Another Big Year in Retina

The Latest Developments in Retinal Disease

Julia A. Haller, MD: Hello. I'm 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. Welcome to Medscape Ophthalmology Insights, coming from the American Academy of Ophthalmology (AAO) meeting in Chicago. This is part of a series of commentaries produced in cooperation between Medscape and Wills Eye Institute. Joining me today are my colleagues, Dr. Carl Regillo and Dr. Allen Ho of Wills Eye Institute. Dr. Regillo is Chief of the Retina Service and Dr. Ho is Director of Research.

We will be discussing the latest developments in retinal disease presented at the meeting -- in particular, treatment advances in age-related macular degeneration (AMD) and retinal vein occlusions. Let's share with our viewers today some of the hot topics coming out of today's meeting. Gentlemen, what is the take-away? Allen, why don't we start with you?

Making Strides in AMD

Allen C. Ho, MD: It is a very exciting time for the treatment of wet macular degeneration. We are at the point where we have made great strides with anti-vascular endothelial growth factor (VEGF) therapy, but with the new Fovista (Ophthotech Corp.; Princeton, New Jersey) anti-platelet-derived growth factor (PDGF) data, we are ready to launch to another level for our patients. That is the latest and most exciting information. Other information is coming out on long-acting delivery devices that may reduce treatment burden for our patients, and we are just starting to see some hints of potential safety and efficacy on new treatments for geographic atrophy, for which we have never before had treatments.

Dr. Haller: Very exciting. Carl, do you have any comments about this?

Carl D. Regillo, MD: It's another big year in retina. We continue to make great strides in AMD, both wet and dry, and we are starting to see some progress in dry AMD from the exciting work with stem cells and other potential good treatments. The bar for wet AMD might be rising. We have a therapy that looks like it will produce better vision results, and that's really exciting.

Dr. Haller: Where do you see the combination therapy fitting in with your AMD treatment? Do you think that you will be adding it after an anti-VEGF agent, or does it remain to be seen as the trials spool out?

Dr. Regillo: For years we have been saying that ultimately the best optimal management for wet AMD is going to be combination therapy to attack this disease from different angles, and that's exactly what this does. The drugs have different mechanisms of action, and we will be using anti-VEGF and anti-PDGF together, upfront, for new wet AMD and will be using this combination regularly to get the very best anatomical and functional results. What to do beyond the first 6 months is unknown.

The Outlook for Vein Occlusions

Dr. Haller: Moving on to vein occlusions, aflibercept was approved recently. Has that changed your management at all, Allen, and have you heard anything here at AAO that has changed your outlook on the treatment of vein occlusions?

Dr. Ho: No. Laser still plays a role in vein occlusions, but first-line therapy, as in diabetic macular edema, has moved towards injection therapy. It's a testament to the science that we have behind the mechanisms of vision loss for macular edema in retinal vein occlusion, AMD, and diabetic macular edema. Anti-VEGF drugs for vein occlusion that have now been approved include aflibercept and ranibizumab, in addition to bevacizumab.

Dr. Haller: Wide-field viewing is coming up in a lot of talks. Are you looking more at ischemia in the periphery when you are dealing with your vein occlusions, Carl?

Dr. Regillo: Absolutely. Encouraging anecdotes in small series suggest that doing laser with a nonperfused retina in the setting of branch or even more central retinal vein occlusion might allow us to get better and more permanent control of the edema, so that maybe we can back off or use less total anti-VEGF treatment over time, and it looks promising. Many of us have dabbled in it and have had some good results. However, that has to be put to the test in large-scale, prospective clinical studies.

Dr. Ho: Not everyone has access to wide-field angiography, so treating physicians are not necessarily behind if they don't have access to that technology. For patients who are recalcitrant, I look to that as an explanation for why patients may not be responding. You might need to increase the frequency of anti-VEGF injections. You might want to consider intravitreal steroids, triamcinolone injections, or dexamethasone intravitreal implant as a way to improve therapy for nonresponsive branch retinal vein occlusion.

New Options for Vitreoretinal Disease

Dr. Haller: Three weeks ago, ocriplasmin was approved by the US Food and Drug Administration (FDA). Do you see yourself looking more at that vitreoretinal interface now that there is a pharmacologic option for treating it?

Dr. Ho: It's intriguing because it was a broad-based approval for symptomatic vitreal macular adhesions, which applies not only to classic disease that we think of in that context (eg, macular holes or vitreofoveal traction) but also to other conditions, such as diabetic macular edema and AMD. If patients aren't responding to wet AMD treatments, maybe it's a barrier that is created by the vitreomacular adhesion that could be released with this new drug. It is very exciting. We expect to have that available to us in January 2013.

Dr. Haller: Are you going to start using it? Where do you see it fitting in to your clinical practice?

Dr. Regillo: This is a whole new class, and it's an exciting development. The other big development this year is to have ocriplasmin approved by the FDA a few weeks ago and in our hands within a few months. It's going to be used in a widespread fashion. Any patient who comes to us with a symptomatic vitreoretinal adhesion with traction in the fovea and/or macular hole will be ideally suited to try this office-based intervention of injecting the drug, with a success rate that is probably in the range of 30%-40%. It could be even higher depending on the characteristics, and it's a nice intermediary step -- perhaps the last step you need to take, and you don't need to do the surgery. Any treatment that keeps patients out of the OR when they have a disease that otherwise has to be managed surgically is a step in the right direction and a big development.

Cell-Based Therapies

Dr. Haller: Is anything else on the horizon that you expect to come out of this meeting? For clinical trials, Wills Eye Institute is one of the busiest places in the world. Are you planning to test any of these drugs or treatments?

Dr. Ho: We presented results^[1] for the population of patients in advanced AMD who don't have any proven treatment. Geographic atrophy is a very different kind of problem. We don't have a specific pharmacologic target, and our preliminary results from a cell-based therapy study show that there may be some signal of improving vision for the patients. It is very preliminary, but the fact that we are doing it and seeing some safety and efficacy signals is very exciting.

Dr. Haller: You have been involved in one of the other cell-based therapies for geographic atrophy and Stargardt macular degeneration. Do you have any thoughts about that approach?

Dr. Regillo: It is another promising approach, very complementary and different in the sense that we hope that stem cells can repopulate dead or missing retinal pigment epithelial cells.

Dr. Haller: When injected under the retina?

Dr. Regillo: Right; injecting a stem-cell-based line of mature retinal pigment epithelial cells -- in essence, a retinal pigment epithelial transplant to repopulate the cells under the retina in hopes of either slowing vision loss or even improving vision. That is another promising approach and we are very excited about that. In addition, there are other ways to approach dry AMD: inhibiting complement, inhibiting the visual cycle in such a way that might reduce the load of toxic metabolites. Some products are coming to testing right now.

Promising Imaging Modalities

Dr. Haller: Walking around the exhibit floor, was there anything exciting, any new lasers or other technologies, or did you find an instrument that you particularly liked that you want to share with the audience?

Dr. Ho: Retina is very fortunate to be enriched with technology that winds up achieving better outcomes for patients. We are trying to understand what is accounting for treatment response, and the imaging modalities that are available are just exploding. In fact, there are some imaging modalities for which we are trying to find an application and working backwards (adaptive optics), such as multimodal imaging and next-generation optical coherence tomography. These are all very exciting and promising and bode well for our understanding of some of the responses that we are seeing with some of these investigational therapies.

Dr. Haller: Were there any new lasers, such as targeted laser or automatic laser, that you don't have to do too much with but set it up and it works for you?

Dr. Regillo: On the surgical front, many refinements are occurring. There has been a tremendous evolution towards good, efficient ways to approach our surgical problems, and right now we are seeing further refinements, not anything that is brand-new in terms of technology.

Dr. Haller: Imaging is probably the hot area where the envelope is being pushed the most.

Dr. Regillo: Absolutely.

Dr. Haller: Thank you, gentlemen. It's a pleasure to be here with you this morning. Thanks for joining us. This is Dr. Julia Haller with Dr. Carl Regillo and Dr. Allen Ho for Medscape Ophthalmology and Wills Eye Institute.