Pegcetacoplan significantly lowers geographic atrophy progression secondary to AMD

According to a new study Pegcetacoplan significantly lowers geographic atrophy progression secondary to AMD. However in order to fully understand the pathognomonic variability in individual lesion development and therapy response, geographic atrophy (GA) progression must be evaluated topographically, says an article published in Ophthalmology Retina.

In order to determine disease activity and the effects of intravitreal pegcetacoplan treatment on the topographic progression of geographic atrophy secondary to age-related macular degeneration as measured in spectral-domain OCT (SD-OCT) by automated deep learning assessment, Wolf-Dieter Vogl and team conducted this study. 

This study evaluated pegcetacoplan in GA patients and was a retrospective review of a phase II clinical trial investigation. In a total of 312 scans, SD-OCT images from 57 eyes receiving monthly therapy, 46 eyes receiving every-other-month (EOM) treatment, and 53 eyes receiving sham injection were included. Using verified deep learning techniques, the retinal pigment epithelium loss, photoreceptor (PR) integrity, and hyperreflective foci (HRF) were automatically segmented. A growth model evaluating the local expansion of GA margins between baseline and one year was used to calculate the local progression rate (LPR). The eccentricity to the foveal center, mean PR thickness, progression direction, and HRF concentration in the junctional zone were all calculated for each individual margin point. Spatial generalized additive mixed-effect models were used to predict the mean LPR in disease activity and the treatment impact conditional on these features.

The key findings of this study were:

The analysis included 31 527 local GA margin sites in total. Low eccentricity to the fovea, a thinner PR layer, or a larger concentration of HRF in the GA junctional zone were associated with increased LPR. 

Researchers demonstrate an average LPR that is much lower when topographic and structural risk factors are taken into account, falling by -28.0% and -23.9% for monthly and EOM-treated eyes, respectively, in comparison to sham.

In conclusion, when compared to sham-treated eyes, pegcetacoplan-treated eyes revealed a considerably slower rate of GA lesion advancement, and an even slower rate of growth toward the fovea. This research may aid in identifying patient cohorts with lesions that advance more quickly and would benefit most from pegcetacoplan therapy. Automated artificial intelligence-based solutions will offer trustworthy direction for the therapeutic management of GA.

Reference: 

Vogl, W.-D., Riedl, S., Mai, J., Reiter, G. S., Lachinov, D., Bogunović, H., & Schmidt-Erfurth, U. (2023). Predicting Topographic Disease Progression and Treatment Response of Pegcetacoplan in Geographic Atrophy Quantified by Deep Learning. In Ophthalmology Retina (Vol. 7, Issue 1, pp. 4–13). Elsevier BV. https://doi.org/10.1016/j.oret.2022.08.003