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Zanzottera, Emma C. MD; Ach, Thomas MD; Huisingh, Carrie MPH; Messinger, Jeffrey D. DC; Freund, K. Bailey MD; Curcio, Christine A. PhD

doi: 10.1097/IAE.0000000000001330
Original Study

Purpose: To enable future studies of retinal pigment epithelium (RPE) fate in the macular atrophy occurring in eyes with neovascular age-related macular degeneration (nvAMD), the authors determined how RPE morphology changes across the transition from health to atrophy in donor eyes with nvAMD.

Method: In RPE–Bruch membrane flat mounts of 5 nvAMD eyes, the terminations of organized RPE cytoskeleton and autofluorescent material were compared. In high-resolution histologic sections of 27 nvAMD eyes, RPE phenotypes were assessed at ±500 μm and ±100 μm from the descent of the external limiting membrane (ELM) toward the Bruch membrane. Thicknesses of RPE, basal laminar deposit (BLamD), and RPE + BLamD were determined. Shapes of the ELM descent were recorded.

Results: Approaching the ELM descent, the percentage of different RPE phenotypes and the thickness of RPE, BLamD, and RPE + BLamD each stayed roughly constant. Compared with a separately described cohort of eyes with geographic atrophy, eyes with nvAMD were more likely to have RPE dysmorphia that did not worsen toward the atrophy border, thinner BLamD overall (3.25 ± 3.46 μm vs. 7.99 ± 7.49 μm for geographic atrophy), and a higher proportion of oblique ELM descents (47.9 vs. 31.9%).

Conclusion: The distribution of RPE phenotypes at the transition to macular atrophy in eyes with nvAMD differs from that in primary geographic atrophy, likely reflecting greater photoreceptor loss and the effects of exudation in nvAMD. This distribution, the shape of ELM descents, and thickness profiles may be useful metrics in clinical studies of macular atrophy using optical coherence tomography and fundus autofluorescence.

Morphologic phenotypes of the retinal pigment epithelium distribute across the transition to atrophy in neovascular age-related macular degeneration in a manner different from primary geographic atrophy, as described separately. Thickness of retinal pigment epithelium–basal laminar deposit may be useful as a metric to distinguish macular atrophy from geographic atrophy by optical coherence tomography.

*Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama;

Department of Clinical Science ‘‘Luigi Sacco,’’ Eye Clinic, Sacco Hospital, University of Milan, Milan, Italy;

Department of Ophthalmology, University Hospital Würzburg, Würzburg, Germany;

§Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama;

Vitreous Retina Macula Consultants of New York, New York, New York; and

**Department of Ophthalmology, New York University School of Medicine, New York, New York.

Reprint requests: Christine A. Curcio, PhD, Department of Ophthalmology, EyeSight Foundation of Alabama Vision Research Laboratories, 1670 University Boulevard, Room 360, University of Alabama School of Medicine, Birmingham, AL 35294-0099; e-mail:

C. A. Curcio is supported by NEI EY06109, Macula Foundation, Inc., 2014 von Sallmann Prize and institutional support from the EyeSight Foundation of Alabama and Research to Prevent Blindness Inc. E. C. Zanzottera is supported by the University of Milan. T. Ach is supported by DFG (German Research Foundation) AC265/1-1, AC265/2-1. KBF is supported by the Macula Foundation, Inc. Acquisition of donor eyes was supported by International Retinal Research Foundation, National Eye Institute P30 EY003039, and the Arnold and Mabel Beckman Initiative for Macular Research. Creation of Project MACULA was additionally supported from the Edward N. and Della L. Thome Memorial Foundation.

K. B. Freund: Consultant for Heidelberg Engineering, Optos, Optovue, Genentech, and Bayer HealthCare. C. A. Curcio: Consultant for Genentech, Merck, Janssen Cell Therapy, Regeneron, and Ora.

E. C. Zanzottera, MD, and T. Ach, MD, are the cofirst authors.

© 2016 by Ophthalmic Communications Society, Inc.