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

Zhongwei Zhou, Huixiang Ju, Mingzhong Sun, Hongmei Chen, Zhongwei Zhou, Huixiang Ju, Mingzhong Sun, Hongmei Chen

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.

Figures

Figure 1
Figure 1
Flow chart of the study selection process.
Figure 2
Figure 2
Forest plot summarizing the relationship of serum and plasma VEGF level in DR patients with those in NDR patients: serum (a) and plasma (b).
Figure 3
Figure 3
Forest plot summarizing the relationship of serum and plasma VEGF level in NPDR patients with those in NDR patients: serum (a) and plasma (b).
Figure 4
Figure 4
Forest plot summarizing the relationship of serum and plasma VEGF level in PDR patients with those in NDR patients: serum (a) and plasma (b).
Figure 5
Figure 5
Forest plot summarizing the relationship of serum and plasma VEGF level in PDR patients with those in NPDR patients: serum (a) and plasma (b).
Figure 6
Figure 6
Metaregression analysis of the relationship between the publication year and the effect sizes in serum and plasma samples: serum (a) and plasma (b).
Figure 7
Figure 7
Sensitivity analysis of included studies: serum (a) and plasma (b).
Figure 8
Figure 8
Visual inspection of funnel plots evaluating potential publication bias of included studies: serum (a) and plasma (b).

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