Progress on Sustained-Delivery Lucentis
JERRY HELZNER, SENIOR EDITOR
■ Despite the remarkable effectiveness demonstrated by Lucentis (and off-label Avastin) in successfully treating wet AMD and other retinal diseases, patients and physicians have been hoping for an alternative to the frequent intravitreal injections that these treatments have involved.
The good news is that a sustained-delivery version of Lucentis is in development and may begin a clinical trial in the not-so-distant future. Rapid progress in this area is the result of a new partnership between Genentech and SurModics, which calls for SurModics to develop a sustained-delivery system for Lucentis.
“SurModics has developed a biode gradable microparticles drug-delivery system, which is currently in toxicity testing,” Michele Libonati, Lucentis Lifecycle Leader, told Retinal Physician as part of a wide-ranging interview re garding future plans for maintaining Lucentis in the forefront of retinal disease therapies. “If all goes well, we will file an IND with the FDA and then begin a clinical trial. We believe that this microparticle system may be able to deliver Lucentis over a period of approximately four to six months.”
In addition to developing a sustained-delivery system for Lucentis, the Genentech-sponsored ongoing HARBOR trial involves using an in creased dose of Lucentis (2 mg vs the current 0.5 mg dose) in an effort to improve visual results.
Though conceding that the competitive landscape has changed with more potential competitors to Lucentis emerging, Ms. Libonati said that Genentech welcomes competition and potential advancements in medicine, as they are good for patients and en hance the medical community's un derstanding of wet AMD.
“Our only goal, as with all of our drugs, is to maximize the benefit to patients,” she asserted. “We would be doing this regardless of the competitive situation.”
In other Lucentis-related areas:
► According to Genentech, the results of the current CATT study, a head-to-head trial comparing Lucentis to Avastin in wet AMD, may not provide all the necessary information to assess the use of Avastin given the company's concerns with the limitations of the trial design, including safety.
► Though Genentech closely follows the results of small, uncontrolled studies using Lucentis to treat a range of retinal diseases, the company's development program includes DME and RVO (both branch and central).
► Although Lucentis is being studied in clinical trials in combination with other treatments, Genentech currently recommends that Lucentis be used as monotherapy, in accordance with its approved indication.
► The company is closely following the progress of a potentially competitive wet AMD treatment, Regenerons VEGF Trap-Eye, which is expected to conclude two pivotal phase 3 trials sometime in 2010.
“We're always looking at competitors and potential competitors,” concluded Ms. Libonati.
■ OD-OS has FDA clearance to market Navilas. In early November, Germany's OD-OS, Inc. received approval to market its Navilas laser in the US for applications such as PRP in diabetic retinopathy. The laser's unique features include a 50-degree field of view and real-time imaging of the retina in color — both mydratic and non-mydratic. Surgeons plan their approach prior to the procedure, and the targets are overlaid onto the surgical field for guidance. Initial accuracy results indicate a microaneurysm hit rate of 92%, said clinical investigator William Freeman, MD. For more information, see 'Focus On' of this issue.
■ Errata. The Nov/Dec 2009 Clinical Trial Update section incorrectly identified Acucela's dry AMD compound. The current name is ACU-4429.
Also, in the article “Perfluoron and Silicone Oil for Complex Retinal Detachments” by Steven M. Cohen, Figure 3 was incorrectly reproduced. The correct figure can be found in Retina, 4th ed., Ryan SJ, Hinton DR, Schacht AP, and Wilkinson CP, eds., Chapter 130, Figure 3.
■ Reprieve on Medicare physician fees. Physicians were spared an imminent 21.2% reduction In 2010 Medicare fees in mid-December when Congress tacked a 60-day extension of the current payment schedule onto a bipartisan defense appropriations bill.
Lawmakers believe that the additional time will allow them to work out a more permanent formula for determining Medicare physician fees that would replace the Sustainable Growth Rate (SGR) formula. The SGR has threatened cuts in physician fees each year.
■ MacuSight drug is fast tracked. MacuSight, a developer of therapeutics for the treatment of severe ocular diseases and conditions, said it has received Fast Track designation from the FDA for Perceiva, the company's proprietary ocular sirolimus product, for the treatment of DME. MacuSight is currently advancing Perceiva in a broad phase 2 clinical program across multiple large ocular indications.
The company recently announced that it had completed enrollment in four separate phase 2 studies evaluating Perceiva as a treatment for DME, wet AMD, and dry eye syndrome. The company plans to announce data from these studies in the first half of 2010.
■ “Consultation” coding eliminated. Beginning with the start of 2010, Medicare has changed its coding procedures so that ophthalmologists will no longer be permitted to code for inpatient and outpatient consultations. Non-Medicare insurance carriers may still permit such coding under existing CPT codes but practices should check with individual carriers.
“There could be a significant loss of income for retinal physicians and other subspecialists, particularly those who practice in an ophthalmology group as an ophthalmic subspecialist,” says coding expert Riva Lee Asbell.
Ms. Asbell advises that all practices should quickly get up to speed on how to request reimbursement for patients who previously fell under the “consultation” category. She says these patients will now have to be categorized as “new patients” or “established patients,” depending on which criteria they meet. She notes that the criteria for a “new patient” changed several years ago and the more recent criteria must be used.
“Subspecialists in a group practice with other ophthalmologists — especially those who are retina specialists — will most acutely feel the loss of income caused by the inability to code for intraoffice consultations,” asserts Ms. Asbell.
Ms. Asbell says practices must now brush up on E/M coding and carefully select the code that best suits the circumstances, is in compliance with Medicare's rules (especially medical necessity) and optimizes reimbursement.
Since these intraoffice referrals now must be coded as established patients, the basic choices will be between certain E/M codes and certain Eye codes.
For additional information, please read Coding Q&A article of this issue.
Ms. Asbell cautions that not understanding the new rules could result in both loss of income and an unwelcome audit. She says that now may be the time to obtain the services of a coding expert if the practice does not already have access to such expertise. RP
TADRS: An Early Detection System for DR
LESLIE GOLDBERG, ASSOCIATE EDITOR
■ Some retinal photos an ophthalmologist colleague had shown him fascinated Steve Liu, PhD. This initial experience led Dr. Liu and his colleagues at Texas A&M's Department of Computer Science and Engineering to develop a computer-based diabetic retinopathy detection system.
The Texas Advanced DR detection system (TADRS) uses computer algorithms to recognize the well-defined symptoms of DR, especially those appearing in the earliest stages. The system is designed as a tool for patients and their care providers to detect and track the DR so that medical interventions can be implemented in a timely manner.
“Ophthalmologists told me how important microaneurysms were in detecting DR in patients. Microaneurysms are the most reliable indicator of DR,” Dr. Liu says. “Since we specialize in computing and mathematics, we did some basic mathematical modeling of objects in the retina. Blood vessels can be easily characterized by mathematical formulation. We used the correlation of blood vessels to build specific applications for the ophthalmologist's needs.”
TADRS involves two key pieces of equipment: a non-mydriatic retinal camera and software that has been developed by Dr. Liu and other re searchers to read the data from the picture of a patient's retina.
Getting an early reading on diabetic retinopathy.
“Using the fundus pictures taken, we analyze and derive numerical properties that are unique for blood vessels, including microaneuyrsms. The next step is to differentiate them,” says Dr. Liu. “ We identify distinct properties that can be formulated into computing procedures and with the retina pictures taken, we are able to generate a map of the blood vessels.”
Dr. Liu says that ophthalmologists are overwhelmed by patient demand. “If we can come up with automated procedures to assist them and screen those most susceptible, we can help improve the rate of care,” says Dr. Liu.
His goal was to design a system that can be used by technicians, not doctors. If the technicians can get quality pictures, the software can process the images and help select those images that need to be viewed by the doctor and the patient can receive a higher level of care. “ We want to keep thing simple. This allows retinal photos to be screened more regularly and conveniently at lower cost.”
Dr. Liu stresses that the software is not to be used for diagnosis — that is to be left to the doctors. He says the strength of the computer is its consistency. “The computer is a tool for making better judgments and better tracking,” says Dr. Liu. “Certain algorithms can derive the information that you want in a consistent way, and this works very well for tracking the change of shape and size in vessel structures.”
TADRS is currently being used in clinical trials in 12 Texas cities coordinated by the Health Science Center in Texas A&M. Jyh-Charn (Steve) Liu may be reached at firstname.lastname@example.org.
Floaters and Flashes: Red Flags for PVD
ANDREW E. MATHIS, PhD, MEDICAL EDITOR
■ If you saw in your office a 62-year-old woman with hypertension presenting with a week-long history of a large floater in the left eye and what she described as a “cloud” in her visual field, how would you diagnose her?
What if, five days earlier, she had seen “light flashes” in the same eye? What if she'd had a perfect refraction performed by an OD exam six months earlier? This is the question posed by a team of physicians from Kingston, Ontario, headed by Sanjay Sharma, MD, MSc, FRCSC, an ophthalmologist and epidemiologist, in an article in the November 25 issue of JAMA.
Retinal physicians and general ophthalmologists may do extensive screening on such a patient, but a general practitioner seeing such a patient may conclude, because of the prevalence of floaters and light flashes as often harmless symptoms, that nothing is wrong. In fact, Dr. Sharma argues, floaters and flashing lights can be a symptom of posterior vitreous detachment and can lead to permanent vision loss.
Dr. Sharma and his colleagues conducted a meta-analysis of 17 previously published articles on PVD with patients presenting with flashes or floaters, and found that patients presenting with such symptoms had a 14% prevalence of retinal tear consequent to PVD.
The Kingston team is using the JAMA article as an opportunity to provide differential diagnosis hints to GPs who may see such patients, as well as a three-step guideline on evaluation and treatment. They also offer comprehensive recommendations for when to refer to a specialist.
In addition, Dr. Sharma has placed a series of videos online at the Insider Medicine Web site, where physicians and patients can learn about general retinal medicine, as well as how to diagnose and treat retinal disorders that cause symptomology, including floaters or flashes of light. Retinal Physician has provided a redirect URL here: http://retinalphysician.vdirect.com.
The JAMA article closes as it opens — with the hypothetical case of a 62-year-old patient with floaters. Dr. Sharma and his colleagues hope that differential diagnosis for PVD will be a more common practice for GPs and ER personnel thanks to their article.