Laser refractive surgery in the form of photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) has become an important means of correcting vision in humans. However, even when it is followed by good healing and achieves suitable correction, refractive surgery is often followed by complications that decrease optical benefit. Among these complications is an increase in ocular higher order optical aberrations, especially spherical aberration and coma, and regression of the original lower order correction over time. ? While recent studies have shed considerable light on the healing response of the cornea to refractive surgery, there is no understanding yet about how this response affects the shape and optical wave aberration structure of the cornea. This is partly due to a lack of appropriate animal models in which to combine such investigations. We have developed an experimental paradigm in which animals are trained to accurately and repeatedly fixate along the optical axis of ophthalmic machines. This allows us to perform optical coherence tomography and wavefront sensing under the same fixation conditions and with the same degree of accuracy and repeatability as in human subjects. These instrument-derived measures can then be correlated with histological studies of corneal biology in the same eyes. Using this animal model, we propose to characterize the cellular substrates of higher order aberrations and regression following PRK by testing the following hypotheses: (1) that corneal wound healing and specifically corneal myofibroblasts, are responsible for a significant proportion of the increase in higher order aberrations after laser refractive surgery, and (2) that regression after laser refractive surgery is primarily due to epithelial hyperplasia induced when the laser ablation shape on the cornea locally ? exceeds a critical slope. Our goal is to understand cellular events during corneal wound healing in terms of their differential ability to alter corneal shape and change the lower and higher order optical wave aberration properties of the eye. This knowledge is essential for the development of both preventative and therapeutic strategies aimed at controlling the cornea's biological response in order to improve reliability and reduce complication rates after laser refractive surgery, it will also be critical to our successful treatment of highly aberrated eyes such as those resulting from corneal transplantation and refractive surgery. ? ?
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