Removal of retinal neovascularization in DL-AAA rabbit model using concurrently applied ultrasound bursts and nanosecond laser pulses

Abstract

Purpose : Retinal neovascularization (RNV) is critical to the pathogenesis of many eye diseases, including diabetic retinopathy, a leading cause of vision loss among working-age adults. A novel, controllable photo-mediated ultrasound therapy (PUT) is demonstrated to treat RNV in an in vivo rabbit model. PUT selectively removes angiogenesis by combining low intensity nanosecond pulse duration laser and ultrasound without damaging surrounding tissue.

Methods : An integrated therapeutic ultrasound (0.5 MHz bursts, 10% duty cycle, 10 Hz), laser treatment system, and CCD camera system was devised. An Nd:YAG laser produced 1064 nm laser pulses with 5-ns pulse duration and 10-Hz pulse repetition rate. Laser treatment was initiated at the beginning of each ultrasound burst with a spot size of 5 mm. An in vivo rabbit model of RNV was developed in 6 Dutch Belted pigmented rabbits with intravitreal injection of DL-alpha-aminoadipic acid (AAA) to induce stable, long-term RNV. Eight weeks after injection, RNV rabbits were treated with PUT and serially monitored for up to 4 weeks after treatment with fundus photography, fluorescein angiography (FA), OCT, and indocyanine green angiography (ICGA).

Results : In the PUT treatment group, RNV in the treatment area was effectively removed with minimal damage to the surrounding retinal and choroidal structures. Rapid regression of RNV was shown within 1-day following treatment, and vessel blockage within the treatment area remained stable for at least 4 weeks with persistent regression of RNV (Fig 1). A significant average reduction in RNV of 58.4% ± 1.9% was observed 21 days after PUT treatment. In the control group, where no treatment was used, persistent RNV remained stable for up to 52 weeks.

Conclusions : The experimental results demonstrate that a single treatment of PUT can rapidly and effectively remove RNV in this rabbit model with effects that persist for at least 1 month. Minimal treatment side effects are observed.

This is a 2021 ARVO Annual Meeting abstract.

 

Figure 1. Late phase FA (top), ICGA (middle), and color fundus photographs (bottom) of rabbit RNV. Prior = 1 day before PUT. Red circle = 5 mm treatment area. The applied ultrasound pressure was 0.48 MPa at 0.5 MHz, and the laser energy was 6 mJ at 1064 nm. Persistent removal of RNV in the treatment area is demonstrated.