EURETINA GUIDELINES

EURETINA has developed a soon-to-be-published set of evidence-based guidelines for the use of anti-VEGF agents in the treatment of neovascular AMD. It will be published in the British Journal of Ophthalmology, said Ursula Schmidt-Erfurth MD, University Eye Hospital in Vienna, Austria. The time is ripe for such guidelines because intravitreal anti-VEGF therapy has proven its potential to reduce the incidence of blindness from AMD, and because data from clinical studies has accrued to a point where it can provide useful insights into the optimal treatment regimens and appropriate diagnostic criteria for the condition, Dr Schmidt-Erfurth said at the 13th EURETINA Congress in Hamburg.

As an illustration of the impact the advent of anti-VEGF agents have had on society, she cited a study conducted in Denmark showing that the incidence of AMD-associated legal blindness in that country per 100,000 people aged 50 years or over fell from 52.2 in 2001 to 25.7 in 2010. The bulk of the reduction occurred in the years after 2006 when anti-VEGF agents first became available (S Bloch et al, Am J Opth,153:2: 209-213I).

Since the condition requires treatment for the lifetime of the patient, retinal specialists can expect an increasing caseload of neovascular AMD patients in years to come. Evidence-based guidelines are therefore crucial to insuring that the available resources are directed towards those patients who are actually likely to benefit and to also insure that those patients receive the optimal regimen. “The management of AMD has to be practical and economic in terms of diagnosis and therapy for the entire population in all subgroups at all times in all patients,” she said.

Dosing and regimen

One of the main controversies regarding anti-VEGF agents in the treatment of neovascular AMD is the question of whether patients should receive the agent on a fixed regimen or PRN basis. The results from the HARBOR Study showed that a 0.5 dosage of ranibizumab (LucentisR, Novartis) was no more effective than a 0.2mg dosage in terms of visual acuity and that a monthly regimen and a PRN regimen achieved similar results with about one third of patients in each group gaining 15 or more letters of BCVA during the first year (Busbee et al Ophthalmology2013; doi: 10.1016/j.ophtha.2012.10.014).

She noted that the decision to treat in the PRN group was based on monthly monitoring with spectral domain OCT and the trial results may therefore represent the best that can be achieved with a PRN regimen.

The findings of the HARBOR study may also add to the emerging evidence that long-term anti-VEGF therapy for neovascular AMD can cause geographic atrophy. The study showed that although patients’ central foveal thickness continued to decrease throughout 24 months of treatment, some of the vision gained during the first year was lost during the second year in all of the treatment groups. “The fact that the retina becomes flatter over time may not be a good thing over the years. There is over-treatment and there is under-treatment. We have to find out how to keep patients between these two extreme poles,” she said.

Ranibizumab vs. bevacizumab

Dr Schmidt-Erfurth noted that the results of the CATT study showed that both ranibizumab and bevacizumab (AvastinR, Genentech) provide results that are highly satisfactory and roughly equivalent, when administered on a fixed monthly regimen. However, the study failed to prove the non-inferiority of bevacizumab to ranibizumab when administered on an as-needed basis (Martin et al, Ophthalmology 2012;119: 1388-1398).

In addition, patients receiving a fixed monthly regimen of ranibizumab had a significantly greater reduction in central retinal thickness than those receiving the PRN ranibizumab regimen and both of the bevacizumab regimens. The study also showed less favourable results for bevacizumab in terms of adverse events. At one year’s follow-up, the proportion of patients with one or more systemic serious adverse events was significantly higher with bevacizumab than ranibizumab (39.9 per cent vs. 31.7 per cent, P = 0.009). The relevance of the finding has been debated on the basis that most were events not of the sort typically associated with VEGF inhibition.

Aflibercept

Aflibercept (EYLEA R, Regeneron), formerly known as VEGF-trap, is the latest addition to the anti-VEGF agent armamentarium and results from the View 1 and View 2 trials indicate that a two-monthly regimen of 0.5mg aflibercept produced results equal to those achieved with monthly injections of 0.2mg ranibizumab. In all treatment arms of the two studies, patients first received three monthly intravitreal injections of the anti-VEGF agent.

“Our recommendation regarding currently available anti-VEGF agents is that ranibizumab, bevacizumab and aflibercept are all effective in neovascular AMD. Aflibercept seems to work slightly better than ranibizumab and ranibizumab is a little bit better than bevacizumab. With the monthly strategy or even a bimonthly strategy these differences are irrelevant, however, when you switch over to a PRN regiment then the differences become more evident,” Dr Schmidt-Erfurth said.