Based on personal clinical experience, Arshad Khanani, MD, explains his current approach to treating wet age-related macular degeneration with anti-VEGF therapy, with special considerations for appropriate dosage and timing of injections, and describes how he assesses patient response to therapy.
Arshad Khanani, MD: In terms of treatment paradigm, most of the retina specialists in the United States use what’s called “treat and extend” approach. No matter what agent you start with, whether it’s bevacizumab, ranibizumab, or aflibercept, most of us will start with 3 loading doses. The idea is that patients in clinical trials gain significant vision with the first 3 loading doses. After that, the visual acuity flattens out. That’s why we start with 3 monthly loading doses. When I’m seeing a patient, I tell them that we’re going to start with three monthly injections. If your disease is well controlled, then we’ll start stretching your treatment intervals and we’ll see. A lot of my patients are still stuck at every-6-weeks injection, while some can go 3 to 4 months between injections.
A good learning was the HARBOR trial with ranibizumab, where we saw that patients’ treatment needs are variable. We can’t put every patient in a box, and we have to individualize treatment based on patients’ needs because it’s a very variable disease. That’s why I start with 3 loading doses. If patient has no fluid, we start extending them by 2 weeks, a very classic “treat and extend” approach that the majority of us use in the United States. We come to the point where we know that if a patient goes longer than that, they’re going to have disease activity again.
All the decisions we are making in our clinic are based on OCT [optical coherence tomography]. The reason is that OCT is objective. It’s not subjective, like visual acuity, which can vary because of dry eye, patient effort, technician effort, or things like that. We really have good historical data from baseline, and every treatment I look at fluid on OCT. I look at their CST [central subfield thickness] on OCT. I look at other parameters and biomarkers, and I want to make sure that their disease is controlled. My goal is to dry the retina completely while safely extending the treatment. That’s what I do, and that’s what most physicians in the United States are doing. But the majority of our patients are stuck at 4 to 8 weeks. That’s why there is a big unmet need of extending that to 3 or 4 months or even 6 months, so we can decrease the treatment burden, because we know that the real-world outcomes are poor in terms of long-term data. Patients don’t get as many injections as they need because of so many factors: coming to clinic, going through the process, and paying for it.
When I’m starting treatment on a patient, I’m following them by OCT every month initially after the loading dose as I extend them. We need to see if the patient is a suboptimal responder to current anti-VEGF treatment. The good news is that most of the patients are responders. It’s actually a durability issue, and this was just published by Mass Eye and Ear, a very nice study that brought patients back a few weeks after the injection and evaluated the response and at their monthly visit to see how they look. If I have a patient who is receiving monthly injections and still has persistent fluid or worsening fluid, I also treat them and bring them back in a week or 2 to look at their OCT to see if there is a response. If there is a response, then I know this is not an issue in terms of non-responder or suboptimal responder, the issue is durability. I’m hoping that with newer agents that are more powerful or addressing alternative pathways, we can treat the patients who are very high need less than monthly or less than every 2 weeks—because there is nothing approved for less than monthly, and there are patients who need more. That’s why it’s exciting to have new things coming down the pipeline, so we can control the disease on these patients who are very high need and need more durability compared with what they’re getting with the current agents.
Transcript Edited for Clarity