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Sarah Kim, Victoria Chen, Marvin Cruz, Jessica Pottenburgh, Osamah Saeedi; Precise quantification of episcleral venous flow rates in human subjects before and after netarsudil 0.02%. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3497.
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© ARVO (1962-2015); The Authors (2016-present)
Netarsudil, a Rho-kinase inhibitor and norepinephrine transporter inhibitor, is known to lower episcleral venous pressure, however, its precise effect on flow rates has not been studied. We have recently developed erythrocyte mediated angiography, EMA, a technique in which autologous fluorescently labeled erythrocytes are reinjected into a human subject permitting the observation and precise quantification of flow rates. The purpose of this study was to quantify the short- and long-term effects of netarsudil on episcleral venous flow rates in treatment-naïve ocular hypertensive and glaucoma suspect subjects using EMA.
This prospective study enrolled treatment-naive ocular hypertensive and glaucoma suspect patients. All subjects underwent anterior segment EMA, conventional indocyanine green angiography, and applanation tonometry at baseline, 1 hour after drop instillation, and 1-2 weeks after once daily topical netarsudil use. A MATLAB program we developed was used to track erythrocytes on EMA angiograms. Vessel diameter was measured using the Automated Retinal Image Analyzer program. Changes in erythrocyte velocity, vessel diameter, estimated blood flow, and IOP were assessed using two-sample unpaired t-tests.
Twelve episcleral vessels of nine eyes of seven patients were analyzed. IOP was reduced from 15.6±3.4 to 10.7±4.1mmHg at 1-hour (p=0.017) and 11.1±4.3mmHg at 1-2 week(s) after therapy initiation (p=0.007). Mean erythrocyte velocities did not differ significantly in this sample from baseline (2.2±1.0 mm/s), at one hour (3.1±1.4mm/s, p=0.063), or at 1-2 weeks (1.8±1.4 mm/s, p=0.219). However, vessel diameter increased from 62.7±14.5um to 100.2±32.3um (p=0.003) after one hour and 85.8±30.9um (p=0.008) after 1-2 weeks. Episcleral blood flow increased significantly from 0.45±0.28μL/min to 1 hour post eyedrop (2.06±02.41μL/min, p=0.033), but not after 1-2 weeks (0.74±0.94μL/min, p=0.121).
We found that netarsudil 0.02% resulted in significant IOP reduction and associated increase in episcleral venous flow rates in treatment-naïve glaucoma suspect patients. This is the first study to our knowledge that quantified the change in episcleral venous blood flow in vivo after a pharmacologic intervention, which can be assessed using EMA. This technology has the potential to offer novel biomarkers for treatments that target the conventional outflow pathway.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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