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

Abstract

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.

Clinical efficacy of OASIS Preloaded Punctal Plug in Comparison to Smart Plug Punctal Plug in Aqueous-Deficient Dry Eye Disease

“…In recent years, with the aging of the population, the use of electronic devices, and environmental factors, the number of patients with dry eye has been on the rise [19][20][21][22] . At present, there are various ways to treat dry eye, mainly including the elimination of incentives, arti cial tear replacement therapy, preservation of own tears, promotion of tear secretion, further combining anti-in ammatory and immunosuppression, and surgical treatments [23][24][25] . However, general incentives are di cult to eliminate, and due to the complex composition of human tears, although there are various arti cial tears for different tear lm components, they still cannot completely replace their own tears.…”

Metabolomics and lipidomics approaches in human tears: A systematic review

“…Two studies did not report any significant age-related effect on the ω3:ω6 (proinflammatory/antiinflammatory) lipid ratio in tears 88 nor on amino acids 53 whereas most studies found that concentrations of both lipids 48,3,5 and metabolites 76,43 were influenced by age.Other factors (e.g.…”

“…In most studies, tear fluid is obtained after cutting the Schirmer strip into multiple pieces (size ranging from 2 to 10mm) and placed in a vial which is centrifuged 49,47,46,48,3,26,[4][5][6] . In contrast, entire Schirmer strip extraction using a solvent 18,23,43 or punches of 4mm in diameter of the front end of the Schirmer strip 29 represent alternative procedures.…”

Metabolomic Alterations in the Tear Fluids of Patients With Superior Limbic Keratoconjunctivitis

“…Moreover, in terms of the high-throughput profiling of the whole metabolome in a disease condition, identifying biomarkers becoming possible ( 18 , 19 ). With advances in technology, untargeted LC–MS metabolomic analysis of tear fluid has been applied in clinical and animal studies of several eye diseases, such as keratoconus ( 12 , 15 , 20 ), dry eye ( 13 , 21 ), and multiple sclerosis ( 16 ). Studies of metabolomics used in eye diseases have been summarized in a recent review article ( 12 ).…”