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

Authors Danis RP, Lavine J, Domalpally A

Received 14 July 2015

Accepted for publication 7 October 2015

Published 20 November 2015 Volume 2015:9 Pages 2159—2174

DOI https://doi.org/10.2147/OPTH.S92359

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cem Ozgonul

Peer reviewer comments 3

Editor who approved publication: Dr Scott Fraser


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

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