Novel Nanosecond Laser and Ultrasound to Selectively Treat Eye Blood Vessels

ABSTRACT / PROJECT SUMMARY
Wet age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed
world. Anti-VEGF therapy is currently the gold standard for wet AMD treatment. However, up to 50% of
patients in the long term have a suboptimal response to anti-VEGF therapy. A better alternative method for
treatment of AMD is urgently needed. We have recently invented a novel, effective, and highly-selective anti-
vascular therapy, termed “photo-mediated ultrasound therapy (PUT)”. PUT is based on microcavitations in
microvessels produced by synergistically applied laser pulses and ultrasound bursts. As demonstrated by our
preliminary studies on clinically relevant animal models, PUT is capable of eliminating the target microvessels
in the choroid without causing unwanted damage to the surround tissue, facilitating optimal treatment outcome
for patients with AMD.
The ultimate goal of our research is to develop and commercialize a new, noninvasive therapeutic technique
for safe and efficient treatment of choroidal neovascularization (CNV) in patients with wet AMD. To achieve the
ultimate goal, the project streamlines to achieve the technological transition, including the following milestones:
(1) to build and verify the Phase I α-prototype on rabbit eye models, (2) to build and verify the Phase II β-
prototype for human subjects, (3) to complete clinical studies, and (4) to define the approval pathway with the
FDA. In this Phase I research, PhotoSonoX LLC, via an established collaboration with the Kellogg Eye Center
at the University of Michigan School of Medicine, will build a clinically ready α-prototype system, and fully test
its safety and efficacy to pave the road to clinical studies in Phase II.
The hypothesis of the Phase I study is that PUT can precisely remove pathologic microvessels in the eye
without causing short-term and long-term damage in the surrounding tissue. To test this hypothesis, the
following specific aims will be accomplished: Aim 1. Develop a clinically ready α-prototype PUT system which
has a reasonable cost and can be tested on clinically relevant rabbit eyes in Phase I and on human eyes in
Phase II. Aim 2. Determine the long-term safety of PUT for treatment of choroidal microvessels on normal
rabbits in vivo. Aim 3. Validate the short and long-term efficacy and safety of PUT for treating pathologic
choroidal neovascularization in vivo on a rabbit model of AMD. The outcome from this research will be proof-
of-concept that the PUT effectively and safely removes pathologic choroidal microvessels to treat AMD. We
expect that the proposed PUT device has great potential to transform our care of patients with AMD by
facilitating targeted and precise therapy while reducing the treatment burden and side effects.PROJECT NARRATIVE
Photo-mediated ultrasound (PUT) therapy utilizes the synergistic application of nanosecond laser with
ultrasound to create microcavitation bubbles which permanently shut down micro-size blood vessels based on
photoacoustic cavitation without requiring any exogenous agent. This study determines the safety of PUT in
treating the choroid and treating pathologic choroidal neovascularization mimicking macular degeneration in
animal models. This study will develop a prototype for clinical translation of this technology.