Photo-mediated ultrasound therapy as a novel method to selectively treat eye vasculature

Abstract

Purpose : Pathologic microvasculature plays a pivotal role in the leading causes of blindness including diabetic retinopathy, retinal vein occlusions, and macular degeneration. Conventional laser treatment results in collateral thermal damage. We developed a novel treatment called photo-mediated ultrasound therapy (PUT), which uses a combination of a low intensity laser concurrently with ultrasound to selectively treats vessels without damaging surrounding tissue. We present the first evaluation of PUT on rabbit choroidal vessels.

Methods : An integrated therapeutic ultrasound (0.5 MHz bursts of 10% duty cycle at a rate of 10 Hz, H107 Sonic Concepts, Bothell, WA) and laser treatment system was devised. A pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (Powerlite, Continuum, Santa Clara, CA) produced 532 nm laser pulses with 3-ns pulse duration and 10-Hz repetition rate at the beginning of each ultrasound burst. Sixty New Zealand white rabbits were used. Fundus photography and indocyanine green angiography (ICGA) were acquired using the Topcon 50EX Fundus Camera and Digital Imaging System (Topcon, Tokyo, Japan). ICGA was performed before, immediately after, and weekly following PUT treatment for 1 month by injecting 0.2 mL/kg of ICG into the marginal ear vein.

Results : Treatment with laser or ultrasound only resulted in no appreciable vascular changes. PUT treatment with laser and ultrasound was able to selectively treat the choroidal vasculature with optimized parameters. Hemorrhage occurred with 2 MPa ultrasound + 150 mJ/cm² laser (estimated at the choroidal layer) whereas 2 MPa ultrasound + 30 mJ/cm² laser caused no effect. The optimal parameters were 2 MPa ultrasound + 75 mJ/cm² laser, which caused edema immediately after treatment. By 1 week, pallor occurred in the region of treatment with greatly diminished choroidal vessels which persisted to 4 weeks (Fig 1). Indocyanine green angiography (ICGA) demonstrated a decrease in number of choroidal vessels in the region by 1 week that persisted to 4 weeks after treatment (Fig 2).

Conclusions : PUT holds significant promise as a novel, non-invasive method to precisely target blood vessels in neurovascular eye diseases by more selectively treating vasculature with minimized side-effects and no systemic photosensitizing dye.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Fundus photos of the treated eye (red circles indicate treated area)

 

ICGA of the treated eye (red circles indicate treated area)