Subspecialty News

New data from Practices and Trends survey; CMS had planned $7 Avastin reimbursement; Sustained-release Lucentis; and more


2009 PAT Survey Results

Treatment Methods Reflect Individual Preferences.


■ The 2009 Practices and Trends (PAT) Survey results show a US retinal community that is generally in agreement on which procedures constitute the safest and most efficacious treatment methods, but also reflects individual physician preferences in when and how specific treatments should be administered.

The latest PAT data, which encompasses the responses of 434 members of the American Society of Retinal Specialists (ASRS), has been generously provided to Retinal Physician by the ASRS and by survey editor Robert A. Mittra, MD, and survey co-editor John S. Pollack, MD.

One of the single greatest areas of agreement shown by the survey is in the initial management of wet AMD patients, which almost two-thirds of survey respondents view as both an acute and chronic disease. Approximately 76% of respondents prefer to begin treatment with three to four intravitreal anti-VEGF injections, followed by treatment based on lesion activity and vision. Another 15% begin with a single anti-VEGF injection and then treat on lesion activity and vision. That translates to 91% of doctors employing somewhat similar treatment plans for initial management of wet AMD.

Among the remaining 9% of retina specialists, 5.54% treat with anti-VEGF injections every four to six weeks on a set schedule and 1.6% use PDT and an intravitreal steroid along with anti-VEGF.

Another area of general agreement is in suggesting a vitamin regimen for patients with non-exudative AMD who are at a high risk of disease progression. In this area, 70% of retina specialists recommend the AREDS formula, 11.83% suggest vitamin C, zinc, and lutein, and 12.76% favor vitamin C, zinc, lutein, and zeaxanthine.

Individual doctor preferences reveal themselves when PDT is used in combination with anti-VEGF therapy. With these patients, 26.74% of respondents perform the PDT procedure on the same day, 11.86% employ PDT one or more days prior to the anti-VEGF injection, 24.19% do PDT one or more days after the anti-VEGF injection, and 36.74% do not use this combination.

Doctors also display their own preferences in suggesting a treatment plan for a 55-year-old with perfused BRVO of three-month duration with symptomatic CME and 20/30 vision. For this patient, 16.63% of respondents prefer observation, 34.64% would inject with Avastin, 1.62% would inject with Lucentis, 6.24% would inject with triamcinolone, 22.4% would use grid laser, and 16.86% would use a combination of laser plus anti-VEGF or steroid.

In other PAT categories, 40.05% of respondents said they routinely wear sterile gloves for performing in-office intravitreal injections, while 57.87% normally don't wear gloves for this procedure. In addition, 38.68% of respondents don't do 25-g vitrectomy while 20.61% do 25-g in less than 10% of their patients.

In terms of performing surgery in an ASC setting, 34.18% of respondents are currently doing the great majority (76% to 100%) of their surgeries in an ASC but almost 42% see themselves as performing 76% to 100% of their surgeries in the ASC setting three years from now. In another survey question that looks ahead, 20.66% of respondents see themselves using only disposable instruments in the future, 33.93 would prefer to use disposable instruments when they are available, 31.36% prefer reusable instruments, and 14.03% are not sure yet.

Lastly, in choosing the vitreoretinal pathology that is most difficult to repair, 47.85% of respondents report that recurrent rhegmatogenous retinal detachment with severe posterior and anterior PVR requiring relaxing retinectomy is about as equally difficult to repair as combined severe diabetic "tabletop" traction detachment of the posterior pole with rhegmatogenous component. Both are considered very difficult to repair.

CMS Had Planned $7 Avastin Reimbursement

Ruling Reversed After Numerous Complaints.


■ In what appears to be a case of rigid bureaucratic regulations trumping real-world decision-making, CMS had set the wheels in motion to reduce reimbursement to ophthalmologists for an intravitreal injection of Avastin from $50 to $7. CMS says the planned reduction — which was reversed on October 27 following numerous complaints — came as a result of a statutory requirement to provide a new code for the cost of the actual amount of Avastin used in an ophthalmic procedure.

"This was the result of a routine update required by law and was certainly not intended to cause an adverse situation for physicians and their patients," CMS Press Officer Ellen Griffith told Retinal Physician. "CMS takes seriously the concerns expressed by ophthalmologists."

The planned reduction drew the immediate ire of Sen. Herb Kohl (D-Wisc.), who, along with the American Academy of Ophthalmology and most of the ophthalmology community, views Avastin as comparable to the much more expensive Lucentis in terms of efficacy and safety. Sen. Kohl has been a leader in Congress in making it easier for ophthalmologists to use Avastin off label as an acceptable substitute for Lucentis, which is reimbursed at approximately $2,000 per injection.

In proposing to reduce the Avastin reimbursement, CMS officials also cited a regulation prohibiting Medicare from paying for costs incurred through use of a compounding pharmacy. Ophthalmologists use compounding pharmacies to break larger vials of Avastin into individual doses.

Genentech manufactures both drugs and has been consistent in asserting that Lucentis was specifically developed for eye care while Avastin was not. However, the company says it has had no involvement in the CMS decision to attempt to reduce reimbursement.

CMS said it reviewed the concerns of Sen. Kohl and the AAO before arriving at the decision to reverse the reduction. If the Avastin payment had actually been reduced to $7, it would most likely have resulted in retina specialists using more Lucentis, which could have cost CMS an estimated $500 million a year in additional Lucentis reimbursement.

Results of the large, ongoing CATT study, which is designed to directly compare the safety and efficacy of Lucentis and Avastin, will not be available until 2011. Data from the CATT study will probably affect future CMS reimbursement policies.

Sustained-Release Planned for Lucentis

SurModics to Design New Delivery System.

■ SurModics, Inc., a provider of drug-delivery and surface-modification technologies to the healthcare industry, has signed an exclusive license and development agreement with Roche and Genentech to use SurModics' proprietary biodegradable microparticles drug-delivery system to develop and commercialize a sustained-release drug-delivery formulation of Lucentis. The agreement further provides Roche and Genentech with opportunities to develop additional compounds for the treatment of ophthalmic diseases.

Though the anti-VEGF drug Lucentis has quickly become the accepted standard of care for wet AMD and is being widely used offlabel to treat other retinal diseases, the need for intravitreal injections every four to eight weeks has created great interest in finding an alternative delivery method.

SurModics claims expertise in a broad range of drug-delivery systems. The company's Web site alludes to several types of approaches that could be used, with a polymer implant deemed to be the most likely vehicle for a sustained-release formulation of Lucentis.

"SurModics' drug-delivery solutions feature a broad set of state-of-the-art drug-delivery microparticles, implants and coatings," reads a description of company capabilities on the Web site. "Our scientists and engineers manipulate our proprietary polymer systems to control drug-delivery rates and provide sustained delivery (typically from weeks to months) for a wide range of compounds from small molecules to proteins. These systems enable site-specific and systemic delivery of drugs, employing durable and biodegradable polymer technologies."

Under the terms of the agreement, SurModics will receive an up-front licensing fee of $3.5 million. In addition, SurModics could be eligible to receive up to approximately $200 million in fees and milestone payments in the event of the successful development and commercialization of multiple products. Roche and Genentech will pay SurModics for its development services and have the right to obtain manufacturing services from SurModics. The company will also receive royalties on product sales.

In the area of ophthalmology, SurModics has already been working with Merck on a sustained-release delivery platform called I-vation, which has been evaluated in a 31-patient phase 2 study, testing the delivery of triamcinolone acetonide for up to two years in patients with diabetic macular edema. The I-vation platform is a nonbiodegradable, helical, nonferrous metal alloy design.

Alcon to Develop Potentia AMD Drug

■ Alcon recently signed its third deal for retinal disease drug-development in as many months. The move — which could also encompass the possible future acquisition of privately held Potentia, Inc. — sends an emphatic message that, following a fallow period in this important area, the company has renewed its strong commitment to developing therapies for retinal disease.

These new initiatives come three years after the company experienced a significant disappointment when its anecortave acetate (Retaane) treatment for wet AMD failed in a pivotal phase 3 trial. The failure was surprising after Retaane raised hopes with an encouraging phase 2 trial and being granted fast-track status by the FDA.

Potentia Pharmaceuticals, a privately held biotechnology company developing medicines for the treatment of AMD, entered into the licensing and purchase option agreements with an Alcon subsidiary in late October. The agreements provide Alcon with a license to develop Potentia's leading drug candidate, POT-4, for the treatment of AMD. The agreements also provide for Alcon to acquire the shares of Potentia if specified development milestones are achieved and if Alcon elects to continue development of POT-4.

"We could not wish for a better company to develop POT-4 into a new treatment option for the millions of patients with macular degeneration," said Cedric Francois, president and CEO of Potentia Pharmaceuticals.

POT-4 was the first complement inhibitor to enter the clinic for ophthalmological use and is being developed as a potential treatment for both dry and wet AMD. Potentia has completed a phase 1 trial for POT-4 in patients with wet AMD. The trial was designed to determine the safety and tolerability of an intravitreal injection of POT-4, as well as its stability and depot-forming properties. In the study, investigators observed only minimal and mild local adverse events related to the injection with no serious adverse events related to the drug itself. The study also found that POT-4 deposits form at doses of 450 micrograms and greater and that the higher the concentration was, the longer the deposits lasted.

"There is a body of science supporting the potential for complement inhibitors in the treatment of retinal disease," said Sabri Markabi, MD, Alcon's senior vice president of research and development and chief medical officer. "Although at a very early stage, Potentia has developed the first complement inhibitor for agerelated macular degeneration and positioned it for phase 2 trials. We look forward to carrying development forward with the goal of treating patients with AMD."

The two other drug-development agreements completed by Alcon in recent months are with AstraZeneca and PhiloGene.

Gene Replacement Combats LCA


■ The fruits of more than a decade of intensive research into gene-replacement therapy for patients afflicted with Leber's congenital amaurosis (LCA) are becoming ever more apparent.

Studies that began with successful restoration of vision to three blind Briard puppies and continued with young adults have now advanced to the achievement of meaningful vision gains in adults and children.

Researchers at the University of Pennsylvania and Children's Hospital of Philadelphia reported in the October 24 issue of Lancet that they had successfully replaced a defective gene that contributes to LCA with the correct gene in a phase 1 trial of 12 patients. The patients, ranging in age from eight to 44, were injected in their worst eye with the correct RPE65 gene, contained in an inert virus. All of the injected patients showed subjective and objective improvement in major measurements of vision, including, dark adaptometry, pupillometry, electroretinography, nystagmus, and ambulatory behavior. The greatest improvement was noted in children, all of whom gained ambulatory vision.

It is estimated that approximately 3,000 people in the Unites States have LCA. The Carver Center at the University of Iowa has an ongoing program under way to identify all LCA patients in this country so that they can have increased access to clinical trials and advanced therapies.

The first Briard puppy treated with gene replacement therapy, Lancelot, is now nine years old and has retained his improved vision. RP


Categorizing uveal melanomas. Researchers at Cleveland Clinic's Cole Eye Institute and Taussig Cancer Institute were awarded $500,000 from the National Cancer Institute for a two-year study to investigate and differentiate uveal melanomas.

The first phase of the two-phase trial will examine methods to categorize patients into high-risk or low-risk categories. Once assigned, high-risk patients will receive a combination of immunotherapy and chemotherapy.

The first phase will be led by Arun D. Singh, MD, ophthalmic oncologist at the Cole Eye Institute. Dr. Singh estimates 1,500 new cases of uveal melanoma are diagnosed each year in the United States. Uveal melanoma is believed to be of two distinct types — a low-risk type and a high-risk tumor that spreads to other organs.

The second phase of the trial will provide use of a combination therapy that seeks to eliminate microscopic tumor seeding, where cancer cells have spread beyond the eye.

"Currently there is not a standard method for distinguishing between types of uveal melanoma, making it difficult to predict what type of risk the cancer may present," Dr. Singh said. "Developing better methods for prognostication will ultimately lead to treatment decisions that preserve vision in low-risk patients, while justifying more aggressive treatment in high-risk cases."

Dr. Meredith new AUPO president. Retina specialist Travis Meredith, MD, Sterling A. Barrett distinguished professor and chair of the department of ophthalmology at the University of North Carolina at Chapel Hill School of Medicine, has been elected president of the Association of University Professors of Ophthalmology (AUPO).

Dr. Meredith has received research grants from the National Eye Institute and several awards from the AAO, including the Lifetime Achievement Honor Award in 2007. He also serves as the chair for the Council of the American Ophthalmological Society.

Microplasmin for advanced DME. ThromboGenics NV announced encouraging results from a phase 2a trial evaluating microplasmin intravitreal injection for the treatment of advanced DME. Microplasmin is a bioengineered form of a natural human fibrinolytic protein.

Previous studies in this advanced patient population have shown that, given the underlying condition, the adhesion between the vitreous and retina tends to be much stronger, as evidenced during vitrectomy. This level of adhesion makes achieving a total posterior vitreous detachment more challenging in patients with advanced DME.

Investigators found that within three days after microplasmin injection, a total PVD in two out of 15 patients was observed in the 125-micron dose group, and by day 28, two additional patients out of 15 in the 75-micron dose group had total PVD. The investigators did not observe total PVD by day 28 in any patients who received 25 microns of microplasmin or the sham injection.

"These encouraging results show that microplasmin is able to nonsurgically induce release of vitreomacular adhesion in some DME patients," said presenter Prof. Peter Stalmans of Leuven, Belgium.

New Pascal photocoagulator. OptiMedica has introduced the Pascal Streamline Photocoagulator with enhanced patterns and more powerful reporting. The instrument provides easy access to tens of thousands of patterns and automatically generates a detailed printed summary of each procedure.

OIS launches EyeScan. Ophthalmic Imaging Systems (OIS) has introduced the OIS EyeScan, a multimodality, portable imaging device that is designed for flexibility, efficiency, and high image quality.

At launch, the EyeScan will have six imaging modules including mydriatic color, fluorescein angiography, stereo optic nerve head, red reflex, corneal fluorescence, and tear film analyzer.

AMD may predict heart disease. A large study found strong evidence that older people who have AMD are at increased risk for coronary heart disease, although not for stroke. This result adds to mounting evidence that AMD and cardiovascular disease may share some risk factors — smoking, high blood pressure, inflammatory indicators such as C-reactive protein, genetic variants such as complement factor H — and disease mechanisms.

The Cardiovascular Health Study (CHS) followed 1,786 white or African American participants, who were free of cardiovascular disease or stroke at the study's outset, for about seven years. The CHS received funding from the National Heart, Lung and Blood Institute, a division of the National Institutes of Health.

The incidence of heart disease was 25.76% in patients with AMD, compared with 18.9% in those without AMD. The association between AMD and heart disease was somewhat stronger in people age 69 to 78 than age 79 and up. Data were adjusted to counter potentially confounding factors like hypertension, diabetes and smoking.

VEGF Trap extension study. VEGF Trap demonstrated a durable response and a good safety profile in an extension study presented at the recent AAO meeting.

David S. Boyer, MD, who followed 117 patients in the CLEAR-IT extension study for two years, reported that 50% of the patients who received VEGF Trap on an as-needed basis required less than four additional doses of the drug in 21 months after receiving three monthly "loading" doses.

Dr. Boyer said that the average vision gain under this regimen was 8.4 letters at 12 months, 7.1 letters at 18 months, and 6.1 letters at 24 months.

QLT to focus on ocular therapies. QLT Inc., the co-developer of PDT for the treatment of wet AMD, has sold its Eligard prostate drug franchise to Tolmar Holding for present and future considerations that could total $230 million. QLT said it will now focus all of its efforts on ocular therapies, including a promising drug-delivery system that utilizes punctual plugs for extended release of glaucoma medication.

DR shows sharp increase. Continuing an increase that has gone on for more than two decades, diabetic retinopathy now affects more than a third of all diabetes patients, according to the latest nationally representative estimate.

The prevalence of the condition appeared to increase across racial and ethnic groups between the 1988-1994 and 2005-2006 iterations of the National Health and Nutrition Examination Survey, Jinan Saaddine, MD, MPH, of the CDC, and colleagues found.

Non-Hispanic blacks had the highest prevalence of DR, and the greatest increase, the researchers reported recently at the American Diabetes Association meeting.

"It could be that we're not doing a good job controlling people with diabetes," Dr. Saaddine said, emphasizing the need for good glycemic and blood pressure management alongside diabetes prevention efforts.

"All the studies have shown that control of these two risk factors will delay the progression of diabetic retinopathy and the vision loss related to it," she noted.

Apologies for medical errors. Doctors who make full and heartfelt apologies for medical errors have a better chance of retaining patients' trust than doctors who provide general explanations of what went wrong, according to a study published in the September issue of the Journal of General Internal Medicine. However, an apology, no matter how heartfelt, may not help to stave off a lawsuit.

Researchers at Johns Hopkins Bloomberg School of Public Health and the University of Florida showed videos of actors portraying physicians apologizing after medical mistakes; some scenarios portrayed a full apology where the "doctors" took full responsibility, while others offered a non-specific or non-apology with no real acceptance of responsibility for the error.

"When viewers thought that the doctor had apologized and taken responsibility, they gave the doctors much higher ratings," says author Albert Wu, MD, MPH, a professor at Johns Hopkins. About 81% of viewers said they still trusted the physician and 56% said they would still refer the physician after the apology, says Dr. Wu. "However, despite the positive reaction to perceived apology or responsibility, viewers were only slightly less inclined to want to sue."