Laser-based corneal collagen cross-linking and method development for the characterization of cross-linking by induced laser scattering

角膜胶原交联允许角膜的机械性质的特定改变，因此是用于治疗几种角膜疾病的创新和已经建立的方法。不同的概念，使用核黄素，其次是紫外线（A）辐射是目前的研究课题。然而，这些概念表现出不期望的副作用。特别是上皮细胞的先决条件去除（磨损）是痛苦的，是一个潜在的感染中心。此外，矫正折射所需的局部交联几乎是不可能的。为了解决这个问题，超短激光脉冲可以诱导跨上皮交联，甚至可能不应用核黄素。我们的方法基于超短激光脉冲，因此交联是强烈局部化的，并提供了最大限度地减少不良副作用的机会。由于角膜机械性能的这种局部变化，非常需要一种能够以μm范围内的空间分辨率测量这种变化的技术。目前描述角膜流变性能的现有技术无法解决由非线性交联引起的局部变化。为了缩小这一差距，需要建立一种用于角膜机械特性的空间分辨测量的非侵入性方法。这正是布里渊光谱学的能力。它可以测量生物组织的体积模量，在这种情况下，特别是体内角膜的体积模量。为了将这种效率低下的方法转化为直接获得体积模量甚至杨氏模量的通用且有效的技术，将利用光致散射效应。这样就可以激发横波来确定剪切模量。杨氏模量由剪切模量和体积模量计算，而不需要未知的泊松比。这使得新的实验验证，一方面转化为临床方法，另一方面。所要求的项目的总体目标是在发展方面的综合方法的发展（1） 一种用于基于飞秒激光的角膜胶原交联的方法，以及（2） 利用激光和布里渊散射的专用方法对诱导的生物力学变化进行空间分辨表征的技术。

Corneal collagen cross-linking allows for a specific modification of the mechanical properties of the cornea and is hence an innovative and already established way for the treatment of several corneal diseases. Different concepts using riboflavin followed by UV(A)-radiation are subjects of current research. However, these concepts exhibit undesirable side effects. Especially the prerequisite removal of the epithelium (Abrasion) is painful and a potential center of infection. Furthermore, localized cross-linking, as needed for the correction of refraction, is almost impossible. Addressing this problem, ultrashort laser pulses may induce transepithelial cross-linking and possibly even without the application of riboflavin. Our approach is based on ultrashort laser pulses hence the cross-linking is strongly localized and offers the chance of minimizing undesirable side effects. As a consequence of this localized change of mechanical properties of the cornea, a technique being able to measure that change with a spatial resolution in the µm regime is highly desirable.Presently available technologies describing the rheological properties of the cornea are unable to resolve the localized changes induced by nonlinear cross-linking. To close this gap, a non-invasive method for the spatially resolved measurement of mechanical properties of the cornea needs to be established. That is exactly, what Brillouin spectroscopy is capable of. It can measure the bulk modulus of biological tissue and in this case especially of the cornea in vivo. To transform this inefficient method into a versatile and efficient technique with direct access to the bulk modulus and even to Young’s modulus, optically induced scattering effects will be exploited. This way transversal waves can be excited to determine the shear modulus. The Young’s modulus is calculated from shear and bulk modulus without the need of the unknown Poisson’s ratio. This enables the validation of new experiments on the one hand and the translation into a clinical method on the other hand.The overall goal of the requested project is the development of an integrative approach in terms of developing(1) a method for fs laser-based corneal collagen cross-linking and(2) a technology for spatially resolved characterization of the induced biomechanical changes exploiting dedicated methods of laser and Brillouin scattering.