To investigate IOP lowering efficacy of rho kinase (ROCK) inhibitors, AMA0076 and Y-39983, after subchronic treatment.Methods
Dutch Belted rabbits (5 rabbits/concentration) were treated daily with a single topical dose of AMA0076 (0.05, 0.1 and 0.4%) or Y-39983 (0.025, 0.05 and 0.1%) in a masked fashion for 14 days. Saline was used as control in the contralateral eye. IOP was measured before, 3 and 7 hours after administration of the treatment. AMA0076 is a locally acting ROCK inhibitor, to reduce side effects such as hyperemia otherwise seen after administration of a ROCK inhibitor.Results
Mean baseline IOP before the start of the experiment was 21.02 ± 0.42 and 20.69 ± 0.39 mmHg for AMA0076 and Y-39983, respectively. Significant IOP reduction was observed in all AMA0076 and Y-39983 treatment groups. A maximal IOP reduction of 39 and 35% was reached with AMA0076 0.1% and Y-39983 0.05%, respectively. Initially, IOP returned to baseline values 24h after administration of AMA0076. After 3 days of treatment with AMA0076 a sustained IOP lowering effect was present, IOP did not return to baseline values, but remained significantly lower for all concentrations of AMA0076 (p<0.05). Treatment with Y-39983 did not show this sustained IOP decrease. As a result of this sustained IOP lowering effect smaller IOP fluctuations were observed in animals treated with AMA0076 compared to Y-39983. Hyperemia was observed with all concentrations of Y-39983 whereas only mild hyperemia was induced after administration of AMA0076 0.4%.Conclusion
Once daily treatment of rabbits with ROCK inhibitor AMA0076 resulted in IOP reduction that was more sustained and associated with smaller peak-through fluctuations than Y-39983.