Nitric Oxide Demonstrates Ability to Improve Outflow

■ In a study of a porcine anterior-segment perfusion model led by Susannah Waxman, MD, of the University of Pittsburgh Department of Ophthalmology and published recently in Investigative Ophthalmology and Visual Science, the effects of nitric oxide (NO) on outflow facility were compared with controls with trabecular meshwork (TM) and after circumferential ab interno trabeculectomy (AIT). Outflow structures were assessed with SD-OCT before and after application of a long-acting NO synthase inhibitor. Scans were processed with a custom macroscript and aligned for automated reslicing and quantification of cross-sectional outflow tract areas.

The researchers found that nitric oxide can dilate vessels of the distal outflow tract and increase outflow facility in a TM-independent fashion. The researchers found that short, focally constricting vessel sections display large-diameter changes and may have a substantial impact on outflow.

The researchers concluded that NO increases trabecular outflow by acting on the guanylyl cyclase pathway. NO also dilates vessels by relaxing their smooth muscles via a protein kinase-dependent activation of K channels. In this study, the researchers hypothesized that NO could increase the outflow facility in a TM-independent manner by dilating aqueous outflow tract vessels. They investigated its effect with and without circumferential AIT, developed an automated, quantitative, and live analysis of the cross-sectional area of intrascleral outflow vessels, and searched for evidence of focal dilation and constriction that may show a reactive outflow regulatory mechanism.

Glaucoma Physician editor-in-chief Nathan Radcliffe, MD, said of the data, “This animal study gives us good evidence that nitric-oxide–releasing glaucoma medications may be additive even in patients who have undergone trabecular bypass or ablative procedures by pulling fluid out of the eye by dilating the distal outflow channels. This also may explain why several TM-acting medications, such as latanoprostene bunod and netarsudil, appear to be additive. This study confirms my personal experience that our current therapies that treat the TM still appear to be effective in trabecular MIGS and prior SLT patients.”