Abstract
Purpose :
Diagnosing Sjögren’s syndrome (SS) underlying ocular surface inflammation is critical due to systemic co-morbidities and complications, however, currently not feasible using available tests. We tested the hypothesis that reduced tear levels of immunoregulatory Thrombospondin (TSP)-1, which also inhibits Matrix Metalloproteinase (MMP)-9, would reflect SS pathology. We performed a prospective observational case-control study to learn about changes in tear TSP-1 and MMP-9 levels in patients with ocular surface inflammation associated with SS vs. Non-SS causes.
Methods :
Total 61 participants (healthy or with clinically significant ocular surface inflammation with or without a definitive diagnosis of SS) were included. In addition to tear sampling, clinical evaluations included non-invasive tear break-up time (BUT), tear osmolarity, Schirmer’s test without anesthesia, and ocular surface staining (lissamine green for conjunctiva and fluorescein for cornea). Tear TSP-1 and MMP-9 levels were determined using custom magnetic bead-based multi-plex assay (MilliporeSigma, Burlington, MA, USA) in a masked fashion. Statistical analysis procedures included regression analysis and Fisher’s Exact test.
Results :
Average tear TSP-1 and MMP-9 levels in healthy participants (control group) were 322 and 12.2 ng/ml respectively. Significantly higher proportion of participants with SS-associated ocular surface inflammation than non-SS causes had tear TSP-1 levels below the control group average (55% vs. 29%, OR=3, 95%CI=1.64 to 5.35, p<0.05) and tear MMP-9 levels above the control group average (65% vs. 24%, OR=5.8, 95%CI=4.46 to 19.81, p<0.05). Tear TSP-1/MMP-9 ratio was significantly reduced when ocular surface inflammation was associated with SS as against non-SS causes (B= -2.36, 95% CI= -3.94 to -.0.79, p<0.05), regardless of tear MMP-9 levels. Patients with higher ratio were 72% less likely to have SS (OR=0.28, 95% CI= 0.1 to 0.75, p<0.05) and this ratio showed significant correlations with conjunctival and corneal staining scores (R= -0.3 and R= -0.29, respectively p<0.05).
Conclusions :
Our results are consistent with our hypothesis and indicate that reduced tear TSP-1 level is associated with SS pathology underlying ocular surface inflammation. Thus tear TSP-1/MMP-9 ratio can be a useful test that aids in diagnosis of SS-associated ocular surface inflammation.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.