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Glaucoma specialists focus attention on forthcoming advances, therapies
Specialists in glaucoma anticipate the future availability of a novel triple-action agent, as well as other medical and surgical management developments.
Take home
Specialists in glaucoma anticipate the future availability of a novel triple-action agent, as well as other medical and surgical management developments.
By Cheryl Guttman Krader; Reviewed by Malik Y. Kahook, MD, and Joel S. Schuman, MD
Although options for glaucoma treatment remained unchanged in 2014, initiation of the phase III registration trials for AR-13324 (Rhopressa, Aerie Pharmaceuticals) is generating excitement among glaucoma specialists about the future availability of this novel triple-action agent.
Ophthalmology Times Editorial Advisory Board members Malik Y. Kahook, MD, and Joel S. Schuman, MD, spoke about these and other recent developments relating to medical and surgical glaucoma management.
AR-13324 is the first rho kinase (ROCK)/norepinephrine transporter (NET) drug to advance into a pivotal trial. It acts to specifically target the trabecular meshwork, lowers episcleral venous pressure, and reduces aqueous production.
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The pivotal studies are designed to establish non-inferiority of AR-13324 versus timolol, and results are expected in mid-2015. In addition, AR-13324 is being developed as a fixed combination with latanoprost (Roclatan, Aerie Pharmaceuticals), and results reported earlier this year from a phase IIb study showed the fixed combination met all clinical endpoints. Based on those positive results, planning of phase III studies of the fixed combination is underway. The pivotal trial program is expected to begin in mid-2015 with efficacy results becoming available in 2016.
Discussing AR-13324, Dr. Schuman paid tribute to David Epstein, MD, who passed away in March and who pioneered the research leading to the development of medications acting on the trabecular meshwork.
“It is sad that Dr. Epstein is not alive to see all the continuing progress occurring in the field that he stimulated,” commented Dr. Schuman, Distinguished Professor and Chairman of Ophthalmology, The Eye and Ear Foundation Endowed Chair in Ophthalmology, University of Pittsburgh School of Medicine, and Director, UPMC Eye Center, Pittsburgh.
Both Dr. Schuman and Dr. Kahook were cautiously optimistic about the promise of AR-13324, which so far has demonstrated good IOP-lowering activity and a favorable safety profile.
“We look forward to more data on efficacy as well as adverse events,” said Dr. Kahook, The Slater Family Endowed Chair in Ophthalmology and Professor of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora. “Hyperemia remains the big question for all rho kinase inhibitors, and we should start hearing more about how AR-13324 performs in this respect as the clinical trial program expands.”
Dr. Schuman also observed the potential for new adverse events to emerge as AR-13324 is studied in the larger populations being enrolled in the phase III studies.
Surgical options
Studies of multiple investigational surgical techniques are ongoing. Dr. Kahook mentioned the presentation of 2-year data from the randomized Hydrus II study comparing the Schlemm canal microstent (Hydrus, Ivantis) in combination with phacoemulsification with phacoemulsification alone as noteworthy. As reported by Thomas Samuelson, MD, in October at the annual meeting of the American Academy of Ophthalmology, Hydrus II was the first randomized, controlled trial in which a MIGS device lowered IOP by >20%, without medications, statistically more often than cataract surgery alone at 2 years.
“Stability of the treatment effect has been a metric of interest for judging the value of minimally invasive glaucoma surgical procedures, and the 2-year data from the Hydrus implant were encouraging. The fact that patients not only maintained significant IOP-lowering compared with baseline but also reduced dependence on medication was exciting for many glaucoma specialists,” said Dr. Kahook, who is also Chief, Glaucoma Service, & Director, Glaucoma Fellowship, University of Colorado Anschutz Medical Campus.
Both Dr. Kahook and Dr. Schuman observed there is good uptake of available MIGS procedures. However, Dr. Schuman noted that some glaucoma specialists are not too enthusiastic about these techniques because of the lack of strong data supporting their efficacy and durability.
OCT advances lead diagnostics technology
Systems for structural and functional imaging of the posterior segment of the eye are continuing to advance. No new options became available in the United States in 2014, but they may be on the market soon.
Dr. Schuman noted that swept-source OCT is now commercially available outside of the United States, and he anticipates its release here is on the horizon.
Speaking about its benefits, Dr. Schuman explained that swept-source OCT provides faster, broader imaging with deeper penetration compared with spectral domain OCT (SD-OCT).
“It generates an increased amount of information with a single scan, and offers enhanced visualization of the choroid without compromising imaging of structures anterior to the choroid,” he said.
Development of OCT angiography is also continuing. While not yet commercially available, Dr. Schuman said this technique should be coming soon, and he considers it an exciting advance.
“OCT angiography will allow us to see the vasculature in the macula, the optic nerve, and the peripapillary region using a quick noninvasive test that avoids the need for exogenous contrast agents,” he noted.
“In addition, compared with fluorescein angiography, OCT angiography can resolve smaller vessels,” he said. “Therefore, I expect it will be a valuable tool for improving our understanding of a variety of diseases, including glaucoma, diabetic retinopathy and macular degeneration.”
Progress is also being made in the development of functional imaging with OCT. Dr. Schuman noted that findings from investigations that have been conducted with the technique suggest it should provide a less technician dependent, more precise, and hopefully more accurate measurement of blood flow in the retina and optic nerve.
“The MIGS procedures are still trying to find their place in the glaucoma treatment algorithm,” Dr. Schuman said. “In the meantime, however, it should be stressed that they need to be used in the right setting, which is patients with early or perhaps moderate disease.
“Surgeons performing ab interno trabeculectomy with the Trabectome device (NeoMedix) or implanting a single trabecular bypass microstent (iStent, Glaukos) should not expect to achieve IOPs in the low teens, and that limitation may also apply to other procedures that are still investigational,” he said. “When patients need a low IOP, surgeons should still be considering traditional trabeculectomy or a tube implant.”
Dr. Schuman also expressed concern about the marketing of the trabecular microbypass stent in the United States as a single device considering its modest IOP-lowering effect.
“Available evidence indicates that two or more of these devices need to be implanted in order to get significant reduction in IOP,” he said. “Consistent with those data, the iStent is sold outside the United States with two devices in each package, and the second generation of the trabecular microbypass stent (iStent inject) is being developed with more than one stent preloaded in the injector system.”
Dr. Kahook added that we will see new minimally invasive devices coming to the market in 2015, including a novel goniotomy device from New World Medical that acts by removing the diseased trabecular meshwork from an ab interno approach.
“MIGS surgery is here to stay, and we will continue to see new innovations that enhance IOP lowering while preserving the favorable adverse even profile that MIGS is synonymous with today,” he said.
Trabeculectomy adjunct
In January 2014, Ocular Therapeutix received FDA approval for use of its hydrogel product (ReSure Sealant) to seal clear corneal incisions after cataract surgery. Dr. Kahook noted that he has been using the product off-label in some trabeculectomy cases, combining it with suturing to achieve watertight closure.
“In particular, I find ReSure to be useful in cases with thin conjunctiva where needle passes can lead to buttonholes or poor wound sealing,” he said. “The hydrogel sealant acts to augment the closure achieved by sutures alone.”
Dr. Kahook explained that placement of the hydrogel sealant over the sutures and at the unsutured edges of the incision is intended to enhance patient comfort and to provide a belt and suspenders approach to prevent incision leaking.
“It should be noted that ReSure Sealant does not have the tensile strength to close conjunctival wounds unassisted by sutures, and its utility in routine cases has never been studied,” he added.
Patient education and engagement
The problem of poor patient adherence with use of glaucoma medications is nothing new. However, as noted by Dr. Schuman, the message from Alan Robin, MD, about the need to recognize patients have problems properly administering their topical drops seems to be getting more attention, and deservedly so. Dr. Robin spoke on the topic during the 2014 Glaucoma Subspecialty Day.
“Proper technique for instilling topical ophthalmic medications is an often overlooked aspect of adherence to therapy, and a subject that requires patient education,” Dr. Schuman said. “In trying to improve medication adherence, clinicians need to think not just about asking patients whether or not they are using the medications they have been prescribed, but also about how they are using them.”
Dr. Schuman also stressed that education efforts need to reinforce the importance of a team approach in which the patient is an active member. Although there are a variety of tools for patient education, personal communication remains the best technique, he said.
“Patients need to have ownership in the process of their care and realize that effective management of their disease depends on a concerted effort involving them and the members of their medical team,” Dr. Schuman said.
“Electronic aids and other modalities, such as automated reminders to take medication or devices to guide administration, are helpful for improving adherence,” he said. “Albeit more expensive, the human touch remains most effective.”
Growth in technology startups providing mobile health-care applications, including some specifically targeting ophthalmology patients, continued in 2014. Dr. Kahook noted that for the second year in a row, the lineup of companies presenting at the Ophthalmology Innovation Summit included several showcasing digital ophthalmology technologies.
“We will increasingly see new venture capital-backed tech companies emerging with products designed to enhance the experience of ophthalmology patients as well as ophthalmologists,” Dr. Kahook said.
Malik Y. Kahook, MD
Dr. Kahook is a consultant to Alcon Laboratories, Aerie Pharmaceuticals, Allergan, ClarVista Medical, and the FDA. He has intellectual property interests with Abbott Medical Optics, ClarVista Medical, Glaukos, New World Medical, Oasis, and Prospex Medical.
Joel S. Schuman, MD
Dr. Schuman receives royalties for intellectual property licensed by Massachusetts Institute of Technology and Massachusetts Eye and Ear Infirmary to Carl Zeiss Meditec.
