{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T17:58:08Z","timestamp":1758045488394,"version":"3.44.0"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019004","name":"Deanship of Research, Jordan University of Science and Technology","doi-asserted-by":"publisher","award":["20240036"],"award-info":[{"award-number":["20240036"]}],"id":[{"id":"10.13039\/501100019004","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Keratoconus is a progressive corneal disorder characterized by corneal thinning often leading to significant visual impairment. Recent research suggests a potential role of cortisol in the development and progression of keratoconus. However, the relationship between cortisol levels and keratoconus severity remains poorly understood.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>To investigate the association between hair cortisol levels and keratoconus severity in a Jordanian population, exploring whether cortisol could serve as a potential biomarker for disease progression or stability.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a prospective, observational study at King Abdullah University Hospital in Jordan. Sixty participants aged 18\u201330 years were categorized into three groups: Healthy (n\u2009=\u200920), Progressive Keratoconus (n\u2009=\u200920), and Stable Keratoconus (n\u2009=\u200920). Demographic, clinical, and ocular data were collected, including age, gender, hair cortisol levels, and corneal topography indices (Kmax, Kmean, and thinnest corneal location).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>The median cortisol level was significantly higher in the Progressive Keratoconus group (987 pg\/mL) compared to the Stable group (300 pg\/mL, p-value &lt;0.001). Regression analysis revealed a significant negative association between cortisol levels and stable keratoconus (\u03b2\u2009=\u2009\u22121.31, p\u2009&lt;\u20090.001). No significant association was observed for progressive keratoconus after adjustment for age and gender. Correlation analysis showed no significant associations between cortisol levels and BMI, Kmax, or Kmean. Cortisol levels also did not vary significantly across keratoconus severity categories in either eye.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Elevated cortisol levels may be associated with keratoconus progression, while lower levels appear linked to disease stability. Cortisol could serve as a potential biomarker for disease monitoring; however, further multicenter studies are needed to validate these findings and clarify cortisol\u2019s role in keratoconus pathogenesis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0331670","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T17:34:28Z","timestamp":1757698468000},"page":"e0331670","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between hair cortisol levels and keratoconus: A prospective study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5341-9137","authenticated-orcid":true,"given":"Noor","family":"Alqudah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nosayba","family":"Al-Azzam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leen El","family":"Taani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Al Qudah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdallah","family":"Sharayah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita A.","family":"Al-Rihani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"pone.0331670.ref001","article-title":"Keratoconus.","volume-title":"StatPearls","author":"G Asimellis","year":"2024"},{"issue":"3","key":"pone.0331670.ref002","doi-asserted-by":"crossref","first-page":"101559","DOI":"10.1016\/j.clae.2021.101559","article-title":"Keratoconus: an updated review","volume":"45","author":"J Santodomingo-Rubido","year":"2022","journal-title":"Cont Lens Anterior Eye"},{"issue":"5","key":"pone.0331670.ref003","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.ajo.2009.06.024","article-title":"Prevalence and associations of keratoconus in rural maharashtra in central India: the central India eye and medical study","volume":"148","author":"JB Jonas","year":"2009","journal-title":"Am J Ophthalmol"},{"issue":"1","key":"pone.0331670.ref004","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/sjopt.sjopt_204_21","article-title":"Keratoconus epidemiology: a review","volume":"36","author":"JA Gomes","year":"2022","journal-title":"Saudi J Ophthalmol"},{"issue":"11","key":"pone.0331670.ref005","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1136\/bjo.2005.074955","article-title":"Incidence and severity of keratoconus in Asir province, Saudi Arabia","volume":"89","author":"AA Assiri","year":"2005","journal-title":"Br J Ophthalmol"},{"issue":"2","key":"pone.0331670.ref006","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3109\/09286586.2011.560747","article-title":"Prevalence and associated factors of keratoconus in Jerusalem: a cross-sectional study","volume":"18","author":"M Millodot","year":"2011","journal-title":"Ophthalmic Epidemiol"},{"issue":"1","key":"pone.0331670.ref007","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1177\/112067210201200102","article-title":"Causes of blindness among adult Jordanians: a hospital-based study","volume":"12","author":"MD Al-Bdour","year":"2002","journal-title":"Eur J Ophthalmol"},{"issue":"2","key":"pone.0331670.ref008","doi-asserted-by":"crossref","first-page":"44","DOI":"10.7869\/djo.396","article-title":"Comparison of topographic and biomicroscopic features among symptomatic keratoconic eyes","volume":"29","author":"C Prasannakumary","year":"2018","journal-title":"DJO"},{"key":"pone.0331670.ref009","doi-asserted-by":"crossref","first-page":"795738","DOI":"10.1155\/2015\/795738","article-title":"The genetic and environmental factors for keratoconus","volume":"2015","author":"A Gordon-Shaag","year":"2015","journal-title":"Biomed Res Int"},{"key":"pone.0331670.ref010","doi-asserted-by":"crossref","first-page":"108328","DOI":"10.1016\/j.exer.2020.108328","article-title":"Genetics vs chronic corneal mechanical trauma in the etiology of keratoconus","volume":"202","author":"YS Rabinowitz","year":"2021","journal-title":"Exp Eye Res"},{"key":"pone.0331670.ref011","doi-asserted-by":"crossref","first-page":"102967","DOI":"10.1016\/j.redox.2023.102967","article-title":"Oxidative stress in the eye and its role in the pathophysiology of ocular diseases","volume":"68","author":"EW B\u00f6hm","year":"2023","journal-title":"Redox Biol"},{"issue":"9","key":"pone.0331670.ref012","doi-asserted-by":"crossref","first-page":"19294","DOI":"10.3390\/ijms140919294","article-title":"Oxidative stress in the pathogenesis of keratoconus and Fuchs endothelial corneal dystrophy","volume":"14","author":"KA Wojcik","year":"2013","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0331670.ref013","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.psyneuen.2010.06.012","article-title":"Elevated levels of circulating matrix metalloproteinase-9 are associated with a dysregulated cortisol rhythm\u2014A case-control study of coronary artery disease","volume":"36","author":"A Szymanowski","year":"2011","journal-title":"Psychoneuroendocrinology"},{"issue":"5","key":"pone.0331670.ref014","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.psyneuen.2011.09.009","article-title":"Hair cortisol as a biological marker of chronic stress: current status, future directions and unanswered questions","volume":"37","author":"E Russell","year":"2012","journal-title":"Psychoneuroendocrinology"},{"key":"pone.0331670.ref015","doi-asserted-by":"crossref","DOI":"10.1093\/geront\/gnu174","article-title":"Hair cortisol analysis: a promising biomarker of HPA activation in older adults","volume":"55","author":"KD Wright","year":"2015","journal-title":"Gerontologist"},{"key":"pone.0331670.ref016","doi-asserted-by":"crossref","first-page":"104650","DOI":"10.1016\/j.psyneuen.2020.104650","article-title":"Association between hair cortisol and diurnal basal cortisol levels: a 30-day validation study","volume":"116","author":"N Sugaya","year":"2020","journal-title":"Psychoneuroendocrinology"},{"issue":"1","key":"pone.0331670.ref017","doi-asserted-by":"crossref","first-page":"100624","DOI":"10.1016\/j.xops.2024.100624","article-title":"Relationship of inflammatory mediators (interleukin and cortisol concentrations) with corneal epithelial quantifiable metrics","volume":"5","author":"MR Santhiago","year":"2024","journal-title":"Ophthalmol Sci"},{"key":"pone.0331670.ref018","first-page":"2019","article-title":"Keratoconus: current perspectives","volume":"7","author":"J Vazirani","year":"2013","journal-title":"Clin Ophthalmol"},{"key":"pone.0331670.ref019","doi-asserted-by":"crossref","first-page":"3164734","DOI":"10.1155\/2016\/3164734","article-title":"The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults","volume":"2016","author":"M Nita","year":"2016","journal-title":"Oxid Med Cell Longev"},{"key":"pone.0331670.ref020","doi-asserted-by":"crossref","first-page":"101016","DOI":"10.1016\/j.preteyeres.2021.101016","article-title":"Anterior pituitary, sex hormones, and keratoconus: Beyond traditional targets","volume":"88","author":"D Karamichos","year":"2022","journal-title":"Prog Retin Eye Res"},{"issue":"5","key":"pone.0331670.ref021","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1097\/j.jcrs.0000000000000809","article-title":"Correlation of hair cortisol and interleukin 6 with structural change in the active progression of keratoconus","volume":"48","author":"LR Stival","year":"2022","journal-title":"J Cataract Refract Surg"},{"key":"pone.0331670.ref022","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fmolb.2019.00091","article-title":"Biomarkers in stress related diseases\/disorders: diagnostic, prognostic, and therapeutic values","volume":"6","author":"K Dhama","year":"2019","journal-title":"Front Mol Biosci"},{"issue":"6","key":"pone.0331670.ref023","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3928\/1081597X-20170413-01","article-title":"Increased hair cortisol concentrations in patients with progressive keratoconus","volume":"33","author":"J Lenk","year":"2017","journal-title":"J Refract Surg"},{"issue":"2","key":"pone.0331670.ref024","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1167\/iovs.14-14831","article-title":"Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A","volume":"56","author":"R Shetty","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"2","key":"pone.0331670.ref025","doi-asserted-by":"crossref","first-page":"100364","DOI":"10.1016\/j.xops.2023.100364","article-title":"Prospective observational study evaluating systemic hormones and corneal crosslinking effects in keratoconus","volume":"4","author":"L Van","year":"2023","journal-title":"Ophthalmol Sci"},{"issue":"1","key":"pone.0331670.ref026","doi-asserted-by":"crossref","DOI":"10.1002\/ansa.70003","article-title":"A dual biomarker approach to stress: hair and salivary cortisol measurement in students via LC\u2010MS\/MS","volume":"6","author":"MK Hakeem","year":"2025","journal-title":"Anal Sci Adv"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331670","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T17:34:31Z","timestamp":1757698471000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0331670"}},"subtitle":[],"editor":[{"given":"Georgios","family":"Labiris","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":26,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0331670","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]}}}