Netarsudil lowers intraocular pressure in goniotomy-treated eyes – Tips & Results

Microinvasive glaucoma surgery (MIGS) has become a popular option to facilitate a reduction in intraocular pressure (IOP) when medical therapy has failed adequately or is not a viable option.

These procedures include a variety of approaches, including enhancing aqueous humor outflow through the trabecular meshwork (TM) or other components of the conventional pathway, such as Schlemm’s canal. MIGS is less invasive and therefore carries a lower risk of complications than traditional glaucoma surgeries such as trabeculectomy and glaucoma drainage devices (tube shunts).

However, MIGS does not always reach the target IOP. This poses a significant challenge in glaucoma management, since every millimeter of mercury above the target pressure represents an increased risk of disease progression and eventual vision loss.

Many surgeons believe that prescribing topical eye drops after MIGS does not provide additional IOP reduction, particularly when the procedure is already targeting diseased TM. My colleagues and I set out to test this hypothesis in a specific treatment scenario by evaluating the IOP-lowering effects of Netarsudil eye drops 0.02% (Rhopressa, Aerie Pharmaceuticals) in eyes with prior Kahook Dual Blade (KDB )-goniotomy compared to goniotomy-naive eyes.

KDB goniotomy (KDB, New World Medical), a common MIGS surgery, involves the removal of a small section of the TM to create an opening into Schlemm’s canal to increase aqueous humor outflow. MIGS procedures targeting TM, including KDB goniotomy, experience a “ground effect” of IOP depression due to their inability to further bypass the episcleral venous pressure (EVP) and distal resistance in the conventional drainage pathway .

Netarsudil is a Rho-kinase inhibitor thought to lower IOP through two main mechanisms:

1) increasing aqueous outflow through the TM cells, 2) reducing EVP.1 This MOA is unique compared to other available IOP-lowering pharmacological therapies. Dosed as a drop of QD and typically prescribed as adjunctive therapy, netarsudil has been shown to provide consistent IOP reduction across a range of baseline pressures.

Our retrospective chart review2 analyzed data from 50 eyes of 37 adult glaucoma patients treated with netarsudil between February 2017 and October 2020 at the Mason Eye Institute at the University of Missouri in Columbia, Missouri. The KDB group (n=25) included adult glaucoma patients who had undergone KDB goniotomy with cataract surgery and then started Netarsudil without additional ocular surgeries.

Control eyes (n=25) included those with a history of cataract surgery but without goniotomy or other angle surgery, and were started on netarsudil for at least one month with no additional ocular procedures.

The two groups had comparable baseline characteristics, including age, gender, race, and glaucoma type and severity, baseline pressure, and number of medications (all P≥0.05).

We defined the primary outcome as a ≥20% decrease in intraocular pressure at the 1-month follow-up visit compared to the intraocular pressure measured at the time netarsudil was prescribed. Secondary endpoints included adverse events to medication and frequency of medication discontinuation for any reason.

Upon completion of the analysis, we found that netarsudil had a significantly greater IOP-lowering effect in eyes treated with a prior KDB goniotomy than in eyes with no prior goniotomy.

This effect was independent of the surgical outcome of KDB goniotomy. Eighty percent of KDB treated eyes achieved netarsudil treatment success (defined as at least 20% IOP reduction) compared to 52.0% (13 of 25) of control eyes (p=0.037). The percentage IOP reduction was 29.5 ± 16.1% in the KDB-treated eyes and 19.4 ± 14.0% in the control eyes (p = 0.022).

Based on these results, which we presented at the American Glaucoma Society Annual Meeting, we hypothesize that netarsudil may enable additional IOP-lowering effects through its unique MOA targeting EVP in addition to the trabecular meshwork.

In KDB treated eyes, excision of TM at the nasal angle may allow a greater concentration of netarsudil to travel downstream to the distal drainage system and act on episcleral veins to reduce EVP, producing a synergistic effect.

The overall rate of side effects was 48.0% and were most commonly reported as redness, allergy and blurred vision. Consistent with previous studies, no side effects were serious or vision-threatening, and all resolved after drug discontinuation. The overall discontinuation rate was 58.0% with a median duration of treatment of 5.8 months before discontinuation.

Although adverse events led to some discontinuations, insurance-related challenges were the most common reason, as the timeframe in which these cases were being addressed predates the broad launch of Rhopressa, which received FDA approval in December 2017. Currently 8 out of 10 insured patients are insured with Rhopressa.3

Conclusion
Contrary to popular belief, these data clearly indicate that patients who fail to reach target IOP after angular surgery such as KDB goniotomy may benefit from postoperative use of Netarsudil.

Although side effects such as hyperemia are common, netarsudil is not known to cause systemic side effects and is generally well tolerated. Continuous improvement in insurance coverage makes this drug a viable option for many patients. The once-daily dosing also helps promote adherence.

With all of these factors in mind, and recognizing the importance of getting glaucoma patients to their target IOP, surgeons should consider prescribing this drug to patients with prior angle surgery to provide greater IOP reduction.

Of course, more research is needed to evaluate this and other combination approaches. Therefore, we are in the process of planning a randomized controlled trial to determine whether this result is solely due to the combination of KDB goniotomy and Netarsudil therapy, or whether additional IOP reduction could be achieved through the use of other topical eye drops after different ones MIGS procedure.


About the author

Jella An, MD
P: 240/482-1100
An is an optometrist based in Bethesda, Maryland, and is affiliated with several hospitals in the area, including the University of Missouri Health Care-Columbia and Harry S. Truman Memorial Veterans Hospital. She received her medical degree from McGill University School of Medicine. Haochen (Emily) Xu, BA, contributed to this article.

references
1. Tanna et al. Rho-kinase inhibitors as a novel treatment for glaucoma and ocular hypertension. ophthalmology 2018

2. Xu et al. Comparison of response to netarsudil in Kahook dual blade goniotomy-treated eyes and goniotomy-naïve eyes. Poster presented at: The American Glaucoma Society Virtual Annual Meeting; March 4, 2021.

3. Aerie Pharmaceuticals website: https://rhopressa.com/hcp/savings/. Retrieved September 28, 2021.

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