Retina Society 2017 (Day 2): AMD Session


The second day of the conference kicked off with a symposium where leaders in field (Joan Miller, Jeffrey Luttrull, Johanna Seddon, Mark Nelson, Jeffrey Heier, and Lejla Vajzovic) discussed the molecular basis of AMD as well as imaging features, gene therapies and surgical advances. We were lucky to catch Dr. Jeffery S. Heier, from Ophthalmic Consultants of Boston, who earlier discussed a novel gene therapy that induces RPE cells to produce a molecule similar to ranibizumab in-vivo. The RGX-314 trial uses a proprietary platform where the viral vector adeno-associated virus-8 (AAV8) is delivered in the subretinal space. Inclusion criteria include a definitive response to an intravitreal injection of ranibizumab and 3 separate dose arms have been done thus far. Here are some of his thoughts on this groundbreaking new research: [caption id="attachment_799" align="alignnone" width="4032"]Day 2 Heier 2 Xuejin Chen, Jeffery Heier, Michael Cohen[/caption] Gene therapy has been looked at before, what sets this apart from the rest? Can you explain the potential benefit to subretinal over intravitreal delivery. It’s all about higher expression. REGENXBIO has this proprietary gene therapy platform that gives them higher expression and hopefully, longer expression, and maybe a lower immune response (probably related to lower exposure of AAV8). Up to 70% of people have exposure to AAV2 and have neutralizing antibodies; 30-50% have exposure to AAV8. When determining how to decide intravitreal vs subretinal – it’s the higher expression in the subretinal space (putting the gene therapy product right where you need it) and it’s protection from neutralizing antibodies. What’s the most challenging part of surgery? Careful preparation and planning is key - like all surgery. Understanding where you want to go so you can inject sub-retinal and allow for a large enough bleb that doesn’t go to the area of disease (the reason we don’t want it in the area of disease, is because of underlying scarring or retinal thinning that can predispose to formation of macular hole formation during injection). Standardizing the procedure is also essential; we use the injection device on the vitrectomy machine to achieve a steady state delivery of the product. If this is successful, what role do you see for this surgery in the future scope of our practice? Keep in mind, this is essentially phase I, so phase II and II would be to follow – and there is a great deal of work to do if this is successful. Assuming all of that works out, you could invasion patients who get treated regularly, treated between every 4 and 7 weeks, who have a very high treatment burden – those are patients who would really benefit. Initially, those on quarterly or PRN therapy would not initially consider using this for. Remember, you have AMD, DME, and RVO patients, all who are very anti-VEGF dependent who require frequent injections and monitoring, who would all potentially benefit from this. Dr Lejla Vajzovic, from Duke Eye Center, presented an interesting animal study showing a reduction in complications and greater success at proper medication delivery using intra-operative OCT. What are you thoughts with regards to the RGX-314 study? Would intra-operative OCT be beneficial to have as an aid to these cases? That was certainly a phenomenal presentation, and there are some sub-retinal approaches where that would be highly beneficial for. For this study, especially with experienced surgeons, it is relatively straightforward. Anytime you can more accurately determine where you are, anatomically, it is beneficial, but I don’t feel, in this study, it would add a tremendous amount. Although, we are still very early on. When do you expect phase I result to be completed? We are still in the earlier cohorts, so it will be a little while. What’s the most enjoyable part about having ASRS in your hometown? I love Boston as a city, and I very much enjoy being able to share the sites of the city with many of my close friends and colleagues. Xuejing Chen, MD Vitreoretinal Surgery Fellow Ophthalmic Consultants of Boston/Tufts University Michael Cohen, MD Vitreoretinal Surgery Fellow Ophthalmic Consultants of Boston/Tufts University