Netarsudil effectively lowers IOP of glaucoma patients on maximally tolerated medical therapy: Study
Glaucoma is the second-leading cause of blindness worldwide. Although the pathophysiology of this disease is thought to be multifactorial, intraocular pressure (IOP) is currently the only modifiable risk factor to slow glaucoma progression.
Netarsudil inhibits a Rho-associated protein kinase (ROCK), leading to expansion of the juxtacanalicular trabecular meshwork and dilation of the episcleral veins, which in turn results in increased outflow facility through the conventional outflow pathway. Currently, netarsudil is the only medical therapy for glaucoma that directly targets outflow resistance through the conventional outflow pathway—pilocarpine has an indirect effect on the trabecular meshwork via pupillary constriction.
The pivotal trials for netarsudil demonstrated that it was an effective primary therapy for POAG and OHT, with comparable effectiveness to timolol and latanoprost for a specific patient population. However, few studies exist on the effectiveness of netarsudil on patients with secondary open-angle glaucoma or angle closure glaucoma, patients already on >2 IOP lowering medications, or patients with a history of glaucoma laser or surgery.
It is more commonly used in clinical practice as a supplemental therapy for patients already on multiple topical medications and patients with inadequately controlled IOP despite prior glaucoma laser or surgery; clinical scenarios for which the pivotal trials do not offer clear data. This study by Villegas and Lee seeked to better inform clinicians on the effectiveness of netarsudil in the clinical scenarios for which it is commonly used in real-world practice.
This was a retrospective study of patients started on netarsudil at Stanford University. Exclusion criteria included glaucoma surgery or laser within 6 months of starting netarsudil and other modifications to the baseline medication regimen within 4 weeks of starting netarsudil. The primary outcome was treatment success, defined as IOP reduction meeting a predetermined target, and no further medication, laser, or surgery recommended subsequent to starting netarsudil.
Sixty-two eyes were included, and 36 (58%) achieved treatment success at first follow-up. Mean baseline IOP was 19.5 ± 5.6 mmHg on a mean of 3.5 ± 0.7 ocular hypotensive medications. The mean change in IOP from baseline to first follow-up was −3.53 mmHg (−17%). In patients who achieved treatment success, mean IOP change was −5.22 mmHg (−28.0%). Of the eyes with baseline IOP ≤ 20 mmHg, 69% achieved treatment success, compared to only 17% of eyes with baseline IOP ≥ 21 mmHg (P < 0.05).
In this study, netarsudil was found to be effective in significantly lowering IOP for patients already on MTMT. Moreover, it was successful in achieving a pre-specified target IOP in 58% of eyes for which glaucoma laser or surgery would be the only remaining therapeutic option in the absence of this drug. In these eyes, the IOP reduction was on average a robust 5.22 mmHg, or 28% from pretreatment baseline, which is clinically significant as it resulted in a significantly reduced likelihood of undergoing glaucoma surgery during the study period.
Study results indicate that netarsudil is more likely to successfully achieve a pre-specified target IOP when baseline IOP is ≤20 mmHg. The reason for this may be multifactorial. First, it is likely that patients with a lower baseline IOP require a smaller absolute reduction in IOP in order to meet their IOP target. Secondly, it is possible that eyes with a very high IOP despite otherwise MTMT have more severe aqueous outflow pathway dysfunction that is less likely to respond to netarsudil. Finally, netarsudil's possible effect on episcleral venous pressure may lead to increased effectiveness in eyes with lower baseline IOP. These findings suggest that clinicians should temper their expectations when adding netarsudil in patients with a baseline IOP of ≥21 mmHg.
Adding netarsudil 0.02% once daily to glaucoma patients with inadequate IOP reduction on otherwise maximally tolerated medical therapy can result in significant IOP reduction, thus deferring the need for glaucoma laser or incisional surgery. Treatment success under these circumstances may be more likely when baseline IOP is ≤20 mmHg
Source: Villegas and Lee; Clinical Ophthalmology 2021:15
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