Chapters Transcript Ischemic Eye Conditions/CRAO Course: The Cutting Edges in Stroke OK. Good afternoon. I'm gonna be talking about acute retinal ischemia, big topic, we're gonna try and highlight some key points. I don't have any disclosures. I do have a warning though, for those of you like myself who've spent hours with the ophthalmoscope trying to find the optic disc, I'm sorry, we are gonna be talking about this instrument today, but here's a picture of puppies and kitties getting their eyes checked to hopefully ease some of our fears. All right, I'm gonna be talking about the anatomy, the ideal window for treatment, what treatments are available, and then where do we go from here? Acute retinal ischemia refers to the blockage of blood flow to the inner layers of the retina. It is therefore the retinal equivalent of cerebral stroke and presents with sudden painless loss of vision in one eye. Here's a diagram showing the relevant anatomy with the optic nerve, the eye, and blood supply to the orbit. This is the typical course of an emboli traveling through the internal carotid ophthalmic and then landing in the central retinal artery. Importantly, blood supply to the retina is dual. The inner layers are supplied by the central retinal artery, but the outer layers in the choroid have a different blood supply the ciliary arteries. That's the theory behind why something like hyperbaric oxygen might work. The inner layers become ischemic. You can get hyperoxygenate the outer layers, and oxygen can passively diffuse into those inner layers. It also becomes relevant when we look at fundoscopy in just a second. Similar to cerebral ischemia, retinal ischemia can be transient or permanent. If it's transient, we call it Ayrosis fugax, permanent central retinal artery occlusion or CRAO. Branch retinal artery occlusion is one of the branches of the central retinal artery, BRAO. Now there can be non-arteritic or arteritic type. Non-arteritic is what we just showed that embolist traveling, lodging in the central retinal artery. The arteritic type is far less common. That's an arteritis or inflammation of the CRA, and that's commonly due to giant cellareritis, so important to ask about things like jaw claudication, scalp tenderness, etc. The natural history of BRAO is actually pretty good. CRAO not so much. In fact, 4 out of 5 patients have a final visual acuity of 20/200 or less, and that's the legal definition of blindness. Unlike cerebral ischemia, where patients recover days, weeks, months later, retinal ischemia patients don't tend to don't tend to recover after 7 days. In fact, less than 10% of patients do. These are the two most common locations of embolus and CRAO right here, the central retinal artery, where it pierces the optic nerves gal sheath. There's an area of narrowing. And then also at the laminarobosa, that circle of zen, that mesh-like structure at the optic nerve head, there's also narrowing. Note that both of these are retro bull bars, so you can't appreciate them using a uh ophthalmoscope. The emble is characteristics. This is relevant when thinking about treatment options like thrombolytics. There used to be a question, well, if the clot is coming from the carotid, it's mostly calcified or mostly cholesterol, then can you treat it with thrombolytics? We now know that for all major causes of retinal ischemia, there's at least some degree of fiber in in that clot. This is a a cholesterol plaque in one of the branch arteries. Again, the central retinal artery can't appreciate on fundoscopy. Oh no, OK, that's not what it looked like on my computer, but basically this is a cone beam dyna CT scan showing the relevant anatomy by our amazing neuro IR faculty. Uh, this main artery here is the ophthalmic artery, and you can maybe appreciate a nice sharp bend that's called the bayonet bend in a lot of old anatomic textbooks. The center. retinal artery is that red squiggly line supposed to be superimposed on this image that's the central retinal artery. You can actually appreciate that bend on lateral view angiogram. So here's the internal carotid ophthalmic artery with its nice bend. The central retinal artery comes out around that location. Can't be certain that is the central retinal artery, but that's around where you would expect to find it. Some findings on fundoscopy. Importantly, in acute early CRAO it can be totally normal, but over time you start to see some attenuation of the arteries that arrow is pointing to attenuated arteries that stagnant blood flow. You also start to see diffuse retinal whitening that's because of edema and ischemia of those inner retinal layers. Over time you might ultimately see something called a cherry red spot. This is the fovea of the retina that's the area of maximum visual acuity. It's also the thinnest part of the retina. And so in ischemia, when you lose that inner layer, what you're seeing is the well perfused outer layers at the thinnest part of the retina, that's the cherry red spot. OCT optical coherence tomography, you can see on the left that's a patient with acute retinal ischemia. Um, this nicely shows you the layers of the retina, and on the left you can see how there's edema and thickening of the retina. You might also appreciate that it's a little bit brighter that hyperreflectivity is another key feature. Some patients have a celio retinal artery, so in addition to this uh central retinal artery that supplies most of the fundus or most of the retina, the celiial retinal might uh supply a part of it. This patient actually got lucky. The fovea is supplied by the ciliial retinal artery, so they might have preserved visual acuity despite an occlusion. So on physical exam, it's important to check both visual acuity, essentially the function of the fovea but note in patients with a celial retinal artery it can be normal. So important to also check visual fields for each eye individually. Visual fields give us a better representation of the retina as a whole. So we talked about uh anatomy. Now I'm gonna move forward. What is the ideal window for treatment? Who should we treat and when? So similar mantra, right? Time is brain is the mantra for stroke. Time is retina. In expe experimental models of occlusion of central retinal artery and young and healthy models, irreversible damage was seen at 1.5 hours. However, in elderly atherosclerotic and hypertensive models, ischemia wasn't seen until 4 hours, um. And this principle is called retinal ischemic tolerance we see in myocardial infarction and strokes essentially in patients with atherosclerosis and narrowing of their arteries, these recurrent episodes of non-injurious ischemia prime the retina for later episodes of occlusion. And so each patient actually varies. What is the rate of or what are some factors that determine the rate of ischemia and retinal ischemia? The first, retinal ischemic tolerance. The second is collateral blood flow, so we know that the ophthalmic artery has significant collateral blood flow, but the central retinal artery does as well. You might be able to appreciate some of those peal arteries that form collaterals with the optic nerve sheath, and then more distally at the lamina corbosa or optic nerve head, you can see some collateralization with the ciliary arteries and so there's individual variations in collateral blood flow as well. The location of the embolist is also important, a more proximal emboli, um, you might still have some of this collateral blood flow that can kick into overdrive, but if it's more distal at the optic nerve head, that collateral blood flow becomes less less uh useful. So, knowing that there's individual variation, we're kind of moving away from a time-based model into a penumbra-based model, understanding that there can be individual variations in um ischemic tolerance. Important to note that fundoscopy is essentially like a CAT scan in that once you start to see findings of ischemia on fundoscopy, it might be a little too late to intervene. It's like seeing a well defined hypodensity on CAT scan. So what can we use in the early window? Oh, this is also shows you how cherry red spot is thought to be kind of end stage infarction. So you can see on the end, how once you're able to visualize that cherry red spot nicely, that might indicate irreversible infarction. So what can we use to identify patients in the early window? Optical coherence tomography is one such tool. The thought is that edema accumulates at a time dependent rate. However, it's variable person to person, and at some point there's too much edema where it might be. Reversible and so OCT is being investigated for that. Also that hyperreflectivity is an early biomarker of ischemia, so you can look at OCT even before fundoscopy to see where someone at in their individual cascade similar to perfusion scans. All right, so what are some treatment options that are available? One is TPA. So there's been one randomized clinical trial looking at IV TPA and central retinal artery occlusion. Looked at 16 patients with CRAO within 24 hours of onset. 2 of 8 patients in the TPA arm improved, and they were both the earliest treated patients, 4.5 hours in 6 hours. All the other patients treated beyond 6 hours had no improvement. That kind of falls in line with our golden window and the animal models of around 4.5 hours. You can see here though that those two patients had no sustained benefit. One had carotid stenosis reoccluded. The other patient had something called neovascularization, which is a really rare complication in CRO but can happen in around 10% of patients. And so this was effectively a negative study, though it adds evidence for potential benefit of TPA if done early. This was a meta-analysis. It included 80% of patients in the world literature who were treated with thrombolytics for CRO, and they found that in patients treated within 4.5 hours, statistically significant um improvement compared to patients who got out of place greater than 4.5 hours or no treatment at all with the number needed to treat a 4. There was also, um, an association between early treatment and the likelihood of recovery. In the meta-analysis, 2 of the 100 patients had symptomatic intracranial hemorrhage. One patient had CAA, one was also treated with IV heparin, a low rate though, and we know that in patients without large amounts of cerebral ischemia, uh, low likelihood of symptomatic intracranial hemorrhage. So in summary, 1 negative RCT1 suggestive meta-analysis. There's also been studies looking at intraarterial TPA, the Eagle trial. This looked at CRAO within 20 minutes or 20 hours of onset. Um, they used 50 mg of TPA injected into the ophthalmic artery via a micro catheter and compared that to conservative therapy. The meantime was 13 hours, no patients notably were treated within 4.5 hours, and the results were a negative trial, no difference in visual recovery, and there were some safety outcomes in the intraarterial arm. There was a meta-analysis looking at intraarterial TPA though that suggested possibility of benefit. It was a pooled analysis looking at 5 retrospective cohorts and 1 randomized clinical trial. Unfortunately, how each trial defined visual recovery was different from one line to many lines, but again, adding some data that TPA might be a useful treatment option. So, in summary, 2 negative RCTs, but 2 meta-analysis, possibly suggesting benefit. There's also so-called conservative treatment options, things like ocular massage, anterior chamber paracentesis. Most of these, um, observational studies have been negative, but if you look at the time course for when patients were treated in those trials, similar to the TPA trials, a lot of them weren't getting treatment early on. Um, and so I'm, I'm not sure if we know whether or not these are beneficial or not. It's certainly possible that some of them could be. Ocular massage and intraocular lowering pressure medications for the eye have only been studied in case reports or in conjunction with other therapies. Hyperbaric oxygen, so we talked about the theoretical basis for this. There has been a meta-analysis that suggests it potentially could be beneficial. It's thought that this doesn't recannualize the artery itself, but in addition to treatments that do recantalyze, it can provide oxygen while that process is going on. This is our acute CRO treatment protocol. So when patients coming in within 6 hours of last known well, we first do a fundus photo that's interpreted remotely via telemedicine, CT brain, and then if within 4.5 hours we do consider T and K. We don't have an intraarterial TPA protocol just because data is so limited at Mount Sinai and Hopkins, they do use this protocol. There's a little bit of evidence, but it's accumulating over time. In which they inject alequats of 3 mg of TPA over 5 minutes and they're assessed by an ophthalmologist in the IR suite. Once there's improvement, they stop. There's, like I said, limited data for this, but they're accumulating, um, more and more patients. Where do we go from here? So first and foremost, hopefully we can get more uh patient providers, uh, educated about CRAO and the need to send these patients to the emergency department for potential therapy. There are randomized clinical trials looking at thrombolytics at early time points, the 4.5 hour window. Hopefully we can follow patients beyond 1 month knowing that neovascularization is a potential complication. We do need randomized clinical trials on conservative therapies. I don't think those have been effectively evaluated. And then continuing to explore biomarkers of retinal viability, things like OCT, they complement our time-based approach. Cool, thank you very much. Published December 14, 2023 Created by Related Presenters Levi Dygert, MD View full profile
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