Evaluations of tear protein markers in dry eye disease: repeatability of measurement and correlation with disease.

ABSTRACT

PURPOSE: We characterized tear protein markers in dry eye disease (DED). METHODS: In this prospective study, based on the ocular surface disease index (OSDI) and corneal staining (CS), 95 DED patients (OSDI ≥13) with increasing CS were enrolled into 3 severity groups DE1 (CS <4), DE2 (CS 4-7), and DE3 (CS >7), while 25 asymptomatic subjects with no CS were enrolled into the control group (OSDI <13 and CS = 0). Tear fluid was collected at day 0 and day 7 visits, and concentrations of 43 protein markers were measured by multiplexed immunoassay. RESULTS: We analyzed 22 control and 80 DED subjects. Among 33 markers detectable, good inter-visit repeatability was observed with 25 markers, with intraclass correlation coefficients (ICC) ranging from 0.85-0.60; ICCs were <0.60 in the other 8. Correlation with clinical measures was found with two markers, with absolute partial correlation coefficients >0.40 Interleukin-1 receptor antagonist (IL-1Ra) and IL-8. IL-1Ra and IL-8 correlated with conjunctival staining (0.43, P < 0.001 and 0.35, P < 0.01, respectively), and with Schirmer test (-0.58 and -0.42, P < 0.001). IL-1Ra and IL-8 in DE3 were 4.4- and 2.1-fold higher than in DE1 (P = 0.0001 and 0.0007), and 1.9- and 1.6-fold higher than in DE2 (P = 0.022 and 0.017). IL-1Ra in DE2 was 2.3-fold higher than in DE1 (P = 0.038). CONCLUSIONS: Tear levels of many immune mediators were highly repeatable between visits in DED. Among them, IL-1Ra and IL-8 were associated with clinical signs and disease severity defined by corneal staining.