{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:46:08Z","timestamp":1790675168497,"version":"4.1.0"},"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Region Grand Est, France","award":["17CP-1391-C63"],"award-info":[{"award-number":["17CP-1391-C63"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The steep cornea in keratoconus can greatly impair eyesight. The etiology of keratoconus remains unclear but early injury that weakens the corneal stromal architecture has been implicated. To explore keratoconus mechanics, we conducted two numerical simulation studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A finite-element model describing the five corneal layers and the heterogeneous mechanical behaviors of the ground substance and lamellar collagen-fiber architecture in the anterior and posterior stroma was developed using the Holzapfel-Gasser-Ogden constitutive model. The geometry was from a healthy subject. Its stroma was divided into anterior, middle, and posterior layers to assess the effect of changing regional mechanical parameters on corneal displacement and maximum principal stress under intraocular pressure. Specifically, the effect of softening an inferocentral corneal button, the collagen-based tissues throughout the whole cornea, or specific stromal layers in the button was examined. The effect of simply disorganizing the orthogonally-oriented posterior stromal fibers in the button was also assessed. The healthy cornea was also subjected to eye rubbing-like loading to identify the corneal layer(s) that experienced the most tensional stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Conical deformation and corneal thinning emerged when the corneal button or the mid-posterior stroma of the button underwent gradual softening or when the collagen fibers in the mid-posterior stroma of the button were dispersed. Softening the anterior layers of the button or the whole cornea did not evoke conical deformation. Button softening greatly increased and disrupted the stress on Bowman\u2019s membrane while mid-posterior stromal softening increased stress in the anterior layers. Eye rubbing profoundly stressed the deep posterior stroma while other layers were negligibly affected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These observations suggest that keratoconus could be initiated, at least partly, by mechanical instability\/damage in the mid-posterior stroma that then imposes stress on the anterior layers. This may explain why subclinical keratoconus is marked by posterior but not anterior elevation on videokeratoscopy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0278455","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T14:30:00Z","timestamp":1675348200000},"page":"e0278455","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Biomechanics of keratoconus: Two numerical studies"],"prefix":"10.1371","volume":"18","author":[{"given":"Nicolas","family":"Falgayrettes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Patoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Cleymand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2966-0251","authenticated-orcid":true,"given":"Yinka","family":"Zevering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1427-7567","authenticated-orcid":true,"given":"Jean-Marc","family":"Perone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"pone.0278455.ref001","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":"MS Sridhar","year":"2018","journal-title":"Indian J Ophthalmol"},{"key":"pone.0278455.ref002","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.exer.2014.08.001","article-title":"Regulation of corneal stroma extracellular matrix assembly","volume":"133","author":"S Chen","year":"2015","journal-title":"Exp Eye Res"},{"key":"pone.0278455.ref003","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1167\/iovs.10-5657","article-title":"Three-dimensional analysis of collagen lamellae in the anterior stroma of the human cornea visualized by second harmonic generation imaging microscopy","volume":"52","author":"N Morishige","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"pone.0278455.ref004","volume-title":"Adler\u2019s physiology of the eye","author":"DL Ubels","year":"2011"},{"key":"pone.0278455.ref005","doi-asserted-by":"crossref","first-page":"20150241","DOI":"10.1098\/rsif.2015.0241","article-title":"A structural model for the in vivo human cornea including collagen-swelling interaction","volume":"12","author":"X Cheng","year":"2015","journal-title":"J R Soc Interface"},{"key":"pone.0278455.ref006","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.preteyeres.2009.06.005","article-title":"The use of X-ray scattering techniques to quantify the orientation and distribution of collagen in the corneal stroma.","volume":"28","author":"KM Meek","year":"2009","journal-title":"Prog Retin Eye Res."},{"key":"pone.0278455.ref007","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s10237-012-0466-8","article-title":"The role of 3-D collagen organization in stromal elasticity: a model based on X-ray diffraction data and second harmonic-generated images.","volume":"12","author":"SJ Petsche","year":"2013","journal-title":"Biomech Model Mechanobiol."},{"key":"pone.0278455.ref008","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1006\/exer.1998.0826","article-title":"Type XIII collagen is widely expressed in the adult and developing human eye and accentuated in the ciliary muscle, the optic nerve and the neural retina","volume":"70","author":"M Sandberg-Lall","year":"2000","journal-title":"Exp Eye Res"},{"key":"pone.0278455.ref009","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.ophtha.2014.09.037","article-title":"Ultrastructure of the posterior corneal stroma","volume":"122","author":"U Schl\u00f6tzer-Schrehardt","year":"2015","journal-title":"Ophthalmology"},{"key":"pone.0278455.ref010","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.3928\/1081597X-20080101-15","article-title":"Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery","volume":"24","author":"JB Randleman","year":"2008","journal-title":"J Refract Surg"},{"key":"pone.0278455.ref011","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1136\/bjo.85.4.437","article-title":"The specific architecture of the anterior stroma accounts for maintenance of corneal curvature","volume":"85","author":"LJ M\u00fcller","year":"2001","journal-title":"Br J Ophthalmol"},{"key":"pone.0278455.ref012","volume-title":"(Re-)Discovering A Blueprint Of The Cornea: Structural, Biomechanical, Evolutionary and Developmental Perspectives","author":"M. 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