June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
New Highly Effective and Long-Acting Anti-Glaucoma Drug, New Periorbital Delivery Method
Author Affiliations & Notes
  • David F F Woodward
    Bioengineering, Imperial College London, London, United Kingdom
    JeniVision Inc., Irvine, California, United States
  • Jenny W Wang
    JeniVision Inc., Irvine, California, United States
  • Footnotes
    Commercial Relationships   David F Woodward, JeniVision Inc. (I); Jenny Wang, JeniVision Inc. (I)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4590. doi:
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      David F F Woodward, Jenny W Wang; New Highly Effective and Long-Acting Anti-Glaucoma Drug, New Periorbital Delivery Method. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4590.

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

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Abstract

Purpose : Two features define the future of glaucoma therapeutics: (1) greatly improved ocular hypotensive efficacy (2) a delivery method that improves patient convenience and compliance. Periorbital delivery was contemplated since published ocular drug biodisposition studies demonstrate that the overwhelming majority of drugs applied topically to the ocular surface preferentially accumulate in the sclera and eyelids. These studies were intended to determine whether dermal periorbital delivery of an exceptionally efficacious and potent ocular hypotensive agent 3-[(3’–fluoro-4-fluorobiphenyl-3-carbonyl) amino] phenoxyacetic acid isopropyl ester would fulfil the required criteria for a next generation anti-glaucoma drug.

Methods : : Intraocular pressure was measured in ocular hypertensive and normotensive eyes of conscious cynomolgus monkeys, trained to accept pneumatonometry when under gentle restraint. For periorbital application the compound was formulated in polyethylene glycol and applied radially by using a roller-ball device connected to a cylindrical reservoir.

Results :
: A single 0.006% dose of 3-[(3’–fluoro-4-fluorobiphenyl-3-carbonyl) amino] phenoxyacetic acid isopropyl ester, given as a single eye drop, produced a profound decrease in intraocular pressure in “glaucomatous” monkeys that persisted for one-two weeks. It was not uncommon for a single 0.006% or 0.01% eye drop to reduce intraocular pressure to 6-7 mmHg. Application of a 0.1% dose to the periorbital dermis of ocular normotensive monkeys produced a similarly profound reduction in intraocular pressure, which was well maintained.

Conclusions :
The compound 3-[(3’–fluoro-4-fluorobiphenyl-3-carbonyl) amino] phenoxyacetic acid isopropyl ester possesses efficacy and duration of action properties sufficient to be considered as representative of the next generation of anti-glaucoma agents. Moreover, application to the periorbital skin using a roller-ball device would be a more convenient method of ophthalmic drug delivery than eye drops and is non-invasive in contrast to other “dropless” technologies.

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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