Rubeosis lridis in Retinoblastoma: Histologic Findings and the Possible Role of Vascular Endothelial Growth Factor in Its Induction

Purpose: Iris neovascularization (rubeosis iridis) is a common finding in eyes harboring retinoblastoma. The purpose of the current study is to evaluate the histologic factors that may affect the development of rubeosis iridis in eyes with retinoblastoma and to examine whether vascular endothelial growth factor (VEGF), a hypoxia-induced angiogenic factor, is produced by hypoxic retinoblastoma and retinal cells in these eyes. Materials and Methods: One hundred eighty-one enucleated eyes containing retinoblastoma were the source for the current study. Histologic slides were evaluated for the presence and degree of rubeosis iridis as well as for other histologic factors. Univariate and multivariate statistical analyses were performed to find a correlation between rubeosis iridis and the other histologic factors. Eight of the eyes underwent in situ hybridization with a specific VEGF mRNA probe to locate tumor and retinal cells that may produce this hypoxia-induced angiogenic factor. Results: The amount of tumor necrosis as well as choroidal and optic nerve invasion was found to be one of the most important factors that correlated with the presence and degree of rubeosis iridis in the examined eyes. All eight eyes that underwent in situ hybridization analysis showed strong signals of VEGF mRNA in retinoblastoma cells around necrotic regions and in the outer nuclear layers in areas of detached retina. Conclusions: There exists an association between rubeosis iridis and histologic factors found in advanced stages of retinoblastoma, especially the amount of tumor necrosis. Vascular endothelial growth factor may well be an angiogenic factor that is secreted by the hypoxic retinoblastoma and retinal cells and, reaching the iris, causes (presumably in collaboration with other factors) rubeosis iridis.