Many questions remain regarding anti-VEGF regimen, experts say

VIENNA, Austria — Anti-VEGF therapy has revolutionized the therapeutic approach to age-related macular degeneration, and multicenter clinical trials have validated the use of specific drugs. However, according to Gisele Soubrane, MD, these studies do not provide answers to all the questions physicians face in day-to-day practice.

The number and frequency of injections, the overall duration of the treatment and the long-term prognosis are still a matter for discussion, and no single trial can give a definitive response, she said at the Euretina Congress here.

After presenting an overview of the principal studies on Lucentis (ranibizumab, Genentech), which Ursula Schmidt-Erfurth, MD, defined as "the only officially approved drug which offers high efficacy and safety," she concluded that a flexible regimen, with constant monitoring of the effects of the therapy, is probably the best approach. By adopting this individualized approach, a reduction in the number of intravitreal injections can be achieved, with beneficial effects on the patient's quality of life and a reduction of the public costs involved.

In the MARINA and ANCHOR trials, 80% of the patients who gained lines of vision after the first three monthly injections "did not appear to gain substantial additional benefit by continuation of the monthly treatment for a longer period of time," Dr. Schmidt-Erfurth said.

In the PIER study, the quarterly injections that followed the first three monthly treatments led to an almost equal number of patients who lost, gained or maintained vision. In fact, patients who gained vision were the minority.

"A fixed regimen in quarterly intervals cannot, therefore, be recommended," she noted.

No specific criteria, such as lesion type or size, baseline vision or disease duration, were identified to predict the level of improvement, which led Dr. Schmidt-Erfurth to conclude that "there are no prognostic factors suggesting more intensive, continued therapy as opposed to less intensive therapy with earlier discontinuation."

A flexible approach was proposed by the PrONTO study, in which patients, after the usual three monthly injections, received re-treatment only if one of the following changes was observed during the follow-up visits: a loss of five letters in conjunction with fluid in the macula as detected by optical coherence tomography, an increase in OCT central retinal thickness of at least 100 µm, new onset classic choroidal neovascularization, new macular hemorrhage or persistent macular fluid detected by OCT at least 1 month after the previous injection.

With this flexible and customized approach, encouraging visual acuity and OCT results were achieved, and "the number of ranibizumab injections was substantially reduced, from 11 in the other studies to six per year," Dr. Schmidt-Erfurth said.

Constant monitoring can be a burden, but "since AMD is not a self-limiting disease, a continuous follow-up is mandatory," she said.