 And we're going to talk about retinal vascular disease, it's a two-part lecture, I think I come back maybe in January to finish it up, but this is what we're going to cover, it's retinal vascular disease, not including diabetes, so the diabetic lectures are all separate. So today we'll get through venous occlusions and arterial occlusions and then I'll come back and it's kind of a medley of vascular problems that don't really fit into anywhere else of your lecture series, so it's a little bit of a mixed bag next time. So we'll start by talking about a central retinal vein occlusion, so the pathogenesis of a retinal vein occlusion is vascular endothelial damage that leads to compression of the retinal vein at the laminar crevosa, anyways everybody should know from anatomy where the laminar crevosa is at, so there's an occlusion just right in the central retinal vein there, and then that leads to increased retinal capillary pressure, transudation of fluid and subsequent macular edema. The clinical signs, really the classic clinical signs are going to be four quadrants of hemorrhages, four quadrants of dilated tortuous vessels, and then optic nerve and macular edema. We break up a central retinal vein occlusion into the non-eschemic and the ischemic forms, the non-eschemic is going to be less severe with better vision and they're going to have better vision outcome in the end, almost half of these can resolve on their own, and the fluorescence is going to show prolongation of the retinal circulation time, there will be leakage from breakdown of capillary permeability, but there's really minimal non-perfusion which is compared to the ischemic CRBO, they'll have worse vision to start with, worse vision to end with, more than 10 disc diameters of non-perfusion on the fluorescent angiogram, often they'll have an atheropupillary defect, and the vision loss will be due to ischemia and then neovascular complication. The ischemic CRBO has a really high rate of neovascular complications and without treatment 60% can get rubiosis. So this photo's just going to contrast the ischemic and the non-eschemic variation, so this is, you know, a fairly severe non-eschemic actually, but you can see hemorrhages, tortuous vessels, dilated vessels, but compared to the ischemic form, where it's really severe hemorrhages and optic nerve edema and significant macular edema, as well as a number of cotton wool spots present. A hemiretinal vein occlusion is actually a variation of a central retinal vein occlusion and what happens in a hemiretinal vein occlusion, about 20% of us are superior and inferior draining retinal veins actually meet posterior to the lamina crevosa and so there's an occlusion of one of those draining vessels posterior to the lamina crevosa. So it actually has a really high rate of neovascular complications. It's managed similarly to a central and a branch retinal vein occlusion. You would treat the macular edema like a BRBO with macular grid, anti-vegeth agents, and then the neovascular complications with pan-retinal photocoagulation. So the big risk factors for CRBO or age, hypertension, diabetes, glaucoma and younger patients you want to consider a hyper-coagulable state and medications that could lead to the thrombosis. And then just moving on to, I'll just talk about the branch vein occlusion first and then we'll cover the treatment studies together because they're pretty similar. But a BRBO is a similar pathogenesis. At that common adventitial sheath where the artery and the vein are coming together, there's thickening of the arterial wall and then that compresses the underlying vein leading to turbulent flow andithelial damage and thrombosis. If it's not, if it doesn't start at a Navy crossing site you want to make sure you rule out an inflammatory or vascular type cause. The biggest difference in the risk factors, and this is from the eye disease case control study, diabetes was not found to be an independent risk factor for a branch retinal vein occlusion. So sometimes that'll pop up on OCAPs. The other difference is an increased BMI at the age of 20 is an independent risk factor for a branch retinal vein occlusion. So those are really the two differences. This is a pretty typical clinical picture of a branch retinal vein occlusion. You can see the hemorrhages start in this sector right at this AV crossing site. There's cotton wool spots and then downstream there's this tortuous vein and then they can see macular demon on that picture as well. So this is just what I've mentioned before, the difference in the risk factors. So diabetes is a risk factor for a CRBO and then the BMI and cardiovascular disease for a BRBO. So when they first come into your clinic obviously you're going to be checking the vision. The vision has a big factor, a prognostic factor in how they're going to do ultimately looking for an ather and pupillary defect, measuring the pressure, looking for neovascularization of the iris and then fluorescing, OCT. I think the fluorescing can be really helpful to differentiate from ocular ischemic syndrome or carotid disease and also looking for inflammatory type causes of a vein occlusion. And obviously you want to look at the amount of non-perfusion. And then in my clinic, you know, if they're coming in for the first time with the vein occlusion, I'll have my technicians check the blood pressure in the clinic. Sometimes it's high enough you end up having to send them to the ER. If it's usually high, you know, if they're coming in with a vein occlusion and so I'm usually trying to communicate with the primary care doctor, trying to get them into their primary care doctor for better management of their blood pressure. And then the other risk factors, glaucoma. So looking for cup-to-disc asymmetry or optic nerve cupping and if they're not being treated for glaucoma, getting them in with our glaucoma colleagues to reduce the risks of that. If they really don't have any risk factors and they're under 50, then that's when we would do a hypercoagulable workup. And I think it's important to remember estrogen and oral contraceptives as a risk factor too in women. So this would be kind of your basic hypercoagulable workup that you would start, I don't know, you do it then working with a hematologist, oncologist to help with management and if they need anti-coagulation based on any abnormalities on the hypercoagulable workup. So the causes acutely of vision loss from a retinal vein occlusion are edema and hemorrhage and capillary occlusion. Chronically, patients can develop fibrosis, macular ischemia. They can develop epiretinal membranes. And then the other thing that you're watching for is neovascular glaucoma and complications related to that. And that's usually about three to four months after the initial event. So this is an angiogram of one of my patients that I think demonstrates actually the complications of a branch retinal vein occlusion pretty well. Pretty fluorid neovascularization of the disc. You know, we've started some PRP here. There's still some capillary dropout here. I think that day we kind of tightened up the PRP. You can see collateralizations across the horizontal raffae here. With a branched vein occlusion, you're more likely to get neovascularization of the disc or neovascularization, neovascularization elsewhere. You don't really see rubiosis that often in a branch retinal vein occlusion. It's just not quite as ischemic. This is another angiogram showing that capillary dropout and then this collateralization that's occurring temporarily here. Does anyone have a good way to kind of differentiate collateral blood vessels from neovascular blood vessels? Anyone have any how we figure it out? Because sometimes the collateral, the collateral can really look like neovascular fronds clinically and it can be hard to figure it out. The best way is actually to do an angiogram and collateral blood vessels aren't going to leak and light up like you see. You know, this obviously neovascular blood vessels are really hot and leak pretty vibrantly, but collaterals aren't going to leak like that the fluid's going to stay within that blood vessel wall. So that's just another example of collateralization. And you really will see this in a chronic BRBO. So some people, you know, show up years later. And you can tell that they've had an old BRBO even if they don't remember it based on this pattern here. The collateralization is actually pretty good because it just provides another outflow path and the edema can resolve and they can get better vision once that occurs. So now the studies which are pretty popular to get tested on I think the big studies to really remember are the BVOS, CBOS studies, which were really the first studies really looking at natural history and laser treatment guidelines and those were in the 80s. Score came out next that's try and send alone. And then I think, you know, you'd be most likely to be tested on Bravo and cruise. And it's important to remember that's random is a map looking at a BRBO and a CRBO. So that's when we really let us down the anti-vegeth treatment path for vein occlusions. Obviously, there's studies for a flibrecept as well. And then bevacizumab we use really commonly, but there's no randomized perspective trials on bevacizumab for vein occlusions. So the questions from the BVS study, the first question was, is there a benefit to macular grid for macular edema secondary to a BRBO? And then their second protocol was to determine if there's a benefit for sectoral PRP and preventing neovascular complications. So the results showed improved vision with laser treatment for macular edema. Eyes were treated three months after presentation. So they came in with their vein occlusion, they were watched for three months. And the reason they did that was to let the hemorrhages clear up a little bit, you don't want to do macular laser through fresh, fresh hemorrhages because it takes it up pretty hotly and leaves a fair amount of scarring. So treated eyes 65% improved two lines versus 37% in untreated eyes and the treated eyes were more likely to have vision better than 2040 at three years. And then the second outcome measure was looking at preventative PRP and they found that there was no reason to do PRP until after neovascular complications developed. So you watch them if they develop neovascularization and you start the PRP and the PRP is beneficial in reducing the risk of vitreous hemorrhage. The CBOS study had really similar questions. The first question was, is laser beneficial in preventing neovascular complications? And then the second question, does macular grid decrease vision loss from macular demon? And then they also followed the natural history of the CRBO. So, you know, I've seen this question on my written boards. And really, there was no benefit visually from macular grid laser. It did improve the macular nemo, but there was no improvement in vision outcomes. And so we don't do macular grid laser for central retinal vein occlusions based on this study. And early PRP fell to reduce the risk of neovascular complications. And so we wait till neovascular complications develop and then we start PRP. There was a trend toward better vision, but there was no statistically significant improvement in older patients particularly. So let's just summarize this. So for a BRBO from the BVOS study, we treat macular demon with grid. That was really our standard of care until the anti-veget trials came out. And then we treat neovascularization after it develops. CRBO, treat neovascular complications after they develop and there's no recommendation for macular grid for macular demon. So when I was a resident and fellow, we would have these horrible ischemic CRBOs and we would just watch them. And then when it's crazy now, I was just thinking about it when I was looking at this lecture, like, I just remember doing PRP and these eyes with horrible, horrible hemorrhages. But there was nothing that we really could do for the macular demon. And I think we see obviously we see a lot better outcomes now than we did before. But that was the gold standard until these newer studies came out. So obviously, there's limits from laser, we don't get awesome vision, we do get a couple lines of improvement in vision. But the average vision for a BRBO is 2040, 2050, where today we see a fair amount of BRBOs that have 2025 2030 vision, they're doing a lot better now. And then CRBO had no improvement in vision. So we really don't do anything. So the CDOS study, I mentioned that it was also a natural history study. And so what they found is that the initial vision is the best predictor of outcome. If you come in with vision better than 2040, you're likely going to keep good vision. If it's worse than 2400 at presentation, you're probably going to keep bad vision. And then these middle range group 2050 to 2200, a third will get better, a third will get worse, and a third will just stay the same. That's the natural history. So the next study that came around was the score study. Score was corticosteroids for retinal vein occlusion. And there was a score for BRBO and a score for CRBOs. The primary endpoint was the percentage that gained three lines or more. So they did a, there was a standard of care group, which for BRBO was macular grid for CRBO was observation. And then there was one milligram and four milligram groups. So the score study for BRBO, there was really no difference at one year. And the steroid groups obviously required a fair amount of treatment for elevated IOP, higher rate of cataract surgery. And so the three year results actually found that laser treatment was better than steroids for a BRBO. And so after that study, macular grid kind of remained the standard of care. The score for CRBO study, obviously these patients did a lot better. It was one milligram versus four versus observation. The steroid groups did much better than observation with about a quarter gaining 15 letters. The observation groups only 7% gained 15 letters. So the final recommendations for score for BRBO, keep doing macular grid. CR, well, obviously not anymore. I'm going to go to the anti-vegetarian trials next. But at that time, grid laser remained the standard of care. And then for CRBO, one milligram of IVT is better than observation. This, I think the study was published in 2009, which was, you know, that was, I mean, I'm not that old, but that was a year I finished my fellowship. So it's been a big change over 10 years. Then there was Ozardx studies. Ozardx is the sustained release dexamethasone implant, which lasts in the eye up to three months. And this was called the Geneva study. And patients did really well with the dexamethasone implant, which you guys see us, and we do at the VA all the time for this. And then kind of really the big shift was when anti-vegetarian agents, when their data was released, and anti-vegetarian are a key mediator in vascular permeability and angiogenesis. And so, like I said, Bravo is the ranubizumab study. So remember that they compare two different doses of ranubizumab, 0.3 milligrams and 0.5 milligrams to a sham injection. The ranubizumab groups did significantly better than sham with 50 to 60% of patients gaining 15 letters. Over half of the patients in the sham group required a rescue grid, while only 18 to 19% required grid rescue in the treated groups. Cruz ranubizumab for CRBO, and this was 46 to 47% gained 15 letters, while only 17% in the sham group gained. And they gained pretty quickly, actually, and it was pretty remarkable. So I think Bravo Cruz, I'm pretty sure that was published in about 2010. So it was a little bit after the score study. And then this led to the anti-vegetarian agents being our first line of treatment. I mean, obviously the downsides to the anti-vegetarian agents is that we have to keep doing it. And we're doing over and over and over again. Once, you know, I mean, I have patients that I've been doing their injections for five, six years, you know, I do it every 10 weeks, and they do okay, we try and go 11 or 12, they get fluorid macular edema, they drop two lines, and we shorten it back up. And, you know, there's some evidence that maybe after a year and a half to two years, you might be able to get people off of their anti-vegetarian agents. But there's some of these really ischemic vein occlusions that I don't know, I think I'm just going to be doing them forever. I don't know, hopefully not. But right now I am. If you, you know, if they if you're able to get them off the injections, obviously you need to watch them for any vascular complications, because this can still happen once you stop the anti-vegetarian agents. And then a flibbersupp had their trials to their, they weren't quite as pivotal, but they led to their FDA approval. So we use them commonly. The flibbersupp trials were Galileo and Copernicus, and then the Vibrant study with the BRVO. But I think you're more likely see Bravo cruise on a, on a test than, than these two. Obviously, but Bevacizumab is really what we do first line for most patients. But that's based on retrospectives, case series data. There are, you know, some, some people feel like, you know, you get a better response to a flibbersupp than Bevacizumab. And so we'll often start people on Bevacizumab. And then if we feel like we're not getting the response we like, they consider switching them over to, to a flibbersupp. And you can see a pretty dramatic response in some patients and some patients that doesn't make a difference. Yeah. Usually it's cheaper. Yeah. Lots of insurance companies actually require proving that they fail Bevacizumab before you can get them to pay for a flibbersupp too. And a lot of people people do really well with Bevacizumab. So if you take someone off of anti-vegeta therapy, because you feel like, you know, they've gone long enough, how long do you follow them up for until you say like, all right, you're out of that range of, you know, vascularization. Like they're like, it's a really bad ischemic or, or like a mild, you're talking about a bad one. I still see it. Like if I, I'll watch a monthly for at least six months. Okay. And then I'll spread them out and go every two to three months. And then I'll see them at least twice a year after that, if it's been long enough. Yeah. Yeah. I mean, because really want to monitor for neobascular glaucoma and neobascularization elsewhere, they can get vitreous hemorrhages or TRDs. But, you know, I do have some people that I've done so poorly that we've stopped treating and and they're, I just see them a couple of times a year and make sure that they're still doing okay. Yeah. But initially you'll see them every month off treatment. I can't remember why I put this picture in here. But it's a non ischemic CRBO. Floricine. Oh, I think maybe I just, so this, I think this demonstrates the delay in, in the retinal circulation time. So you can see we're at 33 seconds here. And we still haven't filled our retinal veins. We have laminar flow, but they should be completely filled at this point. Maybe that's why I did it. And this, oh, this is actually one of my patients who came in with a really horrible ischemic CRBO. I don't know how to get good OCTs off access. I should have you guys show me. But anyways, this was his OCT floor and my parody, my started bevacism map. And then after three to four months, this was his OCT didn't touch it at all. And so then I switched them to a flipper sept and after a couple months of a flipper sept, he dried up pretty nicely. And now he's stabilized with this OCT and 2060 vision. And I, I think I've done a couple of Ozzard X trying to get him a little bit further apart. But, but he's doing pretty well compared to where he came in, you know, before we had anti-veg Fs, we wouldn't have gotten that much improvement. So this is kind of what I do. I'll start with a monthly anti-veg F and then I'll try and treat and extend them. I might try switching them to another anti-veg F if I don't like the response. And then I'll add in steroids, sometimes trying to get a further interval. I do do laser grid for persistent macular edema and some of these patients when we're trying to get them off the injections. But I don't do, I really don't do kind of hot focal and we would do at the, I mean, not that any focal is really hot, but I would have him go to mid-bally and I would do a sub-threshold micro pulse laser and see if I can get a longer interval between injections instead of doing laser treatment here. There are milder vein occlusions that you can watch that can resolve on their own, both branch and mild non-eschemic CRBOs. And if they're pretty mild with good vision without macular edema, I'll watch them monthly and they might resolve on their own. But if there's significant, any kind of vision impact, I would start treatment with anti-veget. And then for treating neovascular complications, depending on the severity of the neovascular glaucoma, often our glaucoma people like us to get an anti-veget injection in pretty quickly to try and save whatever is left of the angle. Often you'll have to do an AC tap at the same time to kind of bring the pressure down. There's a little risk of causing a high femo when you do that, kind of that rapid decompression. And then just getting PRP in, they'll often end up needing a tube. So working with glaucoma to kind of get that stabilized. So this is kind of fun. There are some other treatments that people have tried. People have done laser and surgically induced retinal venous and astimoses. And so what people will do is either with a really hot laser or an MBR blade surgery, kind of just create an opening just right at the retinal vein crossing sites and try and create this in astimosis. I've never done that, but I have done a radial optic neurotomy. When I was a fellow, we would do this and you would do have a trectomy and you would go in with a 20 gauge MBR blade and basically just incise the optic nerve nasally down through the lamina crevosa, trying to kind of decompress this bottleneck. And this is kind of this is a resultant scar that you can see. And it's pretty wild to go in and just, you know, stick a blade through the optic nerve. Obviously, you don't see us doing that anymore because we have anti bed Jeffs. We didn't do that when I was a fellow. And then I think this is pretty exciting. Just in the past year, one of the first uses of robotic surgery was done in Belgium where they basically cannulated a retinal vein occlusion, they used aquaplasm using this robotic arm, kind of holding it in the retinal vein for several minutes to release the occlusion. So that could be pretty exciting down the road, if that takes off. Okay, arterial occlusive, how are we doing? Artery occlusions. So we actually kind of did this a little bit in flour scene pretty recently. So I think this should be pretty fresh in everybody's mind. But it cotton wool spot is really a small obstruction of a peripapillary capillary. This is a nerve fiber layer infarct. You'll see inner retinal ischemia and often on OCT you'll see a demon that inner retinal layer is often very superficial will fade over a couple months and most people but in the diabetic you they'll persist for months longer even years. Really, this is never something that you should just say, oh, that's a cotton wool spot. You know, that's going to get better on its own. Like really, you've got to find a cause for a cotton wool spot. It's not normal for somebody to come in with the cotton wool spot. Most commonly, it's going to be diabetes, but you've got to think of more unusual things. If they don't have diabetes, radiation, retinopathy, sickle cell, HIV, collagen, vascular disease, leukemia. So there's your typical cotton wool spot. It's always interesting, you know, these end up in your clinic people, often, you know, they just kind of end up in your clinic, people don't know what they are. They don't know, you know, and it's usually cotton wool spot. They don't, you don't really see much on Fluorescy, the angiogram usually, it's just kind of obscuration of the layers underneath. So, BREO, this is similar to the picture that CJ showed at Fluorescy, but you get blockage of a retinal artery that causes retinal whiting and no pacification of the retina over hours to days. And the causes, so the most frequent cause is going to be emboli and cardiac and carotid are the most likely source. You obviously want to keep a giant cell in your mind whenever these patients come in. And then after that kind of the more rare things, but this is really where your where your money is is emboli phenomenon. So the sources are a cholesterol embolus, platelet fiber embolus or a calcific or cardiac embolus. There's been studies to see are we really good at predicting the source on based on what they look like and the answer is no, we're really not. So you've got to do the full work up. You can't just look at it and say, oh, yeah, that's from the heart. I mean, we can guess, but we're not that good at it. Rarely these are kind of the outliers, fat embolus, talc embolus, CJ mentioned people getting like, procedures, fillers and things developing developing emboli. So this is kind of the different appearances of platelet vibrant embolus kind of fills the vessel and it fragments and can move down the vessel. The cholesterol embolus and the hole in horse plaque often you'll see it a bifurcation. It usually doesn't occlude blood flow. So it's pretty rare for that to cause an artery occlusion. And the calcific embolus, that's kind of that more chalky white and usually that'll launch at the optic nerve head and will cause an arterial occlusion. So here's another example of a hole in horse plaque. It's usually pretty small. The classic description is it's refractile and that typically comes from carotid disease. Calcific another example, pretty chalky white, it's lodged. You can see how the flow is, you know, there's beating of that vessel downstream. And then another example of a platelet vibrant embolus, essential retinal artery occlusion. This is sudden complete loss of vision. The retina is opaque and edematous. There's the classic cherry red spot. And that's due to visualization of the corridor vascular chair through the phobia. The vision loss is usually permanent. Usually they're kind of count fingers hand motion vision. And if they're better than that, then they typically will have a patent silio retinal artery. For NLP or LP vision, that's usually more of a complete ophthalmic artery occlusion and not just a central retinal artery occlusion. There was one yesterday in triage. I saw pictures of that CJ was showing me. Usually, you know, the central retinal artery occlusions, they don't end up in the retina clinic right away. I think usually you guys are the ones triage, the general ophthalmologist, the residents you guys see them on weekends that kind of start the work up. So usually by the time they've gotten to me that most of them have had the work up. But they do end up in our clinic. And it is important like CJ talked about really the most important thing in the central branch retinal artery occlusion is you've got to figure out why this happened prevent it happening to their brain to their other eye. So the thrombosis is happening just right at the level of the laminar crevice. Sometimes you can see a emboli present at the optic nerve head, but often you won't see it. People can do B scans and see kind of a calcific embolus at the laminar crevice I've seen Dr. Harry doing that likes to do that. And which is cool, I think it's really cool. And then the biggest you know, you want to keep giant cell in your mind, of course, when you're working these patients, the lucky few that have a silio retinal artery can get some preservation of vision about a third of eyes have a silir retinal artery where that silir retinal artery is coming from the posterior siliri vessels instead of the central retinal artery 15% the silir retinal artery is supplying circulation to the macula. So those few will have have kind of a wedge of vision. And if they're lucky at all, this person had this kind of this was actually patient of mine that she has a wedge of vision. Unfortunately, it didn't get the phobia. So she doesn't have great vision, but she does have a quarter of vision she can look at it. And then this is a silio retinal artery occlusion. So for a silio retinal artery occlusion, you really got to think of giant cell. That's the main cause of a silir retinal artery occlusion. So for, you know, the management identifying the cause or do you see the risk factors, they do have a higher risk, higher increased risk of mortality after an arterial emboli. As far as ocular therapy, there's a lot of things that have been tried. I've had patients that have gotten to me quickly enough that I've tried to do an ac perisotesis or globe massage, you know, I've seen patients that have been sent for hyperbaric oxygen that didn't really help. But the biggest thing is that stroke work up that needs to happen. And so this was the policy that was mailed out a few years ago. And I'm sure you guys are really familiar with it. But from my understanding of the policy, unless it's changed is that if they come in within seven days of an arterial occlusion, send them to an ER, or to RVR goes to the stroke team and they get admitted and the whole stroke work up happens. If it's after seven days, then we're asked to kind of start the stroke work up. And so I've done it both ways. And I've started the stroke work up. I know it's supposed to be easy to get them into the neurologist quickly. And I kind of ran into some trouble with that. And I kind of had to push my weight around a little bit to get the patient in. But but it happened. But it wasn't quite as smoothly as maybe Dr. Katz and Dr. Warner said it would be. I think you go through the resident rather than a stroke schedule. Oh, really? Oh, the neurology resident? Yeah. Yeah. Yeah. Well, I mean, it happened. But it was a little more of a hassle than I wanted it to be. But anyways, it works really well. I think the easiest is if they come in less than seven days and they go to the ER, then everything goes really smoothly. But it's not always the case. So kind of the stroke work up MRI brain with the stroke protocol, echo, lipids, siderate CRP, A1C, aspirin and statin and the carotid. Stroke, that's a stroke. So treatments, I mentioned the hyperbaric oxygen, I've seen people in town trying that. You know, I know we talked about intrarterial TPA at the other day, and I know you guys mentioned maybe some people are still doing that a little bit. I haven't really seen that recently. That was a few years ago, right? Has anyone done it more recently? When I last year when I was on primary call, I think I saw two patients get first IV TPA, which I don't understand. Well, one of them, I think in your clinic, the young lady. Oh, that was pregnant with them. Yeah. Oh, yeah. Yeah, she didn't help her. Yeah, I think the other guy it may have helped like a liner too. Oh, significant change. I have seen reports of people if there's an embolus just right at the optic nerve head, people try and yag that and try and like resume flow. Obviously, there's a little bit of risk of bleeding. But you don't have, I mean, you have to think you don't have much to lose, right? Because like they're not, you know, so if they're getting quickly enough, I've seen people try that. I've never done it myself. So about 15% of eyes will get neobascularization of the iris. The retinal whitening will fade over a couple weeks and then your left really with a pretty pale optic nerve and these really attenuated blood vessels and you'll have pretty atrophic inner retinal layers and OCT ophthalmic artery occlusion. I have to say I've never, I don't think I've ever seen one of these to be honest. But their vision is reduced to light perception or no light perception. There's really no caroidal retinal filling on floor scene. And then the difference on ERG is that they have an absent A wave as well. There won't be a cherry red spot. And if you do autopsies of patients that have died with giant cells, 76% will have vasculitis of the ophthalmic artery. Other causes would be internal carotid dissection, mu core surgical interventions could lead to this. Have you guys seen any of these? Oh, did I? I could have added an ocular ischemic syndrome. Okay. Questions? Yes? Is there any study that actually look at the efficacy of treating heart rate condition versus just treating with I mean, yeah, there's been so they're, it's hard to do like a randomized controlled clinical trial, right? And they don't come in. I mean, the hard thing about an arterial occlusion is any treatment has to be done within an hour to 90 minutes to preserve retinal function. Most patients present within a week or so. It's pretty rare for someone to get in that quickly. I think the one a couple times I've had patients present that same day. And that's when I would try something like an AC parasitesis or you know, IOP lowering measures. And the goal is to try and dislodge the clot. But there's I think it's a pretty hard thing to study. And the timing is so critical. And any kind of reports are all just small case series that people report like for the YAG laser or the hyperbaric oxygen, all those are just things people try. But I think it's a pretty hard thing to study. cases where you've done something and it was actually versus just well, it's hard to know, right? Because it's like, well, maybe they would have gotten a little bit better on their own. But I did have I did do an EC tap. And then that patient actually that was for CRIO. And that patient actually had some recovery of vision. Not, but that's pretty rare. And that here, that might have been like more of a milder form of a CR, CRIO that they might have gotten a little bit better anyways, because it was pretty mild when I saw them. That's, I mean, usually they don't get to me that quickly, you know, I think usually they're the general ophthalmologist and they get to retina within a week or so. Yeah, because of people, I don't know, I always, because like, I think if I like, lost my vision, I probably freak out, right? But then you talk to like, lay people, like, I'll talk to my husband about that. Like, how did this person just sit around with a retinal detachment and show up Friday afternoon? And he's like, Well, you just think, Oh, it's going to get better, it's going to get better. And you're hoping in your mind, it's going to get better. But then it doesn't actually get better. And so all of a sudden, you're like, I better get the scene by Friday, because I don't want to be like this over the weekend. Like, I think some people just, you know, there's a little bit of that denial if you think maybe it's going to get better. So I think, you know, I don't know, I guess there's been so much education regarding strokes. Maybe it requires more kind of education regarding vision loss as a sign of stroke and more prompt evaluation. And especially like, even if they go to the ER, they're kind of triage down the list, right? Like, you know, you come in with vision loss to the ER, it's not like you're the first one to be seen. Like, if you come in with stroke symptoms, they bump you up pretty quickly. But vision loss, I don't think they get a lot of the priority triage. Some of them I've seen get through very, very quickly. Oh, really? Those are the two that got IATPA. I mean, one of them got metaflighted in the Fimo app. So it really depends, I think, on who the physician triage called. Oh, interesting. Who hears the complaint and says, Oh, yeah, that doesn't sound normal. That makes me see in pretty emergency. Yeah. Yeah. But then you have the other ER attending that says, you know, there's a couple of people established, you know, to be seen more urgently. So yeah, I don't know. I mean, it would be, I mean, I think intra arterial TPA could be successful, but it's risky, right? You know, that procedure is really risky. But I think that could be successful. People could get in quickly enough and triage quickly enough and then get get to the radiation suite quickly enough for the treatment to happen. But, you know, 90 minutes is a really short window before the retina is pretty much gone, you know, what is a combined CRAO-CRBO? Like, like, how can you, how can you tell? So you'll see, it looks, you know, it's pretty rare to get both. And I've seen reports of actually just reading a report last night of a combined CRAO-CRBO that happened after intravitural injections, I think just with the idea of this rise in the IOP causing this combined CRAO-CRBO. And so you'll have delayed filling on the fluorescent angiogram. And then you'll also have a delayed circulation time. Often you'll acutely see a cherry red spot, but it will be associated with vascular tortuosity and retinal hemorrhages. And then the layers of all layers will be pretty ischemic on an OCT down the road.