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Promising Glaucoma Treatments on the Horizon

In the early 1940s, my grandmother was diagnosed with glaucoma. Essentially, the doctor explained that her vision would progressively worsen as she lost more peripheral vision; no treatment was recommended. Today, the patient diagnosed with glaucoma looks forward to aggressive treatment in a wide variety of options with even more in the pipeline.

Historically, topical treatments for glaucoma have been available since the 1860s, when a British physician noticed the potential eye pressure benefits of the calabar bean. There are now four common classes of eye drops routinely prescribed for glaucoma patients, some in multiple formulations, providing physicians with a substantial armamentarium of treatments. Current glaucoma medications reduce intraocular pressure (IOP) by either reducing the production of fluid in the eye, or by increasing its outflow. Prostaglandins, which increase outflow, are now the most prescribed glaucoma treatment worldwide.

A new experimental medication for glaucoma, BOL 303259-X (Bausch and Lomb), seems to lower intraocular pressure as effectively and safely as the gold standard, latanoprost, and might be more potent, say investigators.

Dr. Daniel Moore, Assistant Professor of Opthalmology and Visual Sciences at the University of Kentucky, explains, “This is a slightly modified target of the ‘newest’ class of medications, the prostaglandins (on the market since the mid-1990s).” Currently undergoing a phase III trial, early results suggest it may be as efficacious as current prostaglandins if not slightly superior.

But Moore sees more on the horizon. “A new class of medications — ‘Rho kinase inhibitors’ — are currently in clinical trials and are expected to become available in the next five to 10 years. Early results suggest these medications are equally effective as available agents.” Duke University’s semi-independent pharmaceutical company has one of this new class of drugs starting Phase III of clinical investigation.

This new class of glaucoma drugs promises to act specifically on the eye’s drainage canals, called the trabecular meshwork, a main outflow and blockage site in glaucoma. Rho kinase (ROCK) inhibitors target cells in the trabecular meshwork to enhance aqueous humor outflow. No drugs currently on the market enhance the eye’s fluid outflow in this way. ROCK inhibitors are not yet approved and available for glaucoma patients, and two US companies, Aerie and Altheos, are in early clinical research development.

But the current technology for medication delivery is in itself problematic. “We are fooling ourselves if we believe the current standard of drug delivery is adequate,” says Moore.

To that end, Kentucky General Assembly has under review a new bill, SB118, that if passed will allow refill of eye drops prescriptions in 23 days instead of the routine 30 days. Dr. Sheila Sanders, also at UK’s Ophthalmology and Visual Sciences, says, “It’s so frustrating to have patients running out of their needed medications because eye drops are so challenging to administer.”

Education is key, Sanders and Moore agree. Both physicians work to educate patients on the disease as well as how to effectively use their eye drops.
•    Tip your head back or lie on a couch and look straight up at the ceiling.
•    Hold the bottle perpendicular to the floor and look up at the bottle tip, which should be a few inches above your eye.
•    Pull the lower lid down with one hand.
•    Steady your hands by resting the wrist of the hand holding the bottle onto the hand holding the eye lid.
•    Apply a drop.
•    Keep the bottle from touching the eye or it can become contaminated. And do not attempt to look in a mirror during instillation; this practically guarantees drops will fall to the floor.

Other medication delivery systems are currently in development. Furthest along in the research pipeline is a punctal plug delivery system, developed by QLT, in which a core that is filled with a three-month supply of medication is inserted into a punctal plug. Plug retention is the biggest issue.

Allergan is testing the safety and effectiveness of a brimonidine intravitreal implant in patients with glaucomatous optic neuropathy. The phase 2 trial is comparing a 200 and 400 µg brimonidine tartrate posterior segment implant vs. a sham.

Moore identified a phase I clinical trial underway at UK investigating a subconjunctival depot of a prostaglandin medication. And there are also some preliminary investigations underway looking at special contact lenses that release medication.

However, Dr. Moore cautions, “Placing a drop on the eye is less risky than occluding the tear system with medication or potentially injecting it into the eye. My hope is that the not too distant future provides a completely alternative treatment that is more robust, reliable, tolerable and less invasive.”

By Doris Settles, Staff Writer



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