Intereye Correlation in Bilateral Geographic Atrophy: Morphology and Growth Rates in the Age-Related Eye Disease Study.

Purpose: To evaluate intereye correlation in geographic atrophy (GA) lesion morphology, topography, and growth rates, and whether fellow eyes could improve trial efficiency as internal controls. Design: Secondary analysis of a multicenter, prospective, randomized controlled trial. Participants: Age-Related Eye Disease Study participants with bilateral GA. Methods: Color fundus photographs were used to delineate GA lesions and measure area, perimeter, circularity index, focality, and lesion number. Intereye correlations were evaluated cross-sectionally and longitudinally for 3 GA growth rates (area, square root-transformed, and perimeter-adjusted growth rate). Longitudinal correlations used the first-to-last interval (mean, 5.5 years). Sample-size requirements for paired and unpaired designs were estimated through exploratory power analyses in eyes with 1-year follow-up. Main Outcome Measures: Geographic atrophy size, morphology, topographic distribution, and growth rate. Results: In 226 eyes from 113 patients, moderate-to-strong associations were observed between fellow eyes for GA area (ρ = 0.63), perimeter (ρ = 0.69), circularity index (ρ = 0.56), and across all 4 quadrants (range, ρ = 0.51-0.61). Longitudinally, intereye associations were moderate-to-strong for GA area growth rates (ρ = 0.74), square root-transformed area growth rates (ρ = 0.62), and perimeter-adjusted growth rates (ρ = 0.60). These values reflect the first-to-last interval (mean, 5.5 years); over 1 year, correlations were markedly lower (ρ = 0.53, 0.40, 0.34). By baseline lesion size, intereye correlation was slightly higher for area growth rate in small lesions (≤0.9 disc areas [DAs]) but comparable between area- and perimeter-adjusted rates in larger lesions (>0.9 DA). In exploratory 1-year power analyses, a paired design with within-participant randomization of study and fellow eyes was associated with approximately 40% lower estimated sample-size requirements than an unpaired design (149 pairs vs. 250 eyes per arm for area growth rate); adding a perimeter-adjusted endpoint in lesions >0.9 DA reduced the estimate to 50 pairs per arm. Conclusions: We observed moderate-to-strong inter-eye correlations in GA morphology, topography, and progression. For exploratory designs of local unilateral therapies, fellow eyes may serve as internal controls alongside square root-transformed or perimeter-adjusted endpoints, reducing sample sizes, particularly for lesions >0.9 DA. Because these analyses use color fundus photography rather than fundus autofluorescence, they are hypothesis-generating for modern trials. These correlations may also inform group-level counseling on fellow-eye progression. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.