{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:57:20Z","timestamp":1789077440050,"version":"build-2803163510"},"reference-count":127,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Corneal cross-linking (CXL) using riboflavin and ultraviolet A (UVA) light has become a useful treatment option for not only corneal ectasias, such as keratoconus, but also a number of other corneal diseases. Riboflavin is a photoactivated chromophore that plays an integral role in facilitating collagen crosslinking. Modifications to its formulation and administration have been proposed to overcome shortcomings of the original epithelium-off Dresden CXL protocol and increase its applicability across various clinical scenarios. Hypoosmolar riboflavin formulations have been used to artificially thicken thin corneas prior to cross-linking to mitigate safety concerns regarding the corneal endothelium, whereas hyperosmolar formulations have been used to reduce corneal oedema when treating bullous keratopathy. Transepithelial protocols incorporate supplementary topical medications such as tetracaine, benzalkonium chloride, ethylenediaminetetraacetic acid and trometamol to disrupt the corneal epithelium and improve corneal penetration of riboflavin. Further assistive techniques include use of iontophoresis and other wearable adjuncts to facilitate epithelium-on riboflavin administration. Recent advances include, Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) for treatment of infectious keratitis, customised protocols (CurV) utilising riboflavin coupled with customised UVA shapes to induce targeted stiffening have further induced interest in the field. This review aims to examine the latest advances in riboflavin and UVA administration, and their efficacy and safety in treating a range of corneal diseases. With such diverse riboflavin delivery options, CXL is well primed to complement the armamentarium of therapeutic options available for the treatment of a variety of corneal diseases.<\/jats:p>","DOI":"10.3389\/fphar.2021.686630","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T02:16:15Z","timestamp":1626660975000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":51,"title":["Corneal Cross-Linking: The Evolution of Treatment for Corneal Diseases"],"prefix":"10.3389","volume":"12","author":[{"given":"Duoduo","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn Ka-Ann","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanche Xiao Hong","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Hafezi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Manotosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris Hong Long","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5159","DOI":"10.1167\/iovs.09-3669","article-title":"3D Collagen Orientation Study of the Human Cornea Using X-ray Diffraction and Femtosecond Laser Technology","volume":"50","author":"Abahussin","year":"2009","journal-title":"Invest. 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