Intravitreous Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor 1a in Patients With Proliferative Diabetic Retinopathy

PURPOSE: To determine vascular endothelial growth factor (VEGF) and hypoxia,inducible factor 1a (HIF-1a) in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR). DESIGN: Observational case-control study. METHODS: Serum and vitreous fluid samples were obtained during vitrectomy from 42 eyes of diabetic patients with PDR (17 type I and 25 type 11 diabetes mellitus) and from 23 eyes of nondiabetic patients. Retinopathy of 19 diabetic patients was graded as active and the other 23 graded as quiescent according to retinal neovascularization. VEGF and HIF-1a of serum and vitreous fluid samples were measured by enzyme-linked immunosorbent assay. RESULTS: Both intravitreous VEGF and HIF-1a were higher in diabetic patients with PDR than in control subjects (P < .01 and P < .01, respectively). After adjusting for total intravitreous protein (TP) concentration, intravitreous VEGF/TP and HIF-1a/TP in diabetic patients remained significantly higher too. Correlations between intravitreous VEGF and HIF-1a and intravitreous VEGF/TP and HIF-1a/TP were observed in diabetic patients with PDR (r = 0.730; P < .01; r = 0.531; P < .01, respectively) but not in control subjects. Both intravitreous VEGF and HIF-1a were higher in diabetic patients with active PDR than in those with quiescent PDR (P < .01 and P < .05, respectively). Intravitreous VEGF/TP in patients with active PDR remained higher (P < .05). Correlation between intravitreous VEGF and HIF-1a, as well as correlation between intravitreous VEGF/TP and HIF-1a/TP, were observed in diabetic patients with active PDR and those with quiescent PDR but not observed in control subjects. CONCLUSIONS: Intravitreous VEGF and HIF-1a in diabetic patients with PDR are increased and related mutually. VEGF and HIF-1a, especially VEGF, are associated with the angiogenesis of PDR. (Am J Oph. thalmol 2009;148:883-889. (C) 2009 by Elsevier Inc. All rights reserved.)