Microindentation reveals softening of the equatorial and anterior sclera during early myopia development in tree shrew eyes

Myopia has reached epidemic levels worldwide and significantly increases the risk for blinding diseases such as glaucoma, making it a pressing global health concern. Myopia is commonly associated with biomechanical weakening and remodeling of the sclera, resulting in an excessively elongated eye relative to its optical system. The exact regions of scleral remodeling and tissue softening remain unclear. The purpose of this study was to establish a microindentation testing approach for spatial mapping of scleral stiffness and localization of softened regions. Microindentation tests were performed across entire flat-mounted scleral samples obtained from juvenile tree shrews with either normal visual experience or four days of monocular -5 D lens treatment to induce myopia in one eye, whereas the other eye served as control. Inverse finite element analyses were performed to estimate the apparent modulus at each indentation location, while accounting for large deformations. The generated stiffness maps revealed that scleral stiffness increased with distance from the posterior pole. Compared to normal and control eyes, scleral stiffness was significantly reduced in myopic eyes at the equatorial and anterior scleral regions, but not at the posterior pole. This result was surprising because the posterior pole has previously been regarded as the primary site of scleral remodeling and biomechanical weakening in myopia. Regions that exhibited significant changes in stiffness were also identified as the thinnest scleral regions, suggesting that scleral softening in myopia begins in regions that are most vulnerable to excessive stretching. It remains unclear whether scleral softening at the equatorial and anterior regions during early stages of myopia development is a precursor of biomechanical weakening of the sclera as myopia progresses. This study introduces an indentation-based approach to map scleral stiffness across the entire sclera of tree shrew eyes thus providing higher spatial resolution compared to previous work. This novel approach provides insights into how and where myopic changes may begin, highlighting potential targets for early interventions, such as scleral crosslinking, at structurally vulnerable regions.