Rationale for combination therapy in age-related macular degeneration

Choroidal neovascularization (CNV) is typically characterized as an invasion of blood vessels, but it is important to recognize concurrent inflammatory and mesenchymal cell infiltration. A two component model of CNV can be thought to be composed of a vascular component and an extravascular component. Macular damage is possible through either. Given the redundancy and complex interaction among biologic systems involved in the production of CNV, it is likely that a monotherapeutic approach will not be fully effective. The vascular component of CNV arises through the orchestrated interaction of a number of growth factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which maintains pericyte viability. The vascular component of CNV can be selectively targeted with anti-VEGF and anti-PDGF drugs or nonselectively with such modalities as ionizing radiation. The extravascular component can be targeted selectively by inhibiting specific cytokines such as tumor necrosis factor alpha or nonselectively with antiinflammatory drugs such as corticosteroids.