Netarsudil Joins the Glaucoma Toolbox

Normal-tension glaucoma (NTG) remains one of the more nuanced challenges in glaucoma management, particularly in patients who continue to progress despite seemingly well-controlled IOP. As Zarmeena Vendal, MD, discussed in a recent conversation with I. Paul Singh, MD, these “low-pressure progressors”—a significant source of referrals for both doctors—highlight the limitations of traditional pressure-centric approaches and underscore the need to better understand alternative mechanisms of disease.

In this context, Dr. Vendal presented findings from a randomized study evaluating the additive effects of netarsudil 0.02% (Rhopressa; Alcon) versus brimonidine 0.1% (Alphagan) in NTG patients on latanoprost 0.005% monotherapy (Figure 1). The study enrolled approximately 100 patients who were evenly divided between treatment arms, all of whom had baseline mean IOPs near 14 mm Hg after at least 6 weeks of prostaglandin analog therapy. Importantly, the study design incorporated diurnal IOP measurements (8 AM, 12 PM, and 4 PM) to better capture fluctuations that may contribute to progression in this population.

At 6 weeks, both adjunctive therapies produced additional IOP lowering, but netarsudil demonstrated a greater effect (Figures 2 and 3). Dr. Vendal emphasized that these findings are particularly notable given the low baseline pressures, where further reduction is often physiologically constrained by episcleral venous pressure. The observed efficacy of netarsudil in this setting suggests a mechanism beyond conventional trabecular outflow enhancement, potentially involving the modulation of episcleral venous pressure or other pressure-independent factors. This distinction may be especially relevant in NTG, where patients’ progression is frequently attributed to diurnal fluctuation or vascular contributors rather than absolute IOP alone.

Clinically, Dr. Vendal noted that the implications of these findings extend beyond NTG. While the study focused on normal-tension patients, she described incorporating netarsudil more broadly in those who continue to progress at lower pressures, regardless of their initial diagnosis. In practice, this includes patients with mid-teen IOPs who exhibit structural or functional progression, where traditional escalation strategies may offer limited additional benefit.

As the glaucoma treatment paradigm continues to expand, these data reinforce the importance of mechanism-driven therapy selection. For individuals at the lower end of the IOP spectrum, particularly those with ongoing progression, agents such as netarsudil may provide a meaningful adjunct by targeting pathways not addressed by conventional therapies.