Wet age-related macular degeneration (AMD) is a leading cause of vision loss in the United States. Choroidal neovascularization (CNV), the creation of new blood vessels in the choroid layer of the eye, plays a central role in the pathophysiology of wAMD. Despite advanced anti-VEGF therapy, 20% of patients become legally blind and other 30% suffer significant vision loss after 5 years. Given the significant burden imposed by wAMD on a growing aging population, there is an urgent need for developing new therapeutic techniques to remove microvessels induced by CNV. We developed a safe, noninvasive imaging-guided photo-mediated ultrasound therapy (PUT) technique as a localized antivascular method, and applied it to remove microvessels in the rabbit choroid. This technique promotes cavitation activity in blood vessels by concurrently applying ultrasound bursts and nanosecond laser pulses. The collapse of cavitation can induce damage to blood vessel endothelial cells, resulting in occlusion of microvessels. PUT takes advantages of the high native optical contrast among biological tissues, and has the unique capability to self-target microvessels without causing surrounding damages. Under the guidance of a fundus camera and an optical coherence tomography (OCT) system, our PUT system now has the capability to precisely target the treating area before the treatment procedure (through the fundus camera), and real-time intra-treatment cavitation monitor to evaluate the therapeutic effect (through the OCT system). Additionally, the safety of PUT technique is confirmed by histopathological studies.