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      Age-Related Macular Degeneration: Advances in Management and Diagnosis

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          Abstract

          Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies.

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          Prevalence of age-related macular degeneration in the United States.

          David Friedman, Benita J O'Colmain, Beatriz Mateos Muñoz … (2004)
          To estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender. Summary prevalence estimates of drusen 125 microm or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US Census data and to projected US population figures for 2020 to estimate the number of the US population with drusen and AMD. The overall prevalence of neovascular AMD and/or geographic atrophy in the US population 40 years and older is estimated to be 1.47% (95% confidence interval, 1.38%-1.55%), with 1.75 million citizens having AMD. The prevalence of AMD increased dramatically with age, with more than 15% of the white women older than 80 years having neovascular AMD and/or geographic atrophy. More than 7 million individuals had drusen measuring 125 microm or larger and were, therefore, at substantial risk of developing AMD. Owing to the rapidly aging population, the number of persons having AMD will increase by 50% to 2.95 million in 2020. Age-related macular degeneration was far more prevalent among white than among black persons. Age-related macular degeneration affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.
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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

            Steven D Schwartz, Carl Regillo, Byron L Lam … (2015)
            The Lancet, 385(9967), 509-516
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              Embryonic stem cell trials for macular degeneration: a preliminary report.

              Steven D Schwartz, Jean-Pierre Hubschman, Gad Heilwell … (2012)
              It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients. We started two prospective clinical studies to establish the safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium (RPE) in patients with Stargardt's macular dystrophy and dry age-related macular degeneration--the leading cause of blindness in the developed world. Preoperative and postoperative ophthalmic examinations included visual acuity, fluorescein angiography, optical coherence tomography, and visual field testing. These studies are registered with ClinicalTrials.gov, numbers NCT01345006 and NCT01344993. Controlled hESC differentiation resulted in greater than 99% pure RPE. The cells displayed typical RPE behaviour and integrated into the host RPE layer forming mature quiescent monolayers after transplantation in animals. The stage of differentiation substantially affected attachment and survival of the cells in vitro after clinical formulation. Lightly pigmented cells attached and spread in a substantially greater proportion (>90%) than more darkly pigmented cells after culture. After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision. Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity chart) in the study eye of the patient with Stargardt's macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration (from 21 ETDRS letters to 28). The hESC-derived RPE cells showed no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months. The future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue. Advanced Cell Technology. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Lindsay Farrer: Role: Academic Editor
                Margaret DeAngelis: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): J Clin Med
                Journal ID (iso-abbrev): J Clin Med
                Journal ID (publisher-id): jcm
                Title: Journal of Clinical Medicine
                Publisher: MDPI
                ISSN (Electronic): 2077-0383
                Publication date (Electronic): 12 February 2015
                Publication date Collection: February 2015
                Volume: 4
                Issue: 2
                Pages: 343-359
                Affiliations
                Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA; E-Mails: Yoshihiro_Yonekawa@ 123456meei.harvard.edu (Y.Y.); joan_miller@ 123456meei.harvard.edu (J.W.M.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: Ivana_Kim@ 123456meei.harvard.edu ; Tel.: +1-617-573-3367.
                Article
                Publisher ID: jcm-04-00343
                DOI: 10.3390/jcm4020343
                PMC ID: 4470128
                PubMed ID: 26239130
                SO-VID: 0595c8a5-1f0b-4317-9b18-0069892b45ec
                Copyright © © 2015 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 24 December 2014
                Date accepted : 20 January 2015
                Categories
                Subject: Review

                Keywords: age-related macular degeneration,choroidal neovascularization,fundus autofluorescence,fluorescein angiography,optical coherence tomography,retina,vascular endothelial growth factor,visual impairment
                Data availability:
                Keywords: age-related macular degeneration, choroidal neovascularization, fundus autofluorescence, fluorescein angiography, optical coherence tomography, retina, vascular endothelial growth factor, visual impairment

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