CorMecha

The cornea is a unique tissue featuring several important physiological properties, mainly transparency and refraction, related to crucial biomechanical properties. It exhibits a viscoelastic behaviour which is important for maintaining the corneal curvature despite changes in intraocular pressure (IOP) and various forces applied on cornea, such as external shocks or eye rubbing. Defective mechanical behaviour is involved in various cornea pathologies, mainly keratoconus, which is characterized by localized corneal thinning and steepening with decreased biomechanical strength of the cornea, and results in decreased vision due to high irregular astigmatism and corneal opacification. Development of keratoconus, sometimes basically called ectasia, is a potential complication of corneal refractive surgery. Moreover, myopia correction by corneal refractive surgery shows variable results, which can be explained by inter-individual variability of wound healing responses and biomechanical behaviours. The main underlying hypothesis of this project is that the corneal biomechanical properties are closely related to the corneal multiscale structure, which is a common assumption in all connective tissues, based both on experimental evidence and on numerical simulations. This project further assumes that defective corneal biomechanical properties are caused by a defective structure. Corneal stroma consists of several hundred 1-3 µm thick stacked lamellae made of collagen fibrils (25-30 mm of diameter) aligned and regularly packed to ensure cornea transparency. Lamellae are roughly organized parallel to each other with different orientations, but their size and three-dimensional (3D) organization vary along the depth and extent of the cornea. Vertical stromal striae, corresponding to lamellae undulations, are also present in the posterior stroma and have been shown to be related to biomechanical behaviour. However, this anisotropic hierarchical organization of the cornea and its physiological consequences on cornea biomechanics have been poorly characterized because of the limitations of conventional techniques. This project aims at: (i) setting up an atlas of cornea 3D structure from the sub-micrometer scale (intra-lamellar organization of collagen fibrils) to the millimeter-centimeter scale (lamellae distribution in the full cornea, stromal striae), (ii) accurately measuring the biomechanical properties linked to this structure in physiological conditions and in various pathological conditions, including high IOP, keratoconic corneas and corneas after photo-ablation, and (iii) building a model of corneal biomechanics based on these microstructural and macroscopic data in order to provide an insight into the role of specific stromal structures. It relies on the highly original combination of well-controlled inflation device and state-of-the-art imaging setups, mainly polarization-resolved Second Harmonic Generation microscope. Specific bioimage informatics tools and pipelines will be developed to process the very large data sets (Gb to Tb) generated by this new device and quantify clinically-relevant parameters of interest. Advanced statistical analysis of the series of clinical (corneal topography …), structural (OCT, confocal, SHG…) and mechanical data obtained on the same cornea will then be performed for normal, keratoconic and photo-ablated corneas. The ultimate goals are twofold: (i) to translate the structural features observed with advanced research microscopes into easily-detectable features using commonly used techniques in clinical ophthalmology, in order to enable the diagnosis of structural defects related to defective mechanical properties; (ii) to develop a patient-specific simplified model to serve as a predictive tool by clinicians, mainly to improve refractive surgery procedures.