The hyaloid vascular system (HVS) is known to have an important role in eye development. However, physiological mechanisms of HVS regression and their correlation with developmental eye disorders remain unclear due to technical limitations of conventional ending point examination with fixed tissues. Here, we report comparative optical coherence tomography (OCT) and OCT angiography (OCTA) monitoring of HVS regression in wild-type and retinal degeneration 10 (rd10) mice. Longitudinal OCTA monitoring revealed accelerated regression of hyaloid vessels correlated with retinal degeneration in rd10. Quantitative OCT measurement disclosed significant distortions of both retinal thickness and the vitreous chamber in rd10 compared to WT mice. These OCT/OCTA observations confirmed the close relationship between HVS physiology and retinal neurovascular development. The distorted HVS regression might result from retinal hyperoxia or dopamine abnormality due to retinal remodeling in rd10 retina. By providing a noninvasive imaging platform for longitudinal monitoring of HVS regression, further OCT/OCTA study may lead to in-depth understanding of the physiological mechanisms of HVS regression in normal and diseased eyes, which is not only important for advanced study of the nature of the visual system but also may provide insights into the development of better treatment protocols of congenital eye disorders.