Safety and Efficacy of the Rho-Kinase Inhibitor (Ripasudil) in Bleb Needling after Trabeculectomy: A Prospective Multicenter Study

Abstract

Ripasudil, a rho-associated protein kinase inhibitor ophthalmic solution, shows a protective effect in preventing excessive scarring in vitro. This study aims to evaluate the safety and efficacy of ripasudil for glaucoma patients submitted to the needling procedure. In this prospective, multicenter, single-arm study, we included 20 eyes of 20 patients with glaucoma who underwent the needling procedure without antimetabolites. All patients administered ripasudil after needling for three months. The primary endpoint of this study was the safety of ripasudil in patients, and the secondary endpoint was the change in IOP at 12 weeks after the needling procedure. No serious complications were found in the patients. One eye experienced pruritus and conjunctival follicle, while another eye had conjunctival follicle. These complications were transient and resolved quickly after discontinuation of ripasudil. The mean preoperative IOP was 14.6 ± 4.6 mmHg, which decreased to 11.0 ± 4.7 mmHg (p = 0.0062) at 1 week postoperatively. The IOP reduction effect continued to 12 weeks (11.8 ± 3.1 mmHg; p = 0.0448). The administration of the ROCK inhibitor, ripasudil, after the needling procedure is safe and effective in maintaining IOP for 12 weeks.

Keywords: a rho-associated protein kinase inhibitor; glaucoma; needling; ripasudil; trabeculectomy.

Figure 1

Preoperative and postoperative mean IOPs (mmHg). Error bars show standard deviation. The mean preoperative IOP was lowered immediately after the needling procedure (p = 0.0006, Wilcoxon’s rank sum test). The effect of IOP reduction was continued to 12 weeks (p = 0.0012, Wilcoxon’s rank sum test). Error bars show the standard deviation.

Figure 2

Kaplan–Meier survival plot for absolute success. We characterized absolute success as achieving a >20% reduction in IOP from the preneedling baseline without the use of antihypertensive medications (excluding the instillation of ripasudil). If the IOP exceeded the predefined criteria in two consecutive measurements, failure was deemed to have occurred at the initial time point when the IOP first exceeded the criteria. The necessity for repeat needling or an alternative glaucoma surgical intervention was categorized as a failure.

Figure 3

Kaplan–Meier survival plot for relative success. We characterized relative success as achieving an IOP within the following ranges: (A) 4 mmHg or higher but less than 22 mmHg, (B) 4 mmHg or higher but less than 19 mmHg, (C) 4 mmHg or higher but less than 16 mmHg, or (D) 4 mmHg or higher but less than 13 mmHg. If the IOP exceeded the defined criteria in two consecutive measurements, failure was deemed to have occurred at the initial time point when the IOP first exceeded the above criteria. The necessity for repeat needling or another glaucoma surgical intervention was classified as a treatment failure. Note: Survival rate and censoring of Relative success B were equal to Relative success A.