RUBEOSIS IRIDIS 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 va scular endothelial growth factor (VEGF), a hypoxia-induced angiogenic factor, is produced by hypoxic retinoblastoma and retinal cells in the se eyes. Materials and Methods: One hundred eighty-one enucleated eyes containing retinoblastoma were the source for the current study, Hist ologic slides were evaluated for the presence and degree of rubeosis i ridis as well as for other histologic factors. Univariate and multivar iate statistical analyses were performed to find a correlation between rubeosis iridis and the other histologic factors. Eight of the eyes u nderwent in situ hybridization with a specific VEGF mRNA probe to loca te tumor and retinal cells that may produce this hypoxia-induced angio genic factor. Results: The amount of tumor necrosis as well as choroid al and optic nerve invasion was found to be one of the most important factors that correlated with the presence and degree of rubeosis iridi s in the examined eyes. All eight eyes that underwent in situ hybridiz ation analysis showed strong signals of VEGF mRNA in retinoblastoma ce lls around necrotic regions and in the outer nuclear layers in areas o f detached retina. Conclusions: There exists an association between ru beosis iridis and histologic factors found in advanced stages of retin oblastoma, especially the amount of tumor necrosis. Vascular endotheli al growth factor may well be an angiogenic factor that is secreted by the hypoxic retinoblastoma and retinal cells and, reaching the iris, c auses (presumably in collaboration with other factors) rubeosis iridis .