Geographic atrophy (GA) is the advanced stage of non-neovascular (dry) age-related macular degeneration, defined by the presence of sharply demarcated atrophic lesions of the outer retina. The complement system is integral to the body's natural immune response, and hence its overactivation can lead to tissue damage and inflammation. It has been shown to play a significant role in GA lesion development and progression, and therefore, complement inhibition is emerging as a promising avenue for therapeutic intervention. With the recent approval by the Food and Drug Administration of drugs like SYFOVRE™ (pegcetacoplan injection) and IZERVAY™ (avacincaptad pegol intravitreal solution), there is hope for the development of interventions capable of slowing down or arresting the progression of GA. In particular, gene therapy intervention is gaining traction for halting GA atrophy at the source of our genes. The concept is to insert a gene into the eye that will act as an ocular "bio-factory," producing a desired protein. This can either lead to overproduction of an already available protein or produce a substance not typically generated in the eye. This review aims to provide an overview of the present understanding of GA, encompassing risk factors, prevalence, pathophysiology, and genetic associations. It will also highlight the current landscape of GA treatment, with particular emphasis on gene therapy intervention.
© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.