A promising (but not yet proven) treatment for glaucoma is the use of punctal plugs to deliver an accurate and consistent dosage of glaucoma medication. A major concern in glaucoma treatment is compliance with a medication regimen: ensuring that individuals use their eye drops every day and in the correct dosage. The consequences of poor compliance can lead to surgery, vision impairment, or even blindness.
Small eye drop containers are not easy to handle and use: Patients can administer too much, or too little, glaucoma medication, or can forget a dosage. The goal of punctal plug drug administration research is to develop a way to deliver a consistent level of glaucoma medication in a relatively non-invasive manner.
What are Punctal Plugs?
Punctal plugs are tiny (almost microscopic) tubes/devices that are inserted by an eye doctor into the tear drainage ducts of your eye (called the puncta) that are located in the inner corners of your upper and lower eyelids. Typically, punctal plugs are made from semi-permanent material, such as silicone hydrogel, or a dissolvable substance, such as collagen, which the body eventually reabsorbs. Until recently, the primary use of punctal plugs has been in the treatment dry eye disease.
In glaucoma research, punctal plugs are being investigated as a way to deliver glaucoma medication directly to the eye and release the medication continuously over an extended period of time. You can view a photo of a punctal plug’s relative size, as compared with a U.S. dime, at the Ocular Therapeutix website.
Who is Involved in Punctal Plug Research?
Initially, QLT, Inc., a biotechnology company based in Vancouver, British Columbia, developed a punctal plug delivery system for the glaucoma drug latanaprost. QLT investigated the effectiveness of the Latanoprost Punctal Plug Delivery System in two FDA-sponsored Phase II clinical trials, which indicated that the system could have potential as a glaucoma drug delivery device. In October 2012, however, the company reorganized and is pursuing a different punctal plug design with a new collaborating partner.
Ocular Therapeutix, Inc., a Bedford, Massachusetts-based biotechnology company that develops therapeutic products to address unmet or underserved needs in ophthalmology, is currently testing a punctal plug delivery system for the glaucoma drug Travoprost. The company recently completed a two-month Phase II study of 20 patients with open-angle glaucoma or ocular hypertension at the Umhlanga Hospital Medical Centre and Netcare Alberlito Hospital in South Africa.
About Open-Angle Glaucoma
Glaucoma is a group of eye diseases that damage the optic nerve and is one of the leading causes of vision loss and blindness. Open-angle glaucoma is the most common form of glaucoma.
The eye continuously produces a fluid, called the aqueous (or aqueous humor), that must drain from the eye in order to maintain healthy eye pressure. Aqueous humor is a clear, watery fluid that flows continuously into, and out of, the anterior chamber of the eye, which is the fluid-filled space between the iris and the cornea. It is the aqueous that helps to bring nutrients to the various parts of the eye.
Aqueous fluid drains from the anterior chamber through a filtering meshwork of spongy tissue along the outer edge of the iris (the trabecular meshwork), where the iris and cornea meet, and into a series of tubes, called Schlemm’s canal, that drain the fluid out of the eye. Problems with the flow of aqueous fluid can lead to elevated pressure within the eye.
In primary open-angle glaucoma, the filtering meshwork may become blocked or may drain too slowly. If the aqueous fluid cannot flow out of the eye, or flow out quickly enough, pressure builds inside the eye and can rise to levels that may damage the optic nerve, resulting in vision loss.
Note: Most eye care professionals define the range of normal intraocular (i.e., within the eye) pressure as between 10 and 21 mm Hg [i.e., millimeters of mercury, which is a pressure measurement].
Clinical Trials and Punctal Plug Research
Most clinical trials are designated as Phase I, II, or III, based on the questions the study is seeking to answer:
- In Phase I clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe and effective dosage range, and identify possible side effects.
- In Phase II clinical trials, the study drug or treatment is given to a larger group of people (100-300) to determine if it is effective and to further evaluate its safety.
- In Phase III studies, the study drug or treatment is given to even larger groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
The Ocular Therapeutix Results Thus Far
From an Ocular Therapeutix company statement, which summarizes the South African Phase II clinical trial results:
Ocular Therapeutix, Inc. announced promising results from their sustained release travoprost study for the treatment of glaucoma and ocular hypertension. The pilot Phase II study enrolled twenty patients in South Africa.
Patients with documented open-angle glaucoma or ocular hypertension, with intraocular pressure (IOP) greater than or equal to 24 mm Hg and less than or equal to 34 mm Hg were enrolled in the study, with a mean IOP at the beginning of the study of 28.7 mm Hg.
One punctal plug was administered in each treated eye. Results showed a decrease in IOP of 6.8 mm Hg over two months of treatment. No excessive tearing or other unanticipated adverse events occurred.
The company is planning a United States-based Phase III trial in 2013, with a targeted product launch in 2015.
Additional Information – and Cautions
Despite encouraging initial results, it will be several years before the long-term safety and effectiveness of punctal plugs can be confirmed. Some disadvantages of punctal plugs include impaired tear drainage or becoming dislodged from the tear duct. There is also a risk of eye irritation, excessive tearing, and infection. VisionAware will provide updates on punctal plug research as they become available.