Geographic atrophy of age-related macular degeneration in the Age-Related Eye Disease Study 2 (AREDS2): incidence, clinical characteristics and factors influencing growth rate

Abstract

Purpose : To analyze the prevalence, incidence and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting growth.

Methods : The Age-Related Eye Disease Study 2 (AREDS2) was a randomized controlled trial of oral supplementation for AMD, comprising 4203 participants aged 50-85 years. Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included: GA prevalence and incidence rates, Kaplan-Meier rates, mixed models regression of change in square root of GA area adjusted for covariates including clinical/imaging characteristics and genotype.

Results : At baseline, 517 (6.2%) eyes of 411 (9.8%) participants had pre-existing GA (without neovascular AMD). Of the remaining 6530 eyes at risk, 1099 (17.3%) eyes of 883 participants developed incident GA during mean follow-up of 4.4 years. At onset, incident GA lesions had the following distributions: centrality (33% central, 67% non-central) and focality (25% multifocal, 14% unifocal, 62% other). Over 5 years, risk of neovascular AMD following incident GA was 13% and risk of central involvement following incident non-central GA was 28%. Mean change in square root of GA area was similar in eyes with pre-existing GA (0.29mm/year, 95% CI 0.27-0.30) and incident GA (0.28mm/year, 0.27-0.30). In the combined group, GA growth was significantly faster with non-centrality (p<0.0001 for interaction), multifocality (p<0.0001) and intermediate baseline size (0.75-1.5 disc areas; p<0.0001) but not with AREDS2 treatment assignment (p=0.35) or smoking status (ever/never; p=0.14). Growth was significantly faster with ARMS2 risk genotype (p<0.0001 for interaction) and C3 non-risk genotype (p=0.0001). Additional signals for altered growth were observed with APOE and CFI genotype.

Conclusions : Analysis of GA natural history in the large AREDS2 population provided representative normative data about GA evolution and growth. GA growth rate was significantly influenced by lesion features at onset and by patient genotype. The genetic variants associated with increased growth rate were partially distinct from those known to be associated with risk of incident GA. These findings are relevant to investigations of GA pathogenesis and in clinical trial planning.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.