Tear Cytokine a Promising Biomarker for Dry Eye Severity, Subtypes

Lymphotoxin-α is a protein produced and secreted by activated immune cells. It is found in several areas of the human body, including tears, and can be used as a biomarker for ocular surface health. Clinical applications of this research have not been developed yet, however. Photo: Luis Rojas, OD. Click image to enlarge. In a recent study, a tear lymphotoxin-alpha (lymphotoxin-α or LTA) test accurately identified dry eye disease severity, as well as distinguishing patients with symptoms but no clinical signs, indicating its potential usefulness as a biomarker for disease diagnosis and classification.Researchers evaluated whether LTA, an inflammatory protein found in tears, could improve dry eye diagnosis beyond that of conventional clinical testing. The researchers enrolled 160 adults, including 75 patients with dry eye disease (DED), 55 individuals without DED and 30 patients classified as "pain-without-stain," who reported dry eye symptoms despite lacking “objective signs” of disease. Participants ranged from 18 to 75 years of age, with a mean age of 45 years, 68.1% were women and 31.9% were men.Tear LTA was measured using a point-of-care test requiring 2.2µL of unstimulated tears before performing standard dry eye evaluations, including Ocular Surface Disease Index (OSDI), tear breakup time (TBUT), Schirmer testing, corneal and conjunctival staining, impression cytology and analysis of additional inflammatory biomarkers.Among patients with dry eye, the mean tear LTA concentration was 366pg/mL compared to 1,328pg/mL in controls and 1,619pg/mL in the pain-without-stain group, a prominent difference between the three populations. In their paper on the work for Translational Vision Science & Technology, the authors explained that “LTA 800ng/mL is recommended as the diagnostic cutoff for dry eye.” After using the suggested cutoff, the test agreed with expert clinical diagnosis in 83.9% of cases, with 85.3% sensitivity and 81.8% specificity.Lower LTA levels also corresponded with more advanced-stage disease. Area-under-the-curve analysis (a measure of predictive ability) identified 105pg/mL as the optimal threshold for separating severe from mild-to-moderate DED, while 855pg/mL distinguished mild dry eye from non-DED eyes. An additional threshold of 1,580pg/mL differentiated the pain-without-stain patients from healthy control patients.Patients with the lowest concentrations were reported to show worse symptoms, shorter TBUT, lower Schirmer scores, fewer conjunctival goblet cells and significantly higher levels of  MMP-9 and several  tear proteins. Patients with elevated LTA levels but no clinical staining still demonstrated increased inflammatory markers despite lacking conventional signs of dry eye.The authors concluded that tear LTA “has the potential to distinguish between different subtypes of dry eye,” in their paper, with low concentrations identifying the most severe disease and high concentrations potentially identifying patients with pain-without-stain. They added that larger multicenter studies are needed before LTA thresholds can be adopted for routine clinical use.Click here for the journal source. Yang Y, Wang W, Tan Y, et al. Tear fluid lymphotoxin-alpha as a diagnostic biomarker for the stratification of dry eye disease. Transl Vis Sci Technol. July 2026. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.