Rho Kinase Inhibitors in Glaucoma Management: Current Perspectives and Future Directions

Eleftherios Chatzimichail,1 Eirini Christodoulaki,1 Panagiotis AG Konstas,2 Georgios N Tsiropoulos,3 Efstratia Amaxilati,3 Konstantin Gugleta,1 Zisis Gatzioufas,1,* Georgios D Panos3,4,* 1Department of Ophthalmology, University Hospital of Basel, Basel, 4031, Switzerland; 2Eye Centre of Greece, Pylaia, Thessaloniki, Greece; 3First Department of Ophthalmology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham, UK*These authors contributed equally to this workCorrespondence: Georgios D Panos, First Department of Ophthalmology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, Kiriakidi 1, Thessaloniki, 54636, Greece, Tel +30 231 330 3110, Email [email protected]: Glaucoma is a group of eye conditions characterised by optic nerve damage and visual field loss, representing the leading cause of irreversible blindness worldwide. Glaucoma exerts substantial global impact on visual impairment and blindness. The management of glaucoma has traditionally relied on medications such as prostaglandin analogs, beta-blockers, alpha agonists, and carbonic anhydrase inhibitors, which aim to lower intraocular pressure through various mechanisms. Rho kinase (ROCK) inhibitors have recently emerged as a novel class of antiglaucoma drugs, offering an alternative approach by enhancing aqueous humour outflow through the conventional pathway. Recent clinical studies assessing the efficacy and safety of Ripasudil (K-115) and Netarsudil (AR-13324) have demonstrated promising outcomes in the treatment of various types of glaucoma. Comparative studies have shown that ROCK inhibitors are non-inferior to traditional antiglaucomatous medications, such as beta-blockers and prostaglandins. Additionally, emerging evidence suggests their neuroprotective properties, which may play a role in preserving retinal ganglion cells. Furthermore, positive outcomes have been observed when these agents are used in conjunction with glaucoma filtering surgery, potentially enhancing surgical success rates. Adverse effects, including conjunctival hyperemia, cornea verticillata, conjunctivitis, and blepharitis, have been reported following the use of ROCK inhibitors. However, those side effects appear to be subtle in most cases. This review aims to provide an overview of ROCK inhibitors, focusing on their mechanisms of action, clinical efficacy, safety profiles, and additional benefits for eye health. Furthermore, further potential applications of ROCK inhibitors in glaucoma management are going to be discussed.Keywords: Rho-associated protein kinase, Rho-kinase, ROCK inhibitors in glaucoma, ripasudil, netarsudil, K-115, AR-13324