Anti-VEGF Therapy Presents New Challenges
Specialists discuss how they're using pegaptanib in light of the clinical trial protocol and a possible increase in patient visits.

Dr. Slakter: In December 2004, the FDA approved the anti-VEGF drug pegaptanib sodium (Macugen) for the treatment of neovascular (wet) age-related macular degeneration (AMD). What does that mean to you?

Dr. Johnson: I regard pegaptanib as one of my options for treating AMD, and I include it in my discussions with patients. I don't treat indolent lesions with pegaptanib, and I don't use it for lesions so far advanced that vision isn't likely to decline much further. Pegaptanib is a treatment option for most other CNV lesions.

I find that after discussing risks, benefits, mode and frequency of delivery, most patients who are eligible for verteporfin PDT choose it with or without intravitreal triamcinolone. I tend to follow the Centers for Medicare and Medicaid Services' (CMS) guidelines for determining PDT eligibility.

In my practice, most patients who receive pegaptanib are those we expect won't respond to PDT, usually patients with large, minimally classic or occult lesions.

Even in that subgroup, I question pegaptanib's efficacy because, to my knowledge, the data on that specific subgroup have not been released.

There is some indication that pegaptanib is most effective for small lesions. If we were to tease out the particular subgroup of large, minimally classic or occult lesions, pegaptanib may or may not be effective. Nevertheless, it's an approved treatment, and I usually recommend it to those patients with large lesions.

"I find that after discussing risks, benefits, mode and frequency of delivery, most patients who are eligible for verteporfin PDT choose it with or without intravitreal triamcinolone." — Mark W. Johnson, MD

ALL LESIONS ARE NOT THE SAME

Dr. Slakter: What about extrafoveal and juxtafoveal lesions?

Dr. Johnson: I use laser photocoagulation for extrafoveal lesions. For juxtafoveal lesions that are too close to the foveal center for laser therapy, I steer toward PDT with triamcinolone because I have the most experience with this therapy, and I consider it the most powerful treatment. I don't use pegaptanib for lesions threatening the foveal center because I'm not impressed with the immediacy of its action.

Dr. Reichel: I had a case that underscores the challenges of deciding on an appropriate treatment. I treated an extrafoveal lesion with the laser, and the patient did fine for a couple of months. After that, the lesion recurred and became juxtafoveal, so I performed PDT. The lesion dried up, but in 2 or 3 months was leaking again, and vision declined. I decided to treat with PDT

and triamcinolone, which failed. At this point, I didn't feel the PDT effect was strong enough to warrant another treatment, so I moved on to pegaptanib. When I used pegaptanib, the lesion dried up and the patient's vision improved four lines.

	"We should avoid switching from one treatment to another too quickly. We should wait to see how patients respond before trying a new course." — Richard F. Spaide, MD

Dr. Brucker: These situations will be challenging now that we have another treatment available. When do we switch from PDT to something else? Is there any one treatment now available that will be effective for all forms of AMD disease?

Dr. Fine: We have to remember we're dealing with a disease for which there is no cure. When we treat acute strep infection for example, we expect one course of penicillin to take care of it. But chronic diseases require ongoing intervention. We may never have a "magic bullet" for AMD.

Dr. Spaide: We can make another analogy: Warren Buffett got rich by buying stocks and sticking with them. Other people who traded a lot didn't do so well. Dr. Reichel's decision to switch to pegaptanib worked for one patient. He got better vision, and that's our goal, but usually, we should avoid switching from one treatment to another too quickly. We should wait to see how patients respond before trying a new course.

"We now have the option of using an anti-VEGF treatment, but we don't have clear guidelines." — Jason S. Slakter, MD

YOUR JUDGMENT VS. LABEL PROTOCOL

Dr. Williams: Much of this discussion revolves around the breadth of the pegaptanib label. If the label were restrictive, it would tell us exactly how we may or may not use the drug, and these decisions would be out of our control.

I'm glad to see a broad label because it lets us take a more active role in managing AMD. It's unrealistic to think we can design one trial to cover all patients, because AMD is so complex.

Dr. Slakter: We now have the option of using an anti-VEGF treatment, but we don't have clear guidelines.  How will we manage patients in light of this?

For example, if you want to treat a patient with pegaptanib, will you just bring him in every 6 weeks for an injection?  Will you assess something more than just a clinical exam?