Abstract
Purpose :
To characterize the dynamics of liquid and gel spread of suprachoroidal injections delivered via microneedles in enucleated porcine eyes.
Methods :
Physicochemical formulations were delivered using a microneedle. Enucleated porcine eyes were acclimated to room temperature (~22 C) with intraocular pressure (IOP) stabilized to 17±2 mmHg prior to injections. 1% Seakem LE agarose solution (solidifying @ <37 C) was heated to ~100 C and injected suprachoroidally at volumes ranging from 5 µL to 200 µL. Eye samples were dissected and analyzed two (2) minutes post-injection. Dimethyl sulfoxide (DMSO) was injected suprachoroidally at room temperature (~22 C) with volumes ranging from 1 µL to 10 µL. Eye samples in this test group were immediately frozen to -36 C for approximately 5 minutes and dissected post-injection for analysis. Ultraviolet (UV) fluorescent particles were added to each formulation batch prior to injections to enhance visualization of spread. Image analysis was performed to characterize and quantify spread of physicochemical formulations in a gel state.
Results :
Area of gel coverage ranged from 0.1 cm2 to 2.1 cm2 in agarose injections, volumes ranging from 5 µL to 200 µL. Injections <50 µL resulted in roughly symmetrical spread profiles, but displayed more circumferential spread as injection volume increased to ≥50 µL. Average gel thickness calculations ranged between 0.4 mm to 1 mm with the assumption of uniform gel thickness. Gel coverage for DMSO was observed to occupy a larger area compared to that seen from agarose with 0.1 cm2 to 0.8 cm2 ranges in spread for 1 µL to 10 µL injection volumes.
Conclusions :
Spread profiles of physicochemical formulations delivered suprachoroidally were captured within seconds after injection. SCS injections with Seakem LE agarose displayed more circumferential spreading at injection volumes greater than 50 µL which may be due to the anatomical landscape of the SCS. Higher spread coverage seen in DMSO may be attributable to a relative lower viscosity.This study shows that formulations can cover as large as a few squared centimeters in area within a few seconds of SCS delivery. Less viscous formulations may be capable of occupying larger areas of spread compared to more viscous formulations when delivered suprachoroidally.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.