{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:13:18Z","timestamp":1790143998574,"version":"4.0.1"},"reference-count":27,"publisher":"Bentham Science Publishers Ltd.","issue":"1","license":[{"start":{"date-parts":[[2011,2,11]],"date-time":"2011-02-11T00:00:00Z","timestamp":1297382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"}],"content-domain":{"domain":["openophthalmologyjournal.com","benthamopen.com"],"crossmark-restriction":true},"short-container-title":["TOOPHTJ"],"published-print":{"date-parts":[[2011,2,11]]},"abstract":"\n Purpose:<\/jats:title>\n To compile the safety aspects of the corneal collagen cross-linking (CXL) by means of the riboflavin\/UVA (370 nm) approach.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methodology:<\/jats:title>\n Analysis of the current treatment protocol with respect to safety during CXL.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The currently used UVA dose density of 5.4 J\/cm\n 2<\/jats:sup>\n and the corresponding irradiance of 3 mW\/cm\n 2<\/jats:sup>\n are below the known damage thresholds of UVA for the corneal endothelium, lens, and retina. Regarding the photochemical damages due to the free radicals the damage threshold for endothelial cells is 0.35 mW\/cm\n 2<\/jats:sup>\n . In a 400\u03bcm thick corneal stroma saturated with riboflavin, the irradiance at the endothelial level is about 0.18 mW\/cm\n 2<\/jats:sup>\n , which is a factor of 2 smaller than the damage threshold.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n As long as the corneal stroma treated has a minimal thickness of 400 microns (as recommended), neither corneal endothelium nor deeper structures such as lens and retina will suffer any damages. The light source should provide a homogenous irradiance avoiding hot spots.<\/jats:p>\n <\/jats:sec>","DOI":"10.2174\/1874364101105010014","type":"journal-article","created":{"date-parts":[[2011,4,6]],"date-time":"2011-04-06T02:06:09Z","timestamp":1302055569000},"page":"14-16","update-policy":"https:\/\/doi.org\/10.2174\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Corneal Cross-Linking and Safety Issues"],"prefix":"10.2174","volume":"5","author":[{"given":"Eberhard","family":"Spoerl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hoyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz E","family":"Pillunat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Raiskup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"refR1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1006\/exer.1997.0410","volume":"66","author":"Spoerl E","year":"1998","unstructured":"Spoerl E, Huhle M, Seiler T. \n Induction of cross-links in corneal tissue \n Exp Eye Res \n 1998; \n 66\n : 97-103.","journal-title":"Exp Eye Res"},{"key":"refR2","first-page":"711","volume":"15","author":"Spoerl E","year":"1999","unstructured":"Spoerl E, Seiler T. \n Techniques for stiffening the cornea \n J Refract Surg \n 1999; \n 15\n : 711-3.","journal-title":"J Refract Surg"},{"key":"refR3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s003470050515","volume":"97","author":"Sp\u00f6rl E","year":"2000","unstructured":"Sp\u00f6rl E, Schreiber J, Hellmund K, Seiler T, Knuschke P. \n Studies on the stabilization of the cornea in rabbits \n Ophthalmologe \n 2000; \n 97\n : 203-6.","journal-title":"Ophthalmologe"},{"key":"refR4","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1159\/000074071","volume":"35","author":"Wollensak G","year":"2003","unstructured":"Wollensak G, Sp\u00f6rl E, Reber F, Pillunat L, Funk R. \n Corneal endothelial cytotoxicity of riboflavin\/UVA treatment in vitro \n Ophthalmic Res \n 2003; \n 35\n : 324-8.","journal-title":"Ophthalmic Res"},{"key":"refR5","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1016\/S0886-3350(03)00343-2","volume":"29","author":"Wollensak G","year":"2003","unstructured":"Wollensak G, Spoerl E, Wilsch M, Seiler T. \n Endothelial cell damage after riboflavin-ultraviolet-A treatment in the rabbit \n J Cataract Refract Surg \n 2003; \n 29\n : 1786-90.","journal-title":"J Cataract Refract Surg"},{"key":"refR6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/00003226-200401000-00008","volume":"23","author":"Wollensak G","year":"2004","unstructured":"Wollensak G, Spoerl E, Wilsch M, Seiler T. \n Keratocyte apoptosis after collagen cross-linking using riboflavin\/UVA treatment \n Cornea \n 2004; \n 23\n : 43-9.","journal-title":"Cornea"},{"key":"refR7","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/sj.eye.6700751","volume":"18","author":"Wollensak G","year":"2004","unstructured":"Wollensak G, Spoerl E, Reber F, Seiler T. \n Keratocyte cytotoxicity of riboflavin\/UVA-treatment in vitro \n Eye \n 2004; \n 18\n : 718-22.","journal-title":"Eye"},{"key":"refR8","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1111\/j.1755-3768.2008.01474.x","volume":"88","author":"Wollensak G","year":"2010","unstructured":"Wollensak G. \n Histological changes in human cornea after cross-linking with riboflavin and ultraviolet A \n Acta Opthalmol \n 2010; \n 88\n (2)\n : e17-8.","journal-title":"Acta Opthalmol"},{"key":"refR9","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/S0002-9394(02)02220-1","volume":"135","author":"Wollensak G","year":"2003","unstructured":"Wollensak G, Spoerl E, Seiler T. \n Riboflavin\/ultraviolet-A-induced collagen cross-linking for the treatment of keratoconus \n Am J Ophthalmol \n 2003; \n 135\n : 620-27.","journal-title":"Am J Ophthalmol"},{"key":"refR10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1055\/s-2008-1027221","volume":"225","author":"Sp\u00f6rl E","year":"2008","unstructured":"Sp\u00f6rl E, Raiskup-Wolf F, Pillunat LE. \n Biophysical principles of collagen cross-linking \n Klin Monatsbl Augenheilkd \n 2008; \n 225\n : 131-7.","journal-title":"Klin Monatsbl Augenheilkd"},{"key":"refR11","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/ICO.0b013e3180334f78","volume":"26","author":"Spoerl E","year":"2007","unstructured":"Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T. \n Safety of UVA-riboflavin cross-linking of the cornea \n Cornea \n 2007; \n 26\n : 385-9.","journal-title":"Cornea"},{"key":"refR12","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.jcrs.2009.01.009","volume":"35","author":"Baiocchi S","year":"2009","unstructured":"Baiocchi S, Mazzotta C, Cerretani D, Caporossi T, Caporossi A. \n Corneal cross-linking: riboflavin concentration in corneal stroma exposed with and without epithelium \n J Cataract Refract Surg \n 2009; \n 35\n : 893-9.","journal-title":"J Cataract Refract Surg"},{"key":"refR13","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.jcrs.2008.02.002","volume":"34","author":"Hayes S","year":"2008","unstructured":"Hayes S, O'Brart DP, Lamdin LS, et al. \n Effect of complete epithelial debridement before riboflavin-ultraviolet-A corneal collagen crosslinking therapy \n J Cataract Refract Surg \n 2008; \n 34\n : 657-1.","journal-title":"J Cataract Refract Surg"},{"key":"refR14","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1167\/iovs.09-4524","volume":"51","author":"Kampik D","year":"2010","unstructured":"Kampik D, Ralla B, Keller S, Hirschberg M, Friedl P, Geerling G. \n Influence of corneal collagen crosslinking with riboflavin and ultraviolet-a irradiation on excimer laser surgery \n Invest Ophthalmol Vis Sci \n 2010; \n 51\n : 3929-4.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"refR15","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1055\/s-2007-963492","volume":"224","author":"Koller T","year":"2007","unstructured":"Koller T, Seiler T. \n Therapeutic cross-linking of the cornea using riboflavin\/UVA \n Klin Monatsbl Augenheilkd \n 2007; \n 224\n : 700-6.","journal-title":"Klin Monatsbl Augenheilkd"},{"key":"refR16","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/00004032-200408000-00006","volume":"87","author":"Matthes R","year":"2004","unstructured":"Matthes R. \n Guidelines on limits of exposure to ultraviolet radiation of wavelengths between 180 nm and 400 nm (incoherent optical radiation) \n Health Physics \n 2004; \n 87\n : 171-86.","journal-title":"Health Physics"},{"key":"refR17","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0014-4835(80)80027-3","volume":"31","author":"Andreassen TT","year":"1980","unstructured":"Andreassen TT, Simonsen AH, Oxlund H. \n Biomechanical properties of keratoconus and normal corneas \n Exp Eye Res \n 1980; \n 31\n : 435-1.","journal-title":"Exp Eye Res"},{"key":"refR18","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1097\/ICO.0b013e318030df5a","volume":"26","author":"Mazzotta C","year":"2007","unstructured":"Mazzotta C, Balestrazzi A, Traversi C, et al. \n 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 \n Cornea \n 2007; \n 26\n : 390-7.","journal-title":"Cornea"},{"key":"refR19","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ajo.2008.05.042","volume":"146","author":"Mazzotta C","year":"2008","unstructured":"Mazzotta C, Traversi C, Baiocchi S, et al. \n Corneal healing after riboflavin ultraviolet-A collagen cross-linking determined by confocal laser scanning microscopy in vivo: early and late modifications \n Am J Ophthalmol \n 2008; \n 146\n : 527-33.","journal-title":"Am J Ophthalmol"},{"key":"refR20","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1023\/A:1017989305873","volume":"12","author":"McKegney M","year":"2001","unstructured":"McKegney M, Taggart I, Grant MH. \n The influence of crosslinking agents and diamines on the pore size, morphology and the biological stability of collagen sponges and their effect on cell penetration through the sponge matrix \n J Mater Sci Mater Med \n 2001; \n 12\n : 833-44.","journal-title":"J Mater Sci Mater Med"},{"key":"refR21","unstructured":"K\u00f6hler A. \n \"Gedanken zu einem neuen Beleuchtungsverfahren f\u00fcr mikrophotographische Zwecke\" \n Germany: Zeitschrift fr wissenschaftliche Mikroskopie \n 1893."},{"key":"refR22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1117\/12.306065","volume":"3251","author":"Semchishen VA","year":"1998","unstructured":"Semchishen VA, Mrochen M, Seminogov VN, Panchenko VY, Seiler T. \n Light beam shaping and homogenization (LSBH) by irregular microlens structure for medical applications \n SPIE Proc \n 1998; \n 3251\n : 28-33.","journal-title":"SPIE Proc"},{"key":"refR23","doi-asserted-by":"crossref","unstructured":"Bueller M, Spoerl E, Seiler T, Mrochen M. \n UV collagen cross-linking of the cornea \u2013 safety aspects and design of a UV illumination system \n Progress in Biomedical optics and Imaging Proc SPIE \n 2008; \n 6844\n : 1-11.","DOI":"10.1117\/12.764769"},{"key":"refR24","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.jcrs.2006.01.091","volume":"32","author":"Caporossi A","year":"2006","unstructured":"Caporossi A, Baiocchi S, Mazzotta C, et al. \n Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A rays induced cross-linking of cerneal collagen: preliminary refractive results in an Italian study \n J Cataract Refract Surg \n 2006; \n 32\n : 837-45.","journal-title":"J Cataract Refract Surg"},{"key":"refR25","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1177\/112067210601600405","volume":"16","author":"Mazzotta C","year":"2006","unstructured":"Mazzotta C, Traversi C, Baiocchi S, et al. \n Conservative treatment of keratoconus by riboflavin-uva-induced cross-linking of corneal collagen: qualitative investigation \n Eur J Ophthalmol \n 2006; \n 16\n : 530-.","journal-title":"Eur J Ophthalmol"},{"key":"refR26","first-page":"S720","volume":"24","author":"Wittig-Silva C","year":"2008","unstructured":"Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan LJ, Snibson GR. \n A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results \n J Refract Surg \n 2008; \n 24\n : S720-5.","journal-title":"J Refract Surg"},{"key":"refR27","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ophtha.2008.09.048","volume":"116","author":"Vinciguerra P","year":"2009","unstructured":"Vinciguerra P, Alb\u00e8 E, Trazza S, et al. \n Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking \n Ophthalmology \n 2009; \n 116\n : 369-78.","journal-title":"Ophthalmology"}],"container-title":["The Open Ophthalmology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openophthalmologyjournal.com\/contents\/volumes\/V5\/TOOPHTJ-5-14\/TOOPHTJ-5-14.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openophthalmologyjournal.com\/contents\/volumes\/V5\/TOOPHTJ-5-14\/TOOPHTJ-5-14.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openophthalmologyjournal.com\/contents\/volumes\/V5\/TOOPHTJ-5-14\/TOOPHTJ-5-14.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T09:41:29Z","timestamp":1761298889000},"score":1,"resource":{"primary":{"URL":"https:\/\/openophthalmologyjournal.com\/VOLUME\/5\/PAGE\/14\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,11]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,2,11]]}},"alternative-id":["TOOPHTJ-5-14"],"URL":"https:\/\/doi.org\/10.2174\/1874364101105010014","relation":{},"ISSN":["1874-3641"],"issn-type":[{"value":"1874-3641","type":"print"}],"subject":[],"published":{"date-parts":[[2011,2,11]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Double blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2010-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-10-15","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-11-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-02-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}