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Panos George Christakis, Elvira Agron, Michael L Klein, J. Peter Campbell, Frederick L Ferris, Emily Y. Chew; Development of Geographic Atrophy following Untreated Neovascular Age-related Macular Degeneration—Results from AREDS. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4947.
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© ARVO (1962-2015); The Authors (2016-present)
Recent studies have reported an association between anti-vascular endothelial growth factor (anti-VEGF) treatment and the development of geographic atrophy (GA) in patients with neovascular age-related macular degeneration (NV-AMD). We assessed this association by evaluating the natural history of untreated NV-AMD for the development of GA.
We used data from the Age-Related Eye Disease Study (AREDS), a long-term, multicenter, prospective clinical trial of 4757 participants with varying severity of AMD who were randomized to receive a vitamin/antioxidant and/or mineral formulation or placebo. This cohort was followed from 1992 to 2005 (median follow-up: 10.5 years), prior to the advent and FDA approval of anti-VEGF therapies for NV-AMD. Participants received standardized annual fundus photography which was graded by masked graders at a centralized reading center at the University of Wisconsin.
A total of 1042 eyes developed NV-AMD during follow-up, of which 758 eyes of 664 participants did not have GA prior to NV-AMD and were eligible for analysis (Figure 1). Participants who underwent macular laser (n=325) for NV-AMD were censored at the time of treatment. Of these 758 eyes, 254 eyes developed GA within a mean of 3.1±2.6 years, corresponding to a cumulative GA risk of 54% at 8-years (Figure 2). A total of 123 eyes developed central GA within a mean of 3.3±2.5 years, corresponding to a cumulative central GA risk of 29% at 8-years. Of eyes developing GA which progressed to central GA, the majority (52%) did so within 3 years. There was no difference in the rates of development of GA after NV-AMD based on treatment group, age, sex, race, body mass index, education, or smoking status.
AREDS provides long-term natural history data on the largest reported cohort of participants with untreated NV-AMD. Our results demonstrate that untreated NV-AMD has a very high rate of progression to GA, and that the majority of these cases progress to involve the center of the macula. This is important to consider in the context of recent theories that anti-VEGF therapy may contribute to the development of GA.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Figure 1: Flowchart demonstrating the natural history of GA after untreated NV in AREDS.
Figure 2: Kaplan-Meier Analysis demonstrating the proportion of patients who develop GA untreated NV in AREDS.
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