title: Tear Interferon-Gamma as a Biomarker for Evaporative Dry Eye Disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity The University of Melbourne, Parkville, Victoria, Australia|Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: David Charles
authors.initials: DC
authors.lastname: Jackson
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity The University of Melbourne, Parkville, Victoria, Australia
authors.forename: Weiguang
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity The University of Melbourne, Parkville, Victoria, Australia
authors.forename: Chinn Yi
authors.initials: CY
authors.lastname: Wong
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity The University of Melbourne, Parkville, Victoria, Australia
authors.forename: Edin Jessica
authors.initials: EJ
authors.lastname: Mifsud
authors.affiliation: The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia
authors.forename: Nicholas Andrew
authors.initials: NA
authors.lastname: Williamson
authors.affiliation: The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia
authors.forename: Ching-Seng
authors.initials: CS
authors.lastname: Ang
authors.affiliation: Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia
authors.forename: Algis Jonas
authors.initials: AJ
authors.lastname: Vingrys
authors.affiliation: Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia
authors.forename: Laura Elizabeth
authors.initials: LE
authors.lastname: Downie
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011446:Prospective Studies; D013666:Tears / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007371:Interferon-gamma