Tear cytokine levels in Sjogren's syndrome-related dry eye disease compared with non-Sjogren's syndrome-related dry eye disease patients: A meta-analysis

Background: As a common complication of Sjogren syndrome (SS), SS-related dry eye disease (SS-DED) significantly affects the patients' quality of life. Pro-inflammatory cytokines in tears are widely believed to play a crucial role in the pathogenesis of SS-DED. A systematic literature review with meta-analyses was conducted to provide a quantitative summary of tear cytokine levels in SS-DED compared with non-SS-DED and healthy controls.

Methods: The PubMed, Embase, Web of Science, Ovid, and Scopus databases were searched until June 2022. Original case-control studies investigating tear cytokines in SS-DED patients compared with non-SS-DED or healthy individuals were included. Differences of cytokines levels were compared with random-effects standardized mean differences ± 95% confidence intervals calculated as the effect size.

Results: A total of 15 articles, 809 subjects (302 for SS-DED, 220 for non-SS-DED, and 287 for healthy controls) were included in the study. SS-DED patients had higher tear levels of interferon-gamma, interleukin (IL)-17, IL-1β, IL-2, IL-4, IL-6, and IL-8 as compared to healthy controls. As for comparison between SS-DED and non-SS-DED group, the levels of IL-12p70, IL-17, IL-4, IL-6, IL-8, and tumor necrosis factor-alpha were significantly higher in SS-DED patients compared with the non-SS-DED group. The level of epidermal growth factor was significantly lower in SS-DED patients compared with both non-SS-DED patients and healthy controls.

Conclusion: The findings from this study provide evidence for levels of tear cytokines in SS-DED to become potential diagnostic biomarkers or therapeutic targets. Further studies with a higher number of subjects and improved quality are necessary.