SUBSPECIALTY NEWS

OCT Reimbursement Faces Reductions

Overuse of a transformational technology?

Samantha Stahl, Assistant Editor

■ With cost-cutting now a major priority in health insurance circles, OCT reimbursements will be trimmed in 2011, thanks in part to perceived overuse of this multipurpose technology.

Physicians can expect lower payments when the current OCT billing code, 92135, is replaced with three new codes next year. Coding expert Riva Lee Asbell reports that the newly published CPT book lists one code for anterior segment scanning (92132) and two for posterior segment uses: code 92133 for optic nerve and code 92134 for retina. The posterior segment codes cannot be reported simultaneously for the same patient.

William Rich, III, MD, medical director of health policy for the AAO, reports that the 2011 reimbursement amount recently published in the Federal Register is $48.33, a decrease from the 2010 payment of $52.45.

That 7.9% cut, unwelcome on its own, is dwarfed by an even bigger cut inherent in the newest regulations: the new codes are defined as "unilateral or bilateral," meaning that physicians can no longer receive separate reimbursement for each eye when OCT is used bilaterally, Ms. Asbell says.

Michael Ober, MD, of Southfield, Mich., jokes that "you can practically get an OCT scan at your local gas station for free when you fill up." But he says the proliferation of OCT scans is no laughing matter now that overuse has prompted a decrease in reimbursement. Worse still is the likelihood that companies will turn their focus on efficiency rather than diagnostic innovation.

"We have been blessed with incredible advancement in OCT leading up to spectral domain, which has been driven in large part by the market," says Dr. Ober. "Now market forces will demand OCT technology become cheaper rather than better."

Robert Gibson, Topcon's senior director of marketing, says the company will focus its technology development on multi-use instruments. Systems that have OCT, color fundus, FA, FAF and fundus imaging capabilities offer greater versatility for an investment in the technology.

LETTER

I read with great interest the debate regarding the implantable miniature telescope in the October issue. As a retinal specialist who also cataract surgery, I have received a lot of inquiries regarding this technology. However, I share the concerns voiced by Drs. Fletcher and Colenbrander regarding the safety and efficacy of the IMT. While the acceptance of the image disparity and demonstration of the benefits of magnification as demonstrated with conventional devices is a prerequisite for a patient to receive the IMT, there is no comparison in the study between the benefits derived through conventional external devices versus the more hazardous IMT. I have additional concerns regarding the quality of subsequent diagnostic studies and the limitations on the treatment of the progressive lesions in implanted patients.

— James J. Bedrick, MD, Charlotte, NC

Wet AMD Drug in China Trial

KH902 being developed by Kanghong Biotech.

Jerry Helzner, Senior Editor

■ A little-known entrant in the competition to find new therapies for wet AMD that combine effectiveness and less-frequent dosing is beginning a phase 2 clinical trial in China. The anti-VEGF molecule KH902 is described by its sponsor, Kanghong Biotech, as a gene fusion protein that binds VEGF at a high affinity.

Though little is known about the drug in the US, KH902 has completed preclinical and phase 1 studies in China. The randomized, double-masked, multicenter controlled phase 2 AURORA trial will involve administration of KH902 by intravitreal injection to 120 patients at nine sites in China. The principal investigator is Xiaoxin Li, MD, of Peking University People's Hospital.

The study will include 0.5 mg and 0.2 mg injections of KH902, with each dose size given to one group of patients monthly and another group prn following an initial three-month fixed-dosing phase for all cohorts, according to a description on the Web site www.clinicaltrials.gov.

Primary endpoints over three and 12 months will be improvement in BCVA and changes in physical symptoms and signs. The incidence and extent of any adverse events or reactions will also be recorded.

A secondary endpoint will be measurement of central retinal thickness and other anatomical changes, as evaluated by OCT, color fundus photography, ICG angiography and fluorescein fundus angiography.

The trial is expected to be completed in 2012.

According to the sponsor, preclinical research and phase 1 studies have shown that KH902 "is effective and safe in inhibiting the growth, migration, pullulation of vascular endothelial cells and neovascularization induced by VEGF. This study is designed to confirm the efficacy and safety of multiple injections of KH902 at variable dosing regimen in patients with choroidal neovascularization due to neovascular age-related macular degeneration."

Using SD-OCT Intraoperatively

Information can guide treatment.

■ Researchers from the Rudolph Foundation Clinic in Vienna, Austria, used the Cirrus HD-OCT and a Zeiss surgical microscope to take pre-, intra- and postoperative intraretinal scans of 24 patients who underwent vitreoretinal surgery for such problems as preretinal membrane formation (13), macular hole (8) and retinal detachment (3).

The intraoperative scans were used for: additional membrane peeling when there was incomplete knowledge about the behavior of the macular hole immediately after ILM removal; maintenance of the foveal depression during membrane peeling; acquiring information about invisible fluid accumulation under silicone in a supine position, or to assist with a clinically diagnosed "macula-on" retinal detachment.

The researchers, who reported their findings at the 2010 ARVO meeting, noted that improvements in the technology to facilitate its use and the incorporation of a tracking system are needed. However, they concluded that intrasurgical SD-OCT evaluation does offer additional information to the surgeon.

The Vienna researchers later reported on intraoperative SD-OCT scans of 50 patients. Susanne Binder, MD, spokesperson for the Vienna group, was quoted as saying, "The OCT guided our surgery in a variety of conditions, such as macular pucker, penetrating macular hole and lamellar hole, retinal detachment and silicone oil removal after vitreoretinal surgery. We were able to make decisions for additional membrane peeling in cases where it was incomplete, could see the behavior of the macular hole immediately after [ILM] removal, and of the fovea during membrane peeling. We got information about clinically invisible fluid accumulation under silicone in a supine position. The device helped us greatly in our surgery."

2010 PAT Survey Results

New trends emerge in anti-VEGF injections.

Samantha Stahl, Assistant Editor

■ The 2010 Preferences and Trends (PAT) Survey results reveal both changing habits for anti-VEGF therapy as well as consistent opinions about a variety of retinal procedures.

The 2010 data was generously provided by the American Society of Retinal Specialists and the survey's editor, Robert A. Mittra, MD, and coeditor, Mike Jumper, MD. The ASRS received responses from approximately 340 members in July.

A new section of questions, says Dr. Mittra, focused on anti-VEGF injections for uses other than macular degeneration. For example, while 54.03% of respondents use reduced-fluence photodynamic therapy for chronic central serous retinopathy, 17.01% now use intravitreal Avastin.

The survey found a slight preference for Avastin over Lucentis, with 47.04% of respondents saying they would choose Avastin to treat their own AMD-related, well-defined, one-disc area juxtafoveal CNV, while 42.9% said they would choose Lucentis. "I think it's very telling to see what people would choose for themselves. Cost, of course, is a huge issue for patients, but there is a chance that Avastin lasts a bit longer," Dr. Mittra says.

The PAT data showed shifting trends among retina specialists for many aspects of the procedure. When asked if sterile gloves are routinely used for in-office intraocular injections, 59.17% responded no, while 38.76% said that they normally wear gloves. Dr. Mittra said many doctors have trended away from using sterile gloves over the last few years as they have realized that, because their hands have little to do with the risk for an infection, gloves don't serve much of a purpose for this procedure.

"A lot of initial worry was that there would be a high rate of infection without gloves," he said. In actuality, the infection rate is low; he suggests leaving a drop of betadine on the eye's surface for at least 30 seconds to kill any potential bacteria.

Dr. Mittra pointed out that in past years most doctors checked IOP after an injection, a practice that is quickly falling by the wayside. In a question asking about usual monitoring routines after intravitreal anti-VEGF injections, 20.77% of respondents said they check optic nerve head perfusion and 15.13% said they check IOP. While 7.42% said they do both, a significant 47.77% said they do neither. Practicality has replaced over-burdensome caution. Dr. Mittra reports that in his office, once a patient has initially responded well to anti-VEGF, on subsequent injections "we just make sure a patient can see after the injection before we let them leave. We still check pressure in cataract patients, however."

Retina specialists don't concur about all injection practices, though. Respondents showed a great variance in anesthesia methods for in-office intraocular injections: 25.44% use a topical anesthetic drop, 25.15% use a topical viscous anesthetic, 26.33% use a topical anesthetic (a drop or viscous) and a pledget, and 22.19% use a sub-conjunctival injection of anesthetic. "It's interesting that there's no one clear-cut method even though it's something we do very frequently," said Dr. Mittra.

Another swiftly transforming arena is the treatment of diabetic macular edema. Combination therapy used to be rare for the condition, but the PAT data shows that this is beginning to change: 54.6% of respondents reported that they use a combination between 5% and 50% of the time. Only 10.68% said they rarely use combination therapy (meaning 5% of the time or less), while 29.67% usually use it between 50% and 90% of the time, and 5.04% almost always do.

Promising Data on Fenretinide

Oral medication found to combat GA.

■ ReVision Therapeutics Inc. has announced results from a phase 2b trial suggesting that fenretinide slows lesion growth and preserves visual acuity in patients with geographic atrophy (GA). The data showed that a sustained reduction in retinol binding protein (RBP) levels of 60% to 75% was predictive of positive treatment response to fenretinide. Patients receiving fenretinide who achieved this RBP reduction threshold experienced a 49% slower rate of lesion growth compared to patients receiving placebo.

Visual acuity was also preserved in patients experiencing a sustained RBP reduction. Additionally, fenretinide reduced the incidence of CNV by about 40%. Taken together, researchers believe these results suggest that once-daily oral dosing of fenretinide has the potential to slow progression of dry AMD and prevent the onset of wet AMD in GA patients.

"We are very encouraged because these data demonstrate that fenretinide may improve clinical outcomes for patients with both the dry and wet forms of AMD," says Jason Slakter, MD, clinical professor of ophthalmology at NYU School of Medicine and editor-in-chief of Retinal Physician, who evaluated the lesion image data for the trial and presented the study results at the recent annual meeting of the AAO.

"Additionally, for the first time ever, we may have a biomarker to predict patient response to therapy, as approximately one-third of the patients who achieved a profound and sustained reduction in RBP levels experienced a beneficial treatment effect," Dr. Slakter notes. "I am looking forward to future studies to confirm these results and determine the role fenretinide may play in treating our patients."

The double-masked, placebo-controlled, multicenter study evaluated 246 patients with GA. Patients were randomized into three cohorts and received once-daily, oral doses of 100 mg or 300 mg of fenretinide or placebo for 24 months. Retinal lesion size was measured by color fundus photography, fundus autofluorescence and fluorescein angiography. Patients were also evaluated by contrast sensitivity, reading rate, visual acuity, OCT, the incidence of CNV and serum RBP levels.

This is the largest study to date for an oral therapeutic agent for treatment of GA. Fenretinide, which has been investigated as a treatment for rheumatoid arthritis and other diseases, was well tolerated with no severe drug-related adverse events and no significant effects on normal visual function.

Analysis of the lesion and RBP data at the conclusion of the two-year study showed that 43% of patients in the 300 mg fenretinide arm had a sustained RBP reduction of at least 60% throughout the trial. Those patients had a median lesion size growth of only 30% from baseline, compared to a median lesion size growth of about 50% in the placebo arm. Visual acuity loss in patients who experienced reduced lesion size growth was stabilized from 12 months to 24 months at six letters lost, while patients in the placebo arm showed progressive loss throughout the trial reaching an average loss of 11 letters at 24 months.

At the conclusion of the two-year study, the incidence of CNV in the placebo arm was 22% Meanwhile, CNV incidence in patients receiving either dose of fenretinide was 13 to 14%. The comparable therapeutic effect at both low and high doses of fenretinide suggests a mechanism of action that is not dependent upon reduction of serum RBP.

The accumulation of retinol-derived toxins in the eye is believed to exacerbate lesion growth leading to progression of GA. Inflammation and induction of angiogenic mediators has been implicated in risk and progression of wet AMD. Fenretinide limits the delivery of retinol to the eye through reduction of serum RBP. This slows the accumulation of retinol-derived toxins in the retina, thereby slowing lesion growth. The anti-inflammatory and antiangiogenic properties of fenretinide are thought to provide an additional therapeutic benefit against development of wet AMD.

ReVision Therapeutics, the company now supporting the continued clinical development of fenretinide after purchasing the drug from Sirion Therapeutics earlier this year, is planning a phase 3 clinical trial to begin in 2011.

Goal: Regenerating Retinal Cells

Researchers get major NIH grant.

■ A research team led by principal investigator Kang Zhang, MD, PhD, professor of ophthalmology at the University of California, San Diego's Shiley Eye Center and director of UCSD's Institute of Genomic Medicine, has been awarded a five-year, $4.66 million National Institutes of Health Transformative Award.

Dr. Zhang and co-principal investigators Sheng Ding, PhD, from the Scripps Research Institute and Thomas Reh, PhD, from the University of Washington, received the highest possible scores for their proposal to investigate the regenerative potential of retinal cells. Their long-term goal is to restore visual function lost through diseases such as macular degeneration and retinitis pigmentosa.

"The success of this work could mean a paradigm shift in how retinal disease is treated, and could have broad and profound impact on human disease therapies by utilizing the regenerative power of our own cells," says Dr. Zhang.

Some vertebrates, such as goldfish and newts, have a remarkable ability to regenerate a lost limb or eye — something it was thought no mammal can do, Dr. Zhang explains. However, his group recently showed proof of principle at a small-scale level in mice by turning Muller cells into a type of retinal neuron.

"The human genome is quite similar to that of a newt, but we humans seem to have lost the potential to regenerate our own cells, possibly due to some inhibitory mechanisms," says Dr. Zhang. "We are seeking small molecule chemicals that can block these inhibitions and consequently unlock humans' regenerative potential."

The Transformative Award program, funded through the Office of the NIH Director and the Common Fund, is intended "to support research that has the potential to transform the way we think about and conduct science, so the recipients represent an elite few with truly bold ideas," according to Francis Collins, director of the National Institutes of Health.

The researchers are looking at Muller cells, which are abundant and have the ability to regenerate nerve cells after retinal injury in fish. These cells usually play a supporting role in the central nervous system neurons of humans, such as those present in the eye or brain. This study proposes to use chemicals to turn Muller cells into photoreceptors in the eye — cells that are lost in macular degeneration and retinitis pigmentosa.

Identification of chemicals for Muller cell reprogramming and differentiation will provide new avenues in developing cell-based therapy as well as small-molecule drugs for regenerative medicine, and facilitate new understanding of the mechanisms of trans-differentiation, according to the scientists. Their group plans to screen more than 100,000 compounds in order to identify the chemicals that prompt mouse Muller glia to develop new neurons, conferring the power of regeneration to the mammalian retina.

"Our ultimate goal is to use a chemical approach to turn on the regenerative potential of hibernating stem cells such as Muller cells by introducing a small molecule directly into the eye, perhaps even by eye drop or pill," says Dr. Zhang. He adds that there is no need for surgical transplantation of cells. Instead, the body's own cells would be used and the therapy wouldn't have the risk of rejection or tumors.