Reduced tear thrombospondin‐1/matrix metalloproteinase‐9 ratio can aid in detecting Sjögren's syndrome etiology in patients with dry eye

Differentiating patients with Sjögren's syndrome (SS)‐associated dry eye from non‐SS dry eye is critical for monitoring and appropriate management of possible sight‐ or life‐threatening extraglandular complications associated with SS. We tested whether reduced tear levels of immunoregulatory thrombospondin (TSP)‐1, which also inhibits matrix metalloproteinase (MMP)‐9, would reflect SS pathogenesis aiding the identification of patients with SS‐dry eye. Total of 61 participants, including healthy controls (n = 20), patients with non‐SS dry eye (n = 20) and SS‐dry eye (n = 21) were enrolled prospectively. Tear TSP‐1 and MMP‐9 levels were measured using a custom magnetic bead‐based multi‐plex assay in a masked manner. Analyte concentrations were assessed further according to ocular surface and tear film parameters. Relative to median tear TSP‐1 (308 ng/ml) and MMP‐9 (1.9 ng/ml) levels in the control group, significantly higher proportion of patients with SS‐dry eye than non‐SS had lower tear TSP‐1 levels (55% vs. 29%, odds ratio [OR] = 3, 95% confidence interval [CI] = 1.64 to 5.35, p < 0.05) and higher tear MMP‐9 levels (65% vs. 24%, OR = 5.8, 95% CI = 4.46 to 19.81, p < 0.05), respectively. The tear TSP‐1/MMP‐9 ratio was significantly reduced in patients with SS‐dry eye compared to non‐SS (B = −2.36, 95% CI = −3.94 to −0.0.79, p < 0.05), regardless of tear MMP‐9 levels. Patients with a lower ratio were 2.3 times more likely to have SS (OR = 0.28, 95% CI = 0.1 to 0.75, p < 0.05). This ratio showed significant inverse correlations with clinical parameters (conjunctival and corneal staining scores). Our results denote that tear TSP‐1/MMP‐9 ratio can be useful in identifying patients with dry eye with underlying SS and used as a screening test.