Additional Diagnostic Tools for Anti-VEGF Agents and Using Brolucizumab

Karl Csaky, MD, PhD: Lloyd, let’s talk about a bit about the heterogeneity. We’ve talked about how, as Carl said, fortunately, a significant number of patients do well. But we also have a category of patients for whom the response can be variable. Any additional diagnostic tools that you think about, let’s say at the beginning? Patients come in, you’re in a busy clinic, you’re trying to get through the clinic and make sure they get good treatments. Is there anything that you change, in terms of your diagnostic approach in some of these more problematic patients, in terms of rethinking the diagnosis or when you take a pause? What does that do in terms of your thinking, and what are the additional diagnostic tools you might want to use?

Lloyd Clark, MD: Nancy and Carl hit the nail on the head. Occasionally you get it wrong, and it’s important to understand that, recognize it, and be vigilant about the fact that you’ve got the correct diagnosis. Sometimes patients who don’t respond well are nonresponders for a couple of simple reasons. The first is you’ve picked the wrong agent. There are patients who respond better to certain agents than others. The first thing I do when I see a patient who’s not responding well is I’m not slow to switch agents. We have 3 very good agents—really 4—and some patients respond better to others.

The second is, like Carl, I’m aggressive with treat and extend. Sometimes I’ve got the interval wrong, either initially or in chronic therapy. When we get busy in meeting season, and our clinics get strung out and these patients go an extra week, if you have them on a specific treat-and-extend interval for years and you go an extra week, they feel it and you feel it. I think through it: have I made the correct initial treatment decisions? There are indications for third-line therapy, such as photodynamic therapy, particularly ICG [indocyanine green] in very isolated circumstances. There are clinicians around the United States and around the world who utilize more traditional treatment options than anti-VEGF therapy, meaning those that we’ve used much longer. I don’t have much experience with that.

The reality is that the number of patients who don’t have a significant clinical response is in the single digits. I’ve tended to stick consistently with anti-VEGF therapy, working my way through the various agents to find the best 1 for the patient and then maximize the treatment intervals.

Karl Csaky, MD, PhD: Let’s talk about brolucizumab. Are there indications for using in these patients who have challenging subretinal or intraretinal fluid dynamics? Are there conditions under which you would consider using an agent like brolucizumab as another agent that’s approved but does carry additional concerns and issues?

Carl Regillo, MD, FACS: When you look at the clinical trial data, we see an incremental improvement in terms of drying. That’s real. We’ve seen it in enough patients in multiple clinical trials to suggest that it’s a very effective drying agent. The improvement is incremental compared with what we have available as FDA-approved agents. When you layer on the small but real risk of a devastating complication, it’s a drug I haven’t incorporated into my clinical practice because I don’t think the juice is worth the squeeze, for lack of a better term. It’s a better drug on average. It’s the best drying agent, but I’m not sure that equates into enough of a clinical benefit to expose the patient early in the course of therapy to a devastating complication. I would defer to some of my colleagues on the panel who have more experience. I haven’t had a lot of experience using it.

Karl Csaky, MD, PhD: Any other thoughts? Nancy, Jennifer, Carl? Anything that you feel, it’s in our armamentarium? Just a quick thought about where you do use it or if you use it.

Carl Regillo, MD, FACS: Lloyd was right. He certainly implied it’s last resort or fourth-line drug. We think about using it to get that added durability and drying, and the phase 3 registration study with brolucizumab did indicate faster, better drying compared with aflibercept. I’ve used it and still use it in a few patients, but it’s a very limited use in our wet AMD [age-related macular degeneration] population. The good news is that most patients respond adequately to the 3 drugs we’ve been using, so I don’t feel the need [to use a fourth] to get another week or so of durability, which it probably does give us compared with the other agents. It’s probably not worth the risk, and we should say what that risk is.

The risk of just any intraocular inflammation with the drugs we’ve been using, based on the large-scale clinical trials, is in the range of 1%, 1.5%, maybe up to 2%. Most cases are not severe, and we’ve never seen a direct retinal complication linked to the drugs we’ve been using—vaso-occlusive disease, vasculitis—things that led to some severe reversal or vision loss, that were detected in the brolucizumab studies and after utilization in practice. The rates of those are low: 1% to 2% have a vision problem and a severe adverse effect from brolucizumab, which is just big enough that we don’t use this drug frequently in practice. I’m speaking for most retina specialists in the United States.

This transcript has been edited for clarity.