Clinicopathological findings of retinal angiomatous proliferation

Neovascular membranes obtained from surgical excision of neovascularization for retinal angiomatous proliferation (RAP) were examined histopathologically in an attempt to elucidate the pathogenic mechanism of RAP. Nine eyes of eight patients (mean age, 79 +/- 6 years) who underwent neovascularization excision were studied. Three eyes had stage II with RPE detachment, six had stage III. Immunohistochemical studies were performed to identify von Willebrand factor, vascular endothelial factor (VEGF), CD68 and hypoxia inducible factors (HIF-1 alpha and HIF-2 alpha). Multiple soft drusen were present in the macular area in all patients. In one stage II eye, we observed intraretinal neovascularization as a VEGF-positive mass, CD68-positive macrophage migration and HIF expression. In another stage II eye, neovascularization had extended above the RPE, while VEGF-positive fibroblasts were observed below the RPE. Therefore, in stage II, neither angiographic nor histopathological examinations identified choroidal neovascularization. In one phase III eye, angiography demonstrated choroidal neovascularization and chorioretinal anastomosis. Histopathologically, chorio-retinal communication was observed in the region where the RPE was destroyed, and VEGF-positive neovascularization was also seen below the RPE. The findings of multiple drusen in elderly patients together with macrophage migration and HIF expression surrounding VEGF-positive retinal neovascularization suggest ischemic and inflammatory factors to be associated with the development and progression of RAP.