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

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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.