Antivascular photo-mediated ultrasound therapy and its application in the eye

Antivascular therapy can improve the prognosis of a variety of pathological conditions, including cancer and many eye diseases. By synergistically applying laser pulses and ultrasound bursts, we developed a photo-mediated ultrasound therapy (PUT) technique as a localized antivascular method. PUT takes advantage of the high native optical contrast among biological tissues and has the unique capability to self-target microvessels without damaging surrounding tissue. The technique utilizes an integrated therapeutic ultrasound and laser system. The laser system emits 5-ns, 10-Hz pulses, which is synchronized with 10-ms, 10-Hz ultrasound bursts. Experiments were carried out on chicken yolk sac membrane and rabbit eyes. With radiant exposures around 5 mJ/cm2at 532 nm and ultrasound pressures around 0.4 MPa at 1 MHz or 0.5 MHz, microvessels were able to be removed. Furthermore, ex vivo tests with human blood demonstrated that cavitation was induced when laser and ultrasound were utilized synergistically. On the rabbit eye model, the blood flow in microvessels could be greatly reduced after PUT, and the occlusion of microvessels could last up to 4 weeks. In conclusion, PUT holds significant promises as a non-invasive method to precisely remove microvessels in neurovascular eye diseases by more selectively treating vasculature with minimized side-effects.