Controversies in the treatment of wet AMD

A reader asked the following question:

“My otherwise very healthy 80 year old father was just diagnosed with wet AMD in one eye. The doctor recommended the use of Macugen injections every 6 weeks starting in early Nov. My question is, is this the best way to treat this in terms of newest and most progressive? Or is there any other approved treatment that shows more promising results.”


Here is what a retinal specialist from Florida wrote us:

“Dr. Folk’s recent posting about the use of Avastin for treating wet age-related macular degeneration should not inspire the ophthalmology community to mass action. The physicians using Avastin are doing so based on anecdotal information, with neither significant evidence nor well-controlled studies to support its use for this indication. While I certainly understand how physicians could be intrigued by the Avastin experiments to date, it is surprising how quickly people seem to be jumping to use a drug that has been shown to cause serious adverse effects when used to treat colon and other cancers – and which is not recommended for use in elderly patients due to its side-effect profile.

From a clinical viewpoint, our practice has performed more than 1,100 Macugen injections since January 2005. It is our impression that the majority of patients stabilize or significantly improve their vision over time. There are 2 caveats: the clinical effect may not be noted until the 4th through the 6th treatment (so don’t give up too soon); and there does not seem to be a great correlation between the visual response and the appearance of the fluorescein angiogram and/or OCT.

Let’s re-think our approach here, and until we have more robust and well-controlled data, let’s use the very safe and effective therapies that have been FDA-approved to treat wet AMD.”

So here’s what I think: Macugen® injections are given at six week intervals. The first injection is given at week zero, the second at week six, the third at week twelve, and so on. Therefore a doctor can’t evaluate the result of the fourth injection until 24 weeks, (six weeks after it was given), and the result of the sixth injection until 36 weeks. Macugen® was launched last January 20th, so it’s been available for only about forty weeks. Therefore most retinal docs haven’t yet seen a lot of patients who have had six or more injections. The company who makes Macugen® says the same thing as the doctor advised above, namely that you have to give the drug time to work.

I don’t want to come across as the champion of Avastin®. I will tell you though, why many retinal specialists are not satisfied with Macugen®. The main study on Macugen® (see reference below) contained 1186 patients. After 54 weeks of follow-up, 70% of patients who received Macugen® lost fewer than three lines of vision compared to 55% of patients in the control group. 33% of the patients who received Macugen® had the same or improved vision after one year compared to 23% of the control group. That means that two-thirds of the patients in the Macugen® group lost vision. On average, the patients who received Macugen® lost about 1.5 lines of vision on the visual acuity chart.

Patients come to us because they have already lost vision. They ask us if their vision will improve with treatment. We have to tell them that with Macugen® or with Visudyne®, that it is more likely that their vision will get worse, but that either treatment is still better than doing nothing. The patients don’t like that answer. I don’t like that answer either. We need a better treatment. My Florida colleague is right in stating that the evidence about Avastin is anecdotal. I concluded my October 19th Blog, (http://www.medrounds.org/amd/2005/10/to-retinal-specialists-about.html), stating, “We have to be careful though, since we’ve not followed these patients for very long and we also have the proven treatments of Visudyne® and Macugen®.”

It’s too long though, to have to wait until the fourth or sixth injection (24-36 weeks) for Macugen® to control the choroidal neovascularization. We know that neovascularization grows. I’ve seen it grow after Macugen® and Visudyne® and in general, the larger the area of neovascularization, the greater the area of scarring, and the poorer the visual acuity. Therefore it would be best to stop these vessels right away not six or seven months from now.

A representative from Novartis, who makes Visudyne®, also objected to my statement that if a patient doesn’t respond to one Visudyne® treatment that I might consider Avastin. He said that often three or more treatments are needed before the neovascularization is controlled. So it’s a conundrum. Visudyne® and Macugen® take a while to work, yet meanwhile the neovascularization may be gobbling up more of the patient’s precious macula.

I disagree with the retinal specialist from Florida that the fluorescein and OCT don’t correlate well with the vision. I use both of these tests to tell me whether a patient is responding to treatment. That’s probably enough for today. In the next blog, I’ll tell you what I do. It makes sense to me but I don’t know if it’s right or not. Meanwhile, I would invite any retinal specialist to write in and give us your experience. To be fair, also state whether you have any financial interest in any of these treatments. I don’t.


1. Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR, for the VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004; 351:2805-2816.

2. Klein M, Jorizzo P, Watzke R. Growth features of choroidal neovascular membranes in age-related macular degeneration. Ophthalmology 1989; 96:1416-1421.

3. Sletten KR, Folk JC, Russell SR. Shape and size of choroidal neovascularization in response to sequential photodynamic therapy. Retina 2005, in press.