The Change of Aqueous Humor Cytokine Levels after Anti-VEGF in Diabetic Macular Edema: A Systematic Review and Meta-Analysis

BACKGROUND: Diabetic macular edema (DME) is a vision-threatening complication that severely impairs vision, and VEGF has a certain improvement effect on it as a growth factor. OBJECTIVE: To assess the alterations of different aqueous humor cytokine concentrations after intravitreal antivascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). METHODS: We searched PubMed, EMBASE, and the Cochrane Library from inception up to May 2022 for studies evaluating the alterations of different aqueous humor cytokine concentrations after intravitreal anti-VEGF treatment for diabetic macular edema. The estimates from eligible studies were meta-analyzed by the Hartung–Knapp/Sidik–Jonkman random-effects method. Egger's regression test was used to determine the publications' bias. A 95% confidence interval was calculated across studies. The analysis was performed using STATA™ Version 15 software. RESULTS: Nine eligible studies involving a total of 209 eyes for our systematic review were identified through our search strategy. The mean differences in 1-month and 2-month changes of VEGF were 110.681 pg/ml (P < 0.001) and 283.474 pg/ml (P=0.003), respectively. The mean difference in 2-month changes of interleukin 6 (IL-6) was −24.784 pg/ml (P=0.037). The mean difference in 3-month changes of central macular thickness was 130.372 μm (P < 0.001). CONCLUSIONS: Intravitreal injection of anti-VEGF exerts a protective effect on macular edema secondary to diabetic retinopathy by affecting various cytokine concentrations, especially reducing aqueous VEGF concentrations and interleukin 6 in patients with DME.