Principal Investigator: Jeremiah Brown, Jr., MS, MD
It is notable that the rate of progression of geographic atrophy varies amongst patients, amongst lesion types, and amongst lesion patterns. Some patients are slow progressors, and others progress more quickly. Patients with multifocal lesions progress faster than patients with single lesions. Patients with subfoveal lesions progress more slowly than patients with lesions outside the fovea. Large lesions tend to progress more quickly than small lesions. The current anticomplement therapies appear to slow progression in all patients but to varying degrees depending upon the lesion types. Patients with a larger rim of photoreceptor degeneration determined by OCT analysis of the ellipsoid zone compared to the size of the RPE defect tend to progress faster than patients where the photoreceptor degeneration size more closely matches the size of the RPE cell defect.
In clinical practice, it has become interesting to note that some patients report visual improvement once initiating therapy with the current anticomplement medications. Some of these patients may demonstrate improved visual acuity, others report that the “quality” of their vision is better or that their contrast sensitivity has improved after starting therapy. Our goal is to better understand what is occurring at the level of the photoreceptors and RPE in patients treated with anticomplement therapies and determine if we can predict which patients are more likely to experience improvement in visual acuity.
Advances in artificial intelligence (AI) and machine learning (ML) offer new opportunities to deepen our understanding of these complex biological processes. In the context of anti-complement drugs, AI can be particularly useful for modeling the dynamic interactions between complement activation and photoreceptor survival, helping to identify patterns involved in disease progression and drug efficacy. This research protocol aims to utilize AI-driven approaches to investigate the impact of anti-complement therapies pegcetacoplan and avacincaptad pegol on photoreceptor (ellipsoid zone) and RPE degeneration through segmentation of the outer retinal layer images on OCT b scans. The findings from this research could not only enhance our understanding of the biological mechanisms driving retinal degeneration but also aid in the development research protocols taking into consideration baseline patient characteristics. This will aid in the development of personalized anti-complement therapies.
Research funded by the Macular Degeneration Association