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Research Article: Differential tear metabolomics in blepharokeratoconjunctivitis and herpes simplex keratitis: potential biomarkers for clinical differentiation

Date Published: 2026-07-15

Abstract:
To characterize tear metabolomic differences between active blepharokeratoconjunctivitis (BKC) and herpes simplex keratitis (HSK; epithelial type) and identify diagnostic biomarkers. Tear samples were collected from 24 HSK patients, 19 BKC patients, and 15 healthy controls from October 2020 to 2021. Diagnoses were confirmed by clinical manifestations, medical history, and nested PCR (nPCR). Metabolomic profiling was performed via LC-MS/MS, and data were analyzed using MetaboAnalyst 5.0. Compared to healthy controls, HSK exhibited 21 altered metabolites, while BKC showed 19 altered metabolites. After FDR correction, L-isoleucine, L-phenylalanine, pantothenol were significantly expressed lower in both HSK and BKC. Moreover, 4-dodecylbenzenesulfonic acid, carnosol were lower in HSK-specific, and sorbitol was lower in BKC-specific than in control. A combined panel of metabolites 4-dodecylbenzenesulfonic acid, carnosol and sorbitol showed good specificity and sensitivity for differentiation of BKC/HSK. All of them showed significant differences with area under curve values exceeding 0.79. The disease-specific differential expression of carnosol, 4-dodecylbenzenesulfonic acid in HSK, and sorbitol in BKC provide mechanistic insights into HSV-1 infection and chronic immune-mediated ocular surface inflammation, respectively. The combination of clinical signs with nPCR result and a metabolite panel (4-Dodecylbenzenesulfonic Acid+ Carnosol +Sorbitol) may be optimal for HSK/BKC discrimination.

Introduction:
Blepharokeratoconjunctivitis (BKC) is a chronic ocular surface inflammation involving eyelids, conjunctiva, and cornea, characterized by recurrent lesions ( 1 ). Herpes simplex keratitis (HSK), primarily caused by HSV-1, manifests as epithelial, stromal, or endothelial keratitis ( 2 ). Both diseases can cause vision impairment upon recurrence due to corneal scarring and neovascularization. Despite their different etiologies, both conditions present with similar clinical manifestations, making differential…

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