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Effectiveness of corneal collagen crosslinking in vivo for corneal stiffening

Gatinel, Damien MD

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Journal of Cataract & Refractive Surgery: November 2014 - Volume 40 - Issue 11 - p 1943-1944
doi: 10.1016/j.jcrs.2014.09.026
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Tomita et al.1 investigated shorter duration ultraviolet light exposure in corneal collagen crosslinking (CXL) based on the assumption that higher power delivered over shorter time periods can provide the same corneal strengthening as lower power over longer time periods. The authors concluded that both techniques are effective, as no significant differences were observed in the measured parameters between the accelerated and conventional corneal CXL. However, regardless of the surgical protocol, no statistical difference between several biomechanical parameters could be recorded before and after CXL by 2 different instruments: the dynamic bidirectional applanation device (Ocular Response Analyzer, Reichert Technologies) and the dynamic Scheimpflug analyzer (Corvis ST, Oculus Optikgeräte GmbH). Similar results have been reported in recent publications in which no change in corneal biomechanical parameters indicative of corneal stiffening could be detected after CXL in patients with progressive keratoconus.2,3

As the purported purpose of CXL is to increase the rigidity of the treated cornea by creating chemical bonds between collagen fibers, the lack of documented biomechanical improvement, as in the present study, should be regarded as ineffectiveness. Curvature changes, visual acuity, and topographic changes are secondary effects of what is primarily intended, which is a biomechanical effect of increased resistance. Hence, the absence of postoperative measureable corneal stiffening should logically lead to the conclusion that CXL is not effective on corneas with progressive keratoconus. One could argue the possibility that biomechanical changes induced by CXL are too subtle to be measured by clinically available diagnostic tools or have characteristics not measured well by these technologies. However, such a hypothesis should be verified in situations in which corneal stiffening and weakening are expected. The dynamic bidirectional applanation device and dynamic Scheimpflug analyzer instruments have demonstrated the capability to identify subtle biomechanical differences in untreated keratoconus corneas of different ectatic degree.4,5 The reduction in corneal hysteresis and resistance factor values after laser in situ keratomileusis and surface ablation has also been reported. This strongly suggests that if CXL would significantly improve the biomechanics of the progressive keratoconus corneas (ie, stiffen the cornea), these instruments would be able to measure this change, unless it is suggested that this technique does not induce a simple reversal of the particular biomechanical deficits that characterize keratoconus.

The variation in keratometric readings and visual quality observed after CXL may be due to nonbiomechanical changes such as epithelial remodeling. The prevalent role of the epithelium in observed post-CXL changes is underlined by the fact that the effects of transepithelial CXL appear to be less pronounced than after CXL with deepithelialization, as reported in the literature.

The absence of measurable biomechanical change in living keratoconus corneas after CXL contrasts with the results of ex vivo experimentations, which show significant stiffening effects with standard and some modified CXL protocols, including evidence of increased elastic modulus and increased stiffness. This discrepancy could be due to the fact that CXL results in insignificant mechanical strengthening compared with the weakening caused by the preexisting alteration of the collagen structure. The disorganization of collagen fiber intertwining and compromised structural–mechanical homogeneity induced by the keratoconus disease may be too overwhelming in progressive keratoconus corneas to be improved by CXL in any of its current (ie, accelerated or conventional) in vivo modalities.


1. Tomita M, Mita M, Huseynova T. Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg. 2014;40:1013-1020.
2. Bak-Nielsen S, Pedersen IB, Ivarsen A, Hjortdal J. Dynamic Scheimpflug-based assessment of keratoconus and the effects of corneal cross-linking. J Refract Surg. 2014;30:408-414.
3. Goldich Y, Marcovich AL, Barkana Y, Mandel Y, Hirsh A, Morad Y, Avni I, Zadok D. Clinical and corneal biomechanical changes after collagen cross-linking with riboflavin and UV irradiation in patients with progressive keratoconus: results after 2 years of follow-up. Cornea. 2012;31:609-614.
4. Saad A, Lteif Y, Azan E, Gatinel D. Biomechanical properties of keratoconus suspect eyes. Invest Ophthalmol Vis Sci. 51, 2010, p. 2912-2916, Available at: Accessed August 15, 2014.
5. Ali NQ, Patel DV, McGhee CNJ. Biomechanical responses of healthy and keratoconic corneas measured using a noncontact Scheimpflug-based tonometer. Invest Ophthalmol Vis Sci. 2014;55:3651-3659.
© 2014 by Lippincott Williams & Wilkins, Inc.