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W Daniel Stamer, Guorong Li, Vibhuti Agrahari, Ashim K Mitra, Casey Kopczynski; Rapid reversal of corticosteroid-induced ocular hypertension by netarsudil. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3404. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The goal of the present study was to evaluate the intraocular pressure (IOP)-lowering capabilities of netarsudil, a novel rho kinase inhibitor, in a mouse model displaying the four hallmarks of human corticosteroid-induced ocular hypertension.
IOP was elevated in C57/BL6J mice by subconjunctival injection(s) (10 ml/mg/dose) of a dexamethasone-loaded nanoparticle preparation. Control cohorts of mice received subconjunctival injection(s) of PBS-loaded nanoparticles. IOP was measured daily by rebound tonometry. Effects of 4 days of topical netarsudil (0.04 % QD) were compared to vehicle treatment in mice that were exposed to either three weeks or three months of dexamethasone.
IOP was significantly elevated above control (3.9 ± 0.5 mmHg, mean±SE, p < 0.001) 10 days after dexamethasone-containing nanoparticle injection and remained elevated for four weeks without inducing weight loss/attrition like systemic minipump delivery of dexamethasone. Additional injections of dexamethasone nanoparticles were required on days 13, 28 and 62 to maintain elevated IOP for three months. Netarsudil treatment significantly lowered IOP in ocular hypertensive mice upon the first post-dose measurement, 24 hours after treatment, at both week 3 and month 3. Maximum IOP-lowering was 4.3 ± 1.5 mmHg (p=0.007) for week 3 and 4.4 ± 1.0 mmHg (p=0.001) for month 3 cohorts compared to cohorts treated with vehicle.
Netarsudil rapidly reverses corticosteroid-induced ocular hypertension in both short-term and chronically exposed mice. Since netarsudil has been shown to lower IOP by increasing conventional outflow, these results suggest that morphological changes to resistance-generating conventional outflow tissues are not permanent, and that netarsudil has the potential to prevent IOP elevation if administered concurrently with corticosteroid.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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