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

描述（由申请人提供）：在美国，角膜扩张是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。 缺乏用于解决整个角膜的生物力学特性的临床工具是理解角膜不稳定机制和将潜在的变革性生物工程方法应用于风险筛查和治疗优化的关键障碍。 该研究项目的目标是开发一个强大的基于OCT的模拟平台，用于量化扩张风险并预测对各种角膜治疗的个体反应。 在角膜形状和视觉功能之间的敏感联系的帮助下，目的是识别扩张性疾病的关键结构预测因子，并通过整合的患者特异性生物力学测量和建模开发定制交联治疗的合理方法。 中心假设是角膜中生物力学性质的大小和分布是角膜形状的关键驱动因素。 该假设和用于测试它的方法已经部分地通过申请人在角膜光学相干弹性成像（OCE）和患者特异性有限元（FE）分析研究中的初步工作而开发，所述研究表明材料性质和形状之间的重要依赖性。 将通过以下具体目标检验这一假设：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FE模型用于预测供体眼和患者中角膜干预结果的准确性，以及3）识别圆锥角膜进展、屈光手术后扩张、和交联反应。 根据目标1，OCE将用于供体眼和临床研究，以检验以下假设：人角膜在生物力学特性方面存在固有的区域差异，这些差异通过LASIK、圆锥角膜和胶原交联以特征性方式改变。 在目标1中使用针对所有干预前眼睛的受试者特定几何形状生成FE模型后，目标2将检验以下假设：填充有受试者特定OCE属性数据的模型比填充有理想化整体属性估计值的模型更好地预测结果。 最后，在使用所有正常和圆锥角膜患者作为建模基质的大规模多因素FE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以影响扩张风险， 交联反应 预期的结果包括基于OCT的能力的临床翻译，用于映射角膜生物力学特性和生成能够预测治疗反应的患者特定的计算模型。 基于模拟的优化将支持用于扩张风险的新型可定制计算器和用于增强单个眼睛中胶原交联效果的新算法。 这些结果直接解决了NEI确定的差距，并将为现有和新兴的角膜手术提供新的基于模拟的治疗策略。

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.