To present the current understanding of age-related macular degeneration (AMD) pathogenesis, based on clinical evidence, epidemiologic data, histopathologic examination, and genetic data; to provide an update on current and emerging therapies; and to propose an integrated model of the pathogenesis of AMD.

Review of published clinical and experimental studies.

Analysis and synthesis of clinical and experimental data.

We are closer to a complete understanding of the pathogenesis of AMD, having progressed from clinical observations to epidemiologic observations and clinical pathologic correlation. More recently, modern genetic and genomic studies have facilitated the exploration of molecular pathways. It seems that AMD is a complex disease that results from the interaction of genetic susceptibility with aging and environmental factors. Disease progression also seems to be driven by a combination of genetic and environmental factors.

Therapies based on pathophysiologic features have changed the paradigm for treating neovascular AMD. With improved understanding of the underlying genetic susceptibility, we can identify targets to halt early disease and to prevent progression and vision loss.