 So good morning everybody. I'd like to get started. This is the UVITAS division's presentation, case presentations. We thought that we would try to present kind of an overview of pediatric UVITAS. And what I will do is provide some background information and an introduction and some new developments, and then try to illustrate some of these with case presentations by my colleagues. So pediatric UVITAS definitely not kid stuff. The good, the bad, the ugly, and the potentially horrible. Pediatric UVITAS scares everybody because it's in kids. It is a subject that I think deserves special attention because of the unique diagnostic management issues and therapeutic dilemmas inherent in this population. A history review, assistance, and a complete examination can be really difficult to obtain in a preverbal child. The diagnosis varies with age, with an overrepresentation of infectious ideologies, pediatric-specific masquerade syndrome such as retinal blastoma, and leukemia, unique endogenous syndrome such as JA-associated urocyclitis and calisacus disease, and atypical presentations of familiar diseases in adults such as sore cartosis. This in turn affects the interpretation and choice of laboratory tests. Disease is chronic, recurrent, and insidious with a frequent development of structural complications. Presentation with established pathology or structural complications is in and of itself a risk for the development of further complications as a really graphic manifestation of the diagnostic delay and screen failure in this population. Finally, there is the unique risk of abliopia which heavily influences therapeutic and surgical decision making. Just to give you an idea, pediatric uveitis is about fourfold less common than in adults, but it can represent up to a third of the patients that you see in a tertiary care setting, representing about 20,000 children with uveitis in the United States. There have been some definitive shifts in the anatomic distribution of uveitis in the past decade with an increase in the number of pan-uveitis and intermediate uveitis due thought to be due to better diagnosis and treatment of toxoplasmosis and toxicoriasis. There is obviously referral bias and dependence on geography. Population-based studies show a predominance of anterior uveitis, but at the Brandeis Center we see a lot of intermediate posterior uveitis. In the largest epidemiologic study in the United States, anterior idiopathic uveitis is most common at the NEI and followed by the most common being juvenile idiopathic associated ureocyclitis. But if you look around the world, there is an over-representation and much higher incidence of infectious uveitis in India and in Colombia. Social complications such as cataract macrodema, hypopathy, epidural membrane, and glaucoma and poor visual outcomes are related to the anatomic location, the type of uveitis, and timely referral with poorer prognoses being seen in patients with infectious ideologies, posterior pan-uveitis. Visual impairment and severe visual loss is not uncommon with blindness resulting in up to a third of patients in Colombia. So the differential diagnosis, infectious disease just isn't adult's most common anterior infectious uveitis would be hereditary diseases. However, we do see some unusual things such as bilateral simultaneous uveitis which we see in patients with post-infectious disease such as streptococcal infection or in a non-infectious entity known as TINU tubular institutional uveitis and uveitis syndrome. The most common infectious ideology in children is toxoplasmosis as it is in adults. Again, to underline the fact that non-infectious uveitis, JIA associated ureocyclitis is the most common systemic association in children. But then again there are these unusual syndromes such as early onset of sarcoidosis and blouse syndrome. One must not forget the fact that in kids there can be unidiotic masquerades such as retinoblastoma presenting as a hypobiotic and leukemic infiltration. Therapeutic dilemmas surround the use of corticosteroids for concerns in inducing structural complications such as cataract and ocular hypertension and the use of systemic steroids in inducing growth retardation versus therapeutic timidity with the use of nonsteroidal immunomodulation for fear of toxicity associated with these medications. As we know, kids represent greater surgical risk. They have more exuberant inflammatory response to surgical trauma plus there are inherent complications associated with certain disease diagnosis such as JIA associated ureocyclitis. So the therapeutic approach as in adults is to eliminate active inflammation by any means possible with the appropriate administration of antimicrobial therapy in the cases of infectious diseases and then a stepladder approach using steroids by all routes necessary in order to put out the fire and then the early implementation of steroid sparing immunomodulatory therapy in the cases of non-infectious chronic diseases and in some cases the use of diagnosis and therapeutic attracts me. So we can divide immunomodulatory therapy into conventional and biological treatment. Conventional treatment can be further subdivided into the anti-metabolites, the T-cell transduction inhibitors and the outclading agents. By far we use the anti-metabolites most frequently including methotrexate and mycophenolate mofital sometimes with cyclosporine as an add-on therapy and much less commonly in these days are outletting agents used because of the real toxicity associated with these agents and better alternatives in biological agents. Methotrexate by far is the most common first-line agent in both pediatric and JIA associated ureocyclitis. I'm having inflammatory control in about three-quarters of the patient and a steering sparing effect is that there are about a quarter of patients that don't. So one has a better chance of inducing remission in patients with methotrexate with longer periods of disease inactivity on medication with longer periods of time on medication up to three years in one study in the Netherlands. Biological response modifiers by definition are therapeutic proteins that serve as antagonists to immunoactive molecules such as recombinant antibodies that block cytokines or receptors or cell surface proteins. The idea of course being more specific and targeted therapy and to decrease side effects. The TNF inhibitors are the ones that are most commonly familiar with people and associated with treatment. They are listed here at Tenercept and FlixMab and Adalimumab. Tenercept is great for arthritis but is really not useful in patients with ureocyclitis. InflixMab is a chimeric monoclonal antibody, a mouse-human combination, and Adalimumab is a humanized monoclonal antibody that can be administered subcutaneously whereas inflixMab must be administered intravenously. They both bind membrane bound and soluble TNF alpha. These two agents have been recommended by an expert panel to be first-line agents in patients with base shet cities and then second-line agents in children with JIA-associated ureocyclitis. Just to give you an idea about inflixMab, it shows consistent and sustained reduction of intraocular inflammation, usually at higher doses at shorter infusion intervals that is used in rheumatology and allows systemic taper of IMT and its steroid sparing. The problem, not the problem with this, but one of the things that one must be aware is that it's usually used in combination with an anti-metallic such as the methotrexate in order to prevent the formation of anti-chimeric antibodies which may reduce the efficacy of the medication. One must also know that it's non-remitting and its efficacy may vary in time. Adalimumab or Humera is an effective treatment option to patients that fail a methotrexate. It advantages is that it's humanized, less immunogenic, the last subcutaneous dosing every two weeks, and it is FDA-approved for adults for non-infectious, intermediate, postural, and pancreatitis, and it's been more recently approved for similar indications for pediatric uveitis. I want to draw your attention to the sycamore trial which was included a year ago and concluded early which was a randomized controlled trial of the clinical effectiveness and cost effectiveness of Adalimumab plus methotrexate versus methotrexate alone in a large cohort of patients with JIA uveitis. It showed that there was a definitive advantage in terms of efficacy and time-to-treatment failure with a combination of drugs rather than either drug alone which really supports the common practice of using these drugs in combination of clinical practice. One of us also know that these are not magic bullets, that there is variable response to anti-TNF therapy. There are non-responders with a waning response and treatment-related side effects which may preclude their use. So the options that one has is to use an alternative agent in the same class. So if one is not responding to a humerus, infliximab may be a good choice because you can vary the dose and the frequency. There are other agents in the same class such as Golumumab. And then there are third-line biologic agents for which there is some experience in uveitis such as Orensia, Rituximab, Anacunaridoclizumab, and ectema, or Tocilizumab. I just want to let you know that Golumumab is an anti-TNF agent that can be administered monthly and has been shown to be effective in JAAA in patients that are refractory to other biologic agents. Similarly, Rituximab, which has a different mechanism of action, which is the anti-B-cell mouse-human monoclonal antibody, has been similarly effective in at least two studies in patients with refractory JAAA. So it's here at uveitis. On the other hand, Abaticep, or Orensia, initially was thought to be helpful in this population of patients, but in larger case studies has been shown to be pretty much a coin toss in terms of efficacy. There are a whole slew of other biologic agents for which there's little experience in uveitis, but there's one promising agent, ectema or Tocilizumab, which has been shown to be actually quite effective as a third-line agent, both in terms of anti-inflammatory efficacy and actually in the reduction of macular edema. So what about the outcomes? Well, there are some pretty good retrospective data which shows reduced risk of auto-accomplications in patients with JAAA-associated urocycletus, such as reduction of hypotiny, eburetinal membrane formation, and blindness in the better-seeing eye. With an 86% proof or stabilization of vision with effective immunomodulation in another study, but this result was achieved only with early implementation of this medication. And then in the site cohort, which was the largest retrospective cohort of five very large uveitis practices in the United States, there was a 60% reduction in the risk of visual loss, particularly for the 2050 level. So modifying the prognosis in this very fragile group of patients will require effective immunosuppression and early treatment of intraocular inflammation with the early introduction of IMT therapy. And then I think the identification of eyes that are really at risk for complications of visual loss. So this would include surrogates, disease severity such as presentation with ocular pathology, and then new modalities that are coming to the fore such as laser flare photometry and OCT evaluation of anterior segment flare itself. And then I think that there is a call for the reassessment of screening guidelines for patients with uroocyclitis and vigilant post-marking surveillance and randomized control of clinical trials for patients that are undergoing immunomodulatory therapy. So I would like to hand it over to Dr. Laura Schell, who will present an unusual case and my colleagues who will try to illustrate some of these points. Thank you. So Al, question. With the move to these immunomodulators that we're talking about, is there safety profile such you feel comfortable utilizing them without co-managing with rheumatology? Do you still feel that you need co-management with rheumatology with these? So for children, we co-manage them with rheumatology. I think that we are capable of actually in adults we manage immunomodulatory therapy, including biologic agents here by ourselves. But one of the reasons we co-manage them is a large number of these patients have systemic disease. And so I think that it makes a lot of sense to have that good medical care. We have a really head and glove collaboration with pediatric rheumatology. We do have good collaboration with adult rheumatology, but there is less enthusiasm actually to treat patients with, for example, non-rheumatologic indications that have acute disease. It's hard to get into them. The whole institution talks about how hard it is to get into rheumatology. The best care for children with these diseases is really a collaborative effort with pediatric rheumatology, particularly those children that have rheumatologic disease.