Author: Yoreh Barak (Israel)
Co-authors: Hagay Drori, Matthew Lawrence, Miriam Mangelus, Avner Ingerman, Ifat Sher, Ygal Rotenstreich
Purpose
The suprachoroidal space is a potential route of administration for targeted drug delivery, as well as retinal gene therapy. This study assessed the ocular distribution and tolerance of a high volume of indocyanine green (ICG) suprachoroidal injection in Non-Human Primates (NHP) applying a novel suprachoroidal delivery system (Everads Therapy, Tel Aviv, Israel).
Setting/Venue
This non-GLP study was conducted in an integrated pre-clinical contract research facility.
Methods
Six live and six cadaver NHP eyes received an injection to the suprachoroidal space of either 150 or 200µL ICG per eye. The device’s 27-guage needle was partially and tangentially inserted into the sclera up to a controlled depth set by the device. A blunt tissue separator, made of a wire placed within the needle, was extended and retracted to create an opening into the suprachoroidal space. This was followed by an injection of ICG. The evaluations consisted of ocular dissection and direct visualization of the suprachoroidal space (cadaver eyes), tonometry, slit lamp exam, OCT, and color and ICG fundus imaging immediately and at 1, 3, and 24 h post-injection for the in-vivo eyes.
Results
Suprachoroidal dosing of 150 or 200µL ICG was successfully performed in the inferior region ~2.5 mm posterior to the limbus. Rapid distribution in the macular region was observed, with distribution throughout the posterior pole seen within 24h in all in-vivo eyes. In the cadaver eyes, ICG was notably distributed throughout the suprachoroidal space. In in-vivo eyes, no suprachoroidal bleb was observed and there was negligible ICG reflux immediately post injection. No intravitreal nor subretinal ICG was detected. Color fundus photography and ICG images revealed no retinal detachment, nor any retinal or vitreous hemorrhage. No inflammatory reaction was seen up to 24h post dosing as confirmed by slit lamp examinations. Retinal volume and thickness on OCT showed very small changes immediately after dosing which returned to normal within the first hour and remained stable. Elevations in IOP were observed immediately post injection and spontaneously returned to normal within the first hour after dosing.
Conlusions
Suprachoroidal injection of 150 or 200µL was successfully performed and well tolerated, with rapid distribution in the macular region, and throughout posterior pole by 24 h. Using this novel device to open a tangential path with its blunt tissue separator, followed by injection of therapy, may provide safe and effective delivery of retinal therapies to the macular region and posterior pole.
Financial Disclosure
Everads Therapy Ltd. I am a consultant and receive consultancy fees and options in the company.
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