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Updated: Apr 19, 2026

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Conventional versus accelerated collagen cross-linking for keratoconus
Aris Konstantopoulos1, Jodhbir S Mehta
1Tissue Engineering and Stem Cell Group (A.K., J.S.M.), Singapore Eye Research Institute, Singapore, Singapore; Singapore National Eye Centre (A.K., J.S.M.), Singapore, Singapore; Yong Loo Lin School of Medicine (J.S.M.), National University of Singapore, Singapore, Singapore; Nanyang Technological University (J.S.M.), Singapore, Singapore; and Department of Clinical Sciences (J.S.M.), Duke-NUS Graduate Medical School, Singapore, Singapore.
Abstract:
: Collagen cross-linking (CXL) is a procedure that primarily aims to increase corneal stiffness. Although used for a variety of conditions, it is most commonly applied to the treatment of keratoconus. Collagen cross-linking involves irradiation of the cornea with ultraviolet A (UVA) irradiation after it has been soaked with riboflavin (vitamin B), a photosensitizer. In conventional treatment, based on the Dresden protocol, a minimum corneal thickness threshold of 400 μm is recommended and UVA (370 nm) irradiation of 3 mW/cm irradiance is applied for 30 min, resulting in a cumulative dose of 5.4 J/cm. Evidence presented in this review shows that conventional CXL stabilizes the vision and corneal topographic parameters in the majority of treated patients, with only a small failure rate. It has a good safety profile with no endothelial cell loss and a small risk of corneal infiltration and infection. To reduce the treatment duration, accelerated protocols of similar efficacy have been sought. In accelerated protocols, UVA irradiation of higher irradiance, typically 9 mW/cm, is applied for a shorter time, typically 10 min. The evidence, limited to small studies with short follow-up, shows that they may also stabilize the vision and the ectasia, with no additional safety concerns highlighted. Randomized controlled studies are, however, required to confirm the encouraging results and noninferiority to conventional treatment.
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