Geographic Atrophy Growth Is Strongly Related to Lesion Perimeter: Unifying Effects of Lesion Area, Number, and Circularity on Growth

Abstract

To investigate the underlying reason for the previously observed impact of baseline lesion size, number, and circularity on geographic atrophy (GA) growth rate. Retrospective analysis of a multicenter, prospective, randomized controlled trial. Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration. We manually delineated atrophic lesions on color fundus photographs of 318 eyes with GA followed up over at least 2 visits (mean follow-up duration, 5.1 ± 3.0 years). We calculated GA area growth rate for each eye based on the first and last visit. GA perimeter-adjusted growth rate was defined as the ratio between GA area growth rate and mean GA perimeter between the first and last visit for each eye. GA area growth rate, growth rate of the square root of GA area, and GA perimeter-adjusted growth rate. GA area growth rate was correlated strongly with mean GA perimeter (r2= 0.66). GA area growth rate was associated with baseline GA area (r2= 0.39; P < 0.001), lesion number (r2= 0.10; P < 0.001), and circularity index (r2= 0.28; P < 0.001). The use of the square root of GA area reduced the influence of baseline GA area (but not lesion number or circularity) on GA growth rate. In comparison, GA perimeter-adjusted growth rate (0.098 ± 0.062 mm/year) was not correlated with baseline GA area (r2= 0.005; P= 0.20), lesion number (r2= 0.00009; P= 0.86), or circularity index (r2= 0.007; P= 0.14). GA perimeter-adjusted growth rate was 50.0% higher in eyes whose fellow eyes showed GA at any visit (0.102 ± 0.062 mm/year) than in eyes whose fellow eyes never demonstrated GA during follow-up (0.068 ± 0.049 mm/year). The growth rate of GA area is associated strongly with lesion perimeter. This relationship explains the previously observed influences of baseline GA size, lesion number, and circularity on GA growth rate. GA perimeter-adjusted growth rate is uncorrelated with the 3 morphologic factors and may serve as a surrogate outcome measure to monitor GA progression in future studies.