Corneal collagen crosslinking for corneal ectasias: a review



To review the published literature on corneal collagen crosslinking (CXL).


Importance has been placed on seminal publications, systemic reviews, meta-analyses, and randomized controlled clinical trials. Where such evidence was not available, cohort studies, case-controlled studies, and case series with follow-up greater than 12 months were examined.


Corneal collagen crosslinking with riboflavin and ultraviolet A (UVA) 370 nm radiation appears to be capable of arresting the progression of ectatic corneal disorders, with most studies reporting significant improvements in visual, keratometric, and topographic measurements. Its mode of action at the molecular level is undetermined. Follow-up is limited to 5-10 years but suggests sustained stability and enhancement in corneal shape with time. Nearly all published long-term data and comparative studies are with epithelium-off techniques. Epithelium-on investigations suggest some efficacy but less than with epithelium-off treatments and long-term data are unavailable. Accelerated techniques with higher UVA fluencies and shorter treatments times, delivering the same UVA energy dosage, are the subject of recent investigation, with some laboratory and clinical studies suggesting reduced efficacy compared to the standard 3 mW/cm2 for 30 minutes irradiation procedure. Combined methodologies of CXL with techniques such as photorefractive keratectomy and intrastromal rings show promise but long-term follow-up is indicated. Sight-threatening complications of CXL are rare.


Studies of epithelium-off CXL with irradiation at 3 mW/cm2 for 30 minutes support its efficacy. Refinement in techniques may allow for safer and more rapid procedures with less patient discomfort but require further investigation.

Eur J Ophthalmol 2017; 27(3): 253 - 269

Article Type: REVIEW



David P.S. O’Brart

Article History


Financial support: The author holds a non-commercial research grant from Alcon Inc.
Conflict of interest: None of the authors has conflict of interest with this submission.

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  • Department of Ophthalmology, Keratoconus Research Institute, St. Thomas’ Hospital, London - UK

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