 So the primary and secondary vitreous, which then involutes for the most part but then can have some remnants and that's according to some hypotheses why there is a snowbank. The inflammation occurs in this zone here, the anterior retina, the posterior ciliary body. But the amount of the vitreous cell that you see is all over the, it spills into the vitreous in its entirety. So you can have vitritis that's posterior and anterior and then you have consequent effects on the retinal circulation and we'll talk about peripheral non-perfusion. We'll talk about CME, etc. I don't think this is the Catherine who edits. There you go. Sorry, missed that. So here's a 15-year-old male referred for recurrent vitreous hemorrhage in the setting of recurrent banuviatus. Yes, or he's been told he has banuviatus. It's one plus cell in the ESEE, one plus vitreous cell in haze, optic nerve, edema and hyperemia, and peripheral retinal neurovascularization. So no view. So what kind of uveitis does this kid have? So he's got... What do you not see that would make it banuviatus? I don't see any like retinal or coroid. Yeah, so in order to have banuviatus or posterior uveatus, you need to have retinal or coroid allegiance. So this would be intermediate uveatus. So what would you do next? Eat skin. Okay. Yeah, you want to make sure that the retina is not detached. If you do have a view or if you want to look at the other eye, what could you do? You want to see what's going on. For instance, he's got cell in the other eye. If you don't answer your grammar. So why do patients with intermediate uveatus develop vitreous hemorrhage? You get neurovascularization. And why? And because of retinal and capillary. So there's two reasons actually. We'll go through this and have a couple of examples. But there's people who develop peripheral retinal non-profusion. But then the other reason for neurovascularization is simply inflammatory mediators. So VEGF is actually an acute phasor agent and you can end up with neurovascularization in response simply to inflammation. And it's important to make that distinction. So people often come in with floaters, decreased vision, vitreous cells for vascular sheathing, snowballs, snow banks. What are snowballs, Marshall? The like the posits on the partial plan of that or not great. So they're in the vitreous, little white capacities within the vitreous. They're actually the granulomas. They're Langerhans type granulomas giant cells. That's what you'll see. It's a snow bank. That is when it's on the partial plan. And what is it? So it's a collection of microcures. It's gliosis on the partial plan. Visions often develop cataracts, CME, and we'll talk about the common causes of vision loss in these patients. It accounts for about four to eight percent of referrals to UVA's practices. That kind of holds true in my practice as well. 25 percent of the UVA's in children is intermediate UVA and it's most common between 10 and 40. However, you can see it later on in life. But when you see de novo intermediate UVA's in an older person, you have to think about other diagnoses as well. And it's important to do retinal imaging to make sure that you're not dealing with opposed to your UVA's because sometimes disease such as bird shot, even the lymphoma can masquerade early on as an intermediate UVA's. Some patients are asymptomatic. Most patients present with blurry vision of fluors. Vision is usually 20, 40 or better in a presentation. You'll see pictures cells, no balls, no banks. You get dyskidema in about half the patients who come in. That's why a lot of intermediate UVA's comes to me from neuro ophthalmology. They say this is not optic neuro, this is not an optic neuropathy. This is secondary to vitritus or to intermediate UVA's. So Marshal, what do you see here? Snowballs. Where are they present? That's right. And then you see the snow bank. Sometimes when you want to look for a snow bank, some of the best ways to do it is to have a patient look down. Without a lens, use the indirect and you'll sometimes see this white snow bank. Very stark. You can have peripheral vascular anomalies, very vascularitis, peripheral non-profusion, vascular leakage, neovascularization of the snow bank or elsewhere. Mike, what do you see here? It looks like there's vascular leakage there. So this is a 21 year old with vitritus cell. So what does this look like to you? Is this vascularitis or is this, what if I show it to the other eye? What do you see over there? There's a, it looks like there's like a detachment there. No, no, it's just some blood. So what you see is, you see vitritus, hemorrhage, you see kind of this very phlebitis and vitritus cells. So this is intermediate UVA's and sometimes it can be very, very, the vascularitis component can actually be quite prominent. And that's actually one of the dilemmas in defining vascularitis versus, versus, yeah, so is this vascularitis or is this intermediate UVA's? Sometimes the vascularitis can be bad enough that it looks like it's vascularitis and not intermediate UVA's. The fact that this happens is why intermediate UVA's has all these peripheral vascular anomalies. Arianna, what do you see here? So this is a 17 year old girl who presented to us with vitritus cell and floaters in loss of vision. I see white exudates and it looks like there is a elevation all the way up to the macular, right? So this is actually a patient with intermediate UVA's who developed another kind of peripheral vascular anomaly called a vasoproliferative tumor. It's actually very common in intermediate UVA's where you have kind of this veg after of a mass of anomalous vessels and adventitia that leaks and causes this sub-retinal exudation. So you can in fact get, you know, exudative or you're almost, you have kind of an exudative retinal detachment in patients with intermediate UVA's who happen to have peripheral vascular anomalies and you can see that here as well in her other eye. So that's a, that's a vasoproliferative tumor with exudate heading towards the macular. Rachel, what do you see here? So this is a 22 year old male also with floaters. I thought that was vitritus hemorrhage as well but it's coming directly from the disc. Yeah, so where do you think the neovascularization that's causing this hemorrhage is on the disc? So if you can actually get NVT, what would you, what would you request as a test if you saw something like this, an angiogram? Yeah, so here's the angiogram and you can actually see this tuft of neovascularization coming off, off the optic nerve. And what you really want to know now is, is why is there neovascularization of the disc? This is a patient with intermediate uveitis. Why is there neovascularization of the disc? And we talked about two possibilities, number one peripheral non-perfusion and number two just inflammation. So here's the other eye. So it's an opto study. What do you see here Brad? Peripheral leakage. Right, and? Non-perfusion? Not so much, but definitely there's leakage of the neovascularization. Oh, okay. And here's the other eye. I'm sorry the image is not great, but take my, take my word for it, there's no peripheral non-perfusion, but you do see neovascularization of the disc. So in this case you would treat, how would you treat this NVT? Well, how would you conventionally treat NVT say in diabetics? Do you like BEDGEF or you can do PRP? Yeah, your first answer should be PRP. I know a lot of people are talking about BEDGEF for neovascularization, but in general for diabetes stick with the basics because that's what they're going to test you for on the boards. But in this case, did you see any utility being that there's no non-perfusion of doing PRP? No. Probably not. So how would you treat this? How would you treat the underlying disorder, whatever it is? Yeah, so you treat with steroids or immunosuppression. So certainly you can have patients where there is a lot of peripheral non-perfusion. This is a case where there's kind of these non-leaky shunt vessels and peripheral loss of circulation here and here, and this can certainly be a cause of neovascularization. In this case, you want to both immunomodulate the patient, but you also want to do some laser to the periphery versus this one where there's neovascularization of the disc. And although you don't see peripheral pictures here, there was no non-perfusion and these ones you immunomodulate. And really aggressive anti-inflammatory therapy is the way to go. So there's no role at all for anti-BEDGEF in this? Well, it's remarkable how quickly this neo can regress just if you put the patient on steroids. Now, steroids do have an anti-BEDGEF action. There is some evidence that steroids can diminish the effect of BEDGEF, but that's only one of many roles of steroids. What is a peripheral non-perfusion? Is it permanent or can it recover after the inflammation or the primary radiologist treated? So conventionally, they say that retinal vascular non-perfusion is irreversible, but there is some evidence now, especially in the diabetic studies, that you can have vascular remodeling and reperfusion in certain parts of the retina. So is it fast enough and is it complete enough to prevent the need for laser? Probably not, but there is some evidence that that can happen. These are rare diseases, so there's probably not enough study on revascularization. So when you see neo perform an FA, if you see a capillary dropout, treat with PRP or with peripheral laser, and if there's no capillary dropout, consider immunosuppressive therapy. If you have peripheral traction as a result of neovascularization or vitritis, then consider either vitrectomy or doing cryo to the area. And of course, if you see exudations or an exudative retinal adjustment, first put the patient on steroids, then take the patient back for potentially doing some cryotherapy. You might have already said this, but why do they get MBD? Like, is it just because the inflammatory response sends out the Jeff as well? Yeah, and it's like the same molecule, just different mechanism. Just a different mechanism. It's not from non-perfusion, it's just from inflammation. Did you also make the pink border? Oh, because those were the ones that I edited. Oh, I get it, okay. So what is the primary cause of vision loss in intermediate IVitis? Very good. What are common complications that require co-management with another sub-specialty? Well, you're not a specialist, too. That's true. Or like an RD, I didn't put that one either. Yeah, that too. And other things. You're just assuming that you're too free. I'm just assuming that all of you are going into retina. Antico-UVitis. Maybe you do some long calls. You don't need to have any money. All right, poor control of information can lead to vision loss from CME most commonly. And you know, CME needs to be treated fairly aggressively because it can lead to immaculatrophy. Unlike diabetics where you can maybe let a little bit of CME slide, a child with intermediate IVitis needs to have that treated. You can have vitritis and conventionally vitritis that makes the vision worse than 2040 is it needs to be treated, although that's negotiable. Vitrious hemorrhage can also be an indication for treatment. Cataract is quite common. Most of your Zinicae and Psycletic membranes are less common, but can cause severe vision loss. And if you have patients come in with Psycletic membranes and there's aggressive variant of intermediate IVitis, then that needs to be treated quite aggressively. peripheral retinal detachment and Psycletic membranes with hypotony are really bad prognostic signs. And if untreated, that can lead to tysis. Uh-oh. I'm about to lose. Can I put this in anywhere? Or does it have to be there? So retinal detachment can be tractional from Psycletic membranes or virtual retinal fibrosis. It can be cirrus or exhalative when you talk about VPDs or even just very, very, very, very, you know, large snow banks. And retidogenous, because you do have peripheral retinal, the anomalies and patients who have intermediate IVitis and end up with detachment, you would want to do a buckle and you would want to consider oil. What's going on here? Baby bear. Yeah, okay. There's an IOL up there. It's covered in it. No, it's the same thing in front of everything else. So there's an IOL, trust me. But what's behind the IOL? It's a dense kind of white plaque. So that's a Psycletic membrane. So in its worst state, you can have this sheet of fibrosis that goes from Psycletary body to Psycletary body, crosses the plane. And this eye is hypotenuse because of that, because detaching the Psycletary body becomes contract and fibrosis. So glaucoma is seen in about 8% of these eyes. So it's not as common as say in the glaucoma that you see in aggressive, untreated anterior IVitis. Some of the glaucoma in intermediate IVitis can be steroid related. So, you know, it's very important to check to see if patients are in fact steroid responders before you give them an injection of something. I often do this by putting patients on topical steroids first. Always do gonioscopy when you see glaucoma or at least ocular hypertension in patients with any kind of UVitis that you're treating with steroids. Why? Because what are the possible causes of high pressure inside? We talked about this last time. What can cause high pressure in UVitis? So, yeah, we're from Antiocinicae with fibrosis along the trapezoid. So trapezoiditis, and what you're talking about, what kinds of UVA it is there? So, anti-UVAD is most common in infectious varicillin zoster, herpes simplex CMV, but you're also, there are other things such as toxoplasma and non-infectious things such as sarcoid that can cause a hypertensive UVitis. Similarly, patients with sarcoidosis and that as a cause for intermediate UVitis, they can have high pressure as well. What are other causes for high pressure in UVitis? In intermediate UVitis. So, supposing you've treated the patient with steroids, especially young people, young people are particularly prone to steroid response, and often you have children who you've treated with oral steroids, even they can come in with high pressures. The effect is not as pronounced as that seen in injected steroids, but you can certainly see with oral as well. As I said, OCD is the most common cause of vision loss, and the concordance between OCD and FAB and CME is only 7%. Now, this study was back in the mid, about 2004-2005, so since then OCD has changed a little bit, and that concordance level is probably now disparate, is it probably closer together, but know that not all CME is registered on OCD, and it's sometimes just angiographic. So, here's an example. So, what do you see here, Marshal? This is a pretty normal looking fundus, right? Maybe a little bit of haze. Does this normal? Looks pretty normal. Okay. And that's the FA. Yeah. So, this patient has a pretty normal structure, but the vision's decreased, but the OCD is normal. So, this is a patient with angiographic CME only, with a decrease in vision. So, not all CME is evident. Now, that's more common in young people, because young people have better compensatory mechanisms, where you can have leakage, but not actually develop CME. So, there's a breakdown in the inner blood retinal barrier, and there's leakage from macular capillaries that comes early, and then in the end, you end up with actually this leakage and pooling effect, where you have pooling of dye into these cystic intra-retinal spaces. It's petaloid in appearance. Why? You talked about this? Outer plexiform. What is this? It's a chicken. It's a chicken. Don't ask. And there's often a lot of things. So, when you look at intermediate UVA, there's actually a lot of variability in the outcome and in presentation. So, when I see a patient with intermediate UVA, I just generally stratify them into two different kinds. You can either see a patient with mild indolent disease. Sometimes that doesn't need to be treated. And if you look at this study, this is why Jose Felido sometime back in Mayo Clinic is in Olmsted County. So, granted, that population is probably skewed more towards the Scandinavian side of things. But, in this particular study, they found that not everybody needed treatment. So, in this population, systemic steroids were only required in 23 percent. And steroid sparing therapy was only one required sparing therapy out of 46 patients. Now, this seems very unusual. I mean, I think this is an underestimate of what we normally see. I would say I tend to immunosuppress about 50 percent of patients who come in with intermediate UVAs. But if you look at the survival curve, these are patients who remained at 20, 40 or better. Over the course of 15 years, about 40 percent was vision dropped beneath 20, 40. And that was from cataract or CME or others. So, the visual prognosis is relatively good if treated. In this subgroup, probably, I think severe disease was underrepresented. But it's important to know this, to take home from this study, is that sometimes the treatment can be worse than the disease itself. And so, be careful when you see a patient who's about 20, 25, has floaters, a lot of vascular leakage. Maybe hold off on intravitual steroids or sub-denone steroids until you can prove that things are getting worse. So, there's another Catherine slide. So, just shout out inflammatory causes of intermediate UVAs. Now, what if you, the term parisplanitis, and I think we'll discuss this further out in the lecture, but what does parisplanitis refer to? Idiopathic. Right. But it has to be, it has to have two features. Snowballs and snow banks. So, parisplanitis is a diagnosis of exclusion. And a lot of people tend to use parisplanitis and intermediate UVitis interchangeably. That is not correct. So, just remember. But in the other causes of inflammatory intermediate UVitis, what would you think about? So, MS. So, MS, yes. Charcoidosis. What else? GA. GA, generally not. So, GA generally does not have an association with it. I have seen patients who happen to have GA and intermediate UVitis, but it's not considered a true association. So, charcoidosis, inflammatory bowel disease, that's not difficult. MS, like you said, continue. So, remember we talked about tubular interstitial nephritis associated UVitis. And that's usually kind of an indolent anterior UVitis in patients who are between 10 and 16, generally more common in women. Positive urine beta-2 microglobulin. But it can cause an intermediate UVitis as well. That is not entirely correct, although I have seen a couple of patients with urban gas who call urban gas, but had a little bit of vitreous cell as well. That was probably just reactivated intermediate UVitis that wasn't detected before, and patients had cataract surgery. So, infectious TB. So, Lyme disease, I think we forgot to add that to the animation, but Lyme disease over here, don't check for it. So, if the patient has never left Utah and has never been east of eastern Colorado, don't check for Lyme. Because what if you get a positive Lyme for somebody who's lived in Utah their whole lives? Right? So, Bayesian analysis would suggest that if you have a positive test in a low-prevalence area, that it's most likely to be a false positive. So, the positive predictive value of the test is diminished in a low-prevalence area. Whereas if you did check for Lyme disease in, say, Lyme County, Connecticut, then it's likely to be a true positive. So, have I seen intermediate UVitis that was secondary to Lyme disease? Yes. In fact, I've had a roster of 10 such patients in Long Island. But over here, I have a lot of patients who were unnecessarily treated with IV antibiotics, who shouldn't have, before they got to me. But other things can cause intermediate UVitis as well. Bartonella, Doxychoriasis, Whipple's disease, Syphus, of course, TB, although defined intermediate UVitis in isolation and TB is unusual. Hepatitis C has some association with multiple autoimmune diseases, but intermediate UVitis is one of them. So, we've already talked about this, which is most likely to present as unilateral disease. So, you know, herpetic disease can actually cause intermediate UVitis. So, I've seen patients who come in with an anterior and intermediate UVitis with herpetic disease. And this is, when you see an older person with their first presentation of anterior and intermediate UVitis, may or may not be hypertensive. One of the things you want to think about is infectious disease. Now, other infectious disease entities such as tuberculosis, can't present as unilateral disease, but to see intermediate UVitis in isolation is unusual. So, about one-third of patients with intermediate UVitis in various studies has been shown to be associated with systemic disease. In this particular study, Dan at Sarkoid out of 82, six at MS, two had optic neuritis and by extension probably had MS and two had IBD. So, Sarkoidosis will give you posterior segment inflammation in about a-third. It's the most common syndromic cause of intermediate UVitis for granulomatous changes. So, Sarkoid generally presents with snowball-like capacities. Nervascularization of the disc in Sarkoidosis is actually particularly common. Its multi-system inflammatory disease characterised by non-KZ eating granulomas. Most commonly evident as granulomatous anti-UVitis or intermediate UVitis. However, you can have chlorideitis. You can have vasculitis and the vasculitis of Sarkoid is characteristically very vanilla. In this population in Utah, you'd see it most commonly in the Scandinavian, in people of Scandinavian descent, but it is quite prevalent in African Americans and not surprisingly very common in Africans who are in Africa. And there's actually, it's an interesting disease. There's a gentleman by the name of Biswas who does a lot of metagenomic sequencing studies and he looked at Sarkoid granulomas and found the genome of atypical mycobacteria. Does that mean it's an infectious disease? No, but it could be that there's an infectious trigger. So just like with MS, when patients move to Northern Europe from anywhere, the rate of MS goes up. There's some suggestion that this is an infectious trigger and people feel that Sarkoidosis also has an infectious trigger in an immunologically prone individual. In Sarkoidosis you can have hyaluridinopathy, erythinopnodosum, skin granulomas, adenopathy and neurologic symptoms in about 20%. This chest CT, so if you have a patient with granulomus disease and you have suggestion of Sarkoid on your examination, just go for the chest CT because your chest X-ray will not be as revealing as you'd want. In fact, the hyaluridinopathy seen on chest X-ray with Sarkoidosis can be evanescent in about 70%. So the ocular findings or the neurological findings or the non-pulmonary findings in general may be temporarily discreet. It can happen at different times. So the hyaluridinopathy will resolve and then you develop ocular findings. So sometimes it's important to just bite the bullet and do a chest CT. So if somebody has MS and intermediate uveitis, is this sparse planitis? No. Right, because there's an association. So about, there's several studies and this is if anybody wants to do a tedious prospective study, one suggestion would be to take all patients with MS that you can find referred by neurology, new diagnoses, and then follow them prospectively for five years and see how many develop pro-vascular leakage, retinal vascularitis, or intermediate uveitis. There's a lot of people who consider the MS, intermediate uveitis and MS to be one of the disease defining entities and would be useful to know that. In MS you can have anterior uveitis which is actually the most common, intermediate uveitis which is often symptomatic and retinal vascularitis which is often asymptomatic as well as only caught on incidental angiography. So if you see a patient with intermediate uveitis, say 10-year-old male but no lateralizing neurological symptoms, would you do an MRI? No. So when would you normally do an MRI? So a patient comes in with intermediate uveitis and has a bunch of neurological symptoms, numbness, weakness on either side, yeah that's probably a good idea. It's probably then that you should do an MRI and there's another situation where you should do an MRI as well. Supposing there's a young girl, 13 years old who has intermediate uveitis and you've tried methotrexid and you want to advance to a biologic. That's another situation where you might want to do an MRI. Now why would that be? It's TNF-alpha inhibitors. TNF-alpha inhibitors are relatively contraindicated or actually pretty conclusively contraindicated in patients with demyelinating disease so be careful there. So as a young person or especially a young female with intermediate uveitis, you are more prone to MS and to demyelinating disease so you should be careful there. So as I said before, partial uveitis is not synonymous with intermediate uveitis. It's a subset of intermediate uveitis. It does have a worse prognosis than your, you know, garden variety IU. Has worse vitritis, more severe macular edema and patients tend to present in, in several ways but here's a schematic of various things you can get with, with barge benitis. You definitely have to have the snowball as a snow bank and you often have a lot of kind of CME. So when it comes to, I should just ask you guys, what if you see somebody a de novo patient with, with intermediate uveitis, how would you work them up? Yeah, so all uveitis always take for syphilis and do a direct trap enamel and a non-trap enamel test. So, would you do ACE in a child? No. Right, so just remember that. It's probably not useful. Most children have elevated ACE and then we also talked about older hypertensive and if he's on lysine approved, don't do an ACE. Because we're a middle age hypertensive. Oh, like you? Yeah. I'm sorry, is that protected? Don't depreciate. It's just PHI. Thanks for sharing. You have no problem sharing. PHI information? Yeah. Did you respond? Oh, I got that. Yeah. After all that effort you put into coming up with that joke. Yes. It's too early. Okay. Check for TB. Check for Lyme only in endemic areas. Maybe check for doxocara in young people from endemic areas. But most people with doxocara will have peripheral retinal lesions. There is a subset of diffused doxocoriasis that does not. If the vision is worst in 2030 or 2040, treat. If CME is present, treat. If there's new vascularization or vitreous hemorrhage, these patients should be treated. If there's CME and no significant vitreous haze, it's not unreasonable to start with a steroid and non-steroidal anti-inflammatory drug. The data on this is mixed, but this gives you two advantages. Number one, you can see if you can get rid of the CME. Number two, you can also tell if the patient is a steroid responder. If you put a patient on four times a day, pregnancy alone for a month, then perhaps you'll be able to tell if the patient is going to respond 40 to a subtenon's injection. How long does the steroid response take to develop? Six months. Three weeks. Oh, the permanent IOPS. No, I don't know. But, yes, certainly the longer you have steroid treatment instituted, the more likely you are to develop steroid response hypertension. But three weeks is generally when it starts to emerge. Now, when you do intravitual steroids that affect peaks at six weeks, so make sure you follow patients closely when you have them on steroids. There's actually, there are actually quite a few lawsuits out there where patients were left on topical steroids and the pressures weren't checked. So defend yourself and your patients. If someone had like better than 20, 40 a vision, would you do an FA on all of them to make sure there isn't CME? I do not. Some people do. There's no, there's no strict guidelines on that. Sometimes it's best not to do a test. If the patient's not symptomatic. So if you did it and you found a bunch of leakage, what would you do with that? Would you put this patient an immunosuppression who's fine? So probably not. So if there's vitreous hay as you can try oral steroids or injected steroids, if there's peripheral non-profusion, think about laser. And consider doing immunomodulatory therapy if the disease is chronic, needs oral steroids for longer than two or three months. My first line of treatment is anti-metabolites. You could use methotrexate, cell septum. But then in children, in particular, T cell inhibitors are useful. So what T cell inhibitors are we talking about here? So cyclosporine, what else? So dichrolymus as well. Now the both cyclosporine, what are the side effects of cyclosporine that you want to think about? I'm blood pressure. Yes. And gengible hyperplasia, renal disease, kind of nephrotoxicity, and dichrolymus avoids some of that. So dichrolymus does not give you hypertension, it gives you a lower rate of nephrotoxicity. The only problem is it's harder to get a hold of and it requires drug-level monitoring. That's why a lot of people don't prescribe dichrolymus, but those who use it is far better tolerated, makes you feel less bad than with cyclosporine. Other than that, you can use biologics and there's actually a trend towards using biologics as a first line now in intermediate uveitis. The FDA-approved one is at a lemium ab or humera and it is now indicated in children as well. So that's a good second agent. So my practice, generally I'll see two kinds of intermediate uveitis, kind of this indolent, not particularly symptomatic one with just a few floaters. And then depending on whether or not the patient is 20-40 or worse, has vitreous hemorrhage, has CME, has structural complications that I would treat. If not, then you can observe. Treatment in these patients you may think about deposteroids, injectable steroids, oral steroids, and then you can escalate treatment if you feel that the disease is chronic enough to an anti-metabolite, a T-cell inhibitor, or a biologic. There are some patients who present early with psychedelic membranes with vitreous hemorrhage with potentially with hypotene and severe vision loss and in an amblyogenic age group, then sometimes important to go in and do a vitrectomy. Clear out all the debris, maybe even fix the cataract if there is a significant one, and address the cyclic membrane. Sometimes it's important to leave those patients a phakic because then you can always manage them with the contact lens. Those patients need early immunomodulation. But anyway, so that's all I have. I'm afraid.