CATT: More on Important AMD Trials

A third AMD trial is the Complications of AMD Treatments Trial or CATT. This trial is being chaired by Dan Martin of Emory. It’s due to start in late spring. The study will compare monthly injections using Avastin to monthly injections of Lucentis. It will also compare three monthly injections of Avastin followed by “as needed” injections to the same regimen using Lucentis. The trial should determine whether Avastin or Lucentis is better and whether the “as needed” injection regimen is as good as monthly injections.

“As needed” means that, after three injections of either Avastin or Lucentis, a patient will receive another injection only if there is fluid on the OCT, new vision loss, new hemorrhage or new growth of the neovascularization. The “as needed” regimen is used to reduce the total number of injections that must be given to control the neovascularization and its leakage. AMD patients are not all the same. Some may need monthly injections for a year or more but many will not.

We are also awaiting news whether there will be another trial on the VEGF trap which is manufactured by Regeneron. The VEGF trap has shown excellent visual results in two small studies. The advantage of the trap is that it may need to be injected into the eye only every three months.

New Studies on AMD: DENALI

We’ve discussed before that the drawback of Avastin or Lucentis is that they don’t permanently close the new blood vessels beneath the retina. Most clinicians give three injections of Avastin or Lucenits at monthly or every six week intervals. They then watch the patients and give additional injections on an “as needed” basis. “As needed” means the patient develops visual loss, new hemorrhage, or most commonly new fluid seen on OCT and therefore needs another injection. Phil Rosenfeld of Miami treated patients using this scheme and found that, on average, patients needed about six injections over the first year of treatment. Some patients however, need injections every month. Patients get tired of these injections and each on of them has a small risk of endophthalmitis. Therefore a treatment for AMD that involves fewer injections is needed.

Novartis is sponsoring the DENALI study which will start soon. In DENALI, patients will be randomized to Visudyne at full or half light doses along with Lucentis or to Lucentis alone. The hope is that the patients who receive Visudyne along with Lucentis will have similar visual results as the patients who receive Lucentis alone but will need fewer injections to control the neovascularization. I think patients would like this, namely to have Visudyne and then maybe two or three injections of Lucentis, and then be done. “Done” means that they would have long term control of the neovascularization with good vision.

We won’t know the results of the DENALI study for over a year but they will be important.

~ Jim Folk, MD

New Studies Underway: AREDS 2

Hi. I was in Peru so I haven’t kept up with the blog recently. Thanks to those who e-mailed me to ask if I was okay. I’m fine, although I had a little turista in Peru. Thank heavens for antibiotics.

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There are a lot of trials planned or underway in AMD but here are the following ones that I think are most important at this time:

1. AREDS 2- the first AREDS, (Age-Related Eye Disease Study), proved that supplementation with vitamins C and E, beta-carotene, zinc, and copper, (to reduce zinc related anemia), reduced the progression to severe AMD by about 25% over five years. High doses of these supplements were used to prove whether or not they were effective. Otherwise, if the study had shown no affect, it could’ve been argued that the doses were not high enough.

Recent studies found that diets rich in these vitamins and zinc seemed to be as effective in reducing the risk as the AREDS supplements and these diets contained much lower amounts of the micronutrients in question. Studies have also shown that eating fish, which is high in omega-3 fatty acids, reduced the risk. Some studies found that diets rich in lutein/zeaxathine, which are the yellow pigments in the macula, also appeared to reduce the risk of AMD.

AREDS 2 is testing whether supplementation with omega-3 fatty acids and/or lutein and zexanthine reduces the risk and rate of progression of AMD. Patients in AREDS 2 are allowed to take the supplements, (C, E, beta-carotene, zinc, copper), that were found to be beneficial in AREDS. They will be asked however, if they would be willing to be randomized to a lower dose of zinc (20mg instead of 80mg per day) and/or to no beta-carotene.

Following are the goals of AREDS 2 from the NEI’s website: http://www.nei.nih.gov/neitrials/viewStudyWeb.aspx?id=120 (alternate URL: http://preview.tinyurl.com/2347wx)

1. To study the effects of high supplemental doses of dietary xanthophylls (lutein and zeaxanthin)and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs)(DHA and EPA)on the development of advanced AMD.
2. To study the effects of these supplements on cataract and moderate vision loss.
3. To study the effects of eliminating beta-carotene from the original AREDS formulation on the development and progression of AMD.
4. To study the effects of reducing zinc in the original AREDS formulation on the development and progression of AMD.
5. To contribute data for validation of the photographic AMD scales developed from the Age-Related Eye Disease Study.

I don’t know which group will do best. I also don’t know whether the omega-3 fatty acids and lutein/zexanthine will reduce the risk of developing severe AMD or if they will have side-effects. I would encourage you to join AREDS 2 if you have large drusen without atrophy or neovascularization in at least one eye. The centers participating in the trial are listed on the website.

Tomorrow I will discuss the second study. It’s called the Denali Study and compares PDT with Lucentis to Lucentis alone for the treatment of wet AMD.

~Jim Folk, MD