{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:02:22Z","timestamp":1791928942578,"version":"4.3.4"},"reference-count":52,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2026,6,10]]},"DOI":"10.1167\/iovs.67.6.17","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T12:30:58Z","timestamp":1781094658000},"page":"17","source":"Crossref","is-referenced-by-count":0,"title":["Sex Hormone Imbalance in Keratoconus: Estrogen-Mediated Collagen Remodeling and Biomechanical Weakening"],"prefix":"10.1167","volume":"67","author":[{"given":"Mengyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Gao","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Ma","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengchen","family":"Cui","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaozhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibo","family":"Yang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"1","key":"bib1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/s41572-024-00565-3","article-title":"Keratoconus","volume":"10","author":"Singh","year":"2024","journal-title":"Nat Rev Dis Primers"},{"issue":"4","key":"bib2","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1097\/ICO.0000000000000408","article-title":"Global consensus on keratoconus and ectatic diseases","volume":"34","author":"Gomes","year":"2015","journal-title":"Cornea"},{"key":"bib3","doi-asserted-by":"crossref","DOI":"10.1097\/ICO.0000000000003973","article-title":"Global incidence and prevalence of keratoconus: a systematic review and meta-analysis [printed online ahead of print August 20, 2025]","author":"Sriranganathan","year":"2025","journal-title":"Cornea"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"3473","DOI":"10.2147\/OPTH.S248724","article-title":"Risk factors for development of keratoconus: a matched pair case\u2013control study","volume":"15","author":"Almusawi","year":"2021","journal-title":"Clin Ophthalmol"},{"issue":"9","key":"bib5","first-page":"2356","article-title":"Prevalence and clinical profile of keratoconus in patients presenting at a provincial hospital in KwaZulu, Natal, South Africa: a case study","volume":"14","author":"Gcabashe","year":"2023","journal-title":"J Public Health Afr"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.ajo.2016.12.015","article-title":"Age-specific incidence and prevalence of keratoconus: a nationwide registration study","volume":"175","author":"Godefrooij","year":"2017","journal-title":"Am J Ophthalmol"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.ajo.2018.04.027","article-title":"Prevalence and incidence of keratoconus in South Korea: a nationwide population-based study","volume":"192","author":"Hwang","year":"2018","journal-title":"Am J Ophthalmol"},{"issue":"8","key":"bib8","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1136\/bjo.2010.185868","article-title":"Management of keratoconus: current scenario","volume":"95","author":"Jhanji","year":"2011","journal-title":"Br J Ophthalmol"},{"issue":"3","key":"bib9","doi-asserted-by":"publisher","first-page":"45","DOI":"10.21037\/atm-23-1906","article-title":"Ten-year incidence of keratoconus in relation to sex, age, and thyroid gland dysfunction: a nationwide population-based cohort study (2009\u20132018)","volume":"12","author":"Chung","year":"2024","journal-title":"Ann Transl Med"},{"issue":"2","key":"bib10","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/j.1444-0938.2004.tb03155.x","article-title":"Keratoconus in Asian eyes at a tertiary eye care facility","volume":"87","author":"Saini","year":"2004","journal-title":"Clin Exp Optom"},{"issue":"1","key":"bib11","doi-asserted-by":"publisher","first-page":"102567","DOI":"10.1016\/j.clae.2025.102567","article-title":"Prevalence and factors associated with keratoconus among high school students in Trinidad and Tobago: a cross-sectional population-based study","volume":"49","author":"Ezinne","year":"2026","journal-title":"Cont Lens Anterior Eye"},{"issue":"4","key":"bib12","doi-asserted-by":"publisher","first-page":"e0284454","DOI":"10.1371\/journal.pone.0284454","article-title":"Non-allergic eye rubbing is a major behavioral risk factor for keratoconus","volume":"18","author":"Jaskiewicz","year":"2023","journal-title":"PLoS One"},{"issue":"4","key":"bib13","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1167\/tvst.14.4.14","article-title":"Causal relationship between common allergic diseases and keratoconus: a two-sample mendelian randomization study","volume":"14","author":"Yang","year":"2025","journal-title":"Transl Vis Sci Technol"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"252","DOI":"10.2174\/1874364101711010252","article-title":"Pathophysiology of keratoconus: what do we know today","volume":"11","author":"Soiberman","year":"2017","journal-title":"Open Ophthalmol J"},{"issue":"6","key":"bib15","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1167\/iovs.04-1253","article-title":"Changes in collagen orientation and distribution in keratoconus corneas","volume":"46","author":"Meek","year":"2005","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5","key":"bib16","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1097\/01.ico.0000208820.32614.00","article-title":"Collagenolytic proteinases in keratoconus","volume":"25","author":"Mackiewicz","year":"2006","journal-title":"Cornea"},{"issue":"4","key":"bib17","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.bbadis.2006.01.010","article-title":"Keratoconus: matrix metalloproteinase-2 activation and TIMP modulation","volume":"1762","author":"Smith","year":"2006","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"bib18","doi-asserted-by":"publisher","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":"Shetty","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.exer.2012.09.005","article-title":"Changes in lysyl oxidase (LOX) distribution and its decreased activity in keratoconus corneas","volume":"104","author":"Dudakova","year":"2012","journal-title":"Exp Eye Res"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"109062","DOI":"10.1016\/j.exer.2022.109062","article-title":"Pathogenesis of keratoconus: NRF2-antioxidant, extracellular matrix and cellular dysfunctions","volume":"219","author":"Monteiro de Barros","year":"2022","journal-title":"Exp Eye Res"},{"issue":"6","key":"bib21","doi-asserted-by":"publisher","first-page":"3269","DOI":"10.3390\/ijms23063269","article-title":"Sex hormones and their effects on ocular disorders and pathophysiology: current aspects and our experience","volume":"23","author":"Nuzzi","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"2","key":"bib22","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1167\/iovs.12-10457","article-title":"The effects of estrogen and androgen on tear secretion and matrix metalloproteinase-2 expression in lacrimal glands of ovariectomized rats","volume":"55","author":"Song","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"bib23","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1111\/cxo.12147","article-title":"Sex hormones and the dry eye","volume":"97","author":"Truong","year":"2014","journal-title":"Clin Exp Optom"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1093\/brain\/awq276","article-title":"Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy","volume":"134","author":"Giordano","year":"2011","journal-title":"Brain J. Neurol."},{"issue":"8","key":"bib25","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1016\/j.jcrs.2011.03.038","article-title":"Variations in corneal biomechanical parameters and central corneal thickness during the menstrual cycle","volume":"37","author":"Goldich","year":"2011","journal-title":"J Cataract Refract Surg"},{"issue":"4","key":"bib26","doi-asserted-by":"publisher","first-page":"e291","DOI":"10.1111\/aos.13296","article-title":"Topographic, tomographic and biomechanical corneal changes during pregnancy in patients with keratoconus: a cohort study","volume":"95","author":"Naderan","year":"2017","journal-title":"Acta Ophthalmol"},{"issue":"5","key":"bib27","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.clae.2018.11.015","article-title":"Evaluation estrogen, progesterone and androgen receptor expressions in corneal epithelium in keratoconus","volume":"42","author":"Ayan","year":"2019","journal-title":"Cont Lens Anterior Eye"},{"issue":"1","key":"bib28","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.jcrs.2018.08.036","article-title":"Late-onset progression of keratoconus after therapy with selective tissue estrogenic activity regulator","volume":"45","author":"Torres-Netto","year":"2019","journal-title":"J Cataract Refract Surg"},{"issue":"1","key":"bib29","first-page":"51","article-title":"Androgen-dependent hereditary mouse keratoconus: linkage to an MHC region","volume":"43","author":"Tachibana","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"25534","DOI":"10.1038\/srep25534","article-title":"Endocrine and metabolic pathways linked to keratoconus: implications for the role of hormones in the stromal microenvironment","volume":"6","author":"McKay","year":"2016","journal-title":"Sci Rep"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"828233","DOI":"10.3389\/fmed.2022.828233","article-title":"Associations between keratoconus and the level of sex hormones: a cross-sectional study","volume":"9","author":"Zhao","year":"2022","journal-title":"Front Med (Lausanne)"},{"issue":"5","key":"bib32","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1111\/cen.14578","article-title":"Interpretation of reproductive hormones before, during and after the pubertal transition-Identifying health and disordered puberty","volume":"95","author":"Howard","year":"2021","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"4","key":"bib33","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.3390\/jcm14041256","article-title":"Corneal epithelial thickness maps in eyes with mild and moderate keratoconus","volume":"14","author":"Mlyniuk","year":"2025","journal-title":"J Clin Med"},{"key":"bib34","article-title":"Media matters: phenol red and fetal bovine serum estrogen in traditional cell culture media influence human mesenchymal stromal cell (hMSC) processes and differentiation in a sex-biased manner","author":"Bradford","year":"2025","journal-title":"bioRxiv"},{"issue":"1","key":"bib35","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.juro.2010.09.004","article-title":"The effects of physiological estrogen concentration on the immune response of urothelial carcinoma cells to bacillus Calmette-Gu\u00e9rin","volume":"185","author":"Guise","year":"2011","journal-title":"J Urol"},{"key":"bib36","first-page":"3415","article-title":"Inhibition by female sex hormones of collagen degradation by corneal fibroblasts","volume":"17","author":"Zhou","year":"2011","journal-title":"Mol Vis"},{"issue":"4A","key":"bib37","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1590\/S1519-69842002000400008","article-title":"Determination of the estrous cycle phases of rats: some helpful considerations","volume":"62","author":"Marcondes","year":"2002","journal-title":"Braz J Biol"},{"issue":"6","key":"bib38","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1523\/JNEUROSCI.21-06-01809.2001","article-title":"Estrogen prevents the lipopolysaccharide-induced inflammatory response in microglia","volume":"21","author":"Vegeto","year":"2001","journal-title":"J Neurosci"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"100926","DOI":"10.1016\/j.yfrne.2021.100926","article-title":"On the role of sex steroids in biological functions by classical and non-classical pathways. An update","volume":"62","author":"Pillerov\u00e1","year":"2021","journal-title":"Front Neuroendocrinol"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3389\/fbioe.2019.00066","article-title":"A review of structural and biomechanical changes in the cornea in aging, disease, and photochemical crosslinking","volume":"7","author":"Blackburn","year":"2019","journal-title":"Front Bioeng Biotechnol"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"101016","DOI":"10.1016\/j.preteyeres.2021.101016","article-title":"Anterior pituitary, sex hormones, and keratoconus: Beyond traditional targets","volume":"88","author":"Karamichos","year":"2022","journal-title":"Prog Retin Eye Res"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.preteyeres.2018.05.002","article-title":"Pathogenesis of keratoconus: the intriguing therapeutic potential of prolactin-inducible protein","volume":"67","author":"Sharif","year":"2018","journal-title":"Prog Retin Eye Res"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"108115","DOI":"10.1016\/j.exer.2020.108115","article-title":"Biological functions of tear film","volume":"197","author":"Pflugfelder","year":"2020","journal-title":"Exp Eye Res"},{"issue":"10","key":"bib44","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1210\/js.2019-00178","article-title":"Age-specific serum total and free estradiol concentrations in healthy men in US nationally representative samples","volume":"3","author":"Chadid","year":"2019","journal-title":"J Endocr Soc"},{"issue":"1","key":"bib45","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3928\/1081597X-20151207-10","article-title":"Keratoconus progression induced by in vitro fertilization treatment","volume":"32","author":"Yuksel","year":"2016","journal-title":"J Refract Surg"},{"issue":"9","key":"bib46","first-page":"1779","article-title":"Expression of collagenolytic\/gelatinolytic metalloproteinases by normal cornea","volume":"31","author":"Fini","year":"1990","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"bib47","doi-asserted-by":"publisher","first-page":"9944","DOI":"10.1038\/s41467-025-64889-8","article-title":"Regulation of corneal stromal cell behavior by modulating curvature using a hydraulically-controlled organ chip array","volume":"16","author":"Kim","year":"2025","journal-title":"Nat Commun"},{"issue":"1","key":"bib48","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.jss.2013.05.070","article-title":"Androgens regulate MMPs and the cellular processes of intimal hyperplasia","volume":"184","author":"Mountain","year":"2013","journal-title":"J Surg Res"},{"issue":"16","key":"bib49","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1101\/gad.1564207","article-title":"Cell- and gene-specific regulation of primary target genes by the androgen receptor","volume":"21","author":"Bolton","year":"2007","journal-title":"Genes Dev"},{"issue":"12","key":"bib50","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1007\/s00417-019-04490-0","article-title":"The effect of estrogen and progesterone on porcine corneal biomechanical properties","volume":"257","author":"Walter","year":"2019","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"issue":"2","key":"bib51","first-page":"319","article-title":"Oestrogen-induced changes in biomechanics in the cornea","volume":"84","author":"Spoerl","year":"2007","journal-title":"Exp Eye Res"},{"issue":"6","key":"bib52","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.survophthal.2017.06.009","article-title":"A review of keratoconus: diagnosis, pathophysiology, and genetics","volume":"62","author":"Mas Tur","year":"2017","journal-title":"Surv Ophthalmol"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.6.17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:14Z","timestamp":1791927134000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.6.17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":52,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.67.6.17","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,10]]}}}