Rationale for Combination Therapies for Choroidal Neovascularization

PurposeTo provide a conceptual framework for the development and use of combination therapies for choroidal neovascularization secondary to age-related macular degeneration.DesignLiterature review, integration of data, and creation of hypothesis.MethodsAn assessment of angiogenesis, cancer therapy, and inflammation was performed as they may pertain to choroidal neovascularization. A conceptual framework was created in which therapies for choroidal neovascularization could be evaluated alone or in combination.ResultsAngiogenesis occurs because cells produce angiogenic stimuli to encourage blood vessels to develop. This growth of vessels involves an orchestrated interaction among many mediators offering opportunity to modulate or inhibit the entire process. A two-component model for choroidal neovascularization is proposed. The vascular component of choroidal neovascularization is comprised of vascular endothelial cells, endothelial cell precursors, and pericytes. The extravascular component, which by histopathology appears to be both the source of angiogenic stimuli and often the largest component volumetrically, is comprised of inflammatory, glial and retinal pigment epithelial cells, and fibroblasts. Tissue damage can be caused by either component. Each component can be targeted through as variety of monotherapies. Combination therapies offer the possibility of attacking one component in more than one way or by attacking both components simultaneously.ConclusionsThe two-component model of choroidal neovascularization can be used to evaluate the mechanism of action and possible interactions of these agents in a conceptual framework. Extension of these ideas can help guide development of new treatment agents and approaches.