Rho-kinase inhibitors in the management of glaucoma

ABSTRACT

Introduction: Glaucoma is a group of progressive optic neuropathies in which elevated intraocular pressure (IOP) as a consequence of an increased aqueous humor (AH) outflow resistance, is the main and only clinically modifiable risk factor for its development and progression. Relaxing Trabecular meshwork (TM) tissue, Rho-Kinase (ROCK) inhibitors directly decrease resistance in the conventional AH outflow, thus resulting in a significant IOP-lowering effect.

Areas covered: The progress made in the field of ROCK inhibitors for glaucoma treatment will be discussed, referring to the recent patent literature published mainly in the last 3 years. Development and last studies conducted on the recently approved ripasudil and netarsudil will be described, along with newly reported combinations with other antiglaucoma agents. New molecular entities as ROCK inhibitors will be reported as well as new biological approaches to affect the Rho/ROCK pathway.

Expert opinion: With three drugs currently available on the market belonging to this class, ROCK inhibitors have been definitely validated as therapeutic agents for glaucoma treatment. The literature of the last 3 years confirmed the success of the soft-drug and bis-functional approaches in the design of ROCK inhibitors. However, few completely new molecular scaffolds have been reported.

KEYWORDS:

• Rho kinase inhibitors
• ROCK
• glaucoma
• soft drug
• combination approach

Article highlights

• Before the approval of ripasudil in 2014, no new drugs for the treatment of glaucoma had been introduced on the market since the mid-1990s.

• Rho-Kinase inhibitors are validated agents for glaucoma treatment, with three drugs belonging to this class available on the market.

• Clinical studies conducted in the last years on ripasudil confirmed its safe profile and highlighted its enhanced IOP-lowering effect in long-term therapy.

• The recent approval of a fixed-dose combination (FDC) of netarsudil and latanoprost confirmed the success of the combination approach in glaucoma treatment.

• Some new molecular entities have been reported in the patent literature during the last 3 years, but only few of them have been evaluated specifically as antiglaucoma agents.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.