Ultrasound-mediated transscleral delivery of Avastin to the posterior segment of rabbit eye in vivo

Abstract

Purpose: Due to large molecular size and the unique barriers of the eye, Anti-VEGF antibodies require administration via intravitreal injection for the treatment of Wet Macular Degeneration (AMD). To avoid complications of injections, we investigated the practical efficacy and safety of avastin delivery using a novel needle-free drug delivery system -SonoEye (Seagull Technology).

Methods: SonoEye works by among other things, incorporating drug into a gel and sending out an ultrasonic pulse which propels the drug from the gel into the eye. Optimal parameters for the SonoEye were determined in-vitro. Avastin integrity was verified by Gel Electrophoresis. Safety was assessed with scleral fibroblast cells in vitro using the Resazurin Viability Assay. In vivo transscleral delivery of Avastin was performed on New Zealand White rabbits. The distribution of Avastin in ocular tissues post treatment was determined by ELISA. In-vivo safety was assessed by Optical Coherence Tomography(OCT) and Electroretinography(ERG). Post mortem histological assessment was performed.

Results: Efficacy study: The amount of Avastin delivered by the SonoEye device was proportional to the duration of application and the ultrasonic frequency employed. It was significantly greater (p<0.001) than passive delivery by diffusion. In vivo study revealed that Avastin was present in treated eye tissues with the highest concentrations recorded in the cornea 110ng/g (tissue) and 24ng/g (tissue) in retina/choroid. Safety study: Gel Electrophoresis confirmed no change in the molecular weight or integrity of Avastin released from the gel. Ultrasound caused no decline in fibroblast metabolic activity as measured by Resazurin assay. Repeated use of the SonoEye at the same location on live rabbit eyes over 2 weeks caused no change in the mean posterior retinal thickness measured by OCT. ERG results were unchanged and consistent with pre-treatment measurements and no difference was observed between contralateral and treated eyes. Histological assessment confirmed that there was no retinal pathology post SonoEye use.

Conclusions: The SonoEye device non-invasively and effectively delivered Avastin to the retina/choroid in normal rabbit eyes. This device promises a means of transscleral delivery of anti-VEGF drugs into the eye without intravitreal injection, thereby providing a targeted less invasive alternative to conventional therapies for AMD.

Keywords: 412 age-related macular degeneration • 499 diabetic retinopathy • 609 neovascularization