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Eylea Wins FDA Approval for Wet AMD

But Iluvien implant for DME faces uphill struggle.

By Jerry Helzner, Senior Editor

■ The FDA recently made its longawaited decisions on two major therapies for retinal disease.

In a positive decision, Regeneron's Eylea (formerly VEGF Trap-Eye) won approval to treat wet AMD after the VIEW 1 and 2 trials highlighted the fact that Eylea can be as effective as its main competition, Lucentis, but with fewer doses, at least in the first year. New, 96-week VIEW trial data released in December showed PRN retreatment in the second year was approximately the same for Lucentis and Eylea patients, except for those needing the most intense treatment, where Eylea retained its advantage.

Conversely, the Iluvien sustainedrelease fluocinolone implant for the treatment of DME from Alimera Sciences failed to win approval. Alimera will have to conduct additional trials before the FDA will consider the therapy again.

Eylea's labeling calls for a 2 mg intravitreal injection every two months (following three monthly induction injections) with no need for monthly monitoring. The approved Lucentis 0.5 mg dose is recommended to be injected monthly.

Regeneron's management said that the cost/benefit profile of Eylea would justify pricing the drug at a premium to Lucentis. However, the company said it was responding to the concerns of retina specialists, patients, Medicare and other payers and will price the drug at $1,850 per dose, about $100 less than Lucentis is priced.

Regeneron estimates that, with no need for monthly monitoring, Eylea will cost approximately $16,000 per year per patient, while Lucentis currently costs $29,000 per year to treat each patient. The wild card in this equation is off-label Avastin, which costs about $50 per dose but which has recently been tarnished by safety concerns.

“The approval of Eylea offers a much needed new treatment option for patients with wet AMD,” said Jeffrey Heier, MD, a retinal specialist at Ophthalmic Consultants of Boston and chair of the Steering Committee for the VIEW 1 trial. “Eylea offers the potential of achieving the efficacy we've come to expect from current anti-VEGF agents, but with less frequent injections and no monitoring requirements. This may reduce the need for costly and time-consuming monthly office visits for patients and their caregivers.”

Regeneron's international partner for Eylea is Bayer Healthcare. The drug is currently in late-stage clinical trials for DME and RVO.

In the case of Alimera's steroid implant, the company said it has received a complete response letter (CRL) from the FDA denying approval for Iluvien for the treatment of DME associated with diabetic retinopathy. A CRL is issued by the FDA's Center for Drug Evaluation and Research when their review of an application is completed and questions remain that precludes the approval of the NDA in its current form.

The FDA stated that it was unable to approve the Iluvien NDA because the NDA did not provide sufficient data to support that Iluvien is safe and effective in the treatment of patients with DME. The FDA stated that the risks of adverse reactions shown for Iluvien in the FAME study were significant and were not offset by the benefits demonstrated by Iluvien in these clinical trials.

The FDA has indicated that Alimera will need to conduct two additional clinical trials to demonstrate that the product is safe and effective for the proposed indication. Alimera immediately requested a meeting with the FDA to discuss further steps.

Iluvien is Alimera's investigational, sustained drug-delivery system that releases sub-microgram levels of fluocinolone acetonide for the treatment of DME.

“We continue to believe in Iluvien as a long-term effective treatment option for DME,” said Dan Myers, president and CEO of Alimera. “We are committed to, and have the funds for, pursuing approval in Europe and for evaluating our options in the US.”

Dean McGee Eye Institute Has New Facility.

The center is affiliated with the University of Oklahoma.

■ The Dean McGee Eye Institute has dedicated the Institute's new $46 million, five-story, 78,000-squarefoot, world-class research and clinical facility. The new building, which adjoins the existing original facility built in 1975, doubles the space for research laboratories, expands clinical capacity by 40%, and consolidates all of the clinical care, vision research, teaching and administrative functions into one location.

The Dean McGee Eye Institute in Oklahoma City is affiliated with the Department of Ophthalmology of the University of Oklahoma.

“This new facility will streamline the Dean McGee Eye Institute's operations and enhance our multiple missions and programs by bringing them together under one roof,” said Gregory Skuta, MD, president and CEO of the Dean McGee Eye Institute and chair of the University of Oklahoma College of Medicine's Department of Ophthalmology.

“The tremendous growth of the Institute and our success in recruiting some of the nation's leading research and clinical talent over the last two decades created crowded conditions and forced us to expand into other facilities,” Dr. Skuta noted. “This remarkable new building will foster closer and more effective communication and collaboration as we continue to attract some of the finest minds in the country in vision care and research.”

Serving both adults and children, the Institute's clinical and surgical teams provide more than 150,000 patient visits and 7,000 surgical procedures each year. Dean McGee Eye Institute physicians and scientists hold numerous leadership positions in major professional and scientific organizations. The Institute's residency and fellowship training programs are highly competitive and attract top candidates from throughout the country.

“Translational research is the scientific endeavor to meld basic research with clinical observations to create new and novel treatments,” explained Paul Sieving, MD, director of the National Eye Institute. “Developing future advances in medical care requires close collaborations between physicians and medical researchers. The new building for the Dean McGee Eye Institute provides the very infrastructure needed to facilitate such interactions. This new resource will help ensure the continued and future success of the Eye Institute for decades to come.”

One Cornea/Two Transplants

The synergies of DALK and DMEK.

■ Researchers at the University of Erlangen-Nurnberg, Germany, conducted a 100-patient study in split-cornea transplantation that used a single cornea for two recipients — one a DALK procedure and the other a DMEK case. For each pair of patients, the procedures had to be done within 72 hours of each other.

As reported recently in the American Journal of Ophthalmology, the researchers found a single donor cornea could be used for both recipients in 47 cases. In three eyes, the DALK procedure had to be converted to penetrating keratoplasty (PK) requiring a full-thickness corneal graft. All 50 of the DMEK patients received their transplants.

Six months following surgery, mean BSCVA was 20/36 in the 47 eyes that underwent successful DALK, 20/50 in the three eyes that underwent conversion from DALK to PK, and 20/29 in the 50 eyes that underwent DMEK. Postoperative complications after DALK included Descemet's folds in five eyes and epitheliopathy in three eyes. After DMEK, partial graft detachment occurred in 26 eyes and was managed successfully with intracameral air reinjection. All corneas remained clear up to six months after surgery. No intraocular infections occurred.

The researchers concluded that split use of donor corneal tissue for combined DALK and DMEK procedures in two recipients within three subsequent days is a feasible approach to reduce donor shortage in corneal transplantation in the future.

AAO Exhibits Showcase Industry Innovation

Selected highlights of product announcements from this year's AAO.

■ Each year at the AAO annual meeting, after listening to groundbreaking research in the lecture halls, attendees venture into the exhibit hall to see some of it being applied to realworld practice of ophthalmology. Below is a sampling of some of the latest product innovations on display at this year's meeting in Orlando.

► Formula for corneal power measurements improves IOL selection. OCT pioneer David Huang, MD, has developed a formula for calculating total corneal power measurements via OCT, particularly in prior refractive surgery patients. The software was recently approved for use on the RTVue SD-OCT from Optovue. Net corneal power combines anterior and posterior curvature measurements from OCT scans. Optovue says the software images the posterior corneal surface with very high resolution, allowing it to measure corneal power precisely. “That is what is needed in post-LASIK eyes,” Dr. Huang noted.

Dr. Huang's research found that OCT-based IOL calculation was significantly better than clinical history and contact lens over-refraction methods, and accuracy of OCT-based IOL power calculation compared with Haigis-L after myopic laser vision correction equated to 82% of subjects being within 1D of astigmatism.

“As the segment of post-LASIK cataract patients grows, it is increasingly important that ophthalmologists have an accurate way to determine corneal power,” said Jay Wei, Optovue President and CEO.

► MicroPulse technology may eliminate retinal scarring. In a presentation at the AAO's annual meeting, Victor Chong, MD, reported that the use of Iridex's MicroPulse laser technology on DME patients required less energy, which resulted in less damage and no visible scarring. The company now offers an optional MicroPulse module for its IQ532 (green) laser system and a complete portfolio of infrared, yellow and green laser systems that can deliver MicroPulse laser treatments. Interested surgeons can find additional resources and share their experiences in a new online discussion forum launched by Iridex at www.iridex.com/micropulse.

► New products from Topcon. In addition to the SL-2G slit lamp with LED illumination, the KR-1 auto kerato-refractometer and CV-5000S automated phoropter, Topcon recently debuted the Synergy 2.0 ophthalmic data management system. An update to the company's EyeRoute system, the new software features a new graphical user interface and the EyeRead diabetic retinopathy module, which creates a personalized image-reading network. The Synergy 2.0 community portal allows users to share information with colleagues in real time via a secure platform.

► Medical-grade 3D recorder gets first glance. A new digital recording system, the HVO-3000MT, from Sony Electronics is in development for use with 3D/HD surgical camera systems. The system records surgical footage in standard 2D or 3D, which gives greater depth perception when reviewing procedures.

► Module II of JCAHPO EHR training available in January. Thanks to an educational grant from Compulink, the second part of the Joint Commission on Allied Health Personnel in Ophthalmology's webbased EHR training is slated to be available next month. The course module will focus on patient management, scheduling, insurance, billing and financial management and reporting. The cost will be $10 for members and $15 for non-members.

Compulink also recently partnered with VueCare Media to integrate the company's Vue Simulator, a patient education tool that uses 3D animations, graphics and videos to demonstrate eye conditions to patients and family.

► Synergetics working on new vitrectomy system. VersaVit, a portable vitrectomy platform that can run on battery power, should soon be cleared by the FDA for sale.

► Elevated IOP after dex implant may not influence VA. Srinivas Sadda, MD, recently presented a study on the relationship between IOP elevation and visual acuity in RVO patients treated with the sustained-release dexamethasone implant Ozurdex. He reported at this year's AAO meeting that patients with IOP elevation tended to be younger and male and had a higher baseline retinal thickness than those without elevation. Similar trends of VA improvement were found in both of these groups across time and the findings did not differ by type of RVO, suggesting that IOP elevation after dexamethasone implant may not influence VA improvement.

► New treatment for DME shows early promise. Quiroz-Mercado, MD, reported the results of Allegro's Phase 1 study, which focused on determining the safety and initial efficacy of integrin peptide therapy. The openlabel, single dose study enrolled patients suffering from advanced DME with visual acuity of 20/100 or worse. Eight of the 15 subjects in the study demonstrated three or more lines of BCVA improvement after 90 days and had a definitive improvement in OCT central macular thickness. These effects lasted until the end of the trial, which equates to 90 days off-treatment. Those that did not respond to treatment did not experience any disease progression during the trial.

► Web-based patient education resource helps encourage consumers to visit eye care professionals. Bausch + Lomb recently partnered with popular health information sites WebMD and Medscape to offer tools that explain the importance of maintaining eye health. Resources include assessments to improve eye care knowledge, editorials, videos about common eye concerns and steps to preserve healthy vision in each stage of life.

► Eyemaginations launches features through three new partnerships. The patient education resource Eyemaginations Luma is now compatible with Smart System from M&S Technologies, a computerized vision testing program. Through the partnership, Luma can be controlled through the Smart System using a remote control to present animations in the exam room.

A partnership with First Insight's MaximEyes practice management and EHR system passes diagnostic codes from MaximEyes into Luma to automatically cue relevant educational topics to review with the patient.

Thirdly, connecting with NexTech Practice 2011's EMR system provides an interactive button in the EMR software that directly links to patient education animations within Luma.

► New image-viewing software debuted. Kowa Optimed recently launched Digiversal, an image-viewing software that allows files from multiple instruments and medical facilities to be stored on a central database. The Draw-It feature gives practitioners the ability to make real-time drawings and notations. The software comes as a standalone product and is EHR interface-ready, according to the company.

► New data available about Ista products. Phase 3 study results report that a new low-concentration formulation of the NSAID bromfenac, to be marketed as Prolensa, was statistically significantly better than placebo and met the primary efficacy endpoint of absence of ocular inflammation 14 days following cataract surgery and the secondary efficacy endpoint of elimination of ocular pain on day post-surgery. Ista plans to file Prolensa new drug application in the first quarter of 2012.

Another Ista study found that bepotastine besilate ophthalmic solution 1.5% (Bepreve) was statistically and clinically superior to placebo in reducing ocular itch following exposure to grass pollens. Effects were seen as early as three minutes after allergen exposure and for at least 8 hours after dosing.

A third study evaluated whether bromfenac eyedrops and ranibizumab intravitreal injections would provide added efficacy over ranibizumab alone. Results indicated that combination therapy with an easily administered well-tolerated eyedrop and ranibizumab is efficacious for the treatment of AMD, but further studies are needed to validate findings.

► New intra-operative aberrometer debuts. Wavetec launched at the AAO the Optiwave Refractive Analysis (ORA) system. It's the company's latest diagnostic device designed to aid refractive decisions through intraoperative wavefront aberrometry measurements. The system attaches to a surgical microscope and provides a live, full-field display to guide cataract treatment in real-time, with a high resolution range of –5D to +20D. The software's algorithms aim to improve the accuracy of IOL selections and assist intraoperative astigmatic correction. OM