Incidence of Macular Atrophy after Untreated Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study Report 40

Panos G. Christakis, Elvira Agrón, Michael L. Klein, Traci E. Clemons, J. Peter Campbell, Frederick L. Ferris, Emily Y. Chew, Tiarnan D. Keenan

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Purpose: To report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy. Design: Prospective cohort within a randomized, controlled trial of oral micronutrient supplements. Participants: Age-Related Eye Disease Study (AREDS) participants (55–80 years) who demonstrated nAMD during follow-up (1992–2005), prior to anti–vascular endothelial growth factor (VEGF) therapy. Methods: Color fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression. Main Outcome Measures: Incident macular atrophy after nAMD. Results: Of the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17–2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90–1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3. Conclusions: The rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.

Original languageEnglish (US)
Pages (from-to)784-792
Number of pages9
JournalOphthalmology
Volume127
Issue number6
DOIs
StatePublished - Jun 2020

ASJC Scopus subject areas

  • Ophthalmology

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