Tarheel Health Portal/Anti-VEGF Injections for Age-Related Macular Degeneration

Approximately 1.75 million individuals in the United States suffer from age-related macular degeneration. By, 2020, about 3 millions individuals will suffer from age-related macular degeneration as predicted by the National Eye Institute. The University of North Carolina at Chapel Hill has a very diverse student body. Although age-related macular degeneration is not genetic, it is more prominent in older adults, and there are many adults on campus, including students and faculty. The information below provides perspective on two drugs used to treat age-related macular degeneration, bevacizumab and ranibizumab, and different treatment plans, monthly injections or as needed injections.

What is Age-Related Macular Degeneration?
Age-related macular degeneration (ARMD) is the number one cause of irreversible vision loss for adults. ARMD is the growth of abnormal blood vessels in the macula, which serves as the center of the retina. The retina contains rods and cones that are in charge of receiving light and changing it into neural signals for the brain to use to create an image. As the blood vessels grow, bleeding, swelling, and scarring occur in the macula causing irreversible vision loss primarily for people age 50 or older. Vascular endothelial growth factor (VEGF) is a protein that causes abnormal blood vessels to grow in excessive amounts.

To treat advanced ARMD, patients can get injections of anti-VEGF that work to inhibit the growth of the abnormal blood vessels. There are two main types of anti-VEGF injections: ranibizumab (Lucentis) and bevacizumab (Avastin). Along with the two different injections, there are also two primary treatment plans: receiving injections monthly or as needed. Although Lucentis has been approved by the U.S. Food and Drug Association (FDA) to treat ARMD, it is much more expensive than Avastin with a price tag of approximately $1,950 per dose as compared to $50 per dose. Though it has a much lower price, Avastin has not been FDA approved to treat ARMD; however, it has been FDA approved to treat metastatic cancer of the colon and rectum. Scientists, doctors, and patients are searching for answers as to which drug works better in treating age-related macular degeneration. Another aspect of treatment that is widely questioned is how the frequency of injections can affect the gain in visual acuity. Some treatment plans call for monthly injections while others call for injections as needed. These two different types of treatment plans play a large role in the effectiveness of the treatment.

As vision loss from age-related macular degeneration is increasing, adults with ARMD should take interest in how cost effective their treatment plan is. Although monthly injections can add up to a large sum of money, they may be the most effective way of tackling ARMD. With ranibizumab having such a high price tag, it is understandable why those with ARMD may not want to receive monthly injections of ranibizumab; therefore, receiving Avastin injections monthly is more cost effective than receiving Avastin injections as needed or receiving Lucentis injections monthly or as needed.

Avastin vs. Lucentis
Recently, there has been a lot of controversy over two anti-VEGF injections that are currently being used to treat age-related macular degeneration: bevacizumab (Avastin) and ranibizumab (Lucentis). Ranibizumab is an antibody fragment that was first produced by Genentech, a biotech company. The parts of the antibody that did not bind to VEGF were taken out so that the molecule would be small enough to pass through the eye tissues. In 2005, a year before ranibizumab was approved to treat ARMD by the FDA, a highly respected physician named Phil Rosenfield, MD, PhD released a case series that used bevacizumab as a treatment for ARMD. Bevacizumab was also an anti-VEGF antibody that was produced by Genentech and was known as Avastin. Although Avastin was FDA-approved, it was not approved to treat ARMD; instead, it was known to treat colon cancer. Still, both drugs were very similar. The main difference was that Avastin still contained all the nonbinding parts of the antibody that were taken away in Lucentis.

Study #1
In a study led by Dr. Daniel Martin, a team of scientists and doctors analyzed the visual acuity of ranibizumab versus bevacizumab. The injections were prepared with 0.50 mg of ranibizumab in a 0.05 mL solution and 1.25 bevacizumab in a 0.05 mL solution. There were four treatment groups: bevacizumab monthly, bevacizumab as needed, ranibizumab monthly, and ranibizumab as needed. After one year of treatment, researchers in this study randomly assigned participants who were on monthly treatment plans to either continue monthly or begin an as needed treatment plan with the same drug they had been receiving during the first year of treatment. When simply comparing the effectiveness of the two drugs, they found that the gain in visual acuity was relatively the same throughout the two years of the study. The difference between the gain in visual acuity for both drugs was 1.4 letters when measured with a Snellen test, but both drugs produced a mean visual acuity of a 20/40 Snellen. Within the study, the two drugs produced the same ratio of participants with 20/20 or better to 20/200 or worse. These conclusions show that bevacizumab and ranibizumab have very similar effectiveness, as shown here.

Study #2
In a study conducted by the CATT Research Group, the effectiveness of ranibizumab and bevacizumab on age-related macular degeneration were compared. The method of this study was very similar to the previous study in that it had four randomly assigned treatment groups: bevacizumab monthly, bevacizumab as needed, ranibizumab monthly, and ranibizumab as needed. The CATT Research Group found that after one year of treatment, the mean change in visual acuity for bevacizumab and ranibizumab were the same. Both drugs produced very similar proportions of participants who gained a visual acuity of at least fifteen letters throughout the first 36 weeks of treatment, measured by Snellen tests. When comparing the two drugs’ monthly treatment plan, bevacizumab had a gain of 8.0 letters, and ranibizumab had a gain of 8.5 letters, showing researchers that both drugs have very similar effectiveness.

Monthly vs. As Needed
In the two studies described in the previous section, the methods administered both included a monthly and as needed treatment plan for both drugs. The type of treatment plan can have a large effect on how well the drug works in treating age-related macular degeneration. The advantages of being on a monthly treatment plan are that the drug is constantly being injected and working in the eye tissues; however, the cost of monthly injections adds up very quickly and can be very expensive depending on the drug used. There are also pros and cons to receiving treatment as needed. The biggest advantage is the reduction in how much the patient has to pay; however, tests still have to be done to determine whether or not the patient needs to receive the injection that month, which would be an additional expense. On the other hand, receiving injections as needed could have negative effects on the gain in visual acuity since the drug is not present in the patient as often as it would be if the treatment plan were monthly.

Study #1
Like previously explained, Dr. Daniel Martin and a team of doctors and scientists conducted a study comparing the two drugs, bevacizumab and ranibizumab, and treatment plans, monthly and as needed, using four treatment groups. Once a year had passed, the participants in the monthly treatment plans were randomly reassigned to either continue receiving monthly injections or receiving injections as needed. Those who did change treatment plans kept the same drug. To determine whether a participant needed an injection, patients were evaluated each month and only received the injection if fluid was present on optical coherence tomography (OCT) scans, if hemorrhages were present, if visual acuity had lowered from previous visit, or if a fluorescein angiography showed dye leakage. The study found that those who were receiving injections as needed had a lower gain in visual acuity even if they had received monthly injections during the first year. Each treatment group had a mean gain in visual acuity measured using a Snellen test as listed: ranibizumab monthly gained 8.8 letters, bevacizumab monthly gained 7.8 letters, ranibizumab as needed gained 6.7 letters, and bevacizumab as needed gained 5.0 letters. Those who receiving treatments as needed had a mean gain of 2.4 letters less than those on monthly treatment due to more complications that advanced age-related macular degeneration. Even the participants who received monthly injections within the first year before being reassigned to receiving injections as needed still had a mean decrease of 2.2 letters, which was equivalent to those who had been receiving injections as needed during the entire study. This indicates that switching from monthly to as needed treatment worsens ARMD, as shown in Figure 1. The doctors and scientists also found that those who were switched from monthly to as needed during the study had a higher total retinal thickness and more residual fluid build up, both which contribute to advancing ARMD, than those who received monthly injections for both years.

Comparative Analysis
In a paper discussing different clinical trials, an international retina expert panel consisting of Paul Mitchell, from the Department of Ophthalmology at the University of Sydney, and his colleagues compared multiple studies done on treating age-related macular degeneration with ranibizumab injections. Each of the studies implemented different treatment plans. Two of the studies that they looked at showed that visual acuity gained during the first three months was maintained and improved throughout the two-year study. These two studies’ treatment plans included giving the participants monthly injections. In a third study, the scientists opted to treat their participants with monthly injections for the first three months followed by quarterly injections for the remainder of the two-year study. While the visual acuity of the participants improved during the first three months when they received monthly injections, once they began receiving quarterly injections, the mean visual acuity decreased with an average of 2.2 letters less than the baseline assessment when measured with a Snellen test. The third study indicated that quarterly treatment is not as effective as monthly treatment. The panel concluded that monthly injections produced the most gain in visual acuity, and treatment plans that include less than five injections within the first year usually produce the lowest gain in visual acuity.

How Does ARMD Pertain to You?
The majority of the student population at UNC fall between the range of 18 to 26 year olds. At this point in time, age-related macular degeneration is not as prominent as it is in a population of older adults; however, it can still have an effect on students who may have family suffering from ARMD. With ARMD, it is very difficult to go about doing normal life activities. Family members with ARMD may need assistance doing everyday activities. It is important to watch for signs of family members losing their vision, such as running into things and not being able to see what is straight ahead of them. Losing one's vision is a scary sensation, so it is important that you speak to someone who suffers from ARMD in a respectful way as to not speak down to them. The first thing to do is to take the individual to an optometrist who can diagnose the individual and begin talking about treatment plans. A list of local optometrist in the Chapel Hill area is listed in the following section.

Resources for Those Struggling with ARMD
If you believe you are suffering from ARMD, it is important that you see an optometrist immediately to begin a treatment plan before large amounts of degeneration occur. Below is list of optometrists in the Chapel Hill area.
 * Eye Care Associates
 * Carrboro Family Vision
 * Chapel Hill Eyecare
 * Eye Care Center
 * Carolina Vision Associates
 * Academy Eye Associates

Research on ARMD at UNC
Currently, research is being done on age-related macular degeneration in the UNC School of Medicine Department of Ophthalmology. For more information on the research being done on detecting ARMD, click here.

Further Readings
What Are Your Chances of Suffering from Age-Related Macular Degeneration?

NIH's Facts About Age-Related Macular Degeneration

UNC School of Medicine Information on Age-Related Macular Degeneration

Bright Focus Foundation's Facts and Statistics on Macular Degeneration

Information on Macular Degeneration from the World Health Organization