Date of the defence: 3 february 2025

Title of the thesis: Localized Corneal Stiffening for Refractive Correction: Experiments and Computational Analysis

Brief summary: This thesis explores the suitability of localized corneal cross-linking (CXL) as a treatment for refractive correction. To this purpose, the relationship between the mechanical and refractive changes that CXL induces in the corneal tissue was investigated. Experimental techniques such as optical coherence elastography (OCE), as well as computational approaches such as finite element modeling (FEM), were employed to characterize the optobiomechanical response of the cornea after the treatment. The thesis details the research conducted throughout its various chapters, each describing a different approach to the study. In Chapter 2, the stiffening and consequent refractive changes induced by patterned CXL on porcine corneas were
quantified via ex vivo OCE analysis. It was shown that by localizing the mechanical effect, customized refractive corrections can be achieved. Chapter 3 described an experimental OCE evaluation of the dynamic changes to which the cornea is subjected during CXL treatment, with high temporal and spatial resolution. This study provided novel insights into the subtle changes caused by osmotic gradients in the tissue. Chapter 4 shifts the focus towards the development and calibration of a patient-specific FEM of the localized CXL. A combination of ex vivo mechanical tests and in vivo corneal mechanical quantification was applied to tailor the model to the mechanical response of the individual patient. Finally, in Chapter 5 the FEM was employed to predict CXL-induced refractive changes in a clinical scenario. An evaluation of the different parameters that influence the refractive correction induced by the treatment was made possible by the versatility and accuracy of the developed FEM.
The results presented throughout this work culminated in a predictive computational tool that could potentially assist clinicians in the planning phases of CXL treatment. This research demonstrates how by integrating experimental mechanical tests, novel in vivo imaging techniques such as OCE, and computational tools, an accurate biomechanical analysis of the corneal tissue and its response to surgical treatments can be performed. The present thesis leverages the combination of different biomechanical technologies for the development of accurate predictive models, paving the way for new advancements in the field of personalized medicine.