End of Year Summary, 2005

End of Year Summary and Musings

This year has seen major advances in the treatment of wet AMD:
1. Macugen® became available in February.
2. The results of large trials testing Lucentis® were announced in late summer and early fall.
3. Retinal physicians started to use Avastin® late in the year.
4. Numerous presentations, but few published papers, were presented touting the advantage of using intraocular Kenalog® with Visudyne®.
5. Anecortave acetate, (Retaane®), has just been approved for use in Australia.

So where do we stand? Macugen® has been somewhat of a disappointment. In most cases the blood vessels stop leaking but that is usually only after four or more injections during which the disease can progress. There are few homeruns with Macugen®, meaning that the vision improves after treatment.
Lucentis® appears to be the best treatment for wet AMD.(1,2) In most cases there is an immediate reduction in the fluid beneath and within the retina. Many patients have better visual acuity. In large studies, Lucentis® was the first treatment to cause, on average, an improvement in the vision of patients after twelve months compared to baseline. Intraocular Avastin® appears to be safe and have a similar beneficial effect as Lucentis®.

I’m still not sure about the value of Kenalog® plus Visudyne®. In the short-run, the patients do better than with Visudyne® alone. In the long-run, (say 12-24 months), there may be no difference except that a patient may need fewer treatments to control the neovascularization than with Visudyne® alone. I think Kenalog® might be useful in AMD eyes with small areas of neovascularization and in eyes with neovascularization due to histoplasmosis or multifocal choroiditis. I don’t think it’ll be particularly helpful in AMD eyes with large membranes.

The pharmaceutical companies and many excellent retinal specialists are working feverishly to perform high-quality studies to determine the best treatment in wet AMD. Right now it looks like it will be Lucentis®. The big question though, is how many injections of Lucentis® will be needed to control the neovascularization? Hopefully the neovascularization won’t come back in a majority of patients after stopping the injections. If it does return in most patients, then combination treatments, a depot form of Lucentis® perhaps, or combination treatment with Visudyne® or other drugs will be needed because monthly or even bimonthly injections for the rest of the patient’s life is unpalatable and risky. Visudyne® with Lucentis® could be one combination treatment but I worry about subretinal fibrosis (see next paragraph). Lucentis®, (intraocularly), with Retaane®, (subtenons), may be really good but has to be tested.

Permanent visual loss in many wet AMD patients is caused by subretinal fibrosis or at least a band of scar tissue beneath the RPE on OCT. More eyes treated with Visudyne® and Macugen® seem to have scarring compared to Lucentis® or Avastin® eyes. In Visudyne®’s case, it may be due to the opening of the blood-retinal barrier immediately after treatment.(3) It’s as if the eye responds to the treatment with a wound healing type of reaction. The adjuvant use of Kenalog® doesn’t seem to eliminate the fibrosis. With Macugen®, I think it’s the delay in control of the neovascularization which results in increased scarring.

So what to do now? I think, now that we have good treatments with low risks, we should be more aggressive in treating patients with occult neovascularization. If there is leakage on FFA and fluid on OCT, I may treat immediately even if the vision is good. What if there are no new symptoms and the vision is stable? That’s a tough one. If I’m sure there is a CNV, I may still treat after talking carefully to the patient. If I’m unsure, I’ll see the patient back in one month. I know, I know, some of these patients do well with observation. But I think they are the minority in the long-run. And many of the ones who do well initially come back in a year with reduced vision, a huge area of neovascularization, fibrosis, or a big bleed.

Once again, no one is paying me to tout one treatment over another. These are my opinions based on the treatment of patients at Iowa and talking to other trustworthy and busy retinal experts. Happy Holidays!

References:
1. Miller, J.W., Chung C.Y., Kim,R.Y. for the MARINA Study Group. Randomized , Controlled Phase III Study of Ranibizumab (Lucentis™) for Minimally Classic or Occult Neovascular Age-related Macular Degeneration. Presented at the 23rd Annual Meeting of the American Society of Retinal Specialists. July 18, 2005, Montreal, Canada.

2. Heier, J.S., FOCUS Study Group. Intravitreal Ranibizumab (Lucentis™) with Verteporfin Therapy for Neovascular Age-Related Macular Degeneration: Year One Results. Presented at the 23rd Annual Meeting of the American Society of Retinal Specialists. July 18, 2005, Montreal, Canada.

3. Schmidt-Erfurth, U., Niemeyer M, Geitzenaur W., Michels, S. “Time Course and Morphology of Vascular Effects Associated with Photodynamic Therapy.” Ophthalmology 2005; 112:2061-2069.

Update on Treatments for Wet AMD: Increasing Use of Avastin Injections for AMD

In past blogs we discussed various forms of treatment for neovascular or wet AMD. At The University of Iowa we performed the following treatments for wet AMD during the months of September-November of this year:

You can see that the number of Avastin® injections has increased sharply.

The Avastin® seems to work faster at causing resolution of the fluid and neovascularization than the other two treatments. To my knowledge we have not seen any complications from the Avastin® injections.

The number of Macugen® injections and Visudyne® treatments is holding steady. I don’t know how many of these Macugen® and Visudyne® treatments were repeats and how many were new patients. We should be able to tell if their number is changing in future months.
In the past, I have been impressed with Visudyne® plus intraocular Kenalog® given on the same day. The combination treatment seemed to work well in the short run, perhaps because the Kenalog® caused resolution of the subretinal fluid. After twelve months however, I’m not sure the patients with this combination treatment have done much better than patients who have had Visudyne® alone. The exception may be patients who have small CNV who still seem to do better with the addition of Kenalog® after Visudyne®.


As before, neither I nor my colleagues are paid by any company to promote or perform any treatment. We try to decide what’s best for our patient. I’ll keep you posted.

Avastin and Medicare Compensation

Posted on blog: Because Avastin has yet to be approved for treatment of Macular Degeneration, Medicare will not pay for it.

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Posted by Carrie to Age Related Macular Degeneration on 11/30/2005


Reply:

Avastin® has been FDA approved for the treatment of metastatic colon cancer. Physicians have the right to use an approved drug for any disease however, if they believe it will benefit their patient. For instance we inject drugs such as Kenalog®, antibiotics, and tissue plasminogen activator into the eye to treat various retinal diseases. None of these drugs was originally approved to treat ocular disease. In fact, intravitreal antibiotics are now the standard of care for treating endophthalmitis, and a physician could be sued if he/she didn’t use them in this non-approved fashion.
Medicare has recognized this and generally pays for both the drug and the injection. This is the case in Iowa where Medicare has been reimbursing us for both the Avastin® and the injection. It’s smart for them to do that because Visudyne® and Macugen® are more expensive than Avastin®.

Plaquenil, AMD, and Inflammatory Arthritis

I don’t believe patients with AMD should take hydroxycholoroquine sulfate or Plaquenil®. This drug is often used to treat people with severe arthritis or lupus erythematosis. Hydroxychloroquine accumulates in the Retinal Pigment Epithelium (RPE) and rarely causes vision loss with atrophy of the RPE and photoreceptors. With more sensitive testing however, we have found that some people on this drug appear to have damage to their retinal function yet still have excellent acuity and no symptoms. This may mean that this drug damages the retina (albeit slightly) in more patients than we suspected because we didn’t have sensitive enough tests. AMD affects the same layers, namely the RPE and photoreceptors, as hydroxychloroquine does. It may be harmful to use a drug that can damage the same cells that are struggling anyway in AMD. This can be a difficult decision for a doctor because hydroxycholoroquine is a very effective drug in many arthritic patients. If you have both arthritis and AMD, hopefully your doctor can find an alternative medicine to Plaquenil®. As a side note, there is a recent publication(1), that reported a lower incidence of AMD in patients with rheumatoid arthritis. The authors speculated that the lower incidence of AMD in the arthritis patients may have been due to the anti-inflammatory medicines they had been taking for many years to control their disease. This makes sense, the authors say, since there is new evidence that inflammation plays a role in AMD. This is interesting but preliminary information that will have to be confirmed in other studies. This article doesn’t dissuade me however, from recommending that someone with AMD should not take Plaquenil. There are other medicines that are more anti-inflammatory than Plaquenil and also effective to treat rheumatoid arthritis. Reference: 1. McGeer PL, Sibley J. “Sparing of age-related macular degeneration in rheumatoid arthritis.” Neurobiol Aging. 2005 Aug-Sep;26(8):1199-203.