<p>Ripasudil Hydrochloride Hydrate in the Treatment of Glaucoma: Safety, Efficacy, and Patient Selection</p>

Abstract

Reduction of intraocular pressure (IOP) is the only reliable treatment for glaucoma that maintains the patient's visual function throughout life, and IOP-lowering eyedrops are the mainstay of therapy. Ripasudil hydrochloride hydrate (brand name: Glanatec ophthalmic solution 0.4%; Kowa Company, Ltd., Japan) is a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor that lowers IOP by increasing conventional aqueous outflow. Since the approval of ripasudil eyedrops in 2014, a large store of clinical data has been amassed in Japan. With regard to safety, conjunctival hyperemia is the most common adverse drug reaction (ADR) and is usually transient and mild. Blepharitis and allergic conjunctivitis are other major local ADRs. Systemic ADRs are rare, but we should be wary of allergic reactions. With regard to efficacy, ripasudil is expected to lower IOP in almost all glaucoma subtypes (including primary open-angle glaucoma, secondary glaucoma, and primary angleclosure glaucoma) and in all patterns of treatment initiation (monotherapy, combination therapy, switching therapy, and add-on therapy). However, the status of the trabecular meshwork may affect the IOP-lowering effect of ripasudil. In patient selection, current evidence-based information on the safety and efficacy of ripasudil should be fully considered. As irreversible damage to the trabecular meshwork would considerably affect efficacy, it may be better to start ripasudil treatment during an early stage of glaucoma.

The ROCK Inhibitor Ripasudil Shows an Endothelial Protective Effect in Patients With Low Corneal Endothelial Cell Density After Cataract Surgery

“…The safety of ripasudil is well established, and since 2014 it has been available in Japan for the treatment of glaucoma. 19 , 20 In the present study, we sought to assess whether ripasudil may have broader application in the clinic. We assessed this by using the ROCK inhibitor ripasudil in patients with glaucoma with low corneal endothelial cell density who were undergoing cataract surgery.…”

Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function

“…Some ROCK inhibitors ( Table 4 ) have also been tested in all clinical trial phases for the treatment of glaucoma and ocular hypertension [ 369 ] and could play a role in the treatment of acute lung injury [ 370 ]. Three ROCK inhibitors that indirectly induce F-actin depolymerization through blocking the signaling pathway that leads to NMMII activity [ 371 ] are approved for clinical use: fasudil in Japan for the treatment of cerebral vasospasm (1995) [ 372 ]; ripasudil, also in Japan, for treatment of glaucoma (2014) [ 372 , 373 , 374 ]; and netarsudil, which was authorized in the US after FDA approval [ 375 ]. Fluvoxamine, which is a selective serotonin uptake inhibitor that inhibits actin polymerization, is approved as an anti-depressant [ 376 ].…”

Rho-Kinase Inhibitors – A New Broad-Spectrum Treatment in Ophthalmic Diseases. A Review

“…This fasudil derivative was first approved in Japan in 2014 under the trade name Glanatec ® , previously called K-115 [22]. This drug appears to play an important role in attenuating the evolution of glaucoma through its hitherto known mechanisms of action: it increases the outflow of aqueous humour by altering conventional pathways, on one hand, and neuroprotection, on the other [10,49,93]. Ripasudil 0.4% is currently used in patients with POAG, PACG (primary angle closure glaucoma), uveitic glaucoma, steroid-induced glaucoma, exfoliative glaucoma or in patients with ocular hypertension (OHT) and appears to have a beneficial effect in patients with increase in intraocular pressure (IOP) secondary to uveitis [48,56,58,101].…”