Comparison of Anti-VEGF Treatments for Wet AMD

By Reena Mukamal Edited By Anni Delfaro Published May. 23, 2024 for the American Academy of Ophthalmology

Anti-VEGF drugs can prevent vision loss in patients with wet age-related macular degeneration (AMD), a leading cause of blindness among older Americans. Here’s a guide to the similarities and differences between four anti-VEGF drugs commonly used to treat wet AMD.

Groundbreaking treatments for wet AMD

In the United States, an estimated 20 million Americans have some form of AMD. This disease can diminish central vision in its most advanced form, complicating day-to-day activities such as reading, driving and identifying faces. AMD has two forms – wet and dry. While dry AMD leads to a gradual loss of central vision, wet AMD can lead to a more rapid vision loss. Wet AMD is responsible for 90 percent of all AMD-related blindness.

A decade ago, wet AMD was considered untreatable and two-thirds of those affected could expect to be legally blind within two years of developing the disease. Today, we have a more positive outlook about wet AMD thanks to the introduction of injectable anti-vascular endothelial growth factor (anti-VEGF) drugs. The usage of anti-VEGF drugs has nearly halved the incidence of AMD-related blindness in some countries. Ophthalmologists are now able to help wet AMD patients maintain – and in some cases improve – vision.

“This class of drugs represents a huge leap in treatment for macular degeneration. Doctors have been blown away by the results,” said Rahul Khurana, MD, a clinical spokesperson for the American Academy of Ophthalmology and retina specialist. “Ten years ago, wet AMD was a one-way ticket to blindness, but now I have patients with the condition who are able to read and drive; and some even maintain 20/20 vision.”

Multiple anti-VEGF drugs are available to treat AMD, but four are commonly used for the condition. Three of these, ranibizumab (brand name Lucentis®), aflibercept (brand name Eylea®) and faricimab (brand name Vabysmo®), were designed specifically for the treatment of AMD. A fourth drug, bevacizumab (brand name Avastin®), was originally developed to treat various types of cancer, but is commonly used throughout the world “off-label” in patients with AMD. A higher-strength version of Eylea—Eylea HD®—was most recently introduced as a potentially longer-acting treatment. 

As doctors and the media debate the relative merits and disadvantages of these drugs, the growing collective experience of ophthalmologists indicates that they are all safe and effective treatments for wet AMD.

How do they work?

Wet AMD occurs when abnormal blood vessels begin to grow underneath the retina and leak blood or fluid that blurs central vision. This growth is fueled by a signal protein called vascular endothelial growth factor, or VEGF. Anti-VEGF treatments seek out harmful VEGF molecules and block them. This reduces abnormal growth and leakage, which helps to stabilize vision loss and, in some cases, can improve sight.

Patients can receive treatment in their doctor’s office. The ophthalmologist will place anesthetic and antiseptic drops on the eye to numb and sterilize it, then administer the anti-VEGF drug by injection.

“An eye injection may sound scary, but the needle is very small and the injection is very quick – a fraction of a second,” said Raj Maturi, MD. “Many of my patients are nervous about this the first time, but by the second treatment, they are much more confident in the process and its effectiveness.”

The anti-VEGF medications slow down the disease but do not cure the wet AMD. Therefore, these treatments are typically ongoing. The recommended frequency of these injections varies from every few weeks to every few months. The interval will vary case by case and by the response to a particular drug. Patients will likely require multiple doses over the course of many months. Repeat treatments are often needed for continued benefit.

How are they different?

Lucentis, Eylea, Eylea HD, Avastin and Vabysmo offer similar visual benefits, according to many studies and real-world ophthalmologist experience. The two newest treatments, Vabysmo and Eylea HD, are unique in that they may allow patients to space out their eye injections to three-to-four times per year rather than requiring visits to the ophthalmologist 6 to 12 times per year. Another distinction is that Vabysmo targets two underlying causes of AMD–VEGF and the protein angiopoietin-2–which may provide a longer-lasting effect. 

Here are some other differences that your ophthalmologist may explain to you as you discuss treatment options.

FDA approval

Lucentis, Eylea, Eylea HD and Vabysmo have been FDA-approved for use in the eye. However, Genentech, the company that manufactures Avastin and Lucentis, has not sought FDA approval for Avastin to be used as treatment of wet AMD.

However, Avastin was FDA-approved as a treatment for colon cancer in February 2004, and since then has been used by ophthalmologists around the world to treat wet AMD “off-label” with great results and safety. In fact, half of ophthalmologists prescribe Avastin as a first-line treatment for wet AMD due to effectiveness, cost, and insurance requirements.

Cost

The cost of each drug can vary substantially depending upon your insurance coverage. Your ophthalmologist will help you navigate through insurance benefits, approvals and cost considerations. They can also help you apply incentives and/or financial assistance programs offered by manufacturers and other organizations to subsidize costs.  

Risks

Numerous studies have concluded that there are minimal differences in risk between the drugs. Concerns have been raised about a greater possibility of infection with Avastin. That’s because there is a potential risk for contamination when the drug is being repackaged into smaller doses for the eye. However, when appropriate guidelines are followed for preparing such medicines, this risk is minimal. Additionally, “in the vast majority of cases of eye infection, the source is the surface of the patient’s own eye, rather than contaminated medication or anything else,” said Abdish Bhavsar, M.D., Academy clinical spokesperson and retina specialist. 

Packaging and accessibility

Since Lucentis, Eylea, Eylea HD and Vabysmo are FDA approved for use in the eye, they are manufactured and delivered to ophthalmologists as eye injectables, usually stored in the ophthalmologist’s office and available for use whenever they are needed. 
Avastin, in contrast, is a repackaged drug. It is shipped from the manufacturer to a special pharmacy that repackages it into smaller doses for the eye and then delivers it to doctors’ offices.   

Which treatment is right for you?

Multiple studies have compared these anti-VEGF drugs and found that all are very effective at helping patients retain their ability to see. Your ophthalmologist will help you pick a therapy after reviewing your unique condition and discussing the relative tradeoffs of these treatments.

Patients may differ in how their eyes respond to one treatment versus another. During your course of treatment, your ophthalmologist may switch to another therapy to improve your result or allow you to go longer between injections.