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Anti-VEGF Treatments for Wet Age-Related Macular Degeneration

Joshua Dunaief, MD, PhD

Scheie Eye Institute, University of Pennsylvania

  • Expert Advice
Published on:
A hand holding a vial that contains medication.

Learn what anti-VEGF treatments are and how they are used to manage the wet form of age-related macular degeneration.

People with wet AMD can lose central vision from abnormal blood vessels that grow into the retina. These vessels leak fluid into the retina, causing it to become “wet.” In the short term, this causes painless, reversible distortion or gray-appearing areas in the central vision. If untreated, within few days to weeks, the retina is permanently damaged by the abnormal vessels, fluid, and associated scar tissue, and loss of central vision becomes permanent.

Treatment for Wet AMD

Fortunately, years of intensive research revealed that the retinas of some people with AMD secrete too much of a protein called vascular endothelial growth factor (VEGF), causing the growth and leakage of the blood vessels. This process can be slowed or stopped by injecting drugs into the eye that bind and inhibit VEGF.

Currently, six drugs are used to treat wet AMD: brolucizumab (Beovu®), aflibercept (Eylea®), ranibizumab (Lucentis®), pegaptanib sodium (Macugen®), faricimab-svoa (VABYSMO®), and ranibizumab injection for intravitreal use via ocular implant (SUSVIMOTM)*. There is also a seventh drug, called Avastin® (bevacizumab), approved by the FDA as a blood vessel growth inhibitor to treat colorectal and other cancers, that has been used off-label (i.e., for purposes other than the approved uses) by some doctors to treat AMD.

For most people, they need to be injected into the eye every four to twelve weeks, with the frequency depending on each person’s response. So far, clinical trials have shown that Vabysmo can last the longest, up to four months between injections in some patients. The response is measured using an optical coherence tomography retinal imager, which generates a picture of the retina in less than a minute showing the amount of fluid in the retina.

Each of these drugs can reduce or eliminate the fluid in most people. Avastin is the least expensive, because it is purchased in bulk for “off-label” use, but was shown to have similar efficacy and safety compared to Lucentis in a large clinical trial sponsored by the National Institutes of Health (NIH) and coordinated by the University of Pennsylvania, called the “CATT” trial.

The port delivery system (PDS) is a device implanted into the wall of the eye in the operating room that can store, and slowly release, Lucentis. This device is refilled in the office once every six months. It can result in fewer office visits and treatments. 

The Eye Injection

While the concept of having a drug injected into the eye sounds awful, most people find that it’s not as bad as they originally thought. Numbing medicine is put on the eye, which is carefully cleaned before the injection. The injection itself takes only a few seconds. Many people will feel some eye irritation for about a day, mainly caused by the iodine that’s used to sterilize the eye. The use of iodine is important to decrease the risk of infection. The injections have a good safety record, with a 1 in 1000 chance of infection or retinal detachment. Either of these complications needs to be treated immediately.  Infection usually causes severe eye pain and can be treated by injecting antibiotics into the eye. Retinal detachment causes a few seconds of flashing lights in the peripheral vision followed by new “floaters” and then a “curtain” blocking part of the visual field. It requires surgery to re-attach the retina.

New Treatments on the Horizon for Wet AMD

RGX-314 is an anti-VEGF treatment delivered by gene therapy.  It has the potential to block VEGF for years following a surgical procedure in which a harmless virus, called adeno-associated virus (AAV), carrying the anti-VEGF gene, is injected under the retina. ADVM-022 is another anti-VEGF gene therapy that can be injected into the vitreous in an office procedure, but it can cause inflammation in the eye. RGX-314 is now in phase III (final phase) clinical trials. This approach is more promising now that retinal AAV gene therapy has been approved by the FDA for another disease called Leber’s congenital amaurosis. Results from early clinical trials look promising for safety and efficacy.

Summary

As research to develop more effective and longer lasting treatments for wet AMD continues, comfort during treatment and vision protection should improve.

* As of Oct. 24, 2022, this product is currently under voluntary recall due to a manufacturing problem with the device

About BrightFocus Foundation

BrightFocus Foundation is a premier nonprofit funder of research to defeat Alzheimer’s, macular degeneration, and glaucoma. Through its flagship research programs—Alzheimer’s Disease Research, National Glaucoma Research, and Macular Degeneration Research—the Foundation is currently supporting a $75 million portfolio of 287 scientific projects. BrightFocus has awarded nearly $275 million in groundbreaking medical research funding since inception and shares the latest research findings, expert information, and English/Spanish disease resources to empower the millions impacted by these devastating diseases.  Join our community at brightfocus.org.

About the author

Headshot of Dr. Joshua Dunaief

Joshua Dunaief, MD, PhD

Scheie Eye Institute, University of Pennsylvania

Joshua Dunaief, MD, received his BA magna cum laude in Biology from Harvard (1987), MD/PhD from Columbia College of Physicians and Surgeons (1996), completed ophthalmology residency at the Wilmer Eye Institute, Johns Hopkins in 2000, and medical retina fellowship at Scheie Eye Institute, University of Pennsylvania in 2004.

The information provided here is a public service of BrightFocus Foundation and should not in any way substitute for personalized advice of a qualified healthcare professional; it is not intended to constitute medical advice. Please consult your physician for personalized medical advice. BrightFocus Foundation does not endorse any medical product, therapy, or resources mentioned or listed in this article. All medications and supplements should only be taken under medical supervision. Also, although we make every effort to keep the medical information on our website updated, we cannot guarantee that the posted information reflects the most up-to-date research.  

These articles do not imply an endorsement of BrightFocus by the author or their institution, nor do they imply an endorsement of the institution or author by BrightFocus. 

Some of the content may be adapted from other sources, which will be clearly identified within the article. 

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