Round table: Are physicians ready to adopt intravitreal bevacizumab as routine treatment for ROP?

In this first excerpt from a round table conducted at the 2011 AAPOS meeting, members of the OSN Pediatrics/Strabismus Section address a study that favors intravitreal bevacizumab for treatment of zone 1 ROP.

Robert S. Gold

Scott E. Olitsky

Robert S. Gold, MD: Let’s talk about Avastin (bevacizumab, Genentech) for retinopathy of prematurity. This is an obvious hot topic after the Mintz-Hittner article came out in The New England Journal of Medicine. Where should we, as pediatric ophthalmologists, be going with this treatment?

Scott E. Olitsky, MD: There are two interesting things about this. One is the article itself; the other is the editorial that appeared in the same issue and generated a lot of discussion. The article certainly raises a lot of interesting points. It does not necessarily change what we think is the gold standard yet, but it certainly brings it into question, especially for zone 1 disease. I think we need to be forward-looking and embrace this, and not say “no” to it right now. There has been some discussion that we are not quite ready to really look at Avastin for the treatment of ROP, but I think both the editorial and the article suggest that we are. And that brings up a lot of exciting things, particularly in terms of developing countries that may not have access to laser or the expertise to use laser and where ROP is becoming more of a problem.

So I personally was excited to see the article and the editorial and what they discussed, and I think it opens up the doors for people to start talking to patients about using Avastin as treatment for selected cases and certainly for further research.

Roberto Warman, MD: I have an interesting perspective of what is happening. On the one hand, at the retina department of Bascom Palmer, we have used Avastin for very interesting, unusual things for 3 or 4 years, but we have held off from treating our standard ROP patients, waiting to get more knowledge, more information and multicenter studies. On the other hand, other groups in hospitals working in our area are using Avastin as the primary treatment routinely, averaging probably at least 20 or 30 cases per year, if not more. Of course, we see some of those cases later, and we have discovered interesting things. For example, the retina remains avascular. We finish examining at 47 weeks; that is our official standard. Here we have kids 60 weeks out, and they are still avascular. Now, I am having to do exams every 2 weeks on those kids. Are we going to be seeing every kid every 2 weeks forever? This is a problem. We need to define those things. That is why I do not think we are ready to say, “Yes, I’m happy.” I know it is the way to go. I know we are going to finish doing it. But we are not there. So I say, “Yes, let’s look at it. Let’s be positive, but put on the brakes a little. We’re not there.”

Roberto Warman

Kenneth P. Cheng

Kenneth P. Cheng, MD: I strongly echo what Dr. Warman just said. The history of ROP is such that we know that the use of a multicenter clinical trial is absolutely critical in this disease because no one center has enough patients to put together a study that can accurately give you a safety profile and fully work out the potential complications and downsides of treatment. So while the treatment clearly appears to be very promising, a multicenter clinical trial is the way to go to define how it should be used and when it should be used and, most importantly, to follow the patients, looking at the long-term complications of treatment and getting that information refined.

Infants affected by zone 1 disease right now are in a tough spot, and each physician has to have a long discussion with the family about potential risks and benefits of treatment to the best of his or her knowledge. Hopefully the multicenter clinical trial will be started very soon. There have been meetings and discussions about it already.

Erin D. Stahl, MD: Like Dr. Warman, we have inherited a few of these patients from other hospitals where they have been treated, and we have had to re-treat some of those kids because they have redeveloped active disease after being injected with Avastin. So when treating kids that you inherit, do not just assume that they have been treated and they are stabilized. We see the same thing as Dr. Warman; the children remain avascular and the question is, how long to follow up?

R.V. Paul Chan, MD, FACS: I agree with everything the others have said. I think the important issue is, where do we go from here? I have worked closely with the group in Mexico (Dr. Martinez-Castellanos and Dr. Quiroz-Mercado), and they have been using intravitreal bevacizumab for ROP over the past 5 years. Through our experience, it is clear that intravitreal bevacizumab is effective in promoting regression of treatment-requiring ROP. However, long-term safety has not yet been determined.

Erin D. Stahl

R.V. Paul Chan

The ROP population is a sensitive one. In a developing child, what effect will intravitreal anti-VEGF therapy have on overall development and will it affect the natural history of the developing eye? In addition, it is still unclear what the appropriate dosage of anti-VEGF therapy should be for the treatment of ROP. Therefore, with these questions still present and the fact that laser has historically been shown to work well for most cases, I would still recommend that we include laser in our treatment paradigm. However, I think that we should consider intravitreal bevacizumab for treatment-requiring ROP in zone 1 and in the most aggressive forms of the disease. And most importantly, we need to have a long, detailed discussion with the parents of these children who need treatment.

Dr. Gold: A final comment: In our hospital, in one of our neonatal intensive care units, the hospital has been very cautious about even allowing the treatment. Retina doctors use Avastin only in children who are too sick to have a procedure or to undergo any type of anesthetic procedure, and then still only in selected cases. We have had, in the selected cases, tremendous results from treatment and no adverse effect at this point, but obviously this is early. The hospitals, at least in our area, are being very cautious.

Dr. Cheng: I have a question. The patients you have seen who had been treated previously and whose retina remains avascular, is it really avascular from treatment point or presumably from treatment point, such that huge areas of the retina are avascular?

Dr. Warman: Yes. I have fluorescein documentation done by Nina Berrocal, MD, in a couple of cases that is very impressive. We are watching them. I am not saying that all of them need to be re-treated, but it is tricky. We do not know. I think that is the real answer.

Dr. Cheng: So clearly those patients in all likelihood have significant peripheral visual field defect if they were treated in zone 1 with the Avastin.

References:

• Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603-615.
• Reynolds JD. Bevacizumab for retinopathy of prematurity. N Engl J Med. 2011;364(7):677-678.

• R.V. Paul Chan, MD, FACS, can be reached at Weill Cornell Medical College, 1305 York Ave., 11th Floor, New York, NY, 10021; 646-962-2540; fax: 646-962-0609; email: rvpchan@gmail.com.
• Kenneth P. Cheng, MD, can be reached at 1000 Stonewood Drive, Suite 310, Wexford, PA 15090; 724-934-3333; email: kpc123@verizon.net.
• Robert S. Gold, MD, can be reached at 790 Concourse Parkway South, Suite 200, Maitland, FL 32751; 407-767-6411; fax: 407-767-8160; email: rsgeye@aol.com.
• Scott E. Olitsky, MD, can be reached at Children’s Mercy Hospital and Clinics, 2401 Gillham Road, Kansas City, MO 64108; 816-234-3000; fax; 816-346-1375; email: seolitsky@cmh.edu.
• Erin D. Stahl, MD, can be reached at Children’s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108; email: edstahl@cmh.edu.
• Roberto Warman, MD, can be reached at Miami Children’s Hospital, 3200 SW 60th Court, Suite 103, Miami, FL 33155-4072; 305-662-8390; fax: 305-661-7862; email: rwarman@eyes4kids.com.
• Disclosures: The participants in this round table have no financial interests in the products or companies mentioned in this article.