Evidence does not justify CXL with LASIK

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The risk:benefit ratio for routine corneal collagen crosslinking for primary LASIK cases does not justify routine application.

By Cheryl Guttman Krader; Reviewed by Perry S. Binder, MS, MD

Irvine, CA-Combining routine corneal collagen crosslinking (CXL) with primary LASIK may not be a strategy for preventing postoperative ectasia.

“An assessment of the risk:benefit ratio, based on current evidence, does not justify the routine application of CXL at the time of LASIK,” explained Perry S. Binder, MS, MD, clinical professor of ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine. “Furthermore, how do we justify the additional cost to patients in lieu of what is known about the risks of CXL and postLASIK ectasia and the limited peer-reviewed studies of CXL with primary LASIK?

“Instead of performing CXL with LASIK in a case where there is doubt about the risk of ectasia, surgeons can consider implanting a phakic IOL, or in some cases, performing PRK,” he added.

Fear of the unknown

The fear of not being able to identify patients at risk for ectasia is one reason why surgeons might consider routine CXL at the time of LASIK. However, the risk of postLASIK ectasia has been decreasing due to a variety of factors, Dr. Binder noted.

There is better awareness of the risk(s) leading to better patient selection, as well as better methods for screening. In addition, flap thickness has become more reliable with use of the femtosecond laser, and there are more ways to measure postoperative flap and residual bed thickness.

“We are now much better at detecting and eliminating eyes at risk for developing ectasia, and so the incidence of the risk of ectasia has decreased,” Dr. Binder said.

On the other hand, the routine addition of CXL to LASIK introduces potential complications, including no effect, under- or over-response, corneal scarring, corneal infiltrates, delayed epithelial healing, and endothelial cell damage or loss. Moreover, there is little known about the safety and benefit of combining the two techniques.

Further compounding the uncertainties is the broad variability in the radiation and riboflavin dosages being used for CXL.

Unanswered questions

Pertinent to performing CXL with LASIK, questions remain. How will the intact epithelium affect ultraviolet A penetration to the riboflavin in the interface? What would be the diffusion of riboflavin in either direction after instillation into the LASIK interface?

The safety of performing CXL at the time of LASIK is also not well characterized, due to the limited data on the combined procedure. In theory, however, adding CXL may introduce additional risks.

For example, there may be increases in risk of infection due to longer operative and bed exposure time, as well as for loss of deeper stromal cells. Flap adhesion might also be affected with the potential for an increased risk of dislodgement by superficial trauma.

Furthermore, it is unknown how simultaneous CXL will affect the refractive outcome of LASIK and the stability of the treatment effect considering that the CXL procedure might change the excimer laser ablation rate, corneal compactness, refractive index, and curvature. The possibility that CXL might have an effect on postLASIK IOL power calculations must also be considered.

Dr. Binder observed that establishing a benefit of combining CXL with primary LASIK for reducing the risk of ectasia will be a challenge, considering the low incidence of ectasia and the multiple variables that would need to be controlled.

“A study designed to detect a treatment difference for an adverse event with an incidence of 1% would require an enrollment of 300 patients,” he said. “A study of primary CXL with LASIK would have to stratify patients based on numerous clinical parameters, including thickness of the cornea, flap, and residual stromal bed, patient age, and variables in the CXL technique.

“Considering the confounders and that the risk for postLASIK ectasia is very low, a study investigating the effect of CXL on ectasia would have to be extremely long, include a huge number of eyes, and even then, it may not provide an answer,” he said.

Setting goals

Looking ahead, Dr. Binder outlined a set of goals for standardizing and understanding the effects of CXL before exploring its addition to LASIK. He called for the development of techniques and technology that would allow predictable irradiation of focal areas of the affected cornea and to determine the treatment depth.

In addition, Dr. Binder pointed to the need for more scientific data on deviations from the standard Dresden CXL protocol, particularly with respect to modifications in the irradiation protocol and methods for riboflavin delivery. He also suggested evaluating the use of photosensitizers other than riboflavin.

Perry S. Binder, MS, MD

E: garrett23@aol.com

Dr. Binder has no financial interest in the subject matter. This article is based on Dr. Binder’s presentation during Refractive Surgery 2012 at the annual meeting of the American Academy of Ophthalmology.