Citing numerous studies and case examples, Dr. Reade De Leacy, Assistant Professor of Neurosurgery and Radiology at the Icahn School of Medicine at Mount Sinai, discusses how multidisciplinary teams at the Mount Sinai Health System treat central retinal artery occlusion (CRAO) using neurointerventional techniques.
they have the pleasure of introducing read Delacey. He is assistant professor of neurosurgery and radiology. He's director of neuro interventional spine, he's director of cerebrovascular services at Mount Sinai Queens. Um He did his have the pleasure of introducing read delays. Er once his assistant professor of neurosurgery and radio livestream activating, he did his undergraduate and medical degree at University of Queensland in Australia. He did his residency at Gold Coast University Hospital and uh did multiple fellowships until coming to us at Mount Sinai for his radiology fellowship and Endovascular Fellowship. He is an exceptional mentor, he is technically gifted and he's also very compassionate with his patients. He recently was a recipient of the Coleman Family Award for Excellence and physician communication. Mount Sinai health System, which really is a great honor. Um Thank you very much for Delacey. Look forward hearing you speak. Thank you chris very kind introduction. I'm going to share my screen and just confirm that you can see the slides go to presenting view, is that right? Okay. Yeah. Okay I'm going to minimize that. So as chris introduced my name is Read Delacey on one of the assistant professors in the cerebrovascular group here in Mount Sinai. I'm going to talk today about central retinal artery occlusion and I wanted to be a little bit optimistic and stay defining the role of your intervention rather than is there a role for your intervention? Because I think the former is more accurate looking forward. So no disclosure is really relevant to this talk for today but central retinal artery occlusion Israel Um paper that was published back in 2005, gave uh Sorry an incidence of one presentation per 10,000 ophthalmology visits. And most of us remember from our training back in medical school but basically sudden onset painless loss of vision secondary to inclusion of the central retinal artery. And there's something to remember that it's impaired perfusion to the inner retinal layers. There's actually a dual supply of blood to the globe from the core idol ancillary arteries which actually supply the outer layers of the of the globe itself. Present with decreased visual acuity and on fungus copy the typical findings that we are. Ophthalmologists and neurologists talk about apple retina and a cherry red spot. And it's important to understand that for the diagnosis of this this this entity. You really need a good quality physical exam that focuses on retinal examination which is more or less a bit of a rate limiting step to getting patients treated quickly. And we'll talk more about that a little bit later on. But other investigations cT had to exclude intracranial um causes for presenting with visual loss or excluding stroke mass lesion and as we talked about fungus copy Oktay or flores and retinal angiography. And obviously the last two of those require technical considerations but also expertise considerations. And then blood tests such as Cbc koa GSR looking for masculinity, underlying causes and biochemical analysis. The study the image on the right is actually an oak ct image. And again, we'll touch on this more towards the end of the talk. But basically this is a snapshot that gives you a bit of a topographical appearance of the retina. Talking to some ophthalmology colleagues, this is a more typical finding that you'd see in central retinal artery occlusion. So the arrow traveling across the center of the green box is the slice in which we're looking at the retina which is depicted on the right, the mound on the left and then there's a valley in the amount on the right is essentially the edema or swelling of the inner retinal layer either side of the phobia, around the level of the macular and that apparently is typical for what the ophthalmologist will see in central retinal artery occlusion. So it is important. The natural history suggests that spontaneous visual improvement can occur in some forms of sierra, but we'll talk a little bit about the numbers of that happening a little bit later on. But the extent of improvement really depends on the type and the declaration of the C. R. O. And when ophthalmologists talk to us about response, they're really talking about meaningful improvements. So three lines on a stolen chart or a log march art. And this only really occurs in 10% of patients with spontaneous re perfusion. So 80% of all comers that present with sierra tend to have or will have a final visual acuity of counting fingers or worse. So why what are the impediments that we have to fixing these patients? One is delaying presentations? So they tend not to present as quickly to emergency departments as those with major strokes or moderate strokes. Um And they tend to present their community ophthalmologists or their primary care physicians rather than the first. And of course there's a tremendous lack of standardization in the treatment that that's been offered either conservative or interventional therapy. So ideologically 95% of these patients are trombone bollock. So the cause of Sierra is strong symbolic. So either cardiac or vessel vessel from the multilateral corroborate credit artery with 5% being are terrific. So that zebra that people talk about with giant cell arthritis presenting with uh an ocular visual loss. We talked a little bit about the type of the CRE oh influencing patient outcome and that's the second line there. So is it a complete scenario where the entirety of the retina is losing its blood supply or is there a normal variation in which a patient has a Celia retinal artery? And those patients bouchar schematic, sorry, diagram. But essentially the central visual field, the macular xenophobia can be supplied by a separate artery that arises not from the central retinal artery but by axillary artery. Um This talks a little bit about the natural history. It's a little bit of a busy slide but I'll try and dissect it apart for you. So the top section is visual acuity at initial presentation by type of CRE Oh and essentially what we're looking at is the non are terrific CRE oh variants. So no giant cell arthritis patients and this is complete. And with cilia retinal sparing and you look at the presenting symptoms. So 93% of patients with non arthritic CRE oh will have counting fingers are worse. So really, really debilitated vision in that eye slightly better for patients with that silly. A retinal artery sparing, which makes sense because they have the center of the visual field somewhat preserved. And when you take this section over to the right and you break it down to see what happens with the natural history of these patients over time was spontaneous recapitalization or re perfusion. Essentially the non art critics, only one in five of those patients will get some marginal improvement in their visions. So the natural history is very, very poor. So the cilia retinal artery, Celia retinal artery here is a branch that can come appears through the core, appears through the retinal layers and supply the retina, usually within the temporal quadrants away from the the optic disc towards the macular in the phobia. And obviously that's the center of the visual field. Only about five to at least reported 5-50% of patients will have this normal variation. So it's not a reliable finding. This is fluorescent angiography. So complete Sierra on the left, we don't see any fluorescent traveling through the arterial arcades and this is at 90 seconds. And again, ophthalmology colleagues tell me that you should see the arcade somewhere between 15 and 20 seconds. And this is a patient with cilia, retinal sparing. So phobia, macular region optic disc and there is some preservation with loss of the pacification of the arteries adjacent. So delaying presentation is a major major problem. This gentleman here Harry has published the majority of data looking at how long a retina may survive without adequate perfusion. So he identified that irreversible damage to the retina occurs at 240 minutes after Sierra is specifically in recent monkeys. Not humans, obviously, But no permanent injury occurred in this group of subjects. If retinal flower is restored within just over 90 minutes. No recovery was found over 240 minutes. So, based on the results from these animal studies at least, and some human studies that will talk about incoming slides, it suggests that the tissue, sorry, the time and tissue metric that we use for evaluating and assessing stroke equally applies to the retina with terms to re perfusion is obviously significant impediments to us getting to these patients within this for our kind of time frame again, because problems with diagnosis in the hospital, but even upstream of that, problems with patients presenting promptly. So these are the therapies that have been used or have been investigated any time, that you see a list of this many interventions for a specific condition. It makes you wonder about the effectiveness of any or all of them but not invasive and interruptible. Therapies include I. O. P. Lowering medicines, regulation, ocular massage, hyperbaric oxygen. Sublingual GTm Rice is survived anterior chamber paris and thi sis laser and elected me to track to me and direct central retinal artery massage. I've, et pas and of course interventional therapies which we're going to talk a little bit more about so intricate material. Itics of which the first cases were described back in the mid-80s these days to is obviously the most commonly used drug cryotherapy. Um We were using anterior chamber paris synthesis at Mount Sinai, but that's fallen out of favor. There's been some studies showing that there's no difference between patients that that have that intervention and not. There is a study that was done out of the Mayo center looking at hyperbaric oxygen which had some encouraging results. But obviously most hospitals and many hospitals uh don't have those kind of facilities available readily. And there was an I've to trial that came out of Australia which was an RCT. But again very small numbers, only 18 patients randomized and not really powered as more of a pilot study. Um In terms of Level one evidence, the Eagles study is the only Level one prospective randomized trial. Looking at intra arterial therapy for central retinal artery occlusion is public, published back in 2000 and 10. So they get top marks for naming the study because it's an awesome, awesome name to give to a study. But the European assessment group full ISIS. In the eye. They enrolled between 2002 and 2007 for 85, sorry, 84 patients. So it's very slow to enroll which gives you insight about the rate of which these patients present, but also just the general incidents. Mhm. And as I said, nine centers between Austria and Germany, 40 patients were randomized to conservative therapy and 44 to local infusion therapy included patients between 18 and 75 years old. And interestingly they allowed inclusion if the procedure would be able to start out to 20 hours, which kind of flies in the face of the research done by higher a some years earlier. And primary efficacy outcomes were best corrected visual acuity at one month. And of course primary safety outcomes for intervention the medical therapy and they use him a delusion if the market was over 40 ocular massage for 15 to 30 minutes to Malala. As soon as all of my anterior chamber paris on thesis was not allowed. And patients got beady low dose heparin if they were in the intervention and they got all of these interventions plus direct catheterization of the ophthalmic artery Bowl is patient with 5000 units of heparin and 50 mg of TP A. Um administered directly to the ophthalmic artery with intermittent examinations. And unfortunately they showed no difference in best corrected visual acuity between the two groups at one month. If we look at some of the demographic data on the right, the average time to intervention in the conservative therapy arm was almost 11 hours and in the intervention alarm was out to 13 hours. So really well and truly beyond what we postulate to being a sweet spot for intervention. And these groups. So what we think is a time played a role. But they're significantly less recovery improvement in the log master. That's a scale for assessing visual visual acuity similar to snow and but more used in research applications. So significantly less recovery improvement in the Long March are for each hour loss per treatment. So speed is key. We're thinking and again like we said really really delayed presentations and delayed time of intervention and again the adverse reactions to talk about the safety outcomes. So in the conservative therapy one patient ended up with corneal erosion. And in the lyric therapy group and the I. V. Heparin therapy group to patients developed intracranial hemorrhages and there are a number of more mild eighties throughout both groups. Mostly in the intervention on those things were things like groin hematomas etcetera. So we rewind a little bit a study that came out of the Hopkins group in 2000 and eight. And I say this or I go to this because it's this study that's really informed the way that we practice within the C. V. Group in terms of our interventional strategy for these patients. So this paper was in stroke was a single center non randomised interventional study of consecutive patients. 21 patients got local therapy, 21 patients standard of care, 76% of visual improvement of one line versus 33%. And there were no intracranial bleeds or visceral bleeds or retro peritoneal bleeds. So this is what we do at Mount Sinai. So we infused epa directly into the ophthalmic artery. We only infuse into the blockages relieved or the patient's vision improves on the table and we do it in three mg alec watts at five minute intervals, only up to 22 mg. So from their study and the multi vari logistical regression patients who received with 36 times more likely to have improvement. We look at their time to presentation essentially those that got intervention were on average taken to the interventional suite at 3.5 were just short of 3.5 hours. Which is from onset. Which is truly remarkable when you think about it and the barriers that people have to treating these patients. So you know weaknesses, respect retrospective, non randomized and theoretically they might have caught a number of scenarios that are spontaneously recovered or maybe they had a number of scenarios that had cilia, retinal artery sparing but fluorescent angiography is not practical really in evaluating these patients in most settings. So fast forward to 2021 and this is our group. So it's made up of members of the c. v. team and importantly it's made up with members and leaders with the ophthalmology team. This was published in Clinical ophthalmology earlier this year. So we published a retrospective consecutive series of 15 patients. These patients had to be treated within 12 hours. It was over the last five years from when our records could be could be sourced from the M. R. And the Ssh protocol for RTP was based on Hopkins technique. After treatment of the ATP significant improvement of visual acuity would mean change of .76 on the log mass scale. Now is significant and vision improved by greater than three lines in over 50% of the patients. And of these patients were vision improved. The average was by greater than six lines on dialogue. My child sorry on the Snow and Child which is really quite impressive. And four patients improved from counting fingers at baseline or worse to 28 or better. Mean dose of Tepe was 17 mg and we got to them relatively quickly. But the fastest was 5.5 hours. It's still barriers to care and importantly no adverse events. Uh, is the box plot basically showing and we'll look more so at the at the cut out on the right. But for the patients that had three lines of data At their follow up at three weeks, this is really demonstrates the magnitude of an improvement from presentation. And of course this was statistically significant. Um Similarly same data in the previous graph, just just shown in a different way showing the spread of the change in visual acuity on the stellin chart for those patients that had greater than three lines of improvement. So Mount Sinai Health System, we have data I think at least available to suggest i therapy can lead to better outcomes for sierra patients than the natural history And conservative care strategies when treated very early. Natural history is poor and the risk of intervention using the technique that that we apply. And at least the published data from Hopkins appears to be very, very good. So we've had 36 patients between them with no serious adverse events or bleeding bleeding complications. Mount Sinai is obviously a very large network. We have lots of sites. We have an extremely well organized LBO evaluation and treatment network and well integrated stroke neurology. He'd see the NCIS human radiology services but the missing piece out of that previously had been ophthalmology ophthalmology amount sign at this stage does not have on site coverage. After hours you require for the ophthalmologist to be able to come in dilate the I do for endoscopy duo ct or do flourishing angiogram and on average that takes two hours or more it seems. So that's the rate limiting step that we worked on. A solution. We'll get to that later. We'll talk a little bit about the interventional considerations and I'm just looking at the time I got 10 minutes and just need to make sure that we stay on time. But essentially, so this is the ophthalmic artery of the central artery of the retina. And you have these posteriors. Hillary arteries coming off separate and more approximately and if these arteries that can provide that Sileo retinal artery variant, um again, interesting things about the film psychiatry, it has an odd evolution. The adult ophthalmic artery does not actually arise from a known precursor during its embry a logical development the m biological orbital supplies from a doorstop Tamika tree arising from the vault, the ventral film like archery arising from a super client. I see more distal to its typical position in in the adult Or the a. one and noted bit interesting facts maybe for um uh you know uh other kinds of nonmedical kind of questions. But basically this persistent horses and the middlemen in digital artery via the meaning of filmic or mingolla criminal blanche branches. And this is actually an important consideration. It can persist in adulthood and in patients that have a occlusion with the R. O. Symptoms. You can actually capitalize this branch to deliver to these all invalid over time. And we're left with development of the the more typical position of the ophthalmic artery. Okay, so these are the collateral pathways that can get you to the either the orbit obviously in your intervention and CV. It's important to know about all the pathways that can communicate between the external carotid artery and the internal corroded artery. But basically facial maxillary and superficial temporal all have some divisions that can Eskimos with orbital branches that can Eskimos with your pelvic artery and can pass on to the internal carotid artery, intracranial E. So these are the pathways that we can use. So the F. Model arteries anterior posterior arising from the super medial orbit, the infill lateral trunk arising from super orbital fissure and middlemen in jail, and anterior T. D. Temporal arteries arising from hurdles canal or the lateral margin of the orbital respectively. And lastly but not least inferior orbital and facial arcade. So we do a patient briefly. This is L. B. 50 year old female son on set loss of vision. At four o'clock she was actually at the airport about to fly out of laguardia, past history of coronary disease, hypertension, diabetes and Austria arthritis. She actually has a private ophthalmologists who she managed to get to within two hours from laguardia who examined her dilated or I diagnosed Sierra. This is the typical findings that we're talking about with cr oh so pale disk with a cherry macula, which I read a chariot macula. Sorry, visual acuity. She had some uh some hand movement in the left temporal field timeline was onset of symptoms. Four o'clock saw the ophthalmologist by six o'clock was in the M. S. H. E. D. By 8 39. CT brain was interpreted within about half an hour or less. And we had the patient in the interventional suite uh By 20 minutes past eight and we're delivering teapot by 8:30. Essentially we do CT heads to exclude intracranial lesions. That would be a exclusion for T. P. A delivery and looking for other other evidence of established stroke. So nothing there, no asymmetry, Maybe some white matter disease on the left. Um maybe an old cortical infarct or developing issue in the left cerebral hemisphere and A. C. To essentially the family countries opened. The resolution of sita is not good enough to tell us anything about the central artery of Loretta were written. This is the angiography. So left sided catheter in the common carotid artery runs of the neck runs of the head. We don't see any real coral blush of the ophthalmic artery. This is overloading from bony structures. It's not the globe. These are more magnified views. So subtracted un subtracted showing position of the catheter. Direct calculation of the comic I. A. Tree check angiograms proving that were perf using the globe. Sorry the orbital cavity and this is after delivery of the T. P. A. And you can start to see the profusion and enhancement of the steroidal steroidal blush but also more pronounced profusion enhancement of the soft tissues of the intern extra corn a little bit. And this is the final runs so early and late we're seeing Kuroda Bush and this is the patient's details from our paper. So line pairs sorry outlined perception down to 20 on 50 and time to intervention of six hours. So we do have delays in diagnosis and it's a massive problem. We have a system established now that's in rollout to convert CR a diagnosis in the two a tele retina service. And this has the potential to reduce the diagnostic time gap from the hours that we've seen previously. Down two minutes. New york idea foundation provided a grant by three oct machines which have been placed in the heads at S. H. M. S. W. And Mount Sinai queens. There's the instruction pamphlet for the staff within the centres to use and it really is a plug and play basically place your head into the side of the machine, fill out the details. Take a picture, gives you the images and those can be related to the retin ologists or the ophthalmologist on on call. It went live at the beginning of april and it's being progressively rolled out the other side of that stuff being trained. But this to our knowledge is our one of a kind service for general emergency departments anywhere. Obviously these systems are available and specialist ophthalmology and otolaryngology departments of new york pioneer and the people really championing this these three gentlemen. So Michael Farrow is one of the stroke neurologist. Gareth lima is a retinal specialist, and Richard Rosen is professor of ophthalmology at Mount Sinai and obviously I'm part of part of the team that's that's setting up what you really need is by any partnership from the people that control these patients whose lives are going to be effect by on call. So I can't say enough good things about these two individuals. And of course Dr Farrow and this is a flow chart that we have. So patient presents the edie with Q painless unilateral vision loss less than 12 hours call stroke called retina. Heads up given CTC ta see to have required history exam, written confirmation and Petipa and everything moves in series and in parallel and what we're trying to get is a full ophthalmology consult Far far father. Earlier up the the flow chart then we're seeing it currently and removing the requirement for physicians to have to come into hospital from the home which obviously in most cases is not within the 30 minutes that we have as your interventionists and stroke stroke positions. Thank you guys very much. Happy to take any questions and I'm looking forward to this program. Hopefully increased in the good that we can do for these patients, wow, Very, very impressive. Art Jenkins had a question read like you think this could be treated like M. I. And if there was some sort of suspicion in the field give acute aspirin or something like that with the big educational program, I'm not certain of the indication for aspirin, but theoretically it fits with it does fit with a protocol for am I? The only issue would be that these neurological deficits that we're talking about, an infield delivery of anticoagulants or anti platelets? Maybe a little bit of a risk considering the differentials still includes intracranial pathology until it gets better evaluated in any D setting. So I think at this stage it's probably not not really practical until you get to the point that you have infield triage reliable infield triage in diagnosis of Sciarra. I think this is a pretty amazing work and the idea of bringing diagnostic tools to the shed and getting that up front and shortening the time. As you know, the biggest bane of our existence is delayed presentation. Um I guess one thought is I'd love to get your thought and share with the group and I think steve Rudolph dr Rudolf just made a put a question about this while time is absolutely crucial for getting the patient treated quickly, getting good outcome from the patient. Do you see there being a downside for a patient who is presenting at a delayed time period or as a wake up discovery? Um You know my my impression is there's relatively little downside to giving a couple milligrams of T. Pa into the atomic artery. And it might be uh it might be something worth doing even if it's just to make sure everyone is thinking about it and pushing it and trying um at all times sort of Greece the process to make sure it's occurring efficiently. I'd love to get your thoughts. Yeah. I mean I talk about the 15 patients that we published on and that's obviously not the entire complement of patients that we have intervened upon. We chose that as a line in the sand basically on the background of the Eagle study and the data that they showed for intervention at or around about 10 hours on average. Even though they showed that there was a significant trend towards improvement with early early intervention. I think that we've shown at least with our technique with Hopkins protocol, that the intervention is safe, you know safe in terms of the risk of causing complications related to bleeding. Um Really the question that's unanswered is whether Intervention after 24 hours is going to provide any kind of improvement in the long run the data that we have suggests that any improvement that you really get in perfusion or recovery happens one out sorry up to one week after um actives after after presentation with C. R. E. O. I think we've got a pretty good data at least showing following these patients now out to at least three months that shows that they don't really have a progressive improvement after the three weeks that we see them. Um And I guess that's a long kind of complicated way to say. I don't really know I don't think that we do harm but I'm not sure about what some benefit is going to be. And we just don't have the numbers really to say more than that in a really informed evidence based way, fantastic presentation. We a great question with the new data building showing that there is more higher reckon. Ization rate. TNK can be C. A role for TNK for C. R. E. O. I don't I don't know the answer to that interestingly. The paper that was published on I. V. T. P. A. The randomized trial which came actually out of Melbourne are M. H. Was co authored by Bruce Campbell as well and obviously they're running or they have run prospective elbow trials looking at TNK. I'm not sure whether that's something that's on the radar for them as well. But it's something something that certainly might show benefit because we know that if we can analyze the artery the outcome is going to be better and now you're you know that the recolonization rates with a from political it's a traumatic patients are higher. With. However it is a difficult patient population to study because of the rarity of the pathology. It's rare and you know I think some of the issues with at papa has been finding what the appropriate dose was to avoid the complication of bleeds. Um When you start throwing in a new medication to the mix and I kind of feel like it might be it might be setting back the clock a little bit where you really have to almost do like Phase one trial specifically to find out what the safe safe doses delivery. So that's correct. Thank you have the dose for ivy. So that's been determined by mostly by the Australians. That's what Sharon mentioned the study about looking at people prior to mechanical from back to me. But I wanted to make a comment about increasing the number of treatable patient. As long as we have O. C. T. Available. Uh The Germans just published last year that they could time the onset of the C. R. A. O. With O. C. T. So it's the equivalent of what we do with wake up strokes where we're looking at the difference between the flair and the diffusion. Yeah so it may be possible to increase the number of patients. How do they do it steve, well well they they had patients that where they had the known time of onset and they have O. C. D. S. At different time points. Uh It's an act ophthalmological I'll send it to read so he can send it around. I think that would be great to look at. The other issue is that the american stroke Association just issued a scientific statement on CRE oh it's in stroke last month and It encourages ivy at less than 4.5 hours and endovascular therapy beyond that point. So the real issue is getting the ophthalmologist to know this. Uh We we did some outreach here in Brooklyn. We just contacted almost 100 ophthalmologists and um we haven't done a formal survey but they were not aware of any of this data. So my question is if you have a good ophthalmologist doesn't. O. C. T. In their office, do you need to go any further work in that patient? He directly referred for endovascular therapy by understanding from ACP. Is that the diagnosis is is is fairly evident and it's there to exclude other kinds of intra ocular pathologies like retinal detachment. So if it's consistent and convincing of sierra along with history that fits then then I think that there's certainly room for incorporation incorporating that into a director angio or an expedited treatment protocol. Just in terms of what jay said. Um don't you think that at some point the O. C. T. Can exclude patients from therapy that you can see when it's just too far gone theoretically. I mean I would have loved to have um dr lee Marlboro frozen on the call to answer that because that's out of my my clinical band bandwidth to be honest. Because once you see the cherry red spot, I mean they're still treatable. But we know now from from looking at this over a period of ours and that you can identify it on O. C. T. Before you see anything in the retina that there are some people that we can get very early. The ophthalmologists are right into this. So I've been speaking to lima about this uh you know, putting together a CMI and lecture for them. Kind of an update on stroke that focuses on c r a o mm and we'll be doing that. So we'll drag you in perfect. I mean, we've been talking Gareth and I have been talking about, you know, Mount Sinai is a system that is so well greased and well oiled and structured for stroke intervention. And all the pieces that there for the final part of the puzzle really, where there's an issue in a limitation is the early education and the refer education.
