Visual Function Benefit After Treatment With Pegcetacoplan: Microperimetry Analysis From the Phase 3 Oaks Trial

center dot PURPOSE: To evaluate the impact of pegcetacoplan on its ability to slow the loss of visual function using microperimetry endpoints in eyes with geographic atrophy secondary to age-related macular degeneration (AMD). center dot DESIGN: Post hoc analysis of phase 3 randomized controlled trial data. center dot METHODS: Utilizing data from the OAKS study, which evaluated pegcetacoplan monthly (PM) or every other month (PEOM) vs sham for the treatment of GA secondary to AMD, microperimetry endpoints were assessed at baseline and every 6 months until 24 months, using a 10-2 grid composed of 68 points with a 4-2 threshold strategy. Main outcome measures included the time to development of absolute scotomas in the 4 and 16 central macular points. The number of absolute scotomatous points and mean retinal sensitivity (dB) within the junctional zone extending to 250 mu m on either side of autofluorescence-determined GA border was analyzed for change from baseline. center dot RESULTS: Among 605 patients with subfoveal or nonsubfoveal GA, treatment with pegcetacoplan delayed time to development of absolute scotomas of all 4 central macular points compared to sham at 24 months (PM: hazard ratio [HR]: 0.66 [34% risk reduction]; 95% confidence interval [CI]: 0.46, 0.96; P = .0282; PEOM: HR: 0.64 [36% risk reduction]; 95% CI: 0.44, 0.92; P = .0164). Similarly, PM and PEOM treatment delayed time to development of absolute scotomas of all 16 central points (PM: HR: 0.57 [43% risk reduction]; 95% CI: 0.33, 0.96; P = .0361; PEOM: HR: 0.52 [48% risk reduction]; 95% CI: 0.32, 0.85; P = .0084). Across the junctional zone of GA, pegcetacoplan-treated eyes developed fewer absolute scotomatous points (PM difference vs sham pooled:-0.68 points, P = .1444; PEOM difference vs sham pooled:-1.14 points, P = .0140) and experienced decreased loss of mean retinal sensitivity (PM difference vs sham pooled: 0.56 dB, P = .0650; PEOM difference vs sham pooled: 0.71 dB, P = .0202) compared with sham at 24 months . center dot CONCLUSIONS: Microperimetry demonstrates a reduced rate of visual function loss in the central macula and junctional zone with pegcetacoplan treatment in GA due to AMD. (Am J Ophthalmol 2025;273: 119129. (c) 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC- ND license (http://creativecommons.org/licenses/by-nc- nd/4.0/))