The Long-term Natural History of Geographic Atrophy from Age-Related Macular Degeneration. Enlargement of Atrophy and Implications for Interventional Clinical Trials

Purpose: To report the enlargement rate of geographic atrophy (GA) over time, its relationship to size of atrophy at baseline and to prior enlargement rate, and the implications for designing future treatment trials for GA. Design: Prospective natural history study of GA resulting from age-related macular degeneration. Participants: Two hundred twelve eyes of 131 patients were included in the analysis. Methods: Annual follow-up included stereo color fundus photographs. The areas of GA were identified and measured, and the rate of enlargement of the atrophy was assessed. Sample sizes for clinical trials using systemic treatment and uniocular treatment were determined. Main Outcome Measure: Rate of enlargement of the atrophy. Results: The median overall enlargement rate was 2.1 mm²/year (mean, 2.6 mm²/year). Eyes with larger areas of atrophy at baseline tended to have larger enlargement rates, but knowledge of prior rates of enlargement was the most significant factor in predicting subsequent enlargement rates. There was high concordance between the enlargement rates in the 2 eyes of patients with bilateral GA (correlation coefficient, 0.76). To detect a 25% reduction in enlargement rate for a systemic treatment (α, 0.05; power, 0.80; losses to follow-up, 15%), 153 patients each in a control and treatment group would be required for a trial with a 2-year follow-up period for each patient. For a uniocular treatment, 38 patients with bilateral GA would be required, with the untreated eye serving as a control for the treated eye. Conclusions: Treatment trials for GA with an outcome variable of change in enlargement rate are feasible.