Abstract
Purpose :
To explore the effects of NCX 470, a nitric oxide (NO)-donating prostaglandin analog, on aqueous humor dynamics in ocular normotensive non-human primates.
Methods :
Ocular hypotensive activity after topical dosing with NCX 470 ophthalmic solution 0.1% or its vehicle was tested in ocular normotensive non-human primates (n=6-12) using a randomized, investigator-masked, parallel-group design. Baseline intraocular pressure (IOP) was measured (pneumatonometer, Reichert), after which animals were treated twice daily (10:00AM & 4:00PM) for 3 consecutive days and once (AM dose) on day 4 (experimental day). On day 4 IOP measurements were taken at 90, 180 and 300min after the AM dose. Additionally, on day 4, animals were dosed topically with 10% fluorescein and fluorophotometric scans (Fluorotron Master, OcuMetrics) of the cornea and anterior chamber were taken at 45min intervals throughout the experimental period to address changes in aqueous inflow, outflow facility and uveoscleral outflow.
Results :
Baseline IOP was similar between groups (23.7±0.9 and 23.3±1.1mmHg in NCX 470 0.1% and vehicle, respectively). On day 4, the IOP reductions with NCX 470 were greater than those with vehicle and were sustained throughout the entire experimental period [Change From Baseline (CFB), NCX 470CFB =7.8±0.7, 5.5±0.9 and 6.5±1.0mmHg and VEHCFB=4.8±0.9, 2.9±0.9 and 3.5±1.4mmHg at 90, 180 and 300min post-dosing, respectively]. In addition, NCX 470 increased outflow facility (0.64±0.17 and 0.37±0.09µl/min/mmHg for NCX 470 and vehicle, respectively) and uveoscleral outflow (2.58±0.61 and 1.24±0.26µl/min for NCX 470 and vehicle, respectively) leaving unaltered aqueous inflow (1.93±0.31 and 2.03±0.22µl/min for NCX 470 and vehicle, respectively).
Conclusions :
NCX 470 increased uveoscleral outflow and outflow facility in ocular normotensive non-human primates suggesting that changes in both pathways contribute to the IOP-lowering effect of this compound.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.