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High-level evidence supports the use of anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD), but falls short of recommending any one agent over another in terms of efficacy or safety, said Paul Sternberg Jr., MD.
Nashville, TN-High-level evidence supports the use of anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD), but falls short of recommending any one agent over another in terms of efficacy or safety, said Paul Sternberg Jr., MD.
The American Academy of Ophthalmology (AAO) has issued Preferred Practice Pattern (PPP) guidelines for years, including a recent guideline for AMD.
“There's a strong economic rationale for the primary use of bevacizumab and limited evidence supporting superiority of any regimen other than treatment at four week intervals,” said Dr. Sternberg, G.W. Hale Professor and Chairman, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN.
The AAO discusses the epidemiology of the disease, he said, and re-confirmed what most ophthalmologists already knew-that nearly 90% of the severe vision loss is from the non-neovascular (dry) form of the disease.
“More and more, vision loss is not so much from wet AMD, but from geographic atrophy,” Dr. Sternberg said. “It's probably closer to 40% now, and if we look down the road it's going to be an even greater percent, hence our efforts at treating dry AMD is going to take on even more significance.”
Age is obviously a non-modifiable risk factor, but Dr. Sternberg said clinicians are going to have to work harder on patients who smoke, doing whatever they can to ensure smoking cessation.
The new guideline also evaluated the role of aspirin since the older population is often on aspirin therapy.
“Meta-analyses have suggested that there is no reason for you as a clinician to recommend that a patient stop taking aspirin simply because they have macular degeneration,” he said.
Numerous studies continue to identify risk alleles associated with macular degeneration.
“It seems every month there's a new one that comes along,” Dr. Sternberg said. “There also has been a concurrent emergence of commercially available personalized genetic testing.”
Personalized genetic testing has been used to try to predict the risk of progression of advanced AMD, but several large-scale studies have not confirmed its effectiveness. Genetic testing is also under evaluation as a method to help clinicians determine the benefit of nutritional supplements.
“At this point, the AAO feels that routine genetic testing for risk allele is not recommended for patients with AMD to help define your selection of nutritional supplements,” he said.
The current preferred practice pattern somewhat de-emphasizes the role of fluorescein angiography for this disease.
“Increasingly, we're finding that fluorescein angiography is not nearly as important as may be suggested by the current PPP,” he said. “The emergence of high-resolution optical coherence tomography (OCT) has resulted in a substantial reduction in the utility of intravenous fluorescein angiography. The emergence of OCT angiography may take that even further.”
OCT, however, is rapidly emerging as a critical component in the diagnosis and management of AMD, and in evaluating a patient’s response to treatment.
Treatment of AMD
For early AMD, the rate of progression is quite low at 1.3% over 5 years, Dr. Sternberg said.
The AREDS study was underpowered to demonstrate a benefit for patients with early AMD in nutritional supplementation, but he said it is not recommended. “However, for intermediate AMD the use of the nutritional supplements that were used in the AREDS study is recommended, but without the use of genetic testing to guide these supplements,” he said.
Clinicians are recommended to increase patient awareness about the risk of progression in the fellow eye if the first eye has progressed to advanced AMD.
Anti-VEGF therapies “have become the first-line therapy for treatment and stabilization of disease,” he said.
The anti-VEGFs have much stronger Level 1 evidence to support their use, more so than radiation, acupuncture, electrical stimulation, or macular translocation.
There is limited evidence to support the “superior efficacy of any of the anti-VEGF agents: aflibercept, bevacizumab, or ranibizumab,” he said. “There’s limited evidence to support superior safety of any of the anti-VEGF agents.”
Timing, however, is less controversial-monthly injections “have been demonstrated to be highly effective in reducing vision loss. While beneficial, the other regimens have not been demonstrated to be better than monthly, although there seems to be some evidence emerging that there may be some non-inferiority to some of the other regimens,” Dr. Sternberg said.
Unfortunately, there seems to be a gradual deterioration over time, which may be due to disease progression.
Socioeconomic data show the anti-VEGFs are cost effective compared with past treatments, including laser and photodynamic therapy.
“There is high-level evidence that points to the safety and efficacy of monthly bevacizumab,” he said. “Because there's limited evidence to support superiority of alternative medications with the economic benefit, right now the recommendation supports bevacizumab, as well as the others, but with better economic benefit to bevacizumab.”
Paul Sternberg Jr., MD
This article was adapted from Dr. Sternberg’s presentation at the 2015 meeting of the American Academy of Ophthalmology. Dr. Sternberg has no financial disclosures.