Eyeworld

75 EW GLAUCOMA February 2016 by Tony Realini, MD, MPH be suboptimal would benefit from provided-delivered therapy. Other candidates may be those with phys- ical or cognitive impairments that limit their ability to self-administer topical therapy. Also, patients who are progressing despite apparently well-controlled IOP may benefit from the more continuous IOP reduction provided by sustained release formulations. Less clear is whether patients who are well con- trolled and stable on topical therapy would benefit. Ideally, future studies of these new implants will include 24-hour IOP endpoints, which may demon- strate greater consistency of IOP control with sustained release versus intermittent dosing formulations. Such a benefit might influence the acceptability of these new therapies to third-party providers of pharmacy benefits. EW Editors' note: Dr. Lewis has financial interests with Allergan. Dr. Mansberger has financial interests with Allergan and Envisia Therapeutics. Contact information Lewis: rlewiseyemd@yahoo.com Mansberger: smansberger@deverseye.org IOP-lowering effect over 25 days after a single dose," Dr. Mansberger said. The low-dose implant lowered mean diurnal IOP by approximate- ly 7–8 mm Hg and the high-dose implant by approximately 9–10 mm Hg. The most common adverse events in the low-dose group (n=7) were conjunctival hyperemia and punctate keratitis. The safety profile of the high-dose implant was not reported, but the planned next steps in development focus on further study with the low-dose implant, suggesting that the low-dose device provides the optimal balance of efficacy and safety. Patient selection As these and other related products transition from development to market, the traditional stepped treat- ment approach to glaucoma will be significantly impacted. These devices offer significant potential benefits over daily topical therapy, but come with the increased risks associated with repeated intraocular injections. Which patients in our practices would most benefit from receiving these new therapies? Certainly those in whom adherence with topical therapies is known or suspected to the 2015 American Academy of Ophthalmology (AAO) annual meeting in Las Vegas. In the phase 1/2 study, glauco- ma patients received the bimato- prost SR implant (in 1 of 4 doses) in 1 eye and topical bimatoprost 0.03% in the fellow eye. During 12 months of follow-up, an additional implant injection was allowed as needed. "Bimatoprost SR provided rapid and sustained IOP lowering," Dr. Lewis said. At the primary endpoint of week 16, the mean IOP reduction among the 4 implant doses was 7.2 to 9.5 mm Hg, comparing favorably with the 8.4 mm Hg obtained with topical bimatoprost dosing. "At month 6, 71% of study eyes still had not received topical IOP-lowering rescue medication or a second injection of bimatoprost SR," he added. Interestingly, intracameral dosing seemed to improve the safety profile of bimatoprost. The most common side effect of the prosta- glandins is conjunctival hyperemia. In the phase 1/2 study, the inci- dence of conjunctival hyperemia with onset >2 days after injection (to minimize the impact of injection-re- lated hyperemia) was 7% in the eyes receiving implants versus 17% in the topically treated eyes. Travoprost XR A similar extended release biodegradable implant has been formulated using travoprost (Envisia Therapeutics, Morrisville, N.C.) and is currently in phase 2a evaluation. Preliminary results of this first-time-in-humans study were presented at the 2015 AAO annual meeting by Steven Mansberger, MD, Portland, Ore. The study included 17 eyes scheduled for elective cataract surgery in 1 eye. The cataract eye received either a low-dose or high- dose implant and the fellow eye received topical travoprost 0.004% with data collection over a 4-week period before surgery. After the 4-week trial during cataract surgery, surgeons sampled the aqueous for pharmacokinetics and removed all of the implants for rate-of-release analyses. "The implant demonstrated a robust and statistically significant Several potential products are currently in development T he 1990s saw huge inno- vation in glaucoma drug delivery, with the develop- ment of the prostaglandin analogues, topical carbonic anhydrase inhibitors, adrenergic agonists, and modern fixed com- binations. These drugs and those that have come before and since provide opportunities for individu- alized glaucoma care unparalleled in history. There remains, however, signifi- cant unmet need in glaucoma phar- macology. Glaucoma medications only work if taken regularly and properly. Numerous studies have documented that even well-meaning patients often fail to successfully instill eye drop medications, and even more disheartening, many—if not most—patients often don't even try. Add inconvenience of dosing frequency—up to 3 times daily for some drugs—and intolerability due to side effects, and the overall adher- ence to glaucoma therapy is abjectly poor. A drug that could be delivered easily by the healthcare provider no more than 2–3 times per year while providing comparable efficacy and safety to currently available patient- dosed medications could make a huge difference in adherence, and by extension, to preventing glau- coma vision loss. Several potential products are currently in develop- ment. Bimatoprost SR Furthest along in the development process is bimatoprost SR (Allergan, Dublin), an injectable, biodegrad- able implant containing bimato- prost. The implant comes pre-loaded on an injector designed for delivery through the peripheral cornea. Once injected, the small device resides in the inferior anterior chamber angle and provides continuous intraocular pressure (IOP) reduction for up to 4–6 months. Bimatoprost SR is currently in phase 3 testing. Phase 1/2 study results were presented by Richard Lewis, MD, Sacramento, Calif., at Sustained delivery glaucoma therapy is coming soon A drug that could be delivered easily by the healthcare provider no more than 2–3 times per year while providing comparable efficacy and safety to currently available patient-dosed medications could make a huge difference in adherence, and by extension, to preventing glaucoma vision loss. Several potential products are currently in development.

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