The medications are injected directly into the eye. The eye can safely be injected at the point where the white part of the eye meets the colored part of the eye(the pars plana). Injections in front of the white part of the eye could damage the lens in the eye. Injections too far behind the white part of the eye could injure the retina.
The most serious complication of intravitreal injections is infection. The risk of infection is about 1 in 5,000. Infection can be serious and lead to loss of vision and loss of the eye. Subconjunctival hemorrhage, bleeding on the surface of the eye occurs in 10 percent – 20 percent of treatments. Floaters occur in about 10 percent of treatments. With long term treatments about 10 percent of patients develop increased intraocular pressure.
There are three different anti-VEGF medications injected for wet AMD. They are each slightly different. The biggest difference between the three is cost. Avastin at 100 dollars per dose is much less expensive than Eylea and Lucentis which each cost a little less than 2000 dollars. Studies comparing the efficacy (how well they work) of the medications has shown them to be very similar. Lucentis is a little stronger than Avastin. Eylea is likely a little stronger than Lucentis. Finally, there might be systemic safety issues with the medications. The medication that has the least systemic exposure is Lucentis becasue of the way the drug is designed. The other two, Eylea and Avastin stay in the blood stream after injections in the eye at a very low dose. Studies comparing the safety of the 3 drugs has not shown a significant safety difference among the treatment choices. Avastin is used more than either Eylea or Lucentis as of 2014 in the US. Avastin is not FDA approved for use in the eye but has a long track record of being used in the eye safely.
So the short answer is that there is not much difference among the three different anti-VEGF medications currently in use for wet AMD.
Most patients experience little or no pain with intravitreal injections. Our practice has published a study showing that, with optimal anesthesia, very few patients experience significant pain. For a pdf of the study click here. There are two main ways of numbing the eye for injections. Topical only anesthesia involves using anesthesia drops, gel, and/or cotton soaked swabs. Subconjunctival anesthesia involves using topical anesthesia followed by an injection of subconjunctival lidocaine. There are advantages to each type of anesthesia. Topical only is faster and generally causes less irritation to the eye after treatment. It also carries a decreased risk of subconjunctival hemorrhage. Unfortunately, more people feel significant pain with topical only anesthesia (but not all people). Subconjuntival anesthesia usually affords people better pain control. Main patients treated with intravitreal injecitons following subconjunctival anesthesia don’t even realize they’ve been given an injection because there is no pain. Unfortunately about 5 percent of patients have difficulty with post-injection reactive pain when treated with subconjuctival lidocaine. Also, there is a higher risk of subconjuntival hemorrhage (bleeding on the surface of the ey) with subconjunctival lidocaine. In our study, 90 percent of patients preferred subconjunctival lidocaine and 10 percent preferred topical anesthesia only.
It is impossible to know how many injections each individual patient will need. Some patients require a limited number of injections and some require ongoing therapy for years. Depending on your disease (macular degeneration, retinal vein occlusion, diabetic macular edema) and the drug being used (Lucentis, Eylea, Avastin, Ozurdex, Illuvein), the answer may be slightly different. All medications injected into the vitreous eventually wear off. Most have an effect for only about 1 or 2 months. Also medications used to treat retinal disorders do not cure the disease, they only control it. Most injections are given for macular degeneration. Macular degeneration is a chronic disease and often requires ongoing therapy. Most studies have shown that patients treated more frequently for retinal diseases do better than those treated less frequently. Most retina doctors in the county use a ‘treat and extend’ protocol with intravitreal injections. Monthly injections are given for a time and then treatments are given less frequently and the disease is assessed. If a longer treatment interval results in recurrent disease, then the treatment interval is shortened. If not, the treatment interval can be maintained or lengthened.
Intravitreal injections work. Without treatment, many patients lose their central vision. With treatment, central vision is usually maintained. It is easier to live an independent life when you can see. Therefore, we usually encourage our patients to proceed with treatment regardless of their age.
Patients rarely recover normal vision. Most macular disease causes some permanent damage. Treatment can significantly reduce the risk of vision loss. In addition, most patients see better with treatment than they did before starting treatment. Normal vision is rare. About 10 percent of patients recover normal vision with intravitreal therapy. Most of those patients started with very good vision before therapy.
There are several medications available to treat most retinal diseases. Treatment can take 3 to 6 months before a benefit is realized. If one medication doesn’t work, sometimes switching to a different one helps. In addition, there are sometimes alternative to intravitreal therapy that can be considered if intravitreal therapy is not working. In almost all cases, intravitreal injections are the safest and most effective treatment. For some disorders (especially diabetes), laser can be considered. Some retinal vein occlusions also respond to laser. Wet AMD can be treated with cold laser (photodynamic therapy). Studies have shown that in almost all cases, photodynamic laser is not as effective at improving vision as intravitreal injections.
With many macular disease, distortion can persist for a year or two even when the visual acuity improves. In some cases, as the visual acuity improves, the distortion may become more noticeable because the patient, in seeing better, sees the distortion better. Usually, over time, distortion becomes less bothersome as the eye and the brain adapt to the state of the macula.
Lucentis and Eylea cost almost $2,000 per dose. Ozurdex is over $1,000 per dose. Illuvein is over $5,000 per dose. One reason the medications are so expensive is that research and development of medications is very expensive. It can cost 100 million dollars in research to bring a drug to market. Another reason is that, in the US, Medicare is prohibited from negotiating price of drugs with drug companies. In 2003, Congress and President Bush enacted the “Medicare Prescription Drug, Improvement and Modernization Act,” which established a prescription drug program for Medicare. That legislation expressly prohibited Medicare from negotiating drug prices with pharmaceutical companies.
The anti-VEGF medications are proteins that cannot be administered into the eye in any way other than injection. Topical therapy was tried and did not work. Steroid injections into the eye (ozurdex and illuvein) can be given systemically and topically. The doseage level achieved by these alternate routes does not work to treat most macular disease.
Yes, there are several potentially longer acting treatments being researched. None are close to being approved by the FDA for use outside of research studies. Genetic therapy has the potential to treat a patient with a single treatment. Then the patient would start making their own drug. There is an encapsulated cell technology that might be able to deliver therapy over a few years. Until something long acting is avialable, ongoing treatment with intravitreal injections is the best and most effective treatment for many macular diseases.
Intravitreal injections for wet AMD were approved by the FDA in 2006. So there are many patients who started treatment then and have had over 100 treatments. The needles used for the injections are very small and don’t cause scarring. There may be some adverse affects of long term anti-VEGF therapy. About 10 percent of patients getting long term therapy develop increase intraocular pressure. This could be from inflammation or possibly from the build up of material in the drainage channels in the eye. There may be increased risk of geographic atrophy in some patients receiving long term anti-VEGF therapy. These risks are small and considered acceptable given the tremendous benefit that ongoing anti-VEGF therapy confers on pateints.