Nav: Home

Age-related macular degeneration before and after the era of anti-VEGF drugs

May 02, 2016

In a study of nearly 650 people with the eye disease age-related macular degeneration (AMD), half still had vision 20/40 or better, typically good enough to drive or to read standard print, after five years of treatment with anti-VEGF drugs that are injected into the eye. The authors of the study, funded by the National Eye Institute (NEI) at the National Institutes of Health, say those outcomes would have been unimaginable about 10 years ago, prior to the drugs' availability.

The results were published in the journal Ophthalmology and presented May 2nd at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Seattle.

"This is the most comprehensive study of anti-VEGF therapy for AMD to date," said NEI Director Paul A. Sieving, M.D., Ph.D. "It points to the importance of long-term follow-up in studies evaluating disease treatments."

AMD is the leading cause of vision loss among older Americans. It causes damage to the central part of the retina, the light-sensitive tissue at the back of the eye. AMD often has very few symptoms in its early stages; but in later stages, it causes loss of the central, straight-ahead vision needed for activities like reading and driving.

There are two types of late AMD--geographic atrophy, and the more common neovascular AMD, also known as wet AMD. In neovascular AMD, fragile blood vessels grow under the retina and leak fluid. This usually starts in one eye, and is stimulated by a protein called VEGF. Just 10 years ago, people diagnosed with neovascular AMD were almost certain to develop severe vision loss in their affected eye and likely to lose vision in their other eye, too.

The new study looked at people with AMD who had regular treatment with drugs designed to block VEGF. After five years, 50 percent of them had 20/40 vision or better, 20 percent had 20/200 vision or worse, and the rest were in-between.

Ten years ago, the best available treatment for AMD was photodynamic therapy--in which an intravenous drug (injected into a vein) and laser are used to seal off leaking blood vessels. Past studies have found that just one year after diagnosis, less than 15 percent of patients given this therapy alone retain 20/40 vision, and up to 40 percent decline to 20/200 vision. Without any treatment, less than 10 percent of patients retain 20/40 vision at one year, and up to 75 percent of untreated patients decline to 20/200 vision.

In the U.S., state drivers' licenses generally require 20/40 vision in at least one eye. A best-corrected vision of 20/200 in both eyes is considered legally blind for the purpose of federal disability benefits.

The Comparison of AMD Treatments Trials (CATT) began in 2008 and was designed to compare the anti-VEGF drugs Avastin and Lucentis. VEGF is important in the growth and development of new blood vessels in normal and cancerous tissues. Avastin (bevacizumab) was approved by the Food and Drug Administration in 2004 for the treatment of metastatic colon cancer. Other drugs were later developed specifically to target blood vessels in the retina, with Lucentis (ranibizumab) coming to the market in 2006 and Eylea (aflibercept) in 2011. For treating AMD, the drugs are injected into the eye. Before Lucentis was available, many ophthalmologists began treating the disease with Avastin, which appeared to have similar benefits, at least in the short-term. The difference in the cost of the drugs also made Avastin appealing; the approximate per-dose price was $50 for Avastin and $2000 for Lucentis.

In the trial, more than 1200 participants with neovascular AMD were randomly assigned to receive either Lucentis or Avastin for two years, through monthly or as-needed injections. During that time, the two drugs were equally effective at preserving visual acuity. These results were later confirmed in five multicenter clinical trials around the world.

The current study followed up with CATT participants between March 2014 and 2015, an average of 5.5 years after enrollment in the trial. After two years on their assigned drug, participants were free to work with their eye care providers to choose their own course of therapy. During that 3.5-year period, more than half received at least one treatment with a drug or therapy other than the drug assigned to them. The investigators obtained visual acuity measurements for 647 of 914 participants who were still living.

In addition to the overall effects of anti-VEGF therapy at five years, the investigators compared the outcomes of participants who received Avastin or Lucentis during the trial.

"Some experts had speculated that two years of treatment with ranibizumab might have long-term benefits superior to bevacizumab. However, at five years, there were no differences in visual acuity between the two drugs," said Daniel F. Martin, M.D., chair of the Cleveland Clinic Cole Eye Institute and CATT study chair.

The study also found that after five years, participants assigned to Lucentis during the trial had a higher rate of strokes and heart attacks (7.6 percent) than those assigned to Avastin (4.5 percent). Since most participants received treatments other than their assigned drug after the two year-trial, the investigators are cautious about attributing this difference to the study drugs.

Finally, the study provides information on the general course of AMD with treatment. It was already known that many people with neovascular AMD eventually develop geographic atrophy, which has no treatment. In the trial, participants were more likely to develop geographic atrophy when they received monthly, rather than as-needed injections of Avastin or Lucentis. After the trial, almost all participants stopped monthly injections in favor of as-needed treatment, with an average of 4-5 injections per year. By five years, the rate of geographic atrophy increased from 20 percent of participants at two years to 41 percent at five years. The fraction of participants with geographic atrophy was similar between the Avastin and Lucentis groups.

"Although anti-VEGF treatment has greatly improved the prognosis for patients overall, we still need to find ways to avoid poor vision in these patients and to decrease the burden of ongoing treatment," said Maureen G. Maguire, Ph.D., the study's principal investigator and a professor of ophthalmology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
The CATT studies were supported by cooperative agreements EY017823, EY017825, EY017826, and EY017828 from NEI. For more information, visit (NCT00593450).

For more information about AMD, please see


CATT Research Group. Five-year outcomes with anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology. May 2, 2016.

NEI leads the federal government's research on the visual system and eye diseases. NEI supports basic and clinical science programs that result in the development of sight-saving treatments and address special needs of people with vision loss. For more information, visit

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

NIH...Turning Discovery Into Health®

NIH/National Eye Institute

Related Blood Vessels Articles:

Feeling the pressure: How blood vessels sense their environment
Researchers from the University of Tsukuba discovered that Thbs1 is a key extracellular mediator of mechanotransduction upon mechanical stress.
Human textiles to repair blood vessels
As the leading cause of mortality worldwide, cardiovascular diseases claim over 17 million lives each year, according to World Health Organization estimates.
How high levels of blood fat cause inflammation and damage kidneys and blood vessels
Viral and bacterial infections are not the only causes of inflammation of body tissue.
3D printing, bioinks create implantable blood vessels
A biomimetic blood vessel was fabricated using a modified 3D cell printing technique and bioinks.
When blood vessels are overly permeable
In Germany alone there are around 400,000 patients who suffer from chronic inflammatory bowel diseases.
Nicotine-free e-cigarettes can damage blood vessels
A Penn study reveals single instance of vaping immediately leads to reduced vascular function.
Creating blood vessels on demand
Researchers discover new cell population that can help in regenerative processes.
Self-sustaining, bioengineered blood vessels could replace damaged vessels in patients
A research team has bioengineered blood vessels that safely and effectively integrated into the native circulatory systems of 60 patients with end-stage kidney failure over a four-year phase 2 clinical trial.
Found: the missing ingredient to grow blood vessels
Researchers have discovered an ingredient vital for proper blood vessel formation that explains why numerous promising treatments have failed.
How sickled red blood cells stick to blood vessels
An MIT study describes how sickled red blood cells get stuck in tiny blood vessels of patients with sickle-cell disease.
More Blood Vessels News and Blood Vessels Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#566 Is Your Gut Leaking?
This week we're busting the human gut wide open with Dr. Alessio Fasano from the Center for Celiac Research and Treatment at Massachusetts General Hospital. Join host Anika Hazra for our discussion separating fact from fiction on the controversial topic of leaky gut syndrome. We cover everything from what causes a leaky gut to interpreting the results of a gut microbiome test! Related links: Center for Celiac Research and Treatment website and their YouTube channel
Now Playing: Radiolab

The Flag and the Fury
How do you actually make change in the world? For 126 years, Mississippi has had the Confederate battle flag on their state flag, and they were the last state in the nation where that emblem remained "officially" flying.  A few days ago, that flag came down. A few days before that, it coming down would have seemed impossible. We dive into the story behind this de-flagging: a journey involving a clash of histories, designs, families, and even cheerleading. This show is a collaboration with OSM Audio. Kiese Laymon's memoir Heavy is here. And the Hospitality Flag webpage is here.