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.