{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:10:38Z","timestamp":1785496238503,"version":"3.56.0"},"reference-count":104,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,13]],"date-time":"2017-08-13T00:00:00Z","timestamp":1502582400000},"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>The tear film represents the interface between the eye and the environment. The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome. Despite having a multifactorial origin, the main risk factors are female gender and advanced age. Likewise, morphological changes in several glands and in the chemical composition of their secretions, such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors that maintain a steady ocular surface. Another key factor of recurrence and onset of the disease is the presence of local and\/or systemic inflammation that involves the ocular surface. DE syndrome is one of the most commonly encountered diseases in clinical practice, and many other causes related to daily life and the increase in average life expectancy will contribute to its onset. This review will consider the disorders of the ocular surface that give rise to such a widespread pathology. At the end, the most recent therapeutic options for the management of DE will be briefly discussed according to the specific underlying pathology.<\/jats:p>","DOI":"10.3390\/ijms18081764","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T10:23:12Z","timestamp":1502706192000},"page":"1764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5512-0849","authenticated-orcid":false,"given":"Marcella","family":"Nebbioso","sequence":"first","affiliation":[{"name":"Department of Sense Organs, Policlinico Umberto I, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Del Regno","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Policlinico Umberto I, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-9689","authenticated-orcid":false,"given":"Magda","family":"Gharbiya","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Policlinico Umberto I, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sacchetti","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Policlinico Umberto I, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Plateroti","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Policlinico Umberto I, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-991X","authenticated-orcid":false,"given":"Alessandro","family":"Lambiase","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Policlinico Umberto I, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1046\/j.1442-9071.2003.00634.x","article-title":"Prevalence and associations of dry eye syndrome in an older population: The Blue Mountains Eye Study","volume":"31","author":"Chia","year":"2003","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_2","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":"Dogru","year":"2007","journal-title":"Ocul. Surf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1097\/ICO.0b013e318225415a","article-title":"Distribution of acqueous-deficient and evaporative dry eye in a clinic-based patient cohort: A retrospective study","volume":"31","author":"Lemp","year":"2012","journal-title":"Cornea"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1167\/iovs.10-6997c","article-title":"The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology, and Pathophysiology of the Meibomian Gland","volume":"52","author":"Knop","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S1542-0124(12)70138-6","article-title":"Meibomian gland function and the tear lipid layer","volume":"1","author":"Shine","year":"2003","journal-title":"Ocul. Surf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1167\/iovs.10-6997a","article-title":"The international Workshop on Meibomian Gland Dysfunction: Executive Summar","volume":"52","author":"Nichols","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"International Dry Eye Workshop (2007). Report of the International Dry Eye Workshop (DEWS). Ocul. Surf., 5, 61\u2013204.","DOI":"10.1016\/S1542-0124(12)70079-4"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1167\/iovs.13-13355","article-title":"Biophysical and morphol ogical evaluation of human normal and dry eye meibum using hot stage polarized light microscopy","volume":"55","author":"Butovich","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1167\/iovs.10-6514","article-title":"Human Meibum lipid conformation and thermodynamic changes with Meibomian gland dysfunction","volume":"52","author":"Borchman","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.2147\/OPTH.S114674","article-title":"DEBS\u2014A unification theory for dry eye and blepharitis","volume":"10","author":"Rynerson","year":"2016","journal-title":"Clin. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/j.jaad.2013.04.045","article-title":"New insights into rosacea pathophysiology: A review of recent findings","volume":"69","author":"Steinhoff","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1080\/13543784.2016.1249564","article-title":"Investigational drugs for the treatment of dry eye disease","volume":"25","author":"Nebbioso","year":"2016","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"579","DOI":"10.2340\/00015555-2335","article-title":"Facial Erythema of Rosacea\u2014Aetiology, different pathophysiologies and treatment options","volume":"96","author":"Steinhoff","year":"2016","journal-title":"Acta Derm. Venereol."},{"key":"ref_14","first-page":"2283","article-title":"Pro-and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease","volume":"42","author":"Solomon","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s00417-005-0212-3","article-title":"Tear fluid levels of MMP-8 are elevated in ocular rosacea-treatment effect of oral doxycycline","volume":"244","author":"Maatta","year":"2006","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1001\/archophthalmol.2011.69","article-title":"Effects of age and dysfunction on human Meibomian glands","volume":"129","author":"Nien","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.exer.2009.08.013","article-title":"Age-related changes in the Meibomian gland","volume":"89","author":"Nien","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"825","DOI":"10.18632\/aging.100615","article-title":"Absence of ductal hyper-keratinization in mouse age-related Meibomian gland dysfunction (ARMGD)","volume":"5","author":"Parfitt","year":"2013","journal-title":"Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1097\/ICO.0b013e31820ca468","article-title":"Evaluation of age-related changes in human palpebral conjunctiva and meibomian glands by in vivo confocal microscopy","volume":"30","author":"Wei","year":"2011","journal-title":"Cornea"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.preteyeres.2010.03.001","article-title":"Preservatives in eyedrops: The good, the bad and the ugly","volume":"29","author":"Baudouin","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1097\/IOP.0b013e3182115229","article-title":"Involutional entropion and ectropion of the lower eyelid: Prevalence and associated risk factors in the elderly population","volume":"27","author":"Damasceno","year":"2011","journal-title":"Ophthal. Plast. Reconstr. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0039-6257(98)00037-X","article-title":"Conjunctivochalasis: Literature review and possible pathophysiology","volume":"43","author":"Meller","year":"1998","journal-title":"Surv. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1136\/bjo.2003.025460","article-title":"Clinical characteristics of conjunctivochalasis with or without aqueous tear deficiency","volume":"88","author":"Espana","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1159\/000079478","article-title":"Age-related modifications of corneal sensitivity","volume":"218","author":"Roszkowska","year":"2004","journal-title":"Ophthalmologica"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S70","DOI":"10.1097\/ICO.0b013e3181ae8689","article-title":"The role of oxidative stress and inflammation in dry eye disease","volume":"28","author":"Dogru","year":"2009","journal-title":"Cornea"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/ICO.0b013e31803dcda2","article-title":"Interleukin-6 and tumor necrosis factor-\u03b1 levels in tears of patients with dry eye syndrome","volume":"26","author":"Yoon","year":"2007","journal-title":"Cornea"},{"key":"ref_27","first-page":"862","article-title":"Expressions and clinical significance of OX40 and OX40L in peripheral blood of patients with primary Sj\u00f6gren\u2019s syndrome","volume":"29","author":"Zhu","year":"2013","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ajo.2007.03.055","article-title":"Tear evaporation rates in Sj\u00f6gren syndrome and non-Sj\u00f6gren dry eye patients","volume":"144","author":"Goto","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_29","first-page":"9","article-title":"Keratoconjunctivitis by confocal microscopy after topical cyclosporine","volume":"56","author":"Nebbioso","year":"2012","journal-title":"Panminerva Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3109\/08820538.2012.711416","article-title":"In vivo confocal microscopy in dry eye disease and related conditions","volume":"27","author":"Alhatem","year":"2012","journal-title":"Semin. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/OPX.0b013e318294c184","article-title":"In vivo confocal evaluation of the ocular surface morpho-functional unit in dry eye","volume":"90","author":"Villani","year":"2013","journal-title":"Optom. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/ard.61.6.554","article-title":"European Study Group on Classification Criteria for Sj\u00f6gren's Syndrome. Classification criteria for Sj\u00f6gren syndrome: A revised version of the European criteria proposed by the American-European consensus group","volume":"61","author":"Vitali","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/acr.21591","article-title":"Sj\u00f6gren\u2019s International Collaborative Clinical Alliance (SICCA) Research Groups. American college of rheumatology classification criteria for Sjogren\u2019s syndrome: A data-driven, expert consensus approach in the SICCA cohort","volume":"64","author":"Shiboski","year":"2012","journal-title":"Arthritis Care Res."},{"key":"ref_34","unstructured":"Krachmer, J.H., Mannis, M.J., and Holland, E.J. (2005). Cornea, Elsevier Mosby. [2nd ed.]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.berh.2016.10.007","article-title":"The eye and inflammatory rheumatic diseases: The eye and rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis","volume":"30","author":"Murray","year":"2016","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1136\/bjo.84.1.76","article-title":"Identification of androgen receptor protein and 5\u03b1-reductase mRNA in human ocular tissues","volume":"84","author":"Rocha","year":"2000","journal-title":"Br. J. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.biopha.2013.07.001","article-title":"Iatrogenic dry eye disease: An eledoisin\/carnitine and osmolyte drops study","volume":"67","author":"Nebbioso","year":"2013","journal-title":"Biomed. Pharmacother."},{"key":"ref_38","first-page":"2554","article-title":"Influence of sex on gene expression in human corneal epithelial cells","volume":"15","author":"Suzuki","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1590\/S0004-27492007000300014","article-title":"Total testosterone level in postmenopausal women with dry eye","volume":"70","author":"Duarte","year":"2007","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3109\/02713683.2012.749917","article-title":"Tear osmolarity and ocular surface changes in patient with polycystic ovary syndrome","volume":"38","author":"Gonen","year":"2013","journal-title":"Curr. Eye Res."},{"key":"ref_41","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_42","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1034\/j.1398-9995.2003.00161.x","article-title":"Are asthma and allergies in children and adolescents increasing? Results from ISAAC phase I and phase III surveys in M\u00fcnster, Germany","volume":"58","author":"Maziak","year":"2003","journal-title":"Allergy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3109\/08820538.2013.874483","article-title":"Pathogenesis of vernal keratoconjunctivitis and associated Factors","volume":"30","author":"Nebbioso","year":"2015","journal-title":"Semin. Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1076\/ceyr.19.3.201.5309","article-title":"Altered cytokine balance in the tear fluid and conjunctiva of patients with Sj\u00f6gren\u2019s syndrome keratoconjunctivitis sicca","volume":"19","author":"Pflugfelder","year":"1999","journal-title":"Curr. Eye Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1097\/ICO.0b013e318227fcd9","article-title":"Application of in vivo laser scanning confocal microscopy for evaluation of ocular surface diseases: Lessons learned from pterygium, meibomian gland disease, and chemical burns","volume":"30","author":"Wang","year":"2011","journal-title":"Cornea"},{"key":"ref_46","unstructured":"Ibrahim, O.M., Matsumoto, Y., Dogru, M., Adan, E.S., Wakamatsu, T.H., Shimazaki, J., Fujishima, H., and Tsubota, K. (2010, January 12). In vivo confocal microscopy evaluation of Meibomian gland dysfunction in atopic-keratoconjunctivitis patients. Proceedings of the 64th Congress of Clinical Ophthalmology of Japan, Kobe, Japan."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3109\/08820538.2013.821508","article-title":"Assessment of corneal alterations by confocal microscopy in vernal keratoconjunctivitis","volume":"30","author":"Nebbioso","year":"2015","journal-title":"Semin. Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/S0161-6420(01)00623-6","article-title":"Effects of laser in situ keratomileusis on tear production, clearance, and the ocular surface","volume":"108","author":"Battar","year":"2001","journal-title":"Ophthalmology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1097\/ICO.0b013e31812f67ca","article-title":"Investigation of dry eye disease and analysis of the pathogenic factors in patients after cataract surgery","volume":"26","author":"Li","year":"2007","journal-title":"Cornea"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1016\/S0161-6420(00)00388-2","article-title":"Effect of laser in situ keratomileusis on tear stability","volume":"107","author":"Yu","year":"2000","journal-title":"Ophthalmology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.ajo.2005.10.006","article-title":"The incidence and risk factors for developing dry eye after myopic Lasik","volume":"141","author":"Chen","year":"2006","journal-title":"Am. J. Ophthalmol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0161-6420(98)93055-X","article-title":"Photorefractive keratectomy. A 6 year follow-up study","volume":"105","author":"Stephenson","year":"1998","journal-title":"Ophthalmology"},{"key":"ref_53","first-page":"1813","article-title":"A long-term study of photorefractive keratectomy, 12-year follow-up","volume":"111","author":"Rajan","year":"2004","journal-title":"Ophthalmology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3928\/1081-597X-20020301-02","article-title":"Effect of laser in situ keratomileusis for hyperopia on tear film and ocular surface","volume":"18","author":"Albietz","year":"2002","journal-title":"J. Refract. Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"396","DOI":"10.3928\/1081597X-20080401-14","article-title":"Lasik-associated dry eye and neurotrophic epitheliopathy: Pathophysiology and strategies for prevention and treatment","volume":"24","author":"Ambrosio","year":"2008","journal-title":"J. Refract. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1124\/jpet.102.032797","article-title":"Cellular mechanism of neurogenic infiammation","volume":"302","author":"Richardson","year":"2002","journal-title":"Pharmacol. Exp. Ther."},{"key":"ref_57","first-page":"411","article-title":"Analysis of the keratocyte apoptotis, keratocyte profileration and myofibroblast transormation responses after photorefractive keratectomy and laser in situ keratomileusis","volume":"100","author":"Wilson","year":"2002","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_58","first-page":"11","article-title":"Corneal infiammation following corneal photoablative refractive surgery with excimer laser","volume":"58","author":"Alio","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3928\/1081-597X-20010101-02","article-title":"Corneal Sensitivity and some properties of the tear film after laser in situ keratomileusis","volume":"17","author":"Patel","year":"2001","journal-title":"J. Refract. Surg."},{"key":"ref_60","first-page":"79","article-title":"LASIK and dry eye","volume":"8","author":"Toda","year":"2007","journal-title":"Compr. Ophthalmol. Update"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1136\/bjo.2006.113449","article-title":"Toll-like receptor 3 gene polymorphisms in Japanese patients with Stevens-Johnson syndrome","volume":"91","author":"Ueta","year":"2007","journal-title":"Br. J. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.survophthal.2016.01.004","article-title":"Stevens-Johnson syndrome: The role of an ophthalmologist","volume":"61","author":"Jain","year":"2016","journal-title":"Surv. Ophthalmol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jtos.2016.02.001","article-title":"Acute and chronic ophthalmic involvement in Stevens-Johnson syndrome\/toxic epidermal necrolysis\u2014A comprehensive review and guide to therapy. II. Ophthalmic disease","volume":"14","author":"Kohanim","year":"2016","journal-title":"Ocul. Surf."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.3109\/02713683.2014.987871","article-title":"Signs and symptoms of dry eye in keratoconus patients: a pilot study","volume":"40","author":"Carracedo","year":"2015","journal-title":"Curr. Eye Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Dienes, L., Kiss, H.J., Nagy, Z.Z., Acosta, M.C., Gallar, J., and Kovacs, I. (2015). Corneal sensitivity and dry eye symptoms in patients with keratoconus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141621"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/ICO.0b013e3182632c07","article-title":"Changes in corneal sensation and ocular surface in patients with asymmetrical keratoconus","volume":"32","author":"Cho","year":"2013","journal-title":"Cornea"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ajo.2011.03.006","article-title":"The morphologic characteristics of corneal nerves in advanced keratoconus as evaluated by acetylcholinesterase technique","volume":"152","author":"Faraj","year":"2011","journal-title":"Am. J. Ophthalmol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.ophtha.2004.11.050","article-title":"Infiammatory molecules in the tears of patients with keratoconus","volume":"112","author":"Lema","year":"2005","journal-title":"Ophthalmology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.preteyeres.2004.02.002","article-title":"Pathogenesis of pterygia: Role of cytokines, growth factors, and matrix metalloproteinases","volume":"23","author":"Chui","year":"2004","journal-title":"Progr. Retin. Eye Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3892\/ijmm_00000371","article-title":"Growth factor expression in ophthalmic pterygia and normal conjunctiva","volume":"25","author":"Detorakis","year":"2010","journal-title":"Int. J. Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4302","DOI":"10.1167\/iovs.04-0299","article-title":"Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells","volume":"45","author":"Li","year":"2004","journal-title":"Investig. Ophthalmol. Vis Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/sj.eye.6702186","article-title":"Tear function and goblet cell density after pterygium excision","volume":"21","author":"Li","year":"2007","journal-title":"Eye"},{"key":"ref_73","first-page":"320906","article-title":"Purinergic receptors in ocular inflammation","volume":"2014","author":"Gasull","year":"2014","journal-title":"Med. Inflamm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.exer.2011.06.007","article-title":"Effects of free fatty acids on Meibomian lipid films","volume":"93","author":"Arciniega","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1194\/jlr.R001347","article-title":"Significance of lipid mediators in corneal injury and repair","volume":"51","author":"Kenchegowda","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1096\/fj.11-198036","article-title":"Estrogen negatively regulates epithelial wound healing and protective lipid mediator circuits in the cornea","volume":"26","author":"Wang","year":"2012","journal-title":"FASEB J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"74","DOI":"10.2353\/ajpath.2010.090678","article-title":"Endogenous LXA4 circuits are determinants of pathological angiogenesis in response to chronic injury","volume":"176","author":"Leedom","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1096\/fj.06-7918com","article-title":"Interdependence of lipoxin A4 and heme-oxygenase in counter-regulating inflammation during corneal wound healing","volume":"21","author":"Biteman","year":"2007","journal-title":"FASEB J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.4049\/jimmunol.1500610","article-title":"Female-specific down-regulation of tissue polymorphonuclear neutrophils drives impaired regulatory T cell and amplified effector T cell responses in autoimmune dry eye disease","volume":"195","author":"Gao","year":"2015","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8491","DOI":"10.1073\/pnas.0402531101","article-title":"Neuro-protectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress","volume":"101","author":"Mukherjee","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1001\/archophthalmol.2011.287","article-title":"Recovery of corneal sensitivity, calcitonin gene-related peptide-positive nerves, and increased wound healing induced by pigment epithelial-derived factor plus docosahexaenoic acid after experimental surgery","volume":"130","author":"Cortina","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1167\/iovs.09-3641","article-title":"Neuroprotectin D1 synthesis and corneal nerve regeneration after experimental surgery and treatment with PEDF plus DHA","volume":"51","author":"Cortina","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1146\/annurev.immunol.25.022106.141647","article-title":"Resolution phase of inflammation: Novel endogenous anti-inflammatory and proresolving lipid mediators and pathways","volume":"25","author":"Serhan","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1089\/jop.2010.0019","article-title":"Resolvin E1 improves tear production and decreases inflammation in a dry eye mouse model","volume":"26","author":"Li","year":"2010","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1097\/ICO.0b013e31824988e5","article-title":"The effect of topical pranoprofen 0.1% on the clinical evaluation and conjunctival HLA-DR expression in dry eyes","volume":"31","author":"Liu","year":"2012","journal-title":"Cornea"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/APO.0000000000000032","article-title":"Efficacy of bromfenac sodium ophtlamic solution for treatment of dry eye disease","volume":"4","author":"Fujishima","year":"2015","journal-title":"Asia Pac. J. Ophtalmol. (Phila.)"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.sjopt.2013.06.007","article-title":"Ocular manifestations of graft versus disease","volume":"27","author":"Nassar","year":"2013","journal-title":"Saudi J. Opthalmol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1001\/jamaophthalmol.2013.2385","article-title":"Transcription, translation, and function of lubricin, a boundary lubricant, at the ocular surface","volume":"13","author":"Schmidt","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.exer.2014.06.015","article-title":"Characterization of full-length recombinant human Proteoglycan 4 as an ocular surface boundary lubricant","volume":"127","author":"Samsom","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jtos.2016.08.004","article-title":"A two-week, randomized, double-masked study to evaluate safety and efficacy of lubricin (150 \u03bcg\/mL) eye drops versus sodium hyaluronate (HA) 0.18% eye drops (Vismed\u00ae) in patients with moderate dry eye disease","volume":"15","author":"Lambiase","year":"2016","journal-title":"Ocul. Surf."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.2147\/OPTH.S44688","article-title":"Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled phase 2 clinical trial in patients with dry eye","volume":"7","author":"Meerovitch","year":"2013","journal-title":"Clin. Ophthalmol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1517\/17425255.2014.915026","article-title":"Pharmacokinetic evaluation of diquafosol tetrasodium for the treatment of Sj\u00f6gren\u2019s syndrome","volume":"10","author":"Gicquel","year":"2014","journal-title":"Expert Opin. Drug. Metab. Toxicol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1001\/archophthalmol.2011.364","article-title":"Dry eye disease: An immune-mediated ocular surface disorder","volume":"130","author":"Stevenson","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jtos.2014.12.006","article-title":"Efficacy and safety of topical 0.05% cyclosporine eye drops in the treatment of dry eye syndrome: A systematic review and meta-analysis","volume":"13","author":"Wan","year":"2015","journal-title":"Ocul. Surf."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.ajo.2011.11.003","article-title":"A phase 2 randomized, double-masked, placebo-controlled study of a novel integrin antagonist (sar 1118) for the treatment of dry eye","volume":"153","author":"Semba","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1097\/ICO.0000000000000123","article-title":"Topical cyclosporine a in the treatment of dry eye: A systematic review and meta-analysis","volume":"33","author":"Zhou","year":"2014","journal-title":"Cornea"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.drudis.2016.04.002","article-title":"Modern approaches to the ocular delivery of cyclosporine A","volume":"21","author":"Agarwal","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jtos.2016.01.001","article-title":"Lifitegrast, a novel integrin antagonist for treatment of dry eye disease","volume":"14","author":"Perez","year":"2016","journal-title":"Ocul. Surf."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/rheumatology\/keu417","article-title":"Biologic treatment in Sj\u00f6gren\u2019s syndrome","volume":"54","author":"Sada","year":"2015","journal-title":"Rheumatology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/art.37850","article-title":"Autoimmunity centers of excellence. Rituximab therapy for primary Sj\u00f6gren\u2019s syndrome: An open-label clinical trial and mechanistic analysis","volume":"65","author":"Levesque","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_101","first-page":"1117","article-title":"Treatment of glaucomatous patients by means of food supplement to reduce the ocular discomfort: A double blind randomized trial","volume":"17","author":"Nebbioso","year":"2013","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_102","first-page":"249","article-title":"Curcumin: Therapeutical potential in ophthalmology","volume":"80","author":"Pescosolido","year":"2014","journal-title":"Planta Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/path.2256","article-title":"Down-regulation of PAX6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases","volume":"214","author":"Li","year":"2008","journal-title":"J. Pathol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Ouyang, H., Goldberg, J.L., Chen, S., Li, W., Xu, G.T., Li, W., Zhang, K., Nussenblatt, R.B., Liu, Y., and Xie, T. (2016). Ocular stem cell research from basic science to clinical application: A report from zhongshan ophthalmic center ocular stem cell symposium. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030415"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1764\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:42:15Z","timestamp":1760208135000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,13]]},"references-count":104,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["ijms18081764"],"URL":"https:\/\/doi.org\/10.3390\/ijms18081764","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201705.0161.v1","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,13]]}}}