Eyeworld

EW REFRACTIVE 30 January 2017 by Liz Hillman EyeWorld Staff Writer 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 cor- neas that crosslinking efficacy was equally limited by oxygen, but thick corneas were more affected by UV reduction than thin corneas," Dr. Kling said in her presentation during Refractive Surgery Subspecialty Day. "In this study, we adapted the crosslinking protocol to the cor- neal thickness, so that the same UV energy per corneal volume was administered," Dr. Kling continued. "Therefore, we may conclude that crosslinking in thinner corneas is more effective due to faster oxygen diffusion into the stroma. … In this study we have quantified this rela- tionship." Dr. Kling noted that UV restric- tion decreased viscous components of the cornea while oxygen restric- tion did not. Because rigid materials have a small viscous component, which is typically related to the ex- tracellular matrix and not collagen, Dr. Kling said this shows "oxygen study, he said, adds to that body of research. "All of these little puzzle pieces show us how a single element—oxy- gen—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 are limited by the oxygen diffusion rate rather than UV intensity." The original Dresden crosslink- ing 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 transep- ithelial 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, pro- fessor 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 evalu- ate these protocols, Dr. Hafezi said many have been found less effec- tive at stiffening the cornea. This 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 fur- ther 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, present- ed 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 Research drills down into efficacy of crosslinking protocols for thin corneas Stress-strain curves in porcine corneas demonstrated that oxygen reduction significantly reduced the stiffening effect of crosslinking. Two-dimensional mechanical characterization of corneal samples in a stress-strain extensometer Source (all): Sabine Kling, PhD

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