Intraocular pressure-lowering effects of ripasudil in uveitic glaucoma, exfoliation glaucoma, and steroid-induced glaucoma patients: ROCK-S, a multicentre historical cohort study

Futakuchi, Akiko; Morimoto, Takeshi; Ikeda, Yoko; Tanihara, Hidenobu; Inoue, Toshihiro

doi:10.1038/s41598-020-66928-4

Cited by 33 publications

(25 citation statements)

References 22 publications

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“…The significant reduction in IOP was seen when patients were categorized by type of disease, baseline IOP values, and the number of concomitant pharmaceutical components for glaucoma, with the exception of patients with neovascular glaucoma. In all of the other subtypes of secondary glaucoma assessed in this PMS study, large changes in IOP were observed over 24 months, supporting previous research that has shown that ripasudil is effective in patients with exfoliation, uveitisassociated, and steroid-induced glaucoma [34][35][36]. In the pathogenesis of neovascular glaucoma, fibrovascular proliferative tissue seriously damages the conventional aqueous humor outflow [37], and, as such, this may explain why ripasudil did not significantly reduce IOP in these patients.…”

Section: Confidence Interval Hr Hazard Ratiosupporting

confidence: 83%

Long-Term Intraocular Pressure-Lowering Effects and Adverse Events of Ripasudil in Patients with Glaucoma or Ocular Hypertension over 24 Months

et al. 2022

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Introduction: Glaucoma is a leading cause of irreversible blindness and ripasudil was the first Rho kinase inhibitor approved as antiglaucoma medication. Here we present the final analysis of the ROCK-J study, a large-scale post-marketing surveillance study to evaluate the long-term safety and effectiveness of ripasudil in Japanese patients with glaucoma or ocular hypertension in a real-word clinical setting. Methods: ROCK-J was a 24-month, prospective, open-label, observational study that included ripasudil-naı ¨ve patients with glaucoma or ocular hypertension who were initiating treatment with ripasudil according to the Japanese approved indication between June 1, 2015 and April 30, 2017. The primary safety endpoint was the incidence of adverse drug reactions (ADRs) (including blepharitis, plus assessment of its background factors); the primary efficacy endpoint was change in intraocular pressure (IOP) from baseline to 24 months. Results: A total of 3374 Japanese patients with glaucoma or ocular hypertension were evaluated for safety and 3178 for effectiveness of ripasudil over a mean 524.5-day observational period. Overall, 853 (25.3%) patients experienced adverse drug reactions; the most common were blepharitis (8.6%), conjunctival hyperemia (8.5%), and conjunctivitis (6.3%). Multivariate analyses demonstrated that patients were more likely to experience the ADR blepharitis with ripasudil treatment if they were female (hazard ratio [HR] 1.307; p = 0.040), had comorbid or a previous history of blepharitis (HR 2.178; p = 0.001), or had a history of allergy to pollen (HR 1.645; p = 0.003) or medication (HR 2.276; p \ 0.001). IOP decreased significantly from baseline with ripasudil; the leastsquares mean ± standard error change in IOP from baseline to 24 months was -2.6 ± 0.1 mmHg (p \ 0.001). Significant IOP changes were seen in four types of glaucoma, namely primary open-angle glaucoma, normaltension glaucoma, primary angle-closure glaucoma, and secondary glaucoma, and ocular hypertension. Conclusion: Ripasudil was safe and effective as an antiglaucoma medication with no new safety signals identified and significant reductions in

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Section: Confidence Interval Hr Hazard Ratiosupporting

confidence: 83%

Long-Term Intraocular Pressure-Lowering Effects and Adverse Events of Ripasudil in Patients with Glaucoma or Ocular Hypertension over 24 Months

et al. 2022

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“…Although the preoperative IOP was similar in both groups, the IOP before the administration of ripasudil in the effective group was significantly higher than that found in the non-effective group. Other previous studies reported that the IOP reduction after the administration of ripasudil was associated with higher baseline IOP levels 27 , 28 . Our results support the findings of these previous studies.…”

Section: Discussionmentioning

confidence: 82%

Responsiveness to ripasudil may be a potential outcome marker for selective laser trabeculoplasty in patients with primary open-angle glaucoma

Baba

Hirooka

Nii

et al. 2021

Sci Rep

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We examined responsiveness to ripasudil as a potential factor for predicting the effect of selective laser trabeculoplasty (SLT) when performed for primary open-angle glaucoma (POAG). A total of 70 eyes with no history of glaucoma surgery underwent SLT between January 2015 and June 2019. Patients were divided into two groups, with an intraocular pressure (IOP) decrease of 15% or more due to ripasudil administration before SLT defined as the effective group, while an IOP decrease of less than 15% was defined as the non-effective group. Kaplan–Meier survival analysis was performed. A Cox proportional hazards model assessed the influence of baseline factors on the success. Of the 70 eyes evaluated, treatments were effective in 22 and non-effective in 48. Postoperatively, both groups exhibited IOP reductions for up to 24 months. Success ratios at 12 and 24 months after SLT were 43.5% and 18.5% in the effective versus 24.9% and 9.3% in the non-effective group, which were significantly higher in the effective group (P = 0.03). Presence of a ripasudil effective eye (P = 0.03) was associated with treatment success. Responsiveness to ripasudil may be useful in predicting the therapeutic effect of SLT.

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“…TM outflow promoting drugs include the muscarinic receptor agonist pilocarpine (Osterlin et al, 1994;Toris et al, 2001), rho kinase (ROCK) inhibitors such as Y-27632 (Honjo et al, 2001), ripasudil (Futakuchi et al, 2020) and netarsudil (Lin et al, 2018;Serle et al, 2018) and NO-producing drugs (e.g., latanoprostene bunod; Cavet et al, 2014). While pilocarpine and FP-receptor agonists lower IOP by promoting the release of MPPs from the TM/CM cells to help digest some of the ECM and thereby create holes for AQH to leave the ANC.…”

Section: Pharmaceutical and Cellular Therapeutics To Lower Intraocular Pressurementioning

confidence: 99%

“…Due to their lower efficacy, these drugs are t. o. dosed at least twice-daily (ROCK inhibitors) and ≥ 4-times-daily for pilocarpine. Ripasudil for instance lowered IOP in various forms of glaucoma by 19.4-23.4% from baseline followed over 1-6 months, while netarsudil yielded 23-24% reduction of IOP with OHT/POAG patients followed for 3 months (Futakuchi et al, 2020). The mechanism of action of the ROCK inhibitors is by way of relaxing the TM/CM and allow the larger surface area of the TM to efflux the AQH.…”

Section: Pharmaceutical and Cellular Therapeutics To Lower Intraocular Pressurementioning

confidence: 99%

Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies

Sharif

2021

Front. Pharmacol.

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Damage to the optic nerve and the death of associated retinal ganglion cells (RGCs) by elevated intraocular pressure (IOP), also known as glaucoma, is responsible for visual impairment and blindness in millions of people worldwide. The ocular hypertension (OHT) and the deleterious mechanical forces it exerts at the back of the eye, at the level of the optic nerve head/optic disc and lamina cribosa, is the only modifiable risk factor associated with glaucoma that can be treated. The elevated IOP occurs due to the inability of accumulated aqueous humor (AQH) to egress from the anterior chamber of the eye due to occlusion of the major outflow pathway, the trabecular meshwork (TM) and Schlemm’s canal (SC). Several different classes of pharmaceutical agents, surgical techniques and implantable devices have been developed to lower and control IOP. First-line drugs to promote AQH outflow via the uveoscleral outflow pathway include FP-receptor prostaglandin (PG) agonists (e.g., latanoprost, travoprost and tafluprost) and a novel non-PG EP2-receptor agonist (omidenepag isopropyl, Eybelis®). TM/SC outflow enhancing drugs are also effective ocular hypotensive agents (e.g., rho kinase inhibitors like ripasudil and netarsudil; and latanoprostene bunod, a conjugate of a nitric oxide donor and latanoprost). One of the most effective anterior chamber AQH microshunt devices is the Preserflo® microshunt which can lower IOP down to 10–13 mmHg. Other IOP-lowering drugs and devices on the horizon will be also discussed. Additionally, since elevated IOP is only one of many risk factors for development of glaucomatous optic neuropathy, a treatise of the role of inflammatory neurodegeneration of the optic nerve and retinal ganglion cells and appropriate neuroprotective strategies to mitigate this disease will also be reviewed and discussed.

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Intraocular pressure-lowering effects of ripasudil in uveitic glaucoma, exfoliation glaucoma, and steroid-induced glaucoma patients: ROCK-S, a multicentre historical cohort study

Cited by 33 publications

References 22 publications

Long-Term Intraocular Pressure-Lowering Effects and Adverse Events of Ripasudil in Patients with Glaucoma or Ocular Hypertension over 24 Months

Long-Term Intraocular Pressure-Lowering Effects and Adverse Events of Ripasudil in Patients with Glaucoma or Ocular Hypertension over 24 Months

Responsiveness to ripasudil may be a potential outcome marker for selective laser trabeculoplasty in patients with primary open-angle glaucoma

Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies

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