Role of biomarkers in South Indian Thyroid Eye Disease study (SITED)

Abstract

Purpose: Thyroid eye disease (TED) is a complex autoimmune disease. Early detection with routine disease monitoring using biomarker assessment would help in mitigating TED-associated vision loss. Hence, we performed a non-invasive tear fluid (TF) based screening in patients with TED as part of the South Indian Thyroid Eye Disease Study (SITED). Materials and Methods: We used TF from healthy controls (HC;13 eyes;13 subjects), patients with thyroid dysfunction but without TED (No TED;11 eyes;11 subjects) and patients with TED (18 eyes;18 subjects). TED subjects were further sub-divided into those with and without an active form of the disease. Patients with dysthyroid optic neuropathy (DON) were analyzed separately. The diagnosis of TED was based on Gorman and Bartley’s criteria. Activity was defined as scoring more than 4 in the Vision, Inflammation, Strabismus and Appearance (VISA). Schirmer’s strip was used to collect TF and the levels of IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-22, IFNγ, TNFα, PDGF-AA and PDGF-BB were determined by multiplex ELISA using flow cytometry. Results: Significantly (p < 0.05) higher levels of IL-6 and IL-10 were observed in TED patients compared to HC and No TED subjects. TF levels of IL-6 and IL-10 were significantly higher in active TED patients compared to No TED subjects. Interestingly, TF levels of PDGF-AA were observed to be negatively associated with IL-4 and IL-13. Conclusion: Elevated TF levels of IL-6 and IL-10 can be explored for their role as a non-invasive risk stratification biomarker or as targets to modulate management of TED.