Novel drug development for geographic atrophy.

Geographic atrophy (GA), the advanced stage of dry age-related macular degeneration, has transitioned from an untreatable condition to a field of active therapeutic development. This review outlines the key molecular pathways driving GA progression, including complement system dysregulation, oxidative stress, and chronic inflammation. A marked important therapeutic milestone with the first FDA approvals of complement inhibitors, Pegcetacoplan and Avacincaptad pegol, demonstrated a modest but statistically significant slowing of lesion growth. However, these anatomic benefits have not consistently translated into meaningful functional visual improvement, underscoring the need for additional therapeutic strategies. Beyond complement, the therapeutic landscape is rapidly expanding to include oral agents, topical therapies, implant-based delivery systems, subcutaneous injections, and device-based approaches targeting oxidative stress, neuroprotection, mitochondrial dysfunction, lipid metabolism and proteostasis. Emerging modalities, including gene therapy, stem cell-based repair, and bioelectronic implants, aim to move beyond disease slowing toward durable retinal restoration. Despite progress, significant unmet needs persist. Key challenges include treatment burden associated with frequent intravitreal injections, safety considerations, and the persistent disconnect between anatomic endpoints and functional outcomes. These underscore the necessity for future treatments that not only alter disease anatomy but also effectively preserve patients' vision and improve their quality of life.