Figure 1. Pathologic events in CNV. A: In healthy cells, RPE cells have strong junctional complexes and form a monolayer on Bruch’s membrane separate from the choroidal endothelial cells (CECs). B: Optical coherence tomography (OCT) of a human eye without age-related macular degeneration (AMD). Note the normal architecture of retinal layers, lack of drusen, and good foveal contour. C: With increasing age and related to genetic predisposition, diet, smoking, oxidative stress, and inflammation, Bruch’s membrane and the RPE extracellular matrix change in appearance with the formation of drusen and in composition, with deposition of oxidized lipoprotein, debris, complement, and many other factors that incite inflammatory, oxidative, and angiogenic signaling. Microglia are activated and release cytokines (e.g., tumor necrosis factor alpha, TNF-α) that stimulate RPE cells to express vascular endothelial growth factor (VEGF). Concurrently, CECs activated to migrate toward the RPE monolayer and proliferate into type 1 choroidal neovascularization (CNV). RPE cell–CEC contact initiates events that lead to RPE barrier compromise, which permits cells and growth factors to move from basal to apical aspects. CECs are attracted to migrate across the RPE monolayer and into the sensory retina toward a VEGF gradient to proliferate into type 2 CNV. D: OCT of a human eye with neovascular AMD, showing loss of the architecture of the retina and the RPE monolayer, loss of the foveal depression, and cysts within the inner retinal layers.