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 ¼ 77) were recruited from a single clinical site and categorized into groups based upon tear osmolarity status (n ¼ 62 hyperosmolar, n ¼ 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-c, and TNF-a) 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-c levels (13.3 6 2.0 vs. 4.4 6 1.4 pg/mL, P ¼ 0.03). Cohen's effect size was large (0.8) for changes to tear IFN-c levels. Significant correlations were observed between IFN-c concentration and each of: tear osmolarity (r ¼ 0.34; P ¼ 0.007), total ocular surface staining (r ¼ 0.56, P < 0.0001), and Schirmer test score (r ¼ À0.33, P ¼ 0.003).CONCLUSIONS. Tear hyperosmolarity is specifically associated with higher levels of the proinflammatory cytokine IFN-c, 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.Keywords: dry eye, diagnosis, cytokine, inflammation, osmolarity, tear, interferon-gamma T ear hyperosmolarity is a consequence of reduced lacrimal secretion and/or excessive tear evaporation, and is recognized to be a key pathogenic mechanism in dry eye disease (DED). [1][2][3][4] While historically the clinical assessment of tear osmolarity has been hindered by difficulties associated with tear collection methods and access to laboratory facilities, technological advancements have enabled tear osmolar determinations to become clinically viable. Measurement of tear osmolarity has been suggested to be the single best objective indicator of DED severity.5 A diagnostic cut-off value of 316 mOsmol/L has been described to be highly specific for diagnosing clinically significant DED, yielding a sensitivity of 73% and a specificity of 90%. 6 In DED, abnormal elevation of the osmolarity of the tear fluid is proposed to induce epithelial injury through the activation of inflammatory events at the ocular surface, resulting in the liberation of inflammatory mediators that can induce epithelial cell apoptosis. 1,7 Short-term exposure of cultured human corneal epithelial cells to an hyperosmolar medium can induce IL-6 expression.8 In an animal model of ocular surface disease, tear hyperosmolarity resulted in conjunctival goblet cell death and tear film instability. 9 Fur...

Molecular evidence for the role of inflammation in dry eye disease

“…A number of cytokines have been investigated with respect to their alterations in ocular surface disease, including interferon‐γ which was shown to correlate with tear hyperosmolarity and ocular surface staining, in a primarily evaporative DED cohort, in a recent study described by Jackson et al The results of this study lend support to the consideration of specific cytokines as biomarkers that might be used in point‐of‐care diagnostic testing for DED in clinical practice in the future.…”

Optical Coherence Tomography Reveals Changes to Corneal Reflectivity and Thickness in Individuals with Tear Hyperosmolarity

“…Indeed, altered levels of tear proteins have been documented in heterogeneous clinical populations of dry eye patients. 35–39 …”

Wenn Tränenersatzmittel nicht mehr ausreichen: die Bedeutung von Entzündungsprozessen beim Trockenen Auge. Praktische Aspekte einer antientzündlichen Therapie des Trockenen Auges

“…Als indirekter Nachweis für das Vorliegen einer Entzündungsreaktion kann die Tränenfilmosmolarität herangezogen werden, da eine Hyperosmolarität des Tränenfilms die Expression von Interferon-γ direkt erhöht, d. h. es besteht ein direkter Zusammenhang zwischen diesen beiden Parametern [15,23]. Die Osmolarität korreliert ferner sehr gut mit anderen diagnostischen Tests für das Trockene Auge und auch mit dem Schweregrad der Erkrankung [24,25].…”