Bevacizumab appears safe for neovascular AMD in short term

May 1, 2007

The short-term clinical experience with intravitreal bevacizumab (Avastin, Genentech) supports growing perception that treatment is safe and effective for neovascular age-related macular degeneration.

Key Points

Las Vegas-The short-term experience with intravitreal bevacizumab (Avastin, Genentech) suggests that it appears to be safe and effective for neovascular age-related macular degeneration (AMD), but large prospective studies and longer follow-up are needed, reported Philip Rosenfeld, MD, PhD, here during the American Academy of Ophthalmology annual meeting.

The interest in the use of bevacizumab in the eye is documented by the increasing numbers of publications in the literature, at least 62 in PubMed so far in 2006, Dr. Rosenfeld pointed out.

Safety, efficacy

"We do not know the long-term ocular and systemic safety profile of bevacizumab," Dr. Rosenfeld said. "However, we are beginning to gather more and more information about the drug."

No toxicity associated with the drug has been detected from three in vitro studies published in 2006; no ocular toxicity was detected in studies in tissue culture, cell lines, or explanted retina, he said. When tested in rabbit eyes, no ocular toxicity was detected in four published studies using electrophysiologic and histopathologic analyses. In humans, no ocular toxicity was detected in a multifocal electroretinographic study. In addition, no inflammation was detected in association with bevacizumab in a study of 61 patients with the drug injected intravitreally; interestingly, flare measurements decreased in these patients, according to Dr. Rosenfeld.

The projected systemic complications of high-dose bevacizumab treatment administered every 2 weeks that are of concern to the retina specialist include hypertension, increased risk of heart attack and stroke, and proteinuria. With these concerns in mind, an Internet safety survey was established that included short-term results from 7,000 intravitreal injections of bevacizumab in more than 5,000 patients from 70 centers worldwide.

"No significant inflammation or safety signals were identified," Dr. Rosenfeld said. "However, in this clinician-reported survey, the follow-up was limited, at up to 7 months (mean follow-up 3.5 months), and we really still don't know the long-term effects of bevacizumab."

The combined results from five recently published retrospective studies of bevacizumab with a total of 338 patients with follow-ups from 2 to 3 months showed similar results with modest improvement in visual acuity that corresponded to a decrease in central retinal thickness measured by optical coherence tomography (OCT); no significant safety issues were identified in the five studies, according to Dr. Rosenfeld.

Two prospective studies of bevacizumab also showed decreased retinal thickness and no ocular or systemic toxicity. One study from Lebanon conducted by Bashsur and colleagues used 2.5-mg injections of bevacizumab every month for 3 months; the investigators found an increase in visual acuity and a decrease in the central retinal thickness on OCT after three doses. The second prospective study carried out by Costa and associates used one dose in a dose-escalation trial; the authors found a dose response with respect to visual acuity and OCT findings seen at 6 weeks after injection, which partially reversed by the third month.