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

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.

Vascular endothelial growth factor +405G/C polymorphism as a predictor of diabetic retinopathy

“…These results, no doubt call for the possibility that increased serum VEGF could be involved in the development of DR. This is in accordance with other investigators (Mironidou-Tzouveleki et al 2011;Gonzalez-Salinas et al 2017;Zhou et al 2019).…”

Potential therapeutic effects of endothelial cells trans-differentiated from Wharton’s Jelly-derived mesenchymal stem cells on altered vascular functions in aged diabetic rat model

“…Accumulating data demonstrated that the circulating levels of VEGF were higher in diabetic patients when compared to the healthy control individuals, with a noticeable positive correlation of plasma VEGF levels with diabetic microvascular complications; diabetic nephropathy, retinopathy and peripheral neuropathy [47][48][49]. Diabetes itself, endothelial dysfunction or vascular injury induced hypoxia may increase the production of VEGF.…”

A Network Pharmacology Based Analysis of The Potential Mechanisms of Compound Danshen Dripping Pill for Treatment of Diabetic Retinopathy

“…A total of 97 KEGG pathways were enriched out including the AGE-RAGE and VEGF pathway, uid shear stress and atherosclerosis, apoptosis et al AGE-RAGE and VEGF pathways play critical roles in DR and has been discussed a lot. [19][20][21][81][82][83][84][85][86][87] Except for the biochemical changes, physiological changes also play a role in the process of DR. Hemodynamic dysfunction has been found in DR and may precede clinical DR. [88][89][90][91][92] Hemodynamic parameters, wall shear rate and wall shear stress are suggested reduced in the early stage of DR, as well as retinal blood velocity and ow, which could be markers of microvasculopathy. 88,93,94 Atherosclerosis has also been considered associated with the severity of DR, manifesting increased macrovascular artery intima-media wall thickness and accompanied by wider retinal vessel diameter in DR. [95][96][97] These studies emphasize the vital role of hemodynamic changes in the early stage of DR. CDDP in TCM theory is characterized by improving blood circulation (Pharmacopoeia of the People's Republic of China).…”