 Hi, my name is Marisa La Rochelle and I'm UVIDIS faculty at the Moran Eye Center at University of Utah in Salt Lake City. This is part two of a lecture on UVIDIS for the Comprehensive Eye Provider. So if you haven't already watched the first section, I would suggest doing that, which reviews the way we characterize and grade inflammation in the eye. Our first case is a 38-year-old man presenting with decreased vision. He has pain and redness in the left eye with floaters and it started just 48 hours ago. Non-contributory past medical history exam in that, sorry, that should say OS 2100 in the affected eye. And his slit lamp exam is remarkable for mutton fat, curatic precipitates on his cornea, some anterior chamber inflammation, and then 2 plus vitreous cell and haze in the left eye. Right eye is unaffected. This is a fundus photo of the left eye. Admittedly, there's not 2 plus haze in this photo, but we can see multiple areas of retinal whitening that have started to coalesce in the periphery. There's some associated retinal hemorrhages and then some retinal vasculitis as well. And this photo illustrates a great example that if we're only looking at the posterior pole between the major arcades, we can miss the critical finding. So differential diagnosis for this. This is basically a list of things you don't want to see at 4 p.m. on a Friday and that you don't want to have happen to you or a loved one. Nothing that looks like that photo is good. So top of the list would be acute retinal necrosis or ARN. ARN is due to VZV or HSV. You could also consider CMV retinitis and an HIV patient, but that would be much less likely given the rapidity of onset and the amount of vitritis. Other things on the list include syphilis, toxo, lymphoma, or other inflammatory conditions like bishettes. So I want to emphasize that this is a true ocular emergency. If you don't treat these kind of entities, pick up the phone and call your neighborhood retina specialist now or send it to an emergency room at a tertiary center that has ophthalmology on call. We don't even wait for results. We would inject intraviral antivirals that day to cover ARN because that's something that 24 hours can make a difference. So if this patient walked into my clinic, I would do an anterior chamber tap and send it for viral PCR. I would order blood work to rule out other things, but I wouldn't even wait on results before injecting antivirals into the vitreous to cover for infectious necrotizing retinitis. So acute retinal necrosis, abbreviated ARN. This happens in otherwise healthy patients. So typically in the fifth to seventh decade, but it really can happen at any time. They can start with a severe anterior uveitis that quickly progresses. The triad is occlusive retinal vasculitis, marked vitritis, and then the retinal necrosis is shown as these multiple yellowish white creme lesions that typically start in the periphery and coalesce and then move central. Unfortunately, retinal detachment is high in these patients, even with treatment. And that's due to small retinal holes that happen at the junction of the normal retina and the atrophic retina. And we know without treatment, the fellow eye becomes involved in the majority of cases. So this would be, this is an example of how we would treat this at the Moran Eye Center. There's no specific guidelines. Historically, patients were admitted for IVA cycle vir as the gold standard, but we know that we can achieve similar plasma concentrations with high-dose oral valve cycle vir. So my tip for this case is get your patient to somewhere the way they can get treatment immediately. If you pick up the phone and say the magical words, I have a patient with severe uveitis. They have an acute decline in vision, and I'm seeing some retinal whitening. Any retina provider or uveitis specialist will know the gravity of the situation and the timeliness really matters. Dilate every patient with uveitis, and this is why. We don't want to think a patient just says anterior uveitis, and if we don't dilate the eye and look in the periphery, we could miss retinal necrosis. We also have to dilate the other eye at every visit because we know fellow eye involvement is high. Our second case is a 55-year-old woman. She noticed several months of floaters and also complaints of poor night vision. Exam seems unremarkable at first with 2020 vision in both eyes. She has normal anterior segment, but you do notice one-plus vitreous cells with a trace amount of haze in both eyes. On dilated exam, we notice multiple round, deep, creamy, coroidal or retinocoridal lesions scattered throughout the posterior pole. A differential for that photo would be birchot, coreoretinopathy, also consider things like sarcoid, lymphoma, less likely other white dot syndromes or infectious etiology. In this patient, I would try to rule out the typical things like sarcoid, syphilis, and then I would add on an HLA-A29, and that's a genotype that we know is very highly associated with birchot, coreoretinopathy. I don't typically order an A29 in all UVI-dispatients since we know that this genotype can be found in 7% of the general population, so without a high pre-test probability, it can often lead you down the wrong track, so I only check it as a confirmatory test if I have a high clinical suspicion. And I would get multimodal imaging on this patient. This is a wide field fluorescein angiography which shows retinovascular leakage as well as optic nerve leakage, and it looks like some petaloid leakage in the macula as well. An ICG of the left eye shows many of these hypofluorescent lesions even more than we see on exam. So birchot tends to affect middle-aged people, more commonly Caucasians and females. We see a lot of it in Utah. The vision loss is progressive and painless visual dysfunction, so they often have preserved central visual acuity. It can be 2020 if they don't have macular edema, and they complain of poor contrast sensitivity or trouble in low lighting. The photopsias they describe aren't like the bright flashes of light that happen with retinal detachments, but rather this vague shimmering in their vision. If they have anterior uveitis, it's mild. They do get vitritis, but without the exudation on the parisplania or snow banking that we see in intermediate uveitis or parisplanitis. And then they get these cream-colored deep lesions. They're often more notable in the infranasal quadrant. The abnormal ERG in visual field is why this is an important diagnosis not to miss. This is not an ophthalmic emergency. You don't have to pick up the phone and call retina that day or even that month. But this disease is known for something called retinal rot. So that's a slow deterioration of the retinal function over decades. So if your patient has visual complaints, even if they're 2020, do dilate the eye. Take a look in the back and make sure you're not missing these creamy corridor lesions that could be birdshot. For treatment, we bridge with steroids because they work immediately, either oral prednisone or an intraocular or periocular steroid injection, and then we start immunomodulatory therapy. So I typically start with an anti-metabolite like methotrexate or cellsept, and then often add a second agent like a calcinerine inhibitor or an anti-TNF alpha agent like humira or remicade. So my pearls for this is that patient's symptoms can actually be worse than the exam looks. Especially if they have a blonde fun die. And then once the patient's diagnosed with birdshot disease, we really do pay attention to their subjective complaints about shimmering bitopsias. It's often a clue that they're still active or undertreated. Dilate every patient with uveitis. Our next case is a 21-year-old woman that comes in with blurred vision in the right eye, mild discomfort. And she describes some infection in the eye as a child where she was raised in Venezuela. A vision is only slightly decreased in the affected eye, and the IOP is asymmetric being higher in the affected eye. Her slit lamp exam is notable for mild anterior chamber inflammation of the right eye, as well as vitreous inflammation. And this photo, we can see a relatively clear view in and an unaffected macula of why her vision is still good. And then I'll zoom in on this nasal area of the retina where we see retinal whitening adjacent to this hyperpigmented area of the retina. There's also some mild dysk, hyperemia, maybe blurred dysk margins, nasally. And we can see inflammation of the vessels. So the buzzwords, focal area of retinal whitening adjacent to a pigmented scar may tip off some alarms to you. That's what our residents are trained to identify as ocular toxoplasmosis. Differential anytime we see retinal whitening, always consider acute retinal necrosis, syphilis and TB, or it could be a non-infectious or inflammatory etiology. So a workup would look something like this. The utility of toxoplasma IgG and IgM is actually limited. If it's negative, that can be helpful to rule out ocular toxo. But if it's positive, it just means that it's still a possibility. It doesn't prove anything, since a large percentage of people are seropositive for toxoplasmosis, about one-third worldwide, but as high as 80% in South American or some Latin American countries. Ocular toxoplasmosis is the number one cause of infectious posterior uveitis in the world. We don't see as much of it in Utah, but we still do see cases often in patients that have immigrated from other countries, where it's more common. The classic findings, this yellowish white lesion at the area at the adjacent margin of an old quarry retinal scars is the typical scenario. They can have retinal edema. And then I put an asterisk near vitritus, because sometimes it's not a diffuse vitritus causing haziness, as you can see in the patient that I presented because of the clarity of the fundus photo. At times, it's just a focal clump of vitritus overlying the area of the active retinitis. Again, vascular sheathing, both near the active lesion and in the distant unaffected retina. The anterior uveitis can have mutton fat Kp. And then toxoplasmosis is on the list of causes of uveitis associated with high rather than low intracular pressure. And then lastly, I don't know how to pronounce that, but it refers to the accumulation of whitish exudates within the arteries. Management, the classic triple therapy is sulfidiazine, pyrimethamine. And then we add folenic acid to help combat some of the negative side effects of the other medications, like decreased white blood cells and decreased platelets. There's a whole other list of alternative medications for toxo, such as atovicone, azithromycin, Bactrum, both systemic and intervitural clinomycin is used as well. Oral steroids. So I'm just going to go off on a little tangent here about the use of steroids for toxoplasmosis. If there's a significant inflammatory response with vitritus, then I typically add oral prednisone about two days after starting the antibiotic therapy. So steroids themselves are not contraindicated in toxoplasmosis, but unchecked steroids, meaning without the use of antibiotic therapy is a contraindication, especially periocular intravitural steroids. So I'm just going to show you a couple of pictures from a case I presented at our Morbidity and Blindness Grand Rounds last year. This was a 39-year-old woman that came from Mexico. She presented to an outside provider with panuviitis of the left eye. Vision at that time was 2,200. And then this doctor injected intravitural tramsin alone, twice, actually. And she came to us a couple months later with light perception, only vision, and eventually with a retinal detachment. So this is ocular toxoplasmosis gone rampant in the eye with local steroids. So this is just a reminder. If you're unsure of the diagnosis and haven't ruled out infectious etiology, don't inject steroids in the eye. If there's any question, at least if you start with oral prednisone and the patient worsens, you can turn it off by stopping the medication. So prophylaxis. For patients that have an inactive lesion and a history of recurrence, there's some evidence that shows that Bactrum three days a week or every other day can help prevent recurrences. And you can imagine this would be important for lesions close to the nerve or the macula. Remember, ocular toxoplasmosis is a clinical diagnosis. It can be supported by labs. We already talked about the seropositivity issue. And then PCR of the aqueous only has a sensitivity around the 40 to 50% range. And then differential diagnosis. If you have a patient in your clinic with severe unilateral vitritus, it's a hazy view of the fundus. You think maybe there's some retinal whitening, but you're not sure it could be toxic. It could be arned. You can cover both by injecting intravitual pluscarnate or vancyclivir and the intravitual clindamycin until you get labs back or have a more definitive diagnosis. Just don't inject steroids alone. Dialate every patient with uveitis. This is our last case. A 17 year old man comes in with two weeks of intermittent floaters in the right eye. He has a notable past medical history of acute lymphoblastic leukemia. Status post-abone marrow transplant is also on chemotherapy. So he's very immune suppressed. Visual acuity is still pretty good in both eyes. And then he has trace vitreous cells in the right eye. On fundus examination, macula looks normal, but we can see this large area of white retinal necrosis with associated hemorrhage in that nasal periphery. So differential diagnosis, CMV retinitis. We know it's immunocompromised. Other necrotizing retinitis like VZV or HSV from ARN. And then the other things always to consider are things like typhilis, toxo, or inflammatory causes. So this is CMV retinitis. This patient was actually sent to us with known CMV viremia. We know he's severely immune suppressed. You could confirm CMV with a PCR of the aqueous, but it's a clinical diagnosis. So CMV retinitis occurs in the severely immunocompromised patients. This is the hallmark eye disease in the HIV AIDS era, especially in patients with CD4 counts under 50. Outside of HIV AIDS, another group affected by CMV is the transplant and chemotherapy patient population. They get full thickness retinal necrosis, but only minimal vitreous inflammation since they are immune suppressed and their body can't mount that immune response in the vitreous. There's three classic subtypes. The granular subtype can be more subtle. It happens in the periphery and it's less likely associated with the retinal whitening and hemorrhage. And then the fulminant subtype is that classic blood and then yellowish white necrosis, which gives the pizza pie fundus that residents learn about. And then frosted branch angiotis is when there's whitish lesions along the vasculature, causing the posterior pole to look like there's tree branches covered in snow. So CMV retinitis moves slowly. This is a counterintuitive for a lot of residents when they're learning about retinal necrosis because you would think that if an immunocompromised patient gets a viral infection in the retina that it could just explode and be very severe and fast. But that's just not the way CMV works. CMV just slowly eats through the retina at a rate of about 300 microns per week. That's like one quarter disc diameter per week. So when you see a large area of necrosis from CMV retinitis, we know that it actually took months to get to that point. This is the opposite of what we call ARN or acute retinal necrosis from HSV or VZV where the necrosis happens very rapidly. So to distinguish the two, I'm just made this table comparing ARN and CMV retinitis. ARN or acute retinal necrosis is caused by VZV or HSV whereas CMV retinitis is obviously caused by CMV. And then ARN happens in healthy individuals, otherwise immunocompetent adults. That was the first case I showed in this lecture. And the vitreous inflammation can be severe in patients with ARN where it's mostly absent or only mild in patients with CMV retinitis. And then importantly, the rate of progression, ARN progresses very rapidly. It can really take over the whole eye in a matter of days whereas CMV retinitis occurs slowly in weeks to months. So what if an immunocompromised patient with HIV or AIDS gets ARN with VZV or HSV? Well, then it's called progressive outer retinal necrosis, perhaps the best acronym in all of medicine. And this is a rapidly progressive, often bilateral disease that typically has early involvement of the posterior pole but minimal vitreous inflammation. So it's kind of a combination of the two. So patients with CMV retinitis need systemic treatment and that's because if CMV is in their eye, it means it's somewhere else in their body. It came through their blood and they can have CMV pneumonia, CMV in their lungs or GI disease from it. We often use adjunct intravitural treatment with pancyclovir or foscarinate. But you notice what's not on this list is acyclovir or valcyclovir valtrex because those agents do not cover adequately for a CMV. And clinical pearls for this, knowing you're necrotizing viral UVDs, meaning try to keep in your mind the distinguishing features of ARN versus CMV retinitis, the patient population, they affect and then the time course. Dilate every patient with UVDitis. So I'll just do a quick review of the clinical pearls and this is both from the previous lecture on anterior intermediate UVDitis as well as this lecture. Antior UVDitis with corneal involvement, always think herpetic disease. Isolated anterior UVDitis is not really associated with systemic lupus. So people tend to order way too many ANAs in their workup for UVDitis. Don't forget infectious causes of hypopoean. The obvious non-infectious cause we see is HLAB27, but don't forget about things like infectious endoplamitis. My one to four rule with topical steroids, meaning if they have one plus AC cell, then you use about four times a day of prednisolone acetate. And then Fuchs heterochromic erotocyclitis, the most important part of this disease is managing their intraocular pressure and opening glaucoma. If you have kids with chronic anterior UVDitis, refer early to a tertiary center with pediatric rheumatology or UVDitis specialist that can manage immunosuppression. In a patient with UVDitis and retinal whitening, that's a true ocular emergency. And then examine the posterior pole of older patients that complain of poor night vision, don't always assume it's a cataract. It could be birdshot. Please don't inject steroids into an eye with pan-UVDitis without ruling out infection. And then one other thing I would add for that, distinguishing the ARN versus CMV retinitis. I was taught that the C in CMV retinitis stands for chronic and that's how you remember that CMV retinitis is the slower progressive one compared to ARN. Dilate every patient with UVDitis. That's it. Thanks for listening.