Individualized Characterization of the Distribution of Collagen Fibril Dispersion Using Optical Aberrations of the Cornea for Biomechanical Models.

Purpose: The spatial distribution of collagen fibril dispersion has a significant impact on both corneal biomechanical and optical behaviors. The goal of this study was to demonstrate a novel method to characterize collagen fibril dispersion using intraocular pressure (IOP)-induced changes in corneal optical aberrations for individualized finite-element (FE) modeling. Methods: The method was tested through both numerical simulations and ex vivo experiments. Inflation tests were simulated in FE models with three assumed patterns of collagen fibril dispersion and experimentally on three rhesus monkey corneas. Geometry, matrix stiffness, and the IOP-induced changes in wavefront aberrations were measured, and the collagen fibril dispersion was characterized. An individualized corneal model with customized collagen fibril dispersion was developed, and the estimated optical aberrations were compared with the measured data. Results: For the theoretical investigations, three assumed distributions of fibril dispersion were all successfully characterized. The estimated optical aberrations closely matched the measured data, with average root-mean-square (RMS) differences of 0.29, 0.24, and 0.10 µm for the three patterns, respectively. The overall features of the IOP-induced changes in optical aberrations were estimated for two ex vivo monkey corneas, with average RMS differences of 0.57 and 0.43 µm. Characterization of the fibril dispersion in the third cornea might have been affected by corneal hydration, resulting in an increased RMS difference, 0.8 µm. Conclusions: A more advanced corneal model with individualized distribution of collagen fibril dispersion can be developed and used to improve our ability to understand both biomechanical and optical behaviors of the cornea.

Vulnerability of corneal endothelial cells to mechanical trauma from indentation forces assessed using contact mechanics and fluorescence microscopy.

Corneal endothelial cell (CEC) loss occurs from tissue manipulation during anterior segment surgery and corneal transplantation as well as from contact with synthetic materials like intraocular lenses and tube shunts. While several studies have quantified CEC loss for specific surgical steps, the vulnerability of CECs to isolated, controllable and measurable mechanical forces has not been assessed previously. The purpose of this study was to develop an experimental testing platform where the susceptibility of CECs to controlled mechanical trauma could be measured. The corneal endothelial surfaces of freshly dissected porcine corneas were subjected to a range of indentation forces via a spherical stainless steel bead. A cell viability assay in combination with high-resolution fluorescence microscopy was used to visualize and quantify injured/dead CEC densities before and after mechanical loading. In specimens subjected to an indentation force of 9 mN, the mean ±â€¯SD peak contact pressure P0 was 18.64 ±â€¯3.59 kPa (139.81 ±â€¯26.93 mmHg) in the center of indentation and decreased radially outward. Injured/dead CEC densities were significantly greater (p ≤ 0.001) after mechanical indentation of 9 mN (167 ±â€¯97 cells/mm2) compared to before indentation (39 ±â€¯52 cells/mm2) and compared to the sham group (34 ±â€¯31 cells/mm2). In specimens subjected to "contact only" - defined as an applied indentation force of 0.65 mN - the peak contact pressure P0 was 7.31 ±â€¯1.5 kPa (54.83 ±â€¯11.25 mmHg). In regions where the contact pressures was below 78% of P0 (<5.7 kPa or 42.75 mmHg), injured/dead CEC densities were within the range of CEC loss observed in the sham group, suggesting negligible cell death. These findings indicate that CECs are highly susceptible to mechanical trauma via indentation, supporting the established "no-touch" policy for ophthalmological procedures. While CECs can potentially remain viable below contact pressures of 5.7 kPa (42.75 mmHg), this low threshold suggests that prevention of indentation-associated CEC loss may be challenging.

Depth-Dependent Out-of-Plane Young's Modulus of the Human Cornea.

Purpose/Aim: Despite their importance in accurate mechanical modeling of the cornea, the depth-dependent material properties of the cornea have only been partially elucidated. In this work, we characterized the depth-dependent out-of-plane Young's modulus of the central and peripheral human cornea with high spatial resolution. MATERIALS AND METHODS: Central and peripheral corneal buttons from human donors were subjected to unconfined axial compression followed by stress relaxation for 30 min. Sequences of fluorescent micrographs of full-thickness corneal buttons were acquired throughout the experiment to enable tracking of fluorescently labeled stromal keratocyte nuclei and measurements of depth-dependent infinitesimal strains. The nominal (gross) out-of-plane Young's modulus and drained Poisson's ratio for each whole specimen was computed from the equilibrium stress and overall tissue deformation. The depth-dependent (local) out-of-plane Young's modulus was computed from the equilibrium stress and local tissue strain based on an anisotropic model (transverse isotropy). RESULTS: The out-of-plane Young's modulus of the cornea exhibited a strong dependence on in-plane location (peripheral versus central cornea), but not depth. The depth-dependent out-of-plane Young's modulus of central and peripheral specimens ranged between 72.4-102.4 kPa and 38.3-58.9 kPa. The nominal out-of-plane Young's modulus was 87 ± 41.51 kPa and 39.9 ± 15.28 kPa in the central and peripheral cornea, while the drained Poisson's ratio was 0.05 ± 0.02 and 0.07 ± 0.04. CONCLUSIONS: The out-of-plane Young's modulus of the cornea is mostly independent of depth, but not in-plane location (i.e. central vs. peripheral). These results may help inform more accurate finite element computer models of the cornea.