Macular Degeneration: Hot Topics in Treatment

Treatment Advances for AMD

Diana Do, MD: Hello. I am Dr. Diana Do, Associate Professor of Ophthalmology and Assistant Head of the Retina Fellowship Training Program at the Wilmer Eye Institute of the Johns Hopkins University School of Medicine in Baltimore. Welcome to Medscape Ophthalmology Insights. Joining me is my esteemed colleague, Dr. Julia Haller, Ophthalmologist-in-Chief of the Wills Eye Institute and Professor and Chair of the Department of Ophthalmology at Thomas Jefferson University in Philadelphia. Thank you for joining me, Julia.

Julia A. Haller, MD: It is a pleasure, Diana.

Dr. Do: We are here today at the American Academy of Ophthalmology Meeting in Orlando, Florida. We will be discussing the latest developments in retinal disease presented at this meeting, including treatment advances in age-related macular degeneration (AMD).

Ranibizumab and Bevacizumab Head to Head

One of the highlights of retinal subspecialty day was the presentation of the CATT results.^[1,2] This was a randomized clinical trial that evaluated the efficacy and safety of ranibizumab and bevacizumab for neovascular AMD. In addition, this study evaluated monthly dosing compared with as-needed dosing of these 2 vascular endothelial growth factor (VEGF) inhibitors. Julia, how do you interpret these results and how will they affect clinical care?

Dr. Haller: I get a little bit more out of these presentations on the CATT study every time I hear one. What we are taking away from it is that ranibizumab and bevacizumab are pretty much the same in terms of clinical outcomes, at least to 1 year, when given monthly, and probably when given as-needed, with careful monitoring. The only drug that dropped off a little bit in terms of clinical outcomes was the bevacizumab as needed, and it was very close.

There did seem to be a little bit of a signal that anatomically bevacizumab may not quite measure up to ranibizumab, in looking both at the fluorescein angiograms and at the optical coherence tomography results. Ranibizumab seemed to be a little bit more effective, but that didn't translate into a different clinical outcome at 1 year, so we are eagerly watching to see what happens at the 2-year time point as we go forward.

It is having an impact on our clinical care in terms of how we discuss treatments with our patients. I don't know that many of us are changing what we actually do a whole lot, but we will see.

Dr. Do: This was the first head-to-head comparison of ranibizumab and bevacizumab. Did this study elucidate any safety signals among these 2 agents?

Dr. Haller: The study wasn't powered to definitively answer that question. It just didn't have enough patients, and it is going to take so many to answer that question, but there was a finding in the bevacizumab-treated group of more hospitalizations. That put a little question in our minds, and it is a fact we will be considering as we move forward.

VEGF-Trap-Eye/Aflibercept Trials

Dr. Haller: One of the other hot topics is what we used to call VEGF-Trap-Eye, and now, aflibercept. The VIEW 1 and 2 results were presented.^[3] What was your take on that?

Dr. Do: VEGF-Trap-Eye (aflibercept) is a very unique molecule because it is a fusion protein that theoretically has a higher binding affinity to VEGF than our current monoclonal antibodies. The VIEW 1 and VIEW 2 studies combined were the largest clinical trials for neovascular AMD, and in these clinical trials multiple doses and dosing regimens of VEGF-Trap-Eye were investigated. At 1 year, all doses and dosing regimens of aflibercept were equivalent to monthly dosing of ranibizumab. Of greatest interest, however, aflibercept given every 8 weeks was equivalent to ranibizumab given monthly. This is going to provide clinicians with an agent that is potentially more durable, and this will help reduce the burden of treatments and follow-ups for patients with neovascular AMD.

Dr. Haller: That is really exciting.

Dr. Do: It is. Speaking of aflibercept, results of aflibercept for the treatment of macular edema in central retinal vein occlusion were also presented.^[4] How do you interpret those results?

Dr. Haller: Those results may suggest another place where aflibercept may be useful in clinical practice. That trial looked at monthly dosing with aflibercept vs sham injections for 6 months, and then for the next 6 months patients were able to cross over to aflibercept treatment if they had previously received the sham treatment, or they could continue on an as-needed basis if they were in the treatment group. In the treatment group, over the second 6-month period, patients required only a median of 3 treatments, so they did not require monthly injections and they still maintained a 55% rate of 3 line gainers at the 1 year endpoint. It is exciting to have a new anti-VEGF on the horizon and we are looking forward to using it clinically.

Surprising Results: HARBOR Study

Dr. Do: Definitely. Another big late-breaking development in retinal subspecialty was the presentation of the HARBOR study.^[5] The HARBOR study was a randomized clinical trial evaluating 2 mg of ranibizumab compared with the standard dose of 0.5 mg for neovascular AMD. How do you interpret those results and is 2 mg ranibizumab something that we can expect to see in the future?

Dr. Haller: Those results were a little surprising. The study showed no significant difference with the extra dosing of the ranibizumab. Many people have been doing double-dosing, and this is actually quadruple dosing, and yet it did not show a significant benefit. I think it is going to have some impact.

Ranibizumab Dosing: READ-3 Study

Dr. Haller: Speaking of doubling or quadrupling up on the dose of ranibizumab, you have a lot of experience with that drug in diabetic macular edema and of course the READ-3 study results have come out.^[6] Tell us what you think about that study.

Dr. Do: Yes, we investigated 2 mg of ranibizumab compared with the standard dose of 0.5 mg of ranibizumab in the READ-3 study. The READ-3 study was a randomized clinical trial involving 14 clinical sites in the United States and for the primary outcome at month 6, the higher dose of ranibizumab did not result in more beneficial visual acuity compared with the standard dose. At 1 year, the visual acuity outcomes were similar for the 2 doses, but there was a trend toward the reduced number of injections when using 2 mg of ranibizumab, so further investigation is warranted for the higher dose of ranibizumab.

Thank you for your insights Julia. We have covered many of the highlights from this year's AAO meeting. This is Diana Do with Dr. Julia Haller for Medscape Ophthalmology Insights. Thank you for joining us.