July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Effects of a Soluble Guanylate Cyclase Activator (AL-EF-58-MF61) on IOP and Aqueous Humor Dynamics in Monkeys
Author Affiliations & Notes
  • Shan Fan
    Ophthalmology, Univ of Nebraska Medical Ctr, Omaha, Nebraska, United States
  • Ganesh Prasanna
    Ophthalmology, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States
  • Christopher M Adams
    Global Discover Chemistry, Novartis, Massachusetts, United States
  • Chris Towler
    Technical Research & Development, Novartis, Massachusetts, United States
  • Carol B Toris
    Ophthalmology, Univ of Nebraska Medical Ctr, Omaha, Nebraska, United States
    Case Western Reserve University, Ohio, United States
  • Footnotes
    Commercial Relationships   Shan Fan, None; Ganesh Prasanna, Novartis (E); Christopher Adams, Novartis (E); Chris Towler, Novartis (E); Carol Toris, Novartis (F)
  • Footnotes
    Support  Novartis ; RPB
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3188. doi:
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      Shan Fan, Ganesh Prasanna, Christopher M Adams, Chris Towler, Carol B Toris; Effects of a Soluble Guanylate Cyclase Activator (AL-EF-58-MF61) on IOP and Aqueous Humor Dynamics in Monkeys. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3188.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The purpose of this study was to identify the mechanism by which a soluble guanylate cyclase (sGC) activator, AL-EF-58-MF61, lowers intraocular pressure (IOP) and alters aqueous humor dynamics (AHD) in monkeys with unilateral laser-induced glaucoma following topical ocular dosing.

Methods : Sixteen female cynomolgus monkeys with unilateral laser-induced glaucoma were dosed with two 15µl drops (spaced 5 minutes apart) of AL-EF-58-MF61 or its vehicle to the cornea of both eyes at 10:00 AM on the day before the measurement day. Intraocular pressures (mmHg) were measured by pneumatonometry at 10:00 AM (IOP1), just before the treatment (baseline), and 10:00AM (IOP2) and noon (IOP3) on the day of the AHD measurements. Biometric measurements included anterior chamber depth (ACD, mm), axial length, and lens thickness by A-Scan, cornea diameter by calipers, and central cornea thickness (CCT, mm) by ultrasound pachymetry. Anterior chamber and cornea volumes (AC Vol and K Vol, μl) were calculated. AHD measurements were aqueous flow (Fa, μl/min) by fluorophotometry, outflow facility (Cfl, μl/min/mmHg) by fluorophotometry and by 2-minute tonography (Cton). Uveoscleral outflow was calculated two ways using the Goldmann Equation (Fufl or Futon, μl/min). Order of treatments were randomized and bottles were masked to the investigators.

Results : Drug-treated hypertensive eyes had lower IOP by 20% when compared to baseline IOP1 (p=0.0005) and 12% compared to vehicle treatment (p=0.01) at 24h post-dose. Statistical comparisons were made by two-tailed paired t-tests (p). Results from AHD are summarized in the following table.

Conclusions : AL-EF-58-MF61 reduced IOP in hypertensive eyes by increasing outflow facility and uveoscleral outflow. Numerous biometric differences were noted but CCT did not change thus did not contribute to the IOP effect.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

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