Establishing Quantitative Functional Metrics to Evaluate the Efficacy of Corneal Crosslinking (CXL) Therapeutic Procedures

圆锥角膜及相关扩张性疾病是角膜移植的主要指征，也是美国屈光手术筛查的主要关注点。角膜胶原交联（CXL）已成为通过硬化角膜基质来阻止圆锥角膜进展的唯一有效治疗方法。CXL的安全性和有效性取决于其力学结果，但目前形态学参数而不是生物力学参数用于表征CXL。本提案旨在建立新的功能指标来量化角膜交联（CXL）手术的力学结果，以促进未来对其安全性和有效性的评估。该研究与FDA合作伙伴Ilev博士高度协同，他的实验室一直致力于开发可重复的光辐射安全CXL程序。为了满足这一需求，该实验室开发了布里渊显微镜，该显微镜通过三维分辨率表征原位和体内角膜刚度，从而实现CXL测试方法。我们的中心假设是，通过布里渊显微镜评估的CXL引起的硬化可以用来预测角膜形状，即视觉结果。为了验证这一假设，他们将(1)将布里渊导出的力学指标验证为金标准压缩力学试验；(2)通过诱导充气角膜动态变形，将cxl诱导的力学变化与角膜形态行为联系起来；(3)将CXL后布里渊角膜轮廓与眼压（IOP）升高引起的形态学变化联系起来。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Keratoconus and related ectatic disorders are the leading indication for corneal transplantation and the primary concern of refractive surgery screening in the US. Corneal collagen crosslinking (CXL) has emerged as the only effective treatment to stop keratoconus progression by stiffening the corneal stroma. CXL safety and efficacy is determined by its mechanical outcome, but currently morphological not biomechanical parameters are used to characterize CXL. This proposal aims to establish novel functional metrics to quantify the mechanical outcome of corneal crosslinking (CXL) procedures to facilitate future evaluation of their safety and efficacy. The research is highly synergistic with the FDA collaborator Dr. Ilev, whose lab has been working to develop repeatable and optical radiation safe CXL procedures. To address this need, the lab has developed Brillouin microscopy which enables a CXL test methodology by characterizing corneal stiffness in situ and in vivo with three-dimensional resolution. Our central hypothesis is that the stiffening induced by CXL as evaluated by Brillouin microscopy can be used to predict corneal shape, i.e. visual outcome. To test this hypothesis, they will (1) validate Brillouin-derived mechanical metrics to gold-standard compressive mechanical tests; (2) correlate CXL-induced mechanical changes to cornea morphological behavior by inducing dynamic deformation of the cornea with air-puff; and (3) correlate Brillouin corneal profiles after CXL to morphological changes due to increasing intraocular pressure (IOP).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.