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Laura Elizabeth Downie, Weiguang Zeng, Edin Mifsud, Chinn Yi Wong, Nicholas Williamson, Ching-Seng Ang, Algis J Vingrys, David Jackson; Interferon-gamma as a potential biomarker for the inflammation associated with dry eye disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):404.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye disease (DED) is a highly prevalent, potentially debilitating eye condition that is characterized by tear hyperosmolarity. Inflammation is associated with DED, however whether changes to tear inflammatory cytokines can be used for clinical diagnosis requires further study. We tested a hypothesis that tear hyperosmolarity is associated with specific alterations to the cytokine content of human tears that may provide a diagnostic clinical biomarker for DED.
This prospective, cross-sectional clinical study involved 22 adult participants who were categorized into groups based upon tear osmolarity (n=13 hyper-osmolar, n=9 normo-osmolar). Concentrations of seven cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17A, interferon (IFN)-γ and tumor necrosis factor (TNF)-α) were assayed from tear samples using multiplex cytometric bead array. Group comparisons were undertaken using a two-tailed t-test. Spearman correlations between cytokine concentrations, clinical symptoms and ocular surface signs were determined. Cohen’s effect size was calculated as a quantitative measure of the strength of a finding. The diagnostic potential of a biomarker was determined for changes showing at least large effects, defined by Cohen as an effect size >0.8.
Tear hyperosmolarity was associated with significantly elevated tear IFN-γ levels only (mean±SEM: 235.0 ± 28.5 versus 106.4 ± 15.4 pg/mL, p=0.002). Cohen’s effect size was very large (1.6) only for changes to tear IFN-γ levels. Tear IFN-γ concentration showed significant correlations with each of the following clinical signs: (i) tear osmolarity (r=0.64, p=0.002), (ii) sodium fluorescein tear break-up time (r=-0.61, p=0.003) and (iii) total ocular surface staining (r=0.48, p=0.02).
Tear hyperosmolarity is associated with higher levels of the pro-inflammatory cytokine IFN-γ, which correlates with key clinical parameters of DED. The effect size calculations indicate a potential sensitivity of 79% and specificity of 73%, suggesting that this assay has diagnostic power as a biomarker for inflammation in DED.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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