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      Activated Retinal Pigment Epithelium, an Optical Coherence Tomography Biomarker for Progression in Age-Related Macular Degeneration

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          Abstract

          Purpose

          To summarize and contextualize recent histology and clinical imaging publications on retinal pigment epithelium (RPE) fate in advanced age-related macular degeneration (AMD); to support RPE activation and migration as important precursors to atrophy, manifest as intraretinal hyperreflective foci in spectral-domain optical coherence tomography (SDOCT).

          Methods

          The Project MACULA online resource for AMD histopathology was surveyed systematically to form a catalog of 15 phenotypes of RPE and RPE-derived cells and layer thicknesses in advanced disease. Phenotypes were also sought in correlations with clinical longitudinal eye-tracked SDOCT and with ex vivo imaging–histopathology correlations in geographic atrophy (GA) and pigment epithelium detachments (PED).

          Results

          The morphology catalog suggested two main pathways of RPE fate: basolateral shedding of intracellular organelles (apparent apoptosis in situ) and activation with anterior migration. Acquired vitelliform lesions may represent a third pathway. Migrated cells are packed with RPE organelles and confirmed as hyperreflective on SDOCT. RPE layer thickening due to cellular dysmorphia and thick basal laminar deposit is observed near the border of GA. Drusenoid PED show a life cycle of slow growth and rapid collapse preceded by RPE layer disruption and anterior migration.

          Conclusions

          RPE activation and migration comprise an important precursor to atrophy that can be observed at the cellular level in vivo via validated SDOCT. Collapse of large drusen and drusenoid PED appears to occur when RPE death and migration prevent continued production of druse components. Data implicate excessive diffusion distance from choriocapillaris in RPE death as well as support a potential benefit in targeting drusen in GA.

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          Most cited references113

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          Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies

          The Lancet, 385(9967), 509-516
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            Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: the IN•OCT consensus.

            To develop a consensus nomenclature for the classification of retinal and choroidal layers and bands visible on spectral-domain optical coherence tomography (SD-OCT) images of a normal eye.
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              Five-Year Outcomes with Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials.

              To describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD).
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                iovs
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                May 2017
                : 58
                : 6
                : BIO211-BIO226
                Affiliations
                [1 ]Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama, United States
                [2 ]Eye Clinic, Department of Clinical Science “Luigi Sacco,” Sacco Hospital, University of Milan, Milan, Italy
                [3 ]University Hospital Würzburg, Department of Ophthalmology, Würzburg, Germany
                [4 ]Center for Ophthalmology and Visual Sciences, Lions Eye Institute, University of Western Australia, Perth, Australia
                [5 ]Sir Charles Gairdner Hospital, Perth, Australia
                [6 ]Vitreous Retina Macula Consultants of New York, New York, New York, United States
                [7 ]LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Institute, New York, New York, United States
                [8 ]Department of Ophthalmology, New York University Langone School of Medicine, New York, New York, United States
                Author notes
                Correspondence: Christine A. Curcio, Department of Ophthalmology, EyeSight Foundation of Alabama Vision Research Laboratories, 1670 University Boulevard, Room 360, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0099, USA; curcio@ 123456uab.edu .
                Article
                iovs-58-06-26 IOVS-17-21872
                10.1167/iovs.17-21872
                5557213
                28785769
                6874b882-fe5e-49fd-88d6-d515f058e8e8
                Copyright 2017 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 15 March 2017
                : 4 June 2017
                Categories
                Special Issue

                retinal pigment epithelium,age-related macular degeneration,optical coherence tomography,drusen,hyperreflective foci,transdifferentiation,apoptosis,migration,mie scattering,electron microscopy,stereology

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