 Welcome to UVitis Grand Rounds, this is our ongoing patient round series where we have a subspecialty that, subspecialty themed rounds, we are very lucky to have Dr. Alvi Talley chairing today's meeting and without further ado, Dr. Rai Talley. Thanks Jeff. Thanks for being here, welcome to UVitis Specialty Grand Rounds, I have this illustrious crew of fellows and residents that we would like to present some representative cases that kind of roll through our clinic to illustrate our approach to the diagnosis and treatment of UVitis to arrive at a diagnosis because the diagnosis really matters because it impacts the prognosis and the treatment of our patients. So just by way of introduction as you know, UVitis by definition involves inflammation of the UVL tract but in parlance it really, common parlance, it's intraocular inflammation of the eye, any part of the eye. It can be either infectious or non-infectious and those that are non-infectious are thought to be autoimmune or auto-inflammatory in origin. Importantly, there are masquerade syndromes particularly neoplastic masquerades and so all in all UVitis is not one disease but represents about 30 distinct entities with typical clinical features, course and prognosis. It is not a trivial disease representing between 10 and 15 percent of blindness in the United States and is the fourth leading cause of visual loss after diabetes and age-related macular degeneration making the personal economic impact of potential visual loss possibly greater than that of age-related disease given the fact that the peak onset is in the most productive years of life. So I would like to describe our approach to the UVI of this patient. As William Ossler said, you know, talk to your patients, they will tell you the diagnosis. So the history is extremely important beginning with the ophthalmic history, medical history and then eliciting things that may not come up in history through a review of systems. Then the ocular examination in which we grade the severity and stage of the inflammation and then assess the eye for structural complications in the front of the eye and the back of the eye including posterior sneakia, macular demenocroidal nevascularization. Then a general medical exam is conducted to the extent that it can be carried out in the clinic looking at the patient's skin, their joints for signs of arthritis or deformity and then based on this information formulate a differential diagnosis. So no labs have been performed. This is all history. So the differential diagnosis is formulated and characterized along several dimensions. One has to do with the anatomic location of the inflammation whether or not it is present in the anterior chamber, the vitreous, the retina or coreroid or all three compartments. The pattern of the inflammation particularly in the back of the eyes of pattern recognition is important whether or not the inflammation is predominantly in the retina or in the coreroid or both or whether or not it is a multifocal or a posipocal inflammatory condition. Whether or not it is granulomus or not granulomus by its clinical features. And then the presentation course in laterally. So is this an acute disease? Is it a recurrent acute disease or a chronic disease? Because this will help characterize the type of disease we're talking about, unilateral, bilateral or alternating. Then is this disease purely in the eye? Or what are the systemic host factors that are important? For example, is there a systemic underlying condition that may be associated with the inflammation such as we see in sarcoidosis, multiple sclerosis, spondylitis, AIDS or an iatrogenic immunosuppression? Is there infection present? What are the demographics? The world is shrinking. We see lots of patients from all over the world here in which a certain disease may be more prone in certain populations. And then the associated signs and symptoms. The laboratory is then used after this to exclude infection essentially and to identify systemic disease that may impact mortality or morbidity. And it provides actually important prognostic information for the physician and for the patient. So patient with HLAB27 positive anterior uveitis, we can tell that patient with a certain amount of certainty what the course of their disease is going to be like as opposed to say for example patient with Bay-Shet's disease or Serpigenus which will require a long-term treatment and immunomodulatory therapy. And then a treatment plan is formulated based upon the diagnosis and antimicrobial therapies in the case of infection, a stepladder algorithm employing non-steroidal anti-inflammatory medication with immunomodulatory therapy as needed as either first-line treatment or as part of a steroid-sparing strategy. And then to follow the patient closely to assess treatment and to monitor side effects of treatment. So we're going to kick it off with Dr. Zog who's going to show us one of the diagnoses that we never want to miss. So we're going to just start off by presenting a case. So this is a case of a 42-year-old. This is in 2006 when he first presented. And he's describing some floaters and some light sensitivity, not a lot of pain. He is HIV-positive and his CD4 count by his report is low with a high viral load count. His last CD4 that we could find was 231 at the time of presentation. His visual acuity is 20-40 in each eye, he pinholes a little bit better and his tensions are normal. On his exam he has an anterior chamber cell. He also has a cratic precipitates and then he has vitreous cell. So he has inflammation all over the eye. This is what is, sometimes these don't project all that well, but this is what we're seeing on his exam. So if we look at the right eye you can see that the details of the fundus just are not very clear. So he has some vitritis and then kind of some pigmented, some areas of depigmentation in the periphery and then kind of a circular depigmentation area sort of around the optic nerve, just kind of little areas that are kind of subtle on the fundus findings here. So you have some other imaging done, which doesn't project well again, but it sort of shows those areas where there was some pigment changes, kind of subtle but kind of some almost whitening here. And then on his fluorescein angiogram, this is kind of in the earlier phases of the angiogram, kind of see some patchy filling of the coroid, which can be normal as we go a little bit later. You'll start to see that you have, this is really late in the angiogram and you're seeing kind of this area here that's abnormal, kind of some patchy hypo and hyper fluorescence. This is highlighting one of those areas around the optic nerve. And sometimes these are pretty subtle unless you've been looking at a lot of these. This is an abnormal area that corresponded to the color photos in that eye. And then again here, kind of this area that's a little bit hyper fluorescent, really late in the angiogram. The optic nerve seems to be having some staining as well, maybe even some leakage. Listen, it's not a wide field view, but you can see kind of these almost circular plaque-like areas that are showing up late in the angiogram. So what do you do? You come up with a differential diagnosis. This patient has HIV. He's immunocompromised. His CD4 count is very low. So there's infection is really high on the list in those patients. You also have some infiltrative diseases that could present like this and inflammatory. But we're really thinking about a lot of these infectious things that could be happening to this patient. So what did he have done? He's a high-risk guy, so you kind of have to throw some high-risk things at him. So you do vitreous tap and inject. Try to figure out what's going on back there. He had some boscarnet that was injected into the vitreous. He's also put on the Valtrex. So you're treating CMV and you're also covering some of those herpes viruses as well. And then we did a lab workup. So his lab workup, CD4 count was 217. The biggest thing is that he had an RPR and an FTA that were both positive in him. His toxo was negative. And HIV patients, they can definitely have more than one thing going on. And so sometimes you have to treat multiple infections. But in this case, it looks like syphilis was the main diagnosis here. He had PCR in his vitreous that was done as well at the same time. And CMV and the herpes viruses and toxo were all negative. And anybody that you diagnose with syphilis, the next step is to get cerebral spinal fluid to see if they have involvement in their central nervous system as well. And his was negative. So his diagnosis was syphilitic choreo-retinitis. He was allergic to penicillin, which is the main treatment for this. The good thing about syphilis is it's very treatable. Dr. Vitale likes to desensitize patients and use penicillin. You can use alternative treatments, but this desensitization works really well. So the patient was admitted to the hospital, desensitized, treated with IV penicillin. We talked about his lumbar puncture results, which is important in these patients. And he actually resolved, which is kind of the rule in syphilitic uveitis, is that their vision usually gets better, especially if you can diagnose them early. And so he ended up 20-20 in both eyes. And that was after about a year of follow-up. So this is what his fundus looked like after treatment. So you can still see some subtle changes of pigment going on, but overall things look pretty quiet. The view is much clearer than it was before. So now this gentleman is three years older. Again, HIV is 45 now, in 2009. And he presents with a little bit of pain and decreased vision in his right eye for about four days. Yeah. So he had been off of his HIV regimen for about four months. Does it know why he went off? It's just a big problem. Yeah. I mean, these medications are not cheap, but very effective. So he comes in with hand-motion vision. He has 2-plus anterior chamber cellia, some posterior synechia, pretty extensive area, vitreous cell and haze as well. So again, kind of a pan-uveitis type picture. On his exam, we'll kind of see what his fundus looks like. So this is his right eye. So now he has this large optic nerve mass, essentially, and then really hazy inflammation of the retina as well. So again, HIV-positive patient, re-presenting with a really bad uveitis. Again, you have to step back and wonder what's going on here. Big hyper-autofluorescence here, lots of problems with the vessels, bleeding, haziness, vasculitis, lots of badness going on here. So you get an FAA here that kind of shows some of the same things. Kind of see that patchy kind of inflammation of the retina. This is actually in the uninvolved eye. In the left eye, in that right eye, just really not looking good. Really late in the angiogram. You go out over to the left eye, and he's got a little bit of staining around the disc, which is pretty normal, but he's got these little patches that make you wonder if the left eye's involved as well. So again, you have to take a step back, and your differential is still broad in this patient. CD4 counts now eight. He did have an RPR and an FTA that were again positive. What you do with these usually is you track the treatment of syphilis to make sure that they actually do clear the infection. So his titer had decreased down to one to two back in March of 2007. So his titer is back up with syphilis again. Everything else here was negative. His vitreous sample though, he had some toxo that came back positive on PCR. So he has kind of two things going on at once. But the key here was that in his history, he had a clear historical point that he had a reinfection with syphilis. So he was again introduced to another syphilis case here. So it looked like CMV retinitis. It could have been if you look at the appearance. You have syphilis based on the serologies. And then you have toxo based on the PCR. And then there's all the other different things that still could be involved here. So what do you do with a patient like this? You put them on everything. So valsyclavir for the possibility of any herpes viruses. The anti-toxo, so Bactrim is what he got. And then he had IV penicillin again after desensitization. And then a prednisone taper as well. Got him back up on his heart and then treated him locally also with Predforte, Cyclogell and Zymar. And then in his case, his CD4 count was so low, he had brain imaging as well to rule out any toxolations in his brain. So this is what he looked like a little bit later after some treatment. So he was looking a lot better. A lot of the inflammation is gone. He still has some hemorrhage and obviously the vessels are kind of attenuated from all the damage that had occurred. That was what he looked like when he first came in so you can kind of see the comparison of how much inflammation is down. So in this case this is now a syphilitic pan-Uviatus that was a reinfection in that right eye. And then we had to treat the other things there as well. His CD4 count remained pretty low. It took a little bit of time for that to come up. But he ended up with really poor vision in that right eye long standing because of the damage there. That's what he looked like at the last photos that I could find. So that large optic nerve kind of granulomatous mass was kind of gone there mostly. But still poor vision. I am not 100% sure. Sometimes I can't always tell on going back and looking at cases. But it was negative. It seems that just systemic penicillin really treats it all. And it really clears up the inflammation in the eye too. You can treat locally with steroids to help with that. But most of the time the penicillin alone will help to clear the vitritus and the cell and everything. Okay so we're going to show a couple other cases just to show how tricky syphilis can be. That it really is the great mimicry in the eye. So this is a 35 year old male with a 6 day history of decreased vision in his left eye. He's a high risk individual. He has IB drug use. He tells us that he had a recent HIV test that was negative. He's 2060 in both eyes on testing. This is what his retina looked like. So you can see a pretty clear view to the back of the eye. The vessels look fine. But the optic nerve is swollen here. And then his left eye again a little bit of optic nerve swelling. But you can see kind of this large kind of essentially right over the macula of some depigmentation there. You can see a little bit of hyper fluorescence here on the left eye. The right eye actually looks pretty good. The optic nerve might have a little bit going on in both eyes. On the early stages of the FA what you see here is some hypo fluorescence with some patchy hyper fluorescence. And then later in the angiogram you see that same area with a large kind of crescent shaped hypo fluorescence. And then the optic nerve seems to be staining here as well. So on his, he presented with kind of a classic syphilis is what we would say this looks like. On exam you could almost diagnose this. But you would still go to lab testing in this patient as well. So he had an RPR that was reactive and FTA that was positive. We retested him for HIV and it was positive. He had high CD4 counts. Had an MRI done that was normal. And again after treatment he improved to 2015-2020. So just a quick little case that shows patients can present with something completely different every time with syphilis. And again treatment to resolution of visual acuity is the rule in these patients if you catch them early enough. Okay so another one here, 50 year old Mel complaining of decreased vision. He has optic nerve swelling coming in. The bad thing for this guy is he's NLP in his right eye from birth. He's saying that he had a retinal detachment. He never saw out of that eye and so this eye is just kind of gone. His left eye is baseline vision is 2070. He's decreased down to 2100. No real significant past medical history that we can elucidate from him. He has an APD in that right eye and his eye is actually quiet. And this is what he looked like in his left eye. So you can see it's a little bit of a hazy view. Optic nerve is swollen here and then you've got this area of pigment changes kind of out in the periphery. So on his imaging the main thing that you're seeing here is a swollen optic nerve with some hemorrhages and then same thing here just a swollen optic nerve that kind of leaks late in the angiogram. Maybe even some potential CME there. So what does he have going on? He basically has an optic neuritis of some kind. So he had a lab workup and again his RPR was positive. He ended up being treated again for neurosyphilis. Some of these cases I have limited information on. Dr. Whitelly probably has a lot more but that's another presentation. Just a patient with an optic nerve swelling. So you have to think about syphilis in that case as well. Another patient 29 year old came in with a week of a red pain fly. CD4 counts low. 167 with HIV. He's only had HIV for a week so this is kind of a new diagnosis for him. His visual acuity is down 2050. He has a really exuberant anterior chamber reaction so he has fibrin in his anterior chamber. 3 plus vitreous cell, 2 plus haze, retinal whitening. So again all chambers involved. This is a patient presenting with pan-ubitis. So the differential diagnosis again is very broad in HIV patients. Infection is sort of at the top of your list. This is what his eye look like kind of a bad photo sorry. But what you're seeing is over here in the periphery kind of have these like white areas that are actually above the retina. So kind of these pre-retinal infiltrates and one here as well. A little bit better picture of it. Just kind of some little whitening areas above the retina maybe some in here and up out here as well. So he had a vitreous biopsy and he was admitted for treatment of toxoencephalus and then kind of a workup for this source. And he ended up with CNS and systemic syphilis so his LP was positive and had another good response to penicillin. This is a case of a patient in the UK that was sent to Dr. Vitale. It seemed like it was sent to him as kind of like can you help us with this case? And this is a patient who had PRP and IVT for diabetes. And this is baseline visual acuity so 6 over 12. Essentially about 2040. 6 over 24 would be like 2080. And his vision was worse one month later. Clear to LP in his left eye. So vision just really tanked after this treatment. Had an afferent pupillary defect. Had a lot of inflammation going on in his eye. And he had this testing done over there. So he had an RPR that was positive, a TPPA that was really high. HIV was negative. So again a patient with syphilis and this is just a really classic photo of what syphilis can present with. So it's these pre-retinol whitening areas with kind of a retinitis and optic neuritis. Really pretty impressive inflammation here. You see the vessels are not healthy. You get vasculitis with it. But it's really these kind of white pre-retinol infiltrates that are going on in this patient. Just kind of all over the retina. Alright this is probably my favorite one just because of the history that is the key point in this patient. So this is a 50 year old female. And Dr. Vitale will ask you this question in clinic. Are they a citizen? And at first I always thought that that meant, are they like a US citizen? Do they have their green card or something? I wasn't exactly sure. But it's that they're an upstanding citizen. So church going, upstanding citizen. She has a lot of systemic things going on. So she has polyarthritis. She's having ulcers, rash on her knees, ankles, all kinds of stuff going on. She had been diagnosed with I think bird shot initially. Oh was it mute? Sorry. She was sent to Dr. Vitale for a consult to see how to treat her. And she had some old vitreous cells on exam. Pretty good vision. But kind of a lot of systemic things going on. This is what her eye looked like. It actually looked pretty good on exam. Not a whole lot going on the fundus photo on the right eye. In the periphery maybe there's some pigment stuff going on. But pretty subtle on exam initially. Same thing with the left eye. Not seeing a whole lot on her exam. But her imaging kind of really shows some things that were going on. So what we're seeing on her angiogram is you're seeing kind of these patchy areas that are kind of filling a little bit abnormally. You see just kind of presentation things that are not normal as she's filling her retina here. Same thing. Kind of subtle things. Maybe there's a little bit of haze right in this area here. Kind of just pigment abnormalities and filling defects in the coroids. So it's not. So this is the key point is that she had a benign social history but her husband was having problems with same sex attraction. And they're currently separated. When I was looking up her case her name changed. And so it was like hard for me to tell is this the same patient. But I think we know why her name changed after this. She was RPR FTA positive. She had a positive LP and had IV penicillin treated for syphilis. So one of the issues with syphilis right now is it actually is on the rise from 2012 to 2013. It kind of doubled in rates. And it's mostly still young men having sex with men. And there are about 50,000 cases reported to the CDC a few years back. But there's no reporting that's required. Yeah. In Utah. It's mostly men having sex with men here. It's probably, is the prevalence less in Utah? It's hard to know. So there's different stages to syphilis. The primary stage is pretty rare to have ocular involvement. But you can have ocular involvement in secondary or tertiary. There's also congenital late and late latent syphilis. And again, those are all times that you can see syphilis affecting the eye. If you have somebody in these situations, a lot of times that your treatment may not improve the condition as far as the systemic things and maybe even some of the late things that are going on in the eye. But the key is to prevent further damage with it. So there's no formal reporting. There was a good study that came out from the UK that there were about 50 cases per million of syphilis. And there were about 0.3 per million of syphilitic uveitis. It kind of gives you an idea of how many cases of syphilitic uveitis there are. It's pretty rare. It's still less than 1% of our uveitis cases that are coming in. It's a lot higher in HIV patients though about 16% of them that came in and had uveitis from syphilis. So the presentation, really you name it, it could be anything. So that's why it's called The Great Mimicre. It can present with any sort of presentation. There are a couple of things that are classic, but it can really come as anything. So this just kind of shows we got cut off a little bit here, but every single system is involved. I was thinking maybe ocular plastics got out of it, but extraction motility you can have credular palsy. So it's just everywhere in any of the stages of syphilis. The most common things that you see are vitritis, iritis, KP and retinitis, but you can see again anything. So because of the extreme variability, it's really the history. You have to get uncomfortable with the patient and talk to them about their true risk factors for HIV and STD. STDs. There's two distinct clinical patterns. It's those superficial retinal precipitates. And then just a cute posterior placoid choreo-retinitis, which are two of the cases that I showed. If you had to profile a patient, this is what it would be, HIV positive middle-aged male. There are some classic OCT findings that show kind of disruption of the ISOS junction and then loss of the ELM in this left eye compared to the right eye on this patient. This shows kind of resolution of that with treatment. So you see the ELM come back and the ISOS junction kind of reform. On ICG, you can see early and late confluent hypo fluorescence, which is pretty specific for syphilis. On FA, you usually see this progressive diffuse leakage. And then the hyper-auto fluorescence is what we saw in that placoid type lesion. So the serology, you want to get a non-trepanemal test, a VDRL or an RPR, as well as a trepanemal test. So most of the time it seems like we're checking RPR and FTA. The CDC has this recommendation that they came out with that nobody really follows because there's extra steps in testing. It hasn't been widely adopted. You essentially get an EIA if that's positive, you get an RPR. If that's negative, you get a TPA. No one has really adopted this as of yet. You can do direct testing with PCR or the aqueous. Again, we talked about that a little bit. And then that dark filled microscopy is something that you can potentially do. Tracking treatment, you're using an RPR and a VDRL, the titers to see if they're getting better. So then a couple of key things. If you diagnose syphilis, what do you do next? So the key is that ocular syphilis is neuro syphilis. And so you have to get a CSF evaluation to get a lumbar puncture and always test for HIV. Treatment, there's a bunch of different treatments that you can do that are all approved for neuro syphilis. But IV penicillin is kind of what we do here. Don't treat with local therapy unless you have proper antimicrobials on board. So using steroids is fine as long as you're treating the underlying infection. And then just some take home points. Always consider syphilis in the UVitis patient. The pre-retinal to the acute posterior placoid choreo-retinase are kind of, can be diagnostic of syphilis. You can use enhanced imaging that is helpful. And then serologic diagnosis is really the way that you come up with a conclusion there. And again if ocular syphilis gets syphilis, get CSF and HIV testing. That's it. Okay. So Jim and I are going to present a case quickly. We have two cases left in a limited amount of time. So I'll move through the case presentation quickly. It's a classic representation of a diagnosis we see not too infrequently in the UVitis clinic. So this is a 68-year-old Caucasian woman in 2013 at an outside clinic. She was treated for a super temporal BRVO and related CME with intravitrally vastin. She responded well initially, but then returned to that clinic in 2014 with a recurrence of CME. And along with that was found to have a mild vitritus associated. She, before coming to us as a second opinion referral, she had had two separate approximately one month tapers of Durazol in both eyes. And by the time she got to us, she had been off of any topical treatment for one month. Her chief complaint is blurry vision more on the right than the left. And she also complained of worsening night vision. So these are medications. Most of them are over-the-counter supplements. She's on levotheroxin for thyroid and baby aspirin just for prevention of cardiac complications. Her past medical history hypothyroid, she had a recent mechanical fall from slipping on the floor at home. She has a history of miscarriage. She had knee surgery in the distant past with a complication of a pulmonary embolism afterwards requiring anticoagulation. And recently found out again she had another DVT requiring anticoagulation. She has no history of sex with transmitted disease and no known history of hypertension. Her family history is in non-contributory. She lives in Idaho. She's a retired teacher. She's traveled to Prague in April of last year when we saw her. She has no history of IV drug use and she does not smoke. And her review of systems is only notable for joint swelling, warmth, and redness in her hands. And when you look at her hands she has some sort of, some deformity of her fingers and hands almost like a rheumatological deformity of rheumatoid arthritis. So her vision is 2040 right eye, 2025 left eye. She does not have an APD or remainder of her initial exam as normal, pressures are normal. Enter segment, notably she has a deep and quiet enter chamber, mild cataract. The vitreous is notable for about half plus cell and one plus haze in her eyes. This is pretty equivalent. And then let's go through the photos. This is the funnest photo of a right eye. You can see that the view is somewhat hazy. The view of the optic nerve is a little bit obscured. The vessel is a pure normal. Remember she had a super temporal BRVO that was diagnosed in the past in this size. So there's some tortuosity to this arcade vessel and some collateral that are formed. You know, this looks like a hypopigmented blonde fundus. I'm not sure what to make of these at the moment, but these will be better characterized with further imaging. You know, these hypopigmented spots in the nasal mid periphery. Her left eye looks very similar. One plus haze, disc looks sharp, vessels look normal. Again, blonde fundus, but possibly some interesting hypopigmented lesions in the mid nasal periphery. So before we get to a differential diagnosis, there are other studies we can perform and so we got those. I'll shout out what you would get for this patient. Floricine angiogram, ICG, out of fluorescence OCT. Okay, so let's start with the OCT. So here's a right eye OCT. She's got CME. You can see that this vessel is more engorged than the corresponding inferior arcade vessel. Intra-retinal fluid. Left eye OCT is totally normal. Okay, so interestingly she's got the same amount of vitritis and haze in both eyes. The CME may be due to, you know, related to her BRVO in the right eye. Here's her FA. This is early transit. Right eye. 19 seconds. Vessels are filling normally. This is a wide, we got a wide field angiogram. So this is why it's so minified and zoomed out. A little later, 32 seconds. And then much later, 2.5 minutes. You can see that the optic nerve is lighting up. So there's some staining and leakage from the optic nerve. And interestingly, there is a retinal vascular leakage all over the place. Left eye is very similar. So 43 seconds, 4 minutes. Again, widespread retinal vascular staining with leakage from the vascular optic nerve also stains and leaks late. Here's her ICG. Right eye, 20 seconds. 32 seconds. Looks like, you know, the cord seems to be filling appropriately. Remember, ICG looks at caroidal pathology. 4 minutes. Okay. Now maybe you're starting, we're starting to see some interesting hypopigmented spots in the periphery. And then if you wait long enough, we can see that there is something interesting going on in the mid-periphery here. And these areas are, you know, they correspond to the whitish lesions, the whitish hypopigmented spots we saw on the color photograph. And same thing in the left eye. Early on, you don't see much, but as you get later in the ICG she has this interesting, you know, mid-peripheral ring of hypopigmented area. So let's just throw out some differential diagnosis. Remember, we can think of things that are infectious and non-infectious. Anybody have any ideas? So let's review the case. So this is a 60-plus year old woman, Caucasian. She has blurry vision, trouble with night vision, retinal vascular staining on her FAA, deep caroidal spots on her ICG, history of BRVO in the other eye, which may be a red herring. What are you thinking? Okay. Okay. This is also a bilateral disease, okay, presenting basically equivalent in both eyes, and she has a mild detritus. So any other ideas? Those are good. What's that? TB's on the differential. So good. So let's think about infectious and non-infectious. TB syphilis, you know, POHS is lower on the differential, but lesions don't typically appear like this. Non-infectious. So I don't actually have the diagnosis up here. We'll see the diagnosis in a second. So sarcoid, multifocal corditis, and panubiitis, lymphoma, VKH, mutates, PIC, tipps, etc., those are much lower on the list. So what would you do for workup? So throw out some ideas. Okay. Okay. Right. Okay. What are you thinking of with that? So, you know, the workup, her ANA is negative. We got the ANA and we got some rheumatological testing because of her deformities in her hands and, you know, just to rule out that this would not be a typical presentation for rheumatoid arthritis. Her ACE and lysozyme were normal. FT and RPR were negative. Her PPD was negative. ESR is normal. She had an interesting history of a miscarriage, a PE, and a DVT. So she sort of looked into that as well. Lupus anticoagulatory. So her hypercoagulability labs were normal. Test text area is unremarkable. But as Russell mentioned, her HLA-829 was positive. So what's our diagnosis? Burt shot. So Jim will talk a little bit about Burt shot. Anybody have any questions about the imaging and the workup and, you know, our approach to the diagnosis? So from her history, mild vitritus, trouble with the night vision, blurry vision, the typical features of the FAA, which are retinobascular staining, and then the fundus appearance of these hypopigmented lesions and the nasal periphery, which show up in, which are much more numerous in appearance on ICG, that led us to think about Burt shot. And that is a, this is a classic presentation of Burt shot, I believe. I can go through the utility of this. You sure? Thanks. Alright, so like Nick said, I want to give Brian time to speak, because he's got a good presentation. That's where they get the same. Exactly. So this will kind of answer some of the, of why we ordered the HLA-829 by Dr. Vitelli ordered it. So the classic symptoms with which these patients present include floaters, photopsias, and nyctalopia. I think those are probably the three main ones that you'll hear most often. They can also sometimes describe problems with color vision, and sometimes they will actually tell you they have a spot in their vision where they don't see as well anymore. Oftentimes you'll find that once you start testing, but they don't always notice that until you point it out to them. So blurry vision, our patient actually mentioned blurry vision. They don't always present with that. And that's sort of a key point here, is that visual acuity is not a great marker for activity of this disease. It's kind of like, I guess maybe glaucoma or retinitis pigmentosa in that regard, and that you can have a 2020 patient with really active disease that's rapidly progressive. And you got to look beyond the visual acuity to follow these patients. But this is what they'll typically present complaining of. It's about 1% of referrals to tertiary centers for uveitis. It's a little over 5% of cases of posterior uveitis that we see. It's more often found in women than men, but men certainly have it. Dr. Vitale follows a good number of men with bird shot. Their average age is in the 50s. They're most commonly Caucasian. And then HLA-829 is positive in 90% of patients. But it's also present in 1% of Caucasians in general. So you don't want to just order this test on everyone, because it's not going to be that useful of a test. But if you have suspicion for bird shot, or if it's something that you're worried about missing, this can be a helpful test, because if this is actually negative, that's when it's probably the most useful. If this test is negative, then you probably should start thinking about other diagnoses. So that's why we ordered it. The patient had sort of a classic presentation, and had this disease been negative, we might have had to go down different roads to look for other diagnoses for this patient. On exam, Nick sort of pointed some of these out, but there are yellow lesions that are deep to the retina. They're usually smaller than a disc diameter. They can be asymmetric between eyes. They're often clustered closer to the nerve and most concentrated nasal and inferior to the disc. There's not really, typically, any pigment clumping on them, and these often appear a little bit after symptoms. As Nick pointed out, our patient had a pretty blonde fundus. Sometimes these are a little more obvious on exam. If the patient has a darker fundus, they stand out a little bit more. Also on exam, you'll often see vitreous cell in haze. You can see a retinal vasculitis. You can see discodema and macular edema. So that macular edema might be related to that old BRVO, but it might actually be related to her diagnosis of bird shot. That's sort of up in the air. You can find epiretinal membranes in these patients pretty often. And I say a relatively quiet anterior chamber because you can have half to one plus cell in the anterior chamber in these patients. That's not a rule, but if your patient has a few cells in the anterior chamber that does not rule this diagnosis out, they can have a little bit of inflammation interiorly. The fluorescent angiogram, it depends on the source you read, but there are lots of different descriptions of the spots that you'll see on a fluorescent angiogram depending on the phase of the disease and how active the disease is. You'll often see some abnormalities sometimes correlating with the spots that you see on exam, but there's no consistent pattern with whether they'll be hyper or hypofluorescent, how many spots you'll see, and how well defined they are. Other things that you can see, which we saw, are vessel leakage, disc leakage or staining. You can see neovascularization, which our patient did not have, so that doesn't rule this disease out. You can have that with birdshot. And the classic boards or OCAPS question for those taking that in a little bit is that there's quenching of dye from the ventinal circulation a little earlier than you would expect. So just to sort of review, with our patient we saw the vascular leakage and the disc leakage as well. You see it in the other eye as well. You can sort of see this traveling into the macula and creating a little bit of petaloid leakage as well in the right eye where we saw the macular edema on the OCT. The ICG is really the test that gives this disease away. So if you're suspicious of birdshot, like we mentioned in HLA 829 is helpful and an ICG is always helpful as well. This is where you get the classic hypofluorescent lesions and the intermediate to late phases on the imaging. The lesions typically exceed the number of lesions that you see on exam. Even if they have a darker fundus and the yellow lesions are more obvious you'll often see far more hypo pigmented lesions on the ICG compared to what you saw at the slit lamp. And then you get this diffuse hyperfluorescence of the coroid late on the ICG. The OCT you can see macular edema and sometimes you'll see some outer retinal abnormalities which were not as prevalent in our patient. So just to review the ICG again these are those hypofluorescent spots and we certainly didn't see that many yellow lesions on the color fundus photos but we see a lot of them here. So with further testing which we'll go back to our patient in a minute. The patient can have a negative waveform on full field ERG which basically means that there's a greater decrease in the B wave than the A wave. Late in the disease the entire ERG can go flat. So the B wave tends to go first and the A wave follows. Treatment which we'll get into in a second can actually improve the ERG over time. It's not a change that you'll see after a week of treatment but it can improve a little bit. And the most helpful parts of the ERG are the scotopic B wave amplitudes and the 30 hertz flicker implicit times. Visual fields are also helpful for following these patients long term. They tend to have any number of different changes. They can have peripheral constriction arcute defects, multiple foci of field loss. But the abnormalities in mean deviation can be helpful to follow for these patients. And a 24-2 is not often good enough to really follow these patients long term. You want to get out to that peripheral field. So a 30-2 or a Goldman visual field are helpful. Most of these patients will actually get worse over time if they have no treatment. And the treatment does tend to decrease the chances of bad visual outcomes. What 20% of patients would do just fine without treatment is a good question and it's hard to identify them. So this is a bit of a controversy which will open up to the floor in a couple minutes. Is it worth treating these patients or not? And there's not a general consensus on that answer. If you choose to treat, steroids are generally not sufficient as monotherapy. They're good to start at the beginning and you can add them on top of these other therapies to take care of specific aspects of the disease like macular edema. And they can be oral subtenons or intraocular. But immunomodulatory therapy is really what's helpful for these patients in the long term. And you typically start with an anti-metabolite. And if that's not stabilizing the trick, if that's not stabilizing the disease and keeping it from progressing, you can add these other immunomodulatory medications below. The way you would determine if these medications are helping or not is again not by checking the visual acuity on each visit but by checking how the visual field is changing long term and how the ERG is changing long term and checking active disease at the slitland. For active haze and macular edema and those sorts of things. So you want to look at a lot more than just visual acuity with these patients. I think it's one of the take home messages here. And I'll turn it back to Nick. You want me to just finish this. Save time for Brian. So with our patients specifically we did get Goldman visual fields which shows some general mostly nasal peripheral field loss. Same with the left eye. And if we move on to the ERG, she did have some changes on her ERG with a 30 hertz flicker and the scotopic waves as well. But to get to the real discussion here there are some controversies with this disease which include what's the role of HLA A29. Thank you Dr. Valentine for that question because as I mentioned a lot of people have a positive HLA A29 and don't have bird shot. So when is the right time to order this test? Another question to be asked is should all patients be treated? Because as I mentioned some patients do just fine without treatment and the treatments that I mentioned do have side effects. They're not benign drugs and we're talking about putting patients on these for a very long period of time. They're not going to be on them for three months and then stop. We're talking about years of treatment. How long should patients be treated? And what's the best method and frequency for monitoring the disease? At this institution we tend to follow them with fields and ERGs and seeing them in clinic. And how is remission defined? At what point do you say this disease is stable? We're okay to stop treatment and just watch you. But I'd open it to the floor if anyone has comments on these issues or questions or anything. Yes, that's a good question. I don't know. Do people know that? I'll say on that from an anecdotal standpoint I think most of the residents and fellows here have seen patients from Dr. Vitalli's clinics who have gotten tired of the IMT therapy and have decided to go off of it. And then they come back three years later and you look through their chart and they were stable for a long time. They sort of disappeared for a while and they come back and their ERGs are flat and their fields are much more constricted. That's not exactly a prospective trial but it is kind of upsetting when that happens. You see these large changes when they stop their treatment. Yes, Dr. and Buddy. It tends to be systemic therapy. The intravitrile drugs that we use for these patients tend to be steroids if they're warranted. But no, not intravitrile, not the trixate. All of these are, that's a good question. All of these are systemic systemically administered. I'll turn it over to Brian. Never mind. Thanks. Thank you for your help.