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      Subretinal Drusenoid Deposits and Photoreceptor Loss Detecting Global and Local Progression of Geographic Atrophy by SD-OCT Imaging

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          Abstract

          Purpose

          To investigate the impact of subretinal drusenoid deposits (SDD) and photoreceptor integrity on global and local geographic atrophy (GA) progression.

          Methods

          Eighty-three eyes of 49 patients, aged 50 years and older with GA secondary to age-related macular degeneration (AMD), were prospectively included in this study. Participants underwent spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging at baseline and after 12 months. The junctional zone and presence of SDD were delineated on SD-OCT and FAF images. Linear mixed models were calculated to investigate the association between GA progression and the junctional zone area, baseline GA area, age, global and local presence of SDD and unifocal versus multifocal lesions.

          Results

          The area of the junctional zone was significantly associated with the progression of GA, both globally and locally (all P < 0.001). SDD were associated with faster growth in the overall model ( P = 0.039), as well as in the superior-temporal ( P = 0.005) and temporal ( P = 0.002) sections. Faster progression was associated with GA baseline area ( P < 0.001). No difference was found between unifocal and multifocal lesions ( P > 0.05). Age did not have an effect on GA progression ( P > 0.05).

          Conclusions

          Photoreceptor integrity and SDD are useful for predicting global and local growth in GA. Investigation of the junctional zone is merited because this area is destined to become atrophic. Photoreceptor loss visible on SD-OCT might lead to new structural outcome measurements visible before irreversible loss of retinal pigment epithelium occurs.

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          Most cited references34

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          Subretinal drusenoid deposits in non-neovascular age-related macular degeneration: morphology, prevalence, topography, and biogenesis model.

          To characterize the morphology, prevalence, and topography of subretinal drusenoid deposits, a candidate histological correlate of reticular pseudodrusen, with reference to basal linear deposit (BlinD), a specific lesion of age-related macular degeneration, and to propose a biogenesis model for both lesion. Donor eyes with median death-to-preservation of 2:40 hours were postfixed in osmium tannic acid paraphenylenediamine and prepared for macula-wide high-resolution digital sections. Annotated thicknesses of 21 chorioretinal layers were determined at standard locations in sections through the fovea and the superior perifovea. In 22 eyes of 20 white donors (83.1 ± 7.7 years), SDD appeared as isolated or confluent drusenoid dollops punctuated by tufts of retinal pigment epithelium apical processes and associated with photoreceptor perturbation. Subretinal drusenoid deposits and BlinD were detected in 85 and 90% of non-neovascular age-related macular degeneration donors, respectively. Subretinal drusenoid deposit was thick (median, 9.4 μm) and more abundant in the perifovea than in the fovea (P < 0.0001). BlinD was thin (median, 2.1 μm) and more abundant in the fovea than in the perifovea (P < 0.0001). Subretinal drusenoid deposits and BlinD prevalence in age-related macular degeneration eyes are high. Subretinal drusenoid deposits organized morphology, topography, and impact on surrounding photoreceptors imply specific processes of biogenesis. Contrasting topographies of subretinal drusenoid deposits and BlinD suggest relationships with differentiable aspects of rod and cone physiology, respectively. A 2-lesion 2-compartment biogenesis model incorporating outer retinal lipid homeostasis is presented.
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            Reticular pseudodrusen are subretinal drusenoid deposits.

            To characterize reticular pseudodrusen, a potential risk factor for late age-related macular degeneration. Retrospective, observational case series. Fifty-eight eyes of 33 patients with pseudodrusen (20 female). Consecutive patients with reticular pseudodrusen, diagnosed by their typical appearance and distribution using ophthalmoscopy, the blue channel of color fundus photographs, and near infrared images. The patients were imaged by spectral domain optical coherence tomography (SD OCT), and correlations were made between the near infrared images and the SD OCT images. The SD OCT findings in patients with pseudodrusen were compared with previously reported histologic findings of subretinal drusenoid deposits. The histologic specimens were reevaluated with the additional knowledge of the clinical information. Spectral domain optical coherence tomography and histologic characteristics of pseudodrusen. The mean age of the 33 patients was 81.7 years. The correlating SD OCT scans showed collections of granular hyperreflective material above the retinal pigment epithelium (RPE), in the subretinal space located primarily between the RPE and the boundary between the inner and outer segments of the photoreceptors (IS/OS boundary). In a more advanced stage, this material formed small mounds that broke through the IS/OS boundary. There were no correlates to the deposits seen under the RPE or in the choroid. These findings were similar in character to previously reported histologic characterization of subretinal drusenoid deposits, which had identified the presence of membranous debris, unesterified cholesterol, and complement within the deposits. Pseudodrusen seen by clinical examination may be subretinal drusenoid deposits seen by histologic examination. This unexpected location suggests that potential pathophysiologic mechanisms on both sides of the RPE need to be taken into account in theories related to the development of age-related macular degeneration. Copyright (c) 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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              Age and disease-related structural changes in the retinal pigment epithelium

              As the retinal pigment epithelium (RPE) ages, a number of structural changes occur, including loss of melanin granules, increase in the density of residual bodies, accumulation of lipofuscin, accumulation of basal deposits on or within Bruch’s membrane, formation of drusen (between the basal lamina of the RPE and the inner collagenous layer of Bruch’s membrane), thickening of Bruch’s membrane, microvilli atrophy and disorganization of the basal infoldings. Although these changes are well known, the basic mechanisms involved in them are frequently poorly understood. These age-related changes progress slowly and vary in severity in different individuals. These changes are also found in age-related macular degeneration (AMD), a late onset disease that severely impacts the RPE, but they are much more pronounced than during normal aging. However, the changes in AMD lead to severe loss of vision. Given the many supporting functions which the RPE serves for the retina, it is important to decipher the age-related changes in this epithelium in order to understand age-related changes in vision.
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                05 June 2020
                June 2020
                : 61
                : 6
                : 11
                Affiliations
                [1 ]Christian Doppler Laboratory for Ophthalmic Image Analysis, Vienna Reading Center, Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
                [2 ]Vienna Clinical Trial Center (VTC), Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
                [3 ]Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
                Author notes
                Correspondence: Andreas Pollreisz, Department of Ophthalmology and Optometry, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; andreas.pollreisz@ 123456meduniwien.ac.at.
                Article
                IOVS-19-29208
                10.1167/iovs.61.6.11
                7415285
                32503052
                3c09d306-99ce-4b4a-b82b-4e30c055c4cb
                Copyright 2020 The Authors

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

                History
                : 12 May 2020
                : 26 December 2019
                Page count
                Pages: 7
                Categories
                Retina
                Retina

                age-related macular degeneration,photoreceptor integrity,reticular pseudodrusen,retinal pigment epithelium,subretinal drusenoid deposits

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