Biomechanics of keratoconus: Two numerical studies

Abstract

Background The steep cornea in keratoconus can greatly impair eyesight. The etiology of keratoconus remains unclear but early injury that weakens the corneal stromal architecture has been implicated. To explore keratoconus mechanics, we conducted two numerical simulation studies. Methods A finite-element model describing the five corneal layers and the heterogeneous mechanical behaviors of the ground substance and lamellar collagen-fiber architecture in the anterior and posterior stroma was developed using the Holzapfel-Gasser-Ogden constitutive model. The geometry was from a healthy subject. Its stroma was divided into anterior, middle, and posterior layers to assess the effect of changing regional mechanical parameters on corneal displacement and maximum principal stress under intraocular pressure. Specifically, the effect of softening an inferocentral corneal button, the collagen-based tissues throughout the whole cornea, or specific stromal layers in the button was examined. The effect of simply disorganizing the orthogonally-oriented posterior stromal fibers in the button was also assessed. The healthy cornea was also subjected to eye rubbing-like loading to identify the corneal layer(s) that experienced the most tensional stress. Results Conical deformation and corneal thinning emerged when the corneal button or the mid-posterior stroma of the button underwent gradual softening or when the collagen fibers in the mid-posterior stroma of the button were dispersed. Softening the anterior layers of the button or the whole cornea did not evoke conical deformation. Button softening greatly increased and disrupted the stress on Bowman’s membrane while mid-posterior stromal softening increased stress in the anterior layers. Eye rubbing profoundly stressed the deep posterior stroma while other layers were negligibly affected. Discussion These observations suggest that keratoconus could be initiated, at least partly, by mechanical instability/damage in the mid-posterior stroma that then imposes stress on the anterior layers. This may explain why subclinical keratoconus is marked by posterior but not anterior elevation on videokeratoscopy.

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis

“…It has been proposed that the focal weakness is the initiating event in KC, resulting in a cycle of biomechanical decompensation with increased strain and thinning in the weak area, leading to a focal increase in stress [ 57 ]. In addition, as a risk factor for KC, vigorous eye rubbing was shown sharply increased force to corneas [ 58 ]. In our previous studies, we found that mechanical stretch could induce the expression of the hub genes including IL6 [ 59 ].…”

Keratoconus cone location influences ocular biomechanical parameters measured by the Ocular Response Analyzer

“…One might interpret these results as evidence that the entire cornea weakens in keratoconus, but this interpretation is flawed since none of the methods were able to assess asymmetry. Finite element modeling has identified loss of tissue stiffness, which is localized to a concentric area, as a contributor to keratoconus progression [ 30 ], and several groups have used Brillouin microscopy, a form of non-destructive optical elastography [ 31 ], to demonstrate focal, not global, weakness in keratoconus that is associated with local corneal thinning and steepening [ 32 – 34 ]. In other words, there is an asymmetry in corneal biomechanical parameters, relative tissue weakness adjacent to relative tissue strength, which is typically not accounted for in their clinical assessment of keratoconus.…”

The inclusion of the epithelium in numerical models of the human cornea

“…In the recent literature, an exception to this common way to proceed is represented by an interesting study on the biomechanics of the keratoconus, where the authors model the thin layers with the goal to capture the conditions that lead to the formation of a conus in a diseased cornea [10]. Regrettably, the selection of the material properties of the thin layers is not commented or justified; also the discretized finite element model adopted in the numerical simulation is not shown.…”