 All right guys, we'll get going just because we got three presentations and so we get out on time. So start off with, we'll have Dr. Becky Gincher talking about systemic vasculitis, the most common console. Yes, exactly. All right, so we'll get started. So I'm going to talk today about systemic vasculitis case with some uncommon ocular findings. And as Rhys mentioned, this definitely is our most popular consult and I'll get to a little bit about, you know, kind of why it's important to think about systemic vasculitis and the connections between the eye at the end of my talk. So this is a case, this was a 64-year-old gentleman who was initially seen at the VA and he was referred to the UVA Disclinic for possible Bichette's disease. Only when he presented to us he had sudden onset of red eye and some periorbital edema and a lot of pain at that time. He actually had a similar episode about four months prior, which occurred while he was on xarelto and he also had sudden vision loss at that time. He said that everything was white and he was seen by an ophthalmologist in Idaho at the time and underwent actually a vitreous tap and inject because they thought maybe he had endothelitis despite the fact that he didn't have any kind of eye surgery or anything that would have led them to think about endothelitis. You know, unsurprisingly the cultures were negative in that case and he was then subsequently diagnosed with a pan-UVitis and started on some steroids and also received some topical drops and he actually was doing a little bit better as he started on the steroids and continued down that steroid taper, which he actually completed prior to seeing us, but his vision was still poor and then he had this new onset of pain and redness. On review of systems the only thing really to note was that he did have a cough and no hemoptysis with the cough, no production with the cough and he also had a history of chronic rash on his nose that kind of hadn't really gone away and he had recurrent epistaxis kind of throughout his life, which had been getting worse. In terms of his medical history, notable for a series of DVTs, he's had a lot of DVTs, some while he was on anticoagulants and some while not and then he also had multiple PEs. He had a history of cardiac tamponade and then he also had this history of a nasoceptal perforation, which just was not healing. So that's kind of, you know, important on our list of things that we were asking him and then subsequently, you know, asked about the usual social exposure. There's nothing really remarkable there. In terms of his workup, so we were actually lucky that this patient had previously been followed by rheumatology at the VA and had a quite extensive workup that was already done over the past two years as rheumatology was kind of trying to piece together these little bits from his history with the DVTs and the bowel obstructions and the nasoceptal perforation. So in all of this workup, really the only thing that came back slightly notable was the lupus anticoagulant, which rheumatology didn't seem to be able to make a whole lot out of. So in terms of what he looked like on his exam, his vision in the left eye was quite poor. It was 2,500. Right eye vision was normal. Pressures were normal. His anterior segment exam was unremarkable. But his dilated fundus exam in the left eye revealed some large clumps of vitreous in the anterior vitreous and also significant amounts of organized retinal hemorrhage. And there were also some diffuse peripheral intraretinal hemorrhage as seen on his exam. So rather than describe those findings, I'll just show you some photos. So this is a color fundus photograph of the right eye in this patient, which you can see is unremarkable. But the left eye, when we look a little bit closer, we can start to see some of these diffuse hemorrhages. These were actually kind of scattered throughout the periphery. And then some of this dense vitreous hemorrhage, infratemporally. So we like to do FAs in UVitis. So we got a fluorescing angiogram for this patient. He had a normal arm to retina time. And as we get further down the line, you can start to see some areas of reduced perfusion, kind of infrotemporally. And then a little bit also super nasally in the early phases. And then as we move along, again, you can start to see these areas of intraretinal hemorrhage show up as hypoautofluorescent there. And then, again, some areas of just a little bit of leakage in the superior macula. And then, as you can see, the right eye was essentially unremarkable. So in summary, we have a 64-year-old gentleman who's got a history of recurrent venous thromboembolism, both PEs and DVTs. Lab's only notable for a positive anticoagulant, lupus anticoagulant. And he's got a history of multiple bowel obstructions and a nasal septal perforation. And he's coming in with a unilateral occlusive vasculopathy. So on our differential, we had a couple of things, such as a CRVO with a subsequent recanalization since the fluorescein angiogram was not all that remarkable. We also thought about systemic vasculitis. And in particular, if it were to be the antifospholipid variety based on his laboratory testing, we would expect that to be more of a bilateral presentation. Bechet's disease was, again, thrown out. That was the initial consulting request. But it didn't seem likely given that he didn't have any of the ulcerating mucosal lesions that you would expect to see with Bechet's. And then granulomatosis with polyangiitis was also out there. There is a high risk of thrombotic events in these patients. And we also discussed ocular schemic syndrome, sarcoids, syphilis, the usual entities, and some type of lymphoma. So he was referred back to rheumatology after seeing us. He underwent an initial PRP in the left eye about a week after we saw him that first time. And then he had some additional work up, again, to kind of try to parse through some of these differential diagnoses. And nothing was remarkable. However, in our discussions with rheumatology, they felt really strongly that this looked like an ANCA negative granulomatosis with polyangiitis. So the ANCA testing was not confirmatory in this case, but as we'll discuss a little bit more, there are about 10 to 20% of GPA cases that end up being ANCA negative. So in light of all these findings, we started him on some prednisone. He didn't have any recurrence of his eye symptoms for at least a few months. And based on our discussions with rheumatology, he was started on methotrexate. So I'd like to talk a little bit about GPA or granulomatosis with polyangiitis, formerly known as Wegener syndrome. And it was so named because Wegener identified several patients in the 1930s who came in with common cold symptoms that then progressed to a systemic inflammatory illness, also with uremia. And the clinical features were described, and this term was actually coined in the 1950s by Goldman and Churg. And those clinical features include different types of necrotizing granulomas. So we get necrotizing granulomas in the respiratory tract that includes the upper and lower respiratory tract. We also get systemic necrotizing basculitis. And then in the kidney, particularly tends to cause a segmental glomerular nephritis. However, there are also some incomplete or renal sparing forms which have been described. The peak incidence, our patient was primed for this in the 64 to 75-year-old age range. And then ocular findings are, you know, I've read probably about four or five different papers on this subject. They say it can present in 10% to up to 60% of patients. So the most common findings are a focal necrotizing scleritis and keratitis. Those are, you know, that's usually what you see. You can also see some episcleritis. You can see some retro bulbar masses. Those of you who have rotated on oculoplastics have probably seen some of these nasal acromole duct obstructions that can get pretty bad and sometimes require a DCR. But really, uveitis is a pretty rare presentation. It occurs in about 3% according to a couple of the studies that I read. And in particular, usually presents as an acute anterior uveitis. Pan-uveitis is even less rare, and then occlusive vasculitis is quite rare. So just to show a couple of the key findings, if you are suspecting a patient might have GPA or if you see these findings, you definitely want to think about it. This is the saddle nose deformity, which occurs because of perforation of the nasal septum and some underlying bony erosion. And you can see that pretty clearly when the patient is lying down. And then this is just an example of necrotizing scleritis, which if left untreated can lead to perforation of the sclerar. Pretty rare, but it definitely can cause some vision problems. So I wanted to make a couple of sort of brief points for discussion here. And in this patient, we had an initial presentation with multiple venous thromboembolisms, but really he didn't have the dramatic sinus disease that we would expect to see in GPA. So just in looking at the association between GPA and really any type of systemic vasculitis with venous thromboembolism, there are a couple of good studies summarized in this review by Tamaki et al. And they looked at one study from the French vasculitis study group where 8% of patients developed DVT or a PE by 60 months of follow-up. So that's pretty significant to consider. And then another point of note about the ANCA testing. So in this case, our patient was ANCA negative, but as I mentioned, about 80 to 90% of patients who carry a clinical diagnosis of GPA are actually ANCA positive. And that distribution occurs mostly in the serine protease 3, but about 20% of cases will be myeloperoxidase positive. So we still have 10 to 20% of cases that are ANCA negative. And then in terms of the associations between retinal vasculitis and systemic vasculitis, this is something that we get consulted for a lot. And there's a lot of common misconception outside of the ophthalmology community. I know you all know that the association is not as strong as people think, but it's often suspected and actually rarely linked between systemic vasculitis and retinal vasculitis. There was one study that looked at 207 patients with retinal vasculitis and found only 1.4% of those cases were associated directly responsible with a systemic vasculitis. In another study, again similar findings, actually they looked at about 1,300 patients with systemic vasculitis and retinal vasculitis and found that in 216 patients with systemic vasculitis, only about 16 of those actually had retinal vasculitis that was the cause of their blurred vision. And then lastly, in terms of treatment considerations for this patient, there was a hot off the press review article by Stephen Foster's group that looked at Rituximab and Methotrexate and steroids and they actually found the best induction of remission with Rituximab, with or without steroids. They found remission in 9 of 14 patients and these were all patients with an ANCA-associated systemic vasculitis. And then out of these 22 eyes that they looked at, good visual outcome in 17 of 22. So those are pretty good findings and a good suggestion that Rituximab might be appropriate for this patient. So just to summarize, this patient actually was initially seen about three years ago and just to summarize what's gone on since that time, he did have a drop in his vision back in July of 2016. We started him back on steroids and then in September of 2016, after a lot of discussions with the VA, we got him on Rituximab. He underwent two infusions and then subsequently developed a pneumonia, was taken off the Methotrexate and the Rituximab and developed a large new vitreous hemorrhage requiring a parisplane of atrectomy and endolaser and then eventually got him back on the Methotrexate. We started to do better. And then about a couple months later developed a decent cataract thanks to the various interventions that we did. And actually Eileen did his cataract surgery last May and his vision was pretty great afterwards, 2070, compared to 2500. Then later, this past summer, he developed a hypopian uveitis, so there's been some ups and downs, which responded pretty well to steroids. And then at that time, we started CellSept. And in November, he developed a low B cell count, so taken off the CellSept just to kind of illustrate all of the considerations when putting patients on these types of medications. And then lastly, we saw him in December and he actually developed a new anterior uveitis in the right eye, which was a little concerning and we strongly encouraged rheumatology to consider putting this patient back on Rituximab since he seemed to do pretty well while he was on it. Any questions? Yes, Dr. Harry. Just a question, did ENT folks ever do biopsies on these medications? Is this kind of long biopsies? That's a good question. They do and actually when he was seen by rheumatology, they referred him to ENT. ENT saw him and said, well, we're not going to do anything about that nasal septal perforation and he wasn't inflamed enough to get a good biopsy sample, so they opted not to biopsy, but certainly they can, especially if there's a large granuloma there, large amounts of sinus disease, they definitely can do a biopsy. And that would sort of be the most... I mean, typically we go after the lung to try to get a good biopsy, but if there are no lung lesions, then we can go for the sinus disease.