Abstract
Introduction: There is no effective treatment for geographic atrophy (GA). To help design future GA treatment trials, we conducted a meta-analysis for GA growth rate and its variability in natural history studies. Methods: Literatures were searched up to April 30, 2020. Data were extracted independently by 2 authors and analyzed using random-effects models. Results: The pooled mean GA growth rate was 1.66 mm<sup>2</sup>/year (SD = 1.27 mm<sup>2</sup>/year, I<sup>2</sup> = 97.0%, p < 0.001) from 23 studies (3,078 patients) reported with growth rate in mm<sup>2</sup>/year and 0.33 mm/year (SD = 0.17 mm/year, I<sup>2</sup> = 83.0%, p < 0.001) from 12 studies (1,808 patients) reported with growth rate in mm/year. Larger mean baseline GA area in mm<sup>2</sup> was associated with larger mean growth rate in both mm<sup>2</sup>/year and mm/year (p < 0.001). The sample size at 85% power for detecting 15% reduction in growth rate in a 2-arm GA trial is 464 and 209 patients per arm, respectively, for using mm<sup>2</sup>/year and mm/year as the primary outcome. Discussion/Conclusion: GA natural history studies had a pooled mean (SD) GA growth rate of 1.66 (1.27) mm<sup>2</sup>/year or 0.33 (0.17) mm/year. Because GA growth rate using mm/year requires smaller sample size than using mm<sup>2</sup>/year, GA growth rate in mm/year is recommended as the primary outcome measure for future GA trials.
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