Oculomics: The eye as a window to systemic disease

AbstractObjective: To evaluate the effect of pegcetacoplan on the area of geographic atrophy (GA) and its constituent features (photoreceptor degeneration [PRD], retinal pigment epithelium [RPE] loss, and hypertransmission).Design: Post hoc analysis of the FILLY trial using a deep‐learning model for spectral domain optical coherence tomography (SD‐OCT) auto‐segmentation.Setting: A multicenter trial dataset from 46 participating centres in the United States, Australia and New Zealand.Participants: 246 patients were randomized in a 1:1:1 into pegcetacoplan monthly (PM), pegcetacoplan every other month (PEOM) and sham treatment (pooled) for 12 months of treatment and 6 months of therapy‐free monitoring. Only participants with Heidelberg SD‐OCT were included in longitudinal analyses (n = 197, single eye per participant).Interventions: An auto‐segmentation model quantified the area of each SD‐OCT feature of GA at baseline and at 6, 12 and 18 months. The mean square root area change from baseline was compared across the treatment arms. This was further stratified topographically.Main Outcome Measures: Primary efficacy endpoint was the square root transformed change in area of RPE and outer retinal atrophy (RORA) in each of the treatment arms (PM, PEOM, and pooled sham) at 12 months, with secondary end‐points including RPE‐loss, hypertransmission and PRD.Results: Eyes treated PM showed significantly slower mean change of RORA progression at 12 and 18 months (0.151 mm and 0.277 mm, p = 0.0039; 0.251 and 0.396 mm, p = 0.039, respectively) and RPE‐loss (0.147 mm and 0.287 mm, p = 0.0008; 0.242 mm and 0.410 mm, p = 0.00809). PEOM showed significantly slower mean change of RPE‐loss compared to sham at 12 months (p = 0.0313). Intact macula was preserved in PM compared to sham at 12 and 18 months (p = 0.0095 and p = 0.044).Conclusions and Relevance: The OCT evidence suggests pegcetacoplan slows progression of RORA overall and RPE‐loss specifically whilst protecting the remaining photoreceptors and slowing the progression of healthy retina to RORA.Significance: This post hoc analysis of optical coherence tomography (OCT) scan data from the FILLY randomized controlled phase 2 trial showed that monthly treatment was significantly associated with a slower rate of progression of geographic atrophy as defined by OCT criteria at 12 and 18 months. Furthermore, at the level of the individual retinal layers, there was evidence that monthly pegcetacoplan not only slowed down loss of retinal pigment epithelium, but also reduced the rate of loss of intact macula and isolated photoreceptor loss (which were proposed as novel monitoring targets).