Abstract
Purpose :
Data on long-term outcomes and risk factors for progression of age-related macular degeneration (AMD) beyond 15 years are limited. We performed a retrospective analysis of a subset of participants enrolled in the prospective cohort study, the Age-Related Eye Disease Study (AREDS), who had 20 years of follow-up to evaluate risk factors associated with progression to intermediate and late AMD.
Methods :
We observed AREDS participants through their subsequent participation in either AREDS2 or the NEI extended follow-up protocol after completion of a randomized clinical trial of antioxidant vitamins and minerals. Participants were 55 to 80 years old with no AMD or AMD of varying severity. Annual stereoscopic fundus photographs were graded centrally and evaluated for large drusen, geographic atrophy (GA), and choroidal neovascularization (CNV). Analyses were conducted on 171 surviving participants followed annually. The unit of analysis was the eye, with n=319 for late AMD, n=193 for large drusen, and n=279 for genetics. Kaplan-Meier analyses and multivariable proportional hazard regressions were performed. Covariates included age, sex, race, education level, smoking status, baseline AREDS AMD severity score, 52-single nucleotide polymorphism (SNP) Genetic Risk Score (GRS), and four SNPs.
Results :
Overall, 40% of eyes progressed to late AMD with a mean time to event of 18.6 years (SEM 0.4), and 51% of eyes developed large drusen with a mean time to event of 12.2 years (SEM 0.5). Time to late AMD and large drusen decreased with increasing baseline severity. For progression to late AMD, risk factors included older age (HR 1.1, CI 1.0—1.2, P=.001), higher baseline severity (scale 4-6 vs. 1-3: HR 4.7, CI 2.8—7.8; scale 7-8 vs. 1-3: HR 13.3, CI 6.9—25.6, P<.0001), higher GRS (GRS 1 vs. 0: HR 2.6, CI 1.1—6.2, P=.03; GRS 2 vs. 0: HR 4.9, CI 2.1—11.6, P=.0003), CFH rs1061170 (2 vs. 0 alleles: HR 2.3, CI 1.1—4.6, P=.027), and ARMS2 rs10490924 (2 vs. 0 alleles: HR 2.4, CI 1.4—4.1, P=.002). Baseline AMD score ≥ 1 was the only risk factor for progression to large drusen (HR 3.8, CI 2.3—6.4, P<.0001).
Conclusions :
The risk factors for AMD progression are similar to those described in previous studies and include older age, higher baseline AMD severity score, higher GRS, CFH and ARMS2. This study provides novel insight into long-term progression to large drusen, which does not share the same risk factors as late AMD.
This is a 2020 ARVO Annual Meeting abstract.