Tear interleukin-6 and clinical activity in thyroid eye disease

Thyroid eye disease (TED) is an autoimmune orbital disorder in which interleukin-6 (IL-6) may reflect inflammatory activity. We evaluated tear IL-6 concentrations across disease activity groups, their association with the Clinical Activity Score (CAS), and paired tear-serum differences. This prospective cross-sectional study included 42 adults: 15 with active TED (CAS ≥3), 14 with inactive TED (CAS 0-2), and 13 healthy controls. IL-6 was measured in diluted tear samples collected by micro-volume wash and paired serum using cytometric bead array with flow cytometry. Analyses comprised one-way analysis of variance, paired Student t-tests, and Pearson correlation. Mean tear IL-6 concentrations were 22.33, 8.49, and 3.82 pg/mL in active TED, inactive TED, and controls, respectively, with a significant overall difference across groups (p = 0.002). Tear IL-6 concentrations exceeded serum concentrations in active and inactive TED (p = 0.001 and p = 0.005, respectively), with no significant difference in controls (p = 0.309). In active TED, tear IL-6 correlated positively with CAS (r = 0.55; 95% confidence interval, 0.05-0.83; p = 0.032). These exploratory findings support further investigation of tear IL-6 as a correlate of clinical activity. Unmeasured ocular-surface status, unquantified tear dilution, and extrapolation below the assay's lowest calibrator limit interpretation; larger longitudinal studies incorporating objective ocular-surface assessment and assays validated for tear fluid are needed before clinical application.