{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:08:05Z","timestamp":1791234485708,"version":"4.1.0"},"reference-count":106,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Keratoconus is a potentially blinding condition characterized by progressive thinning and steepening of the cornea, leading to visual impairment due to irregular astigmatism and myopia. While the exact pathophysiology is still unknown, it is believed to involve genetic, environmental, and cellular factors. Treatment options for keratoconus have significantly expanded over the past few decades. Historically, glasses were the primary means of managing mild cases, whereas rigid gas permeable contact lenses were used in moderate to advanced diseases; yet the latter were rarely tolerated by patients with steep cones, in which full-thickness corneal transplantation was often performed. However, a variety of innovative treatments have been introduced in the past decades. Corneal collagen cross-linking (CXL) has revolutionized the field by halting the progression of keratoconus through creating new covalent bonds between individual corneal fibers. Custom, soft, and scleral contact lenses have improved visual outcomes for many patients. Additionally, surgical interventions such as intrastromal ring segments and Bowman layer transplantation have provided alternatives for visual restoration and postponing a potential keratoplasty. Furthermore, innovative cellular and pharmacological KCN treatments are on the horizon, awaiting clinical trials. This review article aims to provide a comprehensive overview of the current treatment options for keratoconus.<\/jats:p>","DOI":"10.3390\/jcm14217491","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T08:14:04Z","timestamp":1761207244000},"page":"7491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Advancements and Innovations in Keratoconus Management: A Review of Current Practices"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-4035","authenticated-orcid":false,"given":"Hyeck-Soo","family":"Son","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Heidelberg, 69120 Heidelberg, Baden-Wuerttemberg, Germany"},{"name":"Wilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Heidelberg, 69120 Heidelberg, Baden-Wuerttemberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert S.","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri S.","family":"Soiberman","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.ophtha.2019.02.029","article-title":"Keratoconus Natural Progression: A Systematic Review and Meta-analysis of 11,529 Eyes","volume":"126","author":"Ferdi","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/ICO.0000000000002150","article-title":"The Prevalence and Risk Factors for Keratoconus: A Systematic Review and Meta-Analysis","volume":"39","author":"Hashemi","year":"2020","journal-title":"Cornea"},{"key":"ref_3","first-page":"574","article-title":"A summary of the findings from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. CLEK Study Group","volume":"72","author":"Szczotka","year":"2001","journal-title":"Optometry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1097\/ICO.0b013e318211401f","article-title":"Contact lenses in the management of keratoconus","volume":"30","author":"Barnett","year":"2011","journal-title":"Cornea"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/01.icl.0000174759.91179.30","article-title":"Use of intralimbal rigid gas-permeable lenses for pellucid marginal degeneration, keratoconus, and after penetrating keratoplasty","volume":"32","author":"Ozbek","year":"2006","journal-title":"Eye Contact Lens"},{"key":"ref_6","first-page":"331","article-title":"High Dk piggyback contact lens system for contact lens-intolerant keratoconus patients","volume":"5","author":"Sengor","year":"2011","journal-title":"Clin. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.1097\/ICL.0000000000000198","article-title":"Improved Vision and Contact Lens Wear Time with Piggy-Back Contact Lens Systems in Children After Penetrating Corneal Trauma","volume":"43","author":"Cromelin","year":"2017","journal-title":"Eye Contact Lens"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/ICL.0b013e31815c859b","article-title":"A comparison of synergeyes versus traditional rigid gas permeable lens designs for patients with irregular corneas","volume":"34","author":"Nau","year":"2008","journal-title":"Eye Contact Lens"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/ICL.0000000000000016","article-title":"ClearKone-Synergeyes or rigid gas-permeable contact lens in keratoconic patients: A clinical decision","volume":"40","author":"Hashemi","year":"2014","journal-title":"Eye Contact Lens"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/ICL.0b013e3181c786a6","article-title":"Scleral lenses in the management of keratoconus","volume":"36","author":"Schornack","year":"2010","journal-title":"Eye Contact Lens"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.clae.2013.02.004","article-title":"Patient ocular conditions and clinical outcomes using a PROSE scleral device","volume":"36","author":"Dimit","year":"2013","journal-title":"Cont. Lens Anterior Eye J. Br. Contact Lens Assoc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ajo.2009.07.037","article-title":"Clinical benefits of the Boston Ocular Surface Prosthesis","volume":"149","author":"Stason","year":"2010","journal-title":"Am. J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jcjo.2017.07.026","article-title":"EyePrintPRO therapeutic scleral contact lens: Indications and outcomes","volume":"53","author":"Nguyen","year":"2018","journal-title":"Can. J. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1097\/ICO.0000000000002588","article-title":"Indications for Wear, Visual Outcomes, and Complications of Custom Imprint 3D Scanned Scleral Contact Lens Use","volume":"40","author":"Silverman","year":"2021","journal-title":"Cornea"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1006\/exer.1997.0410","article-title":"Induction of cross-links in corneal tissue","volume":"66","author":"Spoerl","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/S0002-9394(02)02220-1","article-title":"Riboflavin\/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus","volume":"135","author":"Wollensak","year":"2003","journal-title":"Am. J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/ICU.0000000000001056","article-title":"Update on corneal crosslinking for keratoconus and corneal ectasia","volume":"35","author":"Greenstein","year":"2024","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/j.ophtha.2017.03.052","article-title":"United States Crosslinking Study Group United States Multicenter Clinical Trial of Corneal Collagen Crosslinking for Keratoconus Treatment","volume":"124","author":"Hersh","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lang, S.J., Messmer, E.M., Geerling, G., Mackert, M.J., Brunner, T., Dollak, S., Kutchoukov, B., B\u00f6hringer, D., Reinhard, T., and Maier, P. (2015). Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus. BMC Ophthalmol., 15.","DOI":"10.1186\/s12886-015-0070-7"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1113\/jphysiol.1952.sp004779","article-title":"The Bunsen-Roscoe law for the human eye at very short durations","volume":"118","author":"Brindley","year":"1952","journal-title":"J. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.jcrs.2013.12.014","article-title":"High-irradiance accelerated collagen crosslinking for the treatment of keratoconus: Six-month results","volume":"40","author":"Mita","year":"2014","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/ICO.0000000000001878","article-title":"Comparative Functional Outcomes After Corneal Crosslinking Using Standard, Accelerated, and Accelerated with Higher Total Fluence Protocols","volume":"38","author":"Lang","year":"2019","journal-title":"Cornea"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.2147\/OPTH.S409178","article-title":"Comparison Between Pulsed and Continuous Accelerated Corneal Cross-Linking Protocols","volume":"17","author":"Elkitkat","year":"2023","journal-title":"Clin. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mazzotta, C., Pandolfi, A., and Ferrise, M. (2023). Progressive high-fluence epithelium-on accelerated corneal crosslinking: A novel corneal photodynamic therapy for early progressive keratoconus. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1198246"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1097\/ICO.0000000000002567","article-title":"Comparison of Visual and Tomographic Outcomes of Epithelium-On and Epithelium-Off Accelerated Corneal Crosslinking: A Longitudinal Study","volume":"40","author":"Niyazmand","year":"2021","journal-title":"Cornea"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1097\/ICO.0000000000002092","article-title":"Accelerated Versus Standard Corneal Cross-Linking for Progressive Keratoconus: A Meta-Analysis of Randomized Controlled Trials","volume":"39","author":"Kobashi","year":"2020","journal-title":"Cornea"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1111\/aos.13814","article-title":"Comparison of standard and accelerated corneal cross-linking for the treatment of keratoconus: A meta-analysis","volume":"97","author":"Shajari","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajo.2020.01.006","article-title":"Accelerated Corneal Cross-Linking: Efficacy, Risk of Progression, and Characteristics Affecting Outcomes. A Large, Single-Center Prospective Study","volume":"213","author":"Hatch","year":"2020","journal-title":"Am. J. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/ICL.0000000000000095","article-title":"First proposed efficacy study of high versus standard irradiance and fractionated riboflavin\/ultraviolet a cross-linking with equivalent energy exposure","volume":"40","author":"Krueger","year":"2014","journal-title":"Eye Contact Lens"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"604731","DOI":"10.1155\/2014\/604731","article-title":"Pulsed Light Accelerated Crosslinking versus Continuous Light Accelerated Crosslinking: One-Year Results","volume":"2014","author":"Mazzotta","year":"2014","journal-title":"J. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1097\/j.jcrs.0000000000000488","article-title":"Comparison of pulsed and continuous accelerated corneal crosslinking for keratoconus: 1-year results at a single center","volume":"47","author":"Kang","year":"2021","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s10792-025-03512-7","article-title":"Pulsed light epithelium-off accelerated corneal collagen crosslinking with 30mW\/cm2 irradiance and 7.2 J\/cm2 radiant exposure: 2-year results","volume":"45","author":"Luckmann","year":"2025","journal-title":"Int. Ophthalmol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s00417-024-06622-7","article-title":"Pulsed corneal crosslinking in the treatment of Keratoconus: A systematic review and meta-analysis","volume":"263","author":"Qureshi","year":"2025","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40662-021-00256-0","article-title":"Corneal collagen cross-linking epithelium-on vs. epithelium-off: A systematic review and meta-analysis","volume":"8","author":"Alio","year":"2021","journal-title":"Eye Vis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.ajo.2015.02.005","article-title":"Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: A randomized controlled trial","volume":"159","author":"Soeters","year":"2015","journal-title":"Am. J. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.ophtha.2020.12.023","article-title":"Transepithelial versus Epithelium-off Corneal Collagen Cross-linking for Corneal Ectasia: A Systematic Review and Meta-analysis","volume":"128","author":"Nath","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/APO.0000000000000555","article-title":"Oxygen in Corneal Collagen Crosslinking to Treat Keratoconus: A Systematic Review and Meta-Analysis","volume":"11","author":"Borchert","year":"2022","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1097\/j.jcrs.0000000000000347","article-title":"Customized corneal crosslinking for treatment of progressive keratoconus: Clinical and OCT outcomes using a transepithelial approach with supplemental oxygen","volume":"46","author":"Mazzotta","year":"2020","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"746","DOI":"10.3928\/1081597X-20141021-06","article-title":"Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: Initial clinical outcomes","volume":"30","author":"Vinciguerra","year":"2014","journal-title":"J. Refract. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1007\/s10792-021-01713-4","article-title":"New perspectives in keratoconus treatment: An update on iontophoresis-assisted corneal collagen crosslinking","volume":"41","author":"Vinciguerra","year":"2021","journal-title":"Int. Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/ceo.13918","article-title":"Transepithelial corneal collagen cross-linking using iontophoresis versus the Dresden protocol in progressive keratoconus: A meta-analysis","volume":"49","author":"Wan","year":"2021","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Napolitano, P., Tranfa, F., D\u2019Andrea, L., Caruso, C., Rinaldi, M., Mazzucco, A., Ciampa, N., Melenzane, A., and Costagliola, C. (2022). Topographic Outcomes in Keratoconus Surgery: Epi-on versus Epi-off Iontophoresis Corneal Collagen Cross-Linking. J. Clin. Med., 11.","DOI":"10.3390\/jcm11071785"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Vinciguerra, R., Legrottaglie, E.F., Tredici, C., Mazzotta, C., Rosetta, P., and Vinciguerra, P. (2022). Transepithelial Iontophoresis-Assisted Cross Linking for Progressive Keratoconus: Up to 7 Years of Follow Up. J. Clin. Med., 11.","DOI":"10.3390\/jcm11030678"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1159\/000074071","article-title":"Corneal endothelial cytotoxicity of riboflavin\/UVA treatment in vitro","volume":"35","author":"Wollensak","year":"2003","journal-title":"Ophthalmic Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.2147\/OPTH.S66372","article-title":"Customized epithelial debridement for thin ectatic corneas undergoing corneal cross-linking: Epithelial island cross-linking technique","volume":"8","author":"Mazzotta","year":"2014","journal-title":"Clin. Ophthalmol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kymionis, G.D., Diakonis, V.F., Coskunseven, E., Jankov, M., Yoo, S.H., and Pallikaris, I.G. (2009). Customized pachymetric guided epithelial debridement for corneal collagen cross linking. BMC Ophthalmol., 9.","DOI":"10.1186\/1471-2415-9-10"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jcrs.2008.10.060","article-title":"Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas","volume":"35","author":"Hafezi","year":"2009","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3928\/1081597X-20140523-01","article-title":"Contact lens-assisted collagen cross-linking (CACXL): A new technique for cross-linking thin corneas","volume":"30","author":"Jacob","year":"2014","journal-title":"J. Refract. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/j.jcrs.0000000000000732","article-title":"Comparison of contact lens-assisted and transepithelial corneal crosslinking with standard epithelium-off crosslinking for progressive keratoconus: 24-month clinical results","volume":"48","author":"Malhotra","year":"2022","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e84","DOI":"10.1111\/aos.13828","article-title":"Biomechanical efficacy of contact lens-assisted collagen cross-linking in porcine eyes","volume":"97","author":"Wollensak","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"721","DOI":"10.3928\/1081597X-20191004-01","article-title":"Depth-Dependent Reduction of Biomechanical Efficacy of Contact Lens-Assisted Corneal Cross-linking Analyzed by Brillouin Microscopy","volume":"35","author":"Zhang","year":"2019","journal-title":"J. Refract. Surg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.jcrs.2015.04.007","article-title":"Tailored stromal expansion with a refractive lenticule for crosslinking the ultrathin cornea","volume":"41","author":"Sachdev","year":"2015","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1007\/s10792-020-01526-x","article-title":"Epi-off-lenticule-on corneal collagen cross-linking in thin keratoconic corneas","volume":"40","author":"Cagini","year":"2020","journal-title":"Int. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ajo.2020.12.011","article-title":"Individualized Corneal Cross-linking with Riboflavin and UV-A in Ultrathin Corneas: The Sub400 Protocol","volume":"224","author":"Hafezi","year":"2021","journal-title":"Am. J. Ophthalmol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1097\/ICO.0000000000002492","article-title":"Comparative Analysis of Safety and Efficacy of Topography-Guided Customized Cross-linking and Standard Cross-linking in the Treatment of Progressive Keratoconus","volume":"40","author":"Sachdev","year":"2021","journal-title":"Cornea"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ajo.2016.02.029","article-title":"Customized Corneal Cross-linking: One-Year Results","volume":"166","author":"Seiler","year":"2016","journal-title":"Am. J. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.ajo.2011.04.033","article-title":"Simultaneous topography-guided photorefractive keratectomy followed by corneal collagen cross-linking for keratoconus","volume":"152","author":"Kymionis","year":"2011","journal-title":"Am. J. Ophthalmol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S812","DOI":"10.3928\/1081597X-20090813-10","article-title":"Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided PRK for treatment of keratoconus","volume":"25","author":"Kanellopoulos","year":"2009","journal-title":"J. Refract. Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ajo.2025.02.038","article-title":"Efficacy of Customized Photorefractive Keratectomy with Cross-Linking Versus Cross-Linking Alone in Progressive Keratoconus: A Systematic Review and Meta-Analysis","volume":"274","author":"Zhang","year":"2025","journal-title":"Am. J. Ophthalmol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.ophtha.2012.03.038","article-title":"Combined transepithelial phototherapeutic keratectomy and corneal collagen cross-linking for progressive keratoconus","volume":"119","author":"Kymionis","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1097\/ICO.0000000000000679","article-title":"Long-Term Results of Phototherapeutic Keratectomy Versus Mechanical Epithelial Removal Followed by Corneal Collagen Cross-Linking for Keratoconus","volume":"35","author":"Kapasi","year":"2016","journal-title":"Cornea"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"838","DOI":"10.3928\/1081597X-20201021-01","article-title":"Corneal Cross-linking for Progressive Keratoconus: Up to 13 Years of Follow-up","volume":"36","author":"Vinciguerra","year":"2020","journal-title":"J. Refract. Surg."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1097\/ICL.0000000000001018","article-title":"Long-Term Outcomes After Corneal Cross-linking for Progressive Keratoconus and Corneal Ectasia: A 10-Year Follow-Up of the Pivotal Study","volume":"49","author":"Greenstein","year":"2023","journal-title":"Eye Contact Lens"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1097\/ICO.0000000000000819","article-title":"Corneal Cross-Linking for Pediatric Keratoconus: Long-Term Results","volume":"35","author":"Godefrooij","year":"2016","journal-title":"Cornea"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1097\/ICO.0000000000000591","article-title":"Biomechanics of Corneal Ring Implants","volume":"34","author":"Daxer","year":"2015","journal-title":"Cornea"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.jcrs.2019.01.020","article-title":"Corneal crosslinking and intracorneal ring segments for keratoconus: A randomized study of concurrent versus sequential surgery","volume":"45","author":"Hersh","year":"2019","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1755-3768.2009.01605.x","article-title":"Complications of intrastromal corneal ring segment implantation using a femtosecond laser for channel creation: A survey of 850 eyes with keratoconus","volume":"89","author":"Coskunseven","year":"2011","journal-title":"Acta Ophthalmol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1016\/j.jcrs.2009.05.036","article-title":"Long-term follow-up of intrastromal corneal ring segments in keratoconus","volume":"35","author":"Torquetti","year":"2009","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3928\/1081597X-20180223-01","article-title":"Corneal Allogenic Intrastromal Ring Segments (CAIRS) Combined with Corneal Cross-linking for Keratoconus","volume":"34","author":"Jacob","year":"2018","journal-title":"J. Refract. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1111\/ceo.14411","article-title":"Clinical outcomes of femtosecond laser-assisted corneal allogenic intrastromal ring segment (CAIRS) in the treatment of keratoconus","volume":"52","author":"Kirgiz","year":"2024","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"767","DOI":"10.3928\/1081597X-20231011-01","article-title":"Corneal Allogenic Intrastromal Ring Segments (CAIRS) for Corneal Ectasia: A Comprehensive Segmental Tomography Evaluation","volume":"39","author":"Bteich","year":"2023","journal-title":"J. Refract. Surg."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.4103\/IJO.IJO_1988_23","article-title":"Customized corneal allogenic intrastromal ring segments (CAIRS) for keratoconus with decentered asymmetric cone","volume":"71","author":"Jacob","year":"2023","journal-title":"Indian. J. Ophthalmol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1097\/j.jcrs.0000000000001187","article-title":"Corneal tissue addition keratoplasty: New intrastromal inlay procedure for keratoconus using femtosecond laser-shaped preserved corneal tissue","volume":"49","author":"Greenstein","year":"2023","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ajo.2025.03.028","article-title":"Visual and Topographic Outcomes After Corneal Allogeneic Intrastromal Ring Segments for Keratoconus: A Systematic Review and Meta-Analysis","volume":"276","author":"Friedrich","year":"2025","journal-title":"Am. J. Ophthalmol."},{"key":"ref_75","first-page":"517","article-title":"Long-term outcomes of penetrating keratoplasty in keratoconus: Analysis of the factors associated with final visual acuities","volume":"7","author":"Choi","year":"2014","journal-title":"Int. J. Ophthalmol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ophtha.2010.11.002","article-title":"Deep Anterior Lamellar Keratoplasty as an Alternative to Penetrating Keratoplasty","volume":"118","author":"Reinhart","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1136\/bjo-2023-324230","article-title":"Long-term outcomes of deep anterior lamellar versus penetrating keratoplasty for keratoconus","volume":"108","author":"Borderie","year":"2023","journal-title":"Br. J. Ophthalmol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ajo.2019.01.022","article-title":"Deep Anterior Lamellar Keratoplasty for Keratoconus: Multisurgeon Results","volume":"201","author":"Gadhvi","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1136\/bjo-2024-325810","article-title":"Tomographic and topographic predictive factors of big bubble formation during deep anterior lamellar keratoplasty in keratoconus","volume":"108","author":"Lucchino","year":"2024","journal-title":"Br. J. Ophthalmol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ajo.2020.07.023","article-title":"Femtosecond Laser-Assisted Deep Anterior Lamellar Keratoplasty for Keratoconus: Multi-surgeon Results","volume":"220","author":"Gadhvi","year":"2020","journal-title":"Am. J. Ophthalmol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/ICO.0000000000003103","article-title":"\u201cGroove and Peel\u201d Deep Anterior Lamellar Keratoplasty: How Deep Can You Go?","volume":"42","author":"Son","year":"2023","journal-title":"Cornea"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1177\/11206721221132622","article-title":"Rediscovering a valuable manual Deep Anterior Lamellar Keratoplasty (DALK) technique: Outcomes of 42 \u201cPeeling-off\u201d DALK","volume":"33","author":"Sarnicola","year":"2022","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1001\/jamaophthalmol.2013.5841","article-title":"Midstromal isolated Bowman layer graft for reduction of advanced keratoconus: A technique to postpone penetrating or deep anterior lamellar keratoplasty","volume":"132","author":"Parker","year":"2014","journal-title":"JAMA Ophthalmol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1136\/bjo-2022-322180","article-title":"Collagen type XII is undetectable in keratoconus Bowman\u2019s layer","volume":"108","author":"Rigi","year":"2024","journal-title":"Br. J. Ophthalmol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1097\/ICO.0000000000002871","article-title":"Long-Term Outcomes of Bowman Layer Inlay Transplantation for the Treatment of Progressive Keratoconus","volume":"41","author":"Dapena","year":"2022","journal-title":"Cornea"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jcrs.2018.10.034","article-title":"Bowman layer transplantation using a femtosecond laser","volume":"45","year":"2019","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1177\/11206721231165438","article-title":"Sterile corneal necrosis after bowman layer transplantation","volume":"33","year":"2023","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1097\/ICO.0000000000002740","article-title":"Bowman Layer Onlay Grafting: Proof-of-Concept of a New Technique to Flatten Corneal Curvature and Reduce Progression in Keratoconus","volume":"40","author":"Dapena","year":"2021","journal-title":"Cornea"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ajo.2023.10.004","article-title":"Bowman Layer Onlay Grafting as a Minimally Invasive Treatment for the Most Challenging Cases in Keratoconus","volume":"261","author":"Oellerich","year":"2024","journal-title":"Am. J. Ophthalmol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1097\/ICO.0000000000003260","article-title":"Histological Comparative Analysis of Bowman Layer Grafts Procured Using 3 Different Techniques","volume":"42","author":"Son","year":"2023","journal-title":"Cornea"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1007\/s10792-021-01745-w","article-title":"Femtosecond laser-assisted stromal keratophakia for keratoconus: A systemic review and meta-analysis","volume":"41","author":"Riau","year":"2021","journal-title":"Int. Ophthalmol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3928\/1081597X-20171004-04","article-title":"Femtosecond Laser-Assisted Stromal Lenticule Addition Keratoplasty for the Treatment of Advanced Keratoconus: A Preliminary Study","volume":"34","author":"Mastropasqua","year":"2018","journal-title":"J. Refract. Surg."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Nubile, M., Salgari, N., Mehta, J.S., Calienno, R., Erroi, E., Bond\u00ec, J., Lanzini, M., Liu, Y.-C., and Mastropasqua, L. (2021). Epithelial and stromal remodelling following femtosecond laser-assisted stromal lenticule addition keratoplasty (SLAK) for keratoconus. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-81626-5"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"9774448","DOI":"10.1155\/2022\/9774448","article-title":"Long-Term Clinical Outcomes of Small-Incision Femtosecond Laser-Assisted Intracorneal Concave Lenticule Implantation in Patients with Keratoconus","volume":"2022","author":"Wei","year":"2022","journal-title":"J. Ophthalmol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"S167","DOI":"10.4103\/IJO.IJO_695_23","article-title":"Lenticule addition keratoplasty for the treatment of keratoconus: A systematic review and critical considerations","volume":"72","author":"Liu","year":"2024","journal-title":"Indian. J. Ophthalmol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"39","DOI":"10.17116\/oftalma202213805139","article-title":"Long-term outcomes of bandage therapeutic-optical keratoplasty in the treatment of keratoconus","volume":"138","author":"Avetisov","year":"2022","journal-title":"Vestn. Oftalmol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/S0161-6420(91)32136-5","article-title":"Progression of visual acuity after penetrating keratoplasty","volume":"98","author":"Price","year":"1991","journal-title":"Ophthalmology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ajo.2022.11.019","article-title":"Penetrating Keratoplasty Versus Deep Anterior Lamellar Keratoplasty for Advanced Stage of Keratoconus","volume":"248","author":"Feizi","year":"2023","journal-title":"Am. J. Ophthalmol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/j.1442-9071.2008.01900.x","article-title":"Rapid visual recovery after penetrating keratoplasty for keratoconus","volume":"36","author":"Sutton","year":"2008","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/ICO.0000000000003620","article-title":"Bowman Layer Transplantation with Stromal Inclusion Using Femtosecond Laser: 3-Year Results","volume":"44","year":"2025","journal-title":"Cornea"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1007\/s00417-018-3927-7","article-title":"Bowman layer transplantation: 5-year results","volume":"256","author":"Parker","year":"2018","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1097\/ICO.0000000000001228","article-title":"Cellular Therapy with Human Autologous Adipose-Derived Adult Stem Cells for Advanced Keratoconus","volume":"36","author":"Azaar","year":"2017","journal-title":"Cornea"},{"key":"ref_103","first-page":"4552","article-title":"WNT10A regulates COL12A1 in corneal epithelial cells and suggests Wnt signaling as a therapeutic target","volume":"65","author":"Moon","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1167\/iovs.66.1.52","article-title":"Mechanical Strain of Corneal Epithelium Influences the Expression of Genes Implicated in Keratoconus","volume":"66","author":"Moon","year":"2025","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1167\/iovs.11-9268","article-title":"Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies","volume":"53","author":"Bykhovskaya","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_106","first-page":"2587","article-title":"IVMED 80 eye drops for treatment of keratoconus in patients -Phase 1\/2a","volume":"61","author":"Molokhia","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7491\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T08:25:46Z","timestamp":1761207946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":106,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14217491"],"URL":"https:\/\/doi.org\/10.3390\/jcm14217491","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}