Biomechanical analysis of the cornea and keratoconus

 描述(申请人提供)：圆锥角膜是美国最常见的角膜变性，每2000人中就有1人发病，平均发病年龄为15.4岁。角膜中胶原纤维的组织提供了支持负荷和形成正常角膜形状所必需的机械强度。在圆锥角膜中，角膜的微结构变化破坏了机械稳定性。圆锥角膜外植体表现为胶原取向紊乱，机械模数降低。目前的诊断依赖于年龄和角膜几何特征等间接因素，到目前为止还不能对早期进行性圆锥角膜进行明确诊断。这项拟议的研究将使用最近发展起来的布里渊显微镜来验证机械稳定性的空间局部性退化是圆锥角膜进展的关键驱动因素的假说。第一个具体目标将提高当前布里渊仪器的准确性和速度，以便能够对亚临床、轻度和晚期圆锥角膜患者的角膜进行全面的机械测绘。第二个具体目标将确定由活体测量得出的各种生物力学指标与形态变化进展速度之间的相关性。第三个具体目标将得出基于模型的诊断指标，这些指标与角膜机械不稳定性定量相关，并与临床数据相关。 通过提供体内生物力学指标，这项拟议的研究有望对圆锥角膜患者的临床治疗产生重大影响，从而能够在早期对圆锥角膜的进展速度进行客观评估，并使临床医生能够为进展性圆锥角膜的最佳治疗做出客观、及时的决定。此外，这项研究还将加快布里渊技术向临床的转化。

 DESCRIPTION (provided by applicant): Keratoconus is the most common corneal degeneration in the US, affecting about 1 in 2000 people with a mean onset age of 15.4 years. The organization of collagen fibers in the cornea provides the mechanical strength that is essential to support the load and form the normal corneal shape. In keratoconus, the microstructural changes in the cornea disrupt the mechanical stability. Keratoconus explants showed disrupted collagen orientation and decreased mechanical modulus. Current diagnosis relies on indirect factors such as age and corneal geometrical features and thus far has failed to allow definitive diagnosis of early-stage progressive keratoconus. The proposed research will use recently developed Brillouin microscopy to test the hypothesis that spatially localized degeneration of mechanical stability is a critical driver of keratoconus progression. The first specific aim will improve the accuracy and speed of the current Brillouin instrument to enable comprehensive mechanical mapping of the cornea from patients with subclinical, mild, and advanced keratoconus. The second specific aim will determine the correlation between various biomechanical metrics derived from the in vivo measurements and the rate of progression of morphological changes. The third specific aim will derive model-based diagnostic metrics that are quantitatively related to corneal mechanical instability and correlated with the clinical data. The proposed study is expected to have high impacts on the clinical management of keratoconus patients by providing biomechanical metrics in vivo that will allow objective assessment of the rate of progression of keratoconus prospectively in early stages and enable clinicians to make objective, timely decision for optimal treatments of progressive keratoconus. Moreover, the research will accelerate the translation of the Brillouin technology to the clinic.