Natural History of Geographic Atrophy Secondary to Age-Related Macular Degeneration: Results from the Prospective Proxima A and B Clinical Trials

Purpose: To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD). Design: Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials. Participants: Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N = 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n = 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n = 32). Methods: Changes in visual function and imaging/anatomic parameters were evaluated over time using a mixed model for repeated measurement accounting for key baseline characteristics. Main Outcome Measures: Prespecified end points included change in GA area from baseline, best-corrected visual acuity (BCVA) score assessed by Early Treatment Diabetic Retinopathy Study (ETDRS), and visual acuity under low-luminance (LLVA). Results: At 24 months, adjusted mean (standard error) change in GA lesion area from baseline was 3.87 (0.15) mm² in participants with bilateral GA (Proxima A), 3.55 (0.16) mm² in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm² in the fellow eye intermediate AMD cohort (Proxima B). Progression of GA was greater in patients with baseline nonsubfoveal (vs. subfoveal) GA lesions and tended to increase as baseline low-luminance deficit increased (all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (standard error) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months were −13.88 (1.40) and −7.64 (1.20) in Proxima A, −9.49 (1.29) and −7.57 (1.26) in Proxima B fellow eye CNV cohort, and −11.48 (3.39) and −8.37 (3.02) in Proxima B fellow eye intermediate AMD cohort, respectively. Conclusions: The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline.