The Effect of Pegcetacoplan Treatment on Photoreceptor Maintenance in Geographic Atrophy Monitored by Artificial Intelligence-Based OCT Analysis

Abstract

Purpose: To investigate the therapeutic effect of intravitreal pegcetacoplan on the inhibition of photoreceptor (PR) loss and thinning in geographic atrophy (GA) on conventional spectral-domain OCT (SD-OCT) imaging by deep learning-based automated PR quantification.

Design: Post hoc analysis of a prospective, multicenter, randomized, sham (SM)-controlled, masked phase II trial investigating the safety and efficacy of pegcetacoplan for the treatment of GA because of age-related macular degeneration.

Participants: Study eyes of 246 patients, randomized 1:1:1 to monthly (AM), bimonthly (AEOM), and SM treatment.

Methods: We performed fully automated, deep learning-based segmentation of retinal pigment epithelium (RPE) loss and PR thickness on SD-OCT volumes acquired at baseline and months 2, 6, and 12. The difference in the change of PR loss area was compared among the treatment arms. Change in PR thickness adjacent to the GA borders and the entire 20° scanning area was compared between treatment arms.

Main outcome measures: Square-root transformed PR loss area in μm or mm, PR thickness in μm, and PR loss/RPE loss ratio.

Results: A total of 31 556 B-scans of 644 SD-OCT volumes of 161 study eyes (AM 52, AEOM 54, SM 56) were evaluated from baseline to month 12. Comparison of the mean change in PR loss area revealed statistically significantly less growth in the AM group at months 2, 6, and 12 than in the SM group (-41 μm ± 219 vs. 77 μm ± 126; P = 0.0004; -5 μm ± 221 vs. 156 μm ± 139; P < 0.0001; 106 μm ± 400 vs. 283 μm ± 226; P = 0.0014). Photoreceptor thinning was significantly reduced under AM treatment compared with SM within the GA junctional zone, as well as throughout the 20° area. A trend toward greater inhibition of PR loss than RPE loss was observed under therapy.

Conclusions: Distinct and reliable quantification of PR loss using deep learning-based algorithms offers an essential tool to evaluate therapeutic efficacy in slowing disease progression. Photoreceptor loss and thinning are reduced by intravitreal complement C3 inhibition. Automated quantification of PR loss/maintenance based on OCT images is an ideal approach to reliably monitor disease activity and therapeutic efficacy in GA management in clinical routine and regulatory trials.

Keywords: Automated image analysis; Complement inhibition; Geographic atrophy; Optical coherence tomography; Photoreceptors.