Lucentis / Avastin and PDT

Lucentis® is a great treatment of wet AMD. Lucentis stops the leakage from the new blood vessels and stops them from growing. The only problem is that Lucentis doesn’t usually eradicate the new vessels. That means that many, if not most, patients need injections every month for a prolonged period. Some patients in the MARINA trial had a recurrence of leakage even after twenty-four monthly injections. Each injection carries the risk of endophthalmitis. Retinal physicians are now trying out different treatment schedules to see if their patients can get by with fewer injections. One plan is to give three monthly injections and then, if the patient has no fluid, watch the patient carefully and only treat if the vision drops or the fluid returns.

PDT or Visudyne® treatment is not as good as Lucentis but it can eradicate the new blood vessels permanently. Often the new blood vessels return after the first PDT and the treatment has to be repeated a few times until they are destroyed. The recurrence of the abnormal blood vessels is, in part, due to VEGF which is upregulated in the area of treatment. Lucentis is an antibody to VEGF so it makes sense to combine it with PDT. The idea would be to use the PDT to eradicate the blood vessels with Lucentis to block the upregulation of VEGF so the vessels don’t come back. That may, in turn, reduce the number of injections needed to control the disease.

The problem with this concept is that PDT also affects the normal capillaries in the choroid. The upregulated VEGF may be a protective response that allows the capillaries to grow back in the area that was treated by the laser. So perhaps blocking this response will prevent the capillaries from growing back and result in vision loss. I have now seen two patients who had vision loss after treatment with Avastin® followed by full dose PDT seven to ten days later. Both appeared to have loss of capillaries in the choroid in the area of treatment. Interestingly, both patients noticed the vision loss right after the PDT treatment which may mean that the Avastin somehow sensitized the capillaries to damage from PDT. Regardless, it appears that full dose PDT is probably not advisable after Avastin or Lucentis.

There are a number of doctors that treat with PDT using half the usual light dose. So far that seems not to cause damage to the choroid even after Avastin or Lucentis. We don’t know if this treatment will be as good as Lucentis alone but it should reduce the number of injections needed to control and eventually eradicate the neovascularization.

References

1. Schmidt-Erfurth U, Schlotzer-Schrehard U, Cursiefen C, et al. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 2003;44:4473-80.
   
2. Michels S, Schmidt-Erfurth U. Sequence of vascular events following photodynamic therapy. Invest Ophthalmol Vis Sci 2003;44:2147-54.

AARP and Diet

You may have noticed that I changed the July 25th blog, (Patients with AMD Need Your Help), in which I encouraged you to write AARP magazine. I also appreciate those who wrote AARP because I think they got the message that there is great interest in AMD. AARP magazine is published only six times a year and contains a variety of topics so they don’t have room right now for an article on AMD. I think your letters however, kept AMD on the radar, so to speak. Any more e-mails right now however, would be, as they say in the publishing business, “over the top.”

In the April 17th blog, I discussed a study from the Netherlands, that showed a diet rich in vitamins C and E, beta-carotene, and zinc reduced the risk of AMD by 35%. These results compared favorably with the results of the Age-Related Eye Disease Study (AREDS) which showed a 25% reduction of the risk of progressing to severe AMD in patients given high doses of vitamins C and E, beta-carotene, and zinc. It would be almost impossible however, to get the high doses of vitamins and zinc used in AREDS from diet alone.

In the July 31 blog, I discussed the finding of two recently published studies that showed large reductions in the risk of developing AMD and/or progressing to severe AMD in patient who ate fish once a week. AREDS 2 is studying whether one gram of docosahexaenoic acid (DXE), an omega-3 fatty acid, per day reduces the risk of AMD. AREDS 2 is also studying whether lower doses of beta-carotene or zinc are just as effective in reducing the progression of AMD as higher doses. The study from the Netherlands suggests that lower doses, from diet alone, may be just as effective.

When the original AREDS was being planned, there was a lot of skepticism that vitamin and zinc supplements would reduce the progression of AMD. In fact, most doctors, including myself, thought the study would show that they had no effect. One reason that the doses of vitamins A, E, beta-carotene, and zinc used in AREDS were set so high was to eliminate the criticism that the doses weren’t high enough in the probable event that the study showed no difference between the supplements and placebo groups.

So these results beg the question: Should I get these nutrients through diet or supplements or both? And the answer is (drum roll): I don’t know. I can say the following however:

1. A diet rich in vitamin C, E, beta-carotene, and zinc is effective at reducing AMD.
2. I have a prejudice that getting these nutrients naturally is better than taking a pill.
3. I would recommend that you eat fish that isn’t fried at least once a week.
4. In addition to eating fish, you need to reduce your intake of omega-6 fatty acids.
5. I would still take vitamins at a dose recommended from AREDS until we know more.
6. But, if you can’t tolerate the high doses, you probably will be okay if your diet is good.

I guess I haven’t told you anything new but I thought it was worth summarizing the latest on diet and supplements and the risk of AMD.