 All right, good morning, everyone. Welcome to Grand Rounds. I'm Sean Collin, one of the chief residents. I'll be moderating today. We have three riveting cases and very interesting titles as well. We have two of our chief residents presenting, Cole Swiston and Allie Simpson, as well as one of the pediatric neurology, PGY3 residents, Mary Glenn View presenting. We'll start with Cole Swiston. And a fun fact about Cole, Cole is an avid fisherman, as most of us know. He recently bought a secondhand drift boat and hopefully we'll be able to take that out at some point this spring and he'll have to row the rapids that have been a nemesis for us for the past three years. So Cole, come on up. Instead of shoveling my driveway, I've been shoveling said boat. Okay, so I have a couple of cases that I saw as a PGY3 on primary call that I'm titling 12 beers and a PB and J with a unifying diagnosis, but just kind of a challenging thing to see. So jumping right into it, I'm not gonna give it away, but I'm just gonna present both faces first. First one was an 11-year-old nonverbal boy with autism. He presented, actually he had three exams over the course of a week, one in clinic, one in the ER and one formal E-way. Before ultimately it was discovered the diagnosis. Parents were concerned that he had progressive vision lost both eyes over three or four months. He'd been bumping into walls, falling downstairs more often and had difficulty with his iPad that was uncommon for him. And they noted some intermittent tearing and redness in both eyes. He has some atopic history, including eosinophilic esophagitis allergies, but no known past ocular history up until this issue. They've been using an allergy eye drop for this tearing and then he takes Xeritech and Flonase for his allergies. This was from my exam with him in the ER. Him being nonverbal, going to tell that he was intermittently fixed and following no pupil issues and normal pressures. And then most notably on his exam he did have trace to one plus injection in both eyes with a keratinized appearance to superior conge and then scattered fluorescent uptake to the ball bar congenitiva. The cornea had three plus diffused punctate epithelial erosions in both eyes which were confluent in the right eye with an FB defect, although he did not have any concern for ulceration or infiltrate. Thinking about other etiologies or vision loss in a nonverbal patient with autism, maybe self-harm behavior, there was no cataract, no retinal detachment, though the view to the back of the eye was fairly hazy due to the cornea. And these were pictures from the EUA that you can see just with the ret cam photo there that that superior ball bar conge is quite wrinkled and kind of a very rough keratinized appearance with fluorescent uptake and then an inferior affluent FB defect there. So that's case one, not going to give it away. Similar but separate case was actually just a month later on primary call in the university emergency department at 36 year old male with eye pain, both eyes but right worst than left for five days. He had the same symptoms a few months ago and was treated for an eye infection with some drops, no recent illness, no contact lens use, no trauma for him body and really no prior ocular history up until this issue. It takes no medications. We're able to get a vision on him. It was four, 2800 at the phase in the right eye, 2100 in the left, no improvement pinhole, no pupillary issues, normal fields, extractor movements in the normal IOP in both eyes. Exam for him also had injection of both eyes, right, worst than left, rough, variably staining, keratinized congenitiva, bulbar conge. His right eye did have an inferior infiltrate and ulcer with an overlying FB defect with some thinning and diffuse stromal haze, no ulceration in the left eye yet but did have rough appearing epithelium with diffuse punctate erosions. In that ulcerated eye did have a underlying fribrous reaction in the anterior chamber and then the rest of the exam was limited due to cornea but normal. And so what I did mention for both of these was the importance of social history and diet. So patient one, the boy with autism, his entire diet consists of peanut butter and jelly sandwiches. It refuses to eat anything else. Patient two is very gaunt in appearance. He drinks 12 years a day and eats primarily fast food. And so I did not pick up on this in the first patient in the pediatric ED but with the EUA with Dr. Hoffman, I almost immediately recognized that we should draw serum vitamin A level which was lower than the lower limit of the assay for that patient. And then when I saw this second patient, I said, that looks pretty similar. And with the alcohol use, drew a vitamin A level which was also reduced. I wanted to talk a little bit today about vitamin A deficiency and the ocular manifestations of that which is zero ophthalmia. As far as WHO estimates globally, it's the most common cause of blindness in children with over 250 million children affected and then almost three million with the ocular manifestations. And as we probably know, that's most commonly due to malnutrition in developing countries but in the US, we don't usually think of that as an etiology as most of our foods are fortified with vitamin A, milk, margarine, cereals, some other foods all have vitamin A in them. And so in the US, it's usually a malabsorptive process or a GI tract disorder that will get you to this point but I thought it was interesting that both these cases, both these patients ate their way into or drank their way into vitamin A deficiency. So where do we get it? In the diet, you can have vitamin A in two forms. The preform of the vitamin A, retinol and retinolasters come from animal products, primarily liver, fish, eggs, and then fortified dairy products or from usually plant-based products. You can have pro-vitamin A, crotinoids, alpha beta-carotene and beta-cryptozanthin, comes from leafy green vegetables, sweet potatoes are very high in vitamin A, tomatoes, fruits, and then some vegetable oils. Importantly, in the US, 75% of our vitamin A is consumed in the preformed version and up to 40% of that comes from enriched foods, kind of highlighting that importance in our diet. While globally, depending on diet, usually it's consumed in the pro-vitamin A form and up to 100% of this preformed vitamin A can be absorbed in the duodenum but only 10 to 30% of the pro-vitamin A-crotinoids, hence another reason why we see it less commonly in the US. Vitamin A is a fat-soluble vitamin absorbed in the duodenum. It's kind of oxidized to its retinol and retinoic acid, main active metabolites, and then stored in the liver. It's transported throughout the body for its various needs on retinol-binding protein, which requires zinc, so if you have poor zinc, you can also have low vitamin A, so whenever you're drawing a serum vitamin A, it's also good to draw a serum zinc. In the eye, it serves two very different but important roles for the ocular surface. The congenit corneates needed for maintenance and differentiated of stratified scrimaceous epithelium and the retina. It's very important with the visual cycle, as we know, it's needed for the creation and regeneration of radopsin and that's preferentially in rods. And so as far as symptomatology, and we've all heard of night blindness from Xerophthalmia, that's the most common presenting symptom in 71% of patients, and then the other findings are ocular surface-related. So congenitival cirrhosis, buttoe spots, and corneal cirrhosis are the next most common symptoms. These last four categories, according to WHO, are all just complications related to Xerophthalmia. The corneal ulceration, Trata Malaysia scarring, and the Xerophthalmic fundus is due to longstanding vitamin A deficiency, you can see some posterior pole changes, which will show as well. The nyctalopia can be very subtle, especially in pediatric patients where you might have to observe for a behavior change and in this patient with autism. It's usually the earliest presenting symptom, and the ER changes actually may precede clinical symptoms, and these ERG changes as well as the symptoms can resolve as early as 24 hours after initiation of treatment. So this is a table from a recent paper with a patient with vitamin A deficiency. You can see the first four roads are all dark-adapted ERGs, and then compared to the green representative, normal wave form, quite flat throughout, especially the oscillatory potentials, and then light-adapted, not as affected, and then proceeding after treatment one week, one month, and two months, you can see almost near normalization by one week. And the surface changes actually thought that our patient had a pretty good representation of that caratinized appearance of the condom type, and this condom type will wrinkling in dullness, but toe spots will always be on boards. They're usually these triangular-shaped white to yellow plaques, peri-limbo in the intrapalpibral region, and they just represent a buildup of caratinized debris over an area of a divided-lized conge. Corneal cirrhosis can be mild, as we saw with our patients with PEK, but can progress to crata-malacia, ulceration, secondary infection, and then scarring, which is gonna be the main cause of irreversible vision loss for xeroaphthalmia. Long-standing low-vitamin A can give you this xeroaphthalmic fundus, which is represented by pale white and yellow seed-like spots along the vessels and in the periphery. These are also reversible changes that go away with treatment. And so, like I mentioned, really the only way or what was thought to be the only way that you get irreversible vision loss was corneal scarring. However, there is a rare etiology related to long-standing vitamin A deficiency of optic neuropathy. From what I've been able to see, there's only been about 10 reported cases of this, and the pathophysiology is not fully understood, but we do know that vitamin A plays a role in bone growth and hematopoiesis, and they've looked in animal studies. I think it was cows, and they showed that vitamin A deficient cows had an increased osteoblast activity, including in the optic canal. So narrowing of the optic canal led to subsequent ischemic necrosis of the nerve, and then irreversible vision loss from optic neuropathy. And so, in developed countries, malnutrition is not the most common risk factor. It's usually poor absorption from bariatric surgery or a short guts syndrome bowel resection. Cystic fibrosis, as most of these patients commonly have, pancreatic insufficiency, and lead to poor fat soluble vitamin absorption, chronic diarrhea from inflammatory bowel disease or celiac, and then any sort of chronic liver disease where vitamin A is stored. I put alcohol use disorder on both sides of this. As was illustrated with our patient, he, in all likelihood, had a component of alcoholic hepatitis that was not storing vitamin A, and then, you know, because of the alcohol use did not have a broad diet as well, so had poor intake. And as for poor intake, our patient with autism fits on that side as well in the developmental delay category. And they've actually looked at this. Autism is an unrecognized, relatively common cause of xeroephthalmia in developed countries, and that's because of their propensity for a very narrow diet. And this is a table from a case series of a variety of autism patients with vitamin A deficiency, and this column is their diet, and not just part of their diet, this is their exclusive diet. So it's french fries, rice balls, bacon and blueberry muffins, so it doesn't sound terrible, but you're not gonna get any vitamin A. There was a group in Australia that looked at the most common causes of vitamin A deficiency in children. So it developed country, and while two of these celiac and cystic fibrosis were due to poor absorption, autism was actually in the top three etiologies. As far as diagnosis, this is really a clinical diagnosis of special attention, like I mentioned, to the past medical and social history, looking at the risk factors in resource poor settings, or in the US, you can treat empirically. It's fairly low risk, and especially in patients with really refractory dry eye, it may be a diagnosis to consider, but you can also draw serology, like I mentioned, includes zinc levels, as that's needed for transport throughout the blood, and then supplemental studies, like we saw ERG, or dark adipotometry, and you can do impression cytology of the conjunctiva, which will show you representative pathologic changes that are not completely diagnostic, but suggestive of serothalium. The WHO recommends these various repletion recommendations for vitamin A deficiency, 200,000 international units at days one, two, and two weeks, so three doses. You cut that in half based on the patient's age all the way down to less than six months. If there's a concern for a malabsorptive process or any corneal involvement, it really should be IM. In fact, some patients or some hospitals will admit these patients for intramuscular repletion. In adults, this is the repletion recommendation here, and then support the corneal surface and treat the complications with antibiotic vitamin or drops. Promote corneal healing with doxy or vitamin C, then do not use doxy in children. So our patients, the 36-year-old with alcohol use disorder, he had a right corneal ulcer, which puts him in WHO category X3A. He did have his vitamin A repleted. He had a culture, was started on fortified bank and Tobra drops, and then as well as vitamin C and doxy was told to use erythromycin in the un-ulserated eye. And then I talked to him for a long time. He had quite severe vision loss with risk of corneal scarring without using the drops in close follow-up. And given the opportunity to potentially detox as well, we did offer him admission, but he ultimately felt like he could follow-up and reliably use the drops. Unfortunately, he did not. He forgot the drops in the emergency department, but he did follow-up two days later and then three more times over the next two weeks. Vision did improve somewhat. The pain in the infiltrate did improve. The ulcer was consolidated, but then he was ultimately lost the follow-up, so I don't know his eventual outcome. The patient with autism was category X2 because of the corneal involvement. He was referred to GI as well as his PCP for repletion. He was given large doses. I couldn't find the exact dose that he was given. And then was also given supplements to use long-term. His mom would crush them up and sprinkle them on his peanut butter and jelly sandwiches, which seemed to work. He had a full vitamin panel to look for other deficiencies which only showed vitamin D, deficiency, no other issues. And then within a month, his vitamin A level was low normal, but still normalized. He did end up undergoing a subsequent exam under anesthesia with photos ERG and a VEP with ophthalmology, which I did wanna mention. By that point, as expected, his ERG had normalized, but what we found was that the patient or the parents didn't really feel like his vision was improving at all, just by treatment. And he had reduced P100 amplitude in latency periods for on his VEPs, indicating a possible optic nerve issue. And during that EUA, he did that fundus photos. You can see both nerves are quite pale on both eyes. And then he didn't have a true RNFL OCT, but on these Mac OCTs, you can see that the retina kind of ends at the interplexiform layer. And there's very, very little retinal fiber layer remaining. So here's a representative normal of what we should be seeing. And so he underwent a optic neuropathy workup with an MRI brain. And then the other metabolic studies that I mentioned, but it was ultimately thought that this was one of those rare cases of irreversible vision loss from optic neuropathy related to zero ophthalmia, which was kind of sad. And so kind of some take home points. This is not just a disease of developing countries. You need a keen history to reveal the source of malabsorption or malnutrition in these patients and keep by many deficiency on your differential refractory dry eye. Learn from your mistakes and your mentors, like I mentioned, when I saw the first patient in the ER, I had no idea what was going on. I knew he had very dry red eyes, but I did not think about vitamin A deficiency. I wasn't until I was with Dr. Hoffman in the OR during the EUA that it really clicked. And then when I saw the patient about a month later with alcohol use disorder, I said, that's gotta be vitamin A deficiency. And while 12 years in a PB and J may get you through a primary call shift or a Wednesday night, if you're Catherine who you're not, you're not getting any vitamin A. Happy to answer any questions. Thank you guys. Dr. Olson. But time just briefly, but this is one that can sneak up on you. And when it doesn't make sense, I had a cataract surgery patient that just the vision, he just kept complaining about things even though his vision on the chart turned out that this was this, that he had a bowel absorption syndrome. But the worst I had was a cult where the guru thought that the secret of life was daily LSD and only brown rice. And a person died. So this is a lethal disease, even though it was finally caught, the person was already going into general systemic failure. The corneas were essentially melted down to decimates membrane and the person never recovered. So this is one you gotta have in the back of your head because it could really fool you at times. Just real quick. Yeah, mortality rate, I think it's quoted between five and 25%. And obviously that's because if you're this, at least in the developing world and you're hospitalized for us for this, your nutrition status so poor that the prognosis is quite poor. And that, you know, again, this being lethal, not so much due to the vitamin A deficiency itself, but just the overall nutritional deficiency. Yeah, it's, I mean, it's needed for a lot of our immune function. So they can be pretty profoundly immunocompromised as well and get a variety of secondary systemic infections which can all be lethal. Great. Thank you. All right, thanks Cole. Oh, Srav says, great topic in review after seeing an autistic patient in fellowship on a french fries diet for several years with severe optic atrophy and permanent vision loss. I've started screening every autistic patient and developmental delay patient for poor diet. I ask about multivitamin and suggest starting one if they're not doing it. Thanks for discussing. Thank you, Dr. Bagunta. All right, well, thanks Cole. Up next, we have Allie Simpson who's another one of our chief residents. She's going to be one of our cornea fellows next year. Allie currently living her best life on elective rotation, which is a great rotation to be on the month before your wedding. And she's expecting that Cole and I will be in our best behaviors at her wedding. Her case is not all that is pigmented. I don't think I have any dietary recommendations but we'll see where we go. Okay, so I'm gonna start off with a case as well. The 20-year-old female, no past medical history. Presenting to retina clinic with chronic floaters in the left eye. Visual acuity 2020 in the right eye, 2025 in the left, normal IOP, normal slit lamp exam in both eyes and a normal fundus exam in the right. However, in the left, she kind of had this purple, darkly pigmented lesion, pretty far peripheral. And you can see this optose photo at the time that I don't know if you can see my mouth. That area, inferiorly, is not an artifact. That is actually the tumor that we're talking about. Oh, I put it in my mouth. So the initial ultrasound in 2017 with Dr. Harry showed this large mushroomy tumor of the celery body. And the ACE scan at that time had showed this kind of really regular, high reflective lesion that was about a centimeter in all dimensions. I won't quiz the residents because we just went over this last Friday with Dr. Harry, but this configuration is concerning for melanoma. I think they'll nod their heads and agree, but that this ACE scan does not necessarily correlate. You'd expect something much lower reflectivity for melanoma. And so that allowed us to kind of expand the differential. So a melanoma is a nevus, an adenoma of the pigmented celery body epithelium, which is similar to a chirpy, but of the celery body, meduloepithelioma, melanocytoma, hemangioma, not because of its appearance, but just because of how highly reflective it was on ultrasound were part of the differential. It was recommended that she follow up in four months for repeat exam, and unfortunately she was lost to follow up for three and a half years. So she represented in 2021, she's 24 at this time with progressive left eye pain and vision loss that had been worsening over the past few months. At this point, she's hand motion is centrally in the left eye. She's got an eye pressure of 42 in the left. She's got some mild congenjection, but no specific dilation of any vessels to be concerning for a feeder vessel. Mild corneal edema and a lot of posterior synigae, lots of deposition on the anterior and posterior lens capsule. Unfortunately at this point, there is no red reflex or view of the fundus in the left eye. She saw Dr. Harry again in 2021 where at this UVM, you can kind of see this large mass coming from the celery body. It's a budding the crystalline lens, but it's not fully captured here. And actually a standard B scan couldn't actually characterize the size of this thing either. So this is actually an immersion B scan ultrasound, which you can see this really large celery body lesion. At this point is about a centimeter and a half in all dimensions. It maintained its high reflectivity on A scan, but there was some more vascularity at this point in this exam. So while the A scan continued to be inconsistent with melanoma, there was overwhelming concern that this could be a melanoma. At this point, she's demonstrated there's growth, the tumor, there's a lot of intraocular pigment deposition. And while her work up systemically with imaging and lab work was reassuring, the ambiguity of this possibly being malignant lesion was kind of unacceptable to her. She had just gotten married, she was wanting to start a family. I think there was also some concern about her lack of following up for three and a half years that they didn't want to take any risks. So the patient was offered a nucleation and she elected to proceed. So then I got to see the path with Dr. Ramilas. It was nice to kind of have some continuity, but as you can see, this is a really large tumor. This is actually six fields of view combined together to fully capture this celery body mass. And it is impressively pigmented. A little bit larger, a higher magnification. You can see again, really densely pigmented cells. It's difficult to understand what's going on with the nuclei. This image does show kind of the pseudosys formation within the tumor. So there's no real epithelial lining, but there are cysts throughout. So this is a once bleached histologic section in which you can kind of be able to see some of the architecture. You have this really darkly pigmented cells still with abundant cytoplasm just chock full of pigment. You see some macrophages kind of in the center part of the specimen. But again, it's still a little bit difficult to actually see what's going on with the nuclei. So this is a twice bleached section and now you can really convince yourself that these are bland nuclei, small nucleoli and low not nucleus to cytoplasm ratio in this specimen. That was throughout the entire thing, which is really reassuring for benign lesion. And also helped us make the diagnosis of a celery body, melanocytoma. So melanocytomas, you might also hear them be referred to as menocellular nevi or melanocytoma of the optic disc. They were first just arrived around 1930, but the term melanocytoma started to be used more around 1965. It was coined by Zimmerman. And you'll see melanocytoma of the optic disc a lot in the literature. And the reason is it's most commonly located there. So these lesions can be located anywhere in the UVL tract, just like our case. They have this really common appearance, darkly pigmented. They can just involve the optic nerve or they can kind of spread out and avoid the adjacent core rate and retina. They were rare. I tried so hard to find an incidence to report for you guys, but I couldn't find one. Just know that a lot of this data is coming from case reports and analyses where there's maybe 10 to 20 patients in total reported. These are usually unilateral and they're slightly more common in women with about a 60 to 40 split. The mean age of diagnosis is 50 years, which you can imagine that's the same age that you're starting to worry about more of melanoma in your differential. In one study, they found out about 8% had an association with ocular melanocytosis, but that there were no other ophthalmic diagnoses that predispose someone to developing one of these. These are quite stagnant lesions. The growth is actually quite rare, only about 10 to 15%. One study showed growth over several years. The thought that these may be congenital and that they are amelanotic and then gain their pigmentation throughout life, which is why you're diagnosing them at 50 years, but they don't seem to be growing after that. I always find this surprising that there's not a lot of visual impact for these melanocytomas. One study found about 75% have preserved vision and 26% experience at least mild vision loss and snelin acuity. What is interesting is about 90% of them did have visual field changes and this ran the gamut from a large blind spot, nasal step to arguments. What is visually impactful for these patients are kind of the secondary consequences. So retinal exudation, optic dyskidema or optic nerve ischemia, subretinal fluid and then RVOs like I'm showing here, obviously do have an impact on the vision. There is not a lot of, sorry, a malignant potential for these lesions. Fortunately, so malignant transformation was reported in about one to 2% of cases. However, profound vision loss and growth of these lesions made one concern for malignant transformation. Pathologically, you're gonna expect your classic spindle-shaped melanoma cells among like the parenchyma of our oval melanocytoma cells. So these are typically diagnosed clinically. Fundus photography is really helpful in following them serially and getting measurements, obviously visual fields to kind of gather whether they're experiencing any visual field defects. Unfortunately, FA just kind of shows hypochlorosins throughout the whole angiogram. So it's not entirely helpful, though if you're looking for some of these other consequences like fluid or RVOs, it will show that. Similarly on OCT, again, if you get an OCT through one of these lesions, there's nothing specific, but they can be helpful for looking for retinal pathology. And then of course, ultrasound. So most melanocytomas are small, less than two millimeters, which certainly wasn't our issue in this case. You can imagine trying to infer the internal reflectivity on ultrasound can be quite difficult with this. To the point that in the literature, you're gonna find some reports that are gonna report that melanocytomas are high reflective, while others are gonna say that they're low reflective. I would say most of the reports do all them high reflective though, just like in our case. Prior to the use of ultrasound lesion simulating melanoma, so this was all comers, mevi, melanocytomas, medulla epithelialomas, et cetera, were responsible for about 20% of the nucleations, but now nucleation specimens from melanocytomas are really quite rare. And just to review the A-scan. So what was interesting, these densely cellular lesions, those that have a very homogenous structure like a melanoma are gonna have low internal reflectivity just because of the lack of interfaces, whereas those with multiple interfaces are very heterogeneous, they have cysts or necrosis or pseudosis are gonna have high reflectivity. So things like a homangioma would make me think of that. So the A-scan on the top is one of a melanoma. You can see it has low reflective waves where I've just copied below the A-scan of our lesion that's showing high reflectivity. So in our case, the microscopy showed multiple pseudosis which cause high reflectivity on A-scan. And to our knowledge, this was the first correlation between the histopathology of a large melanocytoma with pseudosis and high reflectivity on A-scan. So we have now reported this and it's in a case report now. My takeaways. Not all of that is pigmented as melanoma. It's not lost on me, especially that I'm going into cornea that this will probably be the only time that I see this tumor, but it was a good reminder to keep the differential broad to share decision-making with patients is key. I think about what the outcome would have been if the diagnostic ambiguity of this lesion hadn't been shared with the patient and how ultrasound kind of helped introduce some of that ambiguity because to her, when the pathology came back benign, she was relieved that she didn't have a malignancy. She had just gotten married. She could start having a family and she no longer had a blind painful eye, but I could imagine if someone was expecting that this to be a melanoma and they were enucleated for a benign lesion that the conversation would probably look a little bit different. And then lastly, Dr. Harry's parting words with us on Friday at our mole lecture was ultrasound is important. And I feel like it was really displayed in this case as well. These ultrasound is important for helping broaden the differential diagnosis. Like in our case, it's helping us gain measurements. It's helping us even tell internally what these tumors may be doing. And I think it was really well demonstrated in this case. Those are my sources. And thank you, Dr. Harry, Dr. Mamelis and Dr. Guy and of course the awesome path fellows who put together the photos for this case. I'm happy to take any questions. There used to be ultrasound fellowships and people who subspecialized in ultrasound. It's another example of a kind of a dying subspecialty. We're lucky to have Dr. Harry. He has expertise, but most places in the country, ultrasound, good strong diagnostic ultrasound is just hopefully what maybe one group has taught the other that expertise doesn't exist in a lot of the country anymore. Can we learn that these are benign and relatively slow growing? Like you said, only like 15 and 20%. Did you see anything in the literature that when they do grow, they're aggressive? Like in this case, 3.5 follow-up years, you can see that almost the entire eye is tumor. Like that's pretty impressive. Yeah. So even if I think diagnostically, if we would have known right off from the start that this was a melanocytoma, that interval growth during that three and a half years, I think we would have still been concerned for malignant transformation. And maybe she would have ended up with an enucleation or at least the biopsy to start, even if we had not considered melanoma in the differential for sure. We have a comment from Dr. Mamelis so we'll unmute him here. Okay, thanks. Can you hear me? Yes, I can. Sorry, I'm moving really slow on crutches. And so I'm just sitting at my desk here. This was interesting for a couple of reasons. First of all, the sheer size of this lesion and the melanocytomas that we usually see granted, they're very rare. So we don't usually see these are quite small or just medium size. And so this one was very large. The other thing that was interesting about this was the fact that there was the high reflectivity on the ultrasound. And that was because of the cysts that were in there. And usually when you see these, the reflectivity is low, which then makes it difficult to discern these from a malignant melanoma. And that's where the difficulty comes up in trying to diagnose these is to discern the melanocytoma, which is benign from a melanoma, which is potentially aggressive. Now, there have been rare cases reported where a true melanocytoma has then turned into a malignant melanoma. And in fact, Dave Apple reported one from here. It was right after I had left my fellowship with David and he reported one here. But these are extremely rare that these go on into melanomas. And so this one was very large. It had high reflectivity. And it's less commonly seen arising from the ciliary body than it is from the optic nerve head, which is where you most commonly see these. But this is only the second ciliary body melanocytoma I've seen in 35 years. So very, very rare lesion. And nicely presented. It really made a very nice case report. Thanks, Dr. Manlis. Any other questions or comments? All right. Well, thank you, Allie. All right. Up next, we have Mary Glenn Veyu. She is again a pediatric neurology, PGI3 resident. Mary Glenn, fun fact, she is from Montana and her favorite activity there is kayaking. She's going to be talking about myelin ligandendrocyte lycoprotein or MOG optic neuritis. All right, everyone, thank you for having me. I'm going to be sharing a case that was recently on our inpatient neurology service. I'm on my adult neuro year. So this is an adult case of MOG optic neuritis. So the patient is a healthy 39 year old female who came in with a week of painful eye movements and progressive bilateral vision loss. And the first symptom that she'd noticed was that pain with eye movement didn't think much of it initially. And then she started to develop a central scatoma that spread outward. She described her vision as walking into a dim room after being outside on a sunny day. She saw a local ophthalmologist early on who didn't really notice anything significant on her visual acuity, visual fields or a fundoscopic exam. And she had an MRI brain without contrast done as an outpatient, which was unremarkable at the time. But over the course of that week, her vision continued to decline and she then had complete loss of her color vision. She described everything as seeming washed out and she could only make out big shapes. So really in terms of her past medical history, there was nothing too significant. She hadn't had any surgeries, trauma, or other ophthalm problems, no similar episodes in the past, no significant neurologic or autoimmune history. And the only medication that she took was Benjamin for weight loss and then no significant travel or exposure history, notably no preceding viruses or vaccinations that she reported. On her exam, as you can see her visual acuity was significantly impaired in both eyes. She did have a RAPD on the right and her visual fields were globally affected. Her color vision was also severely reduced and she was noted to have grade two discadema bilaterally. Her neuro exam, including cranial nerves, her motor exam, sensory exam and coordination were all normal. And she did note full range of motion but pain with extracurricular movement. So we admitted her and obtained MRI brain, face and orbits with and without contrast. And it did show diffuse enlargement and abnormal enhancement of her bilateral optic nerves consistent with bilateral optic neuritis and notably greater than 50% of the optic nerves were enhanced and her MRI and T-spine were normal. There's no other lesions seen on her. So in terms of her diagnosis, she was atypical in terms of her optic neuritis because she had bilateral involvement but the classic tryout of typical or demyelinating optic neuritis involves this variable vision loss, periocular pain, worse with eye movement and color blindness. So in thinking of your differential and what to work up demyelination is obviously a high concern as well as other antibody media processes such as NMO spectrum disorder, MOG, inflammatory autoimmune diseases such as sarcoid, SLE, et cetera, infectious causes, post-infectious or post-vaccination and then it can just be idiopathic as well. So given our high index of suspicion for an inflammatory or autoimmune process in her, given her age, her absence of other infectious systemic signs or symptoms and really no risk factors in her medical history, we started empiric treatment of optic neuritis with one gram per day of IV methyl prednisone and we chose to do five days followed by a six-week oral prednisone taper in her while we awaited further workup. So the lab workup we got on her when she was inpatient, we did CSF studies and her opening pressure cell counts protein glucose bands were all negative including flow and cytology. Her inflammatory markers and other autoimmune labs such as ANCA, ENA, ANA were all unmarkable as well. Her serum aquaporn IV antibody resulted negative and while she was admitted, we did get the results of her CNSD myelinating panel and she was MOG antibody positive. She had a relatively low titer but we did consider that to be positive. We also sent a Mayo encephalopathy autoimmune and perineoplastic panel that eventually did result negative as well. So we diagnosed with MOG optic neuritis and one of the most impressive things to me was to see her dramatic improvement. So on day of discharge her vision was 2040 bilaterally, she'd no longer had an APD, normal visual fields and her color vision was still impacted but was significantly improved. So MOG optic neuritis, in terms of MOG antibody disease optic neuritis is one of the most common clinical manifestations and presentations of this disease. You often see the pain precede the vision loss and the vision loss is typically more severe than in other optic neuritis disorders such as NMO or MS and it typically involves more of the optic nerve. So as in her case, we saw a greater than 50% of the optic nerve affected. You often more commonly see optic disc edema as well than in other causes of optic neuritis. It is more commonly bilateral than in other causes of optic neuritis. So in 50% it's bilateral. It's more likely to be a monophasic course but it does still recur in about 50% of patients. And the best news is that the prognosis is good. So typically most of their lesions resolve over time as opposed to MS lesions or NMO lesions. You're less likely to have CSF bands and the treatment is IV steroids which typically patients respond well to. In the duration of treatment, it doesn't seem like there's a very clear consensus to this but generally three to five days of IV steroids followed by a six to 12 week oral tapers, generally what's recommended. Interfractory cases, plasma exchange can be considered, IVIG can be considered and the length of this course varies as well. So as I said, one of the cool things about this case was being able to have an answer the same hospital admission and be able to provide some prognostication for the patient which rarely happens in neurology. So her five days stay, we were able to say you have MOG optic neuritis and that was very satisfying for me and I think gave her some peace of mind too when she's wondering for this BNMO am I more likely to have recurrent lesions, spinal cord lesions, et cetera. So I think it's awesome that in the past 10 years we've started to identify these discreet antibodies implicated in optic neuritis and they can give us some guidance and give patients some guidance about what to expect. So obviously she'll follow up with neuroophthalmology and autoimmune neurology as an outpatient and continue with occupational therapy until her vision is totally recovered and that's my case. So you think about the underlying problem is metabolic and obviously then there's a strong autoimmune component associated with that but what are some of the other, I mean it can't just be optic neuritis what other presenting symptoms do these people have or is this really just mainly optic neuritis? With MOG antibody disease, well in kids we more commonly see ADEMS so this diffuse demyelination pattern that usually also is monophasic. It can present with spinal cord involvement alone so it can be really highly variable. So it can be a fairly profound problem associated with the nervous system elsewhere but this is the most common and why do we think that it tends to be monophasic and not recurrent? That's a really good question. I tried to look into that too and it seems like if people stay seropositive they're more likely to have relapses but that's really the only thing I can see that's a risk factor for relapse versus just having a monophasic course. So still a bit of a mystery then? I think so, yeah. So that great case and it is very gratifying to see these people. I think that the wonderful thing is that they tend not to have other neurologic conditions like multiple sclerosis and they're not really at risk of becoming paralyzed like neuromyelitis and optica, which is just great. And their visual recovery tends to be really terrific and often not nearly as much optic nerve tissue loss like on OCT as a lot of other optic neuritis is. But the spectrum of presentation is extremely broad as Mary Glenn was saying and in kids they could present like basically in a coma because their entire brain is inflamed and yet they recover. There can be very profound cerebellar and brainstem inflammatory conditions pretty much anywhere that there's white matter can get inflamed. One of the interesting things that has come out with MOG optic neuritis is cryon, chronic relapsing inflammatory optic neuropathy which has always just been a, well I don't know, you just keep getting optic neuritis I don't know why. But as these people keep coming back for follow if we test them for MOG and it turns out I'd say at least half maybe two thirds of those folks actually have MOG and now we have a test for it and now we have some sort of guidance as to where, how to treat them. That has been hugely gratifying. And then also slightly buried was that 50% of these people do recur. So relapsing optic neuritis is not uncommon probably more common than multiple sclerosis. I mean you don't see people with regular multiple sclerosis having relapsing optic neuritis again and again and again whereas somebody with MOG they can 50% of the time. And then finally just a little antibody deal. So the Mayo is the one, they're the ones who developed this antibody test which was terrific. They just have everybody's serum in the entire world who's ever had anything wrong with them. So they are constantly searching for stuff, useful stuff and it's been so great. But when a test gets licensed then other places can do it. So ARUP can test for MOG. So we just learned on Friday at the Wynow meeting Western Intermountain Neurologic Organization meeting there were a couple of folks talking about MOG and of course it turns out that there is a difference. So there is a cell-based assay and turns out that the dead cell-based assay which is what ARUP does is not as sensitive as the live cell-based assay that Mayo does. So if you're kind of thinking about the diagnosis and you've got this equivocal level it's enough to make a diagnosis but if you really wanna know, you still have to go to Mayo. Great case Mary Glenn.