A novel minimally invasive adjustable-depth blunt injector for delivery of therapeutics into the extravascular spaces of the choroid

Abstract

Purpose : To investigate the feasibility and safety of a novel minimally-invasive adjustable-depth blunt injector for pharmaceuticals and cell therapy delivery into the extravascular spaces of the choroid (EVSC).

Methods : An adjustable-depth blunt injector for delivery of therapeutics into the EVSC was developed. Two hundred and fifty microliters containing Indocyanine Green (ICG), sodium fluorescein, iron oxide nanoparticles (IONPs) or 15 million human bone marrow mesenchymal stem cells (hBMSCs) were injected into the EVSC of New Zealand rabbits using the novel injector, 3.5 mm posterior to the limbus. No immunosuppressants were used. Spectral Domain Optical Coherence Tomography (SD-OCT), fundus imaging, electroretinography (ERG) and histology analysis were performed for assessment of injection safety and efficacy.

Results : ICG, fluorescein, IONPs and stem cells were detected across the EVSC in rabbit eyes, covering over 80 percent of the posterior eye surface. Injected IONPs were retained in the EVSC for at least two weeks following injection. Stem cells were retained in the EVSC for 10 weeks following transplantation. No retinal detachment, choroidal hemorrhage or inflammation were detected in any of the injected eyes or contralateral control eyes. No reduction in retinal function was recorded by electroretinogram up to 10 week following cell transplantation.

Conclusions : This novel minimally invasive delivery system may be used to safely inject large volumes of pharmaceuticals and cell therapies into the EVSC from the same location used for intravitreal injections. Therapeutics are introduced into a new treatment reservoir compartment -the EVSC which can serve as a depot, in close proximity to the retinal pigment epithelium (RPE), throughout the surface of the RPE. This system is predicted to enhance the therapeutic effects of treatments for posterior eye disorders. Furthermore, this study demonstrates the safety of hBMSC transplantation in the EVSC compartment and is expected to directly lead to phase I/II clinical trials for hBM-MSC transplantation in retinal degeneration patients.

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