Rho kinase inhibitor safely reduces intraocular pressure

Image: PD Human eyesight with glaucoma

1. Various concentrations of Rho kinase inhibitor K-115 decreased IOP after administration compared to placebo (p<0.05). 

2. The only significant side effect was conjunctival hyperemia, which was painless and resolved within 6 hours.

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Rho kinase inhibitors are a promising new group of glaucoma medications that alter trabecular meshwork, the tissue that is the most likely cause of ocular hypertension. This phase 1 randomized controlled trial demonstrates safety of the Rho kinase inhibitor K-115 and its ability to decrease intraocular pressure (IOP). IOP appears to decrease in a dose-dependent response and lasts for approximately 24 hours, which would make K-115 a reasonable therapeutic agent. While a clinically significant decrease in IOP was observed, the repeat-administration trial showed an insignificant IOP decrease compared to placebo, demonstrating the need for a larger study with more participants. The large magnitude of IOP decrease with the placebo is surprising, and requires further investigation. An additional limitation is that a noncontact tonometer was used to measure IOP. While the study was consistent in only using noncontact tonometry, controversy remains regarding its reliability compared to the gold standard of contact tonometry. Nonetheless, the efficacy of this Rho kinase inhibitor in humans is promising. Further studies are needed to gauge the value of K-115 in glaucoma patients and how K-115 may work synergistically with other antiglaucoma medications to reduce IOP.

Click to read the study in JAMA Ophthalmology

Relevant Reading: Effects of Rho-Associated Protein Kinase Inhibitor Y-27632 on Intraocular Pressure and Outflow Facility

In Depth [randomized study]: A group of 50 healthy volunteers who had no ocular disease was identified. Subjects were randomized to the placebo or K-115, a Rho kinase inhibitor, group. Treatment was administered topically in varied concentrations (0.05%, 0.1%, 0.2%, 0.4%, 0.8%) and in either a single-administration trial or repeat-administration trial. The latter involved administration of K-115 or placebo twice daily for seven days. Slit lamp exams, including IOP measurement, were performed before administration and at several points up to 47 hours post-administration of the last dose. Eye exams were used to check for any drug reactions and serum lab tests were completed. In the single-administration trial, the IOP reduction in the 0.05%, 0.4%, and 0.8% groups was significant compared to placebo 2 hours after administration (p<0.05). In the repeat-administration trial, IOP reduction lasted for 24 hours with maximal IOP reduction occurring 1-2 hours after administration. While IOP reduction was significant at that time point within each treatment group, there was no significant difference between the IOPs of the treatment groups and placebo group. In terms of safety, conjunctival hyperemia was the most common side effect, occurring in 13-100% of patients treated with K-115 but in none given placebo. This finding resolved usually within 5-6 hours. There were no effects on visual acuity.

By Swarup Swaminathan and Andrew Bishara

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