Relationships among Retinal Nonperfusion, Neovascularization, and Vascular Endothelial Growth Factor Levels in Quiescent Proliferative Diabetic Retinopathy.

Ho Ra,Jiwon Baek,Jae Hyun Park,Jin Uk Baek

doi:10.3390/jcm9051462

Abstract

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.

Highlights

Diabetic retinopathy (DR) is one of the most important complications in diabetic patients
Pathognomonic findings of proliferative diabetic retinopathy (PDR) include formation of retinal neovascularization (NV), which can result in vitreous hemorrhage or tractional retinal detachment [7,8]
The study group consisted of all consecutive type 2 diabetic mellitus (DM) patients who underwent intravitreal bevacizumab injection for treatment-naïve quiescent PDR between August 2016 and September 2018 in the Department of Ophthalmology of Bucheon St

Summary

Introduction

Diabetic retinopathy (DR) is one of the most important complications in diabetic patients. Nonperfusion areas (NPAs) are predominantly found in the mid-peripheral retina and are associated with DR severity [4,5,6]. The association between peripheral NP areas and NV was reported using ultra-widefield fluorescein angiography (UWF FA) [5,10]. VEGF injection was reported to be sufficient to cause capillary occlusion with ischemia, thereby creating NP areas [20]. Experimental studies revealed that VEGF can initiate the process of NV formation, which involves other pathways such as inflammation, cellular immunity, and downregulation of angiogenic inhibitors [21,22,23,24]. The purpose of this study was to quantitatively investigate head-to-head relationships among NP areas, NV area and number, and VEGF levels in PDR eyes

Methods

Patients

Image Analysis

Cytokine Analysis

Statistical Analysis

Baseline Demographic and Clinical Features