Decreased Ratio of VEGF165b/VEGF in Aqueous Humor Predicts Progression of Diabetic Retinopathy

Background: Different splicing of vascular endothelial growth factor (VEGF) gene results in 2 families of VEGF, the proangiogenic isoforms (VEGF(xxx)a) and the antiangiogenic isoforms (VEGF(xxx)b). VEGF(165)b is the major antiangiogenic isoform of VEGF and the most studied member of the VEGF(xxx)b family so far. Objectives: To determine the concentration of VEGF(165)b and VEGF in the aqueous humor (AH) in diabetic eyes with or without diabetic retinopathy (DR) and to address the predictive value of VEGF(165)b/VEGF ratio for progression of DR. Methods: AH samples from 20 eyes in healthy controls (CON group), 40 eyes in diabetic patients without DR (nDR group), and 30 eyes in diabetic patients with mild nonproliferative DR (DR group) were collected. All of the patients were followed up for at least 5 years. VEGF(165)b and VEGF levels of AH samples were measured by enzyme-linked immunosorbent assay (ELISA). The predictive value of the initial VEGF(165)b/VEGF ratio for progression of DR was studied. Results: The mean concentration of VEGF(165)b significantly decreased in diabetic eyes vs. controls. The mean concentration of VEGF significantly increased in the DR group vs. the CON group. The VEGF(165)b/VEGF ratio was significantly lower in diabetic patients compared to the CON group. The VEGF(165)b/VEGF ratio was significantly lower in diabetic patients compared to the control group. The mean follow-up was 66.1months (range 60-71 months). The risk of DR progression was greater with a lower VEGF(165)b/VEGF ratio. Conclusion: The VEGF(165)b/VEGF ratio is lower in the AH of DR patients and the decreased ratio of VEGF(165)b/VEGF predicts DR progression.