Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

Ronald P Danis, Jeremy A Lavine, Amitha Domalpally Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA Abstract: Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular deg...

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Autores principales:	Danis RP, Lavine JA, Domalpally A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/49152e22f4544d42b6cc3b51db31ac39
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spelling	oai:doaj.org-article:49152e22f4544d42b6cc3b51db31ac392021-12-02T00:09:46ZGeographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects1177-5483https://doaj.org/article/49152e22f4544d42b6cc3b51db31ac392015-11-01T00:00:00Zhttps://www.dovepress.com/geographic-atrophy-in-patients-with-advanced-dry-age-related-macular-d-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Ronald P Danis, Jeremy A Lavine, Amitha Domalpally Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA Abstract: Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this condition due to the aging of the general population lends urgency to the search for a therapy to ameliorate GA. Keywords: age-related macular degeneration, geographic atrophy, fundus autofluorescence, optical coherence tomography, clinical trialsDanis RPLavine JADomalpally ADove Medical PressarticleOphthalmologyRE1-994ENClinical Ophthalmology, Vol 2015, Iss default, Pp 2159-2174 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ophthalmology RE1-994
spellingShingle	Ophthalmology RE1-994 Danis RP Lavine JA Domalpally A Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
description	Ronald P Danis, Jeremy A Lavine, Amitha Domalpally Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA Abstract: Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusen-related (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascular-associated GA. The increasing prevalence of legal blindness from this condition due to the aging of the general population lends urgency to the search for a therapy to ameliorate GA. Keywords: age-related macular degeneration, geographic atrophy, fundus autofluorescence, optical coherence tomography, clinical trials
format	article
author	Danis RP Lavine JA Domalpally A
author_facet	Danis RP Lavine JA Domalpally A
author_sort	Danis RP
title	Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_short	Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_full	Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_fullStr	Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_full_unstemmed	Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
title_sort	geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/49152e22f4544d42b6cc3b51db31ac39
work_keys_str_mv	AT danisrp geographicatrophyinpatientswithadvanceddryagerelatedmaculardegenerationcurrentchallengesandfutureprospects AT lavineja geographicatrophyinpatientswithadvanceddryagerelatedmaculardegenerationcurrentchallengesandfutureprospects AT domalpallya geographicatrophyinpatientswithadvanceddryagerelatedmaculardegenerationcurrentchallengesandfutureprospects
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Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects

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