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EW REFRACTIVE 96 October 2018 by Liz Hillman EyeWorld Senior Staff Writer equated to a 3.45 D shift. With the corneal steepening treatment, Wang et al. observed a steepening effect that increased gradually over 12 hours before stabilizing at a signifi- cantly higher effective power than baseline. Histological examinations showed no laser-induced damage, and the crosslinking density after 1 week appeared stable, the research- ers stated in the paper. In vivo experiments on a rabbit model assessed effective refractive power at 24 hours, 7 days, and out to 3 months postop, using a similar treatment protocol as that performed on porcine eyes. At 48 hours postop, the myopic treatment group saw a mean 1.74 D change in effective refractive power, and a mean 1.64 D change in effective refractive power was observed by 7 days in the hyperopic treatment group. The study authors wrote that these changes remained stable out to 3 months postop and that there was "no wound or wound-healing response resembling that observed after other refractive surgery … and no collagen disorganization, epithelial cell and stromal [edema], intrastromal vacuole formation or endothelial cell detachment." "[A]ll these features are associat- ed with thermal damage to stromal tissue, so we can thus conclude that no such damage occurred," Wang et al. continued, adding later that con- focal microscopy revealed endothe- lial cell shape and density appeared unchanged between the treated group and controls. "We are very confident in our animal models. They are conclu- sive," Dr. Vukelic said, adding that even in samples that weren't ideal, the method of treatment proved suc- cessful every time. At this point, he and coinvesti- gators are researching how to reduce treatment time from about 35 minutes to 5–6 minutes, Dr. Vukelic said, adding that he hopes to start linking (PiXL) for the last few years as a noninvasive method of topogra- phy-guided, accelerated crosslinking using riboflavin and UVA light for correction of low myopia. Another technique that had recently pub- lished results in an animal model, though clinical trials have not yet been conducted, is femtosecond laser crosslinking. The research on the latter front, led by Sinisa Vukelic, PhD, Fu Foundation School of Engineering and Applied Science, Columbia University, New York, uses a fem- tosecond laser at low-energy pulses at a high-pulse rate to produce a low-density plasma that interacts with water molecules that are then broken, creating reactive oxygen species (ROS), or oxygen radicals, Dr. Vukelic explained to EyeWorld. These radicals interact with the collagen fibrils and form crosslinks, which leads to the known phenomenon of stiffening. Dr. Vukelic thinks this tech- nique could be used to induce customized myopic and hyperopic correction even to the depth of the posterior stroma, without having to remove the epithelium. Dr. Vukelic and coinvestiga- tors published their results of this technique on ex vivo and in vivo animal models in Nature Photonics. 1 Fifteen ex vivo porcine eyes received a flattening treatment, which would be used to correct myopia, and 13 porcine eyes received a steepening treatment, as would correct hyper- opia. Both groups were paired with control eyes, and a separate control study was conducted to evaluate the experimental setup. According to the paper, the depth of the treat- ment was about 220 µm. In terms of the flattening effect, a 12% change in effective refractive power was seen within 8 hours after treatment. This lessened afterward as the cornea stabilized to a refrac- tive power that was about 92% of the initial level, which Wang et al. S urgery in all specialties is continuing to move toward the least inva- sive modes possible, and refractive surgery is no exception. Two methods are making headway based on the concept of collagen crosslinking to stiffen and change corneal shape, inducing a refractive change. Avedro (Waltham, Massachusetts) has been pioneering photorefractive intrastromal cross- Animal model tests of femtosecond laser crosslinking showed positive induction of steepening and flattening effects New noninvasive refractive treatment on the horizon New, noninvasive surgeries, such as epi-on PiXL (Avedro) shown here, hope to capitalize on corneal collagen crosslinking to correct refractive error. Source: Anders Behndig, MD Research highlight " We are very confident in our animal models. They are conclusive. " —Sinisa Vukelic, PhD