Glaucoma

Advances in glaucoma management

Treatment options have expanded to meet individual patient needs.

BY CHRISTINE L. LARSEN, MD

Therapies for glaucoma, the leading cause of irreversible blindness in the world, are designed to either increase the outflow or decrease the production of aqueous humor in order to reduce intraocular pressure (IOP) and preserve visual function. The traditional modes of treatment have included medical therapy and laser for mild to moderate disease or surgery for more advanced cases.

After many years without much change, recent advancements in both the medical and surgical realm have added more options to the glaucoma treatment armamentarium. The following recent developments aim to manage this potentially sight-robbing disease.

Surgery

Advancements in the surgical management of glaucoma have gained much attention. After medication and laser options, the next step, traditionally, was filtering surgery (either trabeculectomy or placement of a glaucoma drainage device). These procedures are often viewed as “high risk, high reward,” as they effectively lower IOP but subject the patient to an increased level of risk.

Minimally invasive glaucoma surgeries (MIGS) have helped to fill the gap between medical management and more invasive surgical procedures. MIGS procedures are minimally disruptive to the ocular tissues and help to bypass the eye’s natural filter (the trabecular meshwork) when it may not function adequately. The iStent (Glaukos) and Trabectome (NeoMedix, Inc.) are two of the more commonly utilized MIGS procedures. The iStent involves the placement of a small stent through the meshwork, allowing aqueous humor to bypass the barrier. The Trabectome works in a similar fashion; however, rather than an implant, electro-cautery ablates the meshwork.

Typically reserved for patients with more advanced disease, several recently developed devices aid in reducing tissue disturbance. The AqueSys XEN 45 Gel Stent and InnFocus MicroShunt both create filtration blebs (similar to trabeculectomy surgery) but require less surgical manipulation of the ocular tissues. Also, the Iridex MicroPulse laser works similarly to trans-scleral cyclophotocoagulation; however, the pulsatile delivery of laser energy to the ciliary processes through the sclera (as opposed to constant) is thought to create less injury to the surrounding structures.

Medication

Until recently, five classes of medications were available to treat glaucoma: prostaglandin analogs, beta blockers, carbonic anhydrase inhibitors, alpha agonists, and parasympathomimetics. These medications work through different mechanisms to reduce aqueous production and/or increase outflow, which reduces IOP. From the mid-1990s until recently, we saw a significant period of time when pharmaceutical advancements in glaucoma treatment remained primarily stagnant. The latest rise in new medication options includes:

• Rho kinase inhibitors: Also known as “ROCK inhibitors,” this new class of medication is the first to both target the outflow of aqueous at the level of the trabecular meshwork and reduce the episcleral venous pressure (the venous system surrounding the eye, “downstream” from the meshwork). Rhopressa (Aerie Pharmaceuticals) is the furthest along in clinical development, currently in Phase 3 trials.

• Trabodenoson (Inotek Pharmaceuticals): In Phase 2 trials, this highly selective adenosine mimetic has shown to significantly reduce IOP. It acts at the trabecular meshwork, improving metabolic activity with an increase in protease upregulation and is thought to restore the natural function of the meshwork. Phase 3 trials are currently ongoing.

• Vesneo (latanoprostene bunod, Bausch + Lomb and Nicox): This nitric oxide-donating prostaglandin analog has a dual mechanism of action. Aqueous humor drainage increases as the latanoprost affects the uveoscleral outflow pathway and the nitric oxide affects the conventional outflow pathway. Phase 3 trials confirmed effective lowering of IOP, and the FDA is expected to complete its review of the eye drop in July 2016.

Drug delivery

Patient compliance with prescribed medications is one of the biggest challenges in treating glaucoma. About 20% of glaucoma patients are not well-managed on topical drops, according to a 2013 article by Anwar, et al in Current Opinion in Ophthalmology. Some barriers to compliance include the inability to correctly and reliably instill eye drops, adverse effects associated with taking eye drops, the number of medications and the complexity of the dosing schedule, understanding the consequences of glaucoma and its treatment, medication cost, and patient forgetfulness.

In light of these multiple hurdles, there has been much focus recently on alternative routes for medication administration.

External modes of drug delivery that have been trialed include ophthalmic rods and Teflon strips inserted into the fornix. Helios (ForSight Vision5) is a bimatoprost-laden polymer-matrix insert embedded in a pliable ring. The ring is positioned under the upper and lower eyelids and rests on the conjunctiva. A physician replaces it every six months. Drug-eluting contact lenses have also been investigated. Contact lenses were created by encapsulating latanoprost-poly(lactic-co-glycolic acid) films in methafilcon by ultraviolet light polymerization. In vitro and in vivo studies showed an early burst of drug release followed by sustained release for one month. Although there have been no human trials, animal results showed aqueous humor concentrations of latanoprost that were equivalent to that with topical therapy, according to a January 2014 Biomaterials article from Ciolino, et al.

In a recent clinical study, Ocular Therapeutix’s sustained-release travoprost punctal plug demonstrated a robust IOP reduction and clinically significant results at three months. The plug inserts through the punctum and resides within the canaliculus, delivering travoprost to the ocular surface for up to 90 days. Also, it contains a visualization aid to monitor retention over the treatment period. After therapy completes, the hydrogel resorbs and exits the nasolacrimal system. Results are comparable to topical brand name prostaglandin analog ophthalmic solutions. Ocular Therapeutix is currently enrolling patients in a Phase 2b clinical trial at multiple sites in the United States.

Injectable administration has also been explored. Durasert/latanoprost (Pfizer/pSivida) is a bioerodible sustained-release latanoprost implant placed in the subconjunctival space. A Phase 1/2 clinical trial designed to assess the safety and efficacy of the implant is underway with plans to advance the product into a multi-center Phase 2 clinical trial (if successful). Intraocular Verisome/latanoprost (Icon Bioscience) is a 20-50 microgram intravitreal injection with 30-gauge needle utilizing Verisome technology (true liquid injection with one week to nine months duration). It is currently in the preclinical stages with promising results. Bimatoprost SR (Allergan) is a sustained-release, prostamide-loaded, bioerodible implant injected into the anterior chamber. It can be performed in the office, ensuring patient compliance. Data from Phase 2 clinical trials suggests that implant efficacy is comparable to daily topical bimatoprost with a duration of four to six months. Phase 3 trials are currently underway. Another anterior chamber depot implant, ENV515 (Envisia Therapeutics), is a biodegradable polymer drug delivery system that uses an extended-release formulation of travoprost. Phase 2a trials are ongoing.

Conclusion

Recent advancements in the surgical and medical treatment of glaucoma have provided practitioners with a broader scope of treatment options. New classes of medications and delivery mechanisms may help to improve patient compliance. New surgical procedures have aided in filling the gap between medication and laser management and the efficacious yet high-risk traditional filtering surgery.

As research and innovation continues, glaucoma treatment can be tailored to the individual patient, meeting their lifestyle needs and providing the appropriate level of risk based on the severity of their disease. OP

Christine L. Larsen, MD, specializes in glaucoma and anterior segment surgery at Minnesota Eye Consultants in Minneapolis, Minnesota. She is an adjunct assistant professor at the University of Minnesota and a member of the American Academy of Opthalmology, the American Society of Cataract and Refractive Surgery, and the American Glaucoma Society. Dr. Larsen is a principal investigator for several ongoing Phase 3 clinical trials. She has no financial interests to disclose.