Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders

Lloyd Paul Aiello, Paul G. Arrigg, Sabera T. Shah, Bruce A. Keyt, Robert L. Avery, Henry D. Jampel, Louis R. Pasquale, Hagen Thieme, George L. King, Mami A. Iwamoto, John E. Park, Hung V. Nguyen, Lloyd M. Aiello, Napoleone Ferrara

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Background: Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. Methods: We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmunoassays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. Results: VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic 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 patients with no neovascular disorders (P<0.001, P<0.001, and P = 0.006, respectively). The mean (±SD) VEGF concentration in 70 samples of ocular fluid from patients with active proliferative diabetic retinopathy (3.6 ±6.3 ng per milliliter) was higher than that in 25 samples from patients with nonproliferative diabetic retinopathy (0.1 ±0.1 ng per milliliter, P = 0.008), 41 samples from patients with quiescent proliferative 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 per milliliter) were higher than those in aqueous fluid (5.6 ±8.6 ng per milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from the same patient; VEGF concentrations in vitreous fluid declined after successful laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells in vitro, as did vitreous fluid containing 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 ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion., Intraocular neovascularization occurs in numerous ischemic retinal disorders, including diabetic retinopathy, ischemic retinal-vein occlusion, and retinopathy of prematurity1,2. This proliferation often results in vitreous hemorrhage, retinal detachment, and neovascular glaucoma, with subsequent visual loss. Although numerous growth factors stimulate angiogenesis in vivo,36 these factors are not consistently increased in proliferative retinopathies5,6 or secreted, as would be expected if they caused intraocular neovascularization at sites distant from those of retinal ischemia. In neovascular retinopathies such as proliferative diabetic retinopathy, there is initially extensive active proliferation of new vessels1,7. Visual loss at this time results from…

Original languageEnglish (US)
Pages (from-to)1480-1487
Number of pages8
JournalNew England Journal of Medicine
Issue number22
StatePublished - Dec 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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