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Enhancing adherence to glaucoma therapy with punctal plug drug delivery platforms.

By Malik Y. Kahook, MD; Jeffrey R. SooHoo, MD; and Leonard K. Seibold, MD

Punctal plugs have the potential to address patient compliance with medication, one of the biggest issues eye care providers face when it comes to caring for glaucoma patients. Barriers to compliance range from cost and forgetfulness to confusion and lack of education. According to Claxton et al, patient compliance on a once-a-day-medication is 79%, and compliance decreases as dosage frequencies rise.1

Below, Malik Y. Kahook, MD; Jeffrey R. SooHoo, MD; and Leonard K. Seibold, MD, review how punctal plugs fit into the glaucoma conversation and review the pros and cons of employing them for glaucoma therapy.

—Walt Whitley, OD, MBA

1. Claxton AJ, Cramer, J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296-1310.

One of the major limitations of medical therapy for glaucoma is patients’ poor adherence to physician-prescribed regimens. It has been estimated that the rate of nonadherence to topical glaucoma therapy is 40% or higher.1-3 Even with multiple methods of addressing the problem, such as memory aids and instillation devices, proper therapy remains a major unmet need for patients around the globe.

In response, over the past decade, several companies have attempted to develop therapeutic strategies that are independent of patients and are administered by the physician. These modalities include insert devices that reside on the ocular surface, slow-release medication depots that are injected into the eye, and punctal plugs that deliver drugs directly into the tear film. The last of these has received a great deal of attention during the past few years.


Poor adherence to glaucoma treatment is an ongoing problem. Patient-independent therapies that demonstrate long-term efficacy, such as punctal plugs, are one potential solution.


Inserting a slow-release medication depot into the punctum provides several advantages. First, standard punctal plugs have been used to manage dry eye disease for decades. This history encourages more immediate acceptance by physicians and patients because there is a track record of safety that does not exist with many other strategies for long-term ophthalmic depots.

Second, punctal plug delivery platforms are minimally invasive interventions. Compared with intraocular injections, for example, they represent a low-risk approach that is on par with more traditional therapies such as topical drops.

Third, a punctal plug approach can leverage existing active pharmaceutical ingredients (APIs) that have a long track record of success and safety.


Like any treatment modality, punctal plugs have drawbacks. For one thing, they are prone to fall out over time, which is not acceptable for the treatment of a chronic disease, when months often elapse between office visits. Overcoming this problem would require either enhanced retention devices or the patient’s awareness that a plug had fallen out of place. In the latter case, a visit to the physician should be scheduled to replace the plug or initiate an alternative therapy.

Another drawback to current designs is that drug delivery is passive, depending on tears to wash into the plug reservoir and transport the active drug back into the tear film. In cases of severe dry eye or lid anatomy pathologies, plugs may not be able to deliver a drug in a predictable manner.

Finally, current APIs may not be ideal for this type of delivery system, either owing to a plug’s inability to hold a large enough depot or because of differences in efficacy with pulsed dosing, as with topical drops, compared to the constant delivery of the same drug retained in a depot.


We have described just a few of the pros and cons of using punctal plugs for the treatment of glaucoma and other ophthalmic diseases, but we believe the drawbacks should be viewed as challenges to overcome rather than deterrents to using this method of treatment. There have been multiple attempts at delivering drugs with punctal plugs over the years, and many have not been able to overcome the limitations described. Several promising technologies in ongoing clinical trials, however, show some hope of becoming commercially available in the coming years.

Courtesy of Mati Therapeutics.

Figure 1. The Evolute in situ (A). The device becomes visible when the eyelid is pulled down (B, C).

Courtesy of Ocular Therapeutix.

Figure 2. OTX-TP is moisture-ctivated and form-fitting upon insertion. It swells to fit comfortably and securely in the canaliculus, according to Ocular Therapeutix (A). Over time, the company’s hydrogel reportedly enables OTX-TP to release travoprost for up to 90 days (B).

Courtesy of Ocular Therapeutix.

Figure 3. The OTX-TP held by surgical forceps.

Mati Therapeutics, a startup company that is continuing work begun at QLT, is developing a long-term punctal plug delivery system (Evolute; Figure 1) that has completed multiple clinical trials for the treatment of glaucoma and other ophthalmic diseases. Earlier studies with this system at QLT reported success in lowering IOP and improved retention of the plug by way of device refinement over time. In a press release, the company reported plug retention ranging from 48% to more than 95%, depending on the duration of follow-up and whether the plug was placed in the upper or low punctum.4 Mati is currently engaged in a phase 2 trial of a latanoprost-delivering plug, with timolol as the active comparator.

Ocular Therapeutix has a proprietary polymer-based punctal plug drug delivery platform. Medication depots with this platform have included therapies for glaucoma, using travoprost as the API, with reported retention of 88% at 75 days.5 The company is also working with ocular allergy and post–cataract surgery steroid depots. The travoprost plug (OTX-TP) is currently in phase 3 trials comparing it with placebo (Figures 2 and 3).

A punctal plug delivery system from Eximore Technologies leverages a nonbiodegradable, nonsilicone polymer composite device to deliver APIs to the tear film. Data on this platform are not widely available, but in vitro and preclinical studies reported to date show promise.6

Overall, the IOP-lowering efficacy of these platforms has not been rigorously tested and reported. To date, with sparse information available, pressure-lowering efficacy appears to range from slightly less than with a topical beta blocker to almost on par with a topical prostaglandin analogue.


As is true with many chronic illnesses, poor adherence to glaucoma treatment is an ongoing problem for patients and their treating physicians. Patient-independent therapies that demonstrate long-term efficacy, such as punctal plugs, are one potential solution. Although punctal plugs’ minimally invasive application, patients’ and doctors’ familiarity with them, and their long-term safety record make this platform attractive, obstacles such as retention and consistent efficacy will have to be overcome. Ongoing clinical trials will be informative in comparing punctal plug therapies with currently available topical medications.

1. Friedman DS, Hahn SR, Gelb L, et al. Doctor-patient communication, health-related beliefs, and adherence in glaucoma results from the Glaucoma Adherence and Persistency Study. Ophthalmology. 2008;115:1320-1327.

2. Friedman DS, Quigley HQ, Gelb L, et al. Using pharmacy claims data to study adherence to glaucoma medications: methodology of the Glaucoma Adherence and Persistency Study (GAPS). Invest Ophthalmol Vis Sci. 2007;48(11):5052-5057.

3. Quigley HA, Friedman DS, Hahn SR. Evaluation of practice patterns for the care of open-angle glaucoma compared with claims data: the Glaucoma Adherence and Persistency Study. Ophthalmology. 2007;114(9):1599-1606.

4. QLT shows positive efficacy trends from data in plug combinations in phase II studies for glaucoma using latanoprost punctal plug delivery system [press release]. Vancouver, British Columbia: QLT; October 24, 2012. Accessed August 28, 2017.

5. Ocular Therapeutix reports on topline results of phase 2b glaucoma clinical trial [press release]. Bedford, MA: Ocular Therapeutix; October 22, 2015. Accessed August 30, 2017.

6. Gebhart F. New technologies on horizon to redefine drug delivery. Ophthalmology Times. Published July 15, 2017. Accessed August 28, 2017.

Malik Y. Kahook, MD
• Slater Family Endowed Chair in Ophthalmology; vice chair, clinical and translational research; director, glaucoma service; and codirector, glaucoma fellowship, department of ophthalmology, University of Colorado School of Medicine, Aurora
• financial disclosure: ownership of patents in the field of punctal plugs for drug delivery to the eye
• 720-848-2020;

Leonard K. Seibold, MD
• associate professor of ophthalmology; codirector, glaucoma fellowship, University of Colorado School of Medicine, Aurora
• financial interest: none acknowledged

Jeffrey R. SooHoo, MD
• assistant professor of ophthalmology; residency director; University of Colorado School of Medicine, Aurora
• financial interest: none acknowledged