# Precisely removing microvessels by photo-mediated ultrasound therapy

> **NIH NIH R01** · UNIVERSITY OF KANSAS LAWRENCE · 2020 · $437,103

## Abstract

Abstract/Project Summary
Wet age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed
world. Anti- vascular endothelial growth factor (VEGF) therapy is currently the gold standard for wet AMD
treatment. However, some patients have poor response to this therapy, or develop resistance over long-term
use. A recent study demonstrated persistent fluid in 53% and 71% of patients treated monthly with ranibizumab
and bevacizumab, respectively. The other study shows that 20% of patients still become legally blind after 5
years of repeat anti-VEGF therapy. Therefore, development of an alternative therapy for AMD patients especially
poor-responders to anti-VEGF therapy is strongly desired by ophthalmology clinic. The ultimate goal of this
research is to study the capability of a new, noninvasive therapeutic technique for safely and efficiently
eliminating choroidal neovascularization (CNV) that causes vision loss in patients with wet AMD. This technique
termed photo-mediated ultrasound therapy (PUT) is agent free with high precision and high selectivity in
removing microvessels. PUT employs cavitation produced by concurrently applied short duration laser pulses
and ultrasound bursts. Importantly, PUT does not induce cavitation through laser vaporization; instead, the
cavitation is produced via photospallation, or tissue cleavage due to transient thermoelastic stress. Therefore,
the laser intensity required for PUT is much lower than conventional retinal laser, significantly reducing the risk
of unwanted damage to the retina.
The objectives of the proposed research are 1) to further understand and optimize PUT removal of microvessels,
and 2) to evaluate the safety and efficacy of image-guided PUT in inducing regression of CNV in a well-developed
animal model. The central hypothesis is that, by combining with an advanced eye imaging system, PUT can
specifically remove microvessels created by CNV without damaging surrounding tissues. Two Specific Aims will
be developed to test this hypothesis. Aim 1): Via the experiments on a well-developed in vitro model and
mathematical modeling, determine to what extent PUT-produced cavitation induces vasoconstriction of a blood
vessel. The role of laser and ultrasound during PUT will be evaluated experimentally in an in vitro whole blood
model by quantifying cavitation bubble formation. Aim 2): Via the studies on a rabbit model, evaluate the efficacy
and safety of imaging-guided PUT for removing single pathological microvessels in the choroid in vivo. To
optimize the technology in anticipation of future studies on personalized treatment of patients, an imaging system
with optical coherence tomography (OCT) and photoacoustic (PA) functions will be integrated for real-time
feedback and guidance. Fundus photography, fluorescein angiography, indocyanine green angiography, OCT,
electroretinography, histopathology, electron microscopy, and immunohistochemistry will be performed up to...

## Key facts

- **NIH application ID:** 9987642
- **Project number:** 5R01EY029489-03
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Xinmai Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $437,103
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987642

## Citation

> US National Institutes of Health, RePORTER application 9987642, Precisely removing microvessels by photo-mediated ultrasound therapy (5R01EY029489-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9987642. Licensed CC0.

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