Image-guided 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 and macular degeneration. Conventional laser treatment results in collateral thermal damage. A novel, image-guided photo-mediated ultrasound therapy (PUT) is developed. PUT can selectively treat blood vessels using low intensity laser concurrently with ultrasound without damaging surrounding tissue under real-time guidance of optical coherence tomography (OCT).

Methods : An integrated therapeutic ultrasound (HIFU, H107 Sonic Concepts, 0.5MHz), laser (NT-242, Ekspla, 532nm laser pulses with 3-6ns pulse duration and 1KHz repetition rate) and OCT (Ganymede-II-HR, Thorlabs) system was devised. Laser was produced at the beginning of each ultrasound burst and focused on the rabbit choroid with 10μm spot size. Twelve New Zealand white rabbits were used. Before treatment, a fundus camera (integrated with the OCT system) was used to select the target vessels. During treatment, the target vessels were monitored in real-time by OCT in B-scan mode for cavitation signals, which can induce microvessel damage through its mechanical effect. The rabbits were monitored for up to 4 weeks after treatment with fundus photography and indocyanine green angiography (ICGA).

Results : Image-guided PUT was able to precisely treat a small area of blood vessels with optimized parameters of 0.5-1.0MPa ultrasound and 50 to 75mJ/cm² laser fluence. During treatment, cavitation signals monitored by OCT can serve as a guide to evaluate therapeutic effect in real-time (Fig 1). Our results show a small area of ischemic pallor occurred in the treated area three days after treatment, indicating blood vessel occlusion. The occlusion was sustained for at least 4 weeks (Fig 2).

Conclusions : With the capability to precisely target blood vessels and precisely control the treatment effects, image-guided PUT holds significant promise as a novel, non-invasive, method to treat eye microvasculature without damaging surrounding neurons and no systemic photosensitizing dye.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

B-scan OCT images of the rabbit eye acquired before (A) and during treatment (B). The difference between pre- and in-treatment (C). Red color indicates the cavitation signals.

 

Fundus photos before treatment (a) and after treatment (b,c). ICGA before (d) and after treatment(e,f). (Red circles indicate treated area, showing nonperfusion in the region of treatment)