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Is the future of glaucoma treatment in delivery systems or new therapies?
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New delivery systems needed
New classes of medication? What would you need? One that is safer than latanoprost, lasting weeks at a time, no ophthalmic adverse events and more comfort than currently available medications. Also, a new mechanism of action would be a plus. This bar is one that is hard to reach, one that is hard to imagine can be achieved within the next few decades after the upcoming introduction of Rho kinase inhibitors.
What is really needed is a way to put medication control in doctors’ hands. Adherence is a major issue. Twenty percent of patients did not visit their eye care provider within 18 months of their initial diagnosis. Forty percent had not filled their initial medication prescription within 2 months of their initial visit at which their glaucoma was diagnosed. Between one-third and 40% persist with their medications at a year, and approximately one-half can correctly name their medications with the appropriate dosing schedule.
More than one-half of patients admit to nonadherence (but we all know they overestimate their adherence). The problem is even more complex: 17% of individuals do not instill their own medications. Of the 83% who do instill their own medications, approximately 20% to 25% of patients believe they are properly instilling medications, miss their eyes when instilling drops and do not get drops into their eyes at all. Many waste medications by instilling multiple drops, and many contaminate their bottles when using the medications. If a medication is not taken or does not reach the target, it is rendered ineffective.
One therefore needs a medication administered by the physician that is long-lasting. The delivery can be intracameral, punctal plug or sub-Tenon’s. The device, if inside the eye, must be biodegradable with no untoward effects (corneal decompensation, inflammation, cataract formation). If subconjunctival or sub-Tenon’s, it must be able to be repeated with minimal conjunctival scarring so that glaucoma surgery can later be successfully performed. The minimal time the device must last should be at least 3 months but 6 months or longer would be ideal.
Patients hate eye drops, so why develop another? More than one-half require more than one, and with this, many people become less adherent. Delivery systems that put IOP lowering in the ophthalmologists’ hands are the only way to go.
Alan L. Robin, MD, is an OSN Glaucoma Board Member. Disclosure: Robin reports he is a consultant and stock owner in Aerie Pharmaceuticals.
Pros and cons for both
Traditionally glaucoma therapy has entailed topical eye drops, laser and surgery for those patients who progress or are uncontrolled on medical therapy.
There are pros and cons to using traditional topical drops vs. new, innovative drug delivery systems.
Topical instillation of eye drops is the most common and most accepted method of delivering a medication to the eye while treating glaucoma. These drops often contain preservatives and penetration enhancers that are toxic to the ocular surface, causing irritation, hyperemia and reduced compliance. These inactive ingredients are necessary due to limited permeability of the cornea, reflex blinking, dilution, and natural clearance and drainage.
Other disadvantages of using topically applied drops may include difficulty with physically applying drops, adhering to the recommended schedule, high co-pays and overall poor patient compliance. Research and innovation are investigating various approaches to enhance the bioavailability of topically applied drops, such as by increasing lipophilicity, viscosity and corneal penetration through unique delivery systems such as DuraSite (InSite Vision).
Implantable drug delivery devices are being studied and may address some of the concerns of patient noncompliance, ocular toxicity and inconsistent control of IOP associated with topically applied drops. Some of these delivery systems include punctal plug or contact lens releasing glaucoma medications, injectables containing biodegradable micro and nanoparticles, and surgically implanted systems. Primary objectives with these new innovations include improving compliance, reduction of side effects and clinically improved efficacy with the potential of managing IOP for several months. There are, however, limitations with sustained drug delivery systems. It is not possible to titrate or stop drug delivery once it is delivered into the eye. This may be a concern if patients are lost to follow-up. Another area of uncertainty is cost and whether Medicare or third-party payers will cover this technology. Systems delivering drug therapies intracamerally are considered a surgical procedure, requiring a skilled surgeon, and the procedure may introduce the risk of infection or endophthalmitis.
Glaucoma is a vision-threatening disease that requires lifelong treatment and patient compliance. Topical IOP-lowering drops have been the gold standard in glaucoma therapy for decades with advantages of easy dosage and application, together with minimum systemic absorption. However, the most concerning disadvantages are poor patient compliance, consistent control of IOP and ocular toxicity with secondary exacerbation of ocular surface disease. Ophthalmology is on the cusp of entering a new golden era of innovation for the treatment of glaucoma with promising and novel therapies in clinical development that have the potential to address concerns with patient compliance, increased efficacy and potentially preserve sight for glaucoma patients.
Alice T. Epitropoulos, MD, FACS, is an OSN Cataract Surgery Board Member. Disclosure: Epitropoulos reports no relevant financial disclosures.