Integration of Mechanical Testing, In Vivo Optical Coherence Elastography and Personalized Finite Element Modeling to Predict Geometrical Outcomes of Corneal Cross-Linking

PURPOSE: Corneal cross-linking (CXL) induces both mechanical and geometrical changes in the cornea, which are typically overlooked in pre-operative planning. We developed and calibrated a patient-specific finite element model (FEM) to predict the topographic alterations resulting from CXL and applied it to three patients with keratoconus (KC) as a proof of concept. METHODS: To calibrate the model, we performed nanoindentation and ex vivo optical coherence elastography (OCE) inflation tests before and after CXL on five human donor corneas. Nanoindentation results tuned the visco-hyperelastic parameters, while ex vivo OCE axial strains were used for validation. Personalized corneal models were generated from the topographies of the three KC patients, with regional stiffness in the affected areas adjusted based on axial strain measured by in vivo pressure-modulated OCE. Simulated CXL outcomes were then compared to 6-month clinical results. RESULTS: CXL induces a 16-fold increase in the fiber-related mechanical parameters and reduces the viscoelasticity time constant by three. In vivo OCE measurements showed an average mechanical weakening of 57% in the KC regions. When compared to the clinical topography at the 6-month follow-up, the CXL-induced curvature changes predicted by the model were -1.5 D vs. -1.76 D, -1.65 D vs. -1.91 D, and -1.76 D vs. -1.57 D, for the three patients, respectively. CONCLUSION: By combining FEM with in vivo corneal mechanical characterization, patient-specific topographic changes can be predicted, which has the potential to improve the planning of CXL treatments.