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Jun 16 2008

Altered Nitric Oxide System in Patients with Open-Angle Glaucoma

posted by: Suraj Afshar, OD

This recent study performed by affiliates of the Medical University of Vienna, Austria investigated the ocular blood flow response to systemic nitric oxide synthase inhibition in patients with primary open-angle glaucoma. This is the first in vivo study to find that there is evidence of an altered ocular nitric oxide/arginine system in patients with glaucoma and normalizing this system, which in turn normalizes ocular blood flow, may be beneficial in neuroprotection of retinal ganglion cells.

Methods/Procedures: The study included 12 patients with POAG, mean age 60, and 12 age-matched comparison subjects. All participants of the study completed a full medical examination, blood cell counts, and ophthalmological exams 4 weeks prior to the study day. All POAG patients were defined based on the Ocular Hypertensive Treatment Study, and excluded other types of glaucoma or those who have had glaucoma surgery. All patients were asked to discontinue their anti-glaucoma medications on the day of the trial. Both patients and comparison subjects were asked to discontinue their regular medications for the day of the trial and refrain from ingestion of caffeine and alcohol 12 hours prior to the trial day.

On the day of the trial patients and comparison subjects were intravenously administered L-NMMA, a competitive inhibitor of NO synthase (NOS). All measurements were taken 10, 20 and 30 minutes after L-NMMA administration. Blood pressure was taken on the upper arm by an automated oscillometric device. Choroidal and optic nerve head blood flow were measured by laser Doppler flowmetry and a regression model was applied to reduce variability. Ocular fundus pulsation amplitude, measuring the pulsatile part of blood flow in the choroidal vasculature, was determined by laser interferometry. Intraocular pressure was measured with a handheld applanation tonometer.

Results: In patients with glaucoma, optic nerve head blood flow and fundus pulsation amplitude were significantly less pronounced than the comparison group during NOS inhibition. Patients with glaucoma also showed a tendency towards reduced choroidal blood flow in response to the L-NMMA. Both study groups demonstrated comparable increase in blood pressure in response to the L-NMMA.

Caveats: Some limitations of the study include the fact that a relatively small sample of patients was used in this study. It is important to consider that patients were on regular antiglaucoma medication and although considered small, there is a minor ocular hemodynamic effect of topical antiglaucoma drugs. In addition, L-NMMA can have many side effects other than the inhibition of NOS, including muscarinic antagonism and blockage of vasodilation caused by amiloride to name a few.

Conclusions: The study data indicates an abnormal nitric oxide system in the optic nerve head and in the choroid in patients with glaucoma as compared to the healthy comparison. The NO system may be an effective and attractive target for therapeutic interventions in glaucoma.

Citation: Kaija Polak, MD; Alexandra Luksch, MD; Fatmire Berisha, MD; Gabriele Fuchsjaeger-Mayrl, MD; Susanne Dallinger, MD; Leopold Schmetterer, PhD. “Altered Nitric Oxide System in Patients With Open-Angle Glaucoma.” Arch Ophthalmol. 2007;125:494-498