Cellular Pathways Point to Potential Glaucoma Breakthrough
New research out of the Icahn School of Medicine at Mount Sinai, New York, describes the basic cellular mechanisms of exfoliation glaucoma for the first time, according to a news release. The study, published in the July issue of PLOS One, could lead to new treatments.1
A team of researchers, including Robert Ritch, MD, Shelley and Steven Einhorn distinguished chair in ophthalmology, New York Eye and Ear Infirmary of Mount Sinai; Audrey Bernstein, PhD, associate professor of ophthalmology, Icahn School of Medicine at Mount Sinai; and J. Mario Wolosin, PhD, professor of ophthalmology, Icahn School of Medicine at Mount Sinai, conducted the study.
Drs. Bernstein and Wolosin coordinated with surgeons at New York Eye and Ear Infirmary of Mount Sinai to collect trabeculectomy tissue samples that would normally be discarded. Researchers grew cells from this tissue and compared them to cells from patients without exfoliation glaucoma. The researchers noticed that the cells from patients with exfoliation glaucoma were much larger than normal and contained an abundance of disorganized vesicles.
This finding, together with the vast literature on neurodegenerative diseases in which protein aggregates form, led to the discovery of a defect in the autophagy system, a process that normally degrades toxic aggregates by enveloping aggregated proteins in vesicles that eventually fuse with the lysosome, the endpoint organelle that acts as the “garbage disposal.” Researchers propose that, in exfoliation cells, the protein aggregates are not properly degraded and are expelled from the cells, leading to protein aggregates elsewhere in the eye that define exfoliation glaucoma. With these findings, researchers can use these cells as a model system to study the mechanisms of the disease to find a cure for exfoliation glaucoma. Additionally, researchers can use the cells to screen drugs that might reverse the condition.
This work was supported by the Research to Prevent Blindness, the MYS Family US Charitable Foundation, the Bright Focus Foundation, and the Glaucoma Foundation.
1. Want A, Gillespie WR, Wang Z, et al. Autophagy and mitochondrial dysfunction in Tenon fibroblasts from exfoliation glaucoma patients. PLOS One. http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0157404. Published July 8, 2016. Accessed September 15, 2016.
Contact Lens Medication Delivery as Effective as Drops
Researchers have shown that a novel contact lens-based system that uses a strategically placed drug polymer film to deliver medication gradually to the eye is at least as effective as daily latanoprost eye drops in a preclinical model for glaucoma, according to a news release.
“We found that a lower-dose contact lens delivered the same amount of pressure reduction as the latanoprost drops, and a higher-dose lens, interestingly enough, had better pressure reduction than the drops in our small study,” said lead author Joseph B. Ciolino, MD, in the press release. Dr. Ciolino is an ophthalmologist at Massachusetts Eye and Ear and an assistant professor of ophthalmology at Harvard Medical School. “Based on our preliminary data, the lenses have not only the potential to improve compliance for patients, but also the potential of providing better pressure reduction than the drops.”
Watch it Now
EyeWire TV reports on a contact lens designed to deliver medication for patients with glaucoma and other conditions requiring treatment with eye drops.
Contact lenses have been studied as a means of ocular drug delivery for nearly 50 years, yet many such lenses are ineffective because they dispense the drug too quickly. The authors of this study, which has been published in Ophthalmology, designed the contact lens to allow for a more controlled drug release.1 The researchers had previously shown in a 2014 study that the lens is capable of delivering medication continuously for 1 month.2
The researchers designed a novel contact lens that contains a thin film of drug-encapsulated polymers in the periphery. The drug-polymer film slows the drug coming out of the lens. Because the drug film is on the periphery, the center of the lens is clear, allowing for normal visual acuity, breathability, and hydration. The lenses can be made with no refractive power or with the ability to correct the refractive error in nearsighted or farsighted eyes.
The effect of this drug-eluting contact lens was assessed in four glaucomatous monkeys. The researchers are currently designing clinical trials to determine safety and efficacy of the lenses in humans.
This study was funded by the National Eye Institute, a technology development grant from Boston Children’s Hospital, and a career development award from Research to Prevent Blindness.
1. Ciolino JB, Ross AW, Tulsan R, et al. Latanoprost-eluting contact lenses in glaucomatous monkeys [published ahead of print on August 24, 2016]. Ophthalmology. doi:10.1016/j.ophtha.2016.06.038.
2. Ciolino JB, Stefanescu CF, Ross AE. In vivo performance of a drug-eluting contact lens to treat glaucoma for a month. Biomaterials. 2014;35(1):432-439.
Xiidra Is Now Available by Prescription in the United States
Watch it Now
Shire’s dry eye drug Xiidra (lifitegrast ophthalmic solution 5%) is now available by prescription in the United States.
Xiidra (lifitegrast ophthalmic solution) 5%, a twice-daily prescription eye drop indicated for the treatment of the signs and symptoms of dry eye disease, is now available by prescription in the United States, according to Shire. The FDA approved Xiidra on July 11, 2016.
Shire offers two patient-focused programs to share information about prescription coverage and savings. Ask iiris is a phone service offering live-person responses to questions regarding information about patients’ insurance coverage, benefits, copays, and product availability in pharmacies. Xiidra iinsider offers information and special offers via text message or email.
Visco360 System Is CE Mark Approved
The Visco360 System (Sight Sciences) is now CE Mark approved, offering ophthalmologists in the EU a clear corneal approach to canaloplasty, according to a company news release. The initial European commercial cases were presented during the European Society of Cataract and Refractive Surgeons (ESCRS) meeting in Copenhagen, Denmark.1
The Visco360 System is a fully integrated, single-handed, single-use device specifically designed for an ab interno approach to Schlemm canal using a single clear corneal incision. The system combines a custom-access cannula, a flexible microcatheter with an atraumatic tip, an internal infusion pump and viscoelastic reservoir, and a wheel that controls advancement and retraction of the microcatheter using one finger.
The Visco360 Viscosurgical System is commercially available in the United States as a manual surgical tool but is investigational for the specific indication of IOP reduction in adult, pseudophakic patients with primary open-angle glaucoma.
1. Körber N. Visco360 viscosurgical instrument for ab interno canaloplasty: technique and first results. Paper presented at: The XXXIV Congress of the ESCRS; September 12, 2016; Copenhagen, Denmark.
Inotek Completes the Recruitment Phase of MATRX-1
Inotek Pharmaceuticals completed the active recruitment phase of MATRX-1, the first pivotal phase 3 trial of trabodenoson for the treatment of glaucoma, according to a company press release. Trabodenoson, the company’s lead clinical candidate, is a first-in-class selective adenosine A1 mimetic that was observed in phase 2 clinical trials to reduce IOP. Topline data from the study are expected in December 2016.
MATRX-1 is a phase 3, randomized, double-masked, placebo-controlled trial that is designed to assess the safety, efficacy, and tolerability of trabodenoson over 3 months of treatment in 335 patients with primary open-angle glaucoma or ocular hypertension. The primary endpoint is reduction of IOP compared with the placebo treatment arm. The study includes three doses of trabodenoson: 3% (1,000 µg) once daily, 4.5% (1,500 µg) twice daily, and 6% (2000 µg) once daily. In addition, the study contains a timolol 0.5% arm to validate the sensitivity of the patient population and serve as an internal control. Enrollment criteria include patients with an IOP ranging from 24 mm Hg to 34 mm Hg, which represents the patients most likely to receive treatment for glaucoma or ocular hypertension.
Allergan Acquires ForSight Vision5
Allergan will acquire ForSight Vision5 for a $95 million upfront payment and a launch milestone payment related to ForSight’s lead development program, a periocular ring that releases bimatoprost over multiple months to lower elevated IOP in glaucoma or ocular hypertension. The transaction is subject to customary closing conditions.
The noninvasive, preservative-free ring rests on the surface of the eye (under the eyelids). A randomized and controlled phase 2 study comparing the investigational ring to twice-daily timolol eye drops demonstrated that a single administration of the ring provided a sustained reduction in IOP for 6 months with a reduction of 4 to 6 mm Hg at the study’s primary endpoint of 12 weeks. Approximately 90% of subjects retained inserts in both eyes for 6 months without clinician assistance.“If approved, this technology could provide an important advance to address the significant challenges of patient compliance and adherence in glaucoma,” noted David Nicholson, chief research and development officer, Allergan, said in a company news release. “Importantly, this technology would also be highly complementary to our ongoing portfolio and development programs that are moving glaucoma treatment toward dropless therapies.”
Roclatan Achieves Primary Efficacy Endpoint in
Mercury 1 Study
Aerie Pharmaceuticals’ Roclatan (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005% achieved its 90-day primary efficacy results in the phase 3 Mercury 1 clinical trial. Roclatan dosed once daily demonstrated statistical superiority over both latanoprost and Aerie’s Rhopressa (netarsudil) at the primary endpoint range of baseline IOPs from above 20 to below 36 mm Hg for each of nine measured time points.
Efficacy levels were consistent across the 90-day period for all arms in the study. Mean diurnal IOP lowering with Roclatan exceeded that with latanoprost by an average of 1.9 mm Hg and exceeded Rhopressa by 2.6 mm Hg. Roclatan reduced mean diurnal IOP to 16 mm Hg or lower in 61% of patients, a significantly higher percentage than observed in the comparator arms. The most common adverse event with Roclatan was hyperemia, which was reported in approximately 50% of patients.
If Mercury 1 and Mercury 2 (an efficacy trial that commenced in March 2016) are successful, Aerie expects to file a new drug application for Roclatan at the end of 2017, according to a news release.
Viewi Device Lets Patients Perform Static Perimetry at Home
The new Viewi device (Cambridge Consultants) works with a smartphone app to let patients perform a static perimetry test at home, according to a company press release. A smartphone is slotted into the portable headset, where it runs a conventional suprathreshold test in less than 5 minutes per eye. The patient presses a button that is connected to the headset via Bluetooth Smart each time he or she sees one of the flashing dots. The results of the static perimetry test are displayed in a nontechnical format on the smartphone for the patient to track and share with his or her physician.
“The Viewi system doesn’t aim to replace the current screening and management system; it’s been designed to augment the clinical tests,” noted Simon Karger, head of surgical and interventional products at Cambridge Consultants, in the press release. “Although the current clinical tests work exceptionally well, the system for glaucoma management is overloaded.”
The Viewi technology can provide an early warning system for people at risk of developing glaucoma, and it can make static perimetry accessible to more patients in developing countries, according to the company. n