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Editors Selection IGR 16-4
Medical Treatment: Investigational drugs
Comment by Carol Toris on:
60621 Effect of AR-13324 on Episcleral Venous Pressure in Dutch Belted Rabbits, Kiel JW; Kopczynski CC, Journal of Ocular Pharmacology and Therapeutics, 2015; 31: 146-151
The report by Kiel and Kopczynski is a rare study that specifically investigated alteration in episcleral venous pressure (EVP) as a means to lower intraocular pressure (IOP). The drug of interest was AR-13324, a combined rho-associated protein kinase (ROCK) inhibitor and norepinephrine transporter (NET) inhibitor. EVP was thought to decrease with drug treatment via its NET inhibition. However, the experimental design could not eliminate a contribution from the ROCK inhibition. AR-13324 was administered to Dutch belted rabbits for two days and the carefully controlled methods by Kiel were used to measure EVP, IOP, arterial pressure, carotid blood flow and heart rate. Compared to baseline or vehicle treatment, the drug decreased EVP and IOP without affecting the cardiovascular parameters. It was concluded that EVP is an important, but not sole contributor to the IOP reduction by AR-13324 in this animal model.
The methods by Kiel are technically challenging and cannot be used in awake animals or humans. Unfortunately, available noninvasive methods are subjective and highly variable. Often, in studies of aqueous humor dynamics, EVP is not measured but rather assumed to be unchanged by the experimental manipulation. The interaction of blood flow, vascular resistances, arteriovenous anastomoses, and muscular veins is so complex that it becomes difficult to assume anything regarding a drug effect on episcleral veins. Both vasodilators and vasoconstrictors have been reported to decrease EVP. Clearly, studies of aqueous humor dynamics are incomplete without assessing the pressure in these veins. Kiel's study reminds us of this point. Improved methods are sorely needed to make accurate EVP assessment more obtainable.
A secondary finding of the Kiel study is that Dutch belted rabbits have normal IOPs in the high range (30 mmHg or more) yet they do not suffer from glaucoma. The arterial pressure in these animals is relatively high making the ocular perfusion pressure high which apparently is protective in these animals. This supports the idea that ocular perfusion pressure may be a more important risk factor for glaucoma than IOP alone.
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