Corneal wound healing: ocular optics after laser surgery

描述(申请人提供)：准分子激光屈光性角膜切削术(PRK)和准分子激光原位角膜磨镶术(LASIK)已成为矫正人类视力的重要手段。然而，即使屈光手术后获得了良好的愈合和适当的矫正，但屈光手术之后往往会出现并发症，从而降低光学效益。这些并发症包括眼球高阶光学像差的增加，特别是球差和彗差，以及随着时间的推移原来的低阶矫正的退化。 虽然最近的研究已经对屈光手术后角膜的愈合反应有了相当大的了解，但对于这种反应如何影响角膜的形状和光波像差结构尚不清楚。这在一定程度上是由于缺乏适当的动物模型来结合这类研究。我们已经开发了一种实验范式，在这种范式中，动物被训练成准确和重复地注视眼科机器的光轴。这使我们能够在相同的固定条件下进行光学相干断层扫描和波前传感，并具有与人类受试者相同的精度和可重复性。然后，这些仪器衍生的测量可以与同一只眼睛的角膜生物学的组织学研究相关联。利用这个动物模型，我们建议通过检验以下假设来描述PRK后高阶像差和退变的细胞底物：(1)角膜伤口愈合，特别是角膜肌成纤维细胞，是激光屈光手术后高阶像差增加的主要原因；(2)激光屈光手术后高阶像差增加的主要原因是当激光切割角膜局部形状时，导致角膜上皮细胞增生。 超过一个临界坡度。我们的目标是了解角膜伤口愈合过程中的细胞事件，了解它们改变角膜形状和改变眼睛低阶和高阶光波像差特性的不同能力。这些知识对于开发旨在控制角膜生物反应的预防和治疗策略是至关重要的，以便提高可靠性和减少激光屈光手术后的并发症发生率，对于我们成功治疗高度像角膜移植和屈光手术引起的高度像差的眼睛也是至关重要的。

DESCRIPTION (provided by applicant): 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.