Speaker
Description
Age-related macular degeneration (AMD) is a primary cause of irreversible vision loss worldwide, causing years of progressive visual decline and reduced quality of life that may culminate in severe visual impairment or blindness. Available therapeutic options are limited to late-stage disease, when irreversible damage to ocular tissues has already occurred and patients experience significant vision loss. Moreover, these treatments often suffer from limited efficacy and a high treatment burden. With an estimated attrition rate of 85-90%, the translation pipeline for AMD therapeutics faces a persistent bottleneck, hindering the development of effective alternative treatments. In this talk, we demonstrate that this translational bottleneck is driven largely by substantial variability in disease presentation and clinical progression among affected individuals. This population-level heterogeneity propagates bias across multiple stages of the translational pipeline, from clinical study design and patient recruitment to molecular analyses and biomarker validation. Integrative analyses across genetics, transcriptomics, proteomics, and clinical phenotyping suggest that this heterogeneity arises from a lack of integration among three core disease dimensions: age, genetic risk profile, and staging of AMD severity. We argue that frameworks combining these axes are required to identify knowledge gaps, clarify disease mechanisms, and support effective therapy development.
