Femtosecond-Laser-based crosslinking of corneal collagen fibers.

• Applicants: Dr. Jeannine Mißbach-Güntner; Professor Dr. Stefan Nolte; Professor Dr. Christoph Russmann
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 428490203

Cross-linking of corneal collagen fibers offers the possibility of specifically modifying the biomechanics of the eye. In addition to the treatment of keratoconus and secondary keratectasia after refractive surgery, refractive correction and prevention of myopia are also potential fields of application. To stabilize the cornea in keratoconus and secondary keratectasia, UV(A)-riboflavin cross-linking is used clinically. There are also first animal experiments which show that it is in principle possible to prevent the development of myopia through scleral cross-linking. In UV(A)-riboflavin cross-linking, riboflavin is applied locally and cross-linked by UV(A) radiation. Although the procedure is clinically effective in principle, the precision is low, so that the exclusive treatment of diseased regions or targeted refraction correction is not possible. In addition, the necessary abrasion of the epithelium and the associated increase in corneal sensitivity leads to pain for the patient and is a possible source of infection. Femtosecond-(fs)-lasers are used with great success as surgical cutting tools in ophthalmology. A laser method without chemicals would also be of great medical benefit for corneal cross-linking. It has recently been shown that corneal collagen fibers can be cross-linked without chemical agents using fs-laser pulses. This made it possible to correct myopia in a murine animal model. The mechanism of action is postulated to be the production of reactive oxygen species by the laser-induced plasma and the subsequent cross-linking of the collagen fibers. In this application the direct excitation of the amino acid via multiphoton excitation is favoured. Based on the published collagen structure and the photochemical properties of the amino acids involved as well as our own experimental data, there is evidence that direct cross-linking of collagen fibers is possible. This is expected to lead to higher specificity, precision and fewer side effects.The overall aim of the proposed project is to investigate corneal cross-linking by direct excitation of the relevant amino acids and to evaluate the translation into clinical application. To this end, 3 working objectives are defined: 1. Definition of the laser parameters for cross-linking corneal tissue and development of a rate equation model to describe the processes;2. Establishment of a methodological platform for the analysis of corneal cross-linking and evaluation of biological effects on tissue;3. Evaluation of the translational potential of the procedure by comparison with the gold standard UV(A) riboflavin crosslinking.This could enable a new agent-free fs-laser procedure for the treatment of keratoconus, secondary keratectasia and myopia.

• DFG Programme: Research Grants