 Good morning. So, welcome to UVitis Subspecialty Day Rounds. The title of our presentation are Infectious Posture UVDDs Diagnoses Not to Miss. We are going to present some common posture UVDDs that are vision threatening, some uncommon ones that are definitely ocular emergencies, and some more unusual posture UVDDs, and some that are ubiquitous and you should always test for. So really the question that you need to ask yourself when you're confronted with a patient that you think has inflammation in their eye is, is it infectious or is it not? This is a very important question. And this is answered really through an accurate and thorough history, complete ophthalmic and physical examination, and then of course the key is the formulation of differential diagnosis. And then laboratory testing and or intraocular fluid sampling is used to confirm or exclude the diagnosis of certain infections or non-infectious diseases. There are certain key considerations. Those are the exposure risks, for example, sexually transmitted diseases, HIV status, tuberculosis exposures, systemic illnesses. These are things that you would glean on your examination review of systems, constitutional symptoms, other organ system involvement, the nutritional status of the patient and their immune status. So whether or not this is acquired or Iodrogenic or through age, as we age our immune status wanes a little bit. And then of course local factors including recent surgery and trauma. The anatomic location of the UVDDs is extremely important, particularly with respect to where in the back of the eye what tissue is involved. For example, is it a retinitis, as you might see in a patient with a necrotizing herpetic retinitis, or is it a corditis, say for example, where TB would more commonly present? Is it a unifocal or posifocal disease, as you might see in toxoplasmosis or multifocal, as you might see in certain types of herpetic infections? And then are the vessels involved? Certain types of UVDDs will affect the veins more than the arteries. And then is the optic nerve involved? Is this a neuroretinitis because your differential diagnosis for neuroretinitis will be different than it is for other infectious ideologies? Laterality is important in that many infectious UVDDs will present unilaterally. For example, necrotizing herpetic retinitis frequently will present unilaterally, although it may become bilateral. Toxoplasmosis, toxoporiasis are frequently unilateral. Other associated signs on the examination such as elevated intraocular pressure, stigmata of herpetic infections such as insectile iris atrophy, corneal scarring, can give you a clue to the diagnosis. But laterality is obviously not always helpful as there are some patients with B-27 associated UVDDs that can present with hypopia on UVDDs. The differential diagnosis, I'd like to think of it in just broad categories. Is it viral? Is it commonly viral? Such as herpes, that would be the most common thing. And then less common infections such as emerging infections depending upon where in the world the patient might be coming from. Bacterial infections, fungal infections, particularly endogenous type of fungal infections, protozoal infections such as toxoplasmosis, and then helminthic. Interocular fluid and tissue sampling is very important, particularly in presentations in which it is really difficult to just make the diagnosis based on pattern recognition. So in the case up here, this no one would mistake this for diagnosis of toxoplasmic retinal corditis, or in an immunocompromised patient in the correct clinical context, this is CMB retinitis. However, you cannot tell just by looking at this what this might be. And in immunocompromised patients, this could be many different diagnoses. As is this multifocal sub-retinal infiltrates in an elderly patient could represent infection, it could represent non-infectious UVIs or malignancy. So that in UVDs in which the etiology is unclear or the response to therapy is atypical or the systemic workup is inconclusive, intraocular fluid analysis either from the anterior chamber of the vitreous or sampling the retina or the cori can be helpful in distinguishing between intraocular infection or malignancy where the differential between this is extremely important in terms of treating the patient and may impact on the systemic health of the patient. Therapeutic principles, obviously, you do not want to treat an infection with steroids without appropriate specific antibiotic cover. The basic principle is to think about this in the broad differential diagnosis. So if you see a patient with an indeterminate diagnosis, you will obtain laboratory testing and you will maybe sample their vitreous or their anterior chamber, but you want to treat broadly with an infection that could most likely destroy the eye, frequently treating with multi-antimicrobial treatment and then withdrawing therapy as your laboratories become available or more information becomes available on the patient. Corticosteroids are useful particularly topically to treat inflammation but should never be used as monotherapy in patients with infectious UVIs. That being said, corticosteroids can be very helpful in treating the inflammatory component of infectious diseases after the appropriate installation and commencement of antimicrobial therapy. In general, we do not treat with intravitral steroids as this can result in unbridled viral replication. And then it is always important to reevaluate your patient on a regular basis and reconsider your diagnosis if they are not responding in the way that you think. So our first presenter is going to be Dr. Shakur. We have the honor of our entire UBI's division presenting here, so I hope you enjoy this. Thanks, Dr. Shakur. Thank you. Where did the computer go? All right, now I have to lower the mic else it has a little bit of a height advantage here. But I'm going to present a couple of patients, but the first one is a resident, sorry, a fellowship nightmare. We've all had a few of those in this one. We really were at a loss as to how we could have proceeded differently. A 61-year-old gentleman, African-American, with a history of systemic sarcoidosis presented to us in California in 2010 in August. And for two months he had a history of blurry vision and photophobia in the left eye, and he'd been diagnosed a few weeks earlier by a local ophthalmologist with anterior uveitis. He's diabetic, hypertensive, has gout, chronic renal disease, and in late 2005 he complained of progressive fatigue, ataxia, falling, and confusion. He's diagnosed with neuro sarcoidosis based on a thoroscopic biopsy of his hyalurilymph nodes, which showed non-KZ18 granulomas. He came in with hydrocephalus, meningocencephalitis, and lymphocytic predominant pleocytosis. He was initially treated with steroids and methotrexate at a fairly low dose, and in 2007 began to have worsening pulmonary sarcoid with restrictive lung disease. In 2009 he was started on treatment with cell sept to a final dose of 3 grams a day, and he began to develop cardiac conduction abnormalities that were presumed secondary to sarcoidosis. Don't forget to check people's hearts when they have sarcoid. His past ocular history was really only significant for cataract extraction in the past, and a history of Zoster to the first division of the trigeminal nerve on the left side. His examination was significant for a little bit of an afferent pulmonary defect, which I thought may just be my imagination. And for the residents, which appendage is this? Anybody? Ashley? The nose. Yes, and what do you see on the nose? Yeah, so it's a nodular kind of dermal, post dermal rash. And what do you call this in sarcoidosis? Anybody? Spurnia. Yeah, so this is very good. So this is lupus burnia, which is an ever hallmark of cutaneous sarcoidosis. He had that. His anterior chamber showed one plus cell, three plus flare. He had one plus cell in his anterior vitreous and a lot of haze. So, and you can see a little bit of posterior vitreous cell in the OCT on both sides. He's diagnosed with anterior and intermediate uveitis, likely secondary to sarcoidosis with a small, small afferent pulmonary defect. His infectious labs were negative. So a few days later, we injected him with a subtenon skin log in the left side. He was seen in follow-up. He reported improvement in his photophobia, but no improvement in vision. And now, although his vision was the same at 2200, he now has a 1.2 log afferent pulmonary defect. And I cannot stress how important it is to actually measure an afferent pulmonary defect. Judith Warner and I would agree on one thing here. But measure them because they do change. And when they change, it's important to image. His cell has improved, his uveitis has improved. His OCT shows a little bit of swelling. But we recommended an MRI to look at his optic nerve. This gentleman does have neuro sarcoidosis. Lee, what do you see on this MRI? Is it part of his brain missing or is this something else? Well, it looks like that, but it's actually, it's a flow artifact from his ventricular shunt. So when things flow rapidly in T1, you end up with a void, a flow void. Anyway, that's just cool. And then his optic nerve over here, this pre-chiasmal optic nerve, you can see a little bit of contrast enhancement. So he was diagnosed with an optic neuropathy. In consultation with our neurophthalmology colleagues in San Francisco and with neurology, we presumed that this was sarcoid optic neuropathy. He was treated with IV-soluble medraw for five days, started on ramicade a week later, continued on cell sept and transitioned to oral prednisone at 60 milligrams. His vision continued to decline until two days later, he was no light perception in the left eye, bad. And then he disappeared for a month. And when he comes back a month later, he complains of decreased vision in his right eye as well as unsteadiness of gait. He is now no light perception in 2040 in the right eye. He's got a complete aphrodiputility effect. And what do we see here? Conradie. So whitening of the retina. But what do you see in somebody with UVA? Would you expect such a clear view? No, right? So that's something to keep a note of. And you can see in the periphery he's got areas of retinal whitening here as well. And his OCT, Chris, if you can tell me where the location of the whitening is. So the inner retina. So you can see like there's a complete loss of retinal architecture over here. So could this be sarcoid panubiitis? That's unlikely on so much immunosuppression. And you certainly don't expect to see retinal whitening. Could it be viral retinitis? So we performed a vitreous tap. We admitted him to neurology for IVA cyclovir. Lumbar puncture was also performed. And this PCR of his vitreous and CSF was positive for varicella zoster virus. We recommended stopping the salimetrol and switching from IVA cyclovir to GAN cyclovir and FOSCARnet. And we started intervitral injections of GAN cyclovir and FOSCARnet alternating at high dose. Unfortunately over the next three days he continued to progress. And the retinal whitening is now splitting his fovea. So this is a gentleman with systemic sarcoidosis presenting initially as neurosarcoidosis. He has anterior and intermediate uveitis. He has retro bulbor optic neuropathy. He was presumptively treated with high dose steroid and immunomodulatory therapy. As you would in somebody with neurosarcoid and optic neuropathy. And he ends up with a necrotizing herpetic retinitis in the right eye and worsening optic neuritis in the left. So optic neuropathy in an immunocompromised person with neurosarcoidosis. And this is progressive outer retinal necrosis in a patient with severe autoimmune disease with an iotrogenic component. So progressive outer retinal necrosis is a rapidly progressive necrotizing retinitis. Usually caused by varicillizastovirus in about 70% and 30% caused by herpes simplex 1 or 2. It's typically seen in patients with a CD4 count of less than 50. Visual outcomes are poor. This has an abysmal prognosis even with antiviral therapy. It's been reported in other immunocompromised states as well including after bone marrow transplant, after lymphoma, after high dose steroid. And classically seen in patients with HIV and AIDS. It's been reported as well just a few years before I saw my patient. When optic neuropathy, which was presumed to be inflammatory in nature, ended up being infectious and treated with systemic corticosteroids. This is a patient treated by Dr. Davis at Baskin-Pammer. So was the optic neuropathy secondary to sarcoidosis a varicillizastor? I think we very well proved to ourselves that it was infectious, unfortunately. How do we treat this patient without exacerbating his systemic disease? Neurology did not want to stop steroids, did not want to stop remiccate and did not want to stop cell sept. Cardiology didn't want to either. This patient was quite ill. With that level of immunosuppression, treatment of this patient's eyes is doomed to fail. What's his prognosis? Well, I can tell you now, five years later, he's still 20-40, but his visual field is less than five degrees. So necrotizing viral retinitis include acute retinal necrosis, progressive outer retinal necrosis, and CMV retinitis. I'll leave out the last one in the interest of time. This is a 54-year-old gentleman referred to us some years back for iritis. When you look in the back, you can see that there's a little bit more going on. Eric, you're going to be my fellow next year, so I might as well pick on you. What do you see here? So kind of this retinal whitening in the periphery, multiple foci, started to become confluent with some hemorrhage, but not a lot. So this is acute retinal necrosis. It's a necrotizing retinitis caused by herpes simplex or varicella zoster. Patients with RNA usually immunocompromise, but it may also be seen in immunocompromise, but it may be seen in the immunocompromise. Patients come in with hot eyes, moderate to significant arthritis, optic discodema, and an optic neuropathy, if not treated promptly. Bilaterality will happen in 70% after a month. It's a clinical diagnosis, but it can be fortified by using PCR for the herpes viruses and for toxoplasma, because there is a atypical toxoplasma with retinitis that can mimic. Conventionally, you treat this with IV acyclovir. Without treatment, there will be involvement in 20% to 70% in the other eye. Systemic acyclovir reduces that risk to 13%. Other treatment protocols, the one that I favor, oral valacyclovir to a dose of 2 grams three times a day, gives you IV equivalent levels. Intervitriolgancyclovir or intravitriophosphonate may be used. Oral prednisone may be added. Aspirin may be associated with better visual outcomes. Late findings do include pigmentary changes. Retinal detachment does happen in about 70%. Barricade laser, however, is controversial. And retinal detachment is complicated. Lots of PVR. You need a buckle. You need oil. Here's an iron retina that seems to be clearing a little bit. You can see that there's very vascular clearing of the retinitis. And ultimately, this progresses into kind of this Swiss cheese appearance with pigmentary changes resolving retinitis. And that's why they get retinal detachment. Here's a 34 year old patient with HIV and a CD4 count at 10. You can see a lot of retinal whitening, a little bit of blood, but not very much. But what stands out here is how clear the view is. The absence of vitritus makes you think about immunocompromised states. This is progressive outer retinal necrosis. A better example, a more typical example than the patient I presented in the beginning. This is a herpetic retinitis in immunocompromised patients with rapidly progressive multifocal lesions, lower level of vitritus and vasculitis. And whereas iron spreads rapidly, this spreads like nobody's business. This can wipe out the entire retina in a couple of days. The treatment for this is either acyclofascinate or gansyclofascinate. IV treatment is recommended. High dose, intravitual gansyclofascinate or their combination. And these progress despite treatment. So in conclusion, remember viral retinitis is not always something you see that you did not cause. Viral retinitis can be iatrogenic. We do immunosuppress more and more patients in this era and do look for infectious UVA2Ds in the immunocompromised. And then most importantly, just as a kind of a wide statement, always dilate the pupil in an eye with UVA2Ds and to UVA2Ds is often not anterior. Thank you to the photographers. Okay, good morning. I'll be presenting three cases today and then do a brief overview of the disease process. This is a mystery diagnosis and we'll do a brief review of the literature. So the first case is a 17-year-old Hispanic man that came in with blurry vision in one eye, mild discomfort. He had a non-contributory past medical and ocular history. Vision in the affected eye was slightly decreased at 2025. He had normal pupils and pressures. And the affected eye had a mild anterior chamber reaction with 2-plus vitreous cell, a little bit of haze. And we can see the photo of the left eye. A little bit of hazy view, just overlying the lesion, which is some retinal whitening along the inferior arcade associated with hemorrhage. And you can see at the lower part of the arcade maybe an area that looks a little more pigmented or atrophic, which we can see in this photo, so a pigmented scar. This is an OCT through the area, normal, temporally. And then on the nasal side, there's a hyperreflective infiltrate of the retina. Fluorescent angiography early shows some blockage in the area of retinal hemorrhage. And then later, some hyperfluorescence or leakage in the area of retinitis and a little bit of retinal vascular leakage. Of note, also in the peripheral retina, distant to the area of activity, there's also some retinal vascular leakage. So this patient has anterior chamber reaction, vitreous inflammation, and a choreorentinal lesion. So that fits the diagnosis of a pan-uveitis. And a unilateral pan-uveitis top of the differential is infection, infection, infection. So ocular toxoplasmosis, a viral retinitis could be syphilis or TB, and then lower on the list would be an inflammatory pan-uveitis. So this patient walked into the clinic. He was young. He had good vision. You don't know what his immune status is. So he received an AC TAP, checking for a viral PCR. And they injected intravitural clindamycin to cover toxo, as well as phosphocarnate to cover viral ideologies. These are the labs that were checked, and they were started on valtrex and back drum. Seeing a couple days later, the serum, toxo IgG was positive, but had a negative IgM, and the PCR was negative for all things checked. However, the sensitivity of PCR for toxoplasmosis of an aqueous sample is under 50%. So with retinal whitening adjacent to a pigmented scar, those are the buzz words for ocular toxoplasmosis. So he was treated as such for presumed ocular toxoplasmosis. He received back drum six to eight weeks BID. He also had azithromycin for a portion of that period, and oral steroids was added a couple days after antibiotics. Final visual acuity was 2020, and this is the resolved lesion, just a hyperpigmented scar. This is a similar case, 21-year-old woman from Venezuela, so also a Hispanic woman. She notes she had some kind of eye infection when she was younger, wasn't sure which eye. Visions mildly affected. Pressures high. Also has a mild anterior chamber reaction and some vitritis. A similar photo, so nasal to the nerve. There's a hyperpigmented corioretinal scar with adjacent retinal whitening. And we can see some periflebitis as well. Interestingly, in the other eye, she has 2020 vision asymptomatic, and she also has a hyperpigmented scar nasal to the nerve with some fibrosis on the nerve. These are the buzz words, focal area of retinal whitening adjacent to a pigmented scar, while the residents are going to nail this case on the moth world boards. Ocular toxoplasmosis. She was uninsured, self-pay, so we were trying to really limit the cost of this work up. It looked really classic. We just did a very limited lab work up, which was normal, ruling out HIV and syphilis, and she was treated as ocular toxo with a great result. And that's the atrophic scar. So a different case with a different outcome. This may seem familiar. I presented this last month at the Grand Rounds for morbidity and blindness. A 39-year-old woman had come to us a year after her symptoms had started. Decreased vision in the left eye. Non-contributory medical history, but she was from Mexico. We looked at outside records, and a year before, she had presented to an outside provider with floaters and blurred vision. Also, what someone else called pink eyes. You can assume some anterior chamber reaction, redness and pain. The vision was 2400 at the time. They noticed a diffuse vitritus, and then diffuse retinal thickening on the OCT, which they were saying was consistent with macular edema. So their plan was to do a work up for panuviatus and see her back a few days later. Vision was unchanged. This was the work up they did for the panuviatus, so they ruled out syphilis. They said they had a normal chest X-ray and PPD, and then they checked VZV and HSV antibodies, which were positive in the serum. We typically don't check them because a lot of us are exposed, and it's not causative for the retinitis. At this point, they felt it was non-infectious and injected intravitural triumphs in a loan. They thought, oh, it improved initially. She went from 2400 to 2200 for a few weeks, and then a couple months later, she comes back with worsening vision again. Now has mutton fat KP, a diffuse vitritus, and so they re-inject Tramsin alone into the eye. So she came to us several months after that. Unfortunately, her vision had declined to light perception only, 2 plus APD. She's had some mild anterior chamber inflammation, now a diffuse PSC cataract from the intravitural steroids. Diffuse vitritus, and this is a photo, very hazy view, but you can see multiple areas of retinal whitening, confluent. Here's another island of retinal whitening, and this is an op-dose photo. It gives us a little bit of a different perspective, and you can see in the infrotemporal quadrant, there's a vessel that looks elevated, so there's a sub-retinal fluid and retinal detachment on ultrasound. So we'll talk a little bit about ocular toxoplasmosis and management, and then we'll come back to that last case. So toxoplasmas and intracellular protozoa infects over a third of the human population worldwide. That number's a lot higher in Latin American and South American countries, over 80%. Most people are exposed either through undercooked meat or more commonly contaminated water or soil. Infection in the retina can be reactivation of a congenital infection, or there's evidence now that most cases are acquired postnatally. And congenital infections typically are bilateral, 75% of the cases, and they're more likely to involve the macula. So congenital at 60% involvement of the macula in acquired cases, less than 40%. Retinal whitening adjacent to a scar. The diagnosis is clinical. Serologies can help, especially to rule it out, and then it's the number one cause of infectious posterior uveitis worldwide. So exam findings, like we mentioned, I put an asterisk near marked vitritis because sometimes it's not a diffuse vitritis, but just a clump of vitreous cells overlying the areas of activity. Or if they're immunocompromised, there can be a lack of vitritis. So vascular sheathing, as we saw on the fluorescein angiography, can be separate from the area of activity. Anterior uveitis can be fine KP or mutton fat KP. High IOP, so that I think second case I showed had an intraocular pressure of 25, and that can be classic. And then these periartereal plaques, which is the term I don't know how to pronounce. So is treatment necessary? In immunocompetent patients, the lesions become inactive with well-defined borders within six to eight weeks, even without treatment. So there's little firm evidence that shows that antimicrobial therapy alters the natural course or the visual outcome disease in immunocompetent patients. So if we think back to that other patient, and as doctors first do no harm, if this patient had never even gone to an eye doctor, she may have fared better in the long run. In 2016, a Cochrane Reviews published looking at antibiotics versus no treatment for toxoplasmosis, and it summarized in this vague statement, treatment with antibiotics probably reduces the risk of recurrence, but there's no good evidence showing that it leads to better visual outcomes. However, absence of evidence of effect is not the same as evidence of no effect. So there's definitely cases, everyone's in agreement for treating. If it's near the fovea or fovea or optic nerve, they're symptomatic, significant vitritis, a large size of a lesion, persistence after time, multiple lesions, and then we always treat pregnant patients, immunocompromised patients, and congenital infections. So there's some providers that will just monitor a peripheral small lesion that's asymptomatic. I think in our department, we treat every active lesion we see. And classic treatments, triple therapy, so sulfidizing, pyrimethamine, and folenic acid. The pyrimethamine causes decreased platelets in white blood cells. That's why we use the folenic acid. And then there's many alternative treatments described in the literature that are better tolerated. And then briefly touch on oral steroids in the use of ocular toxo. So typically, if there's a significant inflammatory vitreous response, I'll add oral steroids 48 hours after starting antibiotic therapy. So steroids themselves aren't contraindicated in ocular toxoplasmosis, but unchecked steroids, meaning the use of steroids, especially periocular steroids in the absence of antibiotic therapy, is a contraindication. So that's stated here. So absolute contraindication. We think it can cause uninhibited retinal necrosis. So inappropriate use. There's many cases in the literature showing disastrous outcomes when we inject intracular steroids in an eye with toxo. And there's some wise words in the middle there from ophthalmologists in a Latin American country reminding us to consider toxoplasmosis for any pan-uviitis in an exposed patient population rather than assuming it's an autoimmune process. And then there is some appropriate way to use intravitral steroids. There's reports of using dexamethasone intravitrally, which is much shorter acting, concurrently with clindamycin intravitrally with good outcomes. For prophylaxis, you can imagine if you have a patient that was recently treated or they have an inactive scar, but that's close to the fovea or the optic nerve, you want to be able to prevent recurrences in the future. So using Bactrum one tab three days a week, so Monday, Wednesday, Friday, has been shown to reduce the risk of recurrence. But typically we thought it was just when they're on that medication. Once they stop it, the recurrence rate goes back to normal. There's some new evidence from a group out of Brazil that shows that Bactrum one tab every other day treating for about a year can have some long-lasting effects. This was a randomized double mass trial with 141 patients. They all had active lesions initially treated with six weeks of Bactrum. Those lesions healed and then they were randomized one to one to receive either Bactrum every other day or placebo for 311 days. So just under a year and they showed the recurrence rate for the treated group was zero for three years compared to an increasing rate of recurrence in the group that received placebo. For pearls, this is a clinical diagnosis. Serology can help rule it out. And then an AC tap, remember the sensitivity is about 50% or less. If you have a patient in your office and you're not sure what it is, they have significant vitritus. You can inject things to cover for multiple etiologies, antivirals, clindamycin. Just don't inject steroids alone if you don't know what it is. And dilate every patient with uveitis. I'm Lynn Hassman, the uveitis fellow. This is a case of multi-coccal corioretinitis and drenching fever. So this is a patient, a 63-year-old female with a five-day history of blurry vision in her right eye that followed a three-week history of a flu-like illness. So she has no significant past medical, ocular, or family history about her review of systems. She has joint pain, muscle pain, fatigue, chills, night sweats. She has a follicular type rash on her arms and legs. She has new frontal headaches, some neck stiffness, kind of some mental slowing, and sinus congestion. So she's obviously sick. Her exposure history is significant for some mosquito bites earlier this summer that this patient presented in the fall. And general HSV. So in the right eye, her vision is 2030. There's one-plus AC cell and a little bit of vitreous cell. And in the right fundus, you can see these round white lesions kind of along the arcades and then extending up above and down below. And it doesn't show well in this picture, but there's also some intra-retinal hemorrhages in the peripheral macula. The left eye, the vision is 2015. There's not really any AC or vitreous cell. But she has a few similar lesions kind of looking superiorly from the optic nerve into the superior periphery. Her fundus autofluorescence is normal in the center of the macula where she didn't have any spots. But along the inferior arcade, especially in the right eye, you can see there's kind of this hyper-autofluorescent lesion with a hypo-autofluorescent center. And if we zoom in a little bit, you can see there's that lesion. It kind of looks like a target. And then there's some other hyper- and hypo-autofluorescent changes in the area that we saw those white lesions. Her fluorescent angiography in the right eye, the more affected eye, shows an early blockage right there in the upper right frame and then late staining, which is typical of an inflammatory lesion. And the left eye has pretty minimal changes. It probably did not show up very well. But in the area where she had those white spots, there's also some staining. The ICG, we can also see these lesions on ICG. And following sort of a similar pattern in the right eye are on the superior and inferior arcades and branching out from there. And then in the left eye into the superior near periphery. So this imaging is basically showing us that the retina is involved. We see that on the fluorescein. And that something is blocking this ICG signal either at the level of the RPE or deeper in the coroid. So the FA and ICG lesions kind of correspond. Again, you can see this pattern that's sort of following the arcades and then branching out. So the OCT, the right eye, you can see starting at the top, the center of the macular, the fovea there, looks pretty normal. The retinal architecture looks normal. There's not a lot of vitreous cell. You can see some early vitreous separation in the nasal side on your right and also some hyperreflectivity of the RNFL there. But then if we move down to the level of the inferior arcade where those lesions were in the right eye, you can see there's vitreous cell, there's vitreous separation, there's hyperreflectivity in the RNFL, as well as along the RPE. You can see this kind of sort of clumps of hyperreflectivity at the level of the RPE and a loss of that overlying ellipsoid layer or the junction between the inner and outer segments of the photoreceptors. And then we have similar changes in the left eye of the less dramatic. The center fovea architecture is normal and then looking kind of superiorly in the left eye in this lower picture, you see some vitreous cell and RNFL hyperreflectivity. So the differential diagnosis for this patient, based on that characteristic appearance of the lesions, sorry to everybody who took boards yesterday and this presentation is coming later, but this is West Nile virus, probably. But we always include some other infectious etiologies in our differential, particularly tuberculosis and syphilis. They can look a lot of different ways. Sarcoidosis would be an inflammatory process that could present in a multitude of ways. And then inflammatory white dot syndromes, including mutes, PIC, multifocal coordinates with panmubiitis, acute posterior multifocal placoid pigment in apathy or ampy and azore. So her laboratory workup showed positive IgM and IgG for West Nile virus and negative workup otherwise. She had a mild thrombocytopenia, probably going along with her acute febrile illness. So West Nile virus clinical infection, the incubation period for this disease is 2 to 14 days and it presents in patients in a variety of ways. The majority of people, 70 to 80%, are totally asymptomatic. There's a mild febrile illness in about 20 to 30%, and then there's neurologic disease in 1%. And neurologic disease is associated with a slightly older demographic, 40s to 60s, not really elderly by any means, but younger people are more likely to be asymptomatic. And then advanced stage and diabetes has also been associated with a more severe neurologic disease. So what do we see in the eye? 40 to 50% of patients with neurologic disease get a chororetinitis. And we see these classic targetoid lesions in multiple stages of healing. That's pretty typical for West Nile virus. In more severe cases, we can see retinal vasculitis and ischemia. So we can see intraretinal hemorrhages, which are a sign of ischemia, definitely vasculitis, and even a neuroretinitis have been described. So West Nile virus is a Flavy virus. It's a single-stranded, small RNA virus. What we know, so the diagram on your right is sort of what we know from animal models, basically the virions are transmitted through the bite of a mosquito and picked up, they infect and are also just endocytosed by the local antigen-percenting cells. So tissue-resonant macrophages, Langerhans cells and other antigen-percenting cells brought to the draining lymph nodes where they actually infect macrophages. The macrophages bring the virus to the spleen and then it's disseminated through the blood. So the virus has multiple proposed mechanisms of getting into the central nervous system. It can either go sort of as a Trojan horse inside a macrophage, which you can kind of see in the bottom here, through the blood-brain barrier, or actually the inflammation alone can cause some blood-brain barrier permeability and the virus can get in that way. And then the virus can transport through the central nervous system via anterograde and retrograde axonal transmission. So interestingly we know from culture, in vitro culture, that it replicates in RPE cells and exits the cells by exocytosis, which is significant because it doesn't destroy the cells like herpes virus, just causes a total necrosis of the cells that infects. This virus actually gets out of the cell and leaves the cell intact. So some pathophysiology questions. Excuse me. Does the virus enter the eye from the CNS via the optic nerve and the neurofiber layer? Does the virus enter via a compromised blood-retinal barrier and then retrograde transport into the central nervous system? So we saw that it was more associated with diabetes and it's been associated also with diabetic retinopathy, which involves a compromise of the blood-retinal barrier. But potentially the virus itself, as it has been shown in mouse models, could cause an endotheliopathy and this diabetic retinopathy-like picture gets into the retina through its own breakdown of the blood-retinal barrier. So can we learn anything from this patient? So this patient, so just kind of zooming in on the presentation, this patient, we saw these white spots. We saw some changes on the autofluorescence and if we kind of zoom in looking at OCT to kind of find out what's involved, this area doesn't really have much going on in autofluorescence, but you see some subtle changes at the level of the RPE. And this other lesion, we also see some subtle changes at the RPE. So then a week later, dramatic increase in the number of white spots and in the autofluorescence and also in the disruption of the RPE and overlying outer retina sometimes and the photoreceptor layer. So two weeks later, we kind of can see some consolidation maybe of these lesions or some healing. So the lesion shown in OCT on your left, we can see almost like a consolidated RPE hyperfluorescence, maybe a scar. Whereas the lesion on the right, although still apparent on autofluorescence, seems to be resolving on OCT. A month later, we kind of see the same picture. We have continued healing of that lesion on the right where that lesion on the left has sort of still this persistent RPE level defect. And then two months later, it's the same thing. So some of these lesions are involving the RPE, as we know from tissue culture. And some of them are leaving a persistent RPE defect or a scar and some of them are healing completely or nearly completely. So that's some evidence for RPE involvement. Others have proposed that this is actually an infection that's coming through the retinal neurofiber layer and the reason they think that is because those lesions seem to not be following the arcades but actually the neurofiber layer. So that's this group, Karala, they kind of show this map of the neurofiber layer and that in their patient, the lesions seem to actually track the neurofiber layer rather than along the arcade. So we actually kind of saw this too, if you recall. We do have lesions along the arcades but then they're tracking actually along kind of the neurofiber layer path in both eyes. And then if we go recall back to the OCT, we did see neurofiber layer hyperfluorescence hyperreflectivity, sorry, as well as these RPE changes. So interestingly, the fact that we see the lesion along a retinal neurofiber layer track but showing up on ICG suggests or tells us that the primary defect, as we saw in OCT, is really not that retinal neurofiber layer but actually the level of the RPE. So possibly the virus is coming in through the neurofiber layer but the pathology seems to really be... the significant pathology seems to be happening at the level of RPE. So conclusion, atomic observations can be important in elucidating viral pathogenesis. Thanks. Okay, just kind of taking you home here. So many of you know that Lynn just took her board examination and sometimes they ask these really crazy questions like on your board examinations. Like, what's the pox next door? And then... So what do Casanova, Idi Amin and Beethoven and Frederick Nietzsche, and at least in my clinic, the church lady, have in common? So they're all at risk for syphilis. And each one of these people had syphilis. So I want to talk to you a little bit about syphilis. It's a very prevalent disease 18 million cases in 2002 in the World Health Organization and 5.6 rather incident cases but 90% of these are in the developing world. And the United States, since they've been keeping records of this in the 40s, there was a very high percentage of cases which has slowly decreased, decreased, decreased with a little blip in the 90s around the HIV-AIDS epidemic and then an all-time low in 2000 only to see this resurgence with both an increase, 17% or 18% increase in primary and secondary cases and also in congenital cases since 2000, the year 2000. There have been discrete epidemics of syphilis in the Pacific Northwest and in San Francisco. There is no formal reporting system in the United States, however there is in the United Kingdom. And it's interesting, it's not very many cases of syphilitic UV-itis that are reported as compared to the number of cases of systemic syphilis. And calling the literature in the United States it represents about 1-5% of UV-AIDS cases that we see in a tertiary care setting. The thing is that there is a really HIV and syphilis travel together. So there's a very high rate of co-infection of these two organisms. So if you have patients that are HIV positive there's a 20% chance that you may have walking or involvement. And then conversely, syphilis can be predictive of HIV co-infection. So always test for both when you suspect either one in a patient. Acquired syphilis is divided into three stages and the primary lesion is the Shankar which occurs two to six weeks after abrasion of the mucous membrane followed by the secondary stage of syphilis six to eight weeks later following hematitis spread of the organisms throughout the body lymph nodes and into the central nervous system. And then this is followed by a variable degree of tertiary syphilis either early late or latent. You have to know that UV-AIDS can occur in any stage of this disease. And it is called the Great Masquerator because it can produce pretty much anything and affect any area of the eye. But about 50% of the time it presents as a posterior UV-AIDS. So that's what we're talking about today and there are certain clinical presentations that are virtually pathogenomic of syphilis. The first is an acute syphilitic posterior placoid corioritinitis. It's a mouthful. And this presents as a uniform circular oval outer coroidal lesion and the typical patient is male HIV positive about a third of the cases. And this is representative example. One can see this circular placoid lesion at the level of the RPE and coroid. And on fluorescein angiography it shows this kind of leopard spotting in the early stage of the angiogram with blocked fluorescence and then blocked fluorescence at the leading edge of this lesion which stains and leaks a little bit later in the later stages of the angiogram. The same patient underwent ICG angiography and ICG angiography shows although not specific can be highly suggested to this disease with a uniform hypotheraussence in the early and late phases of the angiogram as seen here. And this can actually be helpful in certain cases that are very subtle that present in this placoid lesion as I'll show you in a minute. The OCT of this is also quite helpful and it shows discontinuity of the outer segment ellipsoid with irregular nodular hyperreflectivity at the level of the RPE and sometimes subretinal fluid and external limiting membrane disruption. The other distinctive presentation is panneobiasis with superficial pre-retinal exudates. So these are not in the retina, they are just pre-retinal, or small creamy white lesions that seem to be migratory and may actually be frequently over vessels and may be associated with some syphilitic retinitis which is typically mild opacification of the retinine heels without disruption of the pigment epithelium or necrosis of the retinine as Akbar had just described with acute retinal necrosis or necrotizing herpetic retinopathy. And this is seen here in both a patient that's HIV positive and a patient that's HIV negative with these precipitates here that seem to follow the blood vessels. The thing about these precipitates is it's thought to be related to vasculitis and they disappear properly with treatment. Another mode of presentation is really just strictly with optic nerve involvement. This is a gentleman, a 57-year-old patient of mine that presented with sores on his hands and his mouth and his tongue that was a big tip-off as to what was going on with him and he was RPR and FDA positive and I showed this hemorrhage around his disc and hyperflorescence of his optic nerve. There has been a description of a syphilitic outer retinopathy that was described. This is actually a patient of mine that came in with these curvilinear lesions here that were initially described and thought to be azore but it turns out that many of these patients were RPR positive. If a syphilis was diagnosed and if you look really carefully in these areas there really is a plaqueoid lesion and so it's thought that this syphilitic outer retinopathy is really a variant, a subtle variant of the plaqueoid acortoretic retinopathy and ICG can be helpful in that post-treatment complete revision and return to normality in this particular patient. This patient presented three years later with profound reduction in vision and panneuviatis as you can see here. Patients with syphilis can become reinfected so that is always something to keep in mind and this patient had a RPR that was positive he was treated but unfortunately his vision did not recover although his fundoscopic appearance was improved. Syphilis is a clinical diagnosis always considerate in your work of patients with uveitis. There is a highly variable presentation but there are distinctive posterior pole presentations that should make you think of the diagnosis always inquire about other sexually transmitted diseases and in the work up one must always order specific serological testing. Traditionally we have ordered both non-tropanemal and tropanemal tests the RPR and the FTA ABS together. As you know the RPR is positive in the initial stages of the infection and can wane in tertiary syphilis and with treatment whereas the FTA remains positive for life. The CDC has recently recommended a so-called reverse sequence testing in which enzyme immunoassays and chymilluminescent assays are used to screen for patients with toxoplasma with syphilis as they have increased sensitivity as a screening test and the RPR is used to follow the treatment response. So in the case of a patient that is EIA positive and RPR negative which can happen then there's kind of a tiebreaker of a very highly specific and sensitive test called the tropanemal and pallidum particle agglutination test which is like a tiebreaker which would confirm the diagnosis of syphilis. Further testing as I said always test for HIV in a patient with syphilis and vice versa but patients with syphilis ocular syphilis are thought to have neuro syphilis so the CDC recommends that these patients undergo a lumbar puncture and that they have a repeat lumbar puncture if they are positive six months later. The treatment for syphilis is not with a shot of penicillin in the butt it is a neuro syphilitic regimen with intravenous benzothene penicillin for 10 to 14 days or desensitization of a penicillin allergic patient or prokene penicillin with probenicin. Corticosteroids can be useful for patients with anterior segment inflammation but very frequently patients with depending upon the degree of inflammation in the back of the eye will respond to antibiotic treatment alone that being said another board type question is that after or during treatment one can develop a severe inflammatory systemic inflammatory reaction and ocular inflammatory reaction known as the ARICS. Ericsheimer response in which steroids are definitely indicated and can be preventative also one would consider systemic steroids in a patient with structural complications and severe inflammation. So in summary always think about syphilis and if I had to order one test for syphilis it would be an FTA because you can actually treat it and cure it. There are certain it can affect any time and atomic region in the eye but there's certain distinctive presentation that should really make you think about the diagnosis. Serologic testing is imperative as is lumbar puncture in patients with ocular disease. Multimodal imaging can be helpful and the treatment is always with a neurological dosing. And the visual outcomes are generally pretty good and there doesn't really seem to be a it was previously reported that HIV positive patients did more poorly but recent evidence suggests that they're about the same as patients that are HIV negative. So that's syphilis we don't have a whole lot more time but I'd be happy to entertain any questions about the Grand Rantz presentation. Do you have any pushback from Health Department about FTA one point you had to get an RPR before they were able to do it? Yeah, there was that there was actually pushback at AREP but most of the ID people here don't first of all the ID department does not use the reverse sequence testing regularly and they always order the two tests together. It's imperative that the two are ordered together. So we did but we had a conversation with them and tried to reeducate them about what the odd care syphilis is about. All right. Yes, Ashley. So Dr. Lauchel talked about the study showing that there was less recurrence with what the toxo of you used after a movie. Is that something that you guys practice here? Yeah, we do. So the biggest studies that I know about are those ones in Brazil in which the effect lasted for as long as people were on prophylactic Bactrim and they actually have 10-year follow-up on that and the effect lasted while they're on the medication but then the recurrence rate seemed to recur after they're off of Bactrim three times a day. Pretty benign. They're 10% sulfa allergy in Bactrim. You have to be aware of. We do, I do routinely prophylox patients with Bactrim who have lesions that are particularly in monocular patients with lesions that are vision-threatening, closest to the phobia, which many of them are, or to the optic nerve. The other thing is that there is one study that I'm aware of in which treating, so the biggest risk for a reactivation of toxoplasmosis is a previous infection with toxoplasmosis temporally. So if you've had a recent infection you're more apt to have a recurrent infection, which is one of the rationales for patients with toxoplasmosis. The other thing is pathophysiologically it is thought that the organisms are assisted throughout the rotten, not just in the scars. And that for cataract surgery there's one study that suggests that prophyloxically treating patients before and after cataract surgery will reduce the rate of recurrence in the perioperative period for cataract surgery. Just as with viral with herpes. Is that perioperative treatment? Is that to pull those back from herpes? Yeah, so I would give them back from twice a day for a week perioperative and push up a week.