Kymionis and associates published recently their results on high-fluence cross-linking (CXL) for progressive keratoconus. They have analyzed the corneal stromal demarcation line depth after CXL with 9 mW/cm ² of ultraviolet A irradiation for 14 minutes compared to standard Dresden protocol-based CXL with 3 mW/cm ² for 30 minutes. The authors did not observe any significant difference in corneal stromal demarcation line depth between the 2 groups and concluded that their modified-accelerated CXL protocol provides the same treatment depth as the classic Dresden CXL protocol, and it could possibly substitute for classic CXL regarding its efficacy.

These results are interesting and add significantly to current CXL research; however, we would like to highlight some aspects that merit further consideration. Kymionis and associates applied a modified-accelerated CXL protocol with total energy of 7.5 J/cm ² . If we consider that the Dresden CXL protocol delivers total energy of 5.4 J/cm ² , the authors increased the total CXL energy by 40%. Unfortunately, there is only limited evidence regarding the safety of high-fluence CXL and only with total energy of 5.4 J/cm ² . Searching the literature, we discovered that the only modified CXL protocol with increased total energy by 20%–30% has been proposed by the Geneva research group for the management of acanthamoeba keratitis, without any published data on its safety and efficacy.

Increased CXL energy could induce increased keratocyte apoptosis, thereby affecting corneal homeostasis and CXL-associated corneal remodeling in an unpredictable manner. It could also affect the corneal endothelium. These interactions could have long-term effects and their consequences require long-term follow-up. Apart from any considerations regarding the efficacy of accelerated CXL, which strongly interferes with the validity range of the Bunsen-Roscoe law, we believe that implementation of increased CXL energies in clinical practice requires prior documentation of the safety profile in vitro. Whether CXL with increased total energy represents a safe and effective alternative to the classic Dresden protocol-based CXL for the management of progressive keratoconus is yet to be investigated in vitro as well as in vivo.