Serum Vascular Endothelial Growth Factor Levels Correlate with Severity of Retinopathy in Diabetic Patients: A Systematic Review and Meta-Analysis.

Zhongwei Zhou,Huixiang Ju,Hongmei Chen,Mingzhong Sun

doi:10.1155/2019/9401628

Abstract

Background Investigations regarding serum and plasma vascular endothelial growth factor (VEGF) levels in patients with diabetic retinopathy (DR) are conflicting. This meta-analysis is aimed at determining whether serum and plasma VEGF levels are associated with DR and its severity in diabetic patients. Methods PubMed and EMBASE were used to search for published studies, and serum and plasma VEGF levels were compared among DR, nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and nondiabetic retinopathy (NDR) patients. Standardized mean differences (SMD) and 95% confidence interval (CI) were pooled using a random effects model. Results A total of 29 studies comprising 1805 DR (or NPDR or PDR) patients and 1699 NDR patients were included. ELISA was used to evaluate serum or plasma VEGF levels in all except for two studies included in this meta-analysis. Overall, serum VEGF levels were significantly higher in DR patients (SMD: 0.74, 95% CI: 0.44-1.03) than those in NDR patients, while plasma VEGF levels were not in the comparison (SMD: 0.40, 95% CI: −0.13-0.92). Similarly, NPDR (SMD: 0.51, 95% CI: 0.22-0.80) and PDR (SMD: 1.32, 95% CI: 0.79-1.85) patients had higher serum VEGF levels compared with NDR patients, but the difference was not significant in plasma samples (SMD: 0.24, 95% CI: −0.47-0.95; SMD: 0.37, 95% CI: −0.30-1.05). In addition, serum VEGF levels were higher in PDR patients than those in NPDR patients (SMD: 0.87, 95% CI: 0.41-1.33), but plasma VEGF levels were not (SMD: −0.00, 95% CI: −0.31-0.31). The subgroup and metaregression analysis revealed that the study location, study design, and publication year of a study have certain influence on heterogeneity between studies in serum or plasma samples. Conclusions VEGF levels in the serum instead of those in the plasma correlate to the presence and severity of DR in diabetic patients. Further large-scale studies are required to confirm these findings.

Highlights

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus, and it can be clinically classified into nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR), depending on whether or not neovascularization is found in the retina [1, 2]
The additional inclusion criteria were (1) studies in adult subjects, (2) the study population of diabetic patients, (3) DR which was the outcome and the control group consisting of nondiabetic retinopathy (NDR) patients, or (4) the study published in English
The 19 articles were further excluded for lack of necessary data on vascular endothelial growth factor (VEGF) levels, no appropriate comparison groups, and patient samples that overlapped with another study

Summary

Introduction

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus, and it can be clinically classified into nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR), depending on whether or not neovascularization is found in the retina [1, 2].The pathogenesis of DR is extremely complicated. Investigations regarding serum and plasma vascular endothelial growth factor (VEGF) levels in patients with diabetic retinopathy (DR) are conflicting. This meta-analysis is aimed at determining whether serum and plasma VEGF levels are associated with DR and its severity in diabetic patients. PubMed and EMBASE were used to search for published studies, and serum and plasma VEGF levels were compared among DR, nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and nondiabetic retinopathy (NDR) patients. NPDR (SMD: 0.51, 95% CI: 0.22-0.80) and PDR (SMD: 1.32, 95% CI: 0.79-1.85) patients had higher serum VEGF levels compared with NDR patients, but the difference was not significant in plasma samples (SMD: 0.24, 95% CI: −0.47-0.95; SMD: 0.37, 95% CI: −0.30-1.05). Further large-scale studies are required to confirm these findings

Methods

Results

Conclusion