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Background:This study was to examine the expression of total vascular endothelial growth factor (VEGF) and the anti-angiogenic VEGF165b isoform in the vitreous body ofretinopathy ofprematurity (ROP) patients,and to further study the role of the VEGF splicing in the development of ROP.Methods:This was a prospective clinical laboratory investigation study.All patients enrolled received standard ophthalmic examination with stage 4 ROP that required vitrectomy to collect the vitreous samples.The control samples were from congenital cataract patients.The expression of total VEGF and the anti-angiogenic VEGF165b were measured by enzyme-linked immunosorbent assay.Results were analyzed statistically using nonparametric tests.Results:The total VEGF level was markedly elevated in ROP samples while VEGF165b was markedly decreased compared to control group.The relative protein expression level of VEGF165b isoform was significantly decreased in ROP patients which were correlated with the ischemia-induced neovascularization.Conclusions:There was a switch of VEGF splicing from anti-angiogenic to pro-angiogenic family in ROP patients.A specific inhibitor that more selectively targets VEGF165 and controls the VEGF splicing between pro-and anti-angiogenic families might be a more effective therapy for ROP.