Tear interferon-gamma as a biomarker for evaporative dry eye disease

Abstract

PURPOSE. To assess whether tear hyperosmolarity, being diagnostic of dry eye disease (DED), is associated with specific alterations to the cytokine content of human tears that may provide a biomarker for DED. METHODS. In this prospective, cross-sectional, clinical study, participants (n = 77) were recruited from a single clinical site and categorized into groups based upon tear osmolarity status (n = 62 hyperosmolar, n = 15 normo-osmolar). Comprehensive anterior eye clinical assessments were undertaken. Concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) in basal tears were assayed using multiplex cytometric bead array. The main outcome measure was difference in cytokine concentration between groups. Group comparisons were undertaken using 2-tailed t-tests. Cohen’s effect size was calculated for each finding. Spearman correlations between cytokine concentrations, clinical symptoms, and clinical parameters of DED were calculated. RESULTS. Tear hyperosmolarity was specifically associated with increased tear IFN-γ levels (13.3 ± 2.0 vs. 4.4 ± 1.4 pg/mL, P = 0.03). Cohen’s effect size was large (0.8) for changes to tear IFN-γ levels. Significant correlations were observed between IFN-γ concentration and each of: tear osmolarity (r = 0.34; P = 0.007), total ocular surface staining (r = 0.56, P < 0.0001), and Schirmer test score (r = -0.33, P = 0.003). CONCLUSIONS. Tear hyperosmolarity is specifically associated with higher levels of the proinflammatory cytokine IFN-γ, which correlate with key clinical parameters of DED. The calculated effect size (0.8) suggests that this assay has diagnostic power as a biomarker for evaporative DED.