Geographic atrophy severity and mortality in age-related macular degeneration

To examine the association between geographic atrophy (GA) disease characteristics and mortality risk.

We manually delineated color fundus photographs of 209 Age-Related Eye Disease Study (AREDS) participants with GA secondary to age-related macular degeneration to identify total area of atrophy, GA effective radius growth rate, disease laterality, and the presence of foveal center involvement. Associations between GA characteristics and mortality were assessed with Cox proportional hazards models adjusted for health status indicators.

During a median follow-up of 6.8 years, 48 (23.0%) participants with GA died. In adjusted models, accounting for age, sex, and health status, participants with total GA area in the highest quartile had a significantly increased risk of all-cause mortality compared to those with total GA area in the lowest quartile (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.32-8.86; P = 0.011). GA effective radius growth rate, bilateral disease, and the presence of foveal center involvement were not significantly associated with mortality. In a multivariable model, including health status indicators and all GA characteristics, total area of atrophy in the highest quartile remained significantly associated with mortality (HR, 4.65; 95% CI, 1.29-16.70; P = 0.019).

More extensive GA, as indicated by a greater total area of atrophy, was associated with an increased risk of all-cause mortality in our cohort. The extent of GA may reflect the extent of underlying disease processes that contribute to greater mortality risk, further suggesting that GA may be part of a systemic rather than purely ocular disease process.