Two common retinal causes of vision loss are wet age-related macular degeneration (wAMD) and diabetic macular edema (DME). In both of these conditions a signaling protein (called VEGF) is released that promotes blood vessel leakage with loss of vision. A major advance in treatment came about with the development of drugs that block the effect of VEGF. These drugs (called antiVEGF) reduce the risk of vision loss and offer some improvement in vision in patients with wAMD and DME. Unfortunately, these drugs need to be administered as an injection into the eye. Consequently, drug manufacturers work to design drugs offering the best vision with the longest interval between injections (fewer injections).
What drugs are available and how effective are they?
The first drug to reduce the rate of loss of vision in wAMD was Macugen (pegaptanib). It is no longer used because newer drugs are more effective in offering improvement in vision. While Lucentis (ranibizumab) was under development, its parent drug Avastin (bevacizumab) was found to be effective for wAMD. Both Avastin and Lucentis appear more effective than Macugen. Eylea (aflibercept) was developed to block the effect of VEGF and another factor (placental growth factor) involved in blood vessel leakage; consequently, there is moderate evidence that it is more effective than Avastin and Lucentis in DME and offers a longer treatment interval in wAMD. Newer drugs include Beovu (brolucizumab) and Vabysmo (faricimab). There is little evidence to know if they are more effective than Eylea. Finally, Eylea is now formulated in a higher concentration (Eylea HD).
What is the cost of these drugs?
All of the drugs used to treat wAMD and DME are expensive with the exception of Avastin. Avastin was manufactured and priced to treat colon cancer. After it was released, doctors at the Bascom Palmer Eye institute discovered it was effective in treating wAMD. Thus, the small dose needed to inject into the eye costs about $50. This is in contrast to the other drugs on the market, which cost around $2000 per injection.
What are the adverse effects of these drugs in the eye?
Problems may occur from the injection of medications into the eye. The injection itself has risks apart from the drug that is injected; we will not discuss those risks here, but they include pain, elevated eye pressure, hemorrhage, infection, retinal detachment, and loss of vision. The drugs themselves may cause inflammation in the eye. Usually, inflammation causes pain, redness, light sensitivity, floaters, and decreased vision. Typically, it can be treated with drops and it resolves without permanent damage. However, sometimes the inflammation can be severe with permanent loss of vision. Inflammation induced by drugs is very rare with Avastin and Lucentis. It occurs in about 1% of Eylea injections, 2% of Vabysmo injections, and 4-5% of Beovu injections. The inflammation with Beovu may be especially severe with permanent loss of vision. The risk of infection appears less in drugs that are pre-packaged in a syringe for injection (Lucentis and Eylea), and greater in drugs that must be prepared for injection (Avastin, Vabysmo, Eylea HD, and Beovu).
What are the adverse effects of these drugs outside the eye?
There is concern about effects of these drug outside the eye. All of these drugs leave the eye, enter the blood vessels and are removed from the body through the urine. On their way out of the body, there is concern that they may increase the risk of heart attack and/or stroke. There is considerable debate as to whether there is a measurable effect or not. Some have estimated that the systemic risk may be about 1%. However, patients with known risk factors (hardening of the arteries, tobacco use, high blood pressure, high cholesterol, overweight, and diabetes) may be more likely to suffer a heart attack or stroke with the use of antiVEGF drugs. In one study, patients with diabetic macular edema were at 17% (range: 2-33%) higher risk of death when undergoing frequent injections up to 2 years. Another study, demonstrated increased risk of stroke or heart attack in diabetic patients with a history of past stroke or heart attacks. Therefore, this group of patients may benefit from careful drug selection. Of all the drugs, Lucentis is cleared the most rapidly from the body and has the least systemic effects.
Want a summary of the cost, effectiveness, and safety?
Summary:
| AntiVEGF drug | Cost | Effectiveness | Safety |
| Avastin | Cheap: ~$50 | Good | Repackaging* |
| Lucentis | Expensive: ~$2,000 | Good | safest systemically** |
| Eylea | Expensive: ~$2,000 | Better | 1% inflammation |
| Eylea HD | Expensive: ~$2000 | ?Better | 1% inflammation or greater? |
| Vabysmo | Expensive: ~$2,000 | ?Better | 2% inflammation |
| Beovu | Expensive: ~$2,000 | ?Better | 4-5% inflammation |
* Repackaging increases risk of infection, floaters, and discomfort for dull needles
** Especially relevant when repeated injections are required in diabetic patients
What is my professional preference?
I have employed all of these drugs for my patients. When cost is an issue, an insurance company may insist on the use of Avastin. I generally prefer Lucentis in my diabetic patients for its superior systemic safety. Eylea can be helpful to extend treatment intervals (longer time between injections) in wet macular degeneration. Eylea may also be safer in patients who also have glaucoma, or at risk of developing glaucoma. I have been favorably impressed with Vabysmo in extending treatment intervals even further in wAMD, but I am less impressed with any advantage in my patients with DME (diabetic macular edema). I am currently exploring the role of Eylea HD, especially to extend the treatment interval in patients with wet AMD. Due to the risk of inflammation with loss of vision from Beovu, it is not my preferred agent. Lucentis biosimilars (Cimerli and Byooviz) are not my preferred agents at this time…I am awaiting further evidence on their safety and effectiveness.
Are doctors paid by drug companies to use their drugs?
There are varying amounts of profit margins and rebates given to doctors by drug companies in an effort to promote the use of their drugs. Usually, the newer the drug, the greater the inducement. To determine if your doctor is receiving large payments by drug companies, visit the CMS website and enter your doctor’s name in the search box.
For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.
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