Tear Fluid Lymphotoxin-Alpha as a Diagnostic Biomarker for the Stratification of Dry Eye Disease

This study aimed to investigate the diagnostic value of the tear lymphotoxin-α (LTA) concentration for dry eye disease (DED).

A total of 160 subjects-75 patients with DED, 55 individuals without DED, and 30 pain-without-stain patients were included. Ocular Surface Disease Index (OSDI), the tear LTA concentration, tear break-up time (TBUT), MMP-9, IL-1ra, IL-1β, IL-6, IL-8, IL-17, and IFN-γ, and MUC5AC levels, corneal fluorescein staining (CFS), conjunctival lissamine green staining (CLGS), conjunctival impression cytology (IC), Schirmer I test, and conjunctival goblet cell counts were determined.

Tear LTA concentration varied among the three groups, being the lowest in the DED group and the highest in the pain-without-stain group. The overall agreement rate between LTA diagnosis and expert consensus diagnose was 83.85%. The kappa coefficient was 0.670 (P < 0.001). Significant differences in tear LTA concentration were observed among all severity groups. Receiver operating characteristic (ROC) curve analysis revealed cutoff values of 105 pg/mL, 855 pg/mL, and 1580 pg.mL as an exploratory stratification thresholds for distinguishing the severe DED (LTA <105 pg/mL), mild DED (LTA 105 pg/mL to 855 pg/mL), non-DED (LTA 855 pg/mL to 1580 pg/mL), and pain-without-stain groups (LTA > 1580 pg/mL). Moreover, significant differences in the OSDI, the TBUT, CFS results, CLGS results, IC results, MMP-9, IL-1ra, IL-1β, IL-6, IL-8, IL-17, IFN-γ, and MUC5AC concentrations were detected among the different LTA groups.

Throughout the cohort, we explored the potential of tear LTA concentration for the diagnosis and graded classification diagnosis of dry eye.

Tear LTA is a potential biomarker for the graded classification and subtyping of dry eye, and is expected to become a novel biomarker in the diagnosis and management of dry eye.