Corneal Elastography and Patient-Specific Modeling for Simulation-based Therapy

描述(申请人提供)：角膜扩张症是美国视力相关生活质量受损的主要原因，也是角膜移植的主要适应症。 缺乏临床工具来解决整个角膜的生物力学特性是理解角膜不稳定的机制和应用潜在的变革性生物工程方法进行风险筛查和治疗优化的关键障碍。这项研究计划的目标是开发一个基于OCT的强大的模拟平台，用于量化扩张症的风险并预测个人对广泛的角膜治疗的反应。借助角膜形状和视觉功能之间的敏感联系，目标是确定扩张性疾病的关键结构预测因素，并通过整合患者特定的生物力学测量和建模，开发定制的交联剂治疗的合理方法。中心假设是角膜中生物力学特性的大小和分布是角膜形状的关键驱动因素。这一假设和检验方法部分是通过申请人在角膜光学相干弹性成像(OCE)和患者特有的有限元(FE)分析研究中的初步工作开发出来的，这些研究表明材料特性和形状之间存在重要的相关性。该假说将通过以下具体目标进行验证：1)表征正常、手术改变和病理状态下角膜生物力学特性的大小和分布，2)确定弹性成像驱动的有限元模型预测供体眼和患者角膜干预结果的准确性，3)使用患者特定的模拟来确定圆锥角膜进展、屈光手术后扩张和交联性反应的关键生物力学驱动因素。在目标1下，OCE将被用于供眼和临床研究，以检验这一假设，即人类角膜在生物力学性能方面存在固有的区域差异，这些差异可以通过LASIK、圆锥角膜和胶原交联剂以特有的方式改变。在为目标1中的所有介入前眼睛使用特定于对象的几何形状生成FE模型后，目标2将测试这样的假设，即填充了特定于对象的OCE属性数据的模型比使用理想化的整体属性估计的模型更好地预测结果。最后，在使用近视正常和圆锥角膜患者作为建模基础的大规模、多因素有限元模拟中，目标3将确定弹性特性、初始角膜几何形状和手术变量如何相互作用来影响扩张风险和 交联性反应。预期结果包括基于OCT绘制角膜生物力学特性图的能力的临床翻译，以及生成能够预测治疗反应的患者特定计算模型。基于模拟的优化将支持用于扩张症风险的新的、可定制的计算器，以及用于增强个体眼睛中的胶原交联物的效果的新算法。这些结果直接解决了NEI确定的差距，并将使现有和新兴角膜手术的新的基于模拟的治疗策略成为可能。

DESCRIPTION (provided by applicant): Corneal ectasia is a major cause of impaired vision-related quality of life in the United States and a leading indication for corneal transplantation. The lack of clinical tools for resolving biomechanical properties throughout the cornea is a critical barrier to understanding mechanisms of corneal instability and applying potentially transformative bioengineering approaches to risk screening and treatment optimization. The goal of this research program is to develop a robust OCT-based simulation platform for quantifying ectasia risk and predicting individual responses to a broad range of corneal treatments. The objective, which is aided by the sensitive link between corneal shape and visual function, is to identify the key structural predictors of ectatic disease and develop rationl approaches to customized crosslinking therapy through integrated patient- specific biomechanical measurement and modeling. The central hypothesis is that the magnitude and distribution of biomechanical properties in the cornea are key drivers of corneal shape. This hypothesis and the methods for testing it have been developed in part through the applicants' preliminary work in corneal optical coherence elastography (OCE) and in patient-specific finite element (FE) analysis studies that suggest important dependencies between material properties and shape. The hypothesis will be tested through the following specific aims: 1) Characterize the magnitude and distribution of corneal biomechanical properties across normal, surgically altered and pathologic states, 2) determine the accuracy of elastography-driven FE models for predicting outcomes of corneal interventions in donor eyes and patients, and 3) identify the key biomechanical drivers of keratoconus progression, post-refractive surgery ectasia, and crosslinking response using patient-specific simulations. Under Aim 1, OCE will be used in donor eye and clinical studies to test the hypothesis that the human cornea has intrinsic regional differences in biomechanical properties that are altered in characteristic ways by LASIK, keratoconus and collagen crosslinking. After generating FE models using subject-specific geometry for all pre-intervention eyes in Aim 1, Aim 2 will test the hypothesis that models populated with subject-specific OCE property data better predict outcomes than those with idealized bulk property estimates. Finally, in large-scale, multifactorial FE simulations using al normal and keratoconic patients as modeling substrates, Aim 3 will determine how elastic properties, initial corneal geometry and procedure variables interact to influence ectasia risk and crosslinking responses. Expected outcomes include clinical translation of OCT-based capabilities for mapping corneal biomechanical properties and generating patient-specific computational models capable of predicting treatment responses. Simulation-based optimizations will support novel, customizable calculators for ectasia risk and new algorithms for enhancing the effects of collagen crosslinking in individual eyes. These outcomes directly address gaps identified by the NEI and will enable new simulation-based treatment strategies for existing and emerging corneal procedures.