These results match our previous observation of a depth-dependent gradient in stromal collagen interconnectivity in the central cornea, and show that this gradient extends from the central cornea to the limbus. The lack of a preferred distribution of angled fibers with regard to corneal quadrant or radial position likely serves to evenly distribute loads and to avoid the formation of areas of stress concentration.

Transverse shear moduli are two to three orders of magnitude lower than tensile moduli reported in the literature. The profile of shear moduli through the depth displayed a significant increase from posterior to anterior. This gradient supports the hypothesis and corresponds to the gradient of interwoven lamellae seen in imaging of stromal cross-sections.

Examining the cross-section of the human cornea with second harmonic-generated (SHG) imaging shows that many lamellae do not lie parallel to the cornea's anterior surface but have inclined trajectories that take them through the corneal thickness with a depth-dependent distribution. A continuum mechanics-based model of stromal elasticity is developed based on orientation information extracted and synthesized from both X-ray scattering studies and SHG imaging. The model describes the effects of inclined lamella orientation by introducing a probability function that varies with depth through the stroma, which characterizes the range and distribution of lamellae at inclined angles. When combined with the preferred lamellar orientations found from X-ray scattering experiments, a fully 3-D representation of lamella orientation is achieved. Stromal elasticity is calculated by a weighted average of individual lamella properties based on the spatially varying 3-D orientation distribution. The model is calibrated with in vitro torsional shear experiments and in vivo indentation data and then validated with an in vitro inflation study. A quantitative explanation of the experimentally measured depth dependence of mechanical properties emerges from the model. The significance of the 3-D lamella orientation in the mechanics of the human cornea is demonstrated by investigating and contrasting the effects of previous modeling assumptions made on lamella orientation.

A structural model of the in vivo cornea, which accounts for tissue swelling behaviour, for the three-dimensional organization of stromal fibres and for collagen-swelling interaction, is proposed. Modelled as a binary electrolyte gel in thermodynamic equilibrium, the stromal electrostatic free energy is based on the mean-field approximation. To account for active endothelial ionic transport in the in vivo cornea, which modulates osmotic pressure and hydration, stromal mobile ions are shown to satisfy a modified Boltzmann distribution. The elasticity of the stromal collagen network is modelled based on three-dimensional collagen orientation probability distributions for every point in the stroma obtained by synthesizing X-ray diffraction data for azimuthal angle distributions and second harmonicgenerated image processing for inclination angle distributions. The model is implemented in a finite-element framework and employed to predict free and confined swelling of stroma in an ionic bath. For the in vivo cornea, the model is used to predict corneal swelling due to increasing intraocular pressure (IOP) and is adapted to model swelling in Fuchs' corneal dystrophy. The biomechanical response of the in vivo cornea to a typical LASIK surgery for myopia is analysed, including tissue fluid pressure and swelling responses. The model provides a new interpretation of the corneal active hydration control (pump-leak) mechanism based on osmotic pressure modulation. The results also illustrate the structural necessity of fibre inclination in stabilizing the corneal refractive surface with respect to changes in tissue hydration and IOP.

The popularity of refractive surgery to correct the vision of individuals with hyperopia or myopia is increasing. These procedures alter the tissue of the human cornea to cause a change in curvature (refractive power) of the cornea. Radial keratotomy, photorefractive keratectomy, LASIK, and LASEK are all types of refractive surgery. The outcomes of refractive surgical procedures must depend significantly on the biomechanical response of the tissue and therefore on the biomechanical properties of the cornea, or more specifically the corneal stroma which makes up 90% of the tissue. The missing link between computer models of these procedures and predicting patient outcomes is the biomechanical properties of the tissue, including shear modulus. This study aims to characterize the in-plane shear modulus of the corneal stroma through the depth by mechanical testing. Scant data, if any, exists about the shear stiffness and no data includes depth dependence. The stroma consists of sheets of collagenous lamellae in which fibrils are maintained at uniform spacing by glycoaminoglycan molecules. Studies have shown increased interweaving of the lamellae in the anterior third of the stroma compared to the central and posterior thirds [1]. Figure 1 shows the distinct interweaving in the anterior third [2]. It is hypothesized that more interweaving lamellae increases the in-plane shear stiffness. The shear modulus of the full cornea, as well as individual thirds, is examined in this study.