Aqueous Humor Mediator and Cytokine Aberrations in Diabetic Retinopathy and Diabetic Macular Edema: A Systematic Review and Meta-Analysis

PURPOSE: To evaluate the relationship between the aqueous humor levels of VEGF, TNF-α, IL-10, IL-6, IL-12, MCP-1, and IP-10 with DR/DME. METHODS: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched up to October 2018. Systematic review and meta-analysis were conducted. RESULTS: 18 studies comprising 362 cases with DR (100 with DME) and 620 controls without DR were included in this meta-analysis. There was a significant association between VEGF levels in the aqueous humor and DR (standardized mean difference (SMD) 1.94 (95% CI 1.05-2.83)) and DME (1.07 (0.71, 1.42)). Furthermore, a significant correlation was observed between levels of IL-6 and DR (3.53 (0.37, 6.69)), and similarly correlation with DME (1.26 (0.30, 2.21)). The relationship between MCP-1 and DR and DME was significant, in which the SMD was (0.49 (0.09, 0.89)) and (1.49 (0.78, 2.20)), respectively. However, IL-12, IP-10, and TNF-α had no correlation with DR and DME, whereas there was a significant relationship between IL-8 and DME (1.68 (0.97, 2.40)). CONCLUSION: Elevated levels of VEGF, IL-6, and MCP-1 in the aqueous humor were associated with the risk for the presence of DR, and levels of VEGF, IL-6, IL-8, and MCP-1 were associated with the risk of DME. Furthermore, these biomarkers may be used as potential predictors or therapeutic targets for DR/DME.