Tear Inflammatory Cytokine Profiles in Thyroid-Associated Ophthalmopathy

Purpose: To provide a review surrounding the utility of tear inflammatory cytokines in thyroid-associated ophthalmopathy (TAO). Methods: A comprehensive search was performed for published English-language studies reporting the analysis of tear inflammatory cytokines in TAO. Exclusion criteria included in vitro studies describing tear proteomics (without cytokine analysis). Results: Nine studies have been published between 2012 and 2020. An extensive range of inflammatory cytokines have been studied, notably, but not exclusively, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-18, tumor necrosis factors-α, interferons-γ, and vascular endothelial growth factor. Methods of tear collection included unstimulated tear samples from the inferior fornix and Schirmer’s strips, with analysis via multiplex bead array assay or enzyme-linked immunosorbent assay. Mixed findings have been published surrounding the changes in tear inflammatory cytokines in TAO. Active TAO has demonstrated significant differences in various inflammatory cytokines compared with inactive disease and healthy controls. Changes in tear inflammatory cytokines correlate well with various ocular surface disease parameters and disease activity. The role of tear inflammatory cytokines in monitoring treatment response remains to be determined. Conclusion: Tear inflammatory cytokines demonstrate promise as a noninvasive biomarker and may shed light on the pathological mechanisms underlying ocular surface disease and orbital inflammation in TAO. There may be a role in correlation with clinical activity parameters and monitoring of treatment response. Further studies are necessary to validate existing data and its application in the clinical setting, and to explore tear cytokine profiles in other orbital inflammatory diseases (OIDs), including dacryoadenitis.