Report from AAO
Report from AAO
Genetic Testing Companies Respond to AAO Stance
Statement discourages doctors from using tests in AMD.
By Bill Kekevian, Associate Editor
■ The AAO ruffled some feathers at its annual meeting last month when it issued a statement discouraging the use of genetic testing for AMD. The AAO says genetic tests offer little benefit to patients. An increase in genetic-testing companies marketing directly to patients prompted the society to reaffirm its position. Arctic DX, which makes the Macula Risk DNA test for AMD, disagrees, releasing its own statement in reply.
The AAO statement explicitly advises ophthalmologists to avoid genetic testing for complex eye disorders such as AMD and certain types of glaucoma. “AMD is caused by multiple factors, including lifestyle choices such as smoking and diet, as well as genetics,” the statement reads. “Although several genotypes are associated with increased risk for AMD, at this time, genetic testing provides no proven advantage in preventing or treating the disease.”
The recommendation is based on a study in Ophthalmology that stated genetic tests for complex diseases will only become relevant once clinical trials demonstrate patients with specific genotypes can benefit from specific types of therapy or surveillance.1 The AAO states that according to the analysis, “current genetic tests for AMD are flawed and cannot reliably help predict clinical outcomes.”
Arctic DX’s response: “The statement ‘current genetic tests for AMD are flawed’ is invalid and potentially detrimental to patients with advancing disease who could benefit from increased surveillance,” the company’s comment reads.
Arctic DX points to numerous studies on the effectiveness of early treatment for AMD, and even says it generally agrees with the Task Force on Genetic Testing study that the AAO also cites. Although that study advises against routine genetic tests, it also concludes genetic testing can improve the accuracy of diagnoses and reduce the risk of disease occurrence in families at risk.
The AAO insists current comprehensive eye exams are more effective than the available genetic tests for identifying treatable disease. However, Arctic DX challenges that, claiming that its test for predicting the risk of AMD progression is the most accurate method. The company cited a 2007 study that demonstrated early detection as a major contributing factor in preserving vision.
Another diagnostic company, Sequenom Inc., which markets the RetnaGene AMD test, released a study also at the AAO meeting that showed its predictive model of using a combined genotype with phenotype testing was 96% accurate in predicting progression to CNV in patients with AMD.2
A Massachusetts Eye and Ear Infirmary study published in May 2011 acknowledged “a clear genetic influence on disease risk” for AMD. The study points to more than 25 genes that may influence AMD risk.3
1. Stone E, Aldave A, Drack A. Recommendations for genetic testing of inherited eye diseases. Ophthalmology. 2012;119:2408-2410.
2. Perlee L. Combining Genotype and Phenotype to Predict Progression to Choroidal Neovascularization (CNV) in Patients with AMD. Paper presented at American Academy of Ophthalmology, Chicago; Monday, November 12, 2012.
3. Deangelis MM, Silveira AC, Carr EA, Kim IK. Genetics of age-related macular degeneration: current concepts, future directions. Semin Ophthalmol. 2011;26:77-93.
Good, Bad News on Cataract Reimbursements
■ CMS’ recently published final rule to reduce reimbursement for cataract surgery 13.5% in the 2013 Medicare physician fee schedule generated a fair share of angst at the AAO meeting in Chicago last month, but not all is woe for ophthalmology in the year ahead.
Michael X. Repka, MD, AAO medical director for governmental affairs, reported the decrease in valuation was driven by the reduction in time required for cataract surgery — from 35 to 21 minutes, based on a CMS review that involved input from the AAO and ASCRS. “Cataract surgery has gotten better, but it’s also gotten faster,” he explained. “Value is driven to a large extent by time, and that’s important for our members to understand.”
However, Dr. Repka went on to highlight the good news from CMS for ophthalmologists. For one, cataract surgery will not be revalued for another five years. Further, he added, “I want to remind everyone that payments from Medicare on top of the fee schedule have increased to ophthalmologists.”
Bonus programs such as the Physician Quality Reporting System and e-prescribing initiative, in which ophthalmologists have participated with success, have gone a long way toward offsetting reductions in Medicare reimbursements for the specialty, he pointed out.
Dr. Repka offered more good news for cataract surgeons when CMS provided clarification on physician fees when they use a femtosecond laser for cataract surgery. Coverage and payment for cataract surgery performed with a “bladeless, computer-controlled laser” should follow the same rules as conventional cataract surgery, CMS says — that is, cataract removal and the insertion of conventional IOLs is fully covered whichever incision method is used. Physicians are permitted to charge beneficiaries for non-covered services when implanting a presbyopia-correcting or astigmatism-correcting IOL.
First-in-class lOP-lowering Drug Shows Promise
Trabodenoson shown to restore outflow via the trabecular meshwork.
■ Preliminary results of a phase 2 clinical trial evaluating the efficacy and safety of the eyedrop trabodenoson in primary open-angle glaucoma or ocular hypertension has successfully achieved its primary and secondary endpoints, according to a presentation by Inotek Pharmaceuticals at AAO.
In the 144-patient trial, trabodenoson reduced IOP by about 7 mm Hg at 28 days and was safe and well tolerated with less eye irritation than currently approved glaucoma treatments, Inotek CEO Paul Howes said. Trabodenoson is a first-in-class, highly selective A1 subtype adenosine mimetic that binds to epithelial cells in the trabecular meshwork, increasing outflow and lowering IOP, the company said.
“These phase 2 trabodenoson results are highly encouraging, with the efficacy and safety data suggesting the potential for a glaucoma treatment with a profile superior to currently approved drugs,” said Rudolf A. Baumgartner, MD, chief medical officer at Inotek. “Additionally, based on pharmacodynamics observed in this study, we are also encouraged by the possibility of once-daily dosing, and look forward to exploring this profile in future trials.”
Jonathan Myers, MD, of Wills Eye Institute, Philadelphia, added, “Trabodenoson is one of the most promising glaucoma drug candidates in development, based on its novel mechanism of action, the safety and efficacy observed to date and the potential for once-daily dosing.”
Trabodenoson appears to restore the permeability to fluid of the trabecular meshwork, he said. “If these data are borne out in further clinical evaluation, trabodenoson could shift the paradigm of treatment for patients with glaucoma,” Dr. Myers said.
Based on the phase 2 results, Inotek is planning a comprehensive late-stage clinical development program for trabodenoson.
Outlook for Faster Device Approvals Brightens
But FDA reviews for ophthalmic drugs is a different story.
■ Faster and more streamlined FDA reviews of ophthalmic devices are in the offing with the implementation of new user fees on device companies, attendees at the fourth annual Ophthalmology Innovation Summit (OIS) heard in Chicago last month, a day before the AAO meeting.
Two FDA officers addressed the gathering, giving divergent outlooks for their respective divisions: Wiley Chambers, MD, supervisory medical officer for the Division of Transplant and Ophthalmology Products; and Malvina Eydelman, MD, director of the Division of Ophthalmic, Neurologic and Ear, Nose and Throat Devices.
Dr. Eydelman noted the implementation of the Medical Device User Fee Amendments of 2012, or MDUFA III, with the signing of the FDA Safety and Innovation Act in July, would have “a tremendous impact” on her division. MDUFA III went into effect October 1 and sunsets in five years. “It allows us funding for increased staffing and reduction of the reviewer-to-manager ratio,” she said.
MDUFA III authorizes the FDA to collect about $595 million in user fees over five years, allowing for the hire of more than 200 full-time-equivalent employees. Dr. Eydelman said her division was split into two divisions: Ophthalmic and Ear, Nose and Throat Devices; and Neurological and Physical Medicine. Of 1,441 device applications the previously combined division received in 2012, nearly a third, or 447, were for ophthalmic devices, she said.
The 40 reviewers in the new ophthalmic and ENT unit all have experience with ophthalmic devices, she said. “I really think it is a huge step forward for ophthalmic devices,” Dr. Eydelman told the OIS.
On the pharma side, the outlook was just the opposite, despite the reauthorization of the Prescription Drug User Fee Act, known as PDUFA V, as it is the fifth authorization of the act. “We are not anticipating having any new staff with PDUFA V; we did not get any new staff before,” Dr. Chambers told OIS. “In the reorganization that occurred within our division last year, ophthalmic drugs was placed with transplant products and we were told we were overstaffed.” He noted the division now has fewer ophthalmology budget managers than it did last year.
Both Drs. Chambers and Eydelman said their divisions were taking steps to streamline and shorten review cycles, specifically by codifying a pre-review process to help would-be applicants get their paperwork in order for drug and device approvals.
Drs. Chambers and Eydelman spoke on a panel with three venture capitalists whom have invested in ophthalmic start-ups. All three agreed that streamlining the FDA process should generate more investments in the life sciences. “These acts should have a significant impact on the regulatory process,” added panel moderator Richard Lindstrom, MD, of Minnesota Eye Consultants.
Endoscopy-assisted Vitreoretinal Surgery On the Horizon
The EndoOptiks E2 system has been found useful in complex retinal procedures.
Andrew E. Mathis, Ph.D., Medical Editor
■ Endoscopy can be a useful adjunct for vitrectomy, dye-assisted membrane peeling and anterior-segment and pars plana cyclophotocoagulation, according to Jorge G. Arroyo, MD, who discussed the EndoOptiks E2 laser and endoscopy system and its applications in retina during Retina 2012 Subspecialty Day at the AAO meeting.
“The E2 also allows us to work in areas of the eye that are normally very difficult to visualize, like peeling ciliary body membranes in patients with hypotony,” Dr. Arroyo says. “The endoscope allows us to attack and remove those membranes in those sorts of challenging cases.”
Dr. Arroyo, associate professor of ophthalmology at Harvard Medical School and on staff at Beth Israel Deaconess Medical Center in Boston, sees a growing role for endoscopy in vitreoretinal surgery. “Whether or not people need it for 90% of their cases, probably not,” he says. “But I do think it will be useful in more challenging, complex cases, especially having to do with the periphery.”
He continues, “Our standard ways of visualizing the retina work quite well for the posterior pole. It’s just that when you work in the retinal periphery, it’s hard to see what you’re doing.”
Dr. Arroyo also sees a role for the E2 in panretinal photocoagulation. The E2 comes equipped with an 810-nm diode laser with a 175-W xenon light source.
Regarding perennial concerns about phototoxicity to the retina, Dr. Arroyo is cautious but does not think endoscopes will pose any greater danger to the retina than light pipes already in use.
Dr. Arroyo also addressed gauge size, another constant issue in vitreoretinal surgery, with 25-gauge vitrectomy systems now common and 27- and 29-gauge instruments in development. The 23-gauge endoscope probe of the E2 is considered minimally invasive, but Dr. Arroyo says, “We run into the realities of physics, and I’m not 100% sure that the probes are going to get any smaller.” OM
Arroyo JG. Current role of endoscopy in vitreoretinal surgery. Presented at: Retina 2012 AAO Subspecialty Day; November 9, 2012; Chicago, IL.
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