Pegcetacoplan Helps Slow Visual Decline in Eyes with Extrafoveal GA

Patients with study eye GA lesions ≥250μm from the foveal center were more likely to have multifocal GA and better BCVA and quality of life than patients with GA lesions <250μm from the foveal center.  Photo: Anna Bedwell, OD. Click image to enlarge. The current goal of geographic atrophy (GA) treatment with pegcetacoplan or avacincaptad pegol is to slow the growth of lesions, preserve retinal tissue and minimize the negative impact of the condition on patient quality of life. Researchers and clinicians alike are keenly interested in understanding treatment effects on vision, by far the most important outcome for patients. From the 24-month secondary endpoints in the OAKS and DERBY trials, there was no clinically meaningful difference between pegcetacoplan- and sham-treated eyes best-corrected visual acuity (BCVA) and 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) under normal lighting conditions. These findings were somewhat expected, as current studies demonstrate the lack of correlation between GA lesion growth and BCVA, as well as the known fluctuations in BCVA in eyes with GA <250μm from the fovea.A recent study published in American Journal of Ophthalmology performed a post-hoc analysis to evaluate the effect of pegcetacoplan on visual function and patient quality of life measures based on the baseline distance of GA lesions from the center of the fovea. These researchers determined that pegcetacoplan treatment demonstrated a potentially meaningful slower decline in visual acuity and QoL for patients with GA lesions ≥250μm from the foveal center. The change in visual acuity and QoL seen with pegcetacoplan treatment for patients with GA lesions <250μm from the foveal center were within the limits of variability.The post-hoc analysis included all 888 study patients with GA. BCVA (using ETDRS acuity) and NEI VFQ-25 were assessed at baseline and every four and six months, respectively, to completion at month 24 in both pegcetacoplan-treated eyes and sham (observed) eyes. Eyes were stratified based on OCT-derived GA lesion location ≥250µm (n=192) or <250µm (n=696) from the foveal center. From baseline to month 24, GA lesions in pegcetacoplan-treated eyes grew a mean of 4.1mm2; mean GA lesion growth in sham-treated eyes was 5.2mm2. Pegcetacoplan-treated eyes with GA lesion margins ≥250μm from the foveal center demonstrated directionally slower decline in visual acuity (5.6 fewer letters lost) and QoL (4.0 fewer points lost) from baseline at 24 months compared with sham. A greater proportion of patients with GA lesions ≥250μm from the foveal center were female compared with patients with GA lesions <250μm from the foveal center. The change in visual acuity (BCVA, mean -1.6 letters) and QoL (NEI VFQ-25, −2.3 points) in pegcetacoplan-treated eyes with GA lesion margins <250μm from the foveal center were within the limits of variability compared with sham.“A change of at least five ETDRS letters, which translates to one line of vision, is considered to have an approximately ≥90% probability of representing a true change in VA rather than a random variation in eyes with VA better than 20/100,” the researchers noted in their paper.“As a post-hoc analysis, this study is not designed or powered to determine statistical significance,” they added. “This, in addition to the small number of patients in the GA lesion ≥250μm from the foveal center subgroup, limits the generalizability of the study findings.”The study concluded that understanding the potential benefits of pegcetacoplan treatment for GA based on lesion location may enhance patient-provider discussions, patient follow-up and patient motivation to continue with long-term treatment for continued benefit. Click here for the journal source. Chiang A, Davis M, Stevens W, et al. Visual acuity and quality of life outcomes with pegcetacoplan treatment: a post-hoc analysis from the OAKS and DERBY Trials. Am J Ophthalmol. May 29, 2025. [Epub ahead of print].