Evaluation of Suprachoroidal Injection in Cadaveric and Preclinical Models.

Purpose: The suprachoroidal space (SCS) is a new route for delivering therapeutics to the posterior eye. Reliably reaching the SCS is difficult in humans and animal models and necessitates thorough validation of drug delivery techniques. This study quantified SCS coverage in human cadaveric eyes using micro-computed tomography (μCT) and developed injectors optimized for preclinical animal anatomy resulting in reliable SCS access. Methods: Dynamic μCT captured volumetric images during a 100 µL SCS injection in 10 cadaveric human eyes from five donors. Quantitative measurements of injection coverage, thickness, distribution, and center of volume were calculated. To improve preclinical SCS delivery, our novel TS-Micro injector was scaled to accommodate non-human primate (NHP) anatomy. Devices were tested in vivo (30 total injections, 14 animals) where delivery success was evaluated via direct visualization, and intraoperative imaging. Results: Delivery to the SCS was successful in 100% of uncompromised human cadaver eyes (80% of all eyes). Injections of 100 µL in human SCS covered 33.3% ± 5.9%. Four-dimensional μCT showed that infusate initially spreads circumferentially from the injection point then posteriorly. Delivery to NHP eyes was successful in 95% of procedures resulting in coverage consistent to human cadaveric testing. Conclusions: Results provide the first quantifiable measurement of SCS injection spread in human anatomy with validation of suprachoroidal drug delivery in the NHP that mirrors coverage in human. Translational Relevance: Cell and gene therapies require precise delivery for therapeutic efficacy, necessitating quantification of delivery in preclinical and human anatomy, as inaccurate delivery impacts efficacy of drug candidates and confounds toxicology/dose range studies.