{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T08:07:03Z","timestamp":1785571623028,"version":"3.56.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF-2019R1C1C1007917"],"award-info":[{"award-number":["NRF-2019R1C1C1007917"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"crossref","award":["HI19C0481"],"award-info":[{"award-number":["HI19C0481"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This nationwide population-based study investigated the incidence rate of and risk factors for the progression to corneal transplantation in patients with keratoconus in South Korea using claims data from the Health Insurance Review and Assessment service. Among the entire South Korean population, 10,612 patients newly diagnosed with keratoconus between January 2010 and June 2015 were identified and included in the study. During the study period, 124 patients (1.17%) underwent corneal transplantation, with an average follow-up period of 2.97\u2009\u00b1\u20091.59\u00a0years. The incidence rate of corneal transplantation in patients with keratoconus was 4.46 cases per 1000 person-years. The rate of corneal transplantation for keratoconus was relatively low in South Korea compared to other countries. Multivariate Cox regression analysis revealed that male sex (HR 2.37; 95% CI 1.61\u20133.50; P\u2009&lt;\u20090.001), severe atopic dermatitis (HR 2.32; 95% CI 1.02\u20135.28; P\u2009=\u20090.044), obstructive sleep apnea (HR 9.78; 95% CI 1.36\u201370.10; P\u2009=\u20090.023), and intellectual disability (HR 4.48; 95% CI 1.33\u201315.11; P\u2009=\u20090.016) significantly increased the risk of progression to corneal transplantation. In patients with keratoconus, male sex, severe atopic dermatitis, obstructive sleep apnea, and intellectual disability were associated with an increased risk of corneal transplantation.<\/jats:p>","DOI":"10.1038\/s41598-021-92133-y","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T10:04:25Z","timestamp":1623751465000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Corneal transplantation for keratoconus in South Korea"],"prefix":"10.1038","volume":"11","author":[{"given":"Sungsoon","family":"Hwang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Young","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisang","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyunga","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hui","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"92133_CR1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/0039-6257(84)90094-8","volume":"28","author":"JH Krachmer","year":"1984","unstructured":"Krachmer, J. H., Feder, R. S. & Belin, M. W. Keratoconus and related noninflammatory corneal thinning disorders. Surv. Ophthalmol. 28, 293\u2013322 (1984).","journal-title":"Surv. Ophthalmol."},{"key":"92133_CR2","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/S0039-6257(97)00119-7","volume":"42","author":"YS Rabinowitz","year":"1998","unstructured":"Rabinowitz, Y. S. Keratoconus. Surv. Ophthalmol. 42, 297\u2013319 (1998).","journal-title":"Surv. Ophthalmol."},{"key":"92133_CR3","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1097\/00006324-199703000-00025","volume":"74","author":"JL Olivares Jimenez","year":"1997","unstructured":"Olivares Jimenez, J. L., Guerrero Jurado, J. C., Bermudez Rodriguez, F. J. & Serrano Laborda, D. Keratoconus: Age of onset and natural history. Optom. Vis. Sci. 74, 147\u2013151 (1997).","journal-title":"Optom. Vis. Sci."},{"key":"92133_CR4","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1111\/j.1442-9071.2009.02009.x","volume":"37","author":"CN McGhee","year":"2009","unstructured":"McGhee, C. N. 2008 Sir Norman McAlister Gregg Lecture: 150 years of practical observations on the conical cornea\u2014What have we learned?. Clin. Exp. Ophthalmol. 37, 160\u2013176 (2009).","journal-title":"Clin. Exp. Ophthalmol."},{"key":"92133_CR5","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.jcrs.2003.12.005","volume":"30","author":"S Kwitko","year":"2004","unstructured":"Kwitko, S. & Severo, N. S. Ferrara intracorneal ring segments for keratoconus. J. Cataract Refract. Surg. 30, 812\u2013820 (2004).","journal-title":"J. Cataract Refract. Surg."},{"key":"92133_CR6","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1016\/j.jcrs.2014.01.047","volume":"40","author":"P Pena-Garcia","year":"2014","unstructured":"Pena-Garcia, P., Alio, J. L., Vega-Estrada, A. & Barraquer, R. I. Internal, corneal, and refractive astigmatism as prognostic factors for intrastromal corneal ring segment implantation in mild to moderate keratoconus. J. Cataract Refract. Surg. 40, 1633\u20131644 (2014).","journal-title":"J. Cataract Refract. Surg."},{"key":"92133_CR7","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/S0002-9394(02)02220-1","volume":"135","author":"G Wollensak","year":"2003","unstructured":"Wollensak, G., Spoerl, E. & Seiler, T. Riboflavin\/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am. J. Ophthalmol. 135, 620\u2013627 (2003).","journal-title":"Am. J. Ophthalmol."},{"key":"92133_CR8","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1097\/ICO.0b013e318030df5a","volume":"26","author":"C Mazzotta","year":"2007","unstructured":"Mazzotta, C. et al. Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: Ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans. Cornea 26, 390\u2013397 (2007).","journal-title":"Cornea"},{"key":"92133_CR9","doi-asserted-by":"publisher","first-page":"746","DOI":"10.3928\/1081597X-20141021-06","volume":"30","author":"P Vinciguerra","year":"2014","unstructured":"Vinciguerra, P. et al. Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: Initial clinical outcomes. J. Refract. Surg. 30, 746\u2013753 (2014).","journal-title":"J. Refract. Surg."},{"key":"92133_CR10","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/S0161-6420(94)31313-3","volume":"101","author":"SJ Tuft","year":"1994","unstructured":"Tuft, S. J., Moodaley, L. C., Gregory, W. M., Davison, C. R. & Buckley, R. J. Prognostic factors for the progression of keratoconus. Ophthalmology 101, 439\u2013447 (1994).","journal-title":"Ophthalmology"},{"key":"92133_CR11","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.ajo.2006.07.026","volume":"142","author":"MO Gordon","year":"2006","unstructured":"Gordon, M. O. et al. Baseline factors predictive of incident penetrating keratoplasty in keratoconus. Am. J. Ophthalmol. 142, 923\u2013930 (2006).","journal-title":"Am. J. Ophthalmol."},{"key":"92133_CR12","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1136\/bjo.2010.185868","volume":"95","author":"V Jhanji","year":"2011","unstructured":"Jhanji, V., Sharma, N. & Vajpayee, R. B. Management of keratoconus: Current scenario. Br. J. Ophthalmol. 95, 1044\u20131050 (2011).","journal-title":"Br. J. Ophthalmol."},{"key":"92133_CR13","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1097\/ICO.0000000000001083","volume":"36","author":"D Sarezky","year":"2017","unstructured":"Sarezky, D., Orlin, S. E., Pan, W. & VanderBeek, B. L. Trends in corneal transplantation in keratoconus. Cornea 36, 131\u2013137 (2017).","journal-title":"Cornea"},{"key":"92133_CR14","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1097\/ICO.0000000000000408","volume":"34","author":"JA Gomes","year":"2015","unstructured":"Gomes, J. A. et al. Global consensus on keratoconus and ectatic diseases. Cornea 34, 359\u2013369 (2015).","journal-title":"Cornea"},{"key":"92133_CR15","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.ophtha.2015.10.035","volume":"123","author":"MA Woodward","year":"2016","unstructured":"Woodward, M. A., Blachley, T. S. & Stein, J. D. The association between sociodemographic factors, common systemic diseases, and keratoconus: An analysis of a Nationwide Heath Care Claims Database. Ophthalmology 123, 457-465 e452 (2016).","journal-title":"Ophthalmology"},{"key":"92133_CR16","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/aos.13961","volume":"97","author":"S Bak-Nielsen","year":"2019","unstructured":"Bak-Nielsen, S., Ramlau-Hansen, C. H., Ivarsen, A., Plana-Ripoll, O. & Hjortdal, J. A nationwide population-based study of social demographic factors, associated diseases and mortality of keratoconus patients in Denmark from 1977 to 2015. Acta Ophthalmol. 97, 497\u2013504 (2019).","journal-title":"Acta Ophthalmol."},{"key":"92133_CR17","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.ajo.2005.05.029","volume":"140","author":"SW Reeves","year":"2005","unstructured":"Reeves, S. W., Stinnett, S., Adelman, R. A. & Afshari, N. A. Risk factors for progression to penetrating keratoplasty in patients with keratoconus. Am. J. Ophthalmol. 140, 607\u2013611 (2005).","journal-title":"Am. J. Ophthalmol."},{"key":"92133_CR18","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.ajo.2018.04.027","volume":"192","author":"S Hwang","year":"2018","unstructured":"Hwang, S., Lim, D. H. & Chung, T. Y. Prevalence and incidence of keratoconus in South Korea: A nationwide population-based study. Am. J. Ophthalmol. 192, 56\u201364 (2018).","journal-title":"Am. J. Ophthalmol."},{"key":"92133_CR19","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1016\/j.ophtha.2013.12.024","volume":"121","author":"SJ Park","year":"2014","unstructured":"Park, S. J., Choi, N. K., Park, K. H. & Woo, S. J. Nationwide incidence of clinically diagnosed retinal vein occlusion in Korea, 2008 through 2011: Preponderance of women and the impact of aging. Ophthalmology 121, 1274\u20131280 (2014).","journal-title":"Ophthalmology"},{"key":"92133_CR20","doi-asserted-by":"publisher","first-page":"578","DOI":"10.5021\/ad.2015.27.5.578","volume":"27","author":"JE Kim","year":"2015","unstructured":"Kim, J. E. et al. Consensus guidelines for the treatment of atopic dermatitis in Korea (Part II): Systemic treatment. Ann. Dermatol. 27, 578\u2013592 (2015).","journal-title":"Ann. Dermatol."},{"key":"92133_CR21","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1111\/1346-8138.13392","volume":"43","author":"H Saeki","year":"2016","unstructured":"Saeki, H. et al. Clinical practice guidelines for the management of atopic dermatitis 2016. J. Dermatol. 43, 1117\u20131145 (2016).","journal-title":"J. Dermatol."},{"key":"92133_CR22","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.clae.2007.03.001","volume":"30","author":"H Wagner","year":"2007","unstructured":"Wagner, H., Barr, J. T. & Zadnik, K. Collaborative longitudinal evaluation of keratoconus (CLEK) study: Methods and findings to date. Contact Lens Anterior Eye 30, 223\u2013232 (2007).","journal-title":"Contact Lens Anterior Eye"},{"key":"92133_CR23","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.ajo.2005.03.078","volume":"140","author":"BA Fink","year":"2005","unstructured":"Fink, B. A. et al. Differences in keratoconus as a function of gender. Am. J. Ophthalmol. 140, 459\u2013468 (2005).","journal-title":"Am. J. Ophthalmol."},{"key":"92133_CR24","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1097\/ICO.0b013e31817f815a","volume":"27","author":"A Ertan","year":"2008","unstructured":"Ertan, A. & Muftuoglu, O. Keratoconus clinical findings according to different age and gender groups. Cornea 27, 1109\u20131113 (2008).","journal-title":"Cornea"},{"key":"92133_CR25","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.preteyeres.2018.05.002","volume":"67","author":"R Sharif","year":"2018","unstructured":"Sharif, R., Bak-Nielsen, S., Hjortdal, J. & Karamichos, D. Pathogenesis of keratoconus: The intriguing therapeutic potential of prolactin-inducible protein. Prog. Retin. Eye Res. 67, 150\u2013167 (2018).","journal-title":"Prog. Retin. Eye Res."},{"key":"92133_CR26","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.ophtha.2005.10.009","volume":"113","author":"IC Kuo","year":"2006","unstructured":"Kuo, I. C., Broman, A., Pirouzmanesh, A. & Melia, M. Is there an association between diabetes and keratoconus?. Ophthalmology 113, 184\u2013190 (2006).","journal-title":"Ophthalmology"},{"key":"92133_CR27","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1172\/JCI116481","volume":"91","author":"DG Dyer","year":"1993","unstructured":"Dyer, D. G. et al. Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J. Clin. Investig. 91, 2463\u20132469 (1993).","journal-title":"J. Clin. Investig."},{"key":"92133_CR28","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1006\/exer.1997.0410","volume":"66","author":"E Spoerl","year":"1998","unstructured":"Spoerl, E., Huhle, M. & Seiler, T. Induction of cross-links in corneal tissue. Exp. Eye Res. 66, 97\u2013103 (1998).","journal-title":"Exp. Eye Res."},{"key":"92133_CR29","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1136\/bjo.73.10.816","volume":"73","author":"RJ Harrison","year":"1989","unstructured":"Harrison, R. J. et al. Association between keratoconus and atopy. Br. J. Ophthalmol. 73, 816\u2013822 (1989).","journal-title":"Br. J. Ophthalmol."},{"key":"92133_CR30","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1097\/ICO.0b013e31818d37fa","volume":"28","author":"B Yeniad","year":"2009","unstructured":"Yeniad, B., Alparslan, N. & Akarcay, K. Eye rubbing as an apparent cause of recurrent keratoconus. Cornea 28, 477\u2013479 (2009).","journal-title":"Cornea"},{"key":"92133_CR31","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1076\/ceyr.16.8.792.8989","volume":"16","author":"AJ Tuori","year":"1997","unstructured":"Tuori, A. J. et al. The immunohistochemical composition of corneal basement membrane in keratoconus. Curr. Eye Res. 16, 792\u2013801 (1997).","journal-title":"Curr. Eye Res."},{"key":"92133_CR32","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/S1367-0484(03)00022-5","volume":"26","author":"M CristinaKenney","year":"2003","unstructured":"CristinaKenney, M. & Brown, D. J. The cascade hypothesis of keratoconus. Contact Lens Anterior Eye 26, 139\u2013146 (2003).","journal-title":"Contact Lens Anterior Eye"},{"key":"92133_CR33","doi-asserted-by":"publisher","first-page":"641708","DOI":"10.1155\/2014\/641708","volume":"2014","author":"KK Abu-Amero","year":"2014","unstructured":"Abu-Amero, K. K., Al-Muammar, A. M. & Kondkar, A. A. Genetics of keratoconus: Where do we stand?. J. Ophthalmol. 2014, 641708 (2014).","journal-title":"J. Ophthalmol."},{"key":"92133_CR34","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1097\/ICO.0b013e31823f8acd","volume":"31","author":"PK Gupta","year":"2012","unstructured":"Gupta, P. K., Stinnett, S. S. & Carlson, A. N. Prevalence of sleep apnea in patients with keratoconus. Cornea 31, 595\u2013599 (2012).","journal-title":"Cornea"},{"key":"92133_CR35","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1097\/ICO.0b013e318243e446","volume":"31","author":"MA Saidel","year":"2012","unstructured":"Saidel, M. A. et al. Prevalence of sleep apnea syndrome and high-risk characteristics among keratoconus patients. Cornea 31, 600\u2013603 (2012).","journal-title":"Cornea"},{"key":"92133_CR36","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/j.1755-3768.1992.tb02101.x","volume":"70","author":"OH Haugen","year":"1992","unstructured":"Haugen, O. H. Keratoconus in the mentally retarded. Acta Ophthalmol. (Copenh) 70, 111\u2013114 (1992).","journal-title":"Acta Ophthalmol. (Copenh)"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92133-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92133-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92133-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T09:56:42Z","timestamp":1670061402000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92133-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,15]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["92133"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-92133-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,15]]},"assertion":[{"value":"4 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12580"}}