Andrew Lee, MD, and Andrew Carey, MD, sit down on another episode of the NeuroOp Guru to discuss IAT for CRAO within 16 hours.
Editor's note - This transcript has been edited for clarity.
Hello and welcome to another edition of the NeuroOp Guru. I'm here with my good friend Drew Carey from the Wilmer Eye Institute, Johns Hopkins Hospital Hi Drew.
And today, we're going to be talking about intra-arterial thrombolysis for central retinal artery occlusion within 16 hours.
So Drew, maybe you could tell the audience a little bit about why this was even necessary. Don't we know that clot busting works?
Well, we have randomized control trials for clot busting in diseases like acute myocardial infarction, and brain infarcts. But we don't have any randomized control trials for central retinal artery occlusions, or branch retinal artery occlusions. These are rare conditions, the public's not quite as aware that these might be strokes. And it's been really hard to try and recruit patients for studies.
So we don't have any level 1 evidence, which is one of the reasons these authors wanted to look into using this for our central retinal artery occlusion which is an eye stroke. And since 2013, the American Heart Association and the American Stroke Association put out a joint statement saying that these are considered CNS strokes, they are equivalent to brain strokes and need to be evaluated in such a manner.
And what about this timing? 16 hours or less? Doesn't that seem long to you? Or that's what they had to do?
You know, it does seem long. If you asked me what I thought the recovery time for vision in central retinal artery occlusion would be, I would have told you it's probably less than 16 hours. But we certainly know from brain studies that things like intravenous TPA for clot busting is certainly not done at 16 hours. That, you know is FDA approved label was originally 3 hours and extended to 4.5 hours in some patients, 6 hours in some patients.
We do know that intra-arterial thrombolysis can be done at longer intervals in brain strokes. and certainly when they use it for things like acute myocardial infarctions, heart attacks, they can do it later. Because you know it's localized, so lower risk of things like a brain bleed as a major complication.
And so this was intra-arterial thrombolysis versus conservative therapy. What does conservative therapy to you mean?
You know, there's a lot of things doctors have tried over time, ocular massage, IOP lowering eyedrops. Sometimes people will do things like anterior chamber paracentesis to try to abruptly lower the IOP and create a pressure gradient from behind the clot to try and break it loose. And so those are kind of the traditional, conservative therapies.
And we call them conservative because they don't really do much for the patient. But they're probably low risk for systemic complications. Although unskilled practitioners putting a needle into somebody's anterior chamber, they might cause some harm to the eye.
And is that what you do right now, at Hopkins, do you do all these IOP things – stick the needle in the eye? Or it's quite variable and dependent on the practitioner? Or is there a protocol?
Yeah there is not a standard of care out there for these types of measures, because there's really low grade evidence that they're of benefit. You know, if I had somebody in the eye clinic who had sudden painless loss of vision, while they were here, and we could look and see inside the eye and see that they had what looked like, you know, some type of embolus in the central retinal artery.
I would probably try an anterior chamber, paracentesis on the way that I was wheeling them down to an emergency room. The rest of the things, or you know, if it's if it's delayed presentation like it is often, I think risk benefit profile doesn't really favor anything like anterior chamber paracentesis.
So can you just walk us through the results here comparing the intra-arterial, IAT thrombolysis against the conservative group in the table here?
Yeah, absolutely. So of note, this was a retrospective study from prospective registered cohorts and nobody was randomized. They just enrolled patients and see what happened to them. And they had 121 patients that they screened. Twenty patients were excluded for having a branch retinal artery occlusion or some kind of an extra-genic procedure, like maybe they had a facial filler done. And they had 65 patients that went on to be treated in the in the intra-arterial thrombolysis group and 36 in the conservative group. And then they had 42 of those patients in the intra-arterial group were excluded.
So final numbers, 23 patients in the thrombolysis group and 30 in the conservative management group. They all had really bad vision at baseline on the order of a logMAR, visual acuity of 2.7 to 2.3. And only the group that got intra-arterial thrombolysis saw any improvement in vision at 1 week. They improved from a mean of 2.7 to 2.3 log units. And at final vision, they improved to 2.3 log units. And those that were deemed to have clinically significant vision improvement at 1 week, which was 3 lines of Snellen, or .3 logMAR. They saw 48% in the IAT group and and 27% in the conservative group.
So that was a big difference. Although the final vision, you know, still not great, 2.3 logMAR. With the interquartile range of 1.9 to 2.7, you're still seeing like, that's 20 over 6000 or something. So It's not like they were coming back to 20/20. And their mean time to treatment was was 9 hours. So perhaps if you could get patients in earlier, they might have better visual outcomes.
What do you think about these photos and these angiograms here pre and post IAT? Can you see a difference? Or it looks the same or what...
Yeah so I think the perfusion definitely improved after they were treated, you know, the central retinal artery perfused, which is great. But that doesn't mean that the vision necessarily recovered that much. Because you infarcted your retina, and after 9 hours, or 16 hours, your retina is still infarcted. And you know, I think the biggest difference between the retina and a brain infarct is we know in a brain infarcture, you're probably not recovering the infarcted part of your brain at 3 hours, but you're recovering the penumbra right? It's the area at risk. And unfortunately, the area at risk, the penumbra and the retina is not the fovea.
That's, you know, it's not our central vision that we really care about. It's more of the peripheral vision. and so what they don't have in this study would be something like Goldmann visual field to see how big is their scotoma? Or how did their ambulatory ability improve? You know, are they able to walk around a room without tripping over stuff? Can they find a door in a room to walk out of? Because they're probably not going to be having reading level of vision with that eye again?
So what should be the take home message for our audience in terms of IAT? And how has it changed your practice, if at all?
Yeah, I think right now that you know, the biggest limiting factor to central retinal artery occlusions is getting the patients evaluated in a timely manner. I think it's nice to know that this is safe. The only complication they had was one patient had a retinal hemorrhage.
There were no patients with dissections or intracranial hemorrhages. And so you know, if there was like a monocular patient who had a central retinal artery occlusion in their only eye, or was it was my only eye, yeah, I'd want it. You know, if they have normal vision in the other eye, you know, we could talk to them. It's reasonable to try, it's safe. They may have some improvement in their central vision, but I think counseling wise, you know, they're not going to be reading with that eye.
They're not going to be driving with that eye. But I think it gives us good information for going forward with, you know, larger randomized controlled trials trying to get patients in earlier. And I think that's the big take home message is, if we want to treat them we got to get them in earlier.
Yeah, I think that that's, that's right. and we always say a stroke in the eye is still a stroke, and stroke can get stroke treatment at a stroke center by a stroke doctor, but we got to get them to the stroke center, within the treatment arm window. So well, that's fantastic, Drew and thank you again. That concludes yet another edition of the NeuroOp Guru and we look forward to seeing you next time.