EyeWorld Asia-Pacific March 2017 Issue

March 2017 44 EWAP refractive Research drills down into efficacy of crosslinking protocols for thin corneas by Liz Hillman EyeWorld Staff Writer Study further establishes essential role of oxygen for efficient biomechanical strengthening T he essential role of oxygen in crosslinking to stiffen the cornea and halt progressive keratoconus is well-known, but the recipient of the Journal of Refractive Surgery Troutman Prize, presented at Refractive Surgery Subspecialty Day ahead of the 2016 American Academy of Ophthalmology annual meeting, described research that further established oxygen’s necessity in the context of newer crosslinking protocols. Sabine Kling, PhD , Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland, presented research published in 2015 that investigated the role of oxygen in biomechanical stiffening in more detail. 1 “We found that reducing the available oxygen at the corneal surface by 50% (by means of a contact lens) …, also reduces the biomechanical stiffening by about 50%,” Dr. Kling told EyeWorld . “The results of this study therefore suggest that current crosslinking protocols are limited by the oxygen diffusion rate rather than UV intensity.” The original Dresden crosslinking protocol, described in the 1990s, includes scraping off the epithelium from corneas at least 400 μm thick and instilling a riboflavin solution for 30 minutes, followed by UV-A irradiation for 30 minutes at 3 mW/cm 2 . Since then, different protocols have been proposed to shorten treatment time (e.g., pulse light accelerated crosslinking), to reduce pain (e.g., epithelium-on or transepithelial crosslinking), and to expand indications for corneas thinner than 400 μm (e.g., swelling the cornea using a hypo-osmolar riboflavin or using a contact lens). Farhad Hafezi, MD, PhD , professor of ophthalmology, University of Geneva, Switzerland, and clinical professor of ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, who was the principle investigator in the research, said there is a large body of evidence supporting the efficacy and safety of the Dresden protocol. Other protocols have been rolled out with little evidence to support their biomechanical efficacy. As researchers stepped in to evaluate these protocols, Dr. Hafezi said many have been found less effective at stiffening the cornea. This study, he said, adds to that body of research. “All of these little puzzle pieces show us how a single element— oxygen—has major implications on this technique,” Dr. Hafezi said. In this study, the researchers used enucleated porcine eyes and murine eyes to represent standard corneas of 400 μm in thickness and thinner corneas, respectively. The eyes were then treated with different crosslinking conditions: a standard crosslinking protocol, a contact lens-assisted protocol, and a corneal swelling protocol, as well as control conditions. Contact lens-assisted protocols and corneal swelling could allow for crosslinking in thinner corneas that are too thin for safe application of the Dresden protocol. After treating the porcine and murine eyes under these conditions, biomechanical measurements of the corneas were taken using a stress– strain extensometer. “We saw in thin and thick corneas that crosslinking efficacy was equally limited by oxygen, but thick corneas were more affected by Stress–strain curves in porcine corneas demonstrated that oxygen reduction signifi- cantly reduced the stiffening effect of crosslinking. Two-dimensional mechanical characterization of corneal samples in a stress–strain extensometer Source (all): Sabine Kling, PhD