{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:26:23Z","timestamp":1792167983333,"version":"4.4.0"},"reference-count":156,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dry eye disease (DED) is a multifactorial syndrome that can be caused by alteration in the quality or quantity of the precorneal tear film. It is considered one of the most common ocular conditions leading patients to seek eye care. The current method for diagnostic evaluations and follow-up examinations of DED is a combination of clinical signs and symptoms determined by clinical tests and questionnaires, respectively. The application of powerful omics technologies has opened new avenues toward analysis of subjects in health and disease. Metabolomics is a new emerging and complementary research discipline to all modern omics in the comprehensive analysis of biological systems. The identification of distinct metabolites and integrated metabolic profiles in patients can potentially inform clinicians at an early stage or during monitoring of disease progression, enhancing diagnosis, prognosis, and the choice of therapy. In ophthalmology, metabolomics has gained considerable attention over the past decade but very limited such studies have been reported on DED. This paper aims to review the application of tear metabolomics in DED.<\/jats:p>","DOI":"10.3390\/ijms20153755","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T11:39:37Z","timestamp":1564659577000},"page":"3755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Tear Metabolomics in Dry Eye Disease: A Review"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9187-3231","authenticated-orcid":false,"given":"Mazyar","family":"Yazdani","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Oslo University Hospital, Ullev\u00e5l, 0450 Oslo, Norway"},{"name":"Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Ullev\u00e5l, 0450 Oslo, Norway"},{"name":"The Norwegian Dry Eye Clinic, 0366 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja Benedikte Prest\u00f8","family":"Elgst\u00f8en","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Oslo University Hospital, 0027 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Rootwelt","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Oslo University Hospital, 0027 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9488-6188","authenticated-orcid":false,"given":"Aboulghassem","family":"Shahdadfar","sequence":"additional","affiliation":[{"name":"Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Ullev\u00e5l, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8ygunn Aass","family":"Utheim","sequence":"additional","affiliation":[{"name":"The Norwegian Dry Eye Clinic, 0366 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor Paaske","family":"Utheim","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Oslo University Hospital, Ullev\u00e5l, 0450 Oslo, Norway"},{"name":"The Norwegian Dry Eye Clinic, 0366 Oslo, Norway"},{"name":"Department of Plastic and Reconstructive Surgery, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Department of Maxillofacial Surgery, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Department of Ophthalmology, Vestre Viken Hospital Trust, 3019 Drammen, Norway"},{"name":"Department of Ophthalmology, Stavanger University Hospital, 4011 Stavanger, Norway"},{"name":"Department of Clinical Medicine, Faculty of Medicine, University of Bergen, 5020 Bergen, Norway"},{"name":"Department of Ophthalmology, S\u00f8rlandet Hospital Arendal, 4604 Arendal, Norway"},{"name":"Department of Life Sciences and Health, Oslo Metropolitan University, 0130 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/BF02854841","article-title":"A new look at dry eye disease and its treatment","volume":"17","author":"Nelson","year":"2000","journal-title":"Adv. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3109\/08820538.2010.488568","article-title":"Dry eye disease","volume":"25","author":"Tavares","year":"2010","journal-title":"Semin. Ophthalmol."},{"key":"ref_3","first-page":"581","article-title":"Diagnosis of dry eye disease and emerging technologies","volume":"8","author":"Zeev","year":"2014","journal-title":"Clin. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1038\/eye.2012.211","article-title":"The effect of pH, dilution, and temperature on the viscosity of ocular lubricants-shift in rheological parameters and potential clinical significance","volume":"26","author":"Rahman","year":"2012","journal-title":"Eye"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ajo.2019.01.026","article-title":"Estimated prevalence and incidence of dry eye disease based on coding analysis of a large, all-age united states health care system","volume":"202","author":"Dana","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jtos.2016.04.005","article-title":"Understanding symptoms and quality of life in patients with dry eye syndrome","volume":"14","author":"Barabino","year":"2016","journal-title":"Ocul. Surf."},{"key":"ref_7","first-page":"71","article-title":"The pathophysiology, diagnosis, and treatment of dry eye disease","volume":"112","author":"Messmer","year":"2015","journal-title":"Deutsches \u00c4rzteblatt Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jtos.2015.11.002","article-title":"Economic and humanistic burden of dry eye disease in Europe, North America, and Asia: A systematic literature review","volume":"14","author":"McDonald","year":"2016","journal-title":"Ocul. Surf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/eye.2016.186","article-title":"Depression and anxiety in dry eye disease: A systematic review and meta-analysis","volume":"30","author":"Wan","year":"2016","journal-title":"Eye"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"46453","DOI":"10.1038\/srep46453","article-title":"The prevalence of depression and depressive symptoms among eye disease patients: A systematic review and meta-analysis","volume":"7","author":"Zheng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jtos.2018.11.003","article-title":"The impact of dry eye disease treatment on patient satisfaction and quality of life: A review","volume":"17","author":"Gomes","year":"2018","journal-title":"Ocul. Surf."},{"key":"ref_12","first-page":"376","article-title":"Insuffisance progressive et atrophie des glandes salivaires et muqueuses de la bouche, des conjonctives (et parfois des muqueuses nasale, laryngee, vulvaire): \u201cSecheresse\u201d de la bouche, des conjonctives, etc","volume":"32","author":"Gougerot","year":"1925","journal-title":"Bull. Soc. Fr. Derm. Syph."},{"key":"ref_13","first-page":"1","article-title":"Zur kenntnis der kerato-conjunctivitis sicca (keratitis filiformis bei hypofunction der tranendrusen)","volume":"11","author":"Sjogren","year":"1933","journal-title":"Acta Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.1016\/j.lpm.2012.05.023","article-title":"Do we need new diagnostic criteria for sj\u00f6gren\u2019s syndrome?","volume":"41","author":"Daniels","year":"2012","journal-title":"La Presse M\u00e9dicale"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Theander, E., and Wollheim, F.A. (2011). A note from Sweden: Recollection of henrik sj\u00f6gren. Sj\u00f6gren\u2019s Syndrome, Springer.","DOI":"10.1007\/978-1-60327-957-4_2"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1001\/archopht.1953.00920020190008","article-title":"Lacrimation in normal eyes","volume":"49","year":"1953","journal-title":"AMA Arch. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S1542-0124(12)70110-6","article-title":"Andrew de roetth (1893\u20131981): Dacryologist who introduced the term dry eye","volume":"2","author":"Murube","year":"2004","journal-title":"Ocul. Surf."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1097\/01.ico.0000214802.40313.fa","article-title":"Dysfunctional tear syndrome: A delphi approach to treatment recommendations","volume":"25","author":"Behrens","year":"2006","journal-title":"Cornea"},{"key":"ref_19","first-page":"221","article-title":"Report of the national eye institute\/industry workshop on clinical trials in dry eyes","volume":"21","author":"Lemp","year":"1995","journal-title":"Eye Cont. Lens"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1542-0124(12)70081-2","article-title":"The definition and classification of dry eye disease: Report of the definition and classification subcommittee of the International Dry Eye Workshop (2007)","volume":"5","author":"Lemp","year":"2007","journal-title":"Ocul. Surf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"Tfos dews ii definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jtos.2016.09.003","article-title":"New perspectives on dry eye definition and diagnosis: A consensus report by the asia dry eye society","volume":"15","author":"Tsubota","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_23","first-page":"81","article-title":"Omics tools for the genome-wide analysis of methylation and histone modifications","volume":"Volume 63","year":"2014","journal-title":"Comprehensive Analytical Chemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/eye.2016.37","article-title":"Introduction to metabolomics and its applications in ophthalmology","volume":"30","author":"Tan","year":"2016","journal-title":"Eye"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1039\/B906712B","article-title":"Systems level studies of mammalian metabolomes: The roles of mass spectrometry and nuclear magnetic resonance spectroscopy","volume":"40","author":"Dunn","year":"2011","journal-title":"Chem. Soc. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1080\/004982599238047","article-title":"\u2018Metabonomics\u2019: Understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data","volume":"29","author":"Nicholson","year":"1999","journal-title":"Xenobiotica"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrm.2016.25","article-title":"Metabolomics: Beyond biomarkers and towards mechanisms","volume":"17","author":"Johnson","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.12688\/f1000research.11495.1","article-title":"New frontiers in metabolomics: From measurement to insight","volume":"6","author":"Riekeberg","year":"2017","journal-title":"F1000Research"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.aca.2004.08.055","article-title":"The ion suppression phenomenon in liquid chromatography\u2013mass spectrometry and its consequences in the field of residue analysis","volume":"529","author":"Antignac","year":"2005","journal-title":"Anal. Chim. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.bbalip.2017.04.006","article-title":"The evolution of lipidomics through space and time","volume":"1862","author":"Gross","year":"2017","journal-title":"BBA Mol. Cell Biol. Lipids"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"152","DOI":"10.5114\/reum.2015.53137","article-title":"Metabolomics and its potential in diagnosis, prognosis and treatment of rheumatic diseases","volume":"53","author":"Zdrojewski","year":"2015","journal-title":"Reumatologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s11095-019-2569-8","article-title":"Review of biomarkers in ocular matrices: Challenges and opportunities","volume":"36","author":"Tamhane","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_33","first-page":"456","article-title":"Investigation of the human tear film proteome using multiple proteomic approaches","volume":"14","author":"Nichols","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1080\/02713683.2018.1514055","article-title":"Tear production levels and dry eye disease severity in a large norwegian cohort","volume":"43","author":"Yazdani","year":"2018","journal-title":"Curr. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000479158","article-title":"Clinical metabolomics and glaucoma","volume":"59","author":"Himmelreich","year":"2018","journal-title":"Ophthalmic Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Marciano, D.P., and Snyder, M.P. (2019). Personalized metabolomics. High-Throughput Metabolomics, Springer.","DOI":"10.1007\/978-1-4939-9236-2_27"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Reinhold, D., Pielke-Lombardo, H., Jacobson, S., Ghosh, D., and Kechris, K. (2019). Pre-analytic considerations for mass spectrometry-based untargeted metabolomics data. High-Throughput Metabolomics, Springer.","DOI":"10.1007\/978-1-4939-9236-2_20"},{"key":"ref_38","unstructured":"Williams, R. (1956). Biochemical Individuality, John Wiley & Sons, Inc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1042\/bj1010792","article-title":"A gas-liquid-chromatographic procedure for separating a wide range of metabolites occurring in urine or tissue extracts","volume":"101","author":"Dalgliesh","year":"1966","journal-title":"Biochem. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1093\/clinchem\/17.8.802","article-title":"Metabolic profiles: Gas-phase methods for analysis of metabolites","volume":"17","author":"Horning","year":"1971","journal-title":"Clin. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/s11306-016-1108-4","article-title":"The metabolome 18 years on: A concept comes of age","volume":"12","author":"Kell","year":"2016","journal-title":"Metabolomics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"605","DOI":"10.2217\/bmm.09.43","article-title":"Genomic and metabolomic advances in the identification of disease and adverse event biomarkers","volume":"3","author":"Mendrick","year":"2009","journal-title":"Biomark. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/j.1755-3768.2009.01516.x","article-title":"Metabonomics\u2014A new approach in ophthalmology","volume":"87","author":"Midelfart","year":"2009","journal-title":"Acta Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"BIO88","DOI":"10.1167\/iovs.17-21809","article-title":"Omics biomarkers in ophthalmology","volume":"58","author":"Lauwen","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.aca.2018.01.060","article-title":"Recent advances in the applications of metabolomics in eye research","volume":"1037","author":"Chen","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1097\/00003226-199811000-00002","article-title":"The pathology of dry eye: The interaction between the ocular surface and lacrimal glands","volume":"17","author":"Stern","year":"1998","journal-title":"Cornea"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/00004397-198002030-00004","article-title":"Structures and fluids involved in the penetration of topically applied drugs","volume":"20","author":"Maurice","year":"1980","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.aanat.2012.10.001","article-title":"Schirmer strip vs. Capillary tube method: Non-invasive methods of obtaining proteins from tear fluid","volume":"195","author":"Posa","year":"2013","journal-title":"Ann. Anat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s10286-018-0526-y","article-title":"The neurobiology of human crying","volume":"29","author":"Bylsma","year":"2019","journal-title":"Clin. Auton. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1080\/02713683.2017.1381270","article-title":"Blink: Characteristics, controls, and relation to dry eyes","volume":"43","author":"Rodriguez","year":"2018","journal-title":"Curr. Eye Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4103\/ijo.IJO_646_17","article-title":"Anatomy of cornea and ocular surface","volume":"66","author":"Sridhar","year":"2018","journal-title":"Indian J. Ophthalmol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1097\/ICO.0000000000001250","article-title":"Central connections of the lacrimal functional unit","volume":"36","author":"Willshire","year":"2017","journal-title":"Cornea"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/eye.1991.65","article-title":"Meibomian gland disease: Classification and grading of lid changes","volume":"5","author":"Bron","year":"1991","journal-title":"Eye"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S199","DOI":"10.1016\/S0039-6257(00)00202-2","article-title":"Dry eye disease: The scale of the problem","volume":"45","author":"Brewitt","year":"2001","journal-title":"Surv. Ophthalmol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1001\/jama.286.17.2114","article-title":"Hormone replacement therapy and dry eye syndrome","volume":"286","author":"Schaumberg","year":"2001","journal-title":"JAMA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/00055735-200212000-00014","article-title":"Ocular manifestations of hepatitis c virus infection","volume":"13","author":"Zegans","year":"2002","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/000992280404300116","article-title":"Vegan diet and vitamin a deficiency","volume":"43","author":"Colev","year":"2004","journal-title":"Clin. Pediatr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/ajcn\/82.4.887","article-title":"Relation between dietary n\u22123 and n\u22126 fatty acids and clinically diagnosed dry eye syndrome in women","volume":"82","author":"Trivedi","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Nebbioso, M., Del Regno, P., Gharbiya, M., Sacchetti, M., Plateroti, R., and Lambiase, A. (2017). Analysis of the pathogenic factors and management of dry eye in ocular surface disorders. Int. J. Mol. Sci., 18.","DOI":"10.20944\/preprints201705.0161.v1"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/GME.0000000000000530","article-title":"Dry eye in postmenopausal women: A hormonal disorder","volume":"23","author":"Sriprasert","year":"2016","journal-title":"Menopause"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1089\/jwh.2018.7041","article-title":"Dry eye disease: Consideration for women\u2019s health","volume":"28","author":"Matossian","year":"2019","journal-title":"J. Womens Health"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/IIO.0000000000000170","article-title":"Effects of aging in dry eye","volume":"57","year":"2017","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/npjamd.2016.3","article-title":"A glimpse at the aging eye","volume":"2","author":"Lin","year":"2016","journal-title":"NPJ Aging Mech. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.clindermatol.2015.11.009","article-title":"An eye on nutrition: The role of vitamins, essential fatty acids, and antioxidants in age-related macular degeneration, dry eye syndrome, and cataract","volume":"34","author":"McCusker","year":"2016","journal-title":"Clin. Dermatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"325","DOI":"10.3109\/08820538.2016.1154168","article-title":"A comprehensive review of sex disparities in symptoms, pathophysiology, and epidemiology of dry eye syndrome","volume":"31","author":"Rapoport","year":"2016","journal-title":"Semin. Ophthalmol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.2174\/1381612822666160614012634","article-title":"Dry eye disease: Present challenges in the management and future trends","volume":"22","author":"Zimmerman","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bron, A.J. (2015). The definition and classification of dry eye disease. Dry Eye, Springer.","DOI":"10.1007\/978-3-662-44106-0_1"},{"key":"ref_69","unstructured":"Benitez-del-Castillo, J.M., and Lemp, M.A. (2013). Ocular Surface Disorders, JP Medical Ltd."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jtos.2017.05.005","article-title":"TFOS DEWS II introduction","volume":"15","author":"Nelson","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Ding, C., T\u00f3th-Moln\u00e1r, E., Wang, N., and Zhou, L. (2016). Lacrimal gland, ocular surface, and dry eye. J. Ophthalmol., 2016.","DOI":"10.1155\/2016\/7397694"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"R72","DOI":"10.1186\/gb-2006-7-8-r72","article-title":"Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors","volume":"7","author":"Mann","year":"2006","journal-title":"Genome Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.jtos.2017.03.006","article-title":"TFOS DEWS II tear film report","volume":"15","author":"Willcox","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1159\/000078776","article-title":"Lachrymal determinations: Methods and updates on biopharmaceutical and clinical applications","volume":"36","author":"Dumortier","year":"2004","journal-title":"Ophthalmic Res."},{"key":"ref_75","unstructured":"Schirmer, O.W.A. (1931). Handbuch der Gesamten Augenheilkunde: Mikroskopische Anatomie und Physiologie der Tr\u00e4nenorgane, Springer."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/00004397-198002030-00006","article-title":"Pharmacokinetics of instilled drugs in the human eye","volume":"20","author":"Nagataki","year":"1980","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_77","first-page":"1996","article-title":"Study of precorneal tear film thickness and structure by interferometry and confocal microscopy","volume":"33","author":"Prydal","year":"1992","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1542-0124(12)70076-9","article-title":"Report of the International Dry Eye Workshop (dews)","volume":"5","author":"Foulks","year":"2007","journal-title":"Ocul. Surf."},{"key":"ref_79","first-page":"291","article-title":"The muco-cutaneous junction of the lidmargin and the distribution of the tear fluid","volume":"66","author":"Wolff","year":"1946","journal-title":"Trans. Ophthalmol. Soc. UK"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.exer.2017.03.013","article-title":"Structure-function relationship of tear film lipid layer: A contemporary perspective","volume":"163","author":"Georgiev","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1167\/iovs.10-6997d","article-title":"The international workshop on meibomian gland dysfunction: Report of the subcommittee on tear film lipids and lipid-protein interactions in health and disease","volume":"52","author":"Butovich","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_82","unstructured":"Kim, T., Donnenfeld, E.D., Holland, E.J., Kanellopoulos, A.J., Mah, F.S., Randleman, J.B., Scoper, S.V., Shamie, N., and Vroman, D.T. (2011). Meibomian Gland Dysfunction, American Society of Cataract and Refractive Surgery."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.exer.2013.05.010","article-title":"Tear film lipids","volume":"117","author":"Butovich","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/7542929","article-title":"The lacrimal gland and its role in dry eye","volume":"2016","author":"Conrady","year":"2016","journal-title":"J. Ophthalmol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1016\/j.ophtha.2017.05.031","article-title":"Meibomian gland disease: The role of gland dysfunction in dry eye disease","volume":"124","author":"Chhadva","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1016\/j.bbamem.2016.02.020","article-title":"Tear film lipid layer: A molecular level view","volume":"1858","author":"Cwiklik","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.exer.2015.05.002","article-title":"The real reason for having a meibomian lipid layer covering the outer surface of the tear film\u2014A review","volume":"137","author":"Millar","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.preteyeres.2016.04.005","article-title":"Goblet cells of the conjunctiva: A review of recent findings","volume":"54","author":"Gipson","year":"2016","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000131066","article-title":"The normal tear film","volume":"Volume 41","author":"Tiffany","year":"2008","journal-title":"Surgery for the Dry Eye"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biochi.2008.07.007","article-title":"Role of lactoferrin in the tear film","volume":"91","author":"Flanagan","year":"2009","journal-title":"Biochimie"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.plipres.2011.03.003","article-title":"Lipidomics of human meibomian gland secretions: Chemistry, biophysics, and physiological role of meibomian lipids","volume":"50","author":"Butovich","year":"2011","journal-title":"Prog. Lipid Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/OPX.0000000000000188","article-title":"Patient acceptability of tear collection in the primary healthcare setting","volume":"91","author":"Quah","year":"2014","journal-title":"Optom. Vis. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.exer.2013.08.010","article-title":"Tear film stability: A review","volume":"117","author":"Sweeney","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2147\/OPTH.S1496","article-title":"The challenge of dry eye diagnosis","volume":"2","author":"Savini","year":"2008","journal-title":"Clin. Ophthalmol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.2147\/OPTH.S89700","article-title":"Associations between signs and symptoms of dry eye disease: A systematic review","volume":"9","author":"Bartlett","year":"2015","journal-title":"Clin. Ophthalmol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/ACI.0000000000000307","article-title":"Tear film assessments for the diagnosis of dry eye","volume":"16","author":"Dohlman","year":"2016","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1001\/jamaophthalmol.2015.0429","article-title":"Variability of tear osmolarity in patients with dry eye","volume":"133","author":"Bunya","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.ophtha.2016.11.008","article-title":"Predictors of discordance between symptoms and signs in dry eye disease","volume":"124","author":"Vehof","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"i4617","DOI":"10.1136\/bmj.i4617","article-title":"Diagnosis, treatment, and monitoring of dry eye disease","volume":"354","author":"Skiadaresi","year":"2016","journal-title":"BMJ"},{"key":"ref_100","first-page":"1","article-title":"Evaluation of the ocular surface disease index questionnaire as a discriminative test for clinical findings in dry eye disease patients","volume":"6","author":"Yazdani","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4053","DOI":"10.1167\/iovs.05-0980","article-title":"Increased levels of diadenosine polyphosphates in dry eye","volume":"47","author":"Peral","year":"2006","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"E132","DOI":"10.1097\/OPX.0b013e318194e767","article-title":"l-carnitine and short chain ester in tears from patients with dry eye","volume":"86","author":"Pescosolido","year":"2009","journal-title":"Optom. Vis. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Galbis-Estrada, C., Martinez-Castillo, S., Morales, J.M., Vivar-Llopis, B., Monle\u00f3n, D., D\u00edaz-Llopis, M., and Pinazo-Dur\u00e1n, M.D. (2014). Differential effects of dry eye disorders on metabolomic profile by 1 h nuclear magnetic resonance spectroscopy. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/542549"},{"key":"ref_104","first-page":"555","article-title":"A metabolomic approach to dry eye disorders. The role of oral supplements with antioxidants and omega 3 fatty acids","volume":"21","author":"Morales","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Pieragostino, D., Agnifili, L., Cicalini, I., Calienno, R., Zucchelli, M., Mastropasqua, L., Sacchetta, P., Del Boccio, P., and Rossi, C. (2017). Tear film steroid profiling in dry eye disease by liquid chromatography tandem mass spectrometry. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071349"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4876","DOI":"10.1021\/pr2004874","article-title":"Characterization of the human tear metabolome by lc\u2013ms\/ms","volume":"10","author":"Chen","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1021\/acs.jproteome.9b00149","article-title":"Integrated tear proteome and metabolome reveal panels of inflammatory-related molecules via key regulatory pathways in dry eye syndrome","volume":"18","author":"Chen","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_108","first-page":"551","article-title":"Pre-analytical errors in the clinical laboratory and how to minimize them","volume":"2","author":"Mukherjee","year":"2013","journal-title":"Int. J. Bioassays"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Villas-Boas, S.G., Nielsen, J., Smedsgaard, J., Hansen, M.A., and Roessner-Tunali, U. (2007). Metabolome Analysis: An introduction, John Wiley & Sons.","DOI":"10.1002\/0470105518"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1177\/0004563217695843","article-title":"Evaluation of commonly used tear sampling methods and their relevance in subsequent biochemical analysis","volume":"54","author":"Rentka","year":"2017","journal-title":"Ann. Clin. Biochem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1097\/00006324-199302000-00012","article-title":"Schirmer test II. A clinical study of its repeatability","volume":"70","author":"Cho","year":"1993","journal-title":"Optom Vis. Sci."},{"key":"ref_112","first-page":"568","article-title":"A shorter schirmer tear test","volume":"73","author":"Nelson","year":"1982","journal-title":"Optom. Mon."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0014-4835(90)90223-H","article-title":"Effects of the schirmer test on the fibrinolytic system in the tear fluid","volume":"50","author":"Stephens","year":"1990","journal-title":"Exp. Eye Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1001\/archopht.1967.00980020260022","article-title":"A histochemical study of the fibrinolytic activity: Cornea, conjunctiva, and lacrimal gland","volume":"77","author":"Pandolfi","year":"1967","journal-title":"Arch. Ophthal."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1089\/jop.2000.16.439","article-title":"Comparison of tear sampling techniques for pharmacokinetic analysis: Ofloxacin concentrations in rabbit tears after sampling with schirmer tear strips, capillary tubes, or surgical sponges","volume":"16","author":"Small","year":"2000","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_116","first-page":"374","article-title":"The effect of collection technique on tear composition","volume":"25","author":"Stuchell","year":"1984","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1590\/S0100-736X2013000200021","article-title":"Comparison of two methods of tear sampling for protein quantification by bradford method","volume":"33","author":"Farias","year":"2013","journal-title":"Pesquisa Veterin\u00e1ria Brasileira"},{"key":"ref_118","first-page":"3130","article-title":"Water-soluble antioxidants in human tears: Effect of the collection method","volume":"42","author":"Choy","year":"2001","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S1542-0124(12)70296-3","article-title":"Basal, reflex, and psycho-emotional tears","volume":"7","author":"Murube","year":"2009","journal-title":"Ocul. Surf."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jchromb.2008.04.031","article-title":"Analytical strategies for LC\u2013MS-based targeted metabolomics","volume":"871","author":"Lu","year":"2008","journal-title":"J. Chromatogr. B"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.trac.2007.08.009","article-title":"Analytical technologies for metabonomics and metabolomics, and multi-omic information recovery","volume":"27","author":"Lindon","year":"2008","journal-title":"Trends Anal. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.csbj.2015.10.005","article-title":"Blood transcriptomics and metabolomics for personalized medicine","volume":"14","author":"Li","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_123","first-page":"269","article-title":"NMR spectroscopic determination of microbiological profiles in infectious diseases","volume":"5","author":"Himmelreich","year":"2004","journal-title":"Trends Appl. Spectrosc."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13547500410001668379","article-title":"Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis","volume":"9","author":"Lindon","year":"2004","journal-title":"Biomarkers"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s11306-016-1094-6","article-title":"Metabolomics enables precision medicine: \u201cA white paper, community perspective\u201d","volume":"12","author":"Beger","year":"2016","journal-title":"Metabolomics"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3109\/02713683.2012.754904","article-title":"Metabolic profile of keratoconic cornea","volume":"38","author":"Kryczka","year":"2013","journal-title":"Curr. Eye Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1755-3768.2011.02271.x","article-title":"Influence of donor age, post-mortem time and cold storage on metabolic profile of human cornea","volume":"91","author":"Kryczka","year":"2013","journal-title":"Acta Ophthalmol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Kryczka, T., Wyl\u0119ga\u0142a, E., Dobrowolski, D., and Midelfart, A. (2014). NMR spectroscopy of human eye tissues: A new insight into ocular biochemistry. Sci. World J., 2014.","DOI":"10.1155\/2014\/546192"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4608","DOI":"10.1038\/srep04608","article-title":"In vitro model suggests oxidative stress involved in keratoconus disease","volume":"4","author":"Karamichos","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s11306-017-1281-0","article-title":"Quantitative metabolomic analysis of the human cornea and aqueous humor","volume":"13","author":"Snytnikova","year":"2017","journal-title":"Metabolomics"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.exer.2012.07.010","article-title":"Tear fluid small molecular antioxidants profiling shows lowered glutathione in keratoconus","volume":"103","author":"Saijyothi","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.exer.2015.03.008","article-title":"Metabolomic composition of normal aged and cataractous human lenses","volume":"134","author":"Tsentalovich","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00496763","article-title":"Collection method dependant concentrations of some metabolites in human tear fluid, with special reference to glucose in hyperglycaemic conditions","volume":"202","author":"Glasius","year":"1977","journal-title":"Albrecht von Graefes Archiv f\u00fcr Klinische und Experimentelle Ophthalmologie"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0014-4835(84)90012-5","article-title":"Catecholamine concentrations in tears","volume":"39","author":"Trope","year":"1984","journal-title":"Exp. Eye Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1076\/ceyr.17.3.257.5213","article-title":"Tear fluid content of electrochemically active components including water soluble antioxidants","volume":"17","author":"Gogia","year":"1998","journal-title":"Curr. Eye Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1373\/clinchem.2006.078543","article-title":"Mass spectral determination of fasting tear glucose concentrations in nondiabetic volunteers","volume":"53","author":"Baca","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.jasms.2006.10.002","article-title":"Analysis of tear glucose concentration with electrospray ionization mass spectrometry","volume":"18","author":"Taormina","year":"2007","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1167\/iovs.08-1889","article-title":"On the lipid composition of human meibum and tears: Comparative analysis of nonpolar lipids","volume":"49","author":"Butovich","year":"2008","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.ajo.2010.11.003","article-title":"Amino acid profiles in human tear fluids analyzed by high-performance liquid chromatography and electrospray ionization tandem mass spectrometry","volume":"151","author":"Nakatsukasa","year":"2011","journal-title":"Am. J. Ophthalmol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.plefa.2017.01.004","article-title":"Identification and profiling of specialized pro-resolving mediators in human tears by lipid mediator metabolomics","volume":"117","author":"English","year":"2017","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1007\/s004240100696","article-title":"Presence of diadenosine polyphosphates in human tears","volume":"443","author":"Pintor","year":"2002","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1124\/jpet.102.041368","article-title":"Presence of diadenosine polyphosphates in the aqueous humor: Their effect on intraocular pressure","volume":"304","author":"Pintor","year":"2003","journal-title":"J. Pharm. Exp. Ther."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1475-1313.2004.00182.x","article-title":"UTP and diadenosine tetraphosphate accelerate wound healing in the rabbit cornea","volume":"24","author":"Pintor","year":"2004","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"7174","DOI":"10.1073\/pnas.95.12.7174","article-title":"A release mechanism for stored ATP in ocular ciliary epithelial cells","volume":"95","author":"Mitchell","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1007\/BF00164671","article-title":"Oxidative reactions in the tear fluid of patients suffering from dry eyes","volume":"233","author":"Augustin","year":"1995","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1006\/exer.1996.0268","article-title":"Inducible expression of na+\/myo-inositol cotransporter mrna in anterior epithelium of bovine lens: Affiliation with hypertonicity and cell proliferation","volume":"64","author":"Cammarata","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_147","first-page":"1823","article-title":"Transport of l-carnitine in human corneal and conjunctival epithelial cells","volume":"16","author":"Xu","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1159\/000070638","article-title":"Age-and gender-related differences in human lacrimal fluid peroxidase activity","volume":"217","author":"Marcozzi","year":"2003","journal-title":"Ophthalmologica"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1136\/bjophthalmol-2012-302705","article-title":"Low levels of 17-\u03b2-oestradiol, oestrone and testosterone correlate with severe evaporative dysfunctional tear syndrome in postmenopausal women: A case\u2013control study","volume":"98","author":"Gagliano","year":"2014","journal-title":"Br. J. Ophthalmol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/00003226-199807000-00002","article-title":"Menopause and tear function: The influence of prolactin and sex hormones on human tear production","volume":"17","author":"Mathers","year":"1998","journal-title":"Cornea"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Sullivan, D.A., Rocha, E.M., Ullman, M.D., Kreuzer, K.L., Gao, J., Toda, I., Dana, M.R., Bazzinotti, D., da Silveira, L.A., and Wickham, L.A. (1998). Androgen regulation of the meibomian gland. Lacrimal Gland, Tear Film, and Dry Eye Syndromes 2, Springer.","DOI":"10.1007\/978-1-4615-5359-5_46"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13479","article-title":"Pro-resolving lipid mediators are leads for resolution physiology","volume":"510","author":"Serhan","year":"2014","journal-title":"Nature"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1167\/iovs.16-19131","article-title":"\u03a9-3 tear film lipids correlate with clinical measures of dry eye","volume":"57","author":"Walter","year":"2016","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/bies.10385","article-title":"Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era","volume":"26","author":"Kell","year":"2004","journal-title":"Bioessays"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3982","DOI":"10.1021\/acs.jproteome.5b00443","article-title":"Global metabonomic and proteomic analysis of human conjunctival epithelial cells (IOBA-NHC) in response to hyperosmotic stress","volume":"14","author":"Chen","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ophtha.2016.12.011","article-title":"A metabolome-wide study of dry eye disease reveals serum androgens as biomarkers","volume":"124","author":"Vehof","year":"2017","journal-title":"Ophthalmology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/15\/3755\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:11:58Z","timestamp":1760188318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/15\/3755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,1]]},"references-count":156,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["ijms20153755"],"URL":"https:\/\/doi.org\/10.3390\/ijms20153755","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,1]]}}}