VASCULAR ENDOTHELIAL GROWTH-FACTOR IN OCULAR FLUID OF PATIENTS WITH DIABETIC-RETINOPATHY AND OTHER RETINAL DISORDERS

Background. Retinal ischemia induces intraocular neovascularization, w hich often leads to glaucoma, vitreous hemorrhage, and retinal detachm ent, presumably by stimulating the release of angiogenic molecules. Va scular endothelial growth factor (VEGF) is an endothelial-cell-specifi c angiogenic factor whose production is increased by hypoxia. Methods. We measured the concentration of VEGF in 210 specimens of ocular flui d obtained from 164 patients undergoing intraocular surgery, using bot h radioimmunoassays and radioreceptor assays. Vitreous proliferative p otential was measured with in vitro assays of the growth of retinal en dothelial cells and with VEGF-neutralizing antibody. Results. VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabeti c retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from pat ients with no neovascular disorders (P<0.001, P<0.001, and P = 0.006, respectively). The mean (+/-SD) VEGF concentration in 70 samples of oc ular fluid from patients with active proliferative diabetic retinopath y (3.6+/-6.3 ng per milliliter) was higher than that in 25 samples fro m patients with nonproliferative diabetic retinopathy (0.1+/-0.1 ng pe r milliliter, P = 0.008), 41 samples from patients with quiescent prol iferative diabetic retinopathy (0.2+/-0.6 ng per milliliter, P<0.001), or 31 samples from nondiabetic patients (0.1+/-0.2 ng per milliliter, P = 0.003). Concentrations of VEGF in vitreous fluid (8.8+/-9.9 ng pe r milliliter) were higher than those in aqueous fluid (5.6+/-8.6 ng pe r milliliter, P = 0.033) in all 10 pairs of samples obtained simultane ously from the same patient; VEGF concentrations in vitreous fluid dec lined after successful laser photocoagulation. VEGF stimulated the gro wth of retinal endothelial cells in vitro, as did vitreous fluid conta ining measurable VEGF. Stimulation was inhibited by VEGF-neutralizing antibodies. Conclusions. Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with i schemic retinal diseases, such as diabetic retinopathy and retinal-vei n occlusion.