Even Better Than Compliance
Devices as simple as a punctal plug may radically change and improve the way we deliver medication to patients’ eyes.
by Elizabeth Yeu, MD
As effective as topical drops are for delivering medication to the eye, drops are plagued by multiple uncertainties. First, drops are wholly dependent on one notoriously unreliable actor: the patient. Even patients with potentially blinding conditions like glaucoma can be startlingly noncompliant about drop-taking. Nor can physicians ensure that pharmacists will fill their prescriptions as written and not, for example, substitute a generic.
In addition, almost all topical eye drops in reusable containers have preservatives to prevent growth of bacteria and other microorganisms. These preservatives are often irritating to the eye, especially when the drop is used heavily or taken continuously over a long period of time, like glaucoma medications. Also, many women don’t like using drops because they cause makeup to run.
The IUD Approach
In theory, an alternative delivery system could make taking ocular medication safer, more convenient, and more certain. Many problems would be solved at once if it were possible to offer ophthalmic medications in a form that does not require continuous reapplication — similar to the sustained release of drug from an IUD to prevent conception.
Sustained release is not a new idea in ophthalmic drugs. LACRISERT® (hydroxypropyl cellulose ophthalmic insert), a rod-shaped, preservative-free, slow-release lubricant placed in the inferior cul-de-sac, dates from the 1970s, when it was developed by Merck as a slow-release vehicle for pilocarpine. It failed at that, but it succeeded (and continues to succeed) for some patients as a lubricant for dry eye.
There are now also several implantable sustained-release devices that deliver drug to the posterior segment. And intracameral and intravitreal drug injections immediately following cataract surgery have shown great potential as means to deliver prophylactic antibiotics and steroids.
Steroid Punctal Plug
One form of “implantable” device is the punctal plug. Plugs have the enormous advantage of being easy to insert and remove — indeed, a significant downside is that plugs can be too removable and fall out on their own. I have been involved in trials of a steroid-eluting plug that, after being placed in the canaliculus, hydrates and molds to the shape of its surroundings, giving it a better than 90% retention rate.
The plug promises to be useful for post-op patients and those with chronic inflammatory conditions like blepharitis and dry eye disease. I think this could be a huge advance. In a different application, if an antihypertensive drug could be embedded in the plug, glaucoma patients could get continuous, low-level drug exposure — ensuring steady drug levels and, hopefully, low and stable intraocular pressures.
So instead of drops, which neither doctors nor patients like, imagine having something that could sit unobtrusively in the puncta and last for 45 or more days, delivering steady, low-level medication all day. Compliance and inconvenience would become nonissues. And the eye would never be without drug, eliminating peak and trough problems.
Novel Applications
Sustained-delivery systems may also turn out to be of value in collagen cross-linking (CXL), where hydrophilic riboflavin solutions don’t penetrate the lipophilic corneal epithelium very well.
One way around the problem is removing the epithelium, but that increases risk and patient discomfort. So the search is on for efficient ways to get riboflavin into the corneal stroma through an intact epithelium. A sustained-release drug implanted hours or days prior to the cross-linking treatment may be one way to accomplish that.
Challenges
One attraction of the punctal plug route for sustained release is that the insertion of a punctal plug is a minor procedure, familiar to both ophthalmologists and dry eye patients. More invasive forms of sustained-release therapy — such as injecting a tiny device into the anterior or posterior chamber, for example — would involve greater risk, including issues of device removal if it became necessary.
A second challenge is: how are these devices going to be priced and reimbursed? There are very well-established benchmarks and guidelines for topical therapeutics, but this is something different. And getting either a drug or a device through regulatory bodies like the FDA is challenge enough — getting approval for something that is both a drug and a device can be daunting.
It will be interesting to see how quickly these devices come to market and how long they will have to be used before health insurers, including Medicare, routinely cover them. Will insurers require that patients try and fail with topical eye drops before reimbursing one of these more advanced treatments? We’ll find out when the next round of sustained-release devices gets to market.
[For more Eyecare Vision of the Future coverage of sustained drug delivery, see this article on an implantable anti-VEGF “biofactory” for wet AMD.]
Elizabeth Yeu, MD, is a corneal, cataract, and refractive surgeon with Virginia Eye Consultants and an assistant professor at Eastern Virginia Medical School.
