 So we're going to go ahead with another one of our last of the second year at Resident Talks. Eileen Huang is going to talk to us about cerebral vasculitis in placoid coreo-retinopathy. And I appreciate her stepping up here without a lot of notice and going ahead. Eileen, you're up. Oh, before one announcements, I want to thank Chet Shelly, A.J. Orman from Alcon, Suzanne Brockes from Baushan Lawn. Their support helps support lunch, breaks, and everything you have enjoyed today. So if you see them out here, please thank them. All right. So I'm going to talk about a patient that I saw with Dr. Shakur and Dr. Bell. So I want to give them credit, as well as I got some input on this from Edward Quigley in the Neuro Radiology Department, who may be related to one of our attendings here. Let's see. So the patient was a 20-year-old female. She said that two weeks prior to her seeing us, she had sudden onset of a central vision loss in her right eye. There was a black spot in her vision. It didn't change or move or grow since it came on. She didn't have any eye pain. She hadn't injured her eye. She also mentioned that she had some numbness on the left side of her body that started a few days before the vision changed, but that had gone away. She did not have any medical history. Her only medication was an oral contraceptive, and she was a university student who did not use drugs, and her review systems was pretty unremarkable. On her initial exam, her visual acuity was 2080 in the right, and 2015 in the left. Her anterior segment exam was unremarkable without inflammation, and in her posterior segment she didn't have any vitreous cell or haze, but she did have these lesions in her posterior pole. You can see that her optic nerves and her vessels are normal, but there are these well demarcated areas of RP atrophy. As well as in the central macula of the right eye, there's this yellowish plaque-wave lesion that has indistinct borders that likely was responsible for her visual symptoms. This is a montage photo demonstrating the fact that there were also lesions in the periphery that were atrophic as well as being hyperpigmented. She had a few lesions in her left eye as well, down here and over here, posterior pole and periphery. On optical coherence tomography, she had some disruption of her inner segment, outer segment junction, as well as some sub-retinal hyperreflectivity. I'd like to ask the residents, or if Dr. Hoffman wants to pitch in with a differential diagnosis. Or Dr. Zog, who always knows the answers, who do you want to give us what we should consider in this case? I was distracted, I apologize. It looked like a sort of pigeon that's coming off the nerve in one eye. Yep, it did look kind of close, and it's also kind of a geographic lesion. There's a lot of peripheral lesions, too, so. Right, birdshot and multifocal, coreoditis and panubiitis would also have those peripheral lesions. Any of the residents want to chime in with what we consider for every type of ubiitis? Thank you, Zog, for answering again, but yes, syphilis, sarcoid and TB. So, Dr. Zog hit on a lot of good points. We should also consider eels, because any time something looks like serpiginous, we got to consider that could be infectious related to TB, VKH, and also ampi, just because of the kind of plaqueoid nature of that central lesion in the right eye. We talked about these, and also Bartonella can cause acoreo-retinitis that looks like this. So, additional testing. Now I'll ask the residents specifically, what else would you like to get? RISC, clinic testing or lab testing? Right, so FAA and ICG, those are things we do for all these inflammatory diseases. How about an MRI of the brain because she had some of that numbness? Let's do a show of hands. Who does not want to do an MRI? Let's say maybe the numbness went away. Anyone not want to do an MRI? Raise your hand now. Anyone who wants to do an MRI? Raise your hand. Okay, Dr. Mamelis, that looks like it's pretty much the consensus. Let's check out that numbness, because that sounded kind of unusual. So here's an autofluorescence, and we can see that those atrophic lesions correspond to hypo-autofluorescence in certain areas with some stippled hyper-autofluorescence. That one poorly defined lesion, the center of the right macula, has some central hypo-autofluorescence that's ringed by hyper-autofluorescence and then more hypo-autofluorescence. That has been described as a cockade pattern in this specific disease. So this is the fluorescein angiogram. Those atrophic appearing lesions are basically turning out to be window defects with some staining around the edges. And the central lesion is blocking early and then staining late, which is kind of classic for active corioretinitis. On ICG, there was hypo-autofluorescence corresponding to all the lesions. There weren't any additional lesions spotted on ICG. So we did get an MRI of the brain. I think the retina fellow who saw this patient was Jim Bell. So he ordered the MRI to be done that very afternoon. And this is the diffusion-weighted imaging on the left, which demonstrates hyperintensity of the bilateral pons. And there's a corresponding dark hypo-intense spot on the parent diffusion coefficient imaging, indicating that these were strokes, so they were ischemic infarcts of her bilateral pons. So the read was done after the patient had left the place where she got the MRI. So Dr. Bell called the patient and had her go to the emergency department, and she was admitted for a stroke workout. They checked her for hypercoagulability, carotid, cardiac disease, sarcoid, syphilis, and TB, and everything came back negative. In consultation with ophthalmology, they felt that her central nervous system disease was likely an inflammatory etiology. So they started her on a high-dose IV steroids, and they followed that with oral steroids. One week later, she had some additional workup. She had a lumbar puncture, which was normal. She had a cerebral angiogram, catheter angiogram, that demonstrated some areas of focal narrowing and irregularity. This was present in multiple vessels in the anterior and posterior circulation. We didn't find any abnormalities of those deep penetrating vessels from the basilar artery that would have supplied her pons, but they may have been too small to see. She had some additional workup for lupus, NA phospholipid antibody syndrome, chogrens, and inca-associated vasculitis, and this was all negative. Dr. Shakur injected an Osardex implant and started her on cell sept to control her ocular disease. And rheumatology started her on rituximab for her presumed central nervous system vasculitis. So the diagnosis was felt to be a rare entity that you might not have heard of, which is a relentless plaqueoid corioredonitis. So on follow-up, she did not have any recurrences at three months, and she had a repeat cerebral angiogram that was normal. So her rituximab was stopped. At six months, she still was doing well in terms of not having any new lesions. And that previously active appearing lesion now looks atrophic with some hyperpigmentation in that area. Unfortunately, her visual acuity didn't get any better, but she said that her central scatoma was subjectively less dark. So I guess at this point we should ask, why is this case interesting? You know, for those of us who are not necessarily uveitis experts. But it's really important because it's one of those diseases that could kill the patient that we could potentially pick up by seeing a patient in the office when they present acutely with symptoms. So I think it's pretty important to know about from that perspective. And then, you know, from a general knowledge perspective, her diagnosis relentless plaqueoid corioretinopathy has only been reported in association with central nervous system disease one previous time. And this is the first time that a patient with this relentless plaqueoid corioretinopathy has had a stroke and had proof of cerebral vasculitis on angiography. So there is one case reported previously in 2009 of relentless plaqueoid associated with central nervous system disease. But that patient just had headaches, no focal neurological symptoms, and they had flare hyperintensities on their MRI but no definite evidence of stroke and their cerebral angiogram was normal. So a little bit more about relentless plaqueoid corioretinopathy. It was described really pretty recently just in the year 2000 by Jones et al. However, you know, we probably would imagine that this disease has likely been around longer and upon looking back at older cases, certain things that were described as recurrent ampy probably fell in this category. It's also been called ampygenous corioretinopathy since it shares characteristics with ampy and serpiginous. That's kind of a mishmash of the two words. Its key characteristics are posterior and peripheral retinal lesions that occur before or simultaneously with the macular lesions. And it's also a progressive disease if untreated in which you can see older healing pigmented lesions like we saw in our patient together with new active lesions that have hazy borders and don't have that hyperpigmentation. As I mentioned, the lesions can look kind of similar to ampy and serpiginous, and this disease shares characteristics of both. So I've put up photos here of ampy, which is acute posterior multifocal placoid pigment epitheliopathy. And you can see these yellow, black-oiled lesions that are not very well-defined. And then here's a patient with serpiginous coroiditis where you can see geographic lesions extending from the nerve. The ways that relentless placoid differs from these diseases is that it has peripheral lesions early on in the disease, whereas ampy almost never has peripheral lesions. And serpiginous usually only involves the periphery after there's extensive macular involvement. So as I mentioned, there's not that much known about the association between relentless placoid and stroke. So I thought I would look at whether ampy and serpiginous have been associated. And indeed, there's a strong association between ampy and stroke. There's been numerous cases published where patients have had neurological signs or symptoms, such as headaches, hemiparesis, seizures, et cetera, that occur soon after the onset of their ocular symptoms. And they demonstrate commonly MRI findings consistent with infarcts, although other things have been found as well. They usually have CSF pleocytosis. And on cerebral angiography, stenosis and vasculopathy have been demonstrated of both large vessels, like the middle cerebral artery and smaller vessels as well. This has been proven on histopathology to correlate with vasculitis in just two cases. In the other cases, there was no histopath available. As you can imagine, if a person develops ampy, you're not going to biopsy their eye. But there was one patient who passed away, and they did, on the autopsy, see definite evidence of vasculitis causing those strokes and vessel irregularities. Ampy is a pretty rare disease to begin with, and the strokes associated with it are pretty rare as well. Just one out of 18 in this case series. And however, the consequences of stroke associated with ampy can be pretty severe. Five out of the 28 published cases of ampy associated stroke resulted in death of the patient from the stroke. So this is really something that you don't want to miss, and you want to catch early and treat, because cerebral vasculitis is treatable. In contrast, serpiginous chlorideitis doesn't have any systemic associations. It may be that this indicates that relentless plaqueoid may share more features with ampy, but it's not currently clear. So the way the diagnosis of central nervous system vasculitis is made is definitively by biopsy, but as you can imagine, biopsy in the brain or the meninges is not something that we want to do unless it's really indicated. And also even biopsy has a limited sensitivity. If there is cerebral angiography evidence of narrowing and dilation in multiple areas of multiple vessels, that's consistent with the vasculitis, but it can also occur in other vasculopathies as well. But can be used to make the diagnosis in the appropriate clinical context, which is what we did in this case. A few terms that are used, I've seen in the literature, vasculitis referred to as angiitis in this context. I've seen the word cerebral substituted for central nervous system just because usually it involves the brain. So central nervous system vasculitis can either be primary or secondary in order to make a diagnosis of primary vasculitis. Secondary causes must be excluded as well as diseases that mimic vasculitis on angiography. Vasculitis of the central nervous system can be due to atypical infection, systemic vasculitis, drugs or connective tissue diseases as well as sarcoidosis. In addition, there are some non-inflammatory vasculopathies that can appear similar to vasculitis on cerebral angiography with that irregularity of the blood vessels, and this includes hyperacquigable states and SUSAC syndrome. In primary vasculitis of the central nervous system, the eye where visual pathway is often involved, most of the time it's due to the cerebral effects of infarction, such as affecting the visual fields, but they can also be associated with optic neuritis and cranial nerve palsies. I've just listed some of the systemic vasculitis here that affect the eye. Cogan syndrome, giant cell granulotosis with polyangitis, bachettes, and sarcoidosis, which is not a vasculitis, but rarely can have vasculitis of the central nervous system, but also does have retinal vasculitis. Some of the mimicers that look similar to the vasculidities on angiography of the brain include lupus or aniphospholipid antibody syndrome, but on histopathology it usually demonstrates that there's vascular occlusion without inflammation, and I believe that's what it demonstrates on fluorescent angiography most of the time, although there may be some leakage. Sussac syndrome is another disease that's characterized by autoimmune mediated arteriolar occlusion without inflammation. This also led me to wonder how the systemic vasculitis were related to retinal vasculitis. I've several times as a resident received a consult to do specifically a fluorescing angiogram because a systemic vasculitis was suspected, and I've just wondered what is the evidence behind that. It's also very curious when the primary team tells me they have no idea what the disease is and they don't need me to examine the eye, they just need me to do a fluorescing angiogram because that's the only way they're going to pick up their vasculitis without biopsying something. So actually systemic vasculitis is very rarely associated with retinal vasculitis. As you saw in that listing of the systemic vasculitis, they're often associated with ocular manifestations and inflammation, but not necessarily retinal vasculitis. Why is that the case? I think that the vasculitis are pretty specific in terms of which organs that they target, but also the way that we diagnose retinal vasculitis, which is by leakage on fluorescent angiography, which can sometimes be due to not an inflammatory process, but due to occlusion or other reasons, is different from how systemic vasculitis are diagnosed, which is by biopsy and pathology demonstrating vessel wall inflammation and necrosis. Going back to the primary central nervous system vasculitis, retinal vasculitis has not been reported in that case. Going back to our case of relentless placoid associated with central nervous system vasculitis, one wonders why did those occur together? And similarly for ampey, there have been some theories proposed for how the disease of the eye is caused by what the etiology of the ocular disease is relative to the cerebral disease. So ampey is thought that it could be a disease of the choroidal vasculature as demonstrated by the hypofluorescence on ICG. And also there is some retinal vasculitis sometimes in ampey and sometimes serious retinal detachments that could be explained by choroidal ischemia. So it could be that ampey is a disease that could affect the blood vessels specifically of just the coroid and the brain. There is only one case in which I mentioned upon autopsy that they did histopathology of the eye and that didn't demonstrate any vasculitis of the choroid but it did demonstrate granulomatous inflammation of the choroid. So I think our case is really interesting because it suggests that maybe there could be a link between relentless placoid and the choroidal vasculature as well but that needs to be further investigated. I think that one technique that could be really useful for both relentless placoid and for ampey would be OCT angiography if that really improves our ability to look at the choroidal vasculature and could tell us whether that's really the fundamental problem in these diseases. So just going back to a summary of what I've talked about relentless placoid is a posterior uveitis. It shares characteristics with both ampey and serpiginous and both ampey and relentless placoid can be associated with strokes that are likely due to cerebral vasculitis and that's something that we as ophthalmologists if we see someone presenting acutely with a disease that could be this we don't want to miss because it's treatable. So we should, you know, refer these patients for neurological workup and treatment as indicated. And just, you know, for those consoles that we get I think it was interesting that cerebral and retinal vasculitis don't often occur together except in the case of Bichette's disease and some, you know, viral infections. Okay, that's it.