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    Novel glaucoma drug lowers IOP by unique combination of mechanisms

    Small study analyzes effects of once-daily dosing on aqueous humor dynamics

    A study of normal volunteers has shown once-daily dosing of netarsudil mesylate ophthalmic solution 0.02% (Rhopressa, Aerie Pharmaceuticals) lowered IOP relative to baseline by increasing outflow facility and decreasing episcleral venous pressure (EVP).1

    Arthur J. Sit, MD, associate professor of ophthalmology, Mayo Clinic, Rochester, MN, and colleagues randomly assigned 10 healthy subjects (mean age 39 ± 14 years) to receive netarsudil 0.02% in one eye and its vehicle in the contralateral eye once daily in the morning for 7 days in a double-masked, vehicle-controlled, paired comparison study to evaluate the effect of netarsudil 0.02%, which inhibits Rho Kinase as well as the norepinephrine transporter, on aqueous humor dynamics (AHD).

    It is generally accepted that aqueous humor secretion and outflow regulation are physiologically important in order to maintain IOP at a normal range.2 Both the ciliary body and the trabecular meshwork are key components of AHD. According to a review article, the uveoscleral outflow pathway “is relatively independent of the IOP,” and as people age, the proportion of aqueous humor leaving the eye decreases.2

     

    Study methods, results

    For this study, outflow facility was measured by digital Schiøtz tonography. EVP was measured by using an objective, computer-controlled venomanometer and image analysis software.

    Aqueous humor flow rate was measured by anterior segment fluorophotometry. AHD variables measured at 1 week were compared with those measured at baseline.

    Mean IOP in the treated eyes decreased from 17.0 ± 2.5 to 12.4 ± 2.2 mm Hg, compared with a decrease of only 0.7 mm Hg in the vehicle-treated eyes. Netarsudil-treated eyes showed an increase in outflow facility of 19% (p = 0.02) and a decrease in EVP of 9% (p = 0.01).

    Outflow facility also increased in netarsudil-treated eyes (p < 0.001). Aqueous humor flow rate and uveoscleral flow rate did not change (p > 0.05). For the vehicle treated eyes, there was no change in any AHD variables.

    Consistent with previous reports on netarsudil, subjects reported conjunctival hyperemia.

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