February is Age-Related Macular Degeneration Awareness Month. Ophthalmology 360 Editorial Advisory Board member Rohit Ross Lakhanpal, MD, of the Retina Care Center in Baltimore, talks about the treatments advancements that have been made for AMD and what his top treatment choice is for this patient population.
Question:
February is Age-Related Macular Degeneration Awareness Month. How can ophthalmologists contribute to the education and conversation around AMD and general eye health?
Rohit Ross Lakhanpal, MD:
I think general ophthalmologists have a really great responsibility because they’re seeing all these patients initially for the most part. The fact that this is the month for leading cause of blindness in the United States, I think we are always aware of it. We see so many patients with it every day. The general ophthalmologist is sort of the gatekeeper for lack of a better term. Whenever they see a patient with any form of macular degeneration, one of the important issues is to grade it properly. I think every general ophthalmologist should be fairly well-versed in terms of the different stages of dry AMD and then when it develops into wet. The other great thing is we have great technology now that most general ophthalmologists have with OCTs. I don’t know a single general ophthalmologist doesn’t have an OCT, and the OCT can help so much in terms of diagnosing.
I think all of that together, the education of the GOs, which is what we do also, we do continuing education events with general ophthalmologists every year, a few times a year, going over all of the new things that are happening. I think we can educate, they can also do their own research and kind of keep up their education of that. Then diagnosing and sending the patient appropriately is very, very important. I think, as I said, they’re the gatekeeper, so we always get them in a timely fashion.
Question:
Can you talk about the importance of early detection of AMD? How do you recommend other eye care providers educate patients and the wider community on the risks and symptoms of AMD?
Rohit Ross Lakhanpal, MD:
Sure. I think any form of macular degeneration, I say the patient should be made aware of. Even if you see drusen, I think small drusen clumped, you go from early stage, which is generally more scattered hard drusen to more soft confluent and then what becomes intermediate drusen, which is the next step between dry and wet. I think recognizing these changes is very, very important for everyone, whether you’re a general ophthalmologist, optometrist, or obviously a retina specialist. The early dry macular stages probably just need to be seen every six months by the general ophthalmologist. I’m happy to see those, but they can follow those.
I think once it gets to the stage of more intermediate, whether it’s clumping of deposits where there’s obviously confluent deposits, I think for most general ophthalmologists that I know, and optometrists, they would prefer to refer the patient at that point for a retinal evaluation by retina specialist only because you’re really right on the cusp of wet AMD. Sometimes these things can start and can start slowly and sometimes they can happen suddenly. I think educating the patient on the stage of what they have and then referring, probably I think intermediate stage is probably the appropriate time. All that stuff is really important.
Then the OCT, again, I brought it up before, but it’s really important in terms of the distinction between dry and wet macular. But the stages I think are very important to explain to the patient so they know their risk. Then if they should take eye vitamins, et cetera, how often they should be seen.
Question:
Can you talk about the treatment options for AMD? How do you determine the best course of treatment for each patient? What are the important factors you consider when determining a care plan?
Rohit Ross Lakhanpal, MD:
Yeah, so it’s interesting because 2024 was the 20th anniversary of the first real anti-VEGF treatment for wet AMD. We’ve only been doing injections literally for about 20 years, 21 years. Before that, we were doing laser treatment or photodynamic therapy treatment for wet AMD. We have come a long way and the progression of drugs has really been quite amazing in terms of the innovation. I think that’s also been really great in terms of wet AMD and that’s why honestly the prognosis is much better today than it was 20 years ago.
We started off with Macugen, which was a specific isomer targeting 160 VEGF, 165. Then Avastin, which is still very much present today, was determined to be effective, along with Lucentis, which was mainly a VEGF blocker, and then aflibercept or Eylea, which was 2011. That was kind of a big breakthrough time. We had 2 drugs that were very effective and the trials were the main reasons that showed that. Both the Genentech ranibizumab trials as well as the aflibercept trials from Regeneron both showed really, really great improvement of vision for the first time in patients versus just stabilization.
Those were two landmark drugs and I think they have done very well over the past 20 years. But the more recent drugs, maybe even better, the Vabysmo, which is a combination of a VEGF blocker and an Ang-2 blocker, has been shown to be very effective. Also we can increase the timing between treatments with these drugs now. Vabysmo and then Eylea HD, which is aflibercept, but it’s 8 mg versus 2 mg. That also has been shown to be very effective, but also you can extend patients longer. The more recent two drugs, we’re seeing longer extensions between visits, which is fantastic.
There’s another treatment pathway, another drug delivery system which has been approved recently called Susvimo, which is an implant, which is also a Genentech implant that can be filled with ranibizumab and it can be implanted and you need just a refill about every 6 months. It’s been shown to be very effective that way too. Also there’s gene therapy down the road.
What does all this mean? Well, it means that the wet AMD landscape is becoming more complicated. There’s more drugs, but that’s also a good thing because we have more choices. How I generally start is basically a patient comes in with wet AMD, we have to look at the lesion size, we have to look at whether there’s blood and or fluid involved, the size of the lesion matters, how long it’s been, there matters. At this point, we’re also tied into other things, which is step therapy.
How do we determine what a patient will receive treatment wise? Unfortunately, some of that is predetermined by the patient’s insurance. If we take the insurance out of the way, I think the ranibizumab and aflibercept drugs are great drugs to start with. If the insurance allows it, I would probably go to either the Vabysmo or the Eylea HD if it would be possible, because we know that those are extremely effective and they have a longer duration of action. Therefore, your treatment interval can be less over time. It’s better for the patient to receive fewer injections and still do well. It’s better for the physician.
I think the 2 newer drugs, if I had to pick right now, if insurance was not an issue, if payment was not an issue, I’d pick Vabysmo or Eylea HD. If not, if you have to do something with a stepwise approach, and sometimes I think ranibizumab or aflibercept 2 mg are great, if you have to start with something else like a biosimilar, so be it. But I think for me, the 2 newer ones are superior and both for the patient and for the physician, and of course, treatment is individualized. You also have to look at all risk benefits for the patient. I only do one, if it’s bilateral we only do 1 eye at a time for the first injection because we want to see how the patient does. We have to be aware of any potential side effects that may happen, frankly, for any of these drugs.
Question:
What are some recent advancements or things on the horizon that you think are important to highlight regarding AMD?
Rohit Ross Lakhanpal, MD:
If we’re talking about strictly wet AMD, then gene therapy is something which is being at in the clinical trial stage at this point. It’s basically, the best way I can describe it, is it’s something where the drug will be produced, the anti-VEGF will be produced basically at certain intervals, and it will continue to be produced. There are some benefits to that, of course, because you get more sort of continuous treatment. There are also some potential things we have to think about, which is that necessarily a good thing long-term? I don’t know. We are treating patients with wet AMD at certain intervals, and we’ve been doing that for many, many years. I have certain patients I’ve been treating for at least 15 years. The question is, does wet AMD treatment, does anti-VEGF treatment long-term; does it have significant side effects to the patient’s retina and maybe elsewhere? The question also becomes about gene therapy is you’re able to treat continuously in a way, but also what’s the negative of that? I think that sort of remains to be seen.
If we’re talking about the other half of AMD, which we haven’t mentioned, but we can a little bit if you want, is geographic atrophy treatment, the dry AMD geographic atrophic changes. Which we do have 2 FDA-approved drugs now, which is amazing in a way because so many drugs have failed this space over the past few years. When I see patients with geographic atrophy, the GA, the geographic atrophy, finding the measuring that and really talking to the patient about the potential treatment options is very important because it used to be a very unmet need. Now we actually do have treatments which can slow the progression, but unfortunately cannot arrest it. The question in that space is, do we have treatment options that can arrest the GA where it is, and also maybe potentially protect some of the vulnerable RP cells in that sort of junctional zone, which are the most high-risk ones to lose in the future.
The way you see those is, on the FAF, you see the areas that are hyperautofluorescent, they are the ones that are probably the higher risk areas, and they’re usually at the junction of healthy retina and unfortunately atrophy. I think the space is actually very exciting. There are some potential treatment options down the road for that. I think for the wet AMD space, we have amazing treatments. Our goal is to eventually just keep extending or hopefully the Susvimo is one of the answers or gene therapy is the answer. We don’t have to see these patients as frequently at all. Again, time will tell with the side effects and the various potential negative effects. I think that’s something we all have to look at.
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