4.2 Review

Status of Rho kinase inhibitors in glaucoma therapeutics-an overview

Journal

INTERNATIONAL OPHTHALMOLOGY
Volume 42, Issue 1, Pages 281-294

Publisher

SPRINGER
DOI: 10.1007/s10792-021-02002-w

Keywords

Glaucoma; Intraocular pressure; Rho-associated kinases; Aqueous humour; Trabecular meshwork; Rho kinase inhibitors

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Rho kinase inhibitors have emerged as a new class of antiglaucoma medication with diverse therapeutic potential in treating glaucoma by lowering intraocular pressure through a different mechanism, while also showing promising effects in neuroprotection and antifibrosis. However, they may come with local adverse effects such as conjunctival hyperaemia, blepharitis, subconjunctival haemorrhages, and cornea verticillata.
Medical management remains the cornerstone of glaucoma management despite advances in the surgical or laser procedures. After a leap of almost two decades of the advent of prostaglandin analogues, recently a new class of drug, Rho kinase (ROCK) inhibitors, has come to limelight because of their varied therapeutic potential in different clinical conditions of eye, especially glaucoma. Their efficacy of lowering intraocular pressure (IOP) by virtue of an entirely different mechanism of decreasing outflow resistance has ignited a series of clinical trials evaluating their potential as monotherapy or as adjunct to existing antiglaucoma medications, and three of them ripasudil, netarsudil and roclatan have even been approved for clinical use in the recent past. There are evidences suggesting their beneficial effects in glaucoma patients even via non-IOP-dependent mechanisms like neuroprotection by improving blood flow to the optic nerve and increasing ganglion cell survival. They can even act as antifibrotic agents and reduce bleb scarring after glaucoma surgery. Hence, their effective role in glaucomatous optic neuropathy is multifaceted primary being improved drainage through the conventional pathway. On the other hand, certain local adverse effects like conjunctival hyperaemia have been reported in substantial proportion of patients, while some others like blepharitis, subconjunctival haemorrhages and cornea verticillata constitute less common side effects. The purpose of this review is to summarize the discovery, evolution and recent update of clinical trials on Rho kinase inhibitors as antiglaucoma medicine and to delineate their role in existing management protocol.

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