A Review of Corneal Collagen Cross-linking – Current Trends in Practice Applications

The Open Ophthalmology Journal 23 July 2018 REVIEW ARTICLE DOI: 10.2174/1874364101812010181



To review the literature on current applications of corneal Collagen Cross-Linking (CXL).


A review of publications on corneal cross-linking was conducted. This included systemic reviews, randomized controlled clinical trials, cohort studies, case-controlled studies and case series. A summary of the publications is tabulated.


The original indication of riboflavin – Ultraviolet-A (UVA) induced corneal collagen cross-linking is to arrest the progression of keratoconus. Studies show that it is effective in arresting the progression of keratoconus and post-LASIK ectasia with the standard Dresden protocol (epithelium-off). There are also improvements in visual, keratometric and topographic measurements over time. Severe complications of cross-linking are rare. The epithelium-on techniques have less efficacy than the Dresden protocol. Accelerated protocols have variable results, with some studies reporting comparable outcomes to the Dresden protocol while other studies reporting less efficacious outcomes. Cross-linking combined with refractive procedures provide better visual outcome but long term studies are warranted. Cross-linking for the treatment of infective keratitis is a promising new treatment modality. Initial studies show that it is more effective for superficial rather than deep infections and for bacterial rather than fungal infections.


Corneal cross-linking is a procedure with an expanding list of indications from the treatment of corneal ectasias to infective keratitis. While the standard Dresden protocol is established as the gold standard treatment for progressive keratoconus, the more recent protocols may require further refinements, investigative and long-term studies.

Keywords: Cornea collagen cross-linking, post-LASIK ectasia, Keratoconus, Infective keratitis, UVA, Dresden protocol.
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