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      Fluorescence Lifetime Patterns of Retinal Pigment Epithelium Atrophy in Patients with Stargardt Disease and Age-Related Macular Degeneration

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          Abstract

          Purpose: To investigate whether autofluorescence lifetime patterns within retinal pigment epithelium (RPE) atrophy differ between age-related macular degeneration (AMD) and Stargardt disease (STGD). Methods: Mean retinal autofluorescence lifetimes were measured in a short and a long spectral channel (SSC: 498–560 nm; LSC: 560–720 nm). Mean retinal fluorescence lifetimes were analyzed with corresponding clinical features, fundus images, fundus autofluorescence intensity images, and optical coherence tomography. Mean fluorescence lifetime values of atrophic areas were compared between the two cohorts and within the same patient to adjacent nonatrophic regions. Results: Mean fluorescence lifetimes within areas with RPE atrophy of 13 patients with STGD (mean age ± SEM 43.7 ± 5 years) and 30 patients with geographic atrophy (mean age: 78 ± 2 years) were analyzed and compared to age-matched healthy participants. The mean area of RPE atrophy in STGD and AMD was 6.6 ± 2.3 mm<sup>2</sup> (range: 0.66–33.17 mm<sup>2</sup>) and 17.5 ± 3.8 mm<sup>2</sup> (range: 0.58–50.02 mm<sup>2</sup>), respectively. In patients with AMD, atrophic areas revealed significantly longer mean fluorescence lifetime values as compared with patients with STGD (SSC: 997 ± 60 vs. 363 ± 26 ps; LSC: 880 ± 46 vs. 393 ± 23 ps; p < 0.0001). Conclusions: This study established that RPE atrophy in patients secondary to STGD and AMD display distinctive mean fluorescence lifetime characteristics. As retinal fluorescence lifetimes within areas of RPE atrophy were significantly longer in AMD patients, the analysis of specific lifetime patterns may provide additional insight into the disease processes and the pathogenetic mechanisms in the development of atrophic patches in AMD and STGD.

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          Most cited references19

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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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            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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              Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration.

              To describe the progression of geographic atrophy (GA) from age-related macular degeneration (AMD) with respect to visual acuity (VA) loss and enlargement of atrophy. A prospectively observed case series. Tertiary retinal referral center. One hundred twenty-three patients with GA due to AMD who completed at least 1 year of follow-up (median follow-up, 3 years) were examined annually. At each examination, a protocol best-corrected VA of each eye was measured, a clinical examination was performed, and color fundus photographs were taken. The areas of atrophy were drawn and measured. Visual acuity loss and enlargement of total and central atrophy. At baseline, median VA was poorer with larger areas of atrophy, but there was wide variation related to sparing of the fovea. Thirty-one percent of all study eyes suffered a three-line VA loss from baseline by 2 years, and 53% had a three-line loss by 4 years. Those eyes with VA better than 20/50 had the highest rate of acuity loss; 27% of these eyes had acuities of 20/200 or worse at 4 years. Visual acuity loss in the GA study eye was similar in patients with bilateral GA and in those with choroidal neovascularization in the fellow eye. Total atrophy enlarged a median of 1.8 Macular Photocoagulation Study disc areas (DA) at 2 years; atrophy within a 4-DA circle centered on the fovea enlarged a median of 0.9 DA. Two (22%) of nine patients with GA in one eye and only drusen without advanced AMD in the fellow eye developed GA in the fellow eye at 2 years. Geographic atrophy is associated with a significant decline in VA over time in many eyes. Areas of atrophy continue to enlarge over time, even when already large at baseline. The combination of reduced VA with enlargement of atrophy, occurring bilaterally in most patients, can lead to significant impairment of visual function.
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                Author and article information

                Journal
                OPH
                Ophthalmologica
                10.1159/issn.0030-3755
                Ophthalmologica
                S. Karger AG
                0030-3755
                1423-0267
                2020
                May 2020
                19 November 2019
                : 243
                : 3
                : 195-206
                Affiliations
                Department of Ophthalmology, Inselspital, Bern University Hospital, and Department of Biomedical Research, University of Bern, Bern, Switzerland
                Author notes
                *Yasmin Solberg, MBBS5, University Hospital Bern, CH–3010 Bern (Switzerland), E-Mail y.solberg@sunrise.ch
                Author information
                https://orcid.org/0000-0002-7467-7028
                Article
                503567 Ophthalmologica 2020;243:195–206
                10.1159/000503567
                31743906
                3debfefa-0cbe-4bcf-8fff-5e350ec37d15
                © 2019 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 14 January 2019
                : 18 September 2019
                Page count
                Figures: 5, Tables: 1, Pages: 12
                Categories
                Research Article

                Vision sciences,Ophthalmology & Optometry,Pathology
                Stargardt disease,Age-related macular degeneration,Fluorescence lifetimes,Atrophy,Fluorescence lifetime imaging ophthalmoscopy

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