Project Summary/Abstract The prevalence of myopia in the U.S. population is constantly growing, increasing the risk for associated blinding diseases such as glaucoma and retinal detachment. A myopic eye is too long for its own optics and there is currently no accepted method to prevent, slow or control myopia progression. Increasing evidence suggest that the eye's axial length is modulated by unknown growth and remodeling mechanisms in the sclera. Our goal is to elucidate these mechanisms and to develop a treatment strategy based on scleral crosslinking (SXL) using subconjunctival injections of a low cytotoxicity collagen crosslink agent. Our central hypotheses are that scleral collagen remodeling underlies myopia progression, and that SXL can be used to control scleral remodeling and inhibit myopia progression. The long-term goal of this project is to elucidate the key growth and remodeling mechanisms in myopia, and to provide a safe and effective treatment modality to control myopia progression. We will use an established experimental model of myopia, innovative imaging techniques, and multi-scale computational simulation tools to gain insight into the mechanisms that underlies scleral remodeling in myopia. We test the hypothesis that SXL inhibits myopia progression while permitting physiological eye development and maintaining retinal structure and function. We will use principals of engineering and material science to quantify scleral remodeling in the sclera and to test the hypotheses that scleral deformations increase at different length-scales during myopia development and decrease after SXL. Support for scleral remodeling control by SXL could be directly translated to a new clinical treatment strategy for myopia. Even if our results do not support the safe usage of SXL for myopia control, the knowledge we gain about scleral growth and remodeling and its quantification would lead to a completely new understanding of the multi-scale mechanisms underlying myopia development, and would provide a powerful platform to develop alternative clinical control modalities of myopia.