Changes in Human Tear Proteome Following Topical Treatment of Dry Eye Disease: Cyclosporine A Versus Diquafosol Tetrasodium

PURPOSE. To compare the changes in human tear proteome and clinical effects following topical cyclosporine A (CsA) 0.05% or diquafosol tetrasodium (DQS) 3% treatment of dry eye disease (DED), and to identify biomarkers for determining disease severity and treatment effectiveness in DED. METHODS. A total of 18 patients were diagnosed with non-Sjogren DED. Nine patients in each group were treated with topical CsA 0.05% or DQS 3% for 4 weeks. Tear samples were collected after evaluation of tear breakup time, corneal and conjunctival erosion staining, and results of Schirmer's test 1 before and after treatment. Proteomes were characterized using liquid chromatography mass spectrometry, and proteins exhibiting a fold change > 1.5 or < 0.67 (P < 0.05) were considered differentially expressed (DEP). RESULTS. A total of 794 proteins were identified, with no significant difference observed between pretreatment and posttreatment conditions. Proteomic analysis identified 54 and 106 DEPs between treatment groups (CsA and DQS, respectively), with gene ontology analysis indicating that both treatments enhanced innate and adaptive immune responses and cellular detoxification. Protein-network analysis showed that inflammation associated with the immune response was primarily responsible for the therapeutic process in both groups. CONCLUSIONS. These results provide insight into the broad scope of changes at the ocular surface in DED and indicated that although both drugs improved the clinical parameters, the activated tear-specific biomarkers differed significantly between treatments. Our findings suggest that the DEPs identified here and those correlated with the clinical parameters might represent candidate biomarkers for DED.