Update on the treatment of neovascular AMD

Hello again. Here are the numbers of the various AMD treatments done at the University of Iowa over the last six months. We also inject a few additional patients with Avastin and Macugen in an outreach clinic.

It’s obvious that that number of treatments using Avastin is increasing steadily. There are two reasons for that. The first is that we are using Avastin in most new patients with wet AMD because we believe it gives the best results. This belief is based on the positive results of the Lucentis trials, recent papers and reports stating excellent results using Avastin, and mainly our positive clinical experience. The second reason that the numbers are increasing is that we’re now using Avastin in patients who have only mild vision loss small areas of occult choroidal neovascularization. We often didn’t treat these patients in the past because: their natural history was not too bad; PDT was not particularly good for treating them; and we hated to commit them to 24 months of Macugen which didn’t seem to help that much anyway. Avastin though works well for treating these patients so the overall number of Avastin injections is increasingt.

We now know that Avastin works very quickly. The fluid beneath the retina starts to decrease within twelve hours after the injection. It is clear that Avastin stops the neovascularization from leaking. It’s also becoming clear however, that Avastin often does not get rid of the neovascularization or cause it to involute into a dry scar. Partsch and colleagues looked at CNV that were removed surgically after treatment with intravitreal Avastin. The neovascular vessels were still open, proliferating, and inflamed. In a small study, Korotkin and colleagues found that neovascularization recurred in some patients even after they had monthly injections of Lucentis for two years. Rosenfield and colleagues reported preliminary results of the PrONTO study. In this study forty patients received three injections of Lucentis at monthly intervals. After seven months of follow-up, fifty percent of the patients needed retreatment.

I usually give three injections of Avastin at 4-6 week intervals in patients with AMD. I then watch them (do not inject them) if the have no fluid after the third injection. I ask them to see me again in three months but warn them to return if their vision decreases. So far, about 40% of the patients have returned but I expect that percentage to increase with longer follow-up. There are a few patients who have looked great after only one or two injections of Avastin and I elected to simply follow them.

My best guess is that over fifty percent of patients will need additional injections periodically because the neovascularization will reactivate with leakage. Perhaps that’s not a bad tradeoff: a patient with AMD gets three injections initially and then has maybe a 60% chance of needing more injections four months down the line. Each time the neovascularization recurs though, there is always the risk of bleeding, scarring, and more visual loss.

We need a treatment that combines the rapid effect of Lucentis or Avastin with another drug that causes involution of the neovascularization. Visudyne combined with Avastin does this but some doctors believe that Visudyne can cause scarring with a drop of vision. It makes no sense to combine Macugen with Lucentis or Avastin since the both act on vascular endothelial growth factor (VEGF) and both need repeated injections.

An intriguing possibility would be combining Lucentis or Avastin with anecortave acetate (Retaane). Retaane is an anti-angiogenic steroid and works at multiple sites to block a variety of enzymes and growth factors involved in neovascularization. It is injected beneath the conjunctiva and Tenon’s capsule superiorly. Retaane lasts six months and has been shown to be as good as Visudyne or Macugen for the treatment of wet AMD. So a treatment involving the injection of either Lucentis or Avastin intraviteally combined with Retaane might achieve long-term involution of the neovascularization. Alcon manufactures Retaane and has been reluctant to permit the intravitreal injection of this drug. The combination of Lucentis or Avastin with Retaane (maybe even intravitreally) could be a real winner. Retaane has been approved in Australia and I’m hoping that some of our colleagues “Down Under” are trying this combination. If you have, please let us know how it worked.

We’ll talk more next week about the toxicity of Lucentis and Avastin.

References:
1. Partsch MC, et al. Immunohistopathologic evaluation of choroidal neovascular membranes following intravitreal bevacizumab (Avastin®) therapy. [ARVO 2006 poster 864/B785]. Available from http://tinyurl.com/gbqsp, program number 864.
2 Korotkin A, et al. An emerging problem: Recurrence of CNV in AMD is common after cessation of 24 month treatment with ranibizuman (Lucentis®). [ARVO 2006 poster 2961]. Available from http://tinyurl.com/gbqsp, program number 2961.
3. Visual acuity outcomes following a variable-dosing regimen for ranibizumab (Lucentis™) in neovascular AMD: The PrONTO Study. [ARVO 2006 poster 2958]. Available from http://tinyurl.com/gbqsp, program number 2958.