Fact sheet: New drugs for age-related macular degeneration

In industrialized countries, age-related macular degeneration (AMD) is the most frequent cause for sight loss. People with AMD gradually lose some or all of their central vision. That means they can only see the outlines of objects clearly, but not the things they are looking at directly or the details that they want to focus on. Many will eventually lose most of their sight. There are now treatments that help reduce the damage to eyesight caused by one type of AMD, “wet” AMD. This fact sheet provides information about new drugs that are the most effective known treatments for this condition. You can learn more about how the eye works, what happens with AMD and other treatments in our feature on AMD.

How does wet AMD damage sight?

Wet AMD is caused by the growth of new, abnormal blood vessels that can bleed into the eye and damage sight. At the back of the eye there is a light-sensitive layer called the retina. The retina processes the images we see into messages that the brain can understand. Those messages are sent by the retina to the optic nerve which is right behind the eyeball. The optic nerve goes into the brain.

In the center of the retina is an important part of the eye called the macula. It is the macula which helps us focus on things and concentrate on details.

When abnormal blood vessels damage the macula, it is called “wet” macular degeneration. This is the most common cause of sight loss in industrialized countries. We still do not know exactly what causes AMD. In some families this disease never occurs, even when people are much older. If a close relative already has AMD, your own risk is higher. It is also known that it happens to smokers more often and earlier than to nonsmokers.

What are the new drugs for AMD, and how do they work?

Until recently, there was only one medicine for the treatment of AMD, called verteporfin (brand name: Visudyne). It can only be used as part of a photodynamic therapy. You can read more about this therapy here.

There are now 2 new drugs that have been approved for use in wet AMD: ranibizumab (brand name: Lucentis) and pegaptanib (brand name: Macugen). Both of these drugs work in the same way: they inhibit the so-called growth factors, substances responsible for abnormal blood vessels growing in the retina. However, they do not get rid of blood vessels that are already there, and they cannot repair existing damage in the macula or retina. The main goal of these drugs is to slow down the progress of AMD.

These are not drugs that you can take as normal tablets or injections. They have to be injected deep into the eye. This is called an intravitreal injection.

First, an anesthetic is put into the top layer of the eye, either by injection, drops or gel, and then the drug itself is injected deeper into the eye with a fine needle. These injections are done once a month at first, and after that treatment might be reduced to once every few months. But it depends how your eyes react. In trials, up to 3 out of 10 people (30%) experienced pain from the injection after the treatment. However, it was usually not so much pain that they stopped using the treatment.

What kind of benefits can be expected from treatment with Lucentis or Macugen?

Some people with AMD have so much damage to their eyesight in the course of one year, that they can notice that their sight has definitely gotten worse. One of the ways of measuring this is by counting how many numbers or letters a person can read on a standard eye chart. There are several trials of Lucentis and Macugen where the number of letters people could read was measured before treatment and then they were re-tested after a year. The results for people who had the injections were compared with the results for people in the trials who got fake injections.

Both medications were able to stop or at least slow down worsening of eyesight in some of the patients. Over the course of one year, in between 55 and 68 out of 100 men and women who had received fake therapy, eyesight remained practically unchanged or did not get considerably worse (55 to 68%). Out of 100 men and women who had received one of the two medications, eyesight in between 70 and 96 people stayed the same or did not get considerably worse (70 to 96%). In other words, out of every 100 people who used this drug, in between 15 and 32 people the drug prevented their sight from getting considerably worse (15 to 32%). In some people, the treatment even improved their eyesight.

That their sight had been preserved was clear for many people, if they were still able to read, for example.
Although we do not yet know the long-term outcome for most of these people, there have already been some results measured after 2 years, and the benefit lasted.

Although it is not possible to say for certain whether one of these drugs is more effective than the other, the results so far have been better for people in the trials of Lucentis.

What are the adverse effects?

Pain is not the only adverse effect of these injections. Most of the adverse effects come from the injection, not the drugs. It is still not clear how often these drugs could impair eyesight. It is hard to be precise about the risks overall, because the drugs are relatively new. However around 1 to 2% of people who receive monthly injections develop a condition called endophthalmitis. This is a serious inflammation of the eyeball, which can severely damage the eye. The higher the dosage of the injections, the greater is the risk of adverse effects.

Injecting fluid into the eye can raise the pressure inside the eye. This is called intraocular pressure. While this usually goes away soon with no problems, it could be harmful for people with increased intraocular pressure (glaucoma) or other eye problems. The rate of people with increased intraocular pressure was about 10% higher in the groups who used Lucentis, for example. This means that intraocular pressure increased in an extra 10 out of 100 people who were treated. If the pressure increases, the eye needs to be monitored after the injection to see if extra treatment is needed to relieve this pressure.

The adverse effects of these drugs may also include “mouches volantes” (also sometimes commonly called floaters): people see points or spots that move along with the eye’s movements. These could occur in 25% of people who take these drugs, but more research is needed to be sure.

The drugs themselves might also cause cardiovascular problems in some people. However, it is difficult to be sure about this until more follow-up results from the trials are reported in coming years. In the meantime, the manufacturers of Lucentis in America have warned doctors that there might be an increased risk of stroke with doses of 0.5 mg. Lower doses of 0.3 mg were effective at reducing loss of vision in the trials, and there has been no similar safety warning about this dose.

What is Avastin and does it work as well as Lucentis and Macugen?

Bevacizumab (brand name: “Avastin”) is another drug that can be injected into the eye to stop abnormal blood vessels from developing. It is very similar to ranibizumab (Lucentis), although it is not exactly the same. Avastin has been approved for use in bowel cancer, but not for treating AMD. This means that using Avastin for AMD is “off-label use”. You can read more about the implications of using drugs “off label” here. Your eye specialist should inform you of what this means.

Avastin is used in AMD because it is much cheaper than the other drugs.  Recently results of the first trial comparing Avastin and Lucentis have been published. These showed that both drugs really have a similar effect. Adverse effects were a little more common in Avastin than they were in Lucentis, though. People with AMD and doctors are now awaiting the results of further trials to see whether these results are confirmed. Currently there are 5 more trials comparing Avastin and Lucentis. As soon as the results are published we will update this information.

Can you combine these drugs with other drugs and treatments for AMD?

Yes, this is generally possible: some people use more than one treatment for their AMD and combine drug therapy with photodynamic therapy, for example. However, there has not been enough research to know what effect these combination therapies have. This is the subject of continuing research. As more research becomes available on these and other ways of treating AMD, we will add it to our information.

You can read more about other treatment options, as well as details about the research into these drugs, in our feature on AMD here.

Author: German Institute for Quality and Efficiency in Health Care (IQWiG)

Next planned update: May, 2014. You can find out more about how our health information is updated here.

© IQWiG (Institute for Quality and Efficiency in Health Care)