Glaucoma: Current and Developing Pharmacologic Treatments

Glaucoma is the second leading cause of blindness worldwide, and as the population ages in the United States its prevalence will continue to increase. When starting a patient on therapy for glaucoma, one has the option of medications, laser, or surgery. Historically, optometrists and ophthalmologists have chosen the former as it is the least invasive and is reasonably successful. These medications aim to reduce aqueous production or improve aqueous outflow, increase uveoscleral outflow, or affect the episcleral venous pressure. Choosing what medication or medications to use makes treating glaucoma more of an art than science. Doctors have to analyze changes in intraocular pressure (IOP) and visual field loss to assess how fast the disease is progressing and when it is time to move on to the next treatment, changes that are often subtle and different from patient to patient. Although pharmacologic treatments for glaucoma have been relatively stagnant the past few years, more and more options are becoming available. This will allow for a more customized approach for both patients and doctors to come up with a winning combination.

Current Available Options

There are multiple available options. Most providers choose prostaglandin analogs (PGAs) as their go-to first-line treatment option. They are effective, offer once-daily dosing, are well tolerated, and reasonably priced. There are multiple brand name and generic options available. The best second-line therapy choice is less agreed upon, and is usually based on many factors related to the patient. Beta blocker medications are effective and can be paired with the PGAs, as can carbonic anhydrase inhibitors and alpha-agaonists.  

More recently, combination medications have become available, which allows for additional medications to be used in a single drop. The use of combination drops is important; recent research in the Indian Journal of Ophthalmology by Davinder S Grover and colleagues found that an increase in number of medications can lead to decreased compliance. Commercially available options include Cosopt (dorzolamide/timolol; Akorn), Combigan (brimonidine/timolol; Allergan), and Simbrinza (brinzolamide/brimonidine; Alcon).  Even more recently, Imprimis Pharmaceuticals in San Diego, California, has launched a line of preservative-free combination drops, which can combine any of the above-mentioned medications. Having a preservative-free option is important because preservatives are a well-studied factor in ocular surface disease.

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Medications in Development

Newer medications with alternative mechanisms of action are being developed with the hopes of better IOP control.  Latanoprostene bunod 0.024% (Bausch & Lomb) is currently in FDA trials and is a combination medication that targets outflow and potentially lowers episcleral venous pressure. Netarsudil 0.02% (Aerie) is a Rho-kinase inhibitor and also inhibits norepinephrine transporters to lower IOP. Netarsudil/latanoprost (Aerie) adds an additional mechanism of action to netarsudil. The hope is that these medications in development will allow for multiple mechanisms of action in a single drop, that can be taken once daily.

Taking the Medications Out of Patients Hands

A recent study in Ophthalmology by Paula Anne Newman-Casey, MD, and colleagues, pointed out, only 15% of patients achieve good adherence to medications at 4 years. Therefore, it is important for patients to have alternative options that would take compliance issues out of patient’s hands, literally. New drug delivery options are rapidly being developed, with platforms for delivery both externally and inside the eye.  

External options use a variety of delivery systems. Ocular Therapeutix has developed a preservative-free travaprost (a prostaglandin) insert that is placed in the canaliculus and can deliver medication for up to 90 days. This is currently in FDA trials.  Allergan is currently investigating a bimatoprost-laden polymer-matrix insert embedded in a compliant ring that will slowly deliver medication over the course of 6 months. Vista Scientific (Andover, Massachusetts) uses a similar device that is worn and completely concealed under the eyelid.  

Inside the eye options include bimatoprost SR (Allergan), which is a depot implant that is injected into the anterior chamber and can release medication for up to 6 months. Another depot implant that is injected and targets the anterior chamber is ENV515 by Envisia Therpeutics. ENV515 is a biodegradable polymer drug delivery system that uses an extended-release formulation of travoprost. The iDose by Glaukos is a titanium implant that is filled with a formulation of travoprost and capped with a membrane designed to allow continuous controlled drug elution into the anterior chamber. Once depleted, the implant can be removed and replaced in a subsequent procedure. 

While we have a handful of options currently available, there is room for improvement. Improved topical agents with improved efficacy and minimal dosing will improve compliance.  Having alternative drug delivery systems with sustained release will also increase compliance.  The future is filled with many new exciting topical medications and a variety of drug delivery systems.