 So, today we're gonna do retinal vascular disease, not including diabetes. I think Emmy has the diabetic lecture. So this is really two parts this week and next week. So, today we'll get through vein occlusions and arterial occlusions, and then next week we'll talk about some more of a hodgepodge of different vascular diseases, ocular, schemic syndrome, hypertension, sickle cell. So, to start with central retinal vein occlusions really, the main signs you're gonna see clinically, you're looking at four quadrants of dilated tortuous vessels with optic nerve edema, four quadrants of intranetal doppelgut hemorrhages, and then you'll often see macular edema. We break up central vein occlusions into the non-eschemic and the ischemic type. Non-eschemic is a milder form with better vision and these can resolve on their own without any treatment. And the ischemic form is much more severe, less perfusion. Typically we say more than 10 disc diameters of non-perfusion. Often you'll see a relative afferent pupillary defect, but not always. And the ischemic variation has a higher risk of neovascular complications and 60% will develop neovascularization without treatment. So, these are just two funnest photographs comparing our non-eschemic and our ischemic central vein occlusion. On your left, you'll have the non-eschemic form with the dilated vessels or tortuous and engorge. You can see four quadrants of intranetal hemorrhages, some optic nerve fullness and hyperemia. And then on the other side, there's the more severe ischemic variation with very engorge dilated, so I'll just use my pointer. You can see how dilated and tortuous these vessels are. Severe hemorrhages with macular edema, cotton wool spots and full-minute optic nerve edema. Looking at the cross section of the optic nerve and the vasculature, the central retinal vein occlusion occurs from thrombosis of the central retinal vein, just add or posterior to the lamina cabrosa. Interestingly, when we talk about a hemirentinal vein occlusion, it's an anatomic variation where the superior and the inferior retinal arteries meet, or veins, excuse me, meet posterior to the lamina cabrosa, and one of them becomes occluded posterior to the lamina cabrosa. So that anatomic variation occurs in about 20% of people and will spare a portion of the retinal vasculature. So here's a photograph of a hemirentinal vein occlusion. It's obviously much more severe than a branch vein occlusion, and you can see that this area of the retina is spared, but this large area is involving, and so that's actually more, we classify it as a central retinal vein occlusion and our management kind of is a combination of both. It's pretty uncommon to see a hemirentinal vein occlusion, but they're out there. So our risk factors for central vein occlusion, the biggest risk factors are age, hypertension, diabetes, glaucoma. If you don't have one of those, then we need to consider a hyperquaggable state and consider a workup and also look at their medication list. You can often see these in younger women. If they're on oral contraceptives, you'll see a vein occlusion in those people as well. And then, so what I'm gonna do, I'll talk about central and then branch vein occlusions and then we'll talk about the studies altogether because a lot of the studies kind of go together pretty well and we'll talk about treatments of both of them together. So a branch vein occlusion is caused by a compression of a vein by an artery in that common adventitial sheath and so usually you'll see this when the arteries are laying on top of the vein and then that compression leads to a thickened arterial, that thickened arterial wall is gonna compress the vein, lead to turbulent flow, endothelial damage and thrombosis. If you don't see it in an AV crossing site, you wanna consider an inflammatory cause. So this is kind of your typical fundus appearance of an acute branch vein occlusion. So you can see the compressions occurring right at this AV crossing site and downstream of that intra-retinal hemorrhages, cotton wool spots, significant macular edema. Our risk factors for a branch vein occlusion, typically patients are in their 60s, hypertension, cardiovascular disease and an increased BMI at age 20. You'll note that these are not on our central vein occlusion risk factors. The other thing that's different between branch and central retinal vein occlusion risk factors is that diabetes didn't make it as an independent risk factor from the eye disease case control study. So that's a pretty typical OCAPS type question. So just comparing the two, the branch vein occlusion, the different risk factors, cardiovascular disease and the BMI at age 20. And then for the central vein occlusion, diabetes is on the list. So if you see a PRBL and the only good risk factor or thing they have to say to you. I don't do it. And that's okay. Yeah, it's just statistics I think. You see it in diabetic patients, but it just didn't make it as an independent. But I don't do a whole big work up if they're diabetic and they have a vein occlusion. Maybe some people will, but I don't. But for OCAPS, it's different. So when you're evaluating a patient with a vein occlusion, your basic exam is really gonna lead you down your prognostic predictions for your patient. So the vision is probably the biggest factor. Worst vision is gonna do poorer overall and less likely to have a good vision down the road. An afferent pupillary defect. If that's present, they have a worse prognosis as well as an increased risk of neovascular disease. Gonioscopy should be done at that first visit looking for subtle neovascularization of the angle and the iris and then every month. What is it? And then at that first visit, you wanna measure the intracular pressure and look at that closely because if they have early neovascularization of the angle, they can have early glaucoma and that would affect your treatment. You'll do a dilated exam, fundus photography, florectin. The florectin can be really helpful in differentiating a vein occlusion from ocular schemic syndrome and then your OCT will all be done at the first visit and then monthly thereafter. So when you're seeing those patients for the first time, obviously you wanna address the eye but then you need to look systemically at what else is going on and what you wanna do as far as work up. I typically will check the blood pressure in my office and if it's high, it's really high, I've sent patients to the ER, if it's moderately high to the primary care doctor, sometimes within that day or that week if it's pretty severe and then if it's not high then you've gotta think well, what kind of work up do we wanna do and who's gonna do the work up? Is it gonna be me or am I gonna work with somebody else to do it and I've done it both ways. If they have glaucoma or if they look like they're at risk for glaucoma then I work with their primary eye doc or get them to a glaucoma specialist to see if that's a risk factor. For your OCAPs, the work up should be done if patients are presenting with a vein occlusion and they're younger than 50 but I've worked up people that are older that have no risk factors too. So this is kind of your standard hypercoagulable work up. These are the more common things, this is what I would typically order as kind of a starting point if I'm doing the work up. These defects are less common and I don't typically order those but I've seen them ordered by hematologists when they're doing the work up so I kind of leave that to them but I've ordered these not infrequently when I'm kind of initiating the work up. So there's a few different reasons why people can lose vision from a vein occlusion. Acutely you'll see edema, hemorrhage or capillary occlusion. The chronic causes of vision loss are ischemia, edema, they can get subretinal fibrosis as edema resolves, pigment changes, neovascular glaucoma and vitreous hemorrhage. An essential vein occlusion, typically the neovascular disease occurs three to four months after that vein occlusion happens. So just some more funnest photographs to show the difference between an acute and chronic vein occlusion. So this is an acute presentation again at that AV crossing site, downstream hemorrhages and cotton wool spots with this tortuous vessel here. That's what you'll see acutely. And here's another acute vein occlusion. Not as good of a picture. And then this is actually someone I saw this week with a chronic vein occlusion. You can see the sclerost vessel, the floor scene showing floor neovascularization despite this sectoral PRP that's been started. And then one of your kind of tip-off signs is this collateralization that you'll see across the temporal raffae out here. And that'll kind of clue you into that they've had an old vein occlusion and that's pretty typical. And this is another patient of mine that's had a vein occlusion for 10 years. And you can see this kind of pruning here and then the downstream, this vessel's dilated and tortuous but this collateralization that's occurring and the kind of pruning of that vascular tree is pretty typical of chronic changes from a vein occlusion. And this is a nice angiogram showing those collateralization that can occur just outside the foveal vascular zone and this can actually lead to resolution of macular edema and a better visual prognosis once this is developed. So really all of our treatments are guided by some pretty large clinical trials. The first of which is the BVOS and the CVOS. So the BVOS came out in the mid-80s, kind of set our gold standard of macular grid laser for branch vein occlusion and macular edema. CVOS came out later in the 90s and then these later studies which are guiding our more current regimens, the SCORE BRAVO, the SCORE BRVO and the CRVO study looked at triumcinolone, the OZARDX trials, I don't think anyone would ever quiz you on Geneva but the OCAPs are gonna quiz you on BVOS, CVOS because those are really landmark trials. The SCORE is a pretty landmark study and then BRAVO Cruise is really where we entered the anti-vegetarian that was with the rhinobizumab. So the highlighted ones are the ones that you would see kind of popped up, I think, on any testing. So, BVOS really was looking at two questions. The first question they were trying to answer, is there a benefit to argon macular grid for macular edema secondary to a branch vein occlusion? 139 patients were enrolled and like I said, this was in the mid-80s. And then the second question was, is there a benefit to sectoral PRP to prevent neovascular disease? So the results found better visual outcomes in people in the group that had macular grid. The visual acuity range for all participants was 2040 to 2200. Treated eyes, 65% improved two lines compared to only 37% in untreated eyes. And treated eyes were more likely to have vision better than 2040 at three years, 60% compared to 34%. The treatment, it's important to note, began three months after presentation. So you weren't doing laser through all the hemorrhages that they presented with. I mean, now we don't do it anyways that quickly. We're doing anti-veg Fs, but at that point, you were letting those initial acute hemorrhages clear and then doing laser after that hemorrhage cleared. As far as the question of PRP and neovascular disease, they found that sectoral PRP decreased risk of hemorrhage from 60% to 30% and recommended sectoral PRP being started after development of neovascular disease. The CVOS came out later in the 90s and really tried to answer the similar questions to the BVOS study. Can photocoagulation decrease neovascular disease and does macular grid decrease vision loss from macular edema? This study also really defined a lot of our natural history from central readily and occlusions as well. So the findings, they did show that macular grid reduced macular edema, but there was no associated visual improvement with that and that PRP failed to reduce the risk of neovascularization. In younger patients, there was a trend toward better visual cuties, macular grid, but no improvement in older patients. So from these two studies, our laser recommendations that really kind of set our standard of care was that macular edema with a branch vein occlusion should be treated with grid pattern after three months and then neovascular disease should be treated with sectoral PRP after the neovascularization develops but not prophylactically. And then similar for CRVO, neovascularization treated after it develops not before. There's no reason to try and prevent it with PRP. And then there was no reason to do macular grid for macular edema in central vein occlusions. So that's what we did till the early 2000s, really when things started changing, really the limits of laser, 35% of patients with a vein occlusion don't respond. The vision is better than untreated, but it's not great vision. Patients are really 20, 40, 20, 50 and then there was no improvement really with a central vein occlusion. To really the best predictor of final vision from a central vein occlusion is what their presenting vision was. So if they're better than 20, 40, they're gonna stay in that range most likely. If they're worse than 20, 400, they'll probably stay that way. This is based on the natural history from the CBOS data. And then in that 20, 50 to 2200 range, a third will get better, a third will get worse and a third are gonna stay the same. So in like 2000, early 2000s, people started doing intravitural steroids and people were having a lot of anecdotal improvement with intravitural steroids and that led to the SCORE study. So that stands for standard care versus corticosteroids for retinal vein occlusions. So there's the SCORE BRVO and the SCORE CRVO study and the primary endpoint was the percentage that gained three lines or more at 12 months and patients were followed for 36 months. So for the SCORE BRVO, they compared the control which was observation with rescue macular grid versus a one milligram intravitural triumcinolone group and a four milligram intravitural triumcinolone group and there's really no significant difference between all three groups and there were more complications with the intravitural triumcinolone group. Intracular pressure was higher, requiring medications, cataract surgery was more common and so the final result at 36 months was that laser was better than intravitural triumcinolone and macular grid kind of remained our standard of care at that point after that study came out. The SCORE CRVO was a little bit different. Same kind of setup, it was one milligram versus four milligrams of triumcinolone and then the observation group, there was no laser for that group obviously and the triumcinolone groups did better than observation with around 26% gaining 15 letters. So at that point, our standard of care for CRVOs was to start triumcinolone, intravitural triumcinolone to treat macular edema. And then shortly thereafter, OzardX was approved, OzardX is an intravitural delivery device of dexamethasone that lasts anywhere from one to three months and a really large study found significant improvement in vision in the OzardX group and then not too long after that we really kind of got our anti-vegete studies. People were doing it before the, they were doing it off-label before it was FDA approved obviously, but then the anti-vegete studies came out. Obviously everybody knows that VEGF is a key mediator in angiogenesis and vascular leakage and so that's the idea behind it, working in vascular occlusions and macular edema associated with that. So our anti-vegete studies that you would need to know would be the BRAVO and CRU studies. They were both Genentech, Sponsor, Granibizumab studies, phase three trials and they studied Granibizumab 0.3 milligrams versus 0.5 milligrams compared to sham and the treated groups approximately 50 to 60% of patients gained 15 letters and those in the sham group, 54% required rescue grid while in the treated group only 18 to 19% required grid laser. And the CRU's trial pretty similar results, kind of the same setup, 0.3 compared to 0.5 compared to observation and the primary endpoint was the change in vision from baseline to six months, 46 and 47% gainers compared to 17% gained 15 letters in the sham group and the improvement was pretty rapid in the treated groups patients just one week after the first injection had already gained nine letters and overall over six months the treated group gained 12 to 15 letters compared to 0.8 in the sham group. So it was pretty exciting to actually be able to offer some improvement for patients. So this is really the big shift in our standard of care is where we started doing anti-vegete agents for branch vein occlusions. Really the biggest drawbacks are the half-life of the medications and the need for continual injections. You guys are doing it at the VA and in all our clinics, it's hard to get people potentially off the injections. It seems like they'll need injections at least for six months and even up to 18 months on average. I have patients where I've been doing injections for three, four years and I can get them to eight weeks but if they go nine weeks they're worse and so I just have to keep doing it every so often I'll try and spread them out again but some people just need that continual injection. A flib receptor ILEA is also approved for branch and central retinal vein occlusions, pretty similar results and similar studies. I would be surprised if anyone's gonna kind of, these weren't really landmark trials, Galileo and Copernicus but they did the Galileo, I think ILEA got its approval for central vein occlusions in 2012 and then the branch vein occlusion came later, that approval just happened in 2014 but very similar results to the other studies. Obviously most of us are really starting with Avastin as an off-label medication. There's not a really landmark huge trial for Avastin and vein occlusions, it's really based more on a smaller case series and retrospective data and kind of extrapolating AMD trials and the CAT trial to vein occlusions. So just to look at a few kind of patients I've seen recently, this is a young, I think he's like 35, your old man who came into me with some weird kind of patchy network in his vision, had been going on a few days and this was his funnest appearance and this was his fluorescent angiogram so you can see his pretty significant macular edema, tortuous vessels that are dilated with four quadrants of blot hemorrhages, really no macular edema. I think he was 20, 30 at this point. Since he was young, he has a history of non-Hodgkin's lymphoma, had a big workup, MRI, whole thing and everything's come back negative but I kind of worked with a hematologist for that because of his other medical problems and I've been seeing him monthly for three months now and he's really improved quite dramatically in his visions 2020 and he's doing well. So I never really found a cause which is kind of weird, you know, but he's doing pretty well and this is obviously somebody that's doing a lot worse, a very severe ischemic CRVO and an older patient of mine and that was what he presented like, I think his vision was count fingers at one foot or something at this day and this is OCT. I have to have one of you show me how you grab OCTs off of axes, is it? Yeah? That's what I did but it's kind of, not great quality. Do you do a screenshot, that's what I was, yeah? Do you, okay. Anyways, so this is what OCT looked like, you know, horrible macular edema. I started with three of Avastin, after the three of Avastin, this is what he looked like so he's still kind of count fingers, not doing great. So I switched him to ILEA and after three ILEA this is what he looked like and he's, you know, 2070 and now I kind of do his maintenance, I did his maintenance injection yesterday and he's, you know, kind of holding that 2070 vision. He's not 2020 or 2030 but he's, you know, appreciably better than he was before he came in but I can't go more than eight weeks between his injections yet but it's been nine months so maybe I'll be able to get him out down the road, hopefully. So for Avain occlusion, for treating the macular edema we typically start with anti-vegetables, I'll start with Avastin, if they don't respond then I'll switch them and if you can get them. So the macular edema's pretty much resolved or pretty stable, then you can try spreading them out. Often if I feel like they're not getting a great response to the anti-vegetables then that's when I bring in the intervitial steroids and the ozardix and then not frequently but sometimes you'll try and augment with laser grid, especially patients that seem like they're gonna have poor follow-up or they're not gonna come back or if they're just not doing well with the injections you might add in some grids still. Do you use the steroids with anti-vegetables? That's a good question. It kind of depends on what the macula's looking like and sometimes I'll do a combination of both. If I feel like I can get more edema down with the steroid I'll add that in and keep the anti-vegetables going. And some people who could just do steroids and you might not need the anti-vegetables, it kind of depends on what they look like. It's not like a set protocol, I would say for that. But I probably don't do it as much as maybe some of the other providers. I like it but I reserve it for people that are pseudophagic that don't have a risk of glaucoma or don't have any really glaucoma factors. I feel like most of my patients respond pretty well to the anti-vegetables agents but it seems like they need them maybe every eight to 10 weeks. If they're not doing well then I add in Ozardx or an IVT and kind of see how they're doing but I don't do it quite as much as the anti-vegetables for sure. But it can be really helpful and some people really need both that steroid effect and the anti-vegetables effect. And then for treating neovascular complications really PRP and then plus or minus anti-vegetables agents if they have really fluorine neovascularization. You know often I'm working with the glaucoma team to kind of treat that and they like the anti-vegetables to try and save the angle especially if they still have an open angle with neovascularization they like that rapid kind of response resolving those vessels so that they can keep the angle open. If they have a closed angle then often the glaucoma doctors are putting in tubes or valves you know to help with the glaucoma. The nice thing about the injections is you can really see a pretty impressive response within 24 to 48 hours as far as neovascularization of the iris. The PRP obviously takes longer several weeks even a few months to see the full effect. So kind of depending on how severe the neovascularization is if it's on the milder side I'll probably just start with PRP but if it's pretty fluorid then I'll combine and do both of them. So any questions about vein occlusions? We'll move on to artery occlusions. So for a branched artery occlusion you'll see this edematous white appearance of the retina and the distribution of the artery. Usually patients will complain of a field defect that's pretty stable. Really you know when you're looking at a white retina there's not a whole lot of things that can cause white retina you're either thinking infarctoschemia, edema, you could have infection or infiltrate or potentially myelin, commotion but there's not a whole lot of things that are causing a white retina. The causes of an arterial occlusion most commonly especially in branched retinal artery occlusions is emboli either from the cardiac or carotid source. Other things to consider would be vasculitis, coagulopathies, trauma, collagen vascular disease and more rarely things like buchettes or leukemia. You know as far as looking at an emboli and trying to decide if it's coming from the carotid or is it coming from the heart, there's been studies, people can't really just look at an emboli and say oh that's a heart and I don't think that's very accurate and I think there's been studies that have looked at that. You can't just look at it and say where it's going to be coming from. I think it's pretty important though that these get a pretty aggressive work up through their primary care doc or their cardiologist and often kind of working with them to get that done. So just examples of the emboli, this cholesterol or hole in horse plaque is often at this bifurcation of a vessel, platelet fiber and you can see pretty well it fills the lumen of the vessel for several disc diameters and then the calcific embolus which is actually more commonly at the optic nerve head. So the hole in horse plaque or the cholesterol embolus is at this bifurcation of the artery, it's very refractile and this is coming from the carotids. It really is pretty rare for this to obstruct flow enough to cause an arterial occlusion and then the calcific embolus, you'll typically see that right at the optic nerve head and you can often see this associated with the central retinal artery occlusion. It's this more chalky white appearance and that's coming from the heart. The platelet fiber fills the vessel completely and can lead to an arterial occlusion. So central retinal artery occlusion patients usually come in with sudden and complete loss of vision with no pain. The retina is very edematous. You get this cherry red spot which do you guys know why you see the cherry red spot? Yeah, you're seeing that carotidal flow kind of through that foveal vascular zone exactly. The visionless is usually permanent. You rarely see people get better from this. Usually that kind of retinal edema and whitening will resolve over a month or so and then you're left with these really a pale optic nerve and really attenuated vessels. If they have NLP vision, it's not gonna be a central retinal artery occlusion. NLP vision is gonna be a complete ophthalmic artery occlusion or carotidal occlusion. So looking back at our cross section, the etiology of a central retinal artery occlusion is thrombosis here at the lamina crevosa. This kind of shows where a set cellular retinal artery is arising from and it's coming from a separate vascular source. It's coming from the posterior ciliary artery that some cellular retinal arteries present in, I think it's about 30% of eyes have a cellular retinal artery and if you're lucky and it's affecting the macular circulation, you can get some vision that'll be preserved. You know, when you're looking, oh, this shows the, so this shows where that cellular retinal artery's coming from here. If you have an occlusion of the cellular retinal artery since it is coming from that carotidal source, you, it's strongly associated with giant stilarteritis so you wanna make sure you're working that up. So here's some examples. This lucky person has a cellular retinal artery preserving this area. Unfortunately, they still have a cherry red spot so their vision's probably not great but they might be able to get some vision out of this area. And this person has a cellular retinal artery occlusion in the setting of a central retinal vein occlusion. So I think the most important thing when you're looking at artery occlusions is really looking at the entire patient and their risk factors and their medical evaluation. There's a high association with cerebral infarcts and an increased risk of mortality. So, you know, this is kind of the protocol that, you know, Dr. Katz worked with the stroke team to set up that we have at the Moran. You guys are probably all pretty widely familiar with this. Does it work pretty well? Yeah, because it's interesting, you know, as like a retina specialist, often like we're seeing the arterial occlusions later, we don't see them in our clinics right that day. Usually they're going to triage or you guys, I think, and so it seems like you guys, at least I haven't really had to facilitate this much since it's been implemented. But the idea is that if you have an arterial occlusion that's occurred within a week, calling the stroke team and getting them admitted to inpatient neurology for a workup, but you guys haven't had much that's been working pretty well. Oh, good, okay. Does the VA do the same thing? Okay, well that's good. So then if it's more than a week, then we start the workup. The workup should include an MRI, an echo, carotid dopplers, you know, some blood work and then starting aspirin and statin, if indicated. There's really not a good treatment for central retinal artery occlusion. You know, people have tried a lot of different things when there's anecdotal reports of some things working. People try ocular massage. So what I would do for that is just put, like a gonial lens on the eye and kind of gently massage the eye. The idea is that you could potentially dislodge the embolus further downstream and maybe get some improvement in vision. I've tried AC TAP, some people do hyperbaric oxidant treatment. There's always anecdotal reports of some things working, but there's really nothing that works great. I've seen reports of people doing yaggles or to an embolus and breaking it up and restoring blood flow that way. You've never seen that? I've also seen, you know, big complications from that, big hemorrhages. Yeah, exactly. And then there's, you know, reports of people doing catheterization of the ophthalmic arti with TPA, with some. Did you? I thought they stopped doing it. Yeah, they said that their policy wasn't to do home. Yeah, that's right. But then I think maybe it just depends with the exempting of neurologists. Oh, that's true. Dr. Joe Witt, like all Dr. Warner, they did it. Oh, really? How's the patient doing? Sure, I don't know. Yeah, I'd heard, I thought a grand round someone said that they stopped doing that. Their policy was to not? Yeah. So it just depends on the neurologist or the interventional radiologist? I think the neurologist, because the neurologist can't flip the phone at all. Oh, okay. Or it's, you know, it's responsible for, you know, the near-accompaniment. So neovascularization is less common, but if it happens it occurs, or it's less common than a vein occlusion, but if it happens it occurs quicker, usually within one to two months. And then just briefly, you know, this is rare. I think I've seen this once, an ophthalmic artery occlusion. Vision will be light perception or NLP. The fluorescent will show no caroidal or retinal filling and you won't have a cherry red spot. And patients who have had an autopsy done with giant cell arthritis, 76% of those will have ophthalmic artery vascularitis. Other causes could be internal carotid dissection, mucor and complications of surgery. Gosh, we got through everything pretty quickly. This is just interesting, to me this is interesting. So I don't know if I can click on this if this will work. So when I was a resident and fellow we were doing radial optic neurotomies for this. I don't know if you've seen this video. It's like, I did this once when I was a fellow, but you basically just take this MVR blade and pierce the optic nerve and you go down to, you know, this, about this depth. I did it a couple of times. We don't do that anymore. Now that this was before we were really commonly doing anti-vegetables. Yeah. So people have tried various surgical interventions for vein occlusions, arterial occlusions and with some success, you know, another thing people do is try and create these retinal chorital anastomoses and they can do that similar to with an MVR blade or with really hot laser. And so what you'll do is say you have a vein occlusion and you kind of pierce the retina down to the depth of the choroid and several quadrants and the idea is just to induce collateral blood flow and, you know, you see reports of that working well, but it's hard to know because some people would get better potentially anyways, but, you know, the patients that I remember doing those radial optic neurotomies were really horrible, ischemic CRVOs with count fingers vision, but, you know, they didn't do great after the surgery either, you know. So I think things are a lot better now. The retinal vange thotomy, people try and kind of, if you have like a branched artery occlusion with an embolized pupil, try and kind of thread a canula or kind of use an MVR to kind of dissect the sheath between an artery and vein and kind of relax that and allow blood flow, but it's not commonly done. So I think, you know, probably the important things are that, you know, obviously for OCAPS it's gonna be the studies, you know, SCORE is really a critical study, BVOS and CVOS, and then the CRU's BRAVO studies are what you really wanna make sure you know. Do you guys remember which one was the one that set macular grid as the standard for BRVOs? BVOS, yeah. And then what was the ranabismab trial for BRVO and CRVO? BRAVO and CRU's, and then the SCORE, which one's SCORE? Yeah, yeah. So SCORE, there was, you know, for BRVOs, no reason to do intervitual trimes in alone, and then, but for CRVO, it showed a benefit. Trying to think, what else? I think the other thing was, which are you more likely to see neovascular disease develop with a CRVO or a CRAO? Yeah. And the timing after CRVO, I don't know if you remember that, it's usually three to four months, yeah, but a CRAO, you'll see it within a month or so. So it's more rapid, but less common. Yeah, Nico? I remember the studies, but the antibodular studies, did they compare it instead of sham to the laser treatment? So they don't, so what they did is they have sham injections, but then if the investigator felt it was warranted, then they would get rescue grid laser. And so I put it in here, the rate of the person, I think I put it in how often they needed rescue grid. But they- Well, what's the reason they didn't compare it to that? Yeah. Well, I mean, essentially they did get grid. You know, so grid laser doesn't start till three months after the vascular occlusion, right? But you can start anti-vegfs right away. So the patients were basically getting intravitual injections or a sham intravitual injections for three months, and then at three months, if they still had macular edema, then you could do a macular grid. Does that make sense? Because that was kind of our standard of care. So I think with, if I put it in here. When do you use it when they're all having macular edema in the first time? Yeah, for, yeah, we were treating macular edema for the vein occlusions. We weren't just treating the vein occlusion. It was only indicated if they had macular edema associated. So for Bravo, it was 54% and the sham group required grid. And then the treated groups, 18 to 20%. And then for Cruz, there's no macular grid. So they were just getting pure sham. Any other questions? Good. All right, so next week we'll do, next week's kind of like a mix of weird vascular topics, but I'll try and pull it together. It doesn't have a nice flowing theme. Well, thanks for coming early.