A Set of Global Metabolomic Biomarker Candidates to Predict the Risk of Dry Eye Disease

Purpose: We used ultraperformance liquid chromatography coupled with quadrupole/time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS/MS) to analyze the metabolic profile of reflex tears obtained from patients with dry eye disorders.

Methods: We performed a cross-sectional study involving 113 subjects: 85 patients diagnosed with dry eye syndrome (dry eye group) and 28 healthy volunteers (control group). Reflex tears (20-30 μl) were collected from the tear meniscus of both eyes of each subject using a Schirmer I test strip. MS data were acquired with a standard workflow by UPLC-Q/TOF-MS/MS. Metabolites were quantitatively analyzed and matched with entries in the Metlin, Massbank, and HMDB databases. Least absolute shrinkage and selection operator (LASSO) regression was conducted to detect important metabolites. Multiple logistic regression was used to identify the significant metabolic biomarker candidates for dry eye syndrome. Open database sources, including the Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst, were used to identify metabolic pathways.

Results: After the LASSO regression and multiple logistic regression analysis, 4 of 20 metabolic biomarker candidates were significantly correlated with Ocular Surface Disease Index score, 42 of 57 with fluorescein breakup time, and 26 of 57 with fluorescein staining. By focusing on the overlap of these three sets, 48 of 51 metabolites contributed to the incidence of dry eye and there were obvious changes in different age groups. Metabolic pathway analysis revealed that the main pathways were glucose metabolism, amino acid metabolism, and glutathione metabolism.

Conclusion: Dry eye syndrome induces changes in the metabolic profile of tears, and the trend differs with age. This evidence reveals the relationship between changes in metabolites, symptoms of dry eye syndrome, and age.