Enhancing CXL safety

Corneal crosslinking (CXL) performed with the corneal epithelium intact (epi-on) does not appear to provide any therapeutic advantage in the treatment of progressive corneal ectasia, reported Frederik Raiskup MD, PhD, FEBO, Dresden, Germany, at the 21st ESCRS Winter Meeting in Maastricht, The Netherlands. “The epi-off (with epithelial removal) technique has been extensively investigated in prospective, randomised, controlled trials. Nevertheless, The Cochrane Collaboration Review Study had concerns regarding the size of the studies and the quality of their evidence,” said Dr Raiskup. Complications after CXL were also a concern. These include persistent epithelial defects, melting processes, infections and the development of permanent stromal scars. This led to researchers asking whether the safety of CXL might be enhanced with a transepithelial (epi-on) procedure that keeps the epithelial barrier function intact and avoids wound-response reactions in the stroma. Keeping the epithelium intact might avoid early postoperative pain as well as complications, he explained. However, intact epithelium serves as a barrier for the riboflavin required in the stroma for CXL, he noted. Thus, new methods were developed to draw riboflavin into the stroma. These include pharmacological cleavage of epithelial tight junctions, iontophoresis and the use of enhanced riboflavin solution. The results of a recent study of transepithelial CXL published by Dr Raiskup et al. were not particularly encouraging. “Although there were no cases of infection, sterile infiltrates or haze, there were postoperative epithelial defects in nearly half of the eyes treated, and marked superficial punctate keratitis or loose epithelium in nearly a quarter,” said Dr Raiskup. Furthermore, nearly half of the procedures were 'failures', as defined by an increase of >1.0D in Kmax at 12 
months postoperatively. These results reflected those of previous studies, which looked at both clinical results and corneal morphology. There were also questions regarding whether the epi-on procedures truly maintained intact epithelium, considering the extensive application of topical preserved anaesthetic and antibiotic solutions prior to the instillation of riboflavin. “To date, the majority of comparative studies strongly suggest that although epi-on CXL is a safe procedure, epi-off CXL is significantly more effective in halting the progression of keratoconus,” said Dr Raiskup. “However, considering the many variables involved in epi-on CXL studies, better designed randomised controlled trials are necessary to prove its efficacy, safety and predictability,” concluded Dr Raiskup. Frederik Raiskup: frederik.raiskup@uniklinikum-dresden.de