Glaucoma is a common eye condition and a major cause of blindness. There are several Cochrane reviews of ways to treat it and these were added to in June 2022 with a new review of a class of drugs called rho kinase inhibitors. We asked lead author, Josefine Freiberg from the University of Copenhagen in Denmark to tell us about the evidence in this podcast.
Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. Glaucoma is a common eye condition and a major cause of blindness. There are several Cochrane reviews of ways to treat it and these were added to in June 2022 with a new review of a class of drugs called rho kinase inhibitors. We asked lead author, Josefine Freiberg from the University of Copenhagen in Denmark to tell us about the evidence in this podcast.
Josefine: Glaucoma is a sight‐threatening eye disease and the most common of its various types is called primary open‐angle glaucoma, which is a leading cause of irreversible blindness worldwide. One way to try to prevent its onset and progression is to reduce the pressure inside the eye, which is what rho kinase inhibitors, or ROKi for short, are intended to do.
The use of eye drops with rho kinase inhibitors was approved in Japan in 2014, in the USA in 2017 and in Europe in 2019. Although these drugs work by lowering the pressure in the eye, they act on different targets than traditional glaucoma medications, such as latanoprost and timolol.
As rho kinase inhibitors become more widely available and used, we decided to do this review to evaluate their efficacy and potential to cause adverse effects. We searched for trials that had compared a rho kinase inhibitor versus placebo or other glaucoma medication in people diagnosed with open-angle glaucoma or ocular hypertension. Our key interest was glaucoma progression, defined as additional visual field defects at least 12 months after a baseline assessment, but there was no direct evidence on this.
Instead, the 17 randomized trials that we found evaluated the effects of treatment by measuring the pressure in the eye and recording adverse events. The trials included a total of nearly 5000 adults diagnosed with primary open‐angle glaucoma or high eye pressure and tested one of two marketed rho kinase inhibitor-based drugs: netarsudil or ripasudil. They varied in treatment duration from 24 hours to 12 months, and 16 of the 17 studies were funded by pharmaceutical companies, while the other did not provide information about its funding.
Turning to the effects on eye pressure, but with reservations because of the limited amount and quality of research to date, the current evidence suggests that monotherapy with a rho kinase inhibitor reduces eye pressure in people diagnosed with primary open‐angle glaucoma or high eye pressure. The findings from the included trials showed that although netarsudil might be better at lowering eye pressure than placebo, traditional drugs such as latanoprost and timolol may reduce the eye pressure even more. The combination of netarsudil and latanoprost probably further reduces eye pressure compared to either drug on its own. We also found that combining ripasudil with timolol may reduce eye pressure compared with timolol monotherapy. However, all the differences were small and might not be clinically significant.
In regard to adverse events, although more people treated with rho kinase inhibitors may have experienced eye-related adverse events, we are not very certain about this because of the inconsistent reporting of adverse events across the trials. However, it is reassuring that we found no evidence of particular serious adverse events after treatment with a rho kinase inhibitor.
In summary, in light of all these uncertainties, we need future trials to be sufficiently large, and to have appropriate follow-up and consistent measurement of patient outcomes if they are to provide reliable information about glaucoma progression, eye pressure and adverse events. This would ensure the robustness of the results and provide confidence in the intermediate‐ and long‐term efficacy and safety of rho kinase inhibitors.
Mike: If you would like to find out more about the existing evidence and watch for future updates of the review if this new research gets conducted, it's available online. Just go to Cochrane Library dot com and search 'glaucoma and ROKi' to find it.