Abstract
Purpose :
The standard volume for intravitreal (IVT) injection in large animals is 50 μL. However more nonclinical studies are requiring larger volumes of 100 μL. A full dose volume of 100 μL has been given to rabbits and Non-Human Primates with no obvious practical volume-related issues, however, no data were available to document the potential short- and longer-term effects, or procedure-related effects of administering 100 μL as single injection. During this study, 50 μL and 100 μL/eye volumes were administered as single injections to rabbits to determine the effects on intraocular pressure (IOP) and on the retina.
Methods :
Dutch Belted rabbits (N = 12, 6/sex) received 0.9% sodium chloride for injection, USP by single IVT injection of 100 μL to the right eye and 50 μL to the left eye. Eyes were evaluated by biomicroscopic and fundoscopic examination (prestudy, Days 2, 7 & 28). IOP was measured using the TonoVet® rebound tonometer (Prestudy, 2, 5, 10 & 20 minutes, Days 2, 7 & 28). Electroretinography (UTAS Bigshot with EMWin) was used to measure retinal function under scotopic (-30dB, -10dB, 0dB) and photopic (1Hz, 29Hz) conditions (prestudy, Days 2, 7 & 28). Eyes and optic nerves were collected for microscopic evaluation on Days 8 (6 rabbits) and 29 (6 rabbits).
Results :
IOP peaked 2-minutes post-dose. The higher dose volume resulted in higher IOP (right eye, 66.8 ± 6.5 mm Hg) but was not dose proportional (left eye, 54.2 ± 3.5 mm Hg). Most eyes (8/12 right eyes and 11/12 left eyes) displayed IOPs comparable to baseline (16.9-18.4 mm Hg) at the 20-minute measurement, regardless of volume received. Electroretinography showed no changes to scotopic or photopic responses and there were no ophthalmic or microscopic changes in the eyes at either volume or any time point.
Conclusions :
Administration of 50 or 100 μL of saline by single IVT injection to rabbits resulted in severe, but transient elevations in IOP. The IOP increase was greater in eyes that received 100 μL, but both returned to baseline after 20 min. The procedure and subsequent IOP spike did not result in any structural or functional changes after 8 or 29 days. These results showed that IVT volumes of 100 μL can be administered in nonclinical studies as a single injection without contributing to volume or procedure related structural or functional changes.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.