (-0.66 to -0.52) and 0.04 (0.02 to 0.1) logMAR
respectively. For 28 (36%) graded as “2”, SDH and BCVA were -0.50
(-0.56 to -0.45) and 0.06 (0.01 to 0.1) logMAR respectively. After
adjusting for the effect of age, the EZ grade had a significant negative
effect on SDH score [F(2,74)=4.94, p=0.01, Partial η2=0.12] but not
on BCVA [F(2,74)=0.13, p=0.89, Partial η2=0.003]. Planned contrasts
revealed that SDH was significantly decreased only when EZ was
graded as 2 compared to 0 [t(74)=-3.1, p=0.03, r=0.12].
Conclusions: There was a small but still statistically significant
decrease in SDH observed in eyes with greater EZ abnormality,
which was not seen for BCVA. As these measurements of central
vision are comparable in terms of ease of use and task simplicity, our
results indicate that SDH might be a better marker of photoreceptor
dysfunction in early/intermediate AMD than BCVA.
Commercial Relationships: Noelia Pitrelli Vazquez, None;
Simon P. Harding, None; Heinrich Heimann, None; Paul C. Knox,
Vital Art & Science Inc (F)
Support: The Dunhill Medical Trust Grant n. R283/0213
Program Number: 4970 Poster Board Number: A0360
Presentation Time: 11:00 AM–12:45 PM
Systemic anti-inflammatory drugs and choroidal
neovascularization: a secondary analysis of CATT study
Joao Barbosa-Breda4, 1, Jennifer Mancio3, Inês Pires Silva2,
Fernando Falcao-Reis4, 1, Amandio A. Rocha-Sousa4, 1. 1Faculdade
de Medicina da Universidade do Porto, Porto, Portugal; 2Oncology,
Instituto Português de Oncologia, Lisboa, Portugal; 3Cardiology,
Centro Hospitalar de Vila Nova de Gaia/Espinho, Porto, Portugal;
4
Ophthalmology, Centro Hospitalar São João, Porto, Portugal.
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ARVO 2016 Annual Meeting Abstracts
Purpose: Although immunological and inflammatory imbalances
have been involved in the development and progression of agerelated macular degeneration (AMD), the benefit of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids remains
controversial. We performed a secondary analysis of the Comparison
of AMD Treatments Trials (CATT) database and evaluated the
association between systemic use of NSAIDs and/or steroids and
signs of progression of neovascular AMD.
Methods: A total of 1149 patients were included and divided into
four groups according to their anti-inflammatory treatment: “just
NSAIDs” (n=474), “just steroids” (n=114), “both” (n=277), “neither”
(n=284). The 1-year and 2-year visual acuity (VA) and total area of
choroidal neovascularization (CNV) were determined and compared
between groups.
Results: The “just steroids” group presented with higher baseline
values for VA and lower total area of CNV lesion, during the 2 years
of follow-up. The mean response profiles of VA and total area of
CNV lesion were parallel and there was no statistically significant
drugclass*time interaction. According to the adjustment analysis,
age seems to be an important covariate when analyzing visual acuity
and also the total area of CNV lesion, while statins and previous or
current smoking did not change the statistical significance.
Conclusions: We did not find an association between systemic use of
anti-inflammatory drugs (NSAIDs or steroids) and the progression of
neovascular AMD. However, there was a better outcome in the “just
steroids” group regarding visual acuity and total area of CNV lesion.
Commercial Relationships: Joao Barbosa-Breda, None;
Jennifer Mancio, None; Inês Pires Silva, None; Fernando FalcaoReis, None; Amandio A. Rocha-Sousa, None
Program Number: 4971 Poster Board Number: A0361
Presentation Time: 11:00 AM–12:45 PM
Comparison of Treatment Outcomes Among Subtypes of
Polypoidal Choroidal Vasculopathy in a Multicenter Randomized
Controlled Study (EVEREST study)
Colin S. Tan1, 2, Louis W. Lim1, 2, Wei Kiong Ngo1, 2, Tock H. Lim1, 2.
1
Ophthalmology, National Healthcare Group Eye Institute, Singapore,
Singapore; 2Fundus Image Reading Center, National Healthcare
Group Eye Institute, Singapore, Singapore.
Purpose: Polypoidal choroidal vasculopathy (PCV) is a disease
characterized by abnormal vascular channels with terminal
dilatations. PCV has high prevalence among some populations
such as Asians, and a variable clinical course. In an earlier series of
patients, we previously described a novel classification of 3 subtypes
of PCV, with differences in long-term clinical outcomes. We aimed
to describe the frequency and characteristics of PCV subtypes among
patients from a multicenter randomized controlled trial, and to
determine the impact of PCV subtypes on clinical outcomes.
Methods: Analysis of 60 patients with symptomatic macular
PCV from the EVEREST Study. Standardized imaging protocols,
including indocyanine green (ICGA) and fluorescein angiography
(FA), were used by the Central Reading Center to confirm the
diagnosis of PCV. The image sets were subsequently graded to
classify PCV into 3 subtypes, and correlated with visual acuity
(VA) and central retinal thickness (CRT). Type A PCV had polyps
with interconnecting channels only, Type B had branching vascular
networks with no leakage on FA, and Type C had branching vascular
networks with significant leakage on FA. VA and retinal thickness on
optical coherence tomography were reviewed monthly throughout the
study.
Results: Of the 60 patients, 54 were gradeable for PCV subtype.
Among these, 8 had Type A PCV (14.8%), 27 had Type B (50%) and
19 had Type C (35.2%). VA and reduction in retinal thickness varied
significantly with PCV subtype. At 6 months, the VA was highest
among patients with Type A compared to Types B and C (80.1 letters
vs. 67.2 vs. 50.4 respectively, p<0.001), with the differences among
the 3 subtypes statistically significant. Type A PCV gained 13 letters
vs. 8.5 (Type B) and 6.9 (Type C) (p<0.001). VA≥20/40 was highest
for Type A compared to Types B and C (100% vs. 51.9% vs. 10.5%,
p<0.001). Retinal thickness improved in all PCV subtypes. At 6
months, the CRT was thickest for Type C PCV followed by Type B
and Type A (201.7 µm vs. 188.7 µm vs. 183.8 µm, p=0.657).
Conclusions: The PCV subtype affects the visual outcome following
treatment, and the PCV subtype classifcation may be applied to
different populations. The distinction in clinical outcomes between
the PCV subtypes is observed in the initial months following the start
of treatment.
Commercial Relationships: Colin S. Tan, Novartis (R), Heidelberg
Engineering (R), Bayer (R); Louis W. Lim, None; Wei Kiong Ngo,
None; Tock H. Lim, Novartis (R), Heidelberg Engineering (R)
Clinical Trial: NCT00674323
Program Number: 4972 Poster Board Number: A0362
Presentation Time: 11:00 AM–12:45 PM
AutoAmsler: Envisioning Secondary Prevention Through Digital
Health
Kaylan Baban2, 1, Kapil Mishra3, Alexandre Ly van manh4,
Kristen Esperanza5, Scott E. Brodie6. 1Medicine, George Washington
University, Washington, DC; 2Preventive Medicine, Icahn School
of Medicine at Mount Sinai, New York, NY; 3Medical Education,
Icahn School of Medicine at Mount Sinai, New York, NY; 4Graduate
Program in Public Health, Icahn School of Medicine at Mount
Sinai, Mount Sinai, NY; 5New York University, New York, NY;
6
Ophthalmology, Icahn School of Medicine at Mount Sinai, New
York, NY.
Purpose: Amsler grid is often digitally reproduced on mobile devices
and web sites, interfaces that allow a greater range of supportive
functionalities (reminders, history tracking, resources), but for which
diagnostic validity has not been demonstrated.
Methods: Cross-over study of 145 eyes in 100 patients with preexisting diagnoses of macular disease. Paper and digital Amsler
grids were viewed with each affected eye individually, to compare
sensitivity of these media in eliciting visually-significant macular
pathology. Each eye served as its own control. Eyes without
macular disease or with BCVA worse than 20/150 were excluded.
Macular pathologies included age-related macular degeneration with
and without neovascularization (n=73), diabetic macular edema
(n=27), and epiretinal membrane (n=32). The primary outcome was
number of visual field defects (VFDs), defined as any scotoma or
metamorphopsia reported by the participant while viewing the grid.
Wilcoxon signed rank test and sign test were used for statistical
analyses. Subjects were also asked to compare the subjective
experience of viewing the grid on paper and digitally.
Results: Among 100 participants, 65% were female (mean age
of 64.4±14.2). Collectively, 145 eyes with macular disease were
assessed. There was no significant difference between media in the
number of eyes reporting VFDs (p = 0.18, two tailed). A discrepancy
between media in the number of VFDs detected per eye, however,
was noted in 21 eyes, with an overall mean difference of 0.12 VFDs
more per eye viewing the digital grid (SD=0.67). This difference,
as evaluated by the Wilcoxon signed rank test, showed greater
sensitivity of the digital version and was statistically significant
(p=0.013) Qualitatively, participants reported greater clarity of the
digital Amsler grid image, ascribed to higher contrast and backlight
illumination.
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ARVO 2016 Annual Meeting Abstracts
Conclusions: The digital Amsler grid was found to be more sensitive
than paper in detecting VFDs in eyes affected by visually-significant
macular disease. These findings support the use of Amsler grid via
digital interfaces as a validated screening tool. The study is a first step
in bringing an evidence-based mobile application for self-screening
to patients with macular disease.
Commercial Relationships: Kaylan Baban, American Macular
Degeneration Foundation (S); Kapil Mishra; Alexandre Ly van
manh, None; Kristen Esperanza, None; Scott E. Brodie, None
Program Number: 4973 Poster Board Number: A0363
Presentation Time: 11:00 AM–12:45 PM
Ultrawidefield (UWF) ICG-Angiography for the Diagnosis and
Treatment of Exudative Age-Related Macular Degeneration
(ARMD)
Mark Nelson. North Carolina Macular Consultants, Winston Salem,
NC.
Purpose: The use of Ultrawide field (UWF) flourescein angiography
reveals the presence of previously non-documented peripheral nonperfusion and neovasculization which has advanced clinical efficacy.
This retrospective, observational study examines whether UWF ICG
angiography provides additional information that contributes to the
diagnosis and management of Exudative ARMD.
Methods: 37 patients had Exudative ARMD, both treatmentnaive and previously treated with anti-VEGF monotherapy and/
or photodynamic therapy with verteportfin. 2.5 ml of 25% sodium
flourescein and 25 mg of indocyanine green were infused separately
through a antecubital vein and imaged using the Optos California
camera. Visualization for up to 200 degrees were obtained.
Results: 32.4% of patients revealed choroidal arterioles on early
transit UWF ICG photos that originated anterior to the major vascular
arcades, traversing to the posterior pole where they were associated
with areas of neovascularization/flourescein leakage found under the
macula. This imaging technique revealed new targets not visualized
on non-UWF imaging.which led to enhanced neovascular and
exudative resolution when treated with photodynamic therapy/antiVEGF/steroid triple combination therapy (described elsewhere).
Conclusions: This pilot study gives insight into the pathophysiology
of the Exudative ARMD neovascular process as it appears that
neovascularization originates peripherally and migrates to the
posterior pole where there might be a higher concentration of tissuebound VEGF. In addtion, visualization of these vessels provide an
opportunity to determine the etiologies of persisent leakage during
the course of anti-VEGF monotherapy which occurs in over one-third
of patients. UWF ICG angiography can also provide clues on how to
enhance clinical efficacy as well as to rationalize the use of expensive
anti-VEGF drugs. It is hopeful that this process, when coupled with
OCT angiography, will give further details into the anatomy of
pathological neovascular vessels.
Commercial Relationships: Mark Nelson, Thromobogenics, Inc.
(C), Optos, Inc. (C), Bausch & Lomb, Inc. (R)
Program Number: 4974 Poster Board Number: A0364
Presentation Time: 11:00 AM–12:45 PM
Treatment of RAP lesions in clinical practice: a 5-year follow-up
Marco Frederico Marques1, 2, João Pedro Marques1, 2, Joao Gil1, 2,
José F. F. Costa1, Maria L. Cachulo1, 2, Isabel Pires1, 2,
Joao Figueira1, 2, Rufino M. Silva1, 2. 1Department of Ophthalmology,
Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;
2
Association for Innovation and Biomedical Research on Light and
Image (AIBILI), Coimbra, Portugal.
Purpose: Given its distinctive features and intrinsic fierceness, RAP
lesions constitute a significant challenge in daily clinical practice.
Data on the long-term treatment effectiveness is scarce, and the
longest reported period of follow-up is of 3 years. The purpose of
this study was to evaluate de 5-year efficacy of IV ranibizumab in the
treatment of RAP lesions, and to identify prognostic-related factors
using multimodal retinal imaging.
Methods: Cross-sectional study including patients with confirmed
diagnosis of RAP and 60 months of follow-up after the first
intravitreal injection of ranibizumab. Treatment was administered
according to a PRN regimen, and in 26 eyes, baseline photodynamic
therapy (PDT) was instituted. Initial evaluation involved a complete
ophthalmological evaluation, complemented with multimodal retinal
imaging. Classification of RAP stage at diagnosis was performed by
a senior retina specialist. Improvement and deterioration of visual
acuity (VA) were defined as an increase or decrease of ≥5 ETDRS
letters from baseline. A stable VA encompassed any values between
these limits.
Results: Forty-seven eyes from 41 consecutive patients were
included. Mean age at diagnosis was 77.2±6.3 years, and mean initial
VA was of 53.7±16.0 ETDRS letters. All eyes were cross-sectionally
evaluated at 60 months of follow-up. An increase from baseline
VA was noted in 13 individuals (27.7%), while VA deterioration
occurred in 27 (57.4%). Stabilization was observed in 7 (14.9%)
eyes. The mean number of IV ranibizumab injections was 9.6±5.5.
The concomitant use of PDT did not add benefits vs. IV ranibizumab
monotherapy in what concerns the visual prognosis (p=0.986) or the
development of geographic atrophy (p=0.551). Subretinal fluid (SRF)
at presentation positively correlated with favorable visual outcomes
(p=0.025).
Conclusions: RAP lesions constitute a distinct neovascular
phenotype of AMD. This study combines the largest population of
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ARVO 2016 Annual Meeting Abstracts
RAP eyes with the longest reported follow-up in a clinical setting.
After 5 years of follow-up, the instituted treatment allowed for
an improvement or stabilization of VA in 42.6% (n=20) of our
population. Baseline subretinal fluid may play an important role in
the prognosis of RAP.
Commercial Relationships: Marco Frederico Marques, None;
João Pedro Marques, None; Joao Gil, None; José F. F. Costa,
None; Maria L. Cachulo, None; Isabel Pires, None; Joao Figueira,
None; Rufino M. Silva, None
Program Number: 4975 Poster Board Number: A0365
Presentation Time: 11:00 AM–12:45 PM
Systemic treatment of macular degeneration with sildenafil
D Jackson Coleman, Stanley Chang, Stephen H. Tsang,
Suzanne Daly, Winston Lee, Harriet O. Lloyd, Ronald H. Silverman.
Ophthalmology, Columbia University Medical Center, New York,
NY.
Purpose: Choroidal ischemia is related to parasympathetic control
of the choriocapillaris, similar to parasympathetic regulation in
pulmonary hypertension and erectile dysfunction. With choroidal
ischemia, the terminal arterioles in the Sattler layer of the
choroid can be upregulated with a phosphodiesterase-5 (PDE5)
inhibitor to increase nitric oxide perfusion and reduce toxic
waste products (Starling’s Law)1. Sildenafil also cross-reacts with
phosphodiesterase-6 (PDE6), which normally promotes acidosis and
Warburg anabolism. Decreased photoreceptor Warburg anabolism
and outer segment genesis decrease retinal pigment epithelium (RPE)
metabolic stress. In a previous long-term series of sildenafil treatment
we found positive visual effects2,3. The purpose of this current
study is to evaluate the effects of systemic sildenafil on macular
degeneration including hard and soft drusen, as well as acquired and
inherited vitelliform lesions in a more diverse patient population.
Methods: Six subjects are being treated with systemic sildenafil,
20 to 40 mg twice daily, with dosage based on patient weight. Bestcorrected visual acuity (BCVA), color fundus and autofluorescence
imaging, Pelli-Robson contrast sensitivity and spectral domainoptical coherence tomography (SD-OCT) mapping of the macula is
performed every 2 months.
Results: There is improved contrast sensitivity, maintenance
of BCVA and evidence on SD-OCT of sub-pigment epithelial
detachment absorption after one year follow-up. Other changes
include decreased lipid in soft (vitelliform-type) lesions but no
observed changes in hard drusen.
Conclusions: Systemic PDE5 inhibitors such as sildenafil may have
a positive effect in treating macular degeneration and may offer
enhancement of intravitreal injection of anti-VEGF agents in wet
AMD. Vision is retained by increased choroidal perfusion and unique
metabolic support of the photoreceptor layer.
REFERENCES:
1. Flower RW, Fryczkowski AW, McLeod DS. Variability in
choriocapillaris blood flow distribution. Investigative ophthalmology
& visual science 1995;36:1247-1258.
2. Kim DY, Silverman RH, Chan RV, et al. Measurement of choroidal
perfusion and thickness following systemic sildenafil (Viagra((R))).
Acta ophthalmologica 2013;91:183-188.
3. Coleman DJ, Silverman RH, Rondeau MJ, Lloyd HO, Khanifar
AA, Chan RV. Age-related macular degeneration: choroidal
ischaemia? The British journal of ophthalmology 2013;97:10201023.
Commercial Relationships: D Jackson Coleman; Stanley Chang,
None; Stephen H. Tsang, None; Suzanne Daly, None; Winston Lee,
None; Harriet O. Lloyd, None; Ronald H. Silverman, None
Support: Research to Prevent Blindness, The Triad Foundation
Clinical Trial: http://www.rascal.columbia.edu/irb, IRB-AAAM7406
Program Number: 4976 Poster Board Number: A0366
Presentation Time: 11:00 AM–12:45 PM
NON-EXUDATIVE TOMOGRAPHIC MORPHOMETRIC
CHANGES IN PATIENTS WITH NEOVASCULAR AGERELATED MACULAR DEGENERATION
LAURA MONJE-FERNANDEZ1, Rosa Dolz-Marco2, María AndreuFenoll2, Roberto Gallego-Pinazo2. 1Ophthalmology, Hospital de
León, VALCABADO DEL PARAMO, Spain; 2Ophthalmology,
Hospital Universitario y Politécnico La Fe, Valencia, Spain.
Purpose: To analyze the clinical relevance and implications of nonexudative signs in the optical coherence tomography (OCT) scans of
patients with neovascular age-related macular degeneration (AMD).
Methods: Retrospective observational study of patients with
treatment-naïve neovascular AMD managed with intravitreal
injections of ranibizumab, and followed for at least 12 months. The
number of intravitreal injections administered, the best corrected
visual acuity (BCVA) evolution, and the central subfield thickness
(CST) throughout the follow-up period were recorded. A detailed
qualitative assessment of the OCT scans was also performed
including the presence of onion sign, outer retinal pseudoswelling,
intraretinal degenerative pseudocysts, subretinal clefts, outer retinal
tubulations (ORT) and geographic atrophy (GA). The association of
these changes with BCVA changes and the particular tomographic
type of neovascular lesion were analyzed.
Results: A total number of 175 eyes of 157 patients (83 women;
mean age 79.7±6.3 years) were included. Type 1 choroidal
neovascularization (CNV) was found in 87 eyes (49.7%), type 2 CNV
in 79 eyes (45.1%), and type 3 CNV in 14 eyes (8.0%). The onion
sign was observed in 18 eyes (10.3%), and was preferably observed
in type 3 CNV. Subretinal clefts were found in 13 eyes (7.4%) and
associated with type 1 CNV. Pseudocysts were observed in 63 eyes
(36.0%), whereas ORT were observed in 44 eyes (25.1%); both
sings were most frequently associated with type 2 CNV. The outer
pseudoswelling was evidenced in 53 eyes (30.3%), related or not to
areas of GA that were found in 41 eyes (23.4%), and associated with
type 2 and 3 CNV. BCVA significantly improved in patients showing
the onion sign, subretinal clefts and pseudoswelling, whereas
ayes with pseudocyst, ORT and GA did not show a significant
improvement of the BCVA.
Conclusions: The visual outcome in patients with neovascular AMD
is directly related to the type of lesion and the presence of exudative
signs. The present study suggest that the presence of non-exudative
signs may also have a significant prognostic value in patients with
neovascular AMD.
Commercial Relationships: LAURA MONJE-FERNANDEZ,
None; Rosa Dolz-Marco, None; María Andreu-Fenoll, None;
Roberto Gallego-Pinazo, None
Program Number: 4977 Poster Board Number: A0367
Presentation Time: 11:00 AM–12:45 PM
PREDICTIVE MODELS OF LONG-TERM ANATOMIC
OUTCOME IN EXUDATIVE AMD TREATED WITH ASNEEDED RANIBIZUMAB
Lucia Gonzalez-Buendia1, 2, Santiago Delgado-Tirado1, 2,
M.Rosa Sanabria3, Itziar Fernández1, 4, Rosa Coco1. 1IOBA
Eye Institute, Valladolid, Spain; 2Hospital Clinico Universitario
Valladolid, Valladolid, Spain; 3Complejo Asistencial de Palencia,
Palencia, Spain; 4Ciber BBN, Valladolid, Spain.
Purpose: To analyze predictors and develop predictive models
of anatomic outcome during ranibizumab as-needed therapy of
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ARVO 2016 Annual Meeting Abstracts
neovascular age-related macular degeneration (AMD) after 4 years of
follow-up.
Methods: Retrospective case series of 194 patients (253 eyes)
treatment-naïve neovascular AMD. Clinical, funduscopic
characteristics and OCT were recorded at baseline, 3 months and
each year until the end of the follow-up. Baseline angiographic
characteristics were also evaluated. R Statistical Software was used
for statistical analysis. Main outcome measure was final anatomic
macular status.
Results: Presence of atrophy and greater number of injections
were associated with geographic atrophy (GA), whereas male
sex, presence of fibrosis, lower vision and lower change in central
macular thickness (CMT) at the end of the follow-up were associated
with fibrotic scar. Higher probability of preserved macular anatomy
was found among patients showing better VA. Contrarily, negative
predictors of preserved macular anatomy, were diagnosis in 2009,
older age, small area of fibrosis/atrophy, presence of pigment
epithelial detachment (PED), atrophy in the fellow eye, and active
AMD in the fellow eye. A suitable predictive model to predict the
risk of preserved macula vs. GA/scar was developed, and included
4 variables: age, baseline VA, number of injections at 3 months and
presence of PED at visit 0.
Conclusions: A new predictive model for final macular status, based
on easily harvested variables in daily clinical routine, is proposed
and, if validated, could be a useful tool for individual patient
management and clinical research studies.
Commercial Relationships: Lucia Gonzalez-Buendia,
NOVARTIS-Spain (F); Santiago Delgado-Tirado, NOVARTISSpain (F); M.Rosa Sanabria, NOVARTIS-Spain (F);
Itziar Fernández, NOVARTIS-Spain (F); Rosa Coco, NOVARTISSpain (F)
Support: Novartis-Spain funded this study. The views expressed
are those of the authors and not necessarily the funding body. The
researchers are independent of the funders.
Program Number: 4978 Poster Board Number: A0368
Presentation Time: 11:00 AM–12:45 PM
Light-adapted RETeval in Age Related Macular Degeneration
and Diabetes Patients
Gloria Wu1, Scott E. Brodie4, Victor Chen2, Don B. Kim3. 1UC San
Francisco School of Medicine, San Jose, CA; 2UC San Diego, La
Jolla, CA; 3UC Berkeley, Berkeley, CA; 4Ophthalmology, Icahn
School of Medicine at Mount Sinai, New York, NY.
Purpose: Using RETeval (firmware version 2.0) with ISCEV
protocol to assess retinal function in patients with diabetes and age
related macular degeneration.
Methods: Inclusion criteria: Dilated fundus examination to 5mm
or more. Controls: no retinal diseases, no diabetes, no AMD, no
glaucoma, no uveitis. AMD patients drusen or small choroidal
neovascular membranes. Va for all patients between 20/20 - 20/50.
Informed consent was obtained. Exclusion criteria: Poor dilation.
Testing was done with RETeval (LKC Technologies Gaithersburg,
MD, firmware version 2.0), using alcohol skin prep and skin
electrodes. Using photopic white flash as defined by ISCEV light
adapted 3 ERG (standard flash “cone” ERG) (LA3), implicit times
(IT) and amplitudes (Amp) and 30 Hz flicker data were obtained from
a retinal practice in San Jose, CA between 6/2014 and 11/2015.
Results: Of 157 patients, 54 patients met the inclusion criteria. Form
54 patients, 172 ERG tests were performed.
Control patients: (n = 15) 8 M, 7 F avg age: 44.3±16.4 yrs, range
20-70.
AMD patients: (n = 13) 6 M, 7 F avg age: 71.4±16.7 yrs, range
43-91.
DM patients: (n = 26) 13 M, 13 F avg age: 64.0±13.6 yrs, range
28-88.
For control ERG LA3 (n=29), IT = 29.5±1.3 msec, Amp = 40.7±11.8
uV. (Coefficient of variation (Cv) = 0.044, 0.29 respectively.) 30 Hz
flicker ERG (n=26), IT = 25.6±0.9 msec, Amp = 28.8±8.1 uV.
(Cv = 0.035, 0.309 respectively.)
For AMD ERG LA3 (n=14), IT = 31.4±2.2 msec, Amp = 29.6±12.8
uV. (Cv = 0.070, 0.43 respectively.) 30 Hz flicker ERG (n= 22),
IT = 27.6±1.8 msec, Amp = 20.9±8.8 uV. (Cv = 0.070, 0.42
respectively.)
For DM ERG LA3 (n=34), IT = 30.6±1.7 msec, Amp = 33.0±15.5 uV.
(Cv = 0.056, 0.47 respectively.) 30 Hz flicker (n=47), IT = 28.5±3.3
msec, Amp = 20.8±11.9. uV. (Cv = 0.12, 0.57 respectively.)
For both C vs AMD and C v DM: IT and AMP, all p values <0.05.
See Table 1.
Conclusions: The RETeval is a new technology allowing for
portability, ease of use and brings electrophysiology to the clinical
practice. In this small study, the RETeval results suggest inner and
outer retina ERG changes in both diabetic and age related macular
degeneration patients. In the future, RETeval may provide additional
visual function testing for retina patients.
Commercial Relationships: Gloria Wu, None; Scott E. Brodie;
Victor Chen, None; Don B. Kim, None
Program Number: 4979 Poster Board Number: A0369
Presentation Time: 11:00 AM–12:45 PM
Agreement of retreatment decision patterns in nAMD primarily
based on OCT and an OCT / FA combination
Cay C. Loesche2, 1, Thulasi Kirupanathan1, Barbara Schmidt2,
Jessica Hirsch1, Klaus-Martin Sell2, Wolfgang Strunk2,
Frank Krummenauer1, 2. 1Institute for Medical Biometry and
Epidemiology, Universität Witten-Herdecke, Witten-Herdecke,
Germany; 2Muelheim Eye Hospital, Muelheim an der Ruhr, Germany.
Purpose: While fluorescein angiography (FA) and optical coherence
tomography (OCT) are both considered important in the primary
diagnostic workup of patients with neovascular age related macular
degeneration (nAMD), it is unclear whether routinely ommiting the
relatively invasive FA in the follow up of these patients carries the
risk of overlooking the need for retreatment. To quantify the risk
of missing an active lesion in a routine clinical health care setting,
a trial of diagnostic agreement and of the resulting therapeutic
decisions based on different diagnostic modalities was performed.
The indication for retretament was thus first solely based on SD-OCT
(spectral domain OCT), then on OCT plus FA and finally on OCT, FA
and ophthalmoscopy.
Methods: A total of 139 consecutive patients of a follow-up clinic
for patients with nAMD seen for the decision of whether to reinject
ranibizumab were included. (63% female, median age 80 years
(51 to 96). For each patient SD-OCT volume scans and a FA were
performed. The indication for a possible re-treatment was then first
based exclusively on the OCT examination, then using the additional
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ARVO 2016 Annual Meeting Abstracts
information from the FA and finally by also considering the findings
of the fundus examination.
A sample size of at least 130 eyes was calculated. The analysis
was based on Cohen’s kappa for pair-wise agreement with a 95%
confidence interval and on the McNemar test for symmetry at a 5%
significance.
Results: The concordance of OCT- vs OCT/FFA based decisions
was estimated 0.90 (Cohen’s kappa 95%, CI 0.81; 0.97). In 5% of
the patients an indication for treatment was seen after the additional
information of the FA, implying a locally significant deviation in
decision patterns (McNemar p=0.016). Concordance of OCT vs
OCT/FFA/ophthalmoscopy based decision was furthermore estimated
0.85 (95%, CI 0.76; 0.94). In contrast to the solely OCT-based
decisions, treatment was seen indicated in an additional 6% of the
patients, whereas in 2 patients (1%) a previous decision for treatment
was taken back (McNemar p=0,109).
Conclusions: Despite encouraging agreement between OCT, OCT/
FFA and OCT/FFA/ophthalmoscopy based treatment decision
patterns for anti-VEGF therapy, the exclusively OCT based
diagnostic procedure carries a notable risk for missing active lesions
in nAMD and thereby the risk of missing necessary treatment.
Commercial Relationships: Cay C. Loesche, None;
Thulasi Kirupanathan, None; Barbara Schmidt, None;
Jessica Hirsch, None; Klaus-Martin Sell, None; Wolfgang Strunk;
Frank Krummenauer, None
Support: Leonhard-Stinnes-Foundation, Muelheim, Germany
Program Number: 4980 Poster Board Number: A0370
Presentation Time: 11:00 AM–12:45 PM
Microperimetry and Fundus Photography in Patients with
Drusen and/or Age-related Macular Degeneration
Michael Kapusta1, 2, Julie-Andree Marinier3, 4, Pierre Forcier3,
David Nguyen-Tri3, Caitlin Murphy3, Olga Overbury3, 1.
1
Ophthalmology, Sir Mortimer B. Davis Jewish General Hospital,
Montreal, QC, Canada; 2Ophthalmology, McGill University,
Montreal, QC, Canada; 3School of Optometry, University of
Montreal, Montreal, QC, Canada; 4Institut Nazareth et Louis-Braille,
Montreal, QC, Canada.
Purpose: The relationship between drusen and pigmentary changes
identified in fundus photos and the overlying retinal sensitivity has
not been well studied. The purpose of this research was to compare
macular drusen and pigment mottling, identified on fundus photos,
to microperimetry of the macula conducted via optical coherence
tomographer/scanning laser ophthalmoscope (OCT/SLO).
Methods: Patients over the age of 50 who had drusen or were
diagnosed with AMD were recruited into the study. Visual acuity was
measured with ETDRS charts. Colour fundus photos were taken and
subsequently were graded using the Age-related Eye Disease Study
(AREDS) grading criteria for AMD. Microperimetry was performed
using the Optos OCT/SLO. Microperimetry images were scaled and
superimposed over fundus photos.
Results: To date, this ongoing study demonstrates a trend of
decreased macular sensitivity over areas of large and/or numerous
drusen or pigment mottling. Many participants showed decreased
macular sensitivity despite maintaining good visual acuity. Some
participants classified as AREDS Category 1 on fundus photos
showed microperimetry comparable to those in more advanced
AREDS categories.
Conclusions: Retinal areas affected by drusen have decreased
sensitivity despite good visual acuity and early AREDS-category
placement. Microperimetry may be useful in early detection of
AMD or identification of AMD patients who are more likely to
advance to later stages. Visual acuity and fundus photos alone may
indicate visual function to be better than it actually is. Combining
microperimetry with fundus photo information can give clinicians
and rehabilitation specialists a more accurate picture of a patient’s
functional status.
Commercial Relationships: Michael Kapusta, None; JulieAndree Marinier, None; Pierre Forcier, None; David Nguyen-Tri,
None; Caitlin Murphy, None; Olga Overbury, None
Support: This study is supported through a partnership among the
Antoine-Turmel Foundation, the FRQS, and the RRSV
Program Number: 4981 Poster Board Number: A0371
Presentation Time: 11:00 AM–12:45 PM
Light and age-related macular degeneration (AMD): retinal light
dose or irradiance (RI) varies inversely with axial length as does
AMD risk
Michael G. Quigley3, 1, Ian Powell2, Walter Wittich4, 5. 1Clinique
Bellevue, Montreal, QC, Canada; 2Powell Inc, Ottawa, ON, Canada;
3
Ophthalmology, Hopital Notre Dame (CHUM), Montreal, QC,
Canada; 4Optometry, School of Optometry, University of Montreal,
Montreal, QC, Canada; 5Centre de recherche interdisciplinaire en
réadaptation de Montréal métropolitain, Montreal, QC, Canada.
Purpose: The role of light in the genesis and evolution of age-related
macular degeneration (AMD) is controversial. Although a metaanalysis of studies attempting to link ambient sunlight exposure to
AMD showed there to be a link, there remains some uncertainty (Sui
GY, BJO 2013). However ambient light exposure is only a proxy
for (RI) because pupil size, hats, sunglasses, and immeasureable
behaviour modifications such as gaze aversion and lid closing will
alter the retinal light dose. Short axial length increases significantly
AMD risk with each millimeter decrease in axial length being
associated with a 29% increased risk of early AMD (Pan CW et
al.,Ophthalmology 2013). We calculate retinal light dose (RI) in a
normal population from the Reykjavik Eye Study (Olsen T et al.,
Acta Ophthalmo Scand 2007) and correlate it with axial length.
Methods: We created a simple one-surface schematic eye to calculate
light flux through the pupil and resultant image size on the retina.
Pupil size is known to be unaffected by refractive error (Winn B
et al., IOVS 1994). From this information, the retinal light dose
(photon equivalents)/mm can be calculated. The calculations were
then transposed to a two dimensional retina for photons/mm2 (RI).
These results were then verified using the ray-tracing feature inside
the optical-design software Opticsoft II (Powell I, Appl Opt 1978).
Results:
Retinal irradiance is inversely proportional to axial length (r=0.95).
A 21mm axial length eye would always be receiving 17% more
photons/mm2 compared to a 23mm axial length eye and 42% more
compared to a 25mm axial length eye.
Conclusions:
Retinal irradiance is inversely proportional to axial length and short
axial length eyes would constantly be receiving a significantly higher
light dose compared to long axial length eyes. AMD risk is also
inversely proportional to axial length. The parsimonious explanation
for this relationship is that light plays a role in the genesis and
evolution of AMD as is theorized (Hollyfield JG, IOVS 2010).
Commercial Relationships: Michael G. Quigley, None;
Ian Powell, None; Walter Wittich
Support: Canada and Quebec revenu agency tax credits
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ARVO 2016 Annual Meeting Abstracts
Program Number: 4982 Poster Board Number: A0372
Presentation Time: 11:00 AM–12:45 PM
Clinical outcomes and OCT analysis of Anti-VEGF treatments
with neovascular aged-related macular degeneration
Pooja G. Garg, Andy Lee, Alice T. Lyon, Rukhsana Mirza,
Amani Fawzi, Manjot Gill. Northwestern University, Chicago, IL.
Purpose: Neovascular age-related macular degeneration (NV-AMD)
is a leading cause of vision loss in Americans who are 50 years and
older. Anti-vascular endothelial growth factor (VEGF) agents have
evolved as the treatment of choice for NV-AMD. Patients fall on a
spectrum of favorable to poor response with treatment. This study
aims to identify the long-term outcomes and correlation to imaging of
anti-VEGF treatments.
Methods: The study design is a retrospective electronic chart
review of patients from 4 physician investigators in a large urban
referral center between March 2008 and October 2015. Methods
were approved by our institution’s IRB. The dataset was restricted
to records of treatment naïve patients with the ICD9 diagnosis code
362.52 for NV-AMD and CPT code 67028 for intravitreal injection.
OCT images were individually analyzed for presence of intraretinal,
subretinal, and sub-RPE fluid.
Results: Over a 7-year period, patients consisted of 154 (70.3%)
females and 65 (29.7%) males greater than 50 years old. Four
investigators treated 115 right eyes and 132 left eyes (219 unique
patients) with 3222 intravitreal injections – 420 Bevacizumab (B);
1243 Ranibizumab (R); 1559 Aflibercept (A). Of these patients, 12
eyes received only one injection (6 B; 1 R; 5 A). The remaining 235
patients received an average of 13.7 ± 12 injections (mean ± SD). At
the initial visit, 17 (7%) patients presented with VA of CF or worse
and 230 patients (93%) had an average initial VA of 0.543 logMAR
(20/69 Snellen). At the final visit, 25 (10%) patients had a VA worse
than CF while 222 patients (90%) had an average final VA of 0.471
logMAR (20/60 Snellen). Over the course of 7-year follow-up, 177
eyes maintained recordable Snellen VA. Of these, 110 eyes (62%)
maintained VA within 2 lines, 21 eyes (12%) lost more than 2 lines,
and 46 (26%) gained more than 2 lines. Of the eyes that gained more
than 2 lines, there was an average of 14.43 injections (10% B; 33%
R; 57% A). Of the eyes that lost more than 2 lines, there was an
average of 21.52 injections (12% B; 42% R; 46% A). The presence or
absence of fluid type on OCT imaging and its correlation with visual
acuity will be reported.
Conclusions: Gathering correlative data on the practical outcomes of
anti-VEGF treatments provide clarity to their everyday use. Future
studies are needed in further understanding the beneficial response of
anti-VEGF on NV-AMD.
Commercial Relationships: Pooja G. Garg; Andy Lee, None;
Alice T. Lyon, None; Rukhsana Mirza, None; Amani Fawzi, None;
Manjot Gill, None
Program Number: 4983 Poster Board Number: A0373
Presentation Time: 11:00 AM–12:45 PM
Cost-Benefit Analysis of Intravitreal Anti-VEGF Medications for
the Treatment of Neovascular Age-Related Macular Degeneration
in a Treat-And-Extend Regimen
Andrew Carey, Stephen R. Russell. Ophthalmology & Visual
Sciences, University of Iowa Hospitals & Clinics, Iowa City, IA.
Purpose: A variety of medications and administration frequencies
have been found to be effective for restoration and preservation
of vision in patients with neovascular Age-Related Macular
Degeneration (nAMD). Anecdotal reports have suggested differences
in duration of action between intravitreal bevacizumab (IVB),
intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA).
Further, treat-and-extend (TAE) regimens have been proposed to
reduce the treatment burden posed by monthly patient visits. The
purpose of this study is to examine the cost-benefit of IVB compared
to IVR and IVA in a TAE regimen.
Methods: We modeled monthly (q4w) and TAE to a 12-week
interval regimens in the hospital-based and ambulatory clinic settings
to examine the costs of exam and injection using IVB, IVR, and IVA
for a self-payer, Medicare, and the Medicare (co-pay) patient. This
theoretical model was then used to look at the cost-benefit ratio of
IVR or IVA to IVB using the visual outcomes and injection frequency
from a retrospective chart review of nAMD patients treated with a
TAE regimen
Results: The results of the theoretical model comparing IVR or IVA
to IVB in the same regimen (either q4w or TAE) demonstrated that
parameters related to highest cost are as follows: in the hospital-based
setting, the cost ratio to the self-payer, Medicare, and the Medicare
patient was approximately 5.0 annually; in the ambulatory clinic
setting, the cost ratio to the self-payer was approximately 6.7 and to
Medicare and the Medicare patient approximately 11.8 annually.
The theoretical model showing the maximal difference between
IVR or IVA (TAE) compared to IVB (q4w) are as follows: in the
hospital-based setting, the cost ratio to the self-payer, Medicare,
and the Medicare patient was approximately 2.7 in the first year
and approximately 1.5 in subsequent years; in the ambulatory clinic
setting, the cost ratio to the self-payer was approximately 3.6 in the
first year and approximately 2.0 in subsequent years and to Medicare
and the Medicare patient approximately 6.3 in the first year and 3.6 in
subsequent years.
Conclusions: The use of IVB over IVR and IVA for the treatment of
nAMD in either a q4w or a TAE regimen can result in significant cost
savings to the self-payer, Medicare, and the Medicare patient.
Commercial Relationships: Andrew Carey; Stephen R. Russell,
None
Program Number: 4984 Poster Board Number: A0374
Presentation Time: 11:00 AM–12:45 PM
Correlations between subjective perception of metamorphopsia
and objective measurement of metamorphopsia among people
with age-related macular degeneration
Steven Bae, Kunyong Xu, Vasudha Gupta, Sanjay Sharma.
Ophthalmology, Queen’s University, Kingston, ON, Canada.
Purpose: Metamorphopsia is a hallmark in patients with age-related
macular degeneration (AMD). The aim of this study is to assess the
correlation between subjectively perceived and objectively measured
metamorphopsia among patients with AMD.
Methods: Patients who were diagnosed with AMD at the Department
of Ophthalmology, Hotel Dieu Hospital, were invited to participate
in this cross-sectional study. Those who had a best-corrected
visual acuity (BCVA) of less than 20/200, vitreomacular adhesion,
vitreomacular traction, epiretinal membrane, macular hole, macular
edema by causes other than AMD, diabetic retinopathy, retinal
detachment, previous retinal surgery, glaucoma, amblyopia, or
strabismus were excluded. The mean score on a 9-item questionnaire
focusing on the symptoms of metamorphopsia was used to capture
the patients’ perception of metamorphopsia. M-CHARTS (Inami,
Japan) was used to quantify the metamorphopsia. The examination
distance was 30 centimeters, and the refraction of the eye was
adjusted to this distance. Patients’ metamorphopsia was scored
horizontally (MH) and vertically (MV). The examination was
repeated 3 times, and the mean value was used for data analysis.
Results: In total, 30 eyes (53.3% wet AMD and 46.7% dry AMD)
of 30 patients were included. The patients were Caucasian (100%)
and female predominant (63.3%) with a mean age of 77.0 years
(SD= 8.30). The BCVA for near and for distance was 0.50 logMAR
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ARVO 2016 Annual Meeting Abstracts
(SD=0.27) and 0.49 logMAR (SD=0.25), respectively. The most
frequently reported metamorphopsia included distortion when
reading a book, newspaper, or display on a computer screen (63.3%),
distortion of frames of windows or bookshelves (33.3%), distortion
of lines of tiles on the bathroom wall (33.3%), distortion of the lines
of a crosswalk or the steps of an overpass (30%), and distortion of
telephone poles or trees (26.7%). The mean score for MV and MH
was 0.37 (SD=0.27) and 0.40 (SD=0.32), respectively. Both MV
(r1) and MH (r2) scores were associated with the mean score of the
subjective perception of metamorphopsia (Spearman rank correlation:
r1=0.70, p<0.0001; and r2=0.64, p=0.0001, respectively).
Conclusions: Patients’ subjective perceptions of metamorphopsia
were correlated with metamorphopsia measured using M-CHARTS.
Objective measurements of metamorphopsia via M-CHARTS may be
an important variable to follow.
Commercial Relationships: Steven Bae, None; Kunyong Xu,
None; Vasudha Gupta, None; Sanjay Sharma, None
Program Number: 4985 Poster Board Number: A0375
Presentation Time: 11:00 AM–12:45 PM
Clinical characteristics and outcomes of Bilateral Neovascular
Age-Related Macular Degeneration in Korean patients
Dae Joong Ma, Hyeong Gon Yu. Seoul national university hospital,
SEOUL, Korea (the Republic of).
Purpose: To investigate the clinical characteristics and outcomes of
bilateral neovascular age-related Macular Degeneration (nAMD) in
Korean patients.
Methods: We retrospectively studied 40 patients with bilateral
nAMD and 80 matched patients with unilateral nAMD.
Results: In the first affected 40 eyes, 19 were typical AMD (47.5%),
12 were polypoidal choroidal vasculopathy (PCV) (30.0%) and 9
were retinal angiomatous proliferation (RAP) (22.5%). In the second
affected 40 eyes, 18 were typical AMD (45.0%), 12 were PCV
(30.0%) and 10 were RAP (25.0%). Overall, 82.5% of patients had
the same disease type in each eye (Cohen kappa=.717).
At initial diagnosis, the second affected eyes had visual acuity (VA)
of 0.60±0.50 logMAR, better than the first eyes, 0.88±0.52 logMAR
(p=.017). Central macular thickness (CMT) were 308.8±85.9 um in
the first affected eyes and 295.5±94.9 um in the second eyes, showed
no difference (p=.515).
Mean follow-up period was 45.6 months, each eyes received 7.7±6.3
anti-VEGF treatments. 9 eyes underwent 13 photodynamic therapies
and 4 eyes underwent 7 surgeries. 4 eyes underwent 6 intravitreal
gas injections and only one eye received 2 subtenon triamcinolone
injections. There was no difference in the counts of treatments
between two groups.
VA was not improved in both groups after follow-up period (p=.149
and .104, respectively). However, CMT was significantly decreased
to 229.5±65.0 um in the first affected eyes and 238.4±57.0 um in the
second eyes (p=.000 and .001, respectively). There was no significant
difference in VA and CMT between two groups after follow-up
period (p=.916 and .517, respectively).
In comparison with the first affected eyes, 80-matched unilateral
nAMD eyes showed no differences between in CMT at initial
diagnosis, follow-up period, counts of treatments, VA and CMT
after follow-up period. However, VA in unilateral nAMD patients at
the initial diagnosis was better, 0.63±0.45 logMAR (p=.011). There
was no difference between the second affected eyes and 80-matched
unilateral nAMD eyes in all analysis.
Conclusions: In bilateral involvement of nAMD, good concordance
of disease type between the first and second affected eyes was
observed. The first affected eyes showed worse VA at the initial
diagnosis. However, treatment outcomes showed no significant
difference among the first and the second affected bilateral nAMD
eyes and unilateral nAMD eyes.
Commercial Relationships: Dae Joong Ma; Hyeong Gon Yu, None
Program Number: 4986 Poster Board Number: A0376
Presentation Time: 11:00 AM–12:45 PM
A Proof of Concept Study of Intravitreal (IVT) LFG316 In
Patients with Neovascular Age Realted Macular Degeneration
(nAMD)
Ron P. Gallemore1, Michael J. Elman3, Mark Milton2, Parisa Zamiri2,
Cynthia L. Grosskreutz2. 1Dept Cell Biology and Histology, Retina
Macula Institute, Torrance, CA; 2Novartis, Mission Viejo, CA;
3
Elman Retina, Baltimore, MD.
Purpose: The risk of developing AMD is strongly associated with
alleles in genes encoding proteins in the alternative complement
pathway. LFG316 is a fully human antibody that inhibits Complment
factor 5 (C5)’s ability to form C5 convertase. In a multicenter,
randomized, sham-controlled, repeat-dose study, the safety,
tolerability, and efficacy of IVT LFG316 were assessed in patients
with nAMD.
Methods: 45 patients with active nAMD were randomized in a 2:1
ratio to receive either 3 monthly doses of 5 mg/50 μL LFG316 (n=30)
or 3 monthly sham injections (n=15). They were followed for 113
days. The primary objective was to evaluate the rate at which patients
required retreatment with an anti-VEGF therapy by day 85. The key
secondary objectives were safety and changes in best corrected visual
acuity (BCVA) and central retinal thickness (CRT). Assessments
included clinical and laboratory evaluations, BCVA, intraocular
pressure measurement, dilated biomicroscopy, fundus photography,
fluorescein angiography, serum pharmacokinetics (total LFG316),
pharmacodynamics (total C5), and immunogenicity.
Results: The majority of patients were Caucasian (96%) and female
(68%). Monthly treatment with IVT LFG316 was safe and well
tolerated. The rate of anti-VEGF retreatment (mean ± SD) was 0.10
± 0.097 per week in the LFG316 treatment arm and 0.08 ± 0.078
per week in the sham treatment arm. The adjusted mean [95% CI]
change in CRT was -27.6 [-113.0, 57.8] μm for the LFG316 treatment
arm and -55.1 [-173.5, 63.3] μm for the sham treatment arm. The
difference in change in CRT between the two treatment arms was not
statistically significant (p= 0.7). After IVT administration very low
levels of LFG316 (the highest observed concentration was 1.49 µg/
mL) was detected in the majority of serum samples up to 14 days post
dose and in approximately 40% of patients at 28 days post dose. The
serum LFG316 concentrations were always much lower than serum
C5 concentrations (~160 µg/mL), indicating that IVT doses did not
systemically suppress complement activity. Anti-LFG316 antibodies
were not detected in any patient.
Conclusions: Monthly IVT doses of 5 mg of LFG316 were well
tolerated and safe. There were no statistically significant differences
in the rate of anti-VEGF retreatment or in changes in BCVA or CRT
between the two treatment groups.
Commercial Relationships: Ron P. Gallemore; Michael J. Elman,
Novartis (F), Jaeb Center (F), Ohr Pharmaceuticals (F), Clearside
(F), Genentecth (F), Alcon (F), Tyrogenix (F), Notal Vision (I),
Merck (F), Allergan (F); Mark Milton, None; Parisa Zamiri, None;
Cynthia L. Grosskreutz, None
Clinical Trial: NCT01535950
These abstracts are licensed under a Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License. Go to http://iovs.arvojournals.org/
to access the versions of record.