Abstract
PURPOSE: Superior limbic keratoconjunctivitis (SLK) and dry eye disease (DED) exhibit similar clinical manifestations, complicating diagnosis. We aimed to compare tear metabolomic profiles and secretory phospholipase A2 (sPLA2) levels in patients with SLK versus patients with DED. METHODS: We established a cross-sectional study involving 56 subjects: 20 patients with SLK, 21 patients with DED, and 15 matched healthy controls (solely for measuring sPLA2). Tear fluids collected via Schirmer strips underwent liquid chromatography with tandem mass spectrometry metabolomic analysis. Metabolites were quantitatively analyzed and matched to metabolic pathways and biomarkers. Metabolic differences between patients with SLK and patients with DED were identified through multivariate statistical analysis. Western blot measured the content of sPLA2 in tears of the three groups. RESULTS: Tear analysis annotated 274 metabolites. Twenty-three metabolites showed significant differences (P < 0.05) between the 2 groups, comprising 20 increased and 3 decreased in SLK. Top differential metabolic pathways were glycerophospholipid, alpha-linolenic acid, and linoleic acid metabolism. Receiver operating characteristic (ROC) analysis showed that five metabolites could be considered as potential biomarkers for distinguishing SLK from DED. Tears PLA2 was significantly higher in SLK than healthy controls (p < 0.05), but without difference between SLK and DED. CONCLUSIONS: The study revealed distinct metabolomic profiles in SLK versus DED tears, with notable changes in glycerophospholipid metabolism and elevated sPLA2 levels in SLK. TRANSLATIONAL RELEVANCE: Tear metabolomics distinguishes SLK from DED at the molecular level through dysregulated glycerophospholipid metabolism. In SLK, compared with controls, this dysregulation coincides with elevated sPLA2, an enzyme hydrolyzing glycerophospholipids, indicating lipid-driven inflammation.