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Congress Hears of Avastin Side Effects
The verdict from the Comparison of AMD Treatments Trial might be in, but news following in its wake continues. In results published this spring from a head-to-head trial initiated by the NEI, researchers reported that patients treated with intravitreal bevacizumab (Avastin) could see as well after one year as those injected with the approved drug, ranibizumab (Lucentis). The dosages were 1.25 mg and 0.50 mg, respectively.1
Monthly anti-VEGF injections produced a mean gain in visual acuity of 8 letters in the bevacizumab eyes, and 8.5 letters in the ranibizumab eyes. The gains with as-needed dosing were 5.9 and 6.8 letters, respectively.
Although visual acuity gains were roughly equivalent, ranibizumab produced a slightly greater decrease in mean central retinal thickness, according to the study.
The rates of death, heart attack and stroke were similar between the two groups. However, serious systemic adverse events occurred in 24.1 percent of bevacizumab patients and in 19.0 percent of the ranibizumab group (p = 0.04). Most were hospitalizations, for conditions not associated with bevacizumab in cancer studies. Further research should be done to clarify this finding, the researchers said.
Meanwhile, three weeks before the CATT findings were made public, results from a study funded by Genentech were released. An abstract of the retrospective study of nearly 78,000 Medicare records was prepared for the spring meeting of ARVO. This analysis found that bevacizumab-treated patients were 57 percent more likely to have a hemorrhagic stroke than ranibizumab patients. However, the 99 percent confidence interval for the hazard ratio was wide, 1.04 to 2.37.2
Lead author Emily W. Gower, PhD, associate professor of ophthalmology and public health at Johns Hopkins University, told Reuters, “The difference in risk of hemorrhagic stroke we found in the first analysis is a difference of 1.5 events per 1,000 person years—a very rare event.” And a broader, though arguably less precise, second analysis showed no significant difference, she said.
Although the significance of the study’s findings is debatable, Genentech representatives took Dr. Gower to Capitol Hill prior to the CATT’s release to do briefings about her results, according to The New York Times.
Congressional support is important to Genentech because, in the wake of CATT, there might be pressure to reduce Medicare costs by covering bevacizumab preferentially. This could not happen without Congress repealing a provision in the health care reform law, which prohibits Medicare from making payment decisions based on comparative effectiveness studies—like CATT.
Medicare spent $536.6 million on ranibizumab in 2008, which covered 35.6 percent of the total anti-VEGF injections. The other 64.4 percent of the injections, using bevacizumab, cost $20.3 million.3
1 Martin, D. F. et al. N Engl J Med
2 Gower, E. W. et al. Adverse event rates following intravitreal injection of Avastin or Lucentis for treating age-related macular degeneration. Presented at the Association for Research in Vision and Ophthalmology, May 3, 2011, Fort Lauderdale, Fla. Online abstract.
3 Brechner, R. J. et al. Am J Ophthalmol
Genentech provided research funding to Johns Hopkins for the Gower et al. study.
Tx for Failed Blebs: Late Needle Revision
A study from the Federal University of Minas Gerais in Belo Horizonte, Brazil, challenges long-held assumptions about bleb needling to fix a failed trabeculectomy.1 It found that needle revision can be performed in completely flat blebs, even many years after trabeculectomy.
“We were able to recover a trabeculectomy performed 30 years ago,” said Heloisa A. Maestrini, MD, PhD, lead author of the prospective case series of 125 eyes in 98 patients with uncontrolled glaucoma. All patients had at least one failed trabeculectomy, a flat filtering bleb and a patent internal ostium on gonioscopy.
The procedure uses a 26-gauge insulin needle to disrupt subconjunctival adhesions. Mitomycin C is injected before the needling procedure to prevent development of new adhesions and to reduce subsequent scar formation. The authors claimed “immediate success” in 92 percent of eyes, meaning that the needling raised the bleb and established aqueous flow. In well over half of the successful cases, IOP fell by more than 50 percent. In some cases, repeat needling was necessary to achieve good IOP control.
Results were consistent with earlier studies, but this study covered new ground, Dr. Maestrini said. In addition to treating only completely flat blebs in the late postoperative period, all procedures were episcleral to avoid overfiltration. “We never introduce the needle into the anterior chamber,” she said. The study also considered safety. Results showed that MMC did not adversely affect the health of the corneal endothelium.
In a surprise finding, not yet published, a longer time between trabeculectomy and needling was associated with success. “The longer the interval, the better the result,” said Dr. Maestrini. “We think that the inflammatory response from the original trabeculectomy, which starts soon after surgery and continues for several months, may lead to failure if bleb needling is performed too early. As time passes, the healing response diminishes and fewer fibroblasts are present, increasing the chance of success.”
Not everyone is a candidate for the procedure. In heavily scarred conjunctiva, Dr. Maestrini prefers a repeat trabeculectomy or a tube implant.
“Needling is worth trying,” she said. “It is fast, cheap, effective and relatively safe. Also, keep in mind that many patients will need a second or a third needling to achieve a good and long-lasting IOP control.”
1 Maestrini, H. A. et al. Ophthalmology
MORE ONLINE. Visit www.eyenetmagazine.org to view a video of the procedure.
Retina Report Update
A Healthy Lifestyle May Help Prevent AMD
Is a healthy lifestyle greater than the sum of its parts? Researchers involved with an ancillary study of the Women’s Health Initiative (WHI) Observational Study are inclined to think so. They report in the April Archives of Ophthalmology that women with healthier habits than their cohorts have an up to threefold reduction in the risk for early age-related macular degeneration (defined as large drusen or pigmentary abnormalities of the retinal pigment epithelium). 1
“It was the first study to look at a combination of diet, exercise, smoking and AMD in quite this way,” said coauthor Karen M. Gehrs, MD, ophthalmologist with the Center for Retina and Macular Disease in Winter Haven, Fla.
In the Carotenoids in Age-Related Eye Disease Study (CAREDS), 1,313 women (aged 55 to 74) reported on their dietary, smoking and exercise patterns at study sites in Iowa City, Iowa, Madison, Wis., and Portland, Ore. An average of six years later, stereoscopic fundus photographs revealed AMD in 202 women, 94 percent of whom had early AMD.
Exercise. Exercise showed the strongest independent inverse association with early AMD, said Dr. Gehrs. The authors note that the time spent exercising each week seemed more important than the strenuousness of the activities. And, although women with a lower body mass index (BMI) had a lower risk of early AMD, exercise was correlated with a lower risk of AMD, regardless of BMI.
Smoking. The CAREDS study supported previous consistent findings pointing to the relationship between smoking and AMD. In CAREDS, women who had smoked more than seven pack-years had a 45 percent increased risk of AMD, but this was not significant after adjusting for diet and exercise.
Diet. Although the study paralleled the results of others that examined the effect of diet on AMD, it was the first to estimate associations between AMD and the dietary patterns recommended by the 2005 U.S. Dietary Guidelines and a Mediterranean diet. Women with the highest healthy eating scores, based on the U.S. Dietary Guidelines, had a 46 percent reduction in risk compared with women who had the lowest scores. And those following a Mediterranean diet had an even greater reduction in risk (66 percent).
“Sampling women at the extremes of dietary intake, we looked at serum levels of lutein and zeaxanthin, which are a surrogate for antioxidants and healthier dietary patterns,” said Dr. Gehrs. Tocopherols, high-sensitivity C-reactive protein and 25-hydroxyvitamin D were also tested. In fact, another CAREDS corollary study also published in April’s Archives found an inverse association between high serum vitamin D and early AMD in women younger than 75.2
The bottom line. “Pay attention to all these factors,” said Dr. Gehrs. “The healthier you are, the less likely you are to develop this chronic disease of aging.”
Women with one healthy behavior were more likely to have other healthy behaviors. These habits share certain biological effects, making independent associations difficult to tease apart, said Dr. Gehrs. Nonetheless, those with the healthiest scores in all three components had a 71 percent lower risk for early AMD compared with those who had the lowest scores.
Women with the least risk for AMD were those who had never smoked; reported about eight hours of moderate or 10 hours of low-intensity activity a week; and had diets lower in fat and higher in median servings of vegetables, fruits, whole grains and a variety of protein sources.
The authors speculate that these healthy behaviors offer synergistic benefits, perhaps collectively counteracting pathogenic mechanisms by lowering oxidative stress, inflammation and blood pressure and by improving blood lipid levels.
Limited by a fairly homogeneous study population and lack of data on genotypes, CAREDS also may have had a selection bias toward healthier participants, said Dr. Gehrs. However, with better representation of less healthy participants, she said, study results would likely be even more impressive.
1 Mares, J. A. et al. Arch Ophthalmol
2 Millen, A. E. et al. Arch Ophthalmol
EyeNet thanks Susan B. Bressler, MD, and Stephen I. Rosenfeld, MD, for their help with this issue’s News in Review.