Tear Levels of Inflammatory Cytokines in Keratoconus: A Meta-Analysis of Case-Control and Cross-Sectional Studies

Purpose. To assess the tear levels of inflammatory cytokines in patients with keratoconus (KC). Design. Systemic review and meta-analysis. Methods. The following electronic databases and search engine were searched: PubMed, EMBASE, Web of Science, and Google Scholar. A systematic search of all relevant studies published through January 2021 was conducted, and the standardized mean difference (SMD) and 95% confidence interval (CI) of cytokine levels were calculated to estimate the pooled effects. Sensitivity analysis, subgroup analysis, and metaregression were applied to explore the sources of heterogeneity. Results. A total of 7 studies with 374 participants (374 eyes) from clinical studies were included. The tear levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were significantly increased in KC compared with normal controls. The SMD of IL-1 beta was 1.93 (95% CI 0.22 to 3.65, P = 0.03). The SMD of IL-6 was 1.22 (95% CI 0.59 to 1.84, P < 0.001). The SMD of TNF-alpha was 1.75 (95% CI 0.66 to 2.83, P = 0.002). There was no significant difference between the two groups on interleukin-4 (IL-4) and interleukin-10 (IL-10). The SMD for IL-4 was 2.36 (95% CI -0.28 to 5.00, P = 0.08) and for IL-10 was 0.30 (95% CI -1.29 to 1.89, P =0.71). Meta-regression analysis indicated that the heterogeneity maybe significantly correlated with the method of detection, the different ages, and the source of population. Conclusions. Our meta-analysis demonstrated that proinflammatory cytokines IL-1 beta, IL-6, and TNF-alpha were increased, indicating that cytokine profile changed in KC tears and inflammation may play an important role in the pathogenesis and development of KC.