Clinical Significance of Tear Matrix Metalloproteinase-9 Reaction Intensity in Thyroid Eye Disease.

Background/Objectives: The objectives of this study were to investigate the association between tear matrix metalloproteinase-9 (MMP-9) grade and thyroid eye disease (TED) activity and to evaluate its discriminatory performance for active TED. Methods: This retrospective cross-sectional study included 322 patients with TED, including 188 with inactive disease and 134 with active disease. Tear MMP-9 reaction intensity was graded from 0 to 3 using InflammaDry, and active TED was defined as a Clinical Activity Score (CAS) of ≥3. Receiver operating characteristic analysis was used to assess discriminatory performance. Multivariable logistic regression was used to evaluate the independent association between a grade 3 result and active TED, adjusting for age, sex, and serum thyroid-stimulating hormone receptor antibody level. The main outcome measures were the association of tear MMP-9 grade with CAS, area under the receiver operating characteristic curve, adjusted odds ratio, and diagnostic performance for active TED. Results: Tear MMP-9 grade was significantly higher in active than in inactive TED and correlated positively with disease activity (Spearman's ρ = 0.253, p < 0.001). Its overall discriminatory performance for active TED was modest (area under the curve, 0.619; 95% confidence interval, 0.552-0.682). A grade 3 result was independently associated with active TED (adjusted odds ratio, 8.65; 95% confidence interval, 2.86-26.17; p < 0.001) and demonstrated high specificity (97.9%) but low sensitivity (19.4%), with a positive predictive value of 86.7% and a positive likelihood ratio of 9.12. Conclusions: Tear MMP-9 grade was associated with TED activity and may provide clinically relevant information regarding ocular surface inflammation in TED.