Relationships among retinal nonperfusion, neovascularization, and vascular endothelial growth factor levels in quiescent proliferative diabetic retinopathy

Purpose: To investigate the relationships among the retinal nonperfusion (NP) area, neovascularization (NV) area, and aqueous humor vascular endothelial growth factor (VEGF) levels in quiescent proliferative diabetic retinopathy (PDR). Methods: Forty-seven eyes from 47 patients with treatment-naïve PDR that did not show macular edema or vitreous hemorrhage were enrolled. NP area, NV number, and NV area were quantitatively measured using ultra-widefield fluorescein angiography in an automated manner. Aqueous humor VEGF level was measured using a bead assay. Results: The NP areas of the total, posterior pole, peripheral retinae, and NV area positively correlated with each other (all p < 0.034). NV number correlated with total NP area, peripheral NP area, and NV area (all p ≤ 0.001). VEGF levels were significantly positively correlated with total, posterior polar, and peripheral NP areas and NV area (r = 0.575, 0.422, 0.558, and 0.362, respectively; all p ≤ 0.012). In eyes with NV in the disc area, the VEGF level was higher compare to eyes without NV in the disc area (208.89 ± 192.77 pg/mL vs. 103.34 ± 132.66, p = 0.010). A multiple linear regression model using NP area, NV area, and NVD demonstrated good prediction for VEGF level (R2 = 0.417, p < 0.001) and revealed a significant contribution of the peripheral NP area in predicting the VEGF level (β = 0.497, p = 0.002). Conclusions: Aqueous humor VEGF levels in quiescent PDR eyes were associated with NP and NV areas, which had positive correlations with each other. In addition, the NP area of the peripheral retina was the most important predictor of VEGF level.