When patients with glaucoma switched from a brand name drug to its generic counterpart, they were more likely to take their medication as directed compared to those who remained on the brand name drug, according to a study published online in Ophthalmology. Researchers at the University of Michigan Kellogg Eye Center and College of Pharmacy studied medication adherence rates 18 months before and after the first generic prostaglandin analogue glaucoma drug became available in March 2011.

Despite the potentially dire consequences for non-adherence, many patients struggle with their drug regimens. Along with known barriers—eye drops can be difficult to use, medication regimens may be complicated, and patients may not understand the consequences of poor adherence—the high cost of copays for brand name drugs is also a deterrent, the study suggests. “Some of my patients take as many as three or four different classes of these medications, and a number end up paying as much as $100 out-of-pocket every month for their medication,” says Joshua D. Stein, MD, MS, glaucoma specialist and health services researcher at the U-M Kellogg Eye Center.

The report drew on a nationwide health-care claims database to study 8,427 patients with open-angle glaucoma who were 40 years and older and were taking PGAs, one of the most commonly prescribed class of drugs for glaucoma. All patients in the study had health insurance.

Dr. Stein and colleagues found that patients who remained on brand name drugs were 39-percent more likely to experience a decline in adherence compared to those who switched to the newly available generic drug latanoprost. The researchers cited several factors associated with improved adherence rates, among them, the use of the generic drug once it became available and lower copays after the generic drug became available.

The Michigan researchers found that black patients had decreased adherence compared to white patients, a concern because blacks tend to have more severe disease and often require a more complex medication regimen. However, a subset of blacks—those who switched to the generic drug—had a substantial improvement in adherence compared to blacks who remained on brand name products.

Dr. Stein observed that a sizeable group of patients—612 individuals or 7.3 percent of the study group—simply discontinued use of treatment altogether at the time the generic drug became available. While it was not clear why this occurred, the researchers urge that clinicians be alert for patients who stop taking their medicine, which can cause worsening of the disease and the need for costly surgical or medical treatment in the future.

“If clinicians suspect that a patient is struggling with medication adherence, it may be a good idea to switch from a brand name to a generic drug,” advises Dr. Stein. He also encourages patients to ask their doctors if a generic alternative is available and appropriate for their circumstances.

Ranibizumab Restores Diabetic Vision Loss
Ranibizumab, commonly used to
treat age-related vision loss, also reverses vision loss caused by diabetes among Hispanic and non-Hispanic whites, according to a new study led by investigators from the University of Southern California Eye Institute.

Diabetic retinopathy and diabetic macular edema are the leading causes of vision loss in working-age adults in the United States, according to the National Eye Institute. Laser surgery is the standard treatment for advanced stages of the disease, but previous research has shown that only 30 percent of patients saw improvement in their vision.

“We found that ranibizumab can save the sight of thousands of working-age individuals suffering from diabetic eye disease, as standard treatments such as laser are not as effective,” said Rohit Varma, MD, MPH, director of the USC Eye Institute, professor and chair of ophthalmology at the Keck School of Medicine of USC and the study’s lead author.

Dr. Varma’s team developed a population-based model that suggests that administering 0.3 milligrams of ranibizumab (Lucentis) every four weeks to patients with diabetic macular edema would reduce the number of cases of vision impairment by 45 percent, or 5,134 individuals, and the number of cases of legal blindness by 75 percent, or 1,275 individuals. The model was based on the approximately 37,000 Hispanic and non-Hispanic white adults with diabetic macular edema in the United States for whom ranibizumab treatment could be used. Because other race and ethnic groups were not included in the study, the authors contend that the treatment may benefit even more people than their results show.

Could Laser Cure AMD?
A new technique reported in
the February issue of the FASEB Journal suggests that during early stages, it might be possible to reverse age-related macular degeneration, a leading cause of blindness that is currently irreversible. The treatment involving a nanosecond laser may also have further implications for other eye diseases such as diabetic macular edema, diabetic retinopathy and retinopathy of prematurity.

“It is hoped that this study will provide a basis for the clinical use of the low energy nanosecond laser in those with early stage age-related macular degeneration and that such a treatment will limit the progression of the disease to the advanced, sight-threatening forms,” said Erica L. Fletcher, OD, PhD, FAAO, a researcher involved in the work from the Department of Anatomy and Neuroscience at the University of Melbourne in Victoria, Australia.

To make their discovery, Dr. Fletcher and colleagues treated a group of individuals with intermediate AMD in one eye with a single session of nanosecond laser treatment. These individuals underwent eye examinations every six months, out to two years post-treatment and the results were compared to an untreated group with early AMD. Anatomical examination of human and mouse eyes was used to determine the effect of the laser on the sensitive light-detecting retina.

In order to determine how this laser may help in limiting AMD, a mouse with a genetic mutation that predisposes it to developing one of the hallmark signs of AMD was treated with the nanosecond laser and structural and gene analysis was performed. Results showed that treating those with early AMD with this new low-energy nanosecond laser may limit disease progression. Importantly, unlike other lasers currently used to treat eye disease, the nanosecond laser does not result in damage to the sensitive retina. This study also showed evidence that nanosecond laser treatment in one eye can also produce positive effects in the other untreated eye. This raises the possibility that monocular treatment may be sufficient to treat disease in both eyes.

“This truly remarkable research is worth watching,” said Gerald Weissmann, MD, editor in chief of the FASEB Journal, “because it may help usher in an era in which age-related macular degeneration is either eliminated or no longer considered a serious disease.” The FASEB Journal is published by the Federation of the American Societies for Experimental Biology.

AMD Drug Choice Goes Beyond Price
Two drugs that treat
macular degeneration are practically interchangeable—except for the price.

Ranibizumab costs up to $2,000 per dose, while bevacizumab is $50 per dose. Researchers at the Stanford University School of Medicine suspected that doctors treating Medicare patients would have a financial incentive to prescribe a more costly drug. So they would be more likely to prescribe ranibizumab than doctors in the Veterans Health Administration, who do not have that incentive.

As it turns out, the prescription practices for these two drugs aren’t that straightforward, the researchers wrote in a Feb. 2 paper in Health Affairs.

“It’s complicated,” said senior author Kate Bundorf, MBA, MPH, PhD, associate professor of health research and policy. “The incentives facing physicians don’t seem to be the only story.”

Researchers examined data from both systems from 2005 to 2011. In 2011, Medicare physicians prescribed the less costly bevacizumab (Avastin) 63 percent of the time. Ranibizumab (Lucentis) was prescribed 37 percent of the time. If all of those injections had been reimbursed at the rate for bevacizumab, Medicare would have saved approximately $1.1 billion, according to a 2011 report by the Office of Inspector General in the Department of Health and Human Services.

In the VA system, ranibizumab was prescribed 52 percent of the time in 2011. Interestingly, however, prescription decisions at the VA varied regionally, with some centers prescribing primarily bevacizumab, others primarily ranibizumab, and others alternating between the two drugs.

Dr. Bundorf said she suspects that patients’ financial incentives may also be influencing prescribing decisions; that is, they may be asking for the less-expensive drug, particularly if they’re covered by Medicare, whose patient co-pays sometimes reflect the cost of the drugs. Some physicians may also be thinking of the system-wide effects when selecting the less expensive drug, she said.

Both drugs are about equally effective at treating macular degeneration. Bevacizumab was originally developed to treat cancer; ranibizumab was designed specifically for eye conditions.

Dr. Bundorf said the study illustrates the need for improvement in both health-care systems; for example, physicians could be offered incentives to select the best drug for the condition and save money.

Eye/Brain Link Sought to Treat Disparate Diseases
Researchers at LSU Health
New Orleans have discovered gene interactions that determine whether cells live or die in such conditions as age-related macular degeneration and ischemic stroke. These common molecular mechanisms in vision and brain integrity can prevent blindness and also promote recovery from a stroke. The paper was published online in Cell Death & Differentiation.

“Studying the eye and the brain might hold the key to creating therapeutic solutions for blindness, stroke and other seemingly unrelated conditions associated with the central nervous system,” says Nicolas Bazan, MD, PhD, Boyd Professor, Ernest C. and Yvette C. Villere Chair of Retinal Degeneration Research, and director of the Neuroscience Center of Excellence at LSU Health New Orleans. “The eye is a window to the brain.”

Dr. Bazan and his research team discovered Neuroprotectin D1, which is made from the essential fatty acid, docosahexaenoic acid. Previous work showed that while it protected cells, the molecular principles underlying this protection were not known.

“During the last few years, my laboratory has been immersed in studying gene regulation,” Dr. Bazan says. “We have uncovered a novel control that makes definitive decisions about whether a retina or brain cell will survive or die when threatened with disease onset. The gene mechanism that we discovered is the interplay of two genes turned on by the messenger Neuroprotectin D1.”

The research team worked with human retinal pigment epithelial cells and an experimental model of ischemic stroke. They discovered novel mechanisms in cells with the ability to activate pathways that crosstalk one to another and then assemble consolidated responses that decide cell fate. The researchers found that the powerful messenger, NPD1, is produced on-demand in the brain and retina and that it elicits a network of positive signals essential for the well-being of vision and cognition. They showed that NDP1 bioactivity governs key gene interactions decisive in cell survival when threatened by disease or injury. They demonstrated that not only does NPD1 protect photoreceptors, but it also promotes remarkable neurological recovery from the most frequent form of stroke in humans.

How RGCs Alter Structure Holds Clue to Glaucoma
To better understand the
cellular changes in retinal ganglion cells and how they influence the progression and severity of glaucoma, researchers at the University of California, San Diego, School of Medicine and Shiley Eye Institute turned to a mouse model of the disease. Their study, published Feb. 10 in Journal of Neuroscience, reveals how some types of retinal ganglion cells alter their structures within seven days of elevated eye pressure, while others do not.

“Understanding the timing and pattern of cellular changes leading to retinal ganglion cell death in glaucoma should facilitate the development of tools to detect and slow or stop those cellular changes, and ultimately preserve vision,” said Andrew D. Huberman, PhD, assistant professor of neurosciences, neurobiology and ophthalmology. Dr. Huberman co-authored the study with Rana N. El-Danaf, PhD, a postdoctoral researcher in his lab.

Retinal ganglion cells are specialized neurons that send visual information from the retina to the brain. Increased pressure within the eye can contribute to retinal ganglion cell damage, leading to glaucoma. Even with pressure-lowering drugs, these cells eventually die, leading to vision loss.

In this study, Drs. Huberman and El-Danaf used a mouse model engineered to express a green fluorescent protein in specific retinal ganglion cells subtypes. This tool allowed them to examine four subtypes of retinal ganglion cells. The different cell types differ by the location in the eye to which they send the majority of their dendrites (cellular branches). Within seven days of elevated eye pressure, all retinal ganglion cells that send most or all of their dendrites to a region of the eye known as the OFF sublamina underwent significant rearrangements, such as reductions in number and length of dendritic branches. Retinal ganglion cells with connections in the ON part of the retina did not.

“We are very excited about this discovery,” Dr. Huberman said. “One of the major challenges to the detection and treatment of glaucoma is that you have to lose a lot of cells or eye pressure has to go way up before you know you have the disease. These results tell us we should design visual field tests that specifically probe the function of certain retinal cells. In collaboration with the other researcher members of the Glaucoma Research Foundation Catalyst for a Cure, we are doing just that and we are confident these results will positively impact human patients in the near future.”  REVIEW