 Hi, history and review systems and complete examiner difficult to obtain, especially in preverbal, uncorrupted children. The differential diagnosis of pediatric pediatrics varies with age, with an overrepresentation really of infectious ideologies in younger children and pediatric specific mass grades. Can you think of one of them that you never want to miss? Anybody? All right. No blast illness. All right. Unique endogenous syndromes in kids. One has a name named after JIA, right, juvenile adiabatic raspberries, and then atypical presentations of familiar syndromes in adult entities like pediatric sarcoid, which is a little bit different. And then, of course, the choice and interpretation of laboratory tests. So certain tests may be physiologically abnormally elevated in a child, like an in-judgment pervergancy. Here, there are management challenges. The onset of inflammation is insidious, chronic bilateral and asymptomatic. So children aren't going to tell you that they have a problem. There's a frequent development of complications with the presentation with established ocular pathology is in itself a risk for development of further complications and is also kind of testimony to the diagnostic delay and screening failure in many of these kids. And then, of course, in children, you have the unique risk of amblyopia. Therapeutic challenges include the use of corticosteroids. So there is systemic corticosteroids in particular, well, can result in growth retardation in children. And of course, there are the accurate complications that we're familiar with. And there is therapeutic timidity with respect to nonsteroidal immunomodulation. And of course, the greater surgical risks that are inherent in kids with exuberant inflammatory response to surgery and the apparent complications of certain disease and incestuous GIA, which have more surgical complications. You guys hopefully read about the epidemiology of this disease. I'm not going to go over it in any kind of detail. It's about fourfold less common in adults. But that doesn't mean that it's not problematic. In a tertiary care setting, it can represent between 2% and 22% of UBI patients. There's a slight female predominance, and it represents a large number of children in the United States, even larger globally. So the anatomic distribution of UBI is in a tertiary care setting. What do you think the most common anterior distribution is? The two most common for pediatric disease. A cute anterior UBI. They anterior for sure. Anterior and intermediate UBI. With posterior and pan-UBI, it's being less well represented. Similarly, in a population-based studies, most of the things that people will see in general practice or out in the community will be anterior predominance. And in adults, things are similarly distributed. There's, of course, referral bias, and depending upon where you're on the world, as to what entity you will see. What do you think the most common, quote, diagnosis in kids is? The most common diagnosis? Well, the most common diagnosis it is, we don't know. Idiopathic or indifferentiated disease in about, you know, 50% of the time. Then the second most common is JAA and parsed minus, then toxoplasmosis. Okay, structural complications certainly affect visual outcome. List two or three structural complications that could affect visual outcome that might be common in kids with pediatric uveitis. Anybody? Cataract. We can have band keratopathy and other epitheliopathies. Right. Macroma. CME. What about in that macula? Macular scar. Okay. A more common than that, maybe? CME. Nice. Yeah, macrodema. Okay. So you've hit most of these in CNVM. So these complications are directly related to the duration of uveitis, as to be expected, and the anatomic location of the disease. Right. So with posterior pan-uveitis having more structural complications and then infectious uveology having a poorer prognosis. The visual outcome and prognosis is very guarded in kids with uveitis with visual impairment and severe visual loss occurring in a significant portion of the population with unilateral lateral blindness occurring in a not insignificant portion of patients. Okay. Differential diagnosis. Non-infectious anterior. What do you think? Just lift off some entities. Okay. Okay. Can you? Right. Kawasaki, early onset sarcoid, Valaus syndrome. And we've gone over this pediatric intermediate uveitis, posterior uveitis, represented by disease in new stitches. Less commonly sarcoid, multifocal basciates. And these are occurring in older children. Infectious anterior disease. What do you think the most common is? Same as in adults. Herpetic. Herpetic. Right. Herpetic. Then Fuchs heterochromic urtipsychitis, you can see in children. And something that post infectious autoimmune uveitis is more commonly seen in kids than in adults or post-vaccination uveitis. And of course, post-tier disease, you have the congenital infections. And then they are listed here. And then, of course, Bartonella and nematode associated disease, Lyme and opomitis. And of course, we can't neglect the really important masquerade syndromes in kids such as retinoplasma, leukemia, GXG and trauma. We can also think about the differential diagnosis in terms of the age of presentation. I think this is semi-useful. So infants, zero to two years old, what kind of things are you going to think about? What would this kind of a picture bring to your mind? What congenital infection might that bring about? I would think torch, like maybe a rubella. Exactly. Torch, that's exactly what this is. So the torch is toxo and other rubella. It's the herpes, congenital syphilis, toxic cryosys, and retinoplasma. Very good. Then in older children between the ages of two and eight, the most common cause of systemic cause of uveitis in children, peak onset is around this age. What would that be, do you think? GIA would be a big one. You got it. Right. Okay. GIA, they're not going to tell you that they have this entity. That's why they're screened. And then of course, these infectious and non-infectious etiologies and these very unusual but still diseases that we see in our clinic, such as mucle wells and blotosyndrome, middle juvenile cranial metastasis. Then in adolescence, we're approaching kind of disease entities that you might also see in adults, such as the most common posture segment disease, toxoplasmosis. It's going to also be a general infection, as you know, intermediate and partial minus, B-27 associated disease. And then of course, these white dots and post-infectious autoimmune type of uveitis. So let's just start out with a case. This is a long case, but it's instructive because it shows you the kind of the course and the many options that are associated with GIA. So this is a kid that I saw when I first got here and I saw him last year, finally, again. So in October of 2002, we presented in the initial evaluation pediatric rheumatology and was diagnosed with oligorticular GIA. It was ANA-positive and was placed on methotrexate 10 milligrams. He was then presented to our clinic on this dose of medication with inflammation in both the sides, bilateral anterior uveitis. The plan was to put him on, treat his topical disease and then what else do you think we could do for him? What other things can we modify in this person's? Plan is on a systemic medication, right? So we could increase the methotrexate, which we did to 15 milligrams a week orally. So the kind of generalized treatment is a paradigm. So I don't like to talk about algorithms so much in uveitis, but really more like treatment approaches because people think of algorithms as that's the only way to do it. But really care must be individualized to the patient. So we start out with topical corticosteroids and then have a very low threshold to transition to steroid sparing immunomodulatory therapy because of the complications associated with both topical corticosteroids and long-term oral steroids. So oral steroids are used as a bridge, sometimes with anti-metabolites or for very severe inflammation. And then the first line of the anti-metabolites and as we will see later, and then biological therapies. So I just want to mention that there was an important paper that was published by Jim Thorn which showed that the risk of cataract development is lower in eyes. They're treated with chronic topical corticosteroids of less than equals to three drops per day. So this is important because there had been the dogma that no cells, no prisoners, but there are some children that really, no matter what you do, they have 0.5 plus cells or they require some topical steroids in order to keep them quiet. So this paper is important in that it showed that in patients that are on two drops or less, the risk of developing cataract, that is an important complication, is pretty low. However, 60% of these patients required another systemic medication or biologic to control their UBI. So this is not for consideration in patients for first-line treatment, but usually those patients that are already on systemic biological therapy. So some of them need kind of a sub-pressive dose, a drop or two a day of type 4K to keep them under control. That being said, the goal is to get them off of steroids completely, and I attempt to do that in all of my patients. Not all of them are successfully able to do that, and I watch them like a hawk to develop an elevated intracurricular pressure. So back to our kid. In June of 2017, he presents within our arthritis flare. It's no real thickening in his knees and some inflammation in his left eye. So what do we do for him? Well, he's got anterior segment inflammation, right? So we've got to treat that. We switched him to subcutaneous methotrexate. And why would we switch him to subcutaneous methotrexate? He wasn't really having any problems taking any oral medication. But why do you think subcutaneous might be the choice? Subcutaneous methotrexate is a little bit more bioavailable, so it works a little bit better. And it is also associated with less frequent nausea, but kids still get nausea. Is that all we could do for him? He's been cooking along for a couple of years with this. Well, we wanted to treat him a little harder, so we started with a biologic agent, and we started with an influx of mad every four weeks. And part of the reason for choosing influx mad was to give him a higher dose and to ensure that he was getting treated because he had to show up for his infusions. We also pulsed almost an oral prednisone to help him pain on a one-week course. So we did pretty well with that. And in 2009, we were able to extend his influx mad interval at molar arthritis of his knees and on influx mad for Q8 weeks in methotrexate at 12.5 with no ocular inflammation. The decision was made to transition him to Adalimumab for ease of administration of his biologic. As you know, Adalimumab is approved for adult uveitis and for JAA, and it is humanized monoclonal antibody, which can be administered subcutaneously at home. For this particular person, that presented certain problems for social reasons, but in any case, we made that decision. Short course of prednisone kept in on 12.5 milligrams of methotrexate. Well, in November, I came back with a flare of uveitis and a decent vision, but still, you know, unacceptably elevated inflammation. The plan here was to start Durazol, which I don't infrequently with children, but he had a lot of information in his eye. And then discontinued chimera, and we started another biologic called Orencia for abidescept, which at the time was showing promise for children with JAA. In, he then represented with low-grade intraocular inflammation, persistent arthritis, and after, you know, six months to nine months, you know, on this medication was declared abyssa failure. Our plan, we went back to what was working, to infliximab, increases methotrexate, and then treated him with topical corticosteroids. This seemed to actually work for him. Okay, he had quiescent uveitis and arthritis, and over the ensuing year, we were able to extend his infliximab interval out from every month to every six weeks, and then to reduce his methotrexate dose and to extend him out to eight weeks. So this is just gives you a little vignette of, you know, it's never over to the fat ladies things, right? You know, in baseball, but it's never really over for JAA either. They don't, there's very good evidence to suggest that a significant proportion of children don't really outgrow their inflammation. And so there are plenty of adults that have had JAA that still have acute inflammation, structural complications, and have many of these patients in the clinic. So you have all read about JAA, and I'll just give you a quick tour of JAA, unless someone else wants to do it for me, but I thought I would save some of the more rarefied entities for you guys. Okay, so this is probably the most important disease for you guys to know about. It encompasses a spectrum of childhood arthritis, and depending upon how you classify it, there are three different classification syndromes. It's called something either juvenile rheumatoid arthritis or juvenile chronic arthritis or juvenile idiopathic arthritis, which is what we use the nationally against rheumatism. So there you have a kid, he's got inflammation of his joints in his hands, the most common form of chronic arthritis in childhood, and the most common systemic association with the erudite cyclitis, you know, comprising up to a third of patients in tertiary care settings in the pediatric population. Okay, so the risk for the development of uveitis, okay, it depends on the classification system, but in the ILIR system, the JAA subtype is very important. Okay, and so what subtype is the most commonly associated with erudite cyclitis in JAA? Anyone? So I'm going to go through it with you. So it's oligoarticular disease. Anybody know what oligoarticular disease is? Or last joints. Right, exactly. Okay, so it can be persistent or extended. Okay, so oligoarticular disease carries about a 30% chance of inflammation. And then in the ILIR system, there are these other categories, rheumatoid factor negative and positive polyarthritis, psoriatic arthritis, which is notoriously difficult to treat. And anthocytus related arthritis, which behaves more like an acute HLAB-27 associated disease and is more common in boys. And then of course, unidentified. ANA positivity carries a significant risk of uveitis. So ANA positive oligoarticular disease is a not so great combination. Then of course, there's younger age of onset of arthritis between two and five years and female sex. So it goes back to Adam and Eve, the females carrying that bad apple here. However, we'll see that it changes in terms of their prognosis. And then there are HLA associations with the development of ebibitis. Okay, the presentation we kind of went over with Damian here. Asymptomatic chronic bilateral non-grinded oligromous erytocycletus. They're not going to tell you that they have disease, peak onset is up to four years of age. This is important in that 90% follow articular disease, but 10% may precede the onset of arthritis. So you have a significant proportion of patients that are smoldering out there before entering into the healthcare system. And many of these patients are the ones that present with really severe complications or those that are held on to by the referring physician too long. Systemic ocular inflammatory activity can be independent. So that you can have arthritis activity without intraocular inflammation and vice versa. Or it can be some of the minutes. Particularly some poor visual prognosis. This is a poor visual prognosis between 2015-20. 100 study at the site study, which was a large retrospective study of five huge ebibitis practices in the United States. So active inflammation. So that's why the mantra is, control of inflammation and active inflammation as described by greater than or equal to one plus AC cell or greater than or equal to 0.5 plus vitreous cell. The presence of posterior sneakia that is a marker for previous diseases, I said to you before a presentation with ocular complications is in itself a risk for the development of future complications and posterior sneak is one of them. And then it turned out prior intraocular surgery, which makes sense because kids that have had surgery for probably have had structural complications. So here you have anterior segment inflammation. Any of you as we talked about before are concurrent with the diagnosis of ebibitis. So there may be a delay with entering into the healthcare system. A shorter interval from the onset of arthritis to ebibitis should belong referral to a specialist. And male sex seem to do poor in terms of visual outcome. Besides, so you identify ocular complications, which I think you guys have identified before. Okay. Bankeratopathy, posterior sneakia, cataract, ocular hypertension, macrodema, every retinal membrane and hypotony. And they occur at a pretty high percentage, right, 34, 29%, 22% per year for eye year. 60% of these patients I present with at least one complication at presentation. Okay. And the incidence of a new complication is about 15% per year. So we have to do a good, better job at controlling inflammation. So therapeutic approach, as we discussed previously, is this kind of therapeutic step ladder with frequent topical steroids using dysthyl predinate with caution because I think this induces ocular hypertension and particularly in children. Oral non-steroidals are frequently used for patients with arthritis and may be steroid-sparing, but I don't use them as primary intention for steroid-sparing therapy and keep them on it, obviously if the child is on it for their arthritis. Periocular and intravitural corticostero are used with caution in children for the very same reasons in that ocular hypertension is more of a complication in kids. And it's a little bit more difficult to, you know, get it out. You don't want to be putting tubes in children if you can help it. Brief, well-defined periods of systemic corticosteroids and then steroid-sparing immunomodulatory. So in our introductory lecture, we went over the classes of medications that were used, the anti-metabolites, including methotrexate, mycophenolate, azithioprene, the calcinary and inhibitory cyclosporontachrolynus. Acolytine agents are really not used for JA these days as we have. Biological therapies. Just a word about methotrexate. It's the first line in JIA and probably the first line in adult uveitis in terms of steroid-sparing medication. And there's good data from the Netherlands where they have huge databases of kids with JIA. And that is useful in counseling the parents for patients with JIA. And that is that, you know, when you put patient on an anti-metabolite or embark upon immunomodulatory therapy, you're talking about a long-term commitment. And so they're not on it for just a year. There's good data to suggest the longer period of time of inactivity, that is longer period of time on medication without steroids, results in a better chance of remission and disease. So we're talking three years is better than one year. And then an older age at the time of withdrawal as was shown that a reduction of nuance of uveitis was less frequent when patients were treated within the first year of diagnosis. There are alternatives to non-responders such as other anti-metabolics, mycophenylate, and isopropyben, which are used less frequently in kids. Cyclosporin is used as less frequently but is well-tolerated in children as opposed to adults at higher doses. And then early... So I don't use this as often as I used to, but I have a very low threshold now that we have good biologics to advance them to biological therapy if they have persistent activity while on an anti-metallic way. So here is a summary table of all the biologics that are in common, that are in use. There are hundreds of other biologics out there in development. And I think you're familiar with many of them, we won't dwell on that, but the ones that are the most common that you might see in that a child might be on would be these three TNF inhibitors. Tenercept is not particularly useful in uveitis, but many kids will be placed on in Tenercept for their arthritis. So it works well for arthritis, but not for uveitis. So if a child comes in on a Tenercept and they have a legal or particular disease and they need to be screened every three months, and they don't have the information arrive and there's no reason to switch them until they develop inflammation, in which case we would switch them to a different biologic such as atalumab. So atalumab, as you know, is FDA approved in adults and in children for uveitis, but not for chronic entry of uveitis, interestingly in adults. And the advantage to this medication is that it's humanized, less immunogenic, and can be administered separately. Whether or not it's more effective than infliximab is a matter of fate. They seem to be equal potent, but infliximab does have a couple of advantages that will in certain cases, such as our first case, as we'll see. You, I just want to bring your attention to the fact that there was a trial that was conducted a multi-centered trial in Great Britain called the Sickmore Trial in which they looked at the clinical effectiveness and cost effectiveness of atalumab plus methotrexate versus methotrexate alone. And basically the study showed confirmed kind of the clinical practice that of the superiority of both the use of both methotrexate and atalumab together rather than methotrexate alone. So there were significant differences in the time to treatment response and a significantly greater portion in the reduction of treatment failure with the combination. Infliximab is also quite useful. The disadvantage being that it needs to be administered subcutaneously. It's a chimera. So it is a mass human antibody and is usually administered together with methotrexate to reduce the chances of anti-infliximab antibodies. Methotrexate also will reduce the incidence of anti-infliximab anti-atalumab antibodies which can also occur and decrease the advocacy of that medication but less frequently occurs less frequently than that with infliximab. The one of the advantages of infliximab is that it can be administered at higher doses. So anywhere from five to 20 milligrams per kilogram you can shorten the infusion interval to monthly and then extend it. So it allows a little bit more flexibility with in terms of dosing. The bottom line is that none of these medications are magic bullets. They are not remitted. That is, it doesn't be rate of remission is low and it doesn't cure the disease. So we have to be willing to use alternative medications and some of those alternatives include alternative medications in the same class, anti-TNF such as galimab or sirtilizumab and that third line biologic agents directed against different cytokines. Biodeseptorensia is one that we with that our patient had it's not particularly effective in uveitis as our experience has born out. Then of course there are other medications against specific cytokines sirtilizumab and tostilizumab which are coming to the fore and have been shown to be useful both in adults and children with refractory GIA. So it doesn't work? Yeah, it does actually. So in both singles centered studies at Hopkins there's a reduced risk about your complications as you can see here and 86% of improvement in visual acuity with patients on IMT that were administered early and the psycho heart which is again this large retrospective to study for this out fairly recently with a 60% reduction in visual loss particularly for the less than 2050 outcome. Okay, we're going to switch gears a little bit. Getting tired? This is a pretty interesting case four-year-old kid with right eye paying for two months parents didn't observe any changes in behavior. This patient was seen in Cincinnati and he had a brief episode of diarrhea that responded spontaneously cousin with paracetamides and really no past medical history. His vision was pretty good. He had anti-segment inflammation in the right eye and it was quiet in the left but he had an inferior pigmented iris mass in the angle. Okay, and that's what this mass looked like here. Okay, and this patient was referred to me by a former attending in the pediatrics department here and she performed a B scan which shows this mass here and did an examination under anesthesia. We're so posture lesions here that were deep, right? So it was beneath retina and then coroid seemed to me in both eyes. So she had a little bit more guts than I would ever have in diagnosing this so that a fluorescent angiogram or in evaluating this patient. Fluorescent angiogram shows some delay in the coral filling but it's really standing on these lesions and there were several filled in the right eye on OCC. These are images from Cincinnati. So she went ahead and decided to work the patient up extensively up the wazoo that's the technical technical name for them but everything I could possibly think of it. Okay, and biopsy this patient. Okay. So I would be a little I would be a little bit hesitant to do that only because of the risk of that you know could represent an RB but I think that she was pretty confident that it represented inflammatory diseases and indeed that's what the pathologies seem to indicate. So she was the child was referred here with a diagnosis of panubias multifocal cordias right eye greater than one thigh. So what is the differential diagnosis that you would think of in a case like this? I mentioned one of them. What would you guys think? I think sarcoid or blouse syndrome would also be on my list. Anything else? Okay. So early onsite sarcoid things that kind of mimic sarcoid like rare diseases such as blouse syndrome or familial system of juvenile granulomatosis Epstein-Barr virus such as red-nose cordias is just a real rare red herring that I've seen twice here common variable immunodeficiency syndrome probably not that rare. Seen it a couple of times here and it may look very much like early onsite sarcoid or multifocal cordias. So the plan was to place the patient on prednisone because we were fairly convinced it did not represent an infectious theology. The patient was already on valetrex and we treated the patient with durazole for a brief period of time in atrophy. And over two months became quiet with flattening of the regions and tapered the valetrex to a suppressive dose and continued the prednisone taper and sure enough there was at least in the posterior pole resolution of these lesions it was resolution of these subrennial fluid just on prednisone. So off of prednisone for a month recurrent ac cell and a new red papzomash on the cheeks and arms and legs. So it was you know kind of giving us more of a clue as to maybe what was happening diagnostically. Sometimes the diagnosis is not you know apparent to you immediately and develops in time. So you're staying in the hunt is usually what is necessary and new symptoms and new signs emerge. So our plan here was since the patient already been on course of steroids when he was a young kid to start immunomodulatory therapy with another steroid bridge. And two months later the patient was quiet. Okay skin rash could resolve the rash was thought to be consistent was not biopsied by the way unfortunately because it was almost evanescent but thought to maybe be consistent with one of two one common one uncommon disease. So we continued methotrexate and prednisone and one of the uncommon diseases we tested for has a nod to mutation. Actually both of these diseases do. And so that was negative and we'll discuss what that mutation represents. So our working diagnosis was sporadic juvenile sarcolysis. And over time the patient did well without reactivation of disease on steroid sparing at the trexate. So sarcolysis is commonly you know is a commonly cited as the cause of childhood UBI's but it's actually not that common. And there are two two types of two forms of it. One is a juvenile or early onset less than five years of age and then there's later onset and the early onset is a little bit different in that it can present with cutaneous papules and plaques and erythema nondosomes that gave us this kind of clue that maybe this patient had early onset sarcolysis he didn't have parliarticular arthritis ocular inflammation any lesion but the other thing is that usually pulmonary disease does not develop in early onset sarcolyd. And recent work has suggested that a significant proportion of these disease will carry certain type of mutation which is present in another rare disease and represents the sporadic one of that disease. So the card not two mutation on chromosome 16. So late onset sarcolydosis is very similar to that in adults with a high proportion of pulmonary disease. Okay, so the phenotype is chronic bilateral granulomus intervirtus with virus nodules. Intermeter posterior virtus and lacrimal gland involvement is uncommon. I suppose if you have you know ACE is physically elevated in children so the lysosome would be better. And older children in chest x-ray then cut the spiral CT and a biopsy. So obviously the only thing that Anna had to biopsy was the eye but if you had a biopsy if you had the skin or a aris nodule to biopsy that would be a place to go first rather than the lung in an older child. And the differential diagnosis is JIA really. So the differentiating features between sarcoid and JIA are non granulomus versus granulomus anterior involvement in JIA where anything any involvement in sarcoid oligoarticular disease less than four joints less than or equal to four joints polyarticular disease in sarcoid. And then in juvenile sarcoid pulmonary involvement can occur but it usually in later onset disease but it's absent in JIA. So the differential diagnosis of childhood sarcoid when you hear a hoof beats you think of what you think of courses but there are zebras. And here's one of them. Here's a child that presents with this kind of granulomus rash. It's polyarthritis granulomus arthritis granulomus anterior uveitis with synechia and multiple coriditis. So here is a zebra that is similar to sarcoid assist in kids. Anybody have an idea of what this might be? We've mentioned it a couple of times already. Is there any pulmonary findings? No pulmonary findings. Flows? Flows, right. So other names for plow so it's a triad of granulomus dermatitis polyarthritis uveitis and the absence of pulmonary disease. Okay, also known as familial juvenile systemic granulomus ptosis plow jabs syndrome they were described at the same time. Anybody want to tell us a little bit about this rare and did you guys read up on any of the rarities? I left it up to you to read what you like. Anybody? A couple of fun facts. Is this what is the kind of onset of this disease usually? Later childhood or early childhood? Early. Early childhood, right. And what are the What about family history? Is that important? Autosomal dominant. Yeah, right. So it's really important, right? So it's an autosomal dominantly inherited disease. And it is phenotypically you know, linked 100% to a certain mutation that we've mentioned a few times. So the nod to mutation. Okay. Triad, dermatitis, arthritis. Anybody know what Campyloid Octi is? Anyhow, it's a flexion deformity of the proximal interflangial joints, absence of pulmonary disease in the kid. Autosomal dominant as you had mentioned, linked chromosome 16 with with the nod to mutation. So most commonly these children will have panubiotis and multiple recorditis and they can develop other simulating diseases. There are less common such as, you know, vasculopathy. But the differential is really early onset sarcoid or NGIA. There are patients with early onset sarcoidosis that do have a nod to mutation. So though they are thought to be the same disease. Okay. We're going to move on to a different disease entity. This was a 10 year old male that was referred to me with non-granomes and interubitis and papillitis which began after fever vomiting and coughing at optic nerve swelling AC inflammation and was treated basically with topical corticosteroids. The complicating factor was that he was living in China with his parents and his parents were diplomats so they came for consultation. He had an exposure in history that was of interest but difficult to really know exactly specifically what all this would mean. He was worked up initially in China and in Singapore where they have very famous, you know, uveitis and ophthalmatory service fairly completely and I say fairly completely because it was incomplete and it showed a few abnormalities but elevated sedrate is certainly non-specific which indicates there's some type of systemic inflammation going on. He had recurrent febrile episodes, you know, joint aches, diarrhea, lost about seven pounds. On examination when we saw him he had reduced vision in his right eye. He had bilateral inflammation that was significant. A posterior senica is structural complications and cells in his vitreous and papillitis in both eyes. What I did not see which is important is any multifocal lesions in the back of his eye I was looking for them because one can see that in this entity not frequently but it can't. So the plan we ordered some we reordered her the workup and we included one item on the workup that was missing previously and I was also based on the patient's review of systems. What one lab was missing in this particular workup and anybody people think of what that might be in a child with bilateral anterior uveitis with a systemic febrile illness. So I would always order beta 2 microglobin of the urine and a patient with bilateral anterior uveitis in a child or in a young adult. We also worked him up for a lot of other entities that given his travel history and his exposure which were interestingly negative except for and I'll tell you his initial treatment was with Durazol and Atropine. His beta 2 microglobin was elevated but the ratio to the CRT was astronomically elevated. His creatinine was okay normal CBC and we suspected that he had a tubular interstitial nephritis and sent him to the renal service who did perform a renal biopsy and I indeed that was that diagnosis was confirmed with the presence of interstitial inflammation with lymphocytes and rare plasma cells and some of these cynical thrombus and of course is the two rules. So TINU is not that common but is something to always think about in kids that present with bilateral simultaneous anterior uveitis and in adults young adults that present similarly. This was one of the other disease entities that you could have read about that I suggested you read about and I think the important thing is that always think about it with bilateral non-granium is recurrent anterior uveitis. Okay nephritis usually precedes the anterior uveitis but it can be occur before or after it can be occur after or can commonly there are usually multiple exacerbations and there can be posterior segment findings in and not insignificant number of patients. So there have been some recent publications actually that have shown a much higher rate of you know multifocal type of cortitis and patients with TINU. So it's something to look for again there's kind of this bimodal distribution with kids and young adults with initially I always thought to have a female predominance but recent publications suggest more males 2% of a tertiary uveitis setting which is and then there is a gene-agri-pre-disposition to develop in the disease exactly why they develop it I don't know it could be an idiopathic response or drug hypersense to the ur-microbial trigger the diagnosis obviously renal biopsies definitive but it's not realistic sometimes to perform a renal biopsie in a kid particularly if they have completely normal you know studies there are diagnostic criteria that was established by Mandeville which include abnormal serum creatinine beta-microbial in the systemic illness the differential diagnosis includes other things that affect the kidneys like you know lupus GPA choverins post streptococcal syndrome I mentioned because that's an important thing to consider in patients with bilateral simultaneous anterior uveitis bachitis disease to be in specific so for treatment topical versus some exterior it's usually worked well however about 9 to 11% of patients can will require IMT and it seems like the nephrologist like to use mycophenylate for this disease so this patient was started on orophenylone and celsapt and has done extremely well and beta-microbial globin is followed either by us or by both us and renal and indicates decrease and certainly renal activity and of course we can see the treatment response in connection with the eye okay so someone's called from consults you know over to primary children's hospital for the kid that has these findings someone feel this one what are we looking at in the hands and the grind and the lips and this child is there is this looks kind of like scalded skin scalded skin okay the skin kind of looks like Kawasaki and what makes you say that the lips and the hands if that child opened its mouth and showed you his tongue what would you see what might you say strawberry tongue right okay so I think that's what this diagnosis is when you tell you the discriminative branch and the fingers and the grind on the lips and this child also had a strawberry tongue tell me about what is it also called Kawasaki studies another name for it everything in ophthalmology is named after some guy right not too many women right but Kawasaki is a guy so it's a more descriptive term is mucocutaneous lumbinoid syndrome right okay children usually less than you know 10 years of age usually Asian South Pacific Islanders okay what is the thing that you really worry about Kawasaki disease it's certainly not their eyes coronary artery environment right exactly so it's a systemic vasculitis with small uh rather small and medium vessels and coronary vasculitis present in its significant portion of patients and can have a fairly high mortality right how about accurate manifestations there's kind of a distinctive accurate presentation that's I don't know why they wouldn't ever ask you this on a board question but they this is the type of stuff that people that write questions ask so what is the most common eye finding in Kawasaki just conjunctivitis right and is there any particular I don't know if conjunctivitis is peculiar to it I'm not sure actually okay it spares the lumbus okay so just keep that in your head for for no reason your subcontinue so it's bilateral conjunctivitis spares the lumbus 90 percent of them so it's a desirable hemorrhage you can have a mild bilateral entry of the items the you can have optic disc and vitreous capacities and dilate renal veins treatment is with IVIG and topical steroids for there hi this is no topical IVIG is very important in reducing you know coronary impairment mortality okay here's an interesting patient that has an unusual well it's not that unusual I learned something with this patient but it's a different anatomic presentation of the disease of a systemic disease so it's an eight-year-old white kid as referred from an outside position seen initially for one month of decreased vision he was diagnosed and I quote put pan you the other snare because I don't think that was the correct diagnostic you know designation with macular you know and they had been placed on PRED forte no matter he had negative review assistance but he did carry a diagnosis of something that I hadn't heard about at the when I first I met this child periodic fevers aplastomatitis pharyngitis and cervical adenitis which is marked by recurrent fevers or ulcers and it's usually well-controlled with systemic steroids I didn't really know that this is a very common autoimmune auto-inflammatory season childhood so family history was actually interesting I so there's a family history of autoimmune disease ulcerative colitis and multiple sclerosis on his examination he had decreased vision in his right eye as to be expected from his presentation and entered chamber cell but dilated funnest examination showed vitritis and of course accurate demon right mild epiretal membrane and peripheral snow banking with inferior parts planet exitates and snowballs by digression greater than left eye noninvascularization so he has an intermediate type of uveitis right associated with some disease right with maybe that maybe associated with a systemic disease he also has snow banking okay so we worked him up to exclude infectious diseases and we gave him a diagnosis of intermediate uveitis with macular unit possibly associated with PF APA so not partial and it's because he has a systemic disease association in fact this was the first of two cases that have been described with this disease association of intermediate uveitis associated with this he was treated with tuple steroids and his CME resolved with a sub-tenons kennelog okay we wanted to spare systemic steroid in in this child in his left eye I think nine months later it came in with a glory onset of a vision it was found to have vitreous hemorrhage in his right eye near vascularization in his left eye on DOA and his plan the plan was to perform the tractomy in the right eye which we did endo laser and peripheral laser in his left eye so it's kind of be interesting this case is interesting and I'll show you why in a minute he had a vitrectomy in his right eye peripheral laser for them in his left eye he then was quiet and stable off of all medications for two years and represents the flare with a decreased vision in his left eye okay the non-vitrectomy in his eye with anterior chamber in vitreous cell um he had macular edema whereas offered IVT and azurex was a little bit older at this time he declined those because he just didn't want to get anything ejected in his eyes sometimes the patients know better and it was placed on oral prednisone and we discussed IMT and he declined it but it resolved over two months okay so you can read about this on your own but this is the most common auto-inflammatory fever disease of fever disorder childhood and usually results spontaneously by the second decade the interesting thing about this case was that as we will see in this discussion of intermediate UVIS and personalized that the child had a vitrectomy in the right eye when he was younger and then really never had a recurrence of inflammation in the right eye following that but any recurrences were in the non-vitrectomy in his eye so there is the thought that maybe in intermediate UVIS that the trectomy may be useful therapeutic introduction in some cases certainly required therapeutic retrectomy right because the other vitrex is not right so we're just going to kind of have a segue here into intermediate UVIS and personalized because I think this is a kind of a good place to think about so let's talk about this is intermediate UVIS and personalized are the same thing so sometimes they're used as interchangeable terms but are they the same thing anyone it's a yes or no question no okay and why is that what is the fundamental difference between Parasplanitis indicates that it is well Parasplanitis is the most common cause of intermediate UVIS and intermediate UVIS has a known etiology like sarcoid whereas Parasplanitis I believe is idiopathic that's very good I think that's a good way to think about it so maybe Parasplanitis is a subcategory of intermediate UVIS right Parasplanitis is the idiopathic variant of intermediate UVIS so intermediate UVIS is a broad term described inflammation that's primarily located in the anterior vitreous cilia body and peripheral retina which may or may not be associated with an infection or systemic disease so you have to exclude infections and systemic diseases and masquerade syndromes in intermediate UVIS whereas Parasplanitis is the idiopathic version of that after things have been excluded but it is usually characterized by the presence of what we call what are commonly referred to as snowballs or snow banks without associated infectious or systemic disease so you'll hear the term snowball in snow banking my mentor you know would cut my snowballs off if we use snowballs as a descriptive term and he would prefer that you actually call them by what they are which are accumulations of fibroglial tissue over vessels within the inferior Parasplanitis or inflammatory cells in the inferior Parasplanitis or vitreous and inflammatory exiates in the vitreous and it's a mouthful but I think it is a little bit more descriptive I don't mind snowballs and some banks I know what you're talking about okay most commonly located inferiorly I think there's a gravitational effect to that but in patients with really severe intermediate or UVIs or with Parasplanitis it can be 360 it can encompass the entire Parasplanitis and it's best visualized by skeletal depression the Parasplanitis snowbank or exidate can be vascularized so I think it's important to actually pay attention to whether or not there are new vessels on the snowbank and then to look for tractional elevation of the of the adjacent retina there are some also some it can be associated with exusative readily attachment with very severe disease very severe disease and then there can be some other structural complications that we talk about that appear not uncommonly in patients with Parasplanitis so this is what we're talking about okay this is Parasplanitis you know infiltrates in the retinal periphery so it's not in the retina it's above the retina in the gel and they're characterized by inflammatory cells and fibroglial homes so why is it important well you know it's not in common so we see a fair amount of intermediate and Parasplanitis in the pediatric UVIS population and it can be up to 15 so in just uiitis in just general uiitis practice about 15 percent and up to a larger percentage in pediatric practices so practices comprising uiitis population so it's most frequently bilateral but it can be asymmetric right and usually in adults occupant in redness is uncommon and the most common presenting symptoms are are floaters blurred vision or decreased central vision due to the more common complications of this disease what what why do you think patients present with decreased central vision in intermediate UVIS and Parasplanitis but structural complications do you think it's the most common cause of decreased vision in that disease see me yeah exactly you know me so it's a little bit different story in kids not terribly different it's just that the disease seems to be a little bit more you know severe so kids do present with antrosegment inflammation pain redness and photophobia you know which is a little less commonly seen in adults here is a really great photograph I think of what vitreous cells look like but this is at least two plus vitreous cell you know these are the Parasplanitis rather vitreous exudates or snowballs vitritis is really the cynic one on of for vitreous inflammation of intermediate UVIS one can also have other structural complications the rental property including cyclic membrane and separation so retinal vasculitis is not unfrequently complicating this disease and it's most most commonly a retinal perinflabitis so inflammation involving the veins vascular occlusion and peripheral ischemic can occur and peripheral neovascularization of the of the retina and the optic nerve can also occur and this can be inflammatory or can be ischemic and a complication of neurovascularization of course as you know ischemic which seems to be a more frequent presenting complication in children you know with 28% versus 6% or 20% in presentation versus 1% adults so why do you think it's important to know whether or not the neovascularization that you might see on the optic nerve or the retinal periphery is inflammatory or ischemic and how would you tell that difference how would you kind of make that determination and what test would you order your FA yeah you do an FA right and what would the FA tell you what might it show you we'll see some examples of that split if there was a lot of leakage you think of it be more like an inflammatory or vasculitis rather than ischemic okay right and if you had on the other hand not perfusion right okay you might think that more of a skin again why is that important just with the treatment those two differ do you think yeah it would be like steroids or you know immune modulating stuff versus maybe laser yeah I think that's very good you know I'm so I've had several cases of patients represented with the evascularization of the disc who's the vast that had no ischemia I on enforcing the angiography and the neovascularization kind of melted away with anti-clinatory so I think it's important and so you spare the patient you know potentially disruptive no laser procedure kind of course macular Dima is the most common form that's decreased central vision so again I hammer home these differential diagnoses lists okay of course it's an academic exercise but they're not long lists right and they're important to think about and you base your you know your his list or your top five where you're top three you know based upon your your systems and your examination so you can have infections right syphilis sarcois syphilis and TV always think of that sarcois you can have art and a lot of toxo osmosis you know really weird infections like levels disease or end up so you know we always perform company and more testing in patients quantifier on gold testing in patients to rule out TV and also because sometimes we anticipate these patients will be placed on steroids systemically or on IMT chest x-ray again probably the most important screen tool for patients with uh sarcoidosis you know what was disease I've seen one case of that and that was diagnosed and then to add no biopsy and if we don't really know sometimes we need to PCR if it's for a cold infection sometimes chest CT is necessary when the chest x-ray is normal but you have a higher suspicion of sarcoidosis and then an MRI may or may not be useful in patients with parcellanitis as we'll discuss a little bit and then if there is the suspicion for a mass-grade syndrome certainly should be diagnosed will attract to me with studies molecular studies and polycytometry for lymphoma okay complications cataract and glaucoma band care top the vitreous hemorrhage didn't need vascularization traction rotten attachment and regmatogist rental attachment can occur and then there are some complications that you don't think about too much that occur more commonly you would think so retinoschesis can occur in a fairly significant portion of patients as you can see here and ultrasound retinoschesis the etiology that is not 100% known and there are two schools of thought on that one is that it is tractional and the other then that it's ischemic it's probably a combination of both macular edema number one epiretinal membrane amylobion kids and then vasop proliferative tumors can occur in a small proportion of patients with parsonitis as you can see here and that needs to be treated you know with usually cryotherapy or laser one very important thing to know about parsonitis particularly in young women is that there is this associated risk between parsonitis and the development of multiple sclerosis there is an HLA dr-1-5 association and it seems that periflabitis may be a risk for increased ms and optic neuritis so it is important when I evaluating a patient with parsonitis that you have made a diagnosis of parsonitis and excluded systemic and infectious ideologies to query the patient about signs and symptoms of multiple sclerosis treatment of pediatric intermediate ubiitis I think you have to if it's if you have significant inflammatory disease early and aggressive treatment particularly in a younger age when you have structural complications that are at presentation significant vitreous opacities and again we use this kind of modified step water approach cryopexy and indirect laser are I think under probably underutilized but may be very effective particularly in patients that have vascularized agitates and parsed plana new vascularization on their on their parsed plana there is one can perform cryopexy or indirect laser there have been studies that date back you know 25 30 years ago that seemed to indicate that that those interventions particularly initially described by auburn with cryopexy that it reduces both inflammation and accurate email but that's kind of like before the age of imt and it's kind of used less frequently it's always used in patients that undergo retractomy but I think that we will find now that we have better you know wide field imaging that we may see more a non perfusion and it may be that patients that have extremely the cost of disease may respond well to cryopexy and indirect laser I just want to bring your attention to paper that we published on the use of immunosuppressive medications and pediatric intermediate you've got us we found that you know I am immunomodulation was used in you know over half of these patients and um you know we were able to get these patients off of steroids in almost every one of those patients without a recurrence so I think that's actually a pretty good outcome you know you don't want to have kids on on steroids and you want to have their inflammation all controlled just bring your attention to another paper this is from plaster's group in which he actually performed therapeutic vitrectomy in patients with recalcitrant uveitis recalcitrant 2 IMT and found that vitrectomy contributed to the control of inflammation both for pure uveism and that complicated by rental vasculitis I don't think that this is done very frequently but it's a very interesting idea vitrectomy in children poses a lot of potential complications for the vitrectinal people in the audience you know either highlights are attached you don't want to create a iatrogenic problem in a kid but if nothing else is working it may be something to consider again I wanted to bring your attention to this idea of peripheral cryolablation because it's been recently kind of resurrected by a paper that was performed from proof from Isla and the the take on messages from this paper which I didn't assign to you is that it resulted in about a fourfold remission rate you know by using peripheral cryolablation in patients of paris planis remission rate that is no medication and it did not as is commonly thought result in greater incidence of retinal attachment so usually I have used this when there's the presence of neovascularization particularly on the paris plana exudate because you cannot really get good laser into an exudate but you can you can cry like and then I did assign this paper to you guys or had you just glance at it remission of intermediate you guys incidence and predictive factors again this is the site group and this was I think four of the five four of the five institutions and you know I won't quiz you on this but there was a lower lower overall the low remission rate as there is in general and you've got us you know except for patients that are placed on cytotoxic therapy which carries great risk so 8.6 percent and the factors that were associated with increased remission included prior protracted me so like my patient Deegan who had the protracted me seemed to have a remission in that I and I think there is interest in the UVS community about actually really studying that question the role of therapeutic protracted me in intermediate UVS I actually try to pitch this idea 10 years ago it's is a really tough study to if you get to sell people on to the at least to the mass group so it's on hold and I think it would be impossible to do as a single center to study this paper also showed that a diagnosis with you know an early diagnosis so that makes sense right so not so severe disease older age of presentation we've been talking about that in terms of pediatrics so kids with partial eyes usually have a poor outcome female sex and and Hispanic ethnicity so prognosis in summary you know a population based study by Donaldson showed a very good outcome right but in tertiary care centers I think the experience is a little bit different more severe end of the spectrum they make of a larger portion of pediatric versus adult uveitis testing should be guided as I said before about you know by your history and view your system so you don't order every test under the sun and we'll talk about what we might how we might choose tests and and therapies for this disease and then as a general rule I mean uveitis is is difficult but then it's easy at the same time I think that your major goal is you want to rule out an infection so you don't want to treat an infectious disease with steroids right so first rule of thumb is rule out an infection and then treat with immunomodulation with either a symmetrical local therapy and then the prognosis is good until it's not good right I so Donaldson shows a good prognosis but you know the our experience with individual patients may be may be different so you can't really apply a population based study to your the patient that's in the chair in front of you and then pay attention to complications and treat them with their site threat so I'm going to just go over a couple of cases of course for minus intermediate type of uveitis so this is a young woman Caucasian female complained of painless blurred vision and floaters for about 18 months and then right I was acintomac she was a college student you know usual no high risk behavior and no unusual travel she didn't really have any significant past medical history other than family history of Hashimoto started so there's a family history of autoimmunity pain in her lower back and knees and her left Achilles and a large circle look no who were thinking about maybe who knows maybe she'll she has a sense and her vision was good in the right eye okay with one plus vitreous cells so there was inflammation in the right eye at least I you know on clinical examination and the patient had some if your vitreous activates and left eye they were more obvious with poorer visual purity and more more hazy view right and vitreous inflammation so this is what a wide field angiogram showed anybody want to kind of describe that yeah this is an angiogram of the right eye and attention is drawn to the vessels in the periphery that show staining like peri vascular staining and yeah yeah very good and waiting for vasculitis staining and what else is it just staining a little bit of leakage in the periphery I would say mostly staining right so and is the inflammation just confined to the periphery there are some vessels in the macular that are staining as well I don't see a lot of staining at the disc what time frame is this angiogram taken at it looks like a late stage it's a kind of a mid mid-phase so I think that's and so what vessels are involved mostly mostly the larger vessels mostly the other looks like a vein to me oh yes you're right so and in the left eye this is the later phase of the angiogram sorry she also had involvement in the left eye with angiographic macrodema in a late study the OCT the right eye showed no macrodema as the angiogram showed but there is significant macrodema in this this eye so differential diagnosis so what category is this an anterior uveitis this is a pan uveitis posterior uveitis intermediate uveitis so bilateral asymmetric intermediate uveitis with CME right exactly excellent description okay so we that's our differential we want to make sure the patient doesn't have an associated systemic disease and we queered her for those things we want to make sure she doesn't have an infectious etiology as well the patient happened to be from the east coast we didn't test her for blindness okay so her workup was unremarkable that was ordered because she had this history of joint disease back pain and in a very small proportion of patients inflammatory bowel disease associated with HLA B-27 can be associated with posterior uveitis and sometimes an inclusive vascularis then the question marks on all of these right do we get a chest CT if she has normal chest is there an MRI do we need to get an MRI part Nellis she has no exposure really UA urinary beta 2 molecule globin there are no multi-fogal diseases or alignments so you think about those things and you base you know the selection of those tests on your clinical suspicion so inflammatory infectious workup or unbekeeling no evidence inflammatory orthopathy and rheumatism and vascular lesion okay so this patient now has a diagnosis of paris planus right young woman with a diagnosis of paris planus you want to ask her about neurological symptoms right so you want to ask her about numbness or tingling in her fingers weakness doll or blotter incontinence certainly a history of sudden visual loss associated with optic neuritis she denied those things so an MRI was not obtained this particular case so the treatment options what are the treatment options here what would you what would you treat this patient with she has you could consider like periocular steroid but because she had leakage on FAM both eyes and evidence of inflation she probably needs just systemic steroids yeah so I would agree with that approach and a lot of the treatment decisions are based on you know the patient and their preferences the 20 year old dancer ballerina and you have to also get the patient to buy into the treatment right so those are those are the options and she didn't tolerate oral prednisone for very long that was the initial choice and so she underwent multiple periocular injections followed by dexamethylxone implant and actually did pretty well okay on her examination she didn't have complete resolution of perifulbitis but it certainly improved and improved significantly in the left eye the macular demon also resolved with some ellipsoid destruction but no significant decrease in the vision this is another case that Dr. Shakur had followed for approximately 10 years and Rachel Patel brought to my attention 26 year old woman who I had presented about 10 years ago gave birth and developed decreased vision on left eye with floaters she underwent an unremarkable laboratory workup on the outside and we started on oral prednisone and on presentation had 2020 visual acuity praised vitreous days no macular demon an inferior snowmangan a few vitreous snowballs so this patient comes in treated worked up and on examination looks pretty good angiogram is I would say pretty unremarkable in terms of vasculitis in both eyes prednisone was tapered to off nine years later she was followed up OCT looks pretty good good vision 10 years later she represents with decreased vision in her left eye angiogram segment cell on her right and left eye vitreous haze on the left and had recently been on prednisone form per her ophthalmologist in Nevada so a recurrence right you can see here this area of eye you know what looks like retinal whitening but is vitreous condensation her angiogram shows diffuse I think capillary leakage in the right eye what do you think about in the left eye same maybe some non-profusion out there or blockage what is that so she has some angiographic macular dema right optic nerve head swelling OCT shows definitive macular dema in her left eye and not a right eye similar to the previous case additional workup was performed which was non-contributory and it was recommended that the patients start prednisone and as well as methotrexate so why would we start methotrexate in this patient anyone why would that be a recommendation remember there are no hard and pass rules or anything so you have a young woman right who uh you know has previously responded to prednisone and you know in at least in my mind you get one shot at a steroid taper prefer or not to have patients on multiple steroid tapers so we would want to place her on a steroid sparing kind of regimen so that she doesn't devolve returns give it a granted it was 10 years later so she deferred methotrexate but we tried prednisone okay so some discussion points to see how we're doing on time okay so in a young female patient with carcinitis when would you do you need to order an MRI on everybody yes or no no okay so why what would what would what would kind of make you want to investigate MS in patients with carcinitis when would you order the MRI if they have symptoms or a history that's consistent with demyelinating disease yeah I think that's true and you know family history may or may not be important I would respect for that I would say on exam if it looks like they have some like optic neuritis or like a lot of periflebitis I think that's a very good point okay so really signs and symptoms of MS and severe vasculitis I think would would make me want to do that okay what are the factors in in in recommending systemic versus local therapy what do you what would do you have to consider in recommending systemic the local therapy another way of asking that question who would be an ideal candidate for local therapy with intermediate units unilateral okay right unilateral disease with I I mean unilateral say they have a vitreous floater are you going to treat them with that today is there something else that you might see on exam that might prompt you to inject steroid in or around the eye macular edema yeah right okay so a structural complication visually significant inflammation asymmetric or unilateral hey we use a periocular and for treatment primarily in that setting and also as a juncture therapy patients that develop macrodema were on systemic therapy great okay so with respect to local therapy you know you know we've kind of talked about this you know what you know factors would you know when would you give a intra vitriol or periocular corkesteroid so symptomatic right presence of macular edema sometimes periocular corkesteroids can be effective in patients that are complaining of vitreous floaters that may be in which they do not have macular edema they have good vision it may it may work well for you know six months or or their bounce okay the other thing is that in some patients that have non-central you know macular edema that may be abutting the phobia or paracentral phobiasis so they have something happening right and if they're angiogram they have a unilateral disease and their angiogram doesn't show significant you know zone one type of leakage a sub-tenants catalog may be useful so when would you consider immunomodulation for patient with paracetamolitis and what would be the best initial choice of therapy when do you consider IMT this thing I just showed you two cases so it's a judgment question right so what factors would make you want to treat the patient systemically and what would make you want to add immunomodulation anyone so you think that it's going to be fairly chronic course or they're not having a great reaction to steroids that have complications diabetes etc I would think about trying to transition over right okay so I think that's that's one consideration right so their prior treatment history is important right whether or not they tolerate steroids or not what about the laterality of their disease right that bilateral disease in which they have already had a course of systemic corticostero and have had a return you might want to offer them immunomodulation right what about the patient and what drug would you choose what category of drugs all those drugs that we talked about usually an anti-metabolite methotrexate first yeah sure anti-metabolite I think that's that would be good what would be the second line if the patient doesn't has recurrent inflammation or macrodema or vascularitis with methotrexate or with cell cell what would you advance them to would you go forward with a biologic you would and what biologic might you what class of biologics might you choose maybe like humera or one of the TNFs and what would you do for sure before you embarked on such therapy rule out TB anything else so 15% risk five years with HLA DR-15 do an MRI of the brain yes I would in this case I would do an MRI of the brain okay for patients in whom I'm considering IMT with anti-TNF so you know quantity of iron gold obviously and for rule out TB and MRI of the brain good so when do you consider laser part of bioglation or quiet oblation for correspondents vitreous hemorrhage detachments traction up here at all my brains okay I'm anything on enforcing angiography that might persuade you to laser if you're seeing some envy okay yeah in the presence of ischemia right okay in the presence of non-procution exactly me vascularization of the of the porous planus snowbank would also be something that I would think about in terms of prioflation what about the presence of a mesopolypter of tumor in us pretty uncommon that would also be something I think by using prioflation okay we I kind of I asked you this question already the treatment options for the treatment of neovascularization and postmenitis the test that would help you decide would be you've got a force wide field force and angiography I think that you know that's an important point and that you want to make sure that you're treating you know an ischemic neovascular disease with appropriately with either anti-vegetable or more laser part of migration but in some cases neovascularization can be completely inflammatory and in the absence of ischemia may melt away with appropriate anti-inflammatory treatment then what factors you know would prompt you to recommend the tractomy innovation with intermediate eyes for postmenitis I think they have a lot of symptomatic floaters that are refractory to your treatment if they have a lot of what I'm starting to hear they have like a lot of symptomatic floaters and stuff that are refractory to treatment that causes a lot of vision okay before you perform the tractomy innovation with symptomatic floaters you might treat them right medically what would be a more immediate installation or performing a the tractomy in a patient with intermediate eyes hammer jaw detachment yeah right exactly so a structural complications that would immediately affect vision which is which is if it was hammering a jaw you know a final detachment exactly okay and then we discussed the fact that it may or may not be therapeutically advantageous okay so intermediate uveitis and part times in essence manufacturers intermediate uveitis part times can be treated either with a lot of treatment options depending upon a variety of factors right local or systemic steroids immunomodulation or some combination thereof and not every eye needs to be treated to maintain good vision the key factors in choosing therapy include the laterality right and the choice of therapy the type and severity of inflammation you know accurate medical comorbidities so you know patients with brittle diabetics might be better candidates for local therapy and steroids bearing therapy the presence of an underlying systemic inflammatory disease obviously you want to treat a disease that's going to affect the patient's health right such as sarcoidosis and patient preference as we have seen you know some patients just don't want to be on steroids and I think that needs to be respected then multiple sclerosis should always be considered in young patients particularly female patients with uveitis and something that we haven't touched upon too much in the differential diagnosis but that one of the very important masquerade syndromes to consider in patients with intermediate uveitis for older eye is primary vitro retinal lymphoma and primary intratural lymphoma so you need to think about these masquerades always for these patients okay so I'm going to push on here we're going to move away and get further back into the eye we still have a little bit of time left about some congenital infections okay so we kind of touch on that what congenital infection would you diagnose here it's like toxo yeah right so most congenital toxoplasmus quote congenital toxoplasmus presents as a macular scar unfortunately so congenital infections includes the torch group right others you know rubella CMV herpes simplex okay and then you know there are some really weird others here that have been recently described and then there are emerging infections that we'll kind of discuss a little bit so just a word about congenital octotoxoplasmosis you know the transmission is directly related and to severity inversely related to gestational age and that I you know almost 40 percent of patients you know with primary maternal infections have been general disease and then 70 percent of these manifests as ocular lesions so the triad of congenital octotoxoplasmosis is cordyrinitis hydrocephalus intracranial calcifications this is an unfortunate girl with hydrocephalus usually congenital toxoplasmosis and you see these calcifications very ventriloly there's been kind of a paradigm shift in the in the thinking about you know toxoplasmosis and then most toxoplasmosis was thought to arise from congenital infections but these days we think that it most of the toxoplasmosis we see are acquired postnatal infections may represent the most significant portion of these disease this has you know important important public health implications in terms of primary prevention of both mother and then children you know preventing disease just the things that you need to remember about congenital toxoplasmosis is cordyrinitis hydrocephalus and intracranial calcification of the classical triad and there can be subclinical development opposed to your involvement okay in a significant portion of eyes right 85 percent develop cordyrinitis after three and a half years um you know the diagnosis I of congenital disease is I you know the presence of IgM or IgA okay a negative IgG helps rule out the disease and PCR may be useful in patients with really significant information the treatment indications for congenital disease is antiparasitic therapy for a year okay for one full year in that I I situation given this the fact that you know 85 percent of patients will develop cordyrinitis after three and a half years so how do you treat congenital disease antiparasitic therapy with full antitoxal plasma therapy older children are treated for the indication similar to adults you know myopic nerve threatening lesions visually significant trials and immunocompromised patients need maintenance survival access I'm not going to dwell on this as it's going to be reviewed or in the infectious or has been in the infectious UBI's with the classical treatments is triple therapy pyramid being so self-adhesive volumic acid this is incredibly difficult to obtain very expensive corticosteroids can be very useful and I a reduced dose in patients with inflammation that's significant but usually only after the initiation of antiparasitic therapy one would avoid a periocular injection or antiparticular injection in any infectious kind of disease particularly toxoplasmosis then alternatives include intravitrial clindamycin or systemic clindamycin Bactrum Zephyrotropon so just want to bring your attention to some of the other others categories of few general infections this kind of looks like a coronal retinal inflammatory disease not dissimilar to toxoplasmosis any grateful dead fans out there well that's Bob Weir he was a rhythm guitar player for the great for dead and his first big song was the other one and anyhow it's an interesting documentary interested in the dead the other virus is lymphocytic coiretinal meningitis virus see all in the okay which is almost clinically indistinguishable when you look in the eye to general toxoplasmosis but it is different entity entirely and it's caused by a single-strand RNA virus and produces symptomatic maternal illness in about two-thirds of the case with vertical transmission eye during episodes of internal viral and it's diagnosed serologically the systemic findings are not completely different but and you know macrocephaly hydrocephalus neurological complications with seizures and the odd care findings include coiretinal scars as I mentioned they are very similar to that seen in general toxoplasmosis and it's differentiated serologically from toxo and by the pattern of the calcifications which are diffuse in toxoplasmosis parent ventricular and LCMD other infections this was a infection that has become a very important congenital infection worldwide particularly in the southern hemisphere and produces this type of maculopathy and can produce congenital and congenital birth syndrome anybody want to hazard a guess as to what this might represent another viral infection is it Zika? Yeah Zika exactly okay so single-stratoid flavivirus mouth flu-like illness can generally congenital infection can produce these kind of accurate colabomas with their torpedo and maculopathy and iris colabomasis for business there's really no treatment for that unfortunately so just going to throw out a couple of quick cases for you four-year-old painless unilateral decreased vision four years old right unilateral painless decreased vision leukocorian stravism so you're thinking differential diagnosis of leukocoria right and that's what you're that's what you see when you look in the eye what what are you thinking in terms of your differential diagnosis or really the primary differential retinoblastoma till pain that's one what about infectious diseases like a talk like a what toxic horror yeah toxic horror right and so that's what this actually represents so oculotoxicoriasis you want to tell me about the oculotoxicoriasis some someone so kids with a history of pico contact with puppies there are a couple of forms of it this room larval migrans and ocularval migrans usually unilateral 90 percent of patients and there are basically three presentations there's this form with the macular with the macular disease and there's a a posterior presentation and then there is one with a purple rhinoloma with a typical vitro renal strand to the to the optic nerve and then an older children may may present with as an end opomitis it's diagnosed clinically by looking in the eye but also serologically and ultrasound is very important excluding calcified regions and retinal blastoma so the most important differential someone had mentioned for oculotoxicoriasis the most important thing to exclude in this age group would be one you've already you've already said sporadic unilateral retinal blastoma but there are other things that it could be end opomitis toxoplasmosis and then there are retinal vascular diseases particularly in the form that presents with particular with peripheral disease the treatment is usually there is no really unified consensus on the treatment of this disease in terms of medical therapy with anti-helminthic disease although albendazole is frequently used periocular and systemic corgis erodes for eyes with severe inflammation and vitro retinal surgery for patients that develop surgical complications such as tractional detachment here's another case that was constructed of a 15-year-old female with history of congenital CMV so she has congenital CMV but and some complications of that with 2D history of photophobia and blurred vision her past medical history she has hearing loss and developmental delay due to the congenital CMV and a history of panuveitis in the fellow eye not the presenting eye with a retinal detachment and LP vision and her vision in the affected eye was down at 2060 normal pressure into your chamber and vitreous cell okay is very instructive to look at her fellow eye so this can tell you something about what you're dealing with in the other eye so here you see a patient with PVR and fibrotic peripheral retina and really necrotic peripheral retina so I'm thinking man I hope this patient doesn't have you know a acute disease in that eye and we have three well you have to think of an infection right so this isn't really that typical of one might see you usually don't have a reactivation of the congenital CMV right so you but this lesion made me think well maybe it's just toxoplasmosis we have to think about that looking at it but then we saw some peripheral retinal whitening in this area so our differential diagnostic consideration given the appearance of the other eye you know panubias renal vasculitis and papillitis and retinitis in the left eye with a history of PVR and mental detachment in the right eye she was worked up which was kind of negative but the number one thing that could I always try to think of the thing that could really destroy the eye what would be your one and two kind of differentials in this child that you would want to exclude that can occur in children pardon yeah right necrotizing exactly necrotizing you know herpetic retinitis these other infections are also possibilities and we would exclude those non-infectious diseases not as likely but possible so here she is next steps it's an EUA her labs were negative she had an AC tap an injection intravitual against cyclovir and a positive test for BZD so IVA cyclovir intravitual against cyclovir and past Carnot and prednisone and laser barricade at day 13 so she Carnot I see this patient now yearly and is doing well with excellent vision but you know you have the thing that was instructed for me in this case was the fellow I and I think and of course thinking of the worst possible thing this child could have so I'm not going to go through the diagnostic criteria this you will you will hear about this already but it's really a clinical diagnosis a retinal necrosis wrapper progression circumferential spread spread occlusive vasculopathy and prominent inflammation so it you make the diagnosis by looking in the eye and then perform eye either an anterior chamber or vitreous biopsies to confirm the diagnosis and treat them at the same time so you don't wait for the result here's a 12 year old male from Idaho unilateral recurrent multifocal quadretinal inflammatory episodes with scan to try this I swear there's some kind of weirdness that goes up in Idaho but there's something in this person's retina it's unusual it's highlighted here does anybody see that dozen yeah dozen right so there's a there's a worm here and then when you show and light on this here is the worm would move okay so this is diffuse subacute unilateral mirror and as it's pretty uncommon here a lot more common in the southwest the United States hematotal infections toxic carotin and two and belly as carrots the raccoon worm and ankylos stoma cranium in the southeast and caribbean but it looks like on em the important thing to know about this is the presentation it's usually in unilateral and depending upon the age of the time of the disease it can look very different so in the early early presentation disease it can look like a white dots in Rome and you have you know a worm that just migrates to the retina and just kind of destroys the retina and the late it can look like a push traumatic on rp this is too late right so you want to identify because the disease at least think about it in a person with unilateral white dots with inflammation and the treatment well you want to burn the worm okay that's the treatment and certainly you'd want to get the worm wait for the worm gets out of the fovea a benzo may be helpful in in killing the worm but in slowing the worm down you know and stunning them so that they if once they reach an area that's safe to laser one can do that an impunity I just want to review things that you guys probably already know and are consulted you know mercilessly immature immunologically immature neonates and hospitalized children on immunosuppression you know important pathogens Canada pseudomonas staph aureus homophilus usually there's an underlying focus or systemic condition extract your focus or underlying systemic condition and the most important thing to exclude is retinoblastoma with no apparent infection this is an eight-year-old we only have a couple of minutes left that presents with unilateral painless decreased vision cervical adenopathy mild fever and a new pet what do we have here cat scratch disease cat scratch disease okay neural retinitis is what you've done you don't know that it's cat scratch disease but that's actually a good thought okay so neural retinitis for sure because they have a partial macular star most the most common diagnosed would be Bartonella species with cat scratch but there are other considerations other infectious considerations that you need to exclude it used to be called idiopath for labors idiopathic stellate neural retinopathy but many of these cases are now thought to be partnolosis there can be idiopathic disease with a recarnate tax I'm not going to go through this too much but I think that it's important that many of the the history is important so there's usually a flu-like illness with regional adenopathy particularly at the side of the cat scratch if they have cat scratch disease they can disseminate infection with fever myology and archaeologists ocular disease includes paranoid ocular glandular syndrome neural retinitis and one can also develop retinitis chorditis and multifocal retinitis that's important to remember and to exclude because one sees that in Bartonella infections which you can see here okay there's no definitive treatment guidelines because most of the time these children do well but if you need to treat them doxycycline supro or is it the remission in adults or is it the remission or a traumatic whether or without with bad men and children because of concerns of problems with teeth and doxycycline finally we have a 16-year-old hiker with a photo of her rash what's this photo this is the diagnosis right here erythema migraines erythema migraines right diagnostic of Lyme disease she's relocated from the east coast I'm Borrelia tick-borne disease I it's always important to ask about it I don't test many people for this unless they have a very strong history due to this bug azotease species it is a spirochial infection with systemic diseases similar to that of syphilis early disseminated and persistent disease with the outdoor manifestations varying depending upon the stage of the disease for the follicular conjunctivitis in the early stage of the disease intermediate vest is the most common present action to disseminate your persistent seed and characterize with persistent disease it is a clinical diagnosis but we need supportive serology and PCR and currently is recommended that there's a two-step process both immunofluorescence or EIA and then west root band with confirmatory west root lining masquerade syndromes sorry for going over a little bit here but again if you have a patient that presents with pink hypopne you want to think about an AML or acute leukemia retinoblastoma and then these other masquerades including endoplasm GXG post-transplanted hystrogreform body and primary central nervous system coloma I want to thank Rachel Patel for helping me with the intermediate uveitis section it was a pleasure to review that with you and then of course my kids for the inspiration of pediatric uveas I hope this was helpful to you and mowly enough for you any questions? you're welcome thanks Dr. you bet I think we reviewed all the intermediate uveitis study guide questions and everything