Relationship of Topographic Distribution of Geographic Atrophy to Visual Acuity in Nonexudative Age-Related Macular Degeneration

Abstract

Purpose: To investigate the topographic distribution of geographic atrophy (GA) and to identify an anatomic endpoint that correlates with visual acuity (VA) in eyes with GA.

Design: Retrospective analysis of a multicenter, prospective, randomized controlled trial.

Participants: The Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration.

Methods: We manually delineated GA on 1654 fundus photographs of 365 eyes. We measured GA areas in 9 subfields on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and correlated them with VA via a mixed-effects model. We determined the optimal diameter for the central zone by varying the diameter from 0 to 10 mm until the highest r² between GA area in the central zone and VA was achieved. We estimated the VA decline rate over 8 years using a linear mixed model.

Main outcome measures: Geographic atrophy area in macular subfields and VA.

Results: The percentage of area affected by GA declined as a function of retinal eccentricity. GA area was higher in the temporal than the nasal region (1.30 ± 1.75 mm² vs. 1.10 ± 1.62 mm²; P = 0.005) and in the superior than the inferior region (1.26 ± 1.73 mm² vs. 1.03 ± 1.53 mm²; P < 0.001). Total GA area correlated poorly with VA (r² = 0.07). Among GA areas in 9 subfields, only GA area in the central zone was associated independently with VA (P < 0.001). We determined 1 mm as the optimal diameter for the central zone in which GA area correlated best with VA (r² = 0.45). On average, full GA coverage of the central 1-mm diameter zone corresponded to 34.8 letters' decline in VA. The VA decline rate was comparable between eyes with initial noncentral and central GA before GA covered the entire central 1-mm diameter zone (2.7 letters/year vs. 2.8 letters/year; P = 0.94).

Conclusions: The prevalence of GA varies significantly across different macular regions. Although total GA area was associated poorly with VA, GA area in the central 1-mm diameter zone was correlated significantly with VA and may serve as a surrogate endpoint in clinical trials.

Keywords: Color fundus photography; Geographic atrophy; Nonexudative age-related macular degeneration; Topography; Visual acuity.