Drug-laser combination proves effective for diabetic blindness

A study shows that combining the drug ranibizumab, or Lucentis, with laser therapy is twice as effective at improving vision for those with diabetic macular edema.

For the first time in a quarter of a century, researchers have identified a new treatment for diabetic macular edema, a potentially blinding disorder that affects about 1 million Americans, researchers said Tuesday.

The treatment uses a drug called ranibizumab, which when administered in combination with laser phototherapy is twice as effective at reversing vision loss as laser therapy alone. Laser therapy to prevent leakage of blood vessels in the retina has been the gold standard since it was introduced in 1985. The findings were reported online in the journal Ophthalmology.

Nearly 50% of those who received both the drug and phototherapy had a visual improvement of at least two lines on an eye chart, compared with 28% of those receiving only phototherapy, researchers found. And only about 5% of those receiving both therapies had further deterioration of vision, compared with 14% of those receiving just phototherapy.

"This will have a major impact on how ophthalmologists will treat macular edema in people with diabetes," said Dr. Neil M. Bressler of the Wilmer Eye Institute at Johns Hopkins University, who led the study. The drug, sold under the brand name Lucentis, is already approved for treatment of macular degeneration, and physicians can use it off-label to treat macular edema, he said.

Macular edema is a form of diabetic retinopathy, which is the most common cause of vision loss in working-age Americans. It is marked by leakage of small blood vessels in the retina, the light-sensitive portion of the eye.

When fluid accumulates in the center of the retina — the macula — the condition is called macular edema. Increased pressure damages the cells, impairing vision. Because the macula is the most important part of the retina for reading, driving and recognizing faces, macular edema can be severely disabling.

Ranibizumab, manufactured by the biotech company Genentech, is what's known as a monoclonal antibody — a protein created to bind to a molecule in a specific way. Injected into the eye, it slows leakage by blocking the receptor for a hormone called vascular endothelial growth factor, or VEGF.

Bressler's team studied 691 diabetics at 52 clinical centers. Some had both eyes treated, for a total of 854 eyes. Patients were divided into four groups — receiving either ranibizumab plus prompt laser treatment, the drug plus delayed laser treatment, laser treatment plus an injected steroid called triamcinolone, or laser treatment plus a sham injection.

After a year of follow-up, nearly 50% of those receiving Lucentis had a visual improvement of two lines on a vision chart, meaning they could read letters that were at least a third smaller than they could read before the study. It didn't matter whether laser treatment was prompt or deferred.

About 28% of those receiving laser treatment alone or in combination with triamcinolone had a similar improvement. But though there were very few complications related to Lucentis — primarily infections associated with the injection — about 30% of those receiving triamcinolone developed high intraocular pressure requiring treatment, and 60% developed cataracts requiring surgery.

The trial was funded by the National Eye Institute, but Genentech donated the expensive drug and contributed $9 million to the cost of the trial.

After earlier small studies suggested that such treatment could benefit macular edema patients, some ophthalmologists have been using Genentech's anti-cancer drug Avastin, which also blocks VEGF receptors, to treat the condition macular edema because it is much cheaper. It costs less than $100 per dose, compared with about $2,000 for Lucentis, and the eye institute has been criticized for testing Lucentis rather than the cheaper drug.

Dr. Frederick L. Ferris III, the institute's clinical director, acknowledged at a news conference that Genentech's financial contributions to the trial had swayed the decision-making process.

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New vasculitis therapy may help patients keep infertility, cancer at bay

A drug previously approved for the treatment of non-Hodgkin’s B cell lymphoma and rheumatoid arthritis, can treat severe ANCA-associated vasculitis as effectively as cyclophosphamide, the current standard therapy, say researchers.

The finding of Rituxan has been presented at the annual meeting of the American College of Rheumatology in Philadelphia.

“The reason this is a big deal is that this is a disease where people would come in and be told ‘listen, we are probably going to be able to get on top of your life-threatening disease by using cyclophosphamide, there is the potential for major side effects down the road from this drug,’” said Robert Spiera, M.D., an associate attending rheumatologist at Hospital for Special Surgery in New York.

“This study provides strong evidence that Rituxan works as well as cyclophosphamide, at least in terms of getting patients into remission, and over that acute hump of being very ill. And, we can treat patients without the likelihood of causing infertility or causing secondary cancers, which have been a concern with the use of cyclophosphamide,” the expert added.

Hospital for Special Surgery was one of nine centers involved in the Phase III trial, which was led by Ulrich Specks, M.D., a professor of medicine in the Department of Pulmonary and Critical Care Medicine at the Mayo Clinic, and John Stone, M.D., MPH, director, Clinical Rheumatology, Massachusetts General Hospital.

Vasculitis, an inflammation of the blood vessels, can damage tissues and organs and, in severe cases, lead to death. Specifically, the study examined something known as ANCA-associated vasculitis that includes Wegener’s granulomatosis and microscopic polyangiitis.

“The reason this is such a significant study is that this is an uncommon but devastating group of diseases,” said Dr. Spiera.

Prior to the use of cyclophosphamide treatment, 70 percent of patients who were diagnosed with severe forms of ANCA-associated vasculitis could be expected to be dead within three years. In the 1970s, doctors discovered that cyclophosphamide was extremely effective at combating the disease and could put people into remission. In the ensuing decades, however, doctors recognized that these drugs came with a price.

“If you followed patients long enough, you found they had a higher risk of leukemias, lymphomas and solid tumors,” said Dr. Spiera, who is also an Associate Professor at Weill Cornell Medical College. “People would sometimes develop terrible infections. Women, almost reliably, would become infertile, as did many men. So, although it was a dramatically effective drug at reducing remissions in these patients, it came at a price.”

In the current study, nine centers enrolled a total of 197 patients with severe Wegener’s granulomatosis or microscopic polyangiitis, two of the more common types of ANCA-associated vasculitis. Patients were given steroids and randomized to receive either the standard treatment with cyclophosphamide or Rituxan given at a dose of 375 mg/m2 weekly for four weeks.

At the time of the data analysis, 84 of the 99 patients in the Rituxan arm and 81 of the 98 patients in the cyclophosphamide arm had completed six months of follow-up. Investigators found that the treatments were equally effective in putting patients into remission and that, in fact, the treatment outcomes looked slightly better in patients receiving Rituxan.

“These results show that the Rituxan worked at least as well as cyclophosphamide,” Dr. Spiera said. “If anything, there was almost a hint of it maybe looking a little better, and even in the short term, it looked safer in some respects. This study shows that there is strong evidence that Rituxan may be an alternative to cyclophosphamide in this disease. It might help manage flares in patients who have gone into remission, and it could be a consideration as first-line therapy, especially in women of child bearing potential who have a good chance of losing their fertility if treated with cyclophosphamide.”

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