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ARVO 2015 Annual Meeting Abstracts 477 Early AMD Wednesday, May 06, 2015 3:45 PM–5:30 PM Exhibit Hall Poster Session Program #/Board # Range: 5127–5166/C0191–C0230 Organizing Section: Retina Contributing Section(s): Clinical/Epidemiologic Research, Genetics, Multidisciplinary Ophthalmic Imaging, Visual Psychophysics/Physiological Optics Program Number: 5127 Poster Board Number: C0191 Presentation Time: 3:45 PM–5:30 PM The effect of A2E and zeaxanthin on visual function: Modelling AMD pathogenesis and treatment in zebrafish D Joshua Cameron1, Eric A. Saidi1, 2, Pinakin G. Davey1. 1Optometry, Western Univ of Hlth Sciences, Pomona, CA; 2Graduate College of Biomedical Sciences, Western Univ of Hlth Sciences, Pomona, CA. Purpose: Age-related macular degeneration is a devastating eye disorder that is characterized by the progressive loss of macular or central vision as patients age. One aspect of AMD’s pathogenesis involves the bisretinoid A2E, which accumulates with age and has been found in greater abundance in AMD eyes. Despite years of study, A2E is still somewhat of an enigma. Carotenoids have been used to delay the progression of AMD, but most studies have focused on combinations of carotenoids rather than individual compounds. We set out to test two hypotheses: 1) intracameral injections of A2E will negatively affect visual function in zebrafish. 2) Injection of zeaxanthin into the zebrafish eye would improve/protect the visual acuity of the zebrafish. Methods: Visual acuity, calculated in cycles per degree, was measured in adult zebrafish to establish a consistent baseline using the optokinetic response. Either Zeaxanthin or A2E were dissolved into phosphate buffered saline (PBS) and injected into the anterior chamber of the right and left eyes. PBS was injected as a control into the anterior chamber of the right and left eyes of a separate group of fish. Visual acuities were measured at 1 week and 3, 8 and 12 weeks post-injection to compare to baseline values. A paired t-test was used to compare visual acuities between subjects injected with zeaxanthin or A2E and PBS. Results: Intraocular injections of 50mM A2E impair visual function in adult zebrafish. 2 weeks after injection visual acuity is significantly reduced (p=0.01 n= 9 for each group). Zeaxanthin injections on the other hand showed a significant improvement in visual acuity, 22% better than before the injection (p=0.02 n=11 for zexanthin and 10 for PBS). This improvement peaked at more than 30% for some fish a few weeks after the injection. The enhanced visual function returned to normal 3 months after the initial injection. Conclusions: A2E caused a significant reduction in visual function while zeaxanthin actually improved visual function in the adult zebrafish. Further studies looking at the histology and other aspects of visual function will help in characterizing the mechanism behind these observed visual acuity changes and aid in understanding the pathogenesis of AMD. Additionally, this platform may serve as a model for studying the etiology of AMD and possible treatments. Commercial Relationships: D Joshua Cameron, None; Eric A. Saidi, None; Pinakin G. Davey, None Support: WesternU Intramural Grant Program Number: 5128 Poster Board Number: C0192 Presentation Time: 3:45 PM–5:30 PM Age-Related Macular Degeneration and Aspirin Use Fadi Shaya, Kent W. Small. Macule and Retina Institute, Glendale, CA. Purpose: To resolve the conflict of Aspirin’s cardiovascular benefits versus its possible adverse effects on age-related macular degeneration (AMD). Aspirin’s overall beneficial effects in reducing heart attacks, stroke and sudden death have long been documented in many large, randomized, controlled trials. Recent data from two smaller AMD epidemiology studies have suggested a deleterious effect on vision in patients with age-related macular degeneration. A balanced analysis of these competing data sets is needed to resolve these issues and aid cardiologists and ophthalmologist in appropriately counseling their patients. Methods: A meta-analysis was performed of six large randomized, controlled trials using aspirin as a preventive for cardiovascular events compared to smaller AMD epidemiological trials evaluating the effects of aspirin on age-related macular degeneration. The cardiovascular prevention studies consisted of a total of 95,000 individuals. The AMD epidemiological studies consisted of 13,062 participants collectively. Results: The combined meta-analyses showed aspirin caused a 32 % reduction in the risk of non-fatal stroke (OR:0.68, 95% CI, 0.59-.79) with regular aspirin users. The study also documented that aspirin users decreased the risk of vascular events by 15 % (OR:0.85, 95 % CI, 0.79-0.93). In the AMD epidemiological studies, Aspirin was associated with the increase in neovascular AMD from 1.9 % in five years, 7 % in ten years, and 9.3 % in fifteen years in regular aspirin users (OR: 2.46, 95 % CI: 1.25-4.83). It is important to note that the odd ratios are significantly smaller in the larger cardiovascular prevention trials than the odd ratios in the smaller AMD epidemiological studies. Conclusions: Overall, the size and quality (very small confidence intervals) of the cardiovascular studies documenting the overall health benefit of aspirin use is much greater than the few smaller AMD epidemiological studies suggesting possible adverse vision effects of aspirin use in age-related macular degeneration. The benefits of aspirin usage include preserving the duration and quality of life by decreasing stroke and heart attack risk. These benefits seem to far outweigh the theoretical risks of possibly exacerbating wet AMD that can be reasonably controlled with anti-VEGF therapy. We strongly recommend that AMD patients should be on aspirin if it is recommended by their primary physician. Commercial Relationships: Fadi Shaya, None; Kent W. Small, None ©2015, 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 2015 Annual Meeting Abstracts Program Number: 5129 Poster Board Number: C0193 Presentation Time: 3:45 PM–5:30 PM Alpha-linolenic acid and risk of age-related macular degeneration: a prospective study over more than two decades of follow-up Juan Wu1, Eunyoung Cho2, 3, Debra A. Schaumberg4, 3, Srinivas Sastry5, Walter Willett1, 3. 1Department of Nutrition, Harvard School of Public Health, Boston, MA; 2Department of Dermatology, Warren Alpert Medical School of Brown University, Providence, RI; 3 Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; 4Department of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT; 5Bethesda Retina, Bethesda, MD. Purpose: Marine-sourced long-chain omega-3 fatty acids (n-3) have been associated with lower risk of AMD in many observational studies. Alpha-linolenic acid (ALA) is the primary n-3 consumed in typical western diet due to its greater availability from plant sources and a small amount is endogenously converted to long-chain n-3. Thus, we aimed to investigate the association between long-term intake of ALA and risk of age-related macular degeneration (AMD). Methods: This prospective study included 81,847 female participants in the Nurses’ Health Study who were ≥ 50 years old. We calculated the intake of ALA from validated food frequency questionnaires collected every four years beginning from 1984. By 2012, we confirmed 1,224 intermediate and 1,023 advanced AMD cases (96% wet AMD). Multivariate Cox proportional hazards model was used to estimate the relative risks (RR’s) and 95% confidence intervals (CI’s). Results: After adjusting for age, BMI, smoking and other suspected risk factors of AMD, cumulative averaged intake of ALA was positively associated with intermediate AMD (comparing extreme quintiles, multivariate RR = 1.32, 95% CI = 1.10 to 1.58; p trend < .001); the RR persisted after further adjustment for correlated dietary risk factors including DHA, linoleic acid, saturated fat and trans fat (RR = 1.30, 95% CI = 1.04 to 1.64; p trend = 0.02). Mayonnaise-type salad dressing, the leading contributor to both the intake and plasma level of ALA in this cohort, was associated with a 28% (95% CI = 1.06 to 1.55) increased risk of intermediate AMD comparing the highest quintile of intake to the lowest. We detected a small amount of understudied trans ALA isomers (0.05% of total fatty acids) in red blood cells among a subsample of women (n = 408) and mayonnaise also significantly predicted one of the trans ALA isomers (p < .001). Intake of ALA was not significantly associated with advanced AMD (RR = 1.09, 95% CI = 0.89 to 1.32; p trend = 0.61). Conclusions: ALA does not appear to protect against AMD and may increase the risk of intermediate AMD. Whether trans ALA is responsible for the positive association deserves further investigation. Commercial Relationships: Juan Wu, None; Eunyoung Cho, None; Debra A. Schaumberg, None; Srinivas Sastry, None; Walter Willett, None Program Number: 5130 Poster Board Number: C0194 Presentation Time: 3:45 PM–5:30 PM Drusen in the Asian pediatric population aged 6-18 yrs Victor Chen1, Don B. Kim2, Gloria Wu3. 1Biology, UC San Diego, Saratoga, CA; 2Biology, UC Berkeley, Berkeley, CA; 3 Ophthalmology, UC San Francisco School of Medicine, San Francisco, CA. Purpose: Non-exudative age related macular degeneration has been reported to be increased in Asians in previous studies Drusen have been reported in adults <55yrs, but is less studied in pediatric patients (pts). This study assesses the appearance of drusen in Asian pediatric patients in a retina practice in San Jose, CA, where 50% of the population is of Asian descent. Methods: Using the EHR, eClinicalWorks, from a retina practice from 1/2013-11/2014, pts were identified who were aged 6-18 years, with CPT code 92250 and non-retina ICD diagnosis codes with Va=20/15-20/30. TRC-50EX Topcon camera, OIS winstation-XP, zoom 3x feature were used to examine color and red-free photos. The OIS winstation AREDS retinal grid was used to identify drusen and measure drusen size. The grid was superimposed on the fundus photo, centered at the fovea. Using the OIS Topcon software 3x zoom feature, all quadrants, para and perifoveal regions were inspected for drusen. This was done in all the fundus photographs with the above criteria. Inclusion criteria: no macular disease, best corrected visual acuity 20/15-20/30. Age range 6-18 years old. Exclusion criteria: poor quality fundus photos, macular disease lesions or macular diagnoses. Results: A total of 54 patients met our inclusion criteria. 35 Asian/ South Asian, 8 Caucasian, 3 Hispanic, 1 African American, and 7 “Other” race. Of those 54, we examined the 35 Asian patients. Average age = 12.14, sd=4.19, males n=18, avg male age=11.61, sd=4.38, females n=17, avg female age=12.71, sd=4.04. 70 photographs were examined in total. 4/70 photos were excluded due to poor vision in the photographed eye. No drusen in 24/70 eyes. The remaining 42/70 eyes had drusen from 25 patients. 17 pts had drusen in both eyes. Patients with drusen ranged from 6-18 yrs in age. Average number of drusen per eye OD = 3.7 ± 2.8. Average number of drusen per eye OS = 3.0 ± 2.3. In total, 135 drusen were counted, all fewer than 65um in diameter (C0 on the AREDS grid). 115 of 135 drusen appeared in the outer quadrants vs. 20 found in the inner quadrants. 74 drusen (55%) appeared in right eyes vs 61 drusen (45%) in left eyes. Conclusions: Drusen can be found in Asian children as early as age 6. A majority of drusen were found in the perifoveal quadrants. Commercial Relationships: Victor Chen, None; Don B. Kim, None; Gloria Wu, None Program Number: 5131 Poster Board Number: C0195 Presentation Time: 3:45 PM–5:30 PM Multifunctional OCT imaging of macular degeneration for vasculature, RPE and choroid investigation Young-Joo Hong1, 4, Masahiro Miura2, 4, Shuichi Makita1, 4, Deepa Kasaragod1, 4, Satoshi Sugiyama1, 3, Yoshiaki Yasuno1, 4. 1 Computational Optics Group, University of Tsukuba, Tsukuba, Japan; 2Ibaraki Medical Center, Department of Ophthalmology, Tokyo Medical University, Ami, Japan; 3New Development, Tomey Corporation, Nagoya, Japan; 4Computational Optics and Ophthalmology Group, Tsukuba, Japan. Purpose: In order to investigate eyes of age-related macular degeneration (AMD) comprehensively, 1-μm Jones-matrix multifunctional optical coherence tomography (JM-OCT) imaging was performed. This study aims at evaluating clinical utility of JMOCT imaging, based on a descriptive case series of AMD. Methods: Eight eyes of 4 AMD cases, including 4 end stage AMD, 1 early stage AMD, 1 drusen, and 2 drusenoid pigment epithelial detachment were imaged with JM-OCT.6 mm × 6 mm areas around the diseased region were scanned with 512 × 1024 A-lines in 6.6 seconds. Intensity OCT, complex decorrelation OCT, birefringence tomography, and degree-of-polarization-uniformity (DOPU) tomography were calculated from a single scan and each tomography represents the structure, vasculature, sub-resolution microstructural property of the tissue, and melanin pigmentation. DOPU and complex decorrelation signals were combined to provide comprehensive angiography. Results: Anormality of retinal pigment epithelium (RPE) was imaged with high DOPU (less pigment) in 4 of 4 end stage AMD cases, and ©2015, 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 2015 Annual Meeting Abstracts it was corresponding to the hypo-fluorescence of short-wavelength autofluorescence (SW-AF) image. In another 4 eyes, SW-AF did not show hypo-fluorescence and their RPE showed low DOPU (pigmented). High birefringence band structure was observed in sclera with less pigment (high DOPU signal) in 3 eyes of end stage AMD. Figure 1 shows a representative case of AMD. High contrast choroidal vasculature and hypo-fluorescence were observed in the abnormal RPE region from near infrared (NIR) AF (a) and SW-AF (b) images, respectively. And the en face projection (c) of complex decorrelation (g) showed similar appearance with NIR-AF, in addition DOPU B-scan (h) showed depth resolved melanin pigment distribution (arrowheads indicate abnormal RPE). In this region, intensity OCT B-scan (d) showed higher penetration into sclera. Birefringence B-scan (f) showed layered structure in the sclera (dashed circle) as high birefringence at anterior sclera (green) and low birefringence (blue) at posterior. The sclera was appeared with high DOPU (less pigment). DOPU encoded complex decorrelation angiography (d) showed distinguished choroidal vasculature at the region of abnormal RPE and less pigmented choroid. Conclusions: The multifunctional imaging with JM-OCT gives comprehensive information about the vasculature, RPE, and choroid with depth resolved imaging. autofluorescence (FAF). On optical coherence tomography (OCT), they appear as hyperreflective lesions in the subretinal space. Over the course of greater than six months, some of these lesions have been described as gradually decreasing in size and resorbing, leaving areas of atrophy and hypoautoflourescence on FAF. This imaging study reviews a series of two pseudovitelliform lesions that underwent sudden and rapid collapse over the course of one month. This represents a new clinical presentation of a known clinical entity. Methods: This is a retrospective case review of a series of two patients with pseudovitelliform lesions that underwent sudden collapse over the course of one month. Results: These two cases both had single large pseudovitelliform subfoveal lesions with typical FAF and OCT characteristics. Visual acuities were stable at that stage at 20/30 and 20/60. There were no signs of subretinal or intraretinal fluid. Both patients were taking prophylactic AREDS formula antioxidant vitamin suppelmentation. Each underwent sudden collapse, with urgent presentation to the clinic, as noted by significant decline in visual acuity, both to 20/100. Visual acuity stabilized after the initial drop, the final level of acuity seemingly corresponding with the degree of subretinal tissue loss. One eye returned to the visual actuity baseline of 20/30 over the course of one month. The other eye further declined and remained at 20/200, also over the course of one month. Both cases developed pigmentary changes on fundus exam and corresponding foveal atrophy on OCT. The eye with persistent low vision appeared to have greater atrophic changes on OCT than the eye that returned to baseline visual acuity. Conclusions: This imaging study describes a new clinical presentation of pseudovitelliform lesions that has not been described in the literature previously. These reported cases underwent sudden collapse of their lesions with rapid subjective decline in visual acuity. Vision then stabilized over the course of one month with the final outcome appearing to correspond with the degree of subretinal atrophy noted on OCT. OCT of pseudovitelliform lesion prior to collapse Commercial Relationships: Young-Joo Hong, TOMEY CORPORATION (F), TOPCON CORPORATION (F); Masahiro Miura, Norvatis (R); Shuichi Makita, TOMEY CORPORATION (F), TOMEY CORPORATION (P), TOPCON CORPORATION (F); Deepa Kasaragod, TOMEY CORPORATION (F), TOPCON CORPORATION (F); Satoshi Sugiyama, TOMEY CORPORATION (E); Yoshiaki Yasuno, TOMEY CORPORATION (F), TOMEY CORPORATION (P), TOPCON CORPORATION (F) Support: Japan Society for the Promotion of Science KAKENHI 2503053 Program Number: 5132 Poster Board Number: C0196 Presentation Time: 3:45 PM–5:30 PM Collapse of Pseudovitelliform Lesions: A New Clinical Presentation Kelly Rue, Lisa C. Olmos. Ophthalmology, USC, Los Angeles, CA. Purpose: Pseudovitelliform lesions appear in the macula as round yellowish deposits that are hyperautoflourescent on fundus OCT 1 month after pseudovitelliform collapse Commercial Relationships: Kelly Rue, None; Lisa C. Olmos, None Support: An unrestricted grant from Research to Prevent Blindness, New York, NY 10022 ©2015, 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 2015 Annual Meeting Abstracts Program Number: 5133 Poster Board Number: C0197 Presentation Time: 3:45 PM–5:30 PM Evidence of subretinal migration of melanin-loaded cells during dry age-related macular degeneration Concetta Li Calzi1, 2, Michel Paques3, Florian Sennlaub4, Kiyoko Gocho5, Jose A. Sahel3, 4, mustapha benchaboune3. 1Ophtalmologie, ILC INSTITUT- private cabinet-, Cannes, France; 2HOPITAL QUINZE-VINGT, Paris, France; 3Clinical Investigation Center 1423, Quinze-Vingts Hospital, Paris, France; 4Vision Institute, Paris, France; 5Chiba Hospital, Chiba, Japan. Purpose: During dry age-related macular degeneration (ARMD), adaptative optics (AO) en face flood imaging improves the resolution of pigmentary changes (Gocho et al, IOVS 2013). This led to the discovery of the presence of numerous migrating hyporeflective clumps within and around atrophic areas. The most likely explanation of these images is taht they are due to the migration of melaninloaded cells (MLCs). Here, we explored in more details the kinetics of MLCs. Methods: Observational clinical study.4°x4° AO fundus images were obtained with a commercially available flood imaging AO camera (rtx1; Imagine Eyes, Orsay, France) within an IRB-approved clinical study in eyes with dry AMD (n=4). Care was taken to capture the progression front. The migration of MLCs was documented by time-lapse imaging (mean interval between sessions 26 days; median follow-up 5 months). Results: Multiple MLCs were seen to migrate within as well at outside of atrophic areas. Approximately 65% of hypereflective clumps were seen to migrate during the observation period. Their mean diameter was 19mm. The density of MLCs ranged from 300 to 800 per mm2. The linear velocity of MLCs peaked at 1um/day. The behaviour of migrating MLCs was somewhat random, with in many adjacent MLCs migrating in opposite directions; however, focal agregations of MLCs were present. Agregation and disaggration of MLCs accounted for the evolution of large pigmentary clumps. The cone mosaic was seen over MLCs in 48% of cases. Conclusions: During dry ARMD, extensive subretinal migration of MLCs throughout the posterior pole is commonly observed, in atrophic as well as in nonatrophic areas. To our knowledge, this is the first demonstration of such subretinal migration. It is likely that these MLCs correspond to the hypereflective dots reported by optical coherence tomography (Coscas et al, 2013). The nature of these cells and their role in the process of ARMD remains to be clarified; likely candidates are sloughed RPE cells (Curcio et al, IOVS 1998) and macrophages. The subretinal space appears thus as a permissive milieu for the transmission of cellular inputs. The random migration is reminiscent of the behaviour of patrolling, non activated inflammatory cells. We therefore believe that this finding may have important consequences for the understanding and monitoring of dry ARMD, as well as for the validation of experimental models of ARMD. Commercial Relationships: Concetta Li Calzi, None; Michel Paques, ImagineEye (C); Florian Sennlaub, None; Kiyoko Gocho, None; Jose A. Sahel, ImagineEye (S); mustapha benchaboune, None Support: ANR-07-LVIE-001 and ANR-09-TECS-009-01 Clinical Trial: NCT01546181 Program Number: 5134 Poster Board Number: C0198 Presentation Time: 3:45 PM–5:30 PM Genetic and clinical factors associated with choroidal vascular hyperpermeability and subfoveal choroidal thickness in polypoidal choroidal vasculopathy Seigo Yoneyama, Yoichi Sakurada, Wataru Kikushima, Fumihiko Mabuchi, Hiroyuki Iijima. Ophthalmology, University of Yamanashi, Chuo, Japan. Purpose: To investigate genetic and clinical factors associated with choroidal vascular hyperpermeability (CVH) and subfoveal choroidal thickness (SCT) in eyes with treatment-naïve polypoidal choroidal vasculopathy (PCV). Methods: We studied the consecutive 149 patients with PCV. Presence or absence of CVH was evaluated on indocyanine green angiography (ICGA). Subfoveal choroidal thickness (SCT) and axial length was measured by spectral domain optical coherence tomography and optical biometry, respectively. Variants of ARMS2 (rs10490924) and CFH (rs800292 and rs1329428) were genotyped using TaqMan technology. Results: Subfoveal choroidal thickness was correlated with axial length and age (p=0.001 and p=0.02, respectively).Though there was not a significant difference in SCT among CFH(rs800292) genotypes, there was a statistical difference in SCT among CFH(rs1329428) and ARMS2(rs10490924) genotypes. (p=0.002 and p=0.006, stepwise regression analysis, respectively).Among 149 eyes with PCV, 35 (23.5%) eyes exhibited CVH on ICGA. There was a significant lower frequency of risk variants in CFH(rs1329428) and ARMS2(rs10490924) in patients with CVH than patients without CVH (p=0.029 and p=0.005, stepwise regression analysis, respectively). Conclusions: In addition to axial length and age, SCT in eyes with PCV were associated with both genetic variants in CFH and ARMS2 gene. Patients with CVH might have a weaker effect on both genetic variants than patients without CVH. Commercial Relationships: Seigo Yoneyama, None; Yoichi Sakurada, None; Wataru Kikushima, None; Fumihiko Mabuchi, None; Hiroyuki Iijima, None Program Number: 5135 Poster Board Number: C0199 Presentation Time: 3:45 PM–5:30 PM Consuming a buttermilk drink containing lutein-enriched eggyolk daily for 1 year improves macular pigment optical density and visual acuity in subjects with early signs of age-related macular degeneration Tos TJM Berendschot1, Sanne van der Made2, Elton R Kelly1, Jogchum Plat2, Aize Kijlstra2. 1University Eye Clinic Maastricht, Maastricht, Netherlands; 2Department of Human Biology, Maastricht University Medical Centre, Maastricht, Netherlands. Purpose: Lutein has been shown to be beneficial in maintaining visual function in age-related macular degeneration (AMD). A dairy beverage has been developed based on lutein-enriched egg yolks and buttermilk. The eggs have been enriched in lutein via the feed of laying hens. The primary aim of this study was to assess the effects of 1-year daily consumption of this dairy drink containing luteinenriched egg-yolks on macular pigment optical density (MPOD) and visual scores in subjects with early AMD. Also, plasma lutein concentrations, and serum lipids and lipoproteins were measured. Methods: One hundred and one subjects were recruited to participate in this one-year, double blind, placebo-controlled intervention trial in subjects with early signs of AMD. Subjects in the lutein group consumed the dairy drink containing 1.4 mg lutein daily. MPOD using heterochromatic flicker photometry, best corrected visual acuity (BCVA), and dark adaptation were measured at the start of the study, ©2015, 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 2015 Annual Meeting Abstracts after 6 months and after 12 months of consuming either the placebo or lutein drink. Plasma lutein concentration was assessed at baseline and at the end of the study. Results: In the lutein group plasma lutein concentration increased significantly from 205 ng/ml at baseline to 399 ng/ml at study end (p<0.001). MPOD increased significantly from 0.45 to 0.52 (p<0.001) and BCVA increased significantly from -0.04 to -0.09 (LogMar, p=0.004). We found no changes in the placebo group. Differences in dark adaptation between both groups were not significant. Conclusions: Daily consumption of a dairy drink containing lutein-enriched egg-yolks for one year improves plasma lutein concentration, MPOD and visual acuity in subjects with early signs of age-related macular degeneration. Commercial Relationships: Tos TJM Berendschot, WO2009078716, US2011015277 (P); Sanne van der Made, Newtricious R&D B.V. (E); Elton R Kelly, None; Jogchum Plat, WO2009078716, US2011015277 (P); Aize Kijlstra, None Support: The project was supported by Europees Fonds voor Regionale Ontwikkeling (OP-Zuid), Dutch Ministry of Economic Affairs, the Province of Limburg and Newtricious R&D B.V. Clinical Trial: NCT00902408 Program Number: 5136 Poster Board Number: C0200 Presentation Time: 3:45 PM–5:30 PM Ultrahigh speed OCT angiography in age-related macular degeneration using swept source optical coherence tomography Eric Moult1, 2, Nadia K. Waheed3, Woo Jhon Choi2, Mehreen Adhi3, Talisa de Carlo3, Benjamin Potsaid4, Vijaysekhar Jayaraman5, Philip J. Rosenfeld6, Jay S. Duker3, James G. Fujimoto2. 1Health Sciences and Technology, Harvard-MIT, Cambridge, MA; 2Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA; 3New England Eye Center, Tufts University Medical Center, Boston, MA; 4Advanced Imaging Group, Thorlabs, Inc, Newtown, MA; 5Praevium Research Inc., Santa Barbara, CA; 6Department of Ophthalmology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, FL. Purpose: To investigate the use of ultrahigh speed swept source optical coherence tomography (SSOCT) angiography for characterizing microvascular changes in patients with age-related macular degeneration (AMD). Methods: A 1050nm wavelength, 400 kHz A-scan rate SSOCT system was used to perform volumetric optical coherence tomography angiography (OCTA) of the retinal and choriocapillaris vasculature in normal volunteers and AMD patients. The normal group consisted of 63 eyes (32 subjects; 40.7 ± 14.1 years; 13 males; 19 females). The AMD group included 17 eyes with wet AMD (15 patients; 79.7 ± 8.3 years; 6 males; 9 females), 35 eyes with dry AMD without geographic atrophy (GA) (26 patients; 77.5 ± 9.0 years; 11 males; 15 females) and 12 eyes with dry AMD with GA (7 subjects; 75.9 ± 6.1 years; 6 males; 1 female). A technique called variable interscan time analysis was developed to differentiate flow impairment from atrophy; the technique works by varying the effective interscan time between repeated B-scans. Results: Choroidal neovascularization (CNV) was visualized in 16 of the 19 eyes with wet AMD. In these 16 eyes the CNV was found above regions of choriocapillaris atrophy. In 14 of these eyes the CNV was surrounded by choriocapillaris alteration. Eyes with dry AMD without GA showed varying severities of choriocapillaris alterations, some of which were associated with drusen and/ or retinal pigment epithelium/ photoreceptor alteration. In all 12 eyes with GA, OCTA showed choriocapillaris atrophy within the GA region. In 10 of these eyes OCTA showed choriocapillaris flow impairment beyond the GA margin. Conclusions: OCTA appears to be a promising modality for noninvasive imaging of retinal and choriocapillaris vasculature in eyes with AMD. CNV located adjacent to GA in a 75 year old AMD patient. (A) En face OCT projection. (B) OCTA of choriocapillaris. (C) En face OCTA projection. (D) Fundus autofluorescence. (E) OCT and (F) OCTA B-scans through the dashed line in (A). Scale bars: 1mm. 75 year old GA patient. (A) Fundus autofluorescence. (B) En face OCT projection. (C) OCTA of retinal microvasculature. (D) OCTA of choriocapillaris. (E) OCTA of choriocapillaris as in (D) but generated using variable interscan time analysis. (F-I) Magnified views. OCT intensity (top) and OCTA (bottom) B-scans through dashed lines in (D) are shown in (J-L). Scale bars: 1mm. Commercial Relationships: Eric Moult, None; Nadia K. Waheed, None; Woo Jhon Choi, None; Mehreen Adhi, None; Talisa de Carlo, None; Benjamin Potsaid, Thorlabs, Inc. (E); Vijaysekhar Jayaraman, Praevium Research Inc., (E); Philip J. Rosenfeld, Carl Zeiss Meditec Inc. (F); Jay S. Duker, Carl Zeiss Meditec Inc. (C), Carl Zeiss Meditec Inc. (F), EyeNetra (I), Hemera Biosciences Inc. ©2015, 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 2015 Annual Meeting Abstracts (I), Ophthotech Corp (I), Optovue Inc. (C), Optovue Inc. (F); James G. Fujimoto, Carl Zeiss Meditec Inc. (P), Optovue Inc. (I), Optovue Inc. (P) Support: This work was supported by the National Institute of Health (NIH R01-EY011289-27, R44-EY022864-01, R44EY022864-02, R01-CA075289-16), Air Force Office of Scientific Research (AFOSR FA9550-10-1-0551 and FA9550-12-1-0499), a Samsung Scholarship, and by a Natural Sciences and Engineering Research Council of Canada Scholarship Program Number: 5137 Poster Board Number: C0201 Presentation Time: 3:45 PM–5:30 PM The effect of small hard drusen on local retinal structure in healthy adults Hilde R. Pedersen1, Inger C. Munch4, 3, Stuart J. Gilson1, Michael Larsen2, 3, Rigmor C. Baraas1. 1Department of Optometry and Visual Science, Faculty of Health Sciences, Buskerud and Vestfold University College, Kongsberg, Norway; 2Department of Ophthalmology, Glostrup Hospital, Copenhagen, Denmark; 3 Department of Ophthalmology, University of Copenhagen, Copenhagen, Denmark; 4Department of Ophthalmology, Roskilde Hospital, Roskilde, Denmark. Purpose: To investigate how small hard drusen affect local retinal structure in healthy adults by high-resolution in-vivo imaging of the retina. Methods: Ninety-seven healthy males and females aged 19–36 yrs, with normal logMAR letter acuity and no observed ocular abnormalities, were included in the study. Color fundus photographs were obtained of the central 45 degrees in both eyes. Any bright element smaller than 63 mm in diameter whose shape, color, or proximity to adjacent abnormality indicated it was not hard exudate, was classified as a small, hard druse. Eyes with drusen were imaged with the Heidelberg Spectralis OCT and the Kongsberg Adaptive Optics Ophthalmoscope II (AO). Retinal layers were analyzed by calculating longitudinal reflectivity profiles (LRP). Cone density and mosaic regularity analysis was performed over and around drusen. Results: One or more small hard drusen were found within the central 20 degrees in 27 eyes in 21 of the 97 subjects, indicating a population prevalence of 21,6 % in this age group. The number of drusen per eye ranged from 1 to 8. Eight drusen per eye were found in one subject, all in a cluster. OCT revealed a granulated retinal pigment epithelium (RPE) complex in the area with multiple drusen. Discrete OCT-visible drusen (33 %) were moderately reflective and associated with localized internal thickening (4.11–7.52 mm) of the RPE complex or elevation of the RPE with slight displacement of the inner/outer segment (IS/OS) layer. One druse was located in Verhoeff’s membrane (VM). The IS/OS layer and the external limiting membrane (ELM) were intact over all drusen, but ELM had reduced reflectivity above the drusen in two eyes. The RPE tended to be more reflective and prominent than VM above drusen. In AO images, drusen were hyperreflective circular or oval elements with blurred edges. The size of discrete drusen ranged from 20 to 56 mm. The cone density and regularity over drusen was not significantly abnormal. The VM druse was hyperreflective and surrounded by discontinuous hyporeflectivity. Conclusions: In this study only one-third of small hard drusen were visible on OCT, all found within or under the RPE. All drusen were visible on AO showing an intact overlying photoreceptor mosaic with moderate alteration of the reflectivity of the adjacent components of the retina. The results may be relevant for the study of very early precursor stages of age-related macular degeneration. Commercial Relationships: Hilde R. Pedersen, None; Inger C. Munch, None; Stuart J. Gilson, None; Michael Larsen, None; Rigmor C. Baraas, None Program Number: 5138 Poster Board Number: C0202 Presentation Time: 3:45 PM–5:30 PM Reticular Macular Disease (RMD): a Two-Compartment Disorder Colleen Cunningham1, Patrick A. Kaszubski1, Hao Cheng1, 3, Hua Hao2, Celine Saade1, K Bailey Freund1, 4, Theodore Smith1. 1 Ophthalmology, New York University School of Medicine, New York, NY; 2Rollins School of Public Health, Emory University, Atlanta, GA; 3Ophthalmology, The First Affiliated Hospital of Guangzhou University, Guangzhou, China; 4Ophthalmology, Vitreous Retina Macula Consultants, New York, NY. Purpose: This study demonstrates spatial and temporal relationships between the 2 processes of RMD, subretinal drusenoid deposits (SDD) and choroidal alterations, in early Age-Related Macular Degeneration (AMD). Methods: 33 eyes (26 subjects) with early AMD/no SDD (RMD) and 18 eyes (16 subjects) with early AMD/SDD (RMD+) underwent enhanced depth imaging spectral domain optical coherence tomography (EDI SD-OCT) in the macula for choroidal thickness (CTh) measurements at 11 points per scan, 475 μm apart, in 5 horizontal B scans, 1 mm apart: a grid of 55 points. These 55 data points were treated as a cluster, to control for within-subject variation, in a generalized estimating equation model of CTh as a function of SDD status, age, gender, OD/OS, and fundus region. Subdividing the sample by total group median age (<=82 and >82 years) allowed analysis of the annual rate of CTh change in 4 groups (RMD+, <=82: 7/18; RMD+, >82: 11/18; RMD-, <=82: 21/33; RMD-, >82: 12/33). Results: CTh was significantly reduced in the subfoveal region in RMD+ eyes compared to RMD- eyes (mean difference= - 12 μm, P=0.02), but not in the nasal or temporal regions. Among subjects <=82 years old, the overall mean CTh was significantly reduced in RMD+ eyes compared to RMD- eyes (mean difference= - 54 μm, P=0.012). Conversely, there was no significant difference in CTh in the older group (>=82 years) between RMD+ and RMD-. In the older age group, with each additional year of age, the choroids of RMD+ eyes got thicker (trend, 4.8 mm/year, p=0.33), while choroids of RMD- eyes got thinner (trend, -0.3 mm/year, p=0.39). Conclusions: Choroidal alterations in RMD vary with age and fundus region. The choroid was thinner in RMD+ than RMDeyes in the subfoveal region. Among subjects <=82 years old, the choroid was significantly thinner overall in RMD+ eyes, but not in older subjects, highlighting the role of age. In RMD+ eyes, CTh dynamics showed a trend to thinning before age 82, followed by thickening after this age, consistent with RMD-associated choroidal stromal fibrosis and thickening as a late development. RMD is a dynamic disease in 2 compartments, SDD in the subretinal space and pathology in the choroid, which must be studied together. ©2015, 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 2015 Annual Meeting Abstracts 12) vs. 18% of eyes without type C (41 of 227), p<0.001). Drusen substructures at baseline were not associated with total GA area or VA at baseline or year 2 (all p>0.05). Conclusions: Intermediate AMD eyes with drusen substructures at baseline were more likely to have non-central GA at year 2. The presence of drusen cores and/or debris on SDOCT may be associated with development of early GA. IR image on left: The 55 point grid for CTh measurements. Regions: red=nasal, yellow=subfoveal, blue=temporal. EDI-OCT image on right: Example of a CTh measurement (blue line). Yellow lines point to SDD. Commercial Relationships: Colleen Cunningham, None; Patrick A. Kaszubski, None; Hao Cheng, None; Hua Hao, None; Celine Saade, None; K Bailey Freund, Bayer HealthCare (C), Genetech (C), Heidelberg Engineering (C), Regeneron (C), Thrombogenics (C); Theodore Smith, Advanced Cell Technologies (C) Support: NIH/NEI Grant R01 EY015520; NIH/NEI Grant R01 EY06109 Program Number: 5139 Poster Board Number: C0203 Presentation Time: 3:45 PM–5:30 PM Classification and Correlation of SDOCT-visualized Drusen Substructures with Drusen Progression in Non-neovascular AMD Malini Veerappan1, Wai T. Wong2, Francisco A. Folgar3, Vincent Tai3, Michelle Michelson4, Katrina Winter3, Sandra Stinnett3, Cynthia A. Toth3, 5. 1Department of Ophthalmology, Duke University School of Medicine, Durham, NC; 2Unit on Neuron-Glia Interactions in Retinal Disease, National Eye Institute, NIH, Bethesda, MD; 3Department of Ophthalmology, Duke University Medical Center, Durham, NC; 4 Trinity College of Arts & Sciences, Duke University, Durham, NC; 5 Department of Biomedical Engineering, Duke University, Durham, NC. Purpose: Intermediate age-related macular degeneration (AMD) is characterized by drusen in the retinal pigment epithelial (RPE) layer. Multiple studies suggest that drusen contain a variety of immumodulatory molecules, including those in the complement cascade, which may manifest as distinct drusen substructures on spectral domain optical coherence tomography (SDOCT). We performed a prospective, observational clinical study to learn how SDOCT-reflective drusen substructures at baseline predict progression of non-neovascular AMD. Methods: Study participants from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study with intermediate AMD in one eye at baseline (n=314) were analyzed for presence of drusen substructures. Through review of SDOCT volumes across the macula, substructures at baseline were divided into 4 categories (see Figure 1). Presence of geographic atrophy (GA), total GA area, and visual acuity (VA) were assessed at baseline and year 2. These outcomes were compared between eyes with and without cores/debris at baseline using Fischer exact test and Wilcoxon rank sum test. Results: Of 239 study eyes with sufficient image quality and followup, 58 (24%) had at least one drusen substructure (min 0, median 0, max 8). Of these, 29 (50%) had type L, 34 (59%) had type H, 11 (19%) had type S, and 12 (21%) had type C. At year 2, 49 eyes had GA. 33% of eyes with substructures (19 of 58) vs. 17% of eyes without substructures (30 of 181) progressed to GA at year 2 (p= 0.014). GA at year 2 may be specifically driven by presence of type H (32% of eyes with type H (11 of 34) vs. 19% of eyes without type H (38 of 205), p=0.071) and type C (67% of eyes with type C (8 of Figure 1. Low-reflective Core (L). High-reflective Core (H). Split Low and High Reflective Core (S). Conical Debris (C). Commercial Relationships: Malini Veerappan, None; Wai T. Wong, None; Francisco A. Folgar, None; Vincent Tai, None; Michelle Michelson, None; Katrina Winter, None; Sandra Stinnett, None; Cynthia A. Toth, Alcon (F), Bioptigen (F), Genentech (F), NIH 1R01EY023039 (F) Support: Genentech FVF44005 Clinical Trial: NCT00734487 ©2015, 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 2015 Annual Meeting Abstracts Program Number: 5140 Poster Board Number: C0204 Presentation Time: 3:45 PM–5:30 PM Estimating the prevalence of subretinal drusenoid deposits (SDD) among older adults with healthy macula and age-related macular degeneration (AMD) with multimodal imaging Anna V. Zarubina, David Neely, Mark E. Clark, Carrie E. Huisingh, Brian C. Samuels, Yuhua Zhang, Gerald McGwin, Cynthia Owsley, Christine A. Curcio. Ophthalmology, University of Alabama at Birmingham, Birmingham, AL. Purpose: To assess SDD prevalence among older adults with healthy macula and early and intermediate AMD using multimodal imaging. Methods: 651 subjects (1302 eyes) ≥60 years old enrolled in the Alabama Study of Early Age-Related Macular Degeneration (ALSTAR) were assessed using SD-OCT, IR and FAF images, and color fundus photographs. Our strict criteria of SDD required identification on ≥1 en face modality and OCT or on ≥2 en face modalities in the absence of OCT findings. Our expanded criteria of SDD required detection on any imaging modality. Eyes with gradable OCT images were assessed for presence and severity of AMD using the AREDS 9-step scale. The number of subjects excluded from the analysis because of incomplete imaging data was specific to the SDD criteria used. SDD was considered present at the person-level if present even in one eye. Results: Using the strict criteria, overall sample prevalence of SDD was 32% (200/616); of those with SDD 123/200 (62%) were affected in both eyes. Persons with SDD were older than those without SDD (70.1 vs 68.7 yrs, p<0.0003). When stratified by AMD status, SDD prevalence was 53% in AMD subjects and 23% in subjects without AMD (p<0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 80% respectively. After age adjustment, those with SDD were 3.5X more likely to have AMD than those without SDD (95% CI 2.4-5.0). Using the expanded criteria, SDD prevalence was 74% (462/622) with 326/462 (70%) affected in both eyes. There was no age difference between subjects with and without SDD, but SDD prevalence was higher among those with AMD compared to those without (85% vs 69%, p<0.0001) and increased with disease severity. After age adjustment, persons with SDD were 2.6X more likely to have AMD compared to those without SDD (95% CI 1.7-4.1). Conclusions: SDD is prevalent in over 1/2 of persons with early to intermediate AMD, and is present in about 1/4 of older adults with healthy maculae, even by stringent SDD criteria. A broader definition of SDD increases its prevalence but may lead to overestimation. SDD prevalence is strongly associated with AMD presence and severity and increases with age. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance. Commercial Relationships: Anna V. Zarubina, None; David Neely, None; Mark E. Clark, None; Carrie E. Huisingh, None; Brian C. Samuels, None; Yuhua Zhang, None; Gerald McGwin, None; Cynthia Owsley, None; Christine A. Curcio, None Support: R01AG04212, R01EY06109; EyeSight Foundation of Alabama; Alfreda J. Schueler Trust; Research to Prevent Blindness. Purpose: Choriocapillaris thickness is associated with the progression of drusen in dry age-related macular degeneration. Local quantification of choriocapillaris thickness has so far been difficult. We report an automated method to segment choriocapillaris and to quantify the local/regional choriocapillaris thickness near drusen in dry-AMD using spectral-domain optical coherence tomography (SDOCT). Methods: Sixty-nine patients with dry AMD underwent OCT imaging using Heidelberg Spectralis SD-OCT with enhanced depth imaging. We segmented choriocapillaris and drusen simultaneously using a graph-based method. The boundary of retinal pigment epithelium (l-RPE), Bruch’s membrane (BM) and the transition surface between choriocapillaris and choroidal vasculature (CC-CV) were thus segmented (see Figure 1). Mean and standard deviation (std.) of regional sub-RPE virtual space (sub-RPE-VS) thickness were then calculated for each patient. A drusen was defined as a group of neighboring A-scans where sub-RPE-VS thickness was greater than mean+2*std. Local average choriocapillaris thicknesses was averaged over the drusen region as well as circular regions of 20, 40, to 160 microns near drusen. Results: Choriocapillaris is significantly thinner (8.46μm) under the drusen (see Figure 2) and it is thicker (9.19μm) just outside the boundary of the drusen. Conclusions: We have developed an automated method to quantify the presence, distribution and size of drusen and measure regional choriocapillaris thickness. Our preliminary results confirm thinner choriocapillaris under drusen that is known from histology studies. Whether the intriguing finding of slightly thickened choriocapillaris just outside of drusen areas can be confirmed is the subject of an ongoing study. Our approach has the potential to better understand the relationships between different structures in the outer retina in dry-AMD. Program Number: 5141 Poster Board Number: C0205 Presentation Time: 3:45 PM–5:30 PM Automated quantification of choriocapillaris thickness near drusen Li Zhang1, Elliott H. Sohn2, Robert F. Mullins2, Milan Sonka1, 2, Michael D. Abramoff1, 2. 1Electrical and Computer Engineering, University of Iowa, Iowa City, IA; 2Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA. ©2015, 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 2015 Annual Meeting Abstracts Figure 1. Automated segmentation of choriocapillaris and drusen (a) Original B-scan; (b) Same B-scan with segmented surfaces. Figure 2. Choriocapillaris thickness averaged over the drusen region as well as circular regions of 20, 40, to 160μm near drusen. Commercial Relationships: Li Zhang, None; Elliott H. Sohn, None; Robert F. Mullins, None; Milan Sonka, University of Iowa (P); Michael D. Abramoff, IDx LLC (C), IDx LLC (I), University of Iowa (P) Support: NIH Grant R01 EY018853, R01 EY019112, R01 EB004640 ©2015, 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 2015 Annual Meeting Abstracts Program Number: 5142 Poster Board Number: C0206 Presentation Time: 3:45 PM–5:30 PM The role of age-related macular degeneration associated variants in drusen progression Joshua D. Hoffman3, Mark J. Van Grinsven1, Jessica Cooke Bailey2, Mariusz Butkiewcz2, Milam A. Brantley4, Chun Li2, William K. Scott5, Margaret A. Pericak-Vance5, Clara I. Sanchez1, Jonathan L. Haines2. 1Diagnostic Image Analysis Group, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH; 3Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN; 4Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN; 5John P. Hussman Institute for Human Genomics, University of Miami School of Medicine, Miami, FL. Purpose: Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the United States (US). Although a multitude of studies have shown that both genetic and environmental factors contribute to the pathogenesis of AMD, little is known on how genetics impacts the disease’s rate of progression. In this analysis we performed a quantitative analysis of drusen progression during the intermediate stage of the disease to understand the influence of AMD genetic variation on this phenotype. Methods: Color fundus photographs deposited by the Age-related Eye Diseases Study (AREDS) to the database of Genotypes and Phenotypes (dbGAP) were retrieved on subjects that showed absence of geographic atrophy (GA) and choroidal neovascularization (CNV) and a baseline diagnosis of intermediate to large drusen. Automated drusen detection and quantification was carried out on all subject eyes and visits that met these criteria using a previously developed algorithm. Drusen progression was tested against 19 previously identified genetic variants using both a cumulative genetic risk score and single variant analyses. Pathway analysis using results from a genome-wide quantitative association analysis of progression rates was carried out using Pathway Analysis by Randomization Incorporating Structure (PARIS). Results: In the 246 subjects AREDS subjects that met our selection criteria we observe significant correlation in bilateral drusen progression (rho = 0.30, p-value = 0.004). We do not observe significant correlation between the 19-variant cumulative genetic risk score and drusen progression (rho = 0.039; p = 0.543). We do not observe a significant association with rs10490924 in ARMS2 (p = 0.161), rs10737680 in CFH (p = 0.156), rs116503776 in C2/CFB (p = 0.713), or rs2230199 in C3 (p = 0.728). Single marker tests of the remaining 15 variants show a nominally significant association with rs943080 in VEGFA (p = 0.028). The most highly associated pathway in our pathway analysis is the cell adhesion molecule pathway (p < 0.0001). Conclusions: In this analysis we attempt to isolate the role of known AMD genetic variation to one aspect of this phenotypically heterogeneous disease. The 19 common variants examined cumulatively and individually do not associate with progression in our dataset, although pathway analysis suggests unidentified loci may be important for drusen progression. Commercial Relationships: Joshua D. Hoffman, None; Mark J. Van Grinsven, None; Jessica Cooke Bailey, None; Mariusz Butkiewcz, None; Milam A. Brantley, None; Chun Li, None; William K. Scott, None; Margaret A. Pericak-Vance, None; Clara I. Sanchez, None; Jonathan L. Haines, None Support: A6019085, EY012118, AG019726, AG044089 Program Number: 5143 Poster Board Number: C0207 Presentation Time: 3:45 PM–5:30 PM Comparison of retinal and choriocapillaris thicknesses following sitting to supine transition in normal and age-related macular degeneration subjects David R. Almeida, Li Zhang, Eric K. Chin, Robert F. Mullins, Murat Kucukevcilioglu, Milan Sonka, Edwin M. Stone, James C. Folk, Michael D. Abramoff, Stephen R. Russell. Ophthalmology, University of Iowa, Iowa City, IA. Purpose: Effects of position on retinal and choroidal structure are absent from the literature yet may provide insights into disease states like age-related macular degeneration (AMD). We set out to evaluate the effect of postural change on retinal and choroidal structures in normal volunteers and subjects with non-neovascular AMD. Methods: Prospective observational case series. Four unaffected volunteers (8 eyes) and 7 subjects (8 eyes) with intermediate AMD. Normal volunteers were selected that had no evidence of ocular disease. Subjects with AMD were required to have at least 10 intermediate sized drusen. Spectral domain optical coherence tomography (OCT) with enhanced depth imaging in upright (sitting) and supine positions. Stable imaging was achieved using a rotating adjustable mechanical arm that we constructed to allow the OCT transducer to rotate 90 degrees. The Iowa Reference Algorithms were used to quantify choroid and choriocapillaris thickness. Main outcome measures included changes in sitting and supine position central macular thickness (CMT, μm), total macular volume (TMV, mm3), choroidal thickness (CT, μm), and choriocapillaris equivalent thickness (CCET, μm). Results: CCET was thinner in normal subjects (9.89 mm) compared to patients with intermediate AMD (16.73 mm) (p = 0.02); there was no difference in overall CT between the two groups (p = 0.38). There was a 15% CCET reduction among normal subjects when transitioning from sitting (9.89 mm) to supine position (8.40 μm) (p = 0.02) versus a CCET reduction of 11.1% from sitting (16.73 μm) to supine (14.88 μm) (p = 0.10) in patients with intermediate AMD. Conclusions: Intermediate AMD appears to be associated with an increase in CCET and with a lack of positional responses that are observed in the CCET of normal eyes. Our results suggest that although outer portions of the choroid do not appear to be responsive to modest positional or hydrostatic pressure, the choriocapillaris capacity is, and this is measurable in vivo. Whether this physiologic deviation that occurs in AMD is related to atrophy, inflammation, or changes in autoregulatory factors or growth factors, remains to be determined. Commercial Relationships: David R. Almeida, None; Li Zhang, None; Eric K. Chin, None; Robert F. Mullins, None; Murat Kucukevcilioglu, None; Milan Sonka, Imaging (P); Edwin M. Stone, None; James C. Folk, None; Michael D. Abramoff, Imaging (P); Stephen R. Russell, None Program Number: 5144 Poster Board Number: C0208 Presentation Time: 3:45 PM–5:30 PM Characteristics of Pseudodrusen investigated using Multi-Modal Imaging including PS-OCT Magdalena Baratsits1, Ferdinand G. Schlanitz1, Katharina Eibenberger1, Bernhard Baumann2, Urike Scheschy1, Alessio Montuoro1, Stefan Zotter2, Michael Pircher2, Christoph K. Hitzenberger2, Ursula Schmidt-Erfurth1. 1Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; 2 Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria. Purpose: The aim of this study was to investigate the characteristics of pseudodrusen (PD) and their organization within the retina in ©2015, 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 2015 Annual Meeting Abstracts patients with early age-related macular degeneration (AMD) by evaluating and cross-linking different imaging techniques with threedimensional delineation of polarization- sensitive optical coherence tomography (PS-OCT) volume scans. Methods: 109 patients with early AMD were examined using SD-OCT, IR-reflectance imaging, and autofluorescence imaging. Furthermore, patients were scanned with a wide-field PS-OCT (scanning area 30°x30°, volume scan 1024x250). The RPE-layer and drusen were segmented by an automated computer algorithm utilizing the polarization-senstive information. Afterwards, the PS-OCT datasets were delineated manually for pseudodrusen. The 3D-map of pseudodrusen was compared with the 3D-map of the RPE layer and drusen, and furthermore to the autofluorescence and IR-reflectance images in order to investigate the structural characteristics at the level of RPE in early AMD. Results: 14 eyes were segmented manually for PD and the imaging characteristics were evaluated by cross-linking the three-dimensional map to autofluorescence and IR-reflectance images. In the threedimensional images, PD did not show distinct borders but rather a plaque-like spreading between the RPE and the photoreceptor layers. Therefore, distinction between certain types of PD was difficult, and most PD seemed to be influenced in their form by other microstructural alterations at the level of the RPE, such as drusen. The combination of drusen- and pseudodrusenmap could explain some imaging characteristics seen in the en-face autofluorescence and reflectance images. Conclusions: Due to the ability of the PS-OCT to detect and segment the RPE layer, grading of pseudodrusen could be done in a more reliable way than before. Certain PD-types were evaluated in their three-dimensional nature for the first time. By segmenting the hyperreflective structures located above RPE a plaque-like deposition found. This matches findings by histologic investigations, and may be caused by the loose-fitting structures between RPE and photoreceptors. The combination of the en-face images extracted from OCT volumes, i.e. RPE layer, drusen- and pseudodrusen maps, could explain the imaging characteristics of early AMD in en-face images such as autofluorescence and IR-reflectance in more detail. Commercial Relationships: Magdalena Baratsits, None; Ferdinand G. Schlanitz, None; Katharina Eibenberger, None; Bernhard Baumann, Canon (F); Urike Scheschy, None; Alessio Montuoro, None; Stefan Zotter, Canon (F); Michael Pircher, Canon (C), Canon (F); Christoph K. Hitzenberger, Canon (F); Ursula Schmidt-Erfurth, Alcon (F), Boehringer (F), Novartis (F), Novartis (F) Program Number: 5145 Poster Board Number: C0209 Presentation Time: 3:45 PM–5:30 PM Reticular pseudodrusen on infrared reflectance are topographically distinct from subretinal drusenoid deposits on en face optical coherence tomography Michael Heiferman, Joshua K. Fernandes, Marion R. Munk, Rukhsana Mirza, Lee M. Jampol, Amani A. Fawzi. Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL. Purpose: Reticular pseudodrusen (RPD), most prominent on infrared reflectance (IR), are a phenotypic finding of age-related macular degeneration (AMD) and a risk factor for increased incidence of progression to late stage AMD. The relationship between RPD and subretinal drusenoid deposits (SDD) has not been systematically evaluated. The goal of this study is to evaluate the quantitative and topographic relationship between RPD on IR and SDD on en-face volumetric spectral-domain optical coherence tomography (SDOCT). Methods: RPD were marked on IR images by a masked observer. SDD were visualized on en-face sections of SD-OCT immediately below the external limiting membrane and identified by a semiautomated technique using NIS-Elements Ar (Nikon Instruments Inc., Tokyo, Japan). Control RPD lesions were generated in a random distribution for each IR image using ImageJ (NIH, Bethesda, MD). Binary maps of control and experimental RPD and SDD were merged and topographically and quantitatively analyzed using ImageJ. Results: 54 eyes of 41 patients diagnosed with RPD were included in this study. The average number of RPD lesions on IR images was 320±44.62 compared to 127±26.02 SDD lesions on en-face (P<0.001). The percentage of total SDD lesions overlapping RPD was 2.91±0.87% compared to 1.73±0.68% overlapping control RPD lesions (P<0.05). The percentage of total SDD lesions between 1-3 pixels of the nearest RPD lesion was 5.08±1.40% compared to 3.33±1.07% between 1-3 pixels of the nearest control RPD lesion (P<0.05). Conclusions: This study identified significantly more RPD lesions on IR compared with SDD lesions on en-face SD-OCT and found that a large majority of SDD (>90% of lesions) were greater than 3 pixels away from the nearest RPD indicating that RPD and SDD are two distinct lesions. The minority of SDD lesions (7.99±2.22%) that were either overlapping or between 1-3 pixels from RPD were more likely to be in that location than predicted by randomly distributed control RPD lesions. Together, our findings indicate that RPD and SDD are two entities that are only occasionally topographically associated, suggesting that at some stage of their development, they could be pathologically related. Distribution of SDD in relation to RPD and randomly located control RPD lesions. Commercial Relationships: Michael Heiferman, None; Joshua K. Fernandes, None; Marion R. Munk, None; Rukhsana Mirza, None; Lee M. Jampol, None; Amani A. Fawzi, None Support: R01EY021470 (AAF), Research to Prevent Blindness, NY (Department of Ophthalmology, Northwestern University) ©2015, 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 2015 Annual Meeting Abstracts Program Number: 5146 Poster Board Number: C0210 Presentation Time: 3:45 PM–5:30 PM Association of drusen substructure findings on SD-OCT with abnormal drusen volumes and progression to choroidal neovascularization in the AREDS2 Ancillary Study Randall C. Gunther1, Cynthia A. Toth1, 3, Malini Veerappan1, Michelle Michelson1, Vincent Tai1, Katrina Winter1, Francisco A. Folgar1, Emily Y. Chew2, Sina Farsiu1. 1Ophthalmology, Duke University Medical Center, Durham, NC; 2Epidemiology and Clinical Applications, National Eye Institute, NIH, Bethesda, MD; 3 Department of Biomedical Engineering, Duke University, Durham, NC. Purpose: To evaluate spectral domain optical coherence tomography (SDOCT) drusen substructures for association with drusen volume and progression to choroidal neovascularization (CNV) Methods: Eyes with intermediate age related macular degeneration (AMD) from the multi-center prospective Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study were analyzed for presence of drusen substructures at baseline. Through qualitative SDOCT grading, substructures were divided into four types: low reflectivity core (L), high reflectivity core (H), split low and high reflectivity core (S), and conical debris (C). After semi-automated SDOCT segmentation, drusen volume within a 5-mm macular field was measured at baseline and year 2. Presence of CNV was assessed at year 2. Outcomes were compared using Wilcoxon rank sum and Fisher exact test. Results: Of 314 baseline study eyes, 273 had SDOCT grading and CNV outcomes available. 226 had both baseline and year 2 drusen volume measurements. Eyes with any substructures were associated with greater drusen volume at baseline (0.094±0.115 mm3 vs. 0.067±0.168 mm3, p<0.001) and year 2. L-type, H-type, and S-type were correlated with higher drusen volume at baseline (L: 0.104±0.119 mm3 vs. 0.070±0.160 mm3 (p<0.001); H: 0.094±0.104 mm3 vs. 0.070±0.164 mm3 (p<0.001); S: 0.148±0.155 mm3vs. 0.070±0.155 (p<0.001)) and year 2. C-type did not correlate with drusen volume. At year 2, 75 eyes had significant increase in drusen volume. 44% of eyes with any drusen substructures (28 of 63) vs. 29% of eyes without substructures (47 of 163) had significant increase in drusen volume over 2 years (p=0.028). No individual substructure types were associated with drusen volume change. 36 of 273 developed CNV by year 2, but there was no difference in frequency of CNV between eyes with any substructures (14%) and eyes without (13%). Conclusions: Drusen substructure presence may be associated with larger drusen volumes in patients with intermediate AMD. L and W type substructures may indicate a risk for both increased drusen volume and progression from intermediate AMD to CNV. Commercial Relationships: Randall C. Gunther, None; Cynthia A. Toth, Alcon (F), Bioptigen (F), Genentech (F), NIH 1RO1EY023039 (F); Malini Veerappan, None; Michelle Michelson, None; Vincent Tai, None; Katrina Winter, None; Francisco A. Folgar, None; Emily Y. Chew, None; Sina Farsiu, Duke University (P), NIH R01EY022691 (F) Support: Grenentech FVF44005 Clinical Trial: NCT00734487 Program Number: 5147 Poster Board Number: C0211 Presentation Time: 3:45 PM–5:30 PM Standardized Assessment of Drusen Measurements from Spectral Domain Optical Coherence Tomography (SDOCT) Scans in Dry Age Related Macular Degeneration (AMD) Amitha Domalpally, Yijun Huang, Dawn Myers, Taylor Starnes, Zhe Liu, Ronald P. Danis, Barbara A. Blodi. Ophthalmology, Fundus Photograph Reading Center, Madison, WI. Purpose: To compare retinal pigment epithelium (RPE) and retinal thickness assessments made with SDOCTin eyes with dry AMD and normal eyes. Methods: Eyes with intermediate AMD or worse in participants between 50 – 85 years of age were evaluated in custom SDOCT segmentation software. After converting to a standardized Digital Imaging and Communications in Medicine (DICOM) format, macular volume scan files from 4 different SDOCT machines were displayed in the same software and segmented for inner limiting membrane (ILM), RPE-drusen complex and Bruch’s membrane (BM) in a display and analysis platform using an algorithm developed at the University of Wisconsin’s Fundus Photograph Reading Center (Huang, et al, PLoS One. 2013 Dec 26;8(12):e82922) (Fig 1 top). Reading center graders reviewed each volume scan and edited boundary line placement if required. Similar segmentation (ILM, RPE and BM – Fig 1 bottom) was performed in SDOCT scans from participants of same age range in whom dry AMD and other confounding abnormalities had been ruled out. Results: The mean central subfield (CSF) retinal thickness was significantly different between eyes with dry AMD (n = 72) and normal eyes (n= 435); 225.8m (SD 39.8) and 245.5m (SD 27.8) respectively. Total retinal volume was also significantly different between the two groups; 7.4mm3(0.5) and 7.6 mm3 (0.5) respectively. In the central subfield, thickness of the RPE-drusen complex was 70.8 m (SD 31.6) and RPE thickness in normal eyes was 33.3 m (SD 4.6) (P<0.001). The RPE-drusen complex volume and RPE volume was also significantly different between the two groups; 1.1 mm3 (SD 0.2) and 0.8 mm3 (SD 0.1). Conclusions: Drusen segmentation can be effectively performed in eyes with dry AMD and can be used as an outcome for clinical trials. Regression in drusen volume towards normal can potentially be identified using custom segmentation. Commercial Relationships: Amitha Domalpally, None; Yijun Huang, EyeKor LLC (I); Dawn Myers, None; Taylor Starnes, None; Zhe Liu, None; Ronald P. Danis, Merck (F); Barbara A. Blodi, None Program Number: 5148 Poster Board Number: C0212 Presentation Time: 3:45 PM–5:30 PM Photoreceptor disorder around subretinal drusenoid deposits and drusen revealed by adaptive optics scanning laser ophthalmoscopy Xiaolin Wang1, Tianjiao Zhang1, 2, Pooja Gordara1, Alexander Meadway1, Mark E. Clark1, Clark D. Witherspoon1, Christopher A. Girkin1, Cynthia Owsley1, Christine A. Curcio1, Yuhua Zhang1. 1Ophthalmology, University of Alabama at Birmingham, Birmingham, AL; 2Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL. Purpose: To describe the microscopic structure of photoreceptors impacted by extracellular lesions residing in the subretinal space and the sub-RPE (retinal pigment epithelium) space in patients with age-related macular degeneration (AMD), using multimodal imaging including a new-generation research adaptive optics scanning laser ophthalmoscope (AOSLO). ©2015, 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 2015 Annual Meeting Abstracts Methods: Twenty-nine patients (n=29) with early to intermediate AMD (grade 2-8 on the AREDS 9-step severity scale) were classified into 3 groups. Group 1 (9 eyes of 7 subjects) have subretinal drusenoid deposits (SDD) only in the macula, Group 2 (13 eyes of 7 subjects) have abundant (more than 20) densely packed small hard drusen (consistent with the clinic appearance of cuticular drusen, 50 – 75 μm diameter) only, and Group 3 (17 eyes of 15 subjects) have medium-large soft drusen (63 - 1000 μm diameter). These lesions were ascertained by presence in color fundus photographs, infrared reflectance, blue reflectance, autofluorescence images, and spectral domain optical coherence tomography (SD-OCT). SDD were classified with a 3-stage OCT-based grading system. The photoreceptor mosaic was assessed with AOSLO. Results: AOSLO disclosed characteristic photoreceptor reflectivity perturbation over different lesion types. For SDD, photoreceptor reflectivity was reduced over stage 1 and stage 2 lesions with an indiscernible mosaic. For stage 3 SDD, AOSLO revealed a distinctive structure showing a hyporeflective annulus surrounding a core that is formed by the lesion material itself but bears a reflectivity superficially resembling photoreceptors (Fig.B1). Around the densely packed small hard drusen, the photoreceptor mosaic was largely visible and contiguous and with reduced, patchy reflectivity (Fig.B2). Around large soft drusen, the photoreceptor mosaic was invisible at the edge and visible on the top (Fig.B3). The en-face appearance of the photoreceptor mosaic was consistent with its cross-sectional structure as rendered by SD-OCT (Fig.C1-C3). Conclusions: The dramatic photoreceptor reflectivity perturbation associated with SDD indicates that SDD may impose more direct and severe impact on overlying photoreceptors than drusen, suggesting that the retinal function in eyes with SDD may be more severely impired. Figure. AOSLO revealed characteristic photoreceptor reflectivity perturbation by different lesion types Commercial Relationships: Xiaolin Wang, None; Tianjiao Zhang, None; Pooja Gordara, None; Alexander Meadway, None; Mark ©2015, 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 2015 Annual Meeting Abstracts E. Clark, None; Clark D. Witherspoon, None; Christopher A. Girkin, None; Cynthia Owsley, None; Christine A. Curcio, None; Yuhua Zhang, None Support: This project is funded by EyeSight Foundation of Alabama (YZ), International Retina Research Foundation (YZ), 5R21EY021903 (YZ), Songs for Sight (CAG), Buck Trust of Alabama (CAG), R01AG04212 (CO), and R01EY06109 (CC) and institutional support from Research to Prevent Blindness, EyeSight Foundation of Alabama, Buck Trust of Alabama, and NIH P30 EY003039. Program Number: 5149 Poster Board Number: C0213 Presentation Time: 3:45 PM–5:30 PM Longitudinal Quantitative OCT Analysis of Drusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration Hongyang Zhang1, 2, Nizar S. Abdelfattah1, David S. Boyer3, Srinivas R. Sadda1. 1Doheny Image Reading Center, Doheny Eye Institute, University of California Los Angeles, Los Angles, CA; 2 Ophthalmology, Guangdong General Hospital, Guangzhou, China; 3 Retina Vitreous Associates Medical Group, Los angles, CA. Purpose: The fellow eyes of patients with late AMD in one eye may be at the highest risk of developing late AMD. Reduction of drusen volume without the development of late AMD has been suggested as a potential therapeutic endpoint in early intervention trials. To determine the relationship between drusen volume and late AMD, we evaluated longitudinal changes in the fellow eye of patients with unilateral neovascular AMD using optical coherence tomography (OCT). Methods: In this retrospective analysis, we analyzed the fellow eye of 42 patients (age range, 69-93 years) who had advanced neovascular AMD in only 1 eye. All patients were treated with intravitreal ranibizumab, pegaptanib, or/and bevacizumab and followed up for two years. In this analysis, we focused on the fellow eye with only evidence of drusen secondary to the non-exudative AMD. All eyes were scanned with the Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin, CA) using a 512 ×128 scan pattern. OCT data at baseline, Month 12, and Month 24 was evaluated using the advanced RPE analysis tool to quantify drusen volume within 3mm and 5mm diameter circles. OCT scans were also evaluated for the development of atrophy or CNV. Results: Drusen without evidence of late AMD were evident in 18 participants (42.9%). After 12 months, none of the eyes developed neovascular disease but two eyes (11.1%) developed geographic atrophy (GA). By 24 months of follow-up, 4 eyes (22.2%) developed GA and no eyes developed CNV. Once the eye progressed to GA it was censored from the quantitative drusen study. After two years, there were no statistically significant changes in drusen area or volume for the cohort overall. There was also no statistically significant (p = 0.38, in 3mm; p=0.10, in 5mm) difference in baseline drusen volume between eyes which developed atrophy compared with those that did not. However, in eyes which developed atrophy by Month 24, drusen volume had decreased at Month 12 by 0.06 ± 0.06 mm3 compared with 0.01 ± 0.04 mm3 in eyes without atrophy. Conclusions: Changes in drusen volume and development of GA can be tracked using SDOCT. Although baseline drusen volume did not appear to predict atrophy development, a decrease in drusen volume was associated with new atrophy. This suggests the potential for drusen volume changes to be used as biomarkers to identify eyes at high risk for progression to atrophy. Commercial Relationships: Hongyang Zhang, None; Nizar S. Abdelfattah, None; David S. Boyer, Aerpio (C), Alcon (C), Alcon (R), Allergan (C), Allergan (R), Bayer (C), Genentech (C), Genentech (R), GS (C), KalVista (C), Neurotech (C), Nicox, Inc (C), Novartis (C), Novartis (R), Ohr (C), Regeneron (R), Regeneron Pharmaceuticals, Inc (C), Santaris (C), Santen (C), ThromboGenics (C); Srinivas R. Sadda, Alcon (C), Allergan (C), Allergan (F), Allergan (R), Carl Zeiss Meditec (C), Carl Zeiss Meditec (F), Carl Zeiss Meditec (R), Genentech (C), Genentech (F), Novartis (C), Optos (C), Optos (F), Optos (R), Roche (C) Program Number: 5150 Poster Board Number: C0214 Presentation Time: 3:45 PM–5:30 PM Reticular Pseudodrusen, Enlarging Geographic Atrophy, and Decreased Choroidal Thickness in Age-Related Macular Degeneration Mariana Rossi Thorell1, Raquel Goldhardt1, Renata Portella Nunes2, Carlos Alexandre de Amorim Garcia Filho2, Giovanni Gregori1, Zohar Yehoshua1, William J. Feuer1, Srinivas R. Sadda3, Philip J. Rosenfeld1. 1Bascom Palmer Eye Institute, Miami, FL; 2Federal University of Sao Paulo - UNIFESP, Sao Paulo, Brazil; 3Doheny Eye Institute, Los Angeles, CA. Purpose: To compare subfoveal choroidal thickness (CT) measurements in eyes with non-exudative age-related macular degeneration (AMD) with and without reticular pseudodrusen (RPD) and eyes with no known ocular disease. Methods: Retrospective study of AMD patients enrolled in the COMPLETE study (30 drusen-only eyes and 30 eyes with geographic atrophy [GA]) compared to an age-distributed normal control group (155 eyes of normal subjects). CT was measured in the subfoveal region using enhanced-depth SD-OCT imaging. Multimodal images were evaluated to detect the presence of RPD in eyes with nonexudative AMD. Results: Three drusen eyes (10%) were diagnosed with RPD. In the GA group, 20 eyes (66.7%) were diagnosed with RPD. After controlling CT for age and axial length, the mean subfoveal CT of the GA group was significantly thinner than the drusen group (p=0.007), but the drusen group was not significantly different than the normal controls (p=0.090). After separating the GA group into eyes with and without RPD, the GA group without RPD had a mean CT (335.3±123.2μm) that was not significantly different from normal eyes (286.1±84.5;p=0.076) or eyes with drusen (315.6±86.2; p=0.45), while the GA group with RPD (213.7±53.1μm) was significantly thinner than the GA group without RPD (p=0.001). In eyes without RPD, increasing area of GA was strongly correlated with decreasing CT (p=0.001). Conclusions: Subfoveal CT measurements in eyes with nonexudative AMD and without RPD were similar to normal ageadjusted control eyes. Choroidal thinning in eyes with non-exudative AMD was associated with the presence of RPD or an increasing area of GA. Commercial Relationships: Mariana Rossi Thorell, Carl Zeiss Meditec (F); Raquel Goldhardt, None; Renata Portella Nunes, ©2015, 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 2015 Annual Meeting Abstracts None; Carlos Alexandre de Amorim Garcia Filho, None; Giovanni Gregori, Carl Zeiss Meditec (F), Carl Zeiss Meditec (P); Zohar Yehoshua, None; William J. Feuer, None; Srinivas R. Sadda, Carl Zeiss Meditec (F); Philip J. Rosenfeld, Carl Zeiss Meditec (F) Support: Grant from Alexion Pharmaceuticals, Carl Zeiss Meditec, Inc. (Dublin, CA), the Macula Vision Research Foundation, an unrestricted grant from Research to Prevent Blindness, the Feig Family Foundation, the Emma Clyde Hodge Memorial Foundation, and the National Eye Institute (R01EY024158, P30EY014801). Program Number: 5151 Poster Board Number: C0215 Presentation Time: 3:45 PM–5:30 PM Changes in Subretinal Drusenoid Deposits (SDD) During Progression to Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in Age-Related Macular Degeneration (AMD) Vivek Kumar1, Patrick A. Kaszubski1, Tal Ben Ami1, Celine Saade1, Ana Rita Santos2, Rufino Silva2, 3, Maria Luz Cachulo2, 3, Jose G. Cunha-Vaz2, Theodore Smith1. 1Department of Ophthalmology, New York University School of Medicine, New York, NY; 2Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal; 3Department of Ophthalmology, Coimbra University Hospital, Coimbra, Portugal. Purpose: This retrospective study utilized 3 imaging modalities to quantitatively analyze SDD evolution in eyes that progressed from early to late AMD over a 2-year follow-up period. We analyzed the change in SDD area within the fundus, both in subjects who progressed to GA and in those who progressed to CNV, with the goal of better understanding the dynamic spatiotemporal nature of SDD and their role in AMD progression. Methods: 25 patients with AMD and unilateral CNV were included. The non-CNV eyes (the study eyes) all underwent indocyanine green angiography (ICG), short-wavelength autofluorescence (AF), and near infrared reflectance (NIR) imaging at baseline and at 2-year follow-up. Study eyes were analyzed for SDD and for the development of late AMD—both CNV and geographic atrophy (GA). SDD area measurements were obtained by two graders utilizing ImageJ software and are expressed as a percentage of total fundus area; binary logistic regression and the Wilcoxon nonparametric test were used for statistical analysis. Results: 8 study eyes developed GA and 17 study eyes developed CNV during the follow-up period. In the eyes that developed CNV, there was a statistically significant decrease in SDD area as seen on AF (P=0.004) and NIR (P=0.027), and the decrease in SDD area approached statistical significance on ICG (P=0.078). By contrast, in the eyes that developed GA, there was no significant change in SDD area as seen on all 3 imaging modalities (ICG: P=0.75, AF: P=0.275, and NIR: P=1). Conclusions: SDD undergo dynamic spatiotemporal changes in eyes with AMD. These lesions can be seen in eyes that progress to late AMD, both GA and CNV, but a decrease in SDD area is seen only during progression to CNV, likely as a result of worse ischemia and increased VEGF in CNV subjects. These results suggest that the SDD lesions migrate, are absorbed by surrounding cells, or are no longer visible due to imaging difficulties secondary to changes present in CNV. All images are from the same subject; A-C at initial imaging, D-F at final follow-up. A&D=ICG, B&E=AF, C&F=NIR Commercial Relationships: Vivek Kumar, None; Patrick A. Kaszubski, None; Tal Ben Ami, None; Celine Saade, None; Ana Rita Santos, None; Rufino Silva, None; Maria Luz Cachulo, None; Jose G. Cunha-Vaz, None; Theodore Smith, None Support: This work was supported by an individual investigator research award from the Foundation Fighting Blindness (RTS), National Institutes of Health/National Eye Institute grant R01 EY015520 (RTS), and unrestricted funds from Research to Prevent Blindness (RTS). Program Number: 5152 Poster Board Number: C0216 Presentation Time: 3:45 PM–5:30 PM Structural correlations of the choriocapillaris, choroid, retina, and RPE using automated OCT-based measurements in AMD Johanna D. Beebe1, Elliott H. Sohn1, Li Zhang2, 3, Robert F. Mullins1, 4 , Michael D. Abramoff4, 3. 1Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA; 2Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA; 3Iowa Institute for Biomedical Imaging, Iowa City, IA; 4Stephen A Wynn Institute for Vision Research, Iowa City, IA. Purpose: Alterations in the choroid play an important role in the pathogenesis of age-related macular degeneration (AMD). Manual and semi-automated methods of segmentation have shown good discrimination of choroidal detail on optical coherence tomography (OCT) but fully automated protocols to detect outer retinal structures in AMD are lacking. This was a pilot study, in which we applied a newly developed method of automated OCT segmentation analysis to study the correlations of choroid, choriocapillaris, retina, and RPE thickness in eyes with AMD. Methods: 38 subjects with AMD had 61 line scan protocol with enhanced depth imaging performed on the Heidelberg Spectralis SDOCT device. Automated segmentation using a graph-based method was used to determine thickness of photoreceptor outer segment length, RPE, choriocapillaris, and choroid. Scans of eyes with CNV were excluded from analysis. These measurements were plotted and a linear regression analysis was used to assess for statistical significance. Results: The mean thickness (μ) + standard deviation (SD) of the choriocapillaris, RPE, OSL, and choroid was 8.73+0.65; 24.2+1.00; 39.02+6.42; 158.21+52.21 respectively. The strongest correlation (r2=0.200) was found between the thickness of the choroid and the OSL. There was also weak correlation between the RPE and the OSL (r2=0.121). All other relationships had an r2 < 0.100. ©2015, 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 2015 Annual Meeting Abstracts Conclusions: Automated segmentation of SD-OCT images can be successfully performed to determine thickness of outer retinal structures of eyes with AMD. There is a plausible correlation between photoreceptor outer segment length and choroid that needs confirmation in a larger data set. Commercial Relationships: Johanna D. Beebe, None; Elliott H. Sohn, None; Li Zhang, None; Robert F. Mullins, None; Michael D. Abramoff, IDx LLC (C), IDx LLC (I), University of Iowa (P) Support: NIH Grant R01 EY018853, R01 EY019112, R01 Program Number: 5153 Poster Board Number: C0217 Presentation Time: 3:45 PM–5:30 PM Factors affecting the conversion rate of the fellow eye of patients with neovascular age-related macular degeneration over 5 years Elizabeth Pearce2, Sobha Sivaprasad1, Victor Chong3. 1Moorfields Eye Hospital, London, United Kingdom; 2King’s College Hospital, London, United Kingdom; 3Oxford Eye Hospital, Oxford University Hospitals, Oxford, United Kingdom. Purpose: To determine whether baseline functional and anatomical features can predict the conversion to neovascular age-related macular degeneration (AMD) in the fellow eye of patients receiving anti-VEGF treatment for neovascular AMD. Methods: In total, 50 patients with neovascular AMD in one eye receiving anti-VEGF treatment were included in the study. The fellow eye has to have good vision (better than 20/40) and was able to perform all the functional and anatomical tests. Best corrected visual acuity (BCVA), retinal sensitivity and fixation stability measured by microperimetry (Nidek MP1), fundus photography, the central subfield thickness (CST) and infra-red imaging obtained by the Heidelberg Spectralis were performed. The drusen area in the central retina was measured by customised software, and the presence of reticular pseudo-drusen was assessed on infra-red imaging. Statistical analysis was performed with Student t-test and Fisher Exact test.The study was approved by local ethical committee. Results: In total, 43 patients has completed the 5 year follow up, 14 (32%) of the study eye has developed neovascular AMD during the follow up. The average age on entry to the study was 74.7 years. There were no significant difference in the age, sex, baseline CST, BCVA, drusen area and fixation stability between those who had developed neovascular AMD as compared those who did not. However, there is a trend that those who converted was more likely but not statistical significant to have poorer retinal sensitivity,10.5 db vs 8.9 db (p=0.1) and more likely to have reticular pseudodrusen 20.7% vs 42.9% (p=0.1). Conclusions: In this pilot study, the conversion rate was comparable to previously reported. Retinal sensitivity and the presence of reticular pseudodrusen might worth to be studied in a larger cohort. Commercial Relationships: Elizabeth Pearce, None; Sobha Sivaprasad, Alimeria Sciences (C), Allergan (C), Bayer (C), Novartis (C); Victor Chong, Allergan (C), Bayer (C), Novartis (C), Quantel Medical (C) Program Number: 5154 Poster Board Number: C0218 Presentation Time: 3:45 PM–5:30 PM Comparing retinal sensitivity and SDOCT volumes in the AMD Phenotype and Genotype study Vincent Tai1, Monica B. Sevilla1, Traci E. Clemons2, Emily Y. Chew3, Frederick L. Ferris3, Sina Farsiu1, Cynthia A. Toth1. 1Ophthalmology, Duke University Medical Center, Durham, NC; 2Statistics, EMMES Corporation, Rockville, MD; 3Epidemiology and Clinical Applications, National Eye Institute, Bethesda, MD. Purpose: To study how drusen volume and retinal pigment epithelium (RPE) abnormal thinning (RAT) on spectral domain optical coherence tomography (SDOCT) are associated with visual function as assessed by best corrected visual acuity (BCVA) and microperimetry retinal sensitivity (MPRS). Methods: SDOCT results were compared with BCVA and macular pattern of microperimetry (CenterVue, Inc, San Jose, CA) in patients with various degrees of age-related macular degeneration (AMD). After semi-automated SDOCT segmentation of the RPE-drusen complex (RPEDC), macular volumes for drusen and RAT were calculated from a SDOCT database of 115 healthy aged eyes1. The area of evaluation was a 2.5mm radius centered on the fovea. For general macular MPRS analysis, a median sensitivity score (MSS) was calculated for all 45 eyes of 42 subjects with MPRS. In a subgroup of 18 eyes (18 subjects) that each had an identical MPRS grid pattern, MPRS from each pattern site was paired with SDOCT volume within a 0.5o radius centered at that site. Volumes were correlated with BCVA by Spearman rank correlation (ρ), and with MPRS score by Kruskal-Wallis analysis. 1. Farsiu S et al. Quantitative Classification of Eyes with & without Intermediate AMD Using OCT. Ophthalmol. 2014 Results: In 53 eyes without neovascular AMD or geographic atrophy, with a BCVA score and with good quality SDOCT volume, mean (±standard deviation) drusen volume was 0.020±0.030 mm3, and the mean RAT volume was 3.48×10-5±7.8×10-5 mm3. Mean BCVA score was 74.34±14.65. BCVA was worse with an increase in drusen volume (p=0.0001). For the 45 eyes with MAIA microperimetry, the mean MSS was 25.76±2.72 dB. Mean drusen volume was 0.021±0.036 mm3 and the mean RAT volume was 4.93×10-5±11.29×10-5 mm3. MSS did not correlate with overall drusen volume (p=0.45). In the sub-group of 18 eyes that used the identical MAIA grid pattern and that could be directly mapped and compared with OCT results, better localized MPRS scores correlated with decreasing drusen volume (p<0.0001) at the MPRS sites. Conclusions: SDOCT measurements of RPEDC and drusen volumes correlated with BCVA. In addition, localized MPRS correlates with the underlying SDOCT drusen volume, while this association is lost when retinal sensitivity across all of the macular sites is compared to general macular volumes. Commercial Relationships: Vincent Tai, None; Monica B. Sevilla, None; Traci E. Clemons, None; Emily Y. Chew, None; Frederick L. Ferris, None; Sina Farsiu, Duke University (P); Cynthia A. Toth, Alcon (F), Bioptigen (F), Genetech (F), NIH 1R01EY023039 (F) Clinical Trial: NCT01778491 Program Number: 5155 Poster Board Number: C0219 Presentation Time: 3:45 PM–5:30 PM Widefield Choroidal Thickness Maps in Dry Age Related Macular Degeneration with and without Reticular Pseudodrusen Giovanni Gregori, Andrew D. Legarreta, Karen Schaal, John E. Legarreta, Brian E. Goldhagen, Emeline R. Ramenaden, Zohar Yehoshua, Philip J. Rosenfeld. Ophthalmology, Bascom Palmer Eye Institute, Miami, FL. Purpose: To obtain and compare choroidal thickness maps of eyes with dry Age Related Macular Degeneration (AMD) over extended retinal regions. Methods: Twenty patients with a diagnosis of dry AMD were imaged using a prototype swept source OCT system from Carl Zeiss Meditec (Dublin, CA). The OCT system had a central wavelength of 1050nm and supported acquisition of 12mmx12mmx3mm raster scans. Each scan used a 512x512 homogeneous sampling scheme. A novel algorithm was developed to segment the anterior a posterior boundaries of the choroid over the full OCT datasets. ©2015, 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 2015 Annual Meeting Abstracts Results: Pointwise thickness maps of the choroid were obtained over the scan area using the automated algorithm. Using the associated OCT fundus images, as well as other en face OCT images, choroidal thickness information can be correlated to retinal landmarks. In particular we examined the relationship between the choroidal thickness and features like geographic atrophy, reticular pseudodrusen, and drusen. The choroid is in general thinner in eyes with reticular pseudodrusen than in eyes without reticular pdeudodrusen, but the precise patterns of choroidal thickness vary significantly across different eyes. Conclusions: There can be considerable variability in choroidal thickness at different retinal locations, in eyes with dry AMD. Also the relationship between local choroidal thickness and other features of dry AMD can assume different patterns in different eyes. The detailed quantitative descriptions of choroidal thickness over extended regions have the potential to improve our understanding of retinal pathology. Commercial Relationships: Giovanni Gregori, Carl Zeiss Meditec (F); Andrew D. Legarreta, None; Karen Schaal, None; John E. Legarreta, None; Brian E. Goldhagen, None; Emeline R. Ramenaden, None; Zohar Yehoshua, None; Philip J. Rosenfeld, Carl Zeiss Meditec (F) Support: NIH Center Core Grant P30EY014801, RPB Unrestricted Award, DOD- Grant# W81XWH-13-1-0048 Program Number: 5156 Poster Board Number: C0220 Presentation Time: 3:45 PM–5:30 PM Automated Segmentation of Reticular Pseudodrusen and Regular Drusen in Eyes with Non-neovascular AMD Zhihong Hu1, Jun Xiao1, 2, Kiran Nandanan1, Srinivas R. Sadda1. 1 Doheny Eye Institute, UCLA, Los Angeles, CA; 2The Second Hospital of Jilin University, Jilin, China. Purpose: To quantify regular drusen (RD) and reticular pseudodrusen (RPD) in optical coherence tomography (OCT) images from eyes with non-neovascular age-related macular degeneration (AMD) using an automated analysis algorithm. Methods: In this IRB-approved study, three groups of subjects underwent spectral domain (SD) OCT imaging in one eye using a macular cube protocol (Spectralis OCT). Group 1 consisted of 17 healthy subjects (referred as “Normal”); group 2 had 6 AMD subjects with only RD (referred as “Non-reticular”); and group 3 included 16 AMD subjects with both RD and RPD (referred as “Reticular”). A graph-based approach was applied to automatically segment 5 sub-retinal boundaries: ellipsoid zone (EZ) outer, interdigitation zone (IZ), retinal pigment epithelium (RPE) inner, RPE outer, and choroid inner (CI). The segmentation was manually corrected as needed by a certified OCT grader. Using these segmented boundaries, three layers were generated for quantitative thickness analysis: (1) RPD layer bounded by IZ and RPE inner, (2) RD layer bounded by RPE outer and CI, and (3) RPE-drusen complex (RPEDC) bounded by EZ and CI. Thicknesses of these layers were computed in a 4mm*4mm grid (including 4 sub-quadrants,) as well as a circular grid (r = 1.44 mm) centered on the fovea. Values were compared among the 3 groups using t-test. Results: Fig. 1 shows the mean regional thicknesses in RPD and RD layers and Fig. 2 shows these values in RPEDC layer. The mean thickness of RPD layer in 4mm*4mm grid was significantly greater (p < 0.01) than in the circular grid (r = 1.44mm) with the highest mean thickness in the superior-nasal quadrant. Conversely, the mean thicknesses of RD and RPEDC layers in 4mm*4mm grid was significantly smaller than that in the circular region for both “Nonreticular” (p < 0.01) and “Reticular” groups (p < 0.01). When RPD and RD were both present, the mean RD layer thickness was greater than that in the “Non-reticular” group in all the regions, but not statistically significant. Conclusions: Automated segmentation analysis suggests that RPD are most extensive/thicker in the superior-nasal quadrant of the macula whereas RD are thicker centrally, highlighting differences in regional distribution of these lesions. The combined RPEDC layer shows a similar regional distribution to RD suggesting that this measure is more driven by the presence of RD. Fig.1 Fig. 2 Commercial Relationships: Zhihong Hu, None; Jun Xiao, None; Kiran Nandanan, None; Srinivas R. Sadda, Allergan (C), Carl Zeiss Meditec (C), Carl Zeiss Meditec (F), Optos (C), Optos (F), Optovue, Inc. (F), Regeneron (C) Support: This work was supported in part by the Beckman Macular Degeneration Research Center and a Research to Prevent Blindness Physician Scientist Award. ©2015, 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 2015 Annual Meeting Abstracts Program Number: 5157 Poster Board Number: C0221 Presentation Time: 3:45 PM–5:30 PM Drusen morphology changes in nonexudative age-related degeneration using spectral domain optical coherence tomography after oral antioxidants supplementation: one-year results. Xavier Valldeperas1, Pau Romera1, Rafael Abos-Herrandiz2, Antoni Sabala1. 1Ophthalmology, Hospital Universitari Germans Trias, Badalona, Spain; 2Primary Health Care Division. Institut Català de la Salut. Barcelona (Spain), Barcelona, Spain. Purpose: To determine drusen morphology (volume and area) changes in nonexudative age-related macular degeneration (AMD) after one year of oral supplementation with AREDS-like formulation. Methods: Patients with AREDS category 2 and 3 AMD were prospectively enrolled in this study, and were randomized to receive daily oral supplementation with lutein (12mg) + zeaxanthin (2mg) + astaxanthin (8mg) + omega-3 fatty acids (docosahexaenoic acid [DHA] 540mg + eicosapentaenoic acid [EPA] 360mg) + vitamin C (40mg) + vitamin E (20mg) + zinc (16mg) + copper (2mg), or observation during one year. ETDRS vision, biomicroscopy, intraocular pressure (IOP), color fundus photography and automatic measurement of drusen with Topcon 3D-OCT 2000 (Topcon, Tokyo, Japan) using the 6 x 6 mm 3D cube scan protocol, were performed in all patients, at baseline and 12 months after. Automated delineation of macular drusen was modified by the investigators when evident segmentation errors occurred. Results: Seventy eyes of 35 patients were included: 18 patients received oral supplementation and the rest were observed. Visual acuity and IOP did not significantly change in either group after 12 months. In the treatment group, drusen count did not significantly change (p=0.715) and increase in drusen area and volume was not statistically significant (p=0.304 and p=0.085, respectively). In the observed group, drusen count significantly increased after 12 months from 13.9±14.1 to 15.5±15.1 (p=0.045), as well as drusen volume (p=0.038). Drusen area in this group remained unchanged during the study period. Conclusions: Patients with oral supplementation with the AREDSlike formulation show a tendency to slow drusen increase, measured with SD-OCT. The clinical relevance of these findings is still unclear and need further comparison with natural history in larger population and longer duration. Commercial Relationships: Xavier Valldeperas, None; Pau Romera, None; Rafael Abos-Herrandiz, None; Antoni Sabala, None Clinical Trial: AC-11-112 (NCT02264938) Program Number: 5158 Poster Board Number: C0222 Presentation Time: 3:45 PM–5:30 PM Analysis of choroidal maps and fundus autofluorescence correlates in non-exudative age-related macular degeneration using swept source optical coherence tomography Vittorio Capuano, Alexandra Miere, Oudy Semoun, Pietro Frascio, Giuseppe Querques, Eric H. Souied. Department of Ophthalmology, Centre hospitalier Intercommunal de Crïteil, Creteil, France. Purpose: To analyze choroidal thickness maps (CMs) and fundus autofluorescence (FAF) in patients with non-exudative age-related macular degeneration (AMD) using swept source optical coherence tomography (Swept-OCT). Methods: CMs imaging were obtained using Swept-OCT (Topcon Medical Systems, Oakland, NJ). A standardized imaging protocol was performed in all patients: radial diameter 9.0 mm scans through the foveal center with automated ETDRS choroidal thickness map (9 sectors). FAF images obtained using Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany) were overlay with Swept-OCT. Eyes were divided in: Group 1, early non-exudative AMD with at least one large soft drusen (>125 mm); Group 2, early non-exudative AMD with intermediate distribution of reticular pseudodrusen; Group 3, late non-exudative AMD / Geographic atrophy (GA); and Group 4, control subjects with no ocular diseases The mean thickness was automatically measured in the “center” sector within 1 mm from the center of the fovea, in 4 “inner ring” sectors (superior, inferior, nasal, and temporal; 1 to 2 mm from the center of the fovea), and in 4 “outer ring” sectors (superior, inferior, temporal, and nasal; 2 to 3 mm from the center of the fovea). Results: A total of 72 eyes of 72 consecutive patients with nonexudative AMD (56 females; mean age 79.1±8.1 years) were included in the analysis. The mean whole choroidal thickness were 157 ± 55 mm, 126 ± 52 mm, 114 ± 38 mm et 18 8± 74 mm (in group 1,2,3 and 4 respectively). The CMs were significantly reduced in Group 2, and 3 compared with group 1 and 4 (p <0.05). A similar reduction in CMs were found in Group 3, compared with group 2. (p 0.001). On the basis of FAF features in Group 3, a total of 70 ETDRS sectors were categorized as hypo-FAF (sectors characterized by > 50% absence of FAF), and 83 ETDRS sectors were categorized as hyper/iso-FAF (sectors characterized by ≤ 50% absence of FAF). No statistical differences in CMs were found among ETDRS sectors with >50% and <50% atrophic (HypoFAF) or preserved retina (Hyper/ IsoFAF) in GA group (p 0.07). Conclusions: CMs reveal a thinner choroid in eyes with GA and Pseudodrusen AMD patients compared with drusen and control subjects on swept OCT. CM in the different ETDRS sectors was not associated with FAF features in eyes with GA. Commercial Relationships: Vittorio Capuano, None; Alexandra Miere, None; Oudy Semoun, None; Pietro Frascio, None; Giuseppe Querques, None; Eric H. Souied, None Program Number: 5159 Poster Board Number: C0223 Presentation Time: 3:45 PM–5:30 PM Microperimetry and Multifocal Electroretinography in Reticular Pseudodrusen and Intermediate Age-Related Macular Degeneration Chi D. Luu1, 2, Zhichao Wu1, Lauren N. Ayton1, 2, Galina Makeyeva1, Robyn H. Guymer1, 2. 1Centre for Eye Research Australia, East Melbourne, VIC, Australia; 2Department of Ophthalmology, University of Melbourne, Melbourne, VIC, Australia. Purpose: Reticular pseudodrusen (RPD) has been increasingly recognized as a risk factor for the development of advanced agerelated macular degeneration (AMD). Although RPD are often present in eyes with features of the early stages of AMD, studies of the impact of RPD on retinal function to date have only been performed in eyes with RPD only. Thus, the purpose of this study was to investigate the influence of RPD on retinal function in eyes with intermediate AMD using microperimetry and multifocal electroretinography (mfERG). Methods: In this prospective cross-sectional study, mfERG, microperimetry, colour fundus photography, near-infrared reflectance (NIR) imaging and spectral-domain optical coherence tomography (SD-OCT) scans were performed in participants with bilateral intermediate AMD (drusen >125 μm). The presence of RPD was defined as groups of hyporeflective lesions against a mildly hyperreflective background on NIR, with corresponding hyperreflective signals above the RPE band on SD-OCT. The presence and extent of pigmentary changes and RPD within the central 3 mm diameter was examined using an Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Drusen volume within the ©2015, 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 2015 Annual Meeting Abstracts central 3 mm diameter was also determined. The influence of these pathological features on microperimetry and mfERG within the same region were examined. Results: A total of 120 eyes of 60 participants (mean age was 70.5 ± 7.2 years, range 51 to 84) were included in this study. There were 39 eyes with RPD and 81 eyes without RPD. Microperimetric sensitivity was not significantly associated with the presence and extent of RPD (β Coefficient = -0.18, p = 0.068), but with drusen volume (β = -5.65, p < 0.001) and extent of pigmentary changes (β = -0.48, p < 0.001). The mfERG implicit time was independently and significantly associated with the presence and extent of RPD (β = 0.38, p = 0.001), drusen volume (β = 3.23, P = 0.023) and the extent of pigmentary changes (β = 0.55, p < 0.001). However, mfERG response amplitude was not significantly associated with the presence and extent of RPD (β = -0.75, p = 0.130). Conclusions: In eyes with intermediate AMD, the presence and extent of RPD had a significant impact on cone-mediated retinal function as measured by mfERG. Microperimetric sensitivity was influenced by AMD features but not by the presence or extent of RPD. Commercial Relationships: Chi D. Luu, None; Zhichao Wu, None; Lauren N. Ayton, None; Galina Makeyeva, None; Robyn H. Guymer, None Support: National Health and Medical Research Council (NH&MRC) Project Grant (#1027624), Macular Disease Foundation Australia (MDFA) Research Grant, Bupa Health Foundation (Australia) and the Menzies Foundation. Program Number: 5160 Poster Board Number: C0224 Presentation Time: 3:45 PM–5:30 PM Choroidal thickness in eyes with central geographic atrophy secondary to Stargardt disease and age-related macular degeneration Renata Portella Nunes1, 2, Potyra R. Rosa1, Raquel Goldhardt1, Mariana Rossi Thorell1, Giovanni Gregori1, William J. Feuer1, Byron L. Lam1, Giovanni Staurenghi3, Philip J. Rosenfeld1. 1Bascom Palmer Eye Institute, Florianopolis, Brazil; 2Ophthalmology and Visual Sciences department, Paulista School of Medicine, São Paulo, Brazil; 3 Deptartment of Clinical Science - Luigi Sacco, University of Milan, Milan, Italy. Purpose: Geographic atrophy (GA) in Stargardt disease (STGD) results from the abnormal accumulation of A2E in photoreceptors, which subsequently causes loss of the retinal pigment epithelium (RPE), photoreceptors, and choriocapillaris. In age-related macular degeneration (AMD), the primary cause of GA is not known. If the presence of GA affects the underlying choroidal thickness (CT), then we might expect eyes with similar amounts of GA, regardless of etiology, to have similar CT measurements. If there’s a difference in the CT measurements underlying GA in AMD and STGD, then this difference might reflect a difference in the underlying pathophysiology leading to GA. To determine if different diseases causing GA have a similar or different affect on subfoveal CT measurements, we compared measurements from eyes with similar areas of GA secondary to AMD and STGD. Methods: Patients with the diagnosis of central GA secondary to STGD and AMD were enrolled in a prospective spectral domain optical coherence tomography imaging study. Subfoveal CT was measured from the central B-scan using an enhanced depth imaging protocol. The area of GA was measured using fundus autofluorescence imaging. Two independent graders measured the subfoveal CT and areas of GA. AMD eyes were divided into those with and without reticular pseudodrusen. CT from all group were compared. Results: A total of 22 eyes of 22 patients were included in the STGD group and in the AMD group, and these eyes were matched with respect to the area of GA. The mean age of the STGD patients was 48.9 (SD 17.1) and 81.8 (SD 6.2) for the AMD patients. Mean area measurements of GA for the STGD and AMD groups were 5.4mm2 (SD 4.1) and 5.1 mm2 (SD 4.0), respectively (P=0.83). After adjusting for age, eyes with STGD had a mean CT measurement greater than the AMD eyes (336.1 vs.198.1mm respectively; p=0.039). But this difference seemed to be driven by AMD eyes with reticular pseudodrusen (RPD) and a single Stargardt case with a very thick choroid. Eyes with RPD had statistically thinner choroids when compared to all other groups. Conclusions: No clinically meaningful difference was observed between the CT in normal eyes and eyes with STGD and AMD without RPD containing similar areas of GA. However, eyes with GA and RPD had significantly thinner subfoveal CT. Commercial Relationships: Renata Portella Nunes, None; Potyra R. Rosa, None; Raquel Goldhardt, None; Mariana Rossi Thorell, None; Giovanni Gregori, Carl Zeiss (F), Carl Zeiss (P); William J. Feuer, None; Byron L. Lam, None; Giovanni Staurenghi, HEIDELBERG ENGINEERING (C), OPTOS, INC. (C), OPTOVUE (S), ZEISS (C); Philip J. Rosenfeld, Alexion Pharmaceuticals (F), Carl Zeiss (F) Program Number: 5161 Poster Board Number: C0225 Presentation Time: 3:45 PM–5:30 PM Stabilization of Visual Acuity with Bilateral Macular Drusen a 10 year prospective study of uniocular peripheral retina argon laser therapy Danny H.-Kauffmann Jokl1, Sankha Amarakoon2, Celine Saade3, Robert Post3, Ansh Johri3, Sander Kesting2, Suzanne Yzer2, Theodore Smith3, Rando Allikmets1, Jan C. van Meurs2. 1Ophthalmology, Columbia University, Bronxville, NY; 2Rotterdam Eye Hospital, Rotterdam, Netherlands; 3New York University, New York, NY. Purpose: Anti VEGF therapy can reduce the neovascular complications of AMD, only AREDS supplements can decrease such progression over a similar time period. Natural history of drusen shows 71% with bilateral medium soft drusen progressing to large drusen and, in 14%, to AMD over 10 years, though, if AMD did not develop, with preservation of good vision. (Chew JAMA Ophthalmol 2014;132:272). Following a serendipitous observation that a retinal laser treatment for an incidental retinal tear in an eye with medium soft drusen, with AMD in the other eye, was followed by diminution of drusen and stabilization of vision over 10 years, we investigated the effect of such treatment on patients with bilateral soft drusen. Methods: Fourteen patients from the Rotterdam Eye Hospital with bilateral macular drusen and visual acuity in each eye from 20/2020/40 consented to a single uniform treatment of 200 argon laser applications (200 microns, 200 mw each) to the anterior superior temporal retina. Eleven subjects (5 M, 6F; ages 58-83) were followed for 10 years (3 subjects died during this period) with clinical examinations and digitalized fundus photos. Drusen areas in each eye were calculated and DNA of all subjects was analyzed for selected AMD-associated SNPs in ARMS2 and CFH, the two major genetic loci for AMD. The masked clinical and genetic data were then correlated. Results: Uniocular visual loss (≤20/100) to AMD in the 10 year follow up period occurred in three (3/11) patients, in each case in the non-treated eye. Bilateral visual loss to AMD occurred in one patient. Two patients with high genetic risk showed a decrease in the drusen area (Fig.1). The same 2 out of eleven (2/11) patients with high genetic risk did not progress to late AMD in 10 years (Fig. 2). There ©2015, 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 2015 Annual Meeting Abstracts was no association between the progression of drusen area and the visual outcome (Fig. 3). Conclusions: Due to the small cohort size, this 10 year prospective pilot study can only suggest that a focal peripheral laser treatment in one eye may provide a mechanism, e.g., an inflammatory response that preserves binocular vision in some subjects with bilateral macular drusen relative to the natural history and does not correlate with the extent of macular soft drusen. A much larger cohort study would be necessary to draw conclusions as to the genetic correlations, if any, with this laser mode of therapy. Results: In a cohort of 30 male and 17 female subjects with CAD, the mean age was 63.5 years (range 44-75). 9 subjects (19.15%) had evidence of SDD on EDI SD-OCT, significantly greater than the known population prevalence by CP of 0.7% (P=<0.001). Allowing for the decreased sensitivity of CP (about 35%) for RMD compared to EDI SD-OCT, significance is still maintained (P=<0.001). Examples of EDI-OCT imaging from a subject with CAD, and a normal control, are demonstrated in Figure 1. Conclusions: While previous studies have shown an overlap between AMD and CAD risk factors, the choroidal alterations of RMD are more strongly indicative of a vascular etiology and thus a potential link to CAD. Our results clearly demonstrate an increased prevalence of SDD among our CAD sample when compared to the prevalence in the general population established by the BDES. These results suggest that RMD and CAD may share a common pathophysiology. Commercial Relationships: Danny H.-Kauffmann Jokl, None; Sankha Amarakoon, None; Celine Saade, None; Robert Post, None; Ansh Johri, None; Sander Kesting, None; Suzanne Yzer, None; Theodore Smith, None; Rando Allikmets, None; Jan C. van Meurs, None Clinical Trial: AAAD5359 Program Number: 5162 Poster Board Number: C0226 Presentation Time: 3:45 PM–5:30 PM The Association Between Reticular Macular Disease (RMD) and Coronary Artery Disease (CAD) Patrick A. Kaszubski, Colleen Cunningham, Vivek Kumar, Camellia Nabati, Rachel M. Cymerman, Theodore Smith. Ophthalmology, New York University School of Medicine, New York, NY. Purpose: Reticular Macular Disease (RMD), a leading risk factor for disease progression in Age-Related Macular Degeneration (AMD), demonstrates both subretinal drusenoid deposits (SDD) and choroidal alterations (vascular involvement). The goal of this study was to compare the prevalence of SDD in subjects aged 30-75 years who have documented cardiovascular disease, specifically CAD, to the established prevalence of RMD by color fundus photography (CP) in the general population (Beaver Dam Eye Study (BDES)) [Klein, R. Am J Ophthalmology 2008]. CAD is a condition that can strike in middle age, while AMD affects the elderly. A middle-aged CAD cohort allows a search for early SDD that could link CAD and AMD/ RMD. Methods: 47 consecutive subjects with documented CAD (ages 40 to 75 years), were enrolled from a cardiology clinic at a large city public hospital. Before undergoing enhanced depth imaging spectral domain optical coherence tomography (EDI SD-OCT) imaging, all subjects completed a questionnaire regarding medical and ocular history. A retina specialist evaluated the images for evidence of SDD and other retinal findings. Chi-square goodness of fit was used for statistical analysis. Figure 1: Top: Normal 75 year old female. Bottom: 59 year old male with CAD. The subretinal space is marked by yellow asterisks. Note SDD in bottom panel. Commercial Relationships: Patrick A. Kaszubski, None; Colleen Cunningham, None; Vivek Kumar, None; Camellia Nabati, None; Rachel M. Cymerman, None; Theodore Smith, Advanced Cell Technologies (C) Support: This work was supported by an individual investigator research award from the Foundation Fighting Blindness (RTS), National Institutes of Health/National Eye Institute grant R01 EY015520 (RTS), and unrestricted funds from Research to Prevent Blindness. ©2015, 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 2015 Annual Meeting Abstracts Program Number: 5163 Poster Board Number: C0227 Presentation Time: 3:45 PM–5:30 PM Retinal Layer Thickness in Drusen and Drusen-Free Retinal Areas in Age-Related Macular Degeneration Lisa Nivison-Smith1, 4, James Rogala2, Barbara Zangerl4, 1, Nagi Assaad3, 4, Erica L. Fletcher5, Michael Kalloniatis4, 1. 1School of Optometry and Vision Science, University of New South Wales, Kensington, NSW, Australia; 2Western University, Pomona, CA; 3 Ophthalmology Department, Prince of Wales Hospital, Randwick, NSW, Australia; 4Centre For Eye Health, University of New South Wales, Kensington, NSW, Australia; 5Department of Anatomy and Neuroscience, University of Melbourne, Parkville, NSW, Australia. Purpose: Drusen are a hallmark of age-related macular degeneration (AMD). However how drusen affect retinal structure at and beyond their borders is still unclear. This study examines changes in retinal thickness which occurs above drusen and compares this to drusenfree areas in the same patient and a normative population. Methods: Spectral domain optical coherence tomography scans through drusen in early to intermediate AMD patients (n=122) or patients with no ocular disease (n=30) seen at the Centre for Eye Health were reviewed and the thickness of individual retinal layers was measured above the druse and in a drusen-free area, 150mm from the drusen edge. Patient written consent was obtained in accordance with the Declaration of Helsinki and approved by the Biomedical Human Research Ethics Advisory Panel of the University of New South Wales. Results: Retinal thickness above drusen was significantly less (p < 0.001) than drusen-free areas (16±1%). Thinning occurred almost exclusively in the outer retinal layers with almost no thinning in the inner retina for single isolated drusen. Inner retinal thickness was however reduced over large confluent drusen (5±1%). Interestingly, the overall retinal thickness of both drusen and drusen-free areas was significantly less to matching eccentricities in the normal population. Conclusions: Drusen caused retinal thinning, mostly by affecting the outer retina. Drusen-free areas in AMD patients were also thinned suggesting the effects of drusen extend beyond the lesion borders. This has implications in the use of presumably “normal” areas of retina in AMD patients for disease assessment. Commercial Relationships: Lisa Nivison-Smith, None; James Rogala, None; Barbara Zangerl, None; Nagi Assaad, None; Erica L. Fletcher, None; Michael Kalloniatis, None Support: NHMRC Grant 1033224, UNSW ECR Grant PS35430 Program Number: 5164 Poster Board Number: C0228 Presentation Time: 3:45 PM–5:30 PM Thickness map of outer retinal layer and choroid in reticular pseudodrusen Reiko Izumi, Ichiro Maruko, Machiko Kimura, Hideki Koizumi, Takahiko Izumi, Tomohiro Iida. Tokyo Women’s Medical University, Tokyo, Japan. Purpose: Although reticular pseudodrusen (RPD) are often first observed in the upper part of the macula, the reason remains unclear. Our purpose in the current study is to evaluate the relationship between the outer retinal layer and the choroid using divided thickness map in Japanese patients with RPD. Methods: Eighteen eyes of 14 patients (average 83 years old) in RPD, determined by color fundus photograph, were included. The eyes with exudative age-related macular degeneration were excluded because of indetermination. 3D-scan was taken using swept source optical coherence tomography (DRI-OCT, Topcon, Japan). Segmentation lines of outer retinal layer (superior border of outer plexiform layer to retinal pigment epithelium; RPE) and choroidal layer (RPE to chorioscleral interface; CSI) were drawn manually within 6mm at the macula. All areas were divided by 9 sectors according to ETDRS grid map style. The eyes in age-matched patients (18 eyes of 17 patients) without retinal and choroidal disorder were also examined as control. Results: Mean outer retinal layer thickness within ETDRS map was significantly thinner in RPD than control (133±12mm vs 143±8mm, P<0.01). Mean choroidal thickness within ETDRS map was also significantly thinner in RPD than control (125±39mm vs 216±77mm, P<0.01). The thicknesses of outer retinal layer and choroid in all areas of ETDRS map were correlated with each other (r=0.22, P<0.01). Especially, the significant correlation was reached at upper areas (inner and outer quadrant) of ETDRS map (r=0.37, P=0.03). Conclusions: Thinning of not only choroid but also outer retinal layer indicates the impairing of the photoreceptors in RPD. The correlations of thicknesses between outer retinal layer and choroid at upper quadrant area may elucidate the origin of RPD development. Commercial Relationships: Reiko Izumi, None; Ichiro Maruko, None; Machiko Kimura, None; Hideki Koizumi, None; Takahiko Izumi, None; Tomohiro Iida, None Program Number: 5165 Poster Board Number: C0229 Presentation Time: 3:45 PM–5:30 PM Change in Outer Retinal Layer Thickness in Subjects with Reticular Pseudodrusen Muneeswar Gupta Nittala1, Yan Luo1, Zhihong Hu1, Ruth E. Hogg2, Rufino Silva3, Giovanni Staurenghi4, Usha Chakravarthy2, Srinivas R. Sadda1, 5. 1Ophthalmology, Doheny Eye Institute, Los Angeles, CA; 2Center for Experimental Medicine, Queen’s University Belfast, Belfast, United Kingdom; 3Ophthalmology Unit, Centro Hospitalare Universitário Coimbra, Coimbra, Portugal; 4Department of Clinical Science Luigi Sacco’ University of Milan, Milan, Italy; 5Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA. Purpose: To evaluate the thickness of the outer retinal layers in subjects with reticular pseudodrusen. Methods: Thirty four eyes of 34 subjects with reticular pseudodrusen (RPD) and 39 eyes of 39 subjects with early non-neovascular agerelated macular degeneration without RPD were enrolled in this prospective study at three clinical sites (Belfast, Coimbra, Milan). These subjects been fallowed up for one year. Spectral domain optical coherence tomography (SD-OCT) volume scans was collected in 3 clinical sites from Belfast, Coimbra and Milan using Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg Germany). Detailed manual segmentation of outer retinal layers was performed using custom designed and validated grading software 3D OCTOR. Thickness measurements were derived for retina, photoreceptor outer segments, RPE+Drusen complex and Choroid layers in both the study cohorts. Results: was no significant difference in retinal thickness and photoreceptor outer segments thickness between study groups. There was significant (p=0.004) difference in RPE+Drusen complex layer thickness in RPD subjects (30.6 ± 3.69 (±SD) mm) compared to those without RPD (28.21 ± 2.35 mm). In contrast, the choroid was significantly thinner (p = 0.04) in RPD subjects with a thickness of149.78 ± 33.56 compared with 162.42 ± 36.24 mm in subjects without RPD. Longitudinal analysis, revealed a small but significant (p = 0.04) thinning (25.53 ± 3.71 mm at baseline vs 24.03 ± 4.32 mm at month 12) in RPD subjects, compared to no significant change over time in subjects with no RPD. Conclusions: The RPE+ Drusen complex layer is significantly thicker and the choroid is significantly thinner in subjects with reticular pseudodrusen. The photoreceptor outer segments appear to thin over time in eyes with RPD. ©2015, 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 2015 Annual Meeting Abstracts Commercial Relationships: Muneeswar Gupta Nittala, None; Yan Luo, None; Zhihong Hu, None; Ruth E. Hogg, None; Rufino Silva, Alcon, Alimera, Allergan, Bayer, Novartis, THEA (C); Giovanni Staurenghi, None; Usha Chakravarthy, None; Srinivas R. Sadda, Carl Zeiss Meditec, Optos, Allergan (R), Carl Zeiss Meditec, Optos, Allergan, Genentech (F), Carl Zeiss Meditec, Optos, Allergan, Genentech, Alcon, Novartis, Roche (C) Clinical Trial: NA Program Number: 5166 Poster Board Number: C0230 Presentation Time: 3:45 PM–5:30 PM Peripapillary choroidal thickness in early age related macular degeneration patients with reticular pseudodrusen Jong-Hyun Oh1, Jaeryung Oh2, Cheolmin Yun2, Young Ho Kim2, Seong-Woo Kim2, Kuhl Huh2. 1Ophthalmology, Dongguk University Ilsan Hospital, Goyang, Korea (the Republic of); 2Ophthalmology, Korea University College of Medicine, Seoul, Korea (the Republic of). Purpose: To investigate peripapillary and macular choroidal thickness (CT) of patients with early age-related macular degeneration (AMD) with or without reticular pseudodrusens (RPD). Methods: We investigated the medical records of 89 eyes of 89 patients with early AMD. Eyes with early AMD were categorized into three groups according to the extent of RPD; no RPD, localized RPD, and diffuse RPD. Peripapillary and macular CT were measured with images obtained by spectral domain optical coherence tomography (SD-OCT). CT in peripapillary and macular area was compared among groups. Results: Both RPD groups were older and female-predominant than non-RPD group (P = 0.007 and P = 0.030, respectively). Macular and peripapillary CT were different among three groups (all, P < 0.001) and both RPD group showed thinner choroid at all areas than those of non-RPD group after adjustment of age and sex (all, P ≤ 0.016). Temporal peripapillary and nasal macular CT at 500 mm and 1500 mm from the fovea in eyes with diffuse RPD were significantly thinner than those in eyes with localized RPD (P = 0.008, P < 0.001 and P = 0.018 respectively). Conclusions: In addition to macular area, peripapillary CT including outside of macula was thinner in eyes with RPD than those without RPD. The papillomacular choroid showed significant changes according to the distribution type of RPD. This result may suggest that choroidal thinning is associated with RPD progression. Commercial Relationships: Jong-Hyun Oh, None; Jaeryung Oh, None; Cheolmin Yun, None; Young Ho Kim, None; Seong-Woo Kim, None; Kuhl Huh, None Support: Korean Ministry of Environment (2012001350010) ©2015, 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].