Abstract Myopia (nearsightedness) is one of the foremost causes of visual impairment worldwide, with severe myopia being linked to several serious eye diseases that can result in permanent blindness. The prevalence of myopia has been increasing and is estimated to affect 50% of the world’s population by 2050. Despite the identification of many risk factors for myopia progression such as age of onset, genetics, visual environment, and peripheral defocus, causes of myopia are not fully understood. Current interventions have shown some success, but without a clear explanation for their mechanism of action. It is therefore critical to investigate the mechanisms underlying myopia development in order to design effective interventions to control the progression of myopia in children, and to delay or ultimately prevent onset altogether. Our long-term goal is to understand the influence of peripheral optical and neural factors on myopia development. The specific objective of this proposal is to test the central hypothesis that optical and neural anisotropy in the human peripheral visual system plays an important role in axial elongation. To achieve these goals we will develop and implement innovative optical tools including a compact scanning ocular wavefront sensor, an open-view scanning adaptive optics vision simulator, and individually-customized contact lenses. Aim 1 is directed at characterizing how different aberration profiles impact through-focus retinal image quality and neural functions. First, measuring lower and higher order ocular aberrations across retinal eccentricity will characterize individual retinal image quality and blur orientations. Neural anisotropy at the same eccentricities will then be evaluated by administering psychophysical tasks while bypassing the ocular optics using a scanning adaptive optics vision simulator. Aim 2 will focus on determining how intrinsic peripheral aberration profiles and eye shape change over time in school children. To do this, we will develop a compact portable scanning wavefront sensor that can be transported to and used in a clinic for measuring longitudinal changes of school children’s optics across retinal eccentricity. This will allow us to delineate relationships between changes in peripheral aberrations at the crucial stages of myopia development, in those children who develop myopia. Aim 3 is proposed to further investigate a role of blur orientations in detecting the sign of defocus and altering directional neural sensitivity in the peripheral retina. To achieve this goal, the retinal response in term of changes in choroidal layer thickness (short-term) and neural sensitivity (long-term) will be examined during and after the peripheral retina is exposed to specific blur orientations.