{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:08:01Z","timestamp":1784092081664,"version":"3.55.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Ophthalmol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize tear metabolomic differences between active blepharokeratoconjunctivitis (BKC) and herpes simplex keratitis (HSK; epithelial type) and identify diagnostic biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fopht.2026.1842136","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:45:38Z","timestamp":1784090738000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential tear metabolomics in blepharokeratoconjunctivitis and herpes simplex keratitis: potential biomarkers for clinical differentiation"],"prefix":"10.3389","volume":"6","author":[{"given":"Zi-wen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Jiangxi Yingtan People\u2019s Hospital","place":["Yingtan, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-ning","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Guangdong Provinical Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmice Center, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Jiangxi Yingtan People\u2019s Hospital","place":["Yingtan, Jiangxi, China"]},{"name":"State Key Laboratory of Ophthalmology, Guangdong Provinical Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmice Center, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-you","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Guangdong Provinical Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmice Center, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1001\/jamaophthalmol.2023.5750","article-title":"Definition and diagnostic criteria for pediatric blepharokeratoconjunctivitis","volume":"142","author":"Morales-Mancillas","year":"2024","journal-title":"JAMA Ophthalmol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-199903000-00002","article-title":"Classification of herpes simplex virus keratitis","volume":"18","author":"Holland","year":"1999","journal-title":"Cornea"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/icu.0000000000000167","article-title":"Blepharokeratoconjunctivitis in children","volume":"26","author":"Hammersmith","year":"2015","journal-title":"Curr Opin Ophthalmol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2147\/opth.s80475","article-title":"Herpes simplex keratitis: challenges in diagnosis and clinical management","volume":"11","author":"Azher","year":"2017","journal-title":"Clin Ophthalmol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2022.01.010","article-title":"Metabolomics and lipidomics approaches in human tears: a systematic review","volume":"67","author":"Khanna","year":"2022","journal-title":"Surv Ophthalmol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108734","article-title":"Identification of potential serum metabolic biomarkers for patient with keratoconus using untargeted metabolomics approach","volume":"211","author":"Daphne Teh","year":"2021","journal-title":"Exp Eye Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.6.1583s","article-title":"Exercise promotes BCAA catabolism: effects of BCAA supplementation on skeletal muscle during exercise","volume":"136","author":"Shimomura","year":"2006","journal-title":"J Nutr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.1007\/s11427-022-2296-0","article-title":"Phenylalanine diminishes M1 macrophage inflammation","volume":"66","author":"Li","year":"2023","journal-title":"Sci China Life Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"380","DOI":"10.3390\/metabo13030380","article-title":"Metabolomics in Corneal Diseases: A Narrative Review from Clinical Aspects","volume":"13","author":"Teo","year":"2023","journal-title":"Metabolites"},{"key":"B10","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1159\/000129395","article-title":"Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. 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