Numerical investigation on epi-off crosslinking effects on porcine corneas

Abstract

Experimental inflation tests, conducted on 90 pig corneas before and after corneal collagen crosslinking (CXL) treatment, are simulated with the finite element method. The experimental sample consists of five groups of corneas treated with different UV-A irradiation times (2.5, 5, 10, 15, and 20 min) at constant irradiance 9 mW/cm2. The linear elastic shell theory is used to estimate the equivalent material stiffness of the corneas, revealing that it increases with the exposure time in CXL corneas. In the view of numerical simulations, a simple mechanical model assuming piecewise constant elastic modulus across the corneal thickness is introduced, to estimate the effective increment of the material stiffness in the anterior stroma and the effective depth of the stiffness increment. The two effective quantities are used in the finite element models to simulate the post-CXL tests. Numerical models are able to describe the mechanical effects of CXL in the cornea. The increment of equivalent material stiffness has to be ascribed to a localized increment of the material stiffness in the anterior layers of the cornea, while the posterior layers preserve the original material stiffness. According to the simplified model, the increment of the material stiffness of the anterior cornea increases with the irradiation dose, while the effective reinforcement depth decreases with the irradiation dose. This trend, predicted by a simple mechanical model by imposing equilibrium and compatibility, has been verified by the numerical calculations that captured the global mechanical response of the corneas in untreated and post-CXL conditions.

Transepithelial Enhanced Fluence Pulsed Light M Accelerated Crosslinking for Early Progressive Keratoconus with Chemically Enhanced Riboflavin Solutions and Air Room Oxygen

“…The finite element analysis provided at increasing irradiation doses proved that the increase in the cross-link density at a comparatively high value of irradiation dose could help improve the material strength, thus increasing the fluence not only provides an increased depth in the demarcation lines, but an increased cornea resistance that is crucial in Epi-On treatments. These clinical and experimental observations confirmed that the way to go for Epi-On CXL treatments is to find a balance between the riboflavin concentration and higher fluence between 8.1 and 10.8 J/cm 2 [ 30 , 31 , 32 , 33 ].…”

“…It was demonstrated [ 30 , 31 , 32 ] that the influence of CXL is characterized by a mechanism-based strain energy function, which not only explicitly depends on the density of the cross-links (as a function of the corneal thickness and UVA irradiation dose), but also relies on the discrepant distribution of cross-links in the proteoglycan matrix and along the fibers. The inflation test experimental data for the IOP-apex displacement relationships of porcine cornea at different irradiation doses of 2.7 J/cm 2 , 8.10 J/cm 2 and 10.8 J/cm 2 , respectively, showed good collimation between the predicted and simulated results, thus addressing that at the same value of IOP, the apex displacement of corneal materials after cross-linking is obviously much smaller than that without cross-linking.…”

Experimental in-vitro investigation on Epi-Off-Crosslinking on porcine corneas

“…The mechanical behavior of the porcine cornea resembles closely the behavior of the human cornea, therefore the results of the present experimental campaign can be used to understand the response of human corneas to CXL procedure. Images of the deforming corneas taken at different pressures provide a large database of results that have been employed for further numerical elaborations [ 22 ]. Nevertheless, synthetic plots of global parameters, such as the applied pressure and the apex displacement, provide an immediate representation of the mechanical behavior and are easily interpreted, understood, and analyzed statistically; furthermore, they are comparable to other studies often synthetized in terms of inflation curves.…”

Orientation and Depth Dependent Mechanical Properties of the Porcine Cornea: Experiments and Parameter Identification

“…Only a few anisotropic mechanical models of the porcine cornea have been derived from such experimental studies (Cornaggia et al, 2020;Elsheikh et al, 2011;Pandolfi and Boschetti, 2015). While many numerical models exist for the human cornea, numerical modeling of the porcine cornea is scarce.…”

“…While many numerical models exist for the human cornea, numerical modeling of the porcine cornea is scarce. The few porcine models available in the literature describe the stroma with the same collagen fiber arrangement as in humans with two orthogonal fiber families (Cornaggia et al, 2020;Elsheikh et al, 2011;Pandolfi and Boschetti, 2015). This modeling approach contradicts the circular arrangement of a single family of collagen in porcine corneas observed in X-ray diffraction analyzes (Hayes et al, 2007).…”