Abstract
Purpose :
Netarsudil 0.02% ophthalmic solution (Rhopressa™; Aerie Pharmaceutical) is a Rho kinase inhibitor recently approved by the FDA for lowering intraocular pressure (IOP) in patients with OAG or ocular hypertension. The purpose of this study was to evaluate for the first time its efficacy and safety in normal and OAG-affected canines, an important translational large animal species.
Methods :
Testing was performed in 5 normal and 5 ADAMTS10-OAG dogs between 1.0-2.7 yrs of age. In each dog, the left or right eye was randomly selected for netarsudil treatment. Contralateral eyes were sham treated with balanced salt solution (BSS). Following a 1-wk baseline period, dogs were treated once daily (q24h) during wk 2, and twice daily (q12h) during wk 3; wk 4 served as washout period. Efficacy was evaluated and compared between treated and sham eyes within each group by diurnal IOP and pupil measurements. Safety measures were assessed by routine ophthalmic examination, gonioscopy and pachymetry, and included conjunctival hyperemia, comfort level, and central corneal thickness (CCT). Statistical analysis was performed to compare IOP, pupil diameter, conjunctival hyperemia, CCT for treated vs. sham eyes within each group.
Results :
Baseline IOPs were 18.5±0.5mmHg (mean±SEM) for normal and 27.8±1.0 mmHg for OAG dogs. Even though mean IOPs were lower with netarsudil vs. sham, the difference was neither significant nor clinically relevant with q24h and q12h administration (q24h-normal: sham 16.0±0.3 mmHg vs. treatment 15.3±0.5 mmHg; q24hr-OAG: sham 26.1± 0.5 mmHg vs. treatment 26.0± 0.6 mmHg; q12hr-normal: sham 15.4±0.4 mmHg vs. treatment 14.4±0.4 mmHg; q12hr-OAG: sham 26.3±3.3 mmHg vs. treatment 25.4±1.0 mmHg). Netarsudil administration resulted in significant, moderate to severe conjunctival hyperemia in all treated eyes; this was more severe in the OAG group (p<0.001). No other adverse effects were observed.
Conclusions :
Except for a 100% incidence of conjunctival hyperemia, topically administered netarsudil 0.02% ophthalmic solution was well tolerated by dogs. The treatment did not result in a significant reduction of IOP in normal and OAG-affected dogs. It remains to be shown if netarsudil has a synergistic effect in canines when combined with other compounds such as latanoprost (Roclatan™; Aerie Pharmaceutical).
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.