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Editors Selection IGR 16-3

Medical Treatment: New Drugs

Comment by Ivan Goldberg on:

It has been almost 20 years since ophthalmologists have had access for our patients to a new class of topical ocular hypotensive agents. As we have been anticipating the arrival of the Rho-kinase inhibitors, which reduce intraocular pressure (IOP) by modulating conventional trabecular aqueous outflow, it is gratifying to see peer-reviewed publications like this one analyzing the potential for these agents; this allows us to consider how we might be able to include them into our treatment paradigms.

Even though it is an open-label study, this prospective assessment of efficacy and safety in a Japanese population over 52 weeks, compares monotherapy with 0.4% ripasudil (K-115) twice daily with its additive effects to commonly used agents: prostaglandins, beta-blockers and finally fixed combinations where the ripasudil was agent number three. Helpfully, the study also sub-divided patients into those with primary open-angle glaucoma (POAG), exfoliative glaucoma and ocular hypertension (OHT) as well as those with lead-in IOPs greater than or less than 21 mmHg.

Not only for the overall group, but for every sub-group as well, the results demonstrated clinically- relevant IOP reduction. For the monotherapy group, IOP reduction was 2.6 (trough) to 3.7 (peak) mmHg; as expected this was somewhat less when ripasudil was added to a betablocker (2.2 to 3.0), less when added to a prostaglandin (1.4 to 2.4), but when added to a fixed combination, notably 1.7 trough and 1.7 peak. As indicated, these would be helpful add-ons for patient management. Also unsurprisingly, efficacy was greater when baseline IOP was higher and less for exfoliative glaucoma than for OHT or POAG.

What about side effects? Conjunctival hyperemia was common (97%) but usually transient and relatively mild. A greater potential limitation was allergic blepharitis and allergic conjunctivitis (mechanism not yet determined) that lead to almost 15% discontinuation, with onset most frequently some 12-36 weeks after initiation.

Given these results, mirroring data for sibling rho-kinase inhibitors under assessment, it seems unlikely these agents will become first-line hypotensives. Their role as add-on agents seems more promising. Congratulations to the authors for pursuing this research.

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