 Infectious posterior urethritis, we don't want to be treating any infections with steroids, obviously. So it's important to differentiate between infectious and non-infectious. So is it infectious or not, right? The most important thing is really accurate and thorough history. Really, you know, I'm beating this into the ground, I know, but it's very, very important. And to try to assess the risk and the exposure to the patient. We presented, Lynn presented the patient last week at the R.C. conference. You know, that really the history was extremely important in really ascertaining the diagnosis of the patient. So a complete exam formulation of differential diagnosis. What are the usual subjects? What are the most likely? And then laboratory testing or tissue biopsies to confirm or exclude, you know, your diagnostic considerations. So exposure risks do the patient have at sexually transmitted disease, HIV, TV, exposure to animals and travel are important. And then systemic illnesses, obviously, constitutional symptoms, other organ systems that may be involved. But you may not think about, you know, GI tract, lymph adenitis, nutrition, you know. Obviously, it can predispose people to relative immunosuppression or make them susceptible, for example, to an endogenous introduction. Endogenous endothermitis from, you know, exogenous introduction of bacteria. Is the patient immunocompromised? Again, this is a relative thing. So obviously a person with, you know, an acquired disease like HIV or cancer, but people can be hydrogenically immunosuppressed, you know, with immunosuppression. Or they may have some, you know, type of immunosuppressive syndrome that you may not think about. And of course, local factors, recent surgery, trauma, either remote trauma or remote surgery. So think about that when a patient comes in with inflammation in their eye and they've got a bleb, okay? Antitank considerations. What is the location? You know, as we've been saying before, the anatomic location of inflammation, according to the sun criteria, is important. What is the primary tissue involved? You know, so certain infections are primarily involved, like red and like toxoplasmosis as opposed to TB, which affects the chloride, focality that makes a difference. Some entities are multifocal and some are not multifocal. We'll review some of that. Are the vessels involved? Okay? So you can have a primary vasculitis, or more often, vessels are associated with an inflammatory or an infectious disease. And then is the nerve involved? Is it a neuro-retinitis? Is it the nerve and the retina together because you have a different set of a differential to think about? Laterality, okay? Many infectious diseases are unilateral, okay? So certainly herpes, spruptoxochoriasis, soxoplasmosis usually present as unilateral, either anterior or posterior segment inflammatory disease. They also, this group of disease, add in their sarcoidosis and fuchs, present with elevated intraocular pressure, okay? It's not always helpful, though, for example, sometimes we are presented with a patient that comes in with hypopia and uveitis, fibrin and the rye, can't see in the back. And what that person really has, the HLAB-27 associated disease. So history is very, very important and you want to certainly differentiate between that and make sure you're not treating infection. So again, thinking in broad categories, think about, you know, what can cause the infection? Is it a virus? Okay? Is it herpes or HIV, HLTV, or some of the more uncommon viral diseases such as West Nile, okay? Dengue, chicken, guinea, rift, valid fever. You know, you might see Dengue here for people who are traveling around, okay? I have seen it in our clinics. Then, of course, bacterial, syphilis, Lyme, TB, Bartonella, fungal disease, the most common is Candida. Then, of course, less common, aspergillus, histo, coxidio, protozole, toxoplasmosis, alamethic, toxocoriasis. Duzend is uncommon, but something to always think about in young person presenting a unilateral wipeout of the retina. You can also think about it in terms of, you know, folkality, okay? Certain entities are posifocal, unifocal, toxo, aquacrysis, multifocal, more infectious entities such as the necrotizing retinities. Then, focacoriditis, toxocoriasis, tuberculosis, syphilis, etc., and multifocalcoriditis, again, TB, histo, syphilis. So, we're going to talk about some of these diseases. Neuroretinitis, we'll talk about briefly. There's a long list here, but the most common is an infectious entity, Bartonelosis, part of cat scratch disease. But you'll also have to think about other entities involved. Then, retinal vasculitis, which is another large topic that I think Dr. Shakur is going to talk to you about. And, you know, it usually is an accompaniment of inflammation, but whether the arteries or the veins are involved in our important differentiating feature. Say, for example, in a patient with necrotizing hermetic retinitis, the arteries are usually involved, as opposed to a person with, for example, sarcoidosis, which is predominantly a venular. And then panneuvidus, of course, syphilis can do anything, Lyme can do anything. All of these other entities can present as a panneuvidus. So, I just want to, I know this is a busy slide, but just kind of bear with me and then look at the picture on the right. So, on the picture on the right, you've got a patient with sectoral iris atrophy, okay? You're thinking maybe they've decreased coronal sensation, unilateral. You're thinking, well, this could be a herpetic infection, dilate this patient, please, okay? Because they may have something going on in the back of their eye. So, there's herpes, okay? You don't want to miss that in the back of their eye. That's a cute retinal lacrosis, okay? CMV retinitis, multifocal retinitis, okay? There are different types of patterns that you can see. We're not going to review that today, but this is the classic pattern of a, you know, so-called pizza pie wedge-shaped retinitis. This is a placoid presentation with a patient with syphilis. This is almost a panthenomonic presentation of syphilis. Toxoplasmosis. Again, this is a classic presentation of toxoplasmosis with a retinitis in a satellite lesion next to an old coronal scar. Here's a patient that comes in, you know, six to 12 months after a cataract extraction. They have a plaque on the posterior capsule of their eye and some inflammation in their eye that gets worse, that gets better slightly with toposteroids, and it gets worse every time you take the steroids where you're thinking, maybe they've got an indolent infection with pyatomies or fungus. This is a patient with Candida endoplamitis with corral infiltrates with satellite lesions frequently associated with infection. The history is very important, obviously. Are they shooting drugs? Are they immunocompromised? Are they in the hospital on, you know, IVs? This is a patient, a young patient with bartinolosis, with involvement of their optic nerve and a partial macular star, you can see here. So this is a neuro-retinitis. You want to think about the differential of that. This is a young person with toxocoriasis with a focal crudal granuloma. And then this is a patient with West Nile virus with typical subacute targetoid lesion that you can see both on examination and on forcing. So again, the patterns are important. Yes? So it can either way. I don't, usually if a patient has a herpetic anterior uveitis, or it was something that you might think is herpetic anterior uveitis, it is herpetic anterior uveitis. They don't necessarily can commonly go together. Most of the cases that I've seen in patients with ARN present with post-year segment inflammation. But I have seen patients who have been referred with anterior uveitis that have not been dilated, that I dilated. And there's a little area of retinitis and those. So we'll talk about ARN. It's a very interesting disease. It doesn't necessarily always present in an explosive manner. You can catch it early. So always dilate a patient with herpetic disease. Okay, so therapeutic principles. You want to institute specific antimicrobial therapy, obviously anti-viral or antibacterial, anti-protosal therapy, either intraocularly or systemically. Because you're sometimes dealing with a disease that can impact the health of the patient. You frequently, when you are faced with a patient that you think is infectious, your differential diagnosis is broad. So I think that it makes sense to treat empirically, okay, considering the most common and the most destructive organisms first, okay, and then withdraw therapy as your differential narrows with laboratory testing and with more history, okay? So you can always withdraw therapy. It's much more difficult to catch up. When you say, oh, wow, we should have thought about this, we ought to do an FDA on the patient, right? And then treating inflammation after appropriate antimicrobial cover is important. Because many of these diseases can destroy the retina, not only because of the direct invasive tissue effects of the organism, but because of the secondary inflammation that's produced by them, okay? And ARN is a good example of that. So systemic corticosteroids are contraindicated, obviously, as monotherapy in an infectious disease, but is helpful after the institution or concurrent with the institution of antimicrobial therapy. So you always want to evaluate a patient with an infectious disease frequently. You know, have an open mind. You know, always reconsider your diagnosis. More data becomes available. A lack of response, you know, may indicate that you're barking up the wrong tree. Okay, so we're going to talk about some entities here. So these five people have something in common. So you've got Casanova, Idiamine, Beethoven, and Frederick Nietzsche, and the church lady. The church lady actually presented to my clinic with a diagnosis of syphilis. So if you're alive, you are at risk for syphilis, okay? Everybody has that risk doctor. It is if I had to order one test in a revised clinic, it would probably be an FDA, okay? Because you can cure this disease. I know it's infrequent, but nevertheless, in most cases, people should be tested for that. So it's prevalent, you know, in the world. In the United States, the incidence was on the decline to 2,000, but it's creeping up again. And there have been these kind of sporadic epidemics of syphilis, particularly in this part of the country. So in Seattle and in San Francisco. So syphilis is out there. It's on the rise. We've made the diagnosis here more frequently in the last couple of years. There's really no formal reporting system for this in the United States. But in Britain, it is there are lots of cases of systemic syphilis. However, the cases of ocular syphilis are less commonly associated with it. And it constitutes about between 1 and 5% of the infectious posterior UVs that you might see in tertiary care center. I think it is extremely important to always think about HIV co-infection in patients that you think may have syphilis and the converse. So patients that are HIV positive should be also tested for syphilis. There is a very high rate of co-infection and not infrequently. And I have actually had this experience with one of the patients I'll present here that, you know, the diagnosis of ocular syphilis led to the diagnosis of HIV in that particular patient. So they travel together. You know that it's caused by troponema pallinum. Other diseases that could cause, you know, troponema disease are syphilis, basal, pinta, and yawns. You know, board question. Of course, very useful. It can be acquired sexually, right, by abraded amicus membranes through sexual contact or congenital latex transplant transplantally. It's disseminated hematogiously throughout the body, then into the lymph nodes and can invade the central nervous system at any stage of the disease. Congenital findings, again, I don't see this very often, but salt, pepper, retinopathy, coroidal scarring, retin, lens, nuclei, interstitial keratitis, glaucoma, and optic acid. So just think about that when you're taking the OCAP examination, okay? Or when you're, you know, doing rounds with Dr. Hartman, you know, and looking at babies under anesthesia. So it's always a consideration for a torch type of infection. I know it's early in the morning. Sorry for this, but you know, there are three stages of the disease, primary, secondary, tertiary. The primary disease is, you know, associated with the, you know, the penile eye or perianal or tonic canker. Two to six weeks post infection. In the patient, the church lady that I mentioned to you, who's a nice lady, upstanding citizen, she was referred to me with the diagnosis of mutes and said she had a little bit of difficulty hearing. And indeed, she had these kind of funny, kind of pre-retinal spots in her retina. And she described this rash on her hands and her palms. And so it was just really her history that led, you know, that led me to the diagnosis more than anything. And I asked her, is there, does she have a possibility that she could have a sexually transmitted disease as well? Not personally, but perhaps my husband, so to open up a big can of worms. She indeed tested positive for syphilis as did her husband. Anyway, so it's important to ask. During secondary syphilis, during six to eight weeks, there's hematodinous spread of the organism, the macular papal rash and adenopathy are characteristic. And it's followed by a variable latent stage of the disease. Churchary disease can be early latent or late latent disease. And the thing for board purposes is that the, that uveitis can occur at any stage of syphilis, usually during the secondary stage of the disease, but it can occur anytime. It can do anything. So it can present anytime and it can do anything it wants. The great imitator, you know, it can present in the anterior segment, and I, intermediate uveitis, optic neuritis, neuropathy, scleritis, episcleritis, interstitial perioditis, but the most common presentation we'll ever have of them is a posterior uveitis. Okay, so I just want to go over a couple of those presentations. There are some distinctive clinical patterns that should really make you think about the diagnosis. So it can do anything. Posterior uveitis is the most common. There are two distinct clinical patterns. One is acute syphilitic posterior placoid cordyretinitis. Uniform, inner and outer cordyretinal inflammation with discrete oval circular yellowish areas in the posterior pole. The typical patient for this is a middle-aged male, about a third of them are HIV positive. And it looks like this. This was a patient actually that came in on a Friday. We saw them, they were seen by the resident, and we took one look at the patient and said, I think this patient has syphilis. Let's test them for syphilis and HIV, and that's exactly what they had. So the presentation is very, very characteristic. The fluorescein angiography shows early blockage and some late staining of the lesion itself. So again, that's not ampy. I mean, it could be if we're bilateral. So anything that affects the pigment epithelium can produce that pattern. And then post-treatment with penicillin only. This is what it looks like. So in most cases, it can be treated just with penicillin. The ICG angiogram is very characteristic that shows a well-demarcated area of hypofluorescence in the early and late phases. It may be pathodermonic of this in the correct clinical setting. The pigment, the OCT shows some very characteristic findings of discontinuity and disruption of the outer retina, the ellipsoid, the regular nodular hyperreflectivity, the pigment epithelium, as you can see in the arrows below, and in some cases, subrenovil fluid and loss of the ELM. The other pattern, which was what the church lady had, was panuviatus with superficial pre-retinol, precipitates your small, creamy, white, and migratory in the back of the eye with mild opacification. It's mild, so it doesn't really, it's not in the retina, but it's pre-retinol and it differentiates it from necrotizing retinitis, and it looks kind of like this. Two different patients, one is a young HIV positive patient, one is an HIV negative patient, both of whom had this presentation. This was another person that was referred from neurophthalmology. It's in the retina. Well, it was actually in the optic nerve, and this patient had a presentation of an optic neuropathy, and really his history was extremely important in differentiating this disease. You know, he was at risk, sores in his hands and his mouth and his tongue, and he was at our parapod. This was a very interesting patient that I saw a while back that had what was described at the time as syphilitic outer retinopathy, which is characterized, as you can see in the slide to the right, these curvilinear infiltrates that were initially thought to be azore, but occurred in RPR positive patients. And in retrospect, in looking at the series of these patients, this is probably a milder form of acute posterior placoid coronary retinopathy. And I think that's what actually this patient had, was a more of a placoid presentation. So this was a 42-year-old guy with a weak history of decreased vision to the 2040s in his right eye, and he had a positive FTA. Again, he was treated with penicillin only and did beautifully. Then he came back three years later with profound reduction in vision in his right eye, with this collection of gliotic material on his optic nerve, hemorrhages, occlusive vasculopathy. So what in the world is going on with this guy? So we retest him, you can get it twice. So he was reinfected. And unfortunately, despite treatment, he looks anatomically a little bit better, but he never really recovered vision on the side. So as a clinical diagnosis with serologic confirmation, always considerate in the differential diagnosis of the aviatus, always inquire about sexually transmitted diseases and HIV risks. And then one needs to perform specific troponemyl serologic testing in the workup. You guys probably know that we obtained an RPR and an FTA together, because the RPR and DRL are non-troponemyl tests. They can become negative in time and with treatment so that a person could be potentially infected with syphilis, not treated, and then present with tertiary syphilis for the positive FTA. So that's why we get them together. In most cases, the FTA remains positive for life. It would be very unusual for it not to. There may be some cases in severely immunosuppressed patients with HIV in which the FTA might be negative. So there is a new kind of recommendation by the CDC that is not universally employed and not necessarily used and it's not adopted here according to the IDE people, but it's reverse sequence serologic testing. We kind of do this in a way, sometimes when we have equivocal results. And that is we screen patients for antibodies to troponemyl antigens with either enzyme immunoassays or cumulus immunoassays. It's highly sensitive but less specific than RPR. So if it is negative, it has a high negative predictive value. So it rules out syphilis, but if it's positive, then there's reflex testing to RPR. If the RPR is positive, then the patient has syphilis. If it is again negative, then there's a highly specific troponemyl pallidum particle agglutination assay, which if it is positive confirms the diagnosis of syphilis. If it is negative, it makes it very, very less likely. So that's just shown here diagrammatically. Further testing, you can always look on dark field microscopy, PCR, HIV testing, obviously, and then CSF. So the recommendation by the CDC is to obtain an LP on any patient that has neurological syphilis. Individuals that have infections in their eye have neurological syphilis by definition. So patients with UVitis that is proved to be syphilis need an LP. And if their LP is positive, then they need to repeat LP in about six months. That's the recommendation of the CDC. Treatment, you have to treat this as if it were neuro syphilis. So not a shot in the butt with benzepine penicillin. Not one undone kind of thing. The patients need to be evaluated by ID. They need to be reported to the centers, to the public health. And their sexual contacts need to be identified. They need to be treated with penicillin G for IV for 14 days. They can be admitted, have a pick line. The alternative to that is procane penicillin G, intramuscular with probenicin. And alternatively in patients that are allergic to penicillin, we've actually desensitized them. Corticosteroids are appropriate, you know, for inflammation in the front of the eye. I would never give a patient a periocular injection of steroids with syphilis. You can consider it with very severe inflammation like we had with that other guy after improvement, after antimicrobial cover. But in many cases it's resolution of inflammation without steroids. Just in terms of prognosis, it was once thought that HIV was preferred a poorer prognostic risk for patients with syphilis through isolated case reports. But a review of the literature suggests that that may not actually be true, that there is really no difference between the severity and presentation, visual outcome between HIV positive and HIV negative patients. And that actually in a more recent review from Hopkins, it suggested that maybe even patients who were HIV negative had a poorer visual outcome, because they may actually have mounted a more severe inflammatory response to the organism, and may have gone undetected for a longer period of time. Okay, so not to beat this into the ground, but syphilis is always something to think about. Any, can occur anywhere. Seolargic testing is imperative. LP is important. Imaging may be very helpful. I'm going to skip Lyme disease, okay, because I'm going to try to cover it in a pediatric talk with you guys in the interest of time. Herpes is very important, okay, most common infectious cause of anterior uveitis, and usually is associated with granulomus or non-granulomus, Kp, that are stellate or can cover the entire epithelium, diffuse stellate Kp's, concentrated beneath the area of keratitis, and usually it's the most common presentation of auger hypertension with uveitis. So, patient comes in with high pressure, and to you guys, you have to think about herpes. There's usually some evidence of concarne or previous herpetic infection, and adendrite stromal keratitis. Corneal sensation is a test that's easy to do, it's often overlooked, but I think it's important to think about. Sectral iris atrophy can be present either simplex or zoster, okay, so it is not pathogenomic zoster that is something that's been perpetuated somehow, and textbooks may come up on a board question. And then you always should ask about prior cutaneous disease, particularly in the V1 distribution of zoster. You know about the treatment for herpetic keratitis with topical antiviral medications, but systemic antiviral medications actually penetrate well into the anterior chamber and are probably very useful for the treatment of anterior uveitis in patients with herpetic keratitis. You should be aware of the fact that CMV, Sadomegalovirus, well-known to produce, you know, CMV retinitis in patients with HIV, can produce a unilateral or bilateral acute and relapsing chronic erudocyclitis in an immunocompetent patient. I haven't really seen very much of this, there have been maybe one or two cases diagnosed as I've been here, one among the Asian and Japanese population, but it is important diagnosis to make in that patients are positive for CMV by PCR, a type of the anterior chamber knot, VZV or HSV, and they respond to specific anti-CMV therapy. So some with systemic valcite, or some people have used a valcycli... ...Gel, Gansikovir Gel. The problem with this disease is that once the antiviral medication is withdrawn, it frequently relapses. So always dilate the eye, right, Tyrant? So here's a patient of a 61-year-old guy that came in with, you know, a five-day history of decreased vision. This was not his first photograph, actually. His first photograph was the day before and he was actually referred in with a putative vein occlusion and he had a very subtle finding of kind of a ground-glass appearance in his temporal macula. He had a history of rheumatoid arthritis and he was on an immunosuppressive medication, an extensive travel history. So we really did an extensive work up on him and he had significant arthritis and we performed a diagnostic retraction, which is really not necessarily to do most of the time, but given his extensive travel history, we did in this particular case, but it was positive for a very solid zoster. And as you can see in this picture, he has retinal whitening and vasculitis and a diagnosis of acute retinal motrosis is made in this particular case. So it was originally described in the 70s in Japan in healthy adults. It is now known to be a spectrum of necrotizing herpetic retinities and can occur in the immunocompromise or immunosuppressed host. The etiology can be varicella herpes simplex 1, herpes simplex 2. CMV is in there, but it produces a different kind of picture. And men are slightly more affected than women. It presents usually unilaterally, two to thirds, but when it was initially described, there was also something called barn, bilateral acute retinal motrosis, that can actually present. So it doesn't necessarily always present unilaterally, but most of the time it does. Usually with an acute decrease in vision, redness, pain, floaters, granular and sanitary, you've got an elevated pressure. Fellow eye involvement can occur anywhere between a week to 20 years after the involvement of the other eye. That has to do with the pathophysiology and the infection, which involves the brain. And for some reason, herpes has this neurocropism, hangs out in the brain. There's an animal model for this, called the bound-silly model, in which it can go to either eye. But in any case, this is a typical presentation. There are presentations which are atypical. When ARN was initially described, there are cases called limited ARN, in which patients just present in these little areas of whitening. So it's not always severe. In the acute phase, usually there are these multiple yellow peripheral retinal lesions that coalesce and progress centripetally to the posterior pole. Vitritis is always present, and there is always a vasculitis. The natural history of this is to, you know, is to resolve in two to three months. But you don't want it to resolve like this, with widespread retinal atrophy, pigmentary changes, optic atrophy, which is a large cause of decreased vision in patients of ARN. And there's a very high instance of retinal attachment. So the diagnosis is clinical. And the AOS Executive Committee came up with some criteria, necrotizing retinitis, occlusive vasculitis, and inflammation in the ACN inventory. So those three should be present to make the diagnosis clinically. But when you suspect this, you want to try to confirm the diagnosis. So in our clinic, if a patient comes in and they have a clinical diagnosis of ARN, we usually obtain some fluid from the anterior chamber. If we are pretty convinced that the diagnosis is ARN, that the differential diagnosis is limited to a viral infection. And the patient is immunosuppressed, and the differential diagnosis is much broader. We need a larger sample of fluid, and that patient probably needs to attract to me because we need to sample the vitreous where the yield is higher, and we have more volume in order to obtain molecular studies for different organisms. In any case, the patient comes in with ARN, we make the diagnosis, or we think about it as a possibility of something that might destroy your retina within five days. So we take some aqueous, and it's highly sensitive and specific for herpes virus, and send it for molecular identification. But in that time, but we don't wait for the result to come back, the patient is treated with intravitraminal injection, usually, of laskarnate and or gansyglovir, sometimes both together. And they are started on oral antiviral medications of high dose. Usually, Valtrex at two grams, three times a day. The classical regimens which we will talk about is really IV acyclovir, 10 milligrams per kilogram every eight hours. So that was the classical regimen, and it still is the preferred treatment for patients with herpes simplex that is affecting their brain. So this can affect the brain, as any neurologic symptoms, they need to be admitted to the hospital for IV therapy. But oral medication obtains an equivalent level in the eye if it is dosed at high doses at two grams, three times a day. Then it is usually, we usually treat them for about seven to 14 days, and they taper the antiviral medication. After 24 hours of therapy, patients are usually begun on systemic corticosteroids because there is a considerable amount of inflammation in the eye in patients with arm. So it is to treat the inflammation. And we keep patients on antiviral treatment. I keep them on almost indefinitely at suppressive doses after this is resolved because it has been shown that patients that are on chronic suppressive antiviral therapy have a decreased risk of involvement of their fellow eye. These are the alternative regimens intravitrile, Foscarnit and Gantz-Cyclovir. Aspirin has been recommended to be begun given the fact that it is an inclusive vasculopathy. And then as I mentioned, Prit and Zone. Rental detachment is a big complication. There is no hard data to suggest whether or not it is effective or not. But in patients, as soon as I can get a view, if they have large swaths of inactive arm, I will put barrier-relation photocoagulation in those eyes to, in the attempt to prevent retinal detachment. There are some patients in which they have come through that barrier. But there are other patients in which I am very, very glad that I did because they developed retinal detachment and the barrier-relation photocoagulation actually prevented it from going into the macular. The prognosis is poor untreated, but it is variable, I think, with treatment. What's cited in the literature really varies tremendously. And the reports for visual outcomes differ depending upon what regimen is treated. There are group from Mark Johnson's group in Michigan that reported fantastic results in patients treated only with intravenous or systemic antiviral medication, whereas the experience of many other people is that it's much more aggressive disease. So I think there is tremendous variation in the disease severity and I think that it has to do with varicella being more virulent. Number two, I think that there are host factors that are critical, actually, that vary from individual to individual in terms of their toll-like receptor processing of these antigens. Just to mention that there is also something called porn. We all know what porn is, right, when you see it, but it's hard to define. So this porn is progressive outer retinal macrosis, which was seen in patients with HIV AIDS with a diagnosis of varicella. So these patients, this is a variation of varicella, but it is usually occurs in profoundly immunosuppressed patients. And you can see that they had this kind of outer retinal involvement because the blood vessels are crystal clear. It has like this cracked mud type of appearance and there's no vitritus because these patients can't really mount an immune response. And unfortunately, these folks do really, really poorly, even with combined treatment with both gencylvir and foscarnit. This was actually a patient that I saw that within 24 hours progressed to this. I mean, it was just unbelievable in a patient with the AIDS epidemic in the bad old days. So NLP in two thirds of the case is usually from optic nerve involvement. I think that it's seen less commonly in these days as is, you know, CMB retinitis, but herpes affects the optic nerve and I think it's one of the reasons why the visual prognosis is poor. You know, I want to be considerate of your time as it's getting late. We could run through toxo and then call it a day if you want to do that. Because I think that I can cover some of the other things in a pediatric lecture on. I will be giving you shortly. But toxoplasma is important to know about. You all know that it's caused by toxoplasma gondii. It's an obligate intercellular parasite. The cat's the natural host. Human's the intermediate host and it can exist as a sporozoa. It can hang out and survive in the soil for a year. So litter boxes are a source of contamination. The tachyzoid is the infectious form and the bradyzoid is the tissue-insisted form. So I think that what happens is patients are exposed to toxoplasmosis and they may get a scar somewhere, but they're probably bradyzoids throughout the retina that you don't actually see. That become active whenever they seem to feel like it. Congenital infection is uncommon. It can be acquired during pregnancy. The transmission risk is directly related whereas the severity of the disease is inversely related to gestational age. So if you have toxoplasmosis in the first trimester it's more likely that you may not carry that pregnancy. Transmission is more common in the later stages of pregnancy. 40% of maternal infections result in congenital disease and 70% of those manifest ocular lesions. The triad that you need to know about is corioretinitis hydrocephalus and intracranial calcifications for congenital syphilis. In the United States syphilis actually the prevalence varies from region to region. It's about 22% in the United States whereas the prevalence of ocular toxoplasmosis is only about 2%. Whereas in Brazil there's much higher prevalence in the general population the higher prevalence of ocular toxoplasmosis. These studies plus the studies of epidemics that have occurred throughout the world and recently in India and in Vancouver suggest that acquired postnatal infection of toxoplasmosis is more common than congenital infection. So the classic teaching is that those scars that you see in toxoplasmosis are the result of a congenital infection. The thinking these days is that there's probably an acquired infection in postnatal period. Which I think is an important point it suggests targets to not only strategies to target pregnant women, but also children that may be at risk for requiring the disease. The risks they talk about vegetables contaminating game, soil probably contaminated water is probably the most common reason why people get toxoplasmosis in an epidemic fashion. So vegetables gain more than lamb, more than ground beef and then contaminate soil such as kitty litter. Something that you may or may not know about toxoplasmosis that it's not toxoplasmosis not all the same. There are three distinct colonial lineages which type one, type two and type three and then there is a typical type and recombinant genotypes. These are antigenically similar but can be distinguished serologically and it's important because these three genotypes differ in their virulence. Type two is the more common type that we see in North America and Europe and it's less virulent than the atypical variety and type one which may be seen more in South America. So you can postulate variants in disease severity and geographic distribution and maybe new epitope arrays may allow for molecular diagnosis and actually distinguishing between them. The clinical presentation the classical clinical presentation is seen here with retinitis adjacent to a quarter renal scar okay, vitritus very frequently a vascularitis can be either an arteritis such as a curilis arteritis which we can show you at some point in time and or a phlebitis and a third of the patients have macular involvement. It can also be acquired so primary acquired toxoplasmosis can present without a quarter renal scar with vitritus and the differential is that their serology is a little bit different they would show an IgM rather than IgG in response. Other presentations are neuro-retinitis papillitis or punctate outer retinal in the process. This was brought up I think recently at a conference another atypical presentation is that in an immunocompromised host so in the picture up into the right you can't in an immunocompromised patient that happens to be toxoplasmosis but you can't really tell that by looking at that picture so that required a biopsy in order to make that diagnosis but it's something to always think about in patients that are immunosuppressed particularly patients with HIV disease 10 to 15% of those patients will have re-enhancing lesions in their brain so a patient with toxoplasmosis in HIV needs to be neuro-imaging. Serologic testing isn't that valuable in patients with with toxoplasmosis it's usually a clinical diagnosis by looking in the eye and getting history of the patient it is helpful if it is negative. If their serology is negative they probably don't have toxoplasmosis but the presence of IGM or IGA is suggestive of acquired disease in adult or congenital infection in things but we do get serology in a lot of patients but if you had a choice a lot of the patients with toxoplasmosis that come in are financially disadvantaged poor patients can't afford that you look at their eye and talk so you treat those patients and not rack up their bill you can get PCR on toxoplasmosis both from the anterior chamber and from the vitreous the yield is higher in the vitreous and it's not as high as the herpetic viral retinitis it's about 60% really in the best possible scenario here's a 60 year old person that presented with his focal area of retinitis this is the differential of toxotoxicriasis her labs were unremarkable but the toxo-IGG was very very high suggesting that diagnosis so what do you treat so if a patient comes to a uveitis clinic the chances are that 90% of those people are going to get treated for toxoplasmosis however a small active peripheral lesion that's not producing any vitreous can be observed because the natural history of that really is to burn out by itself the idea of treatment is to you know preserve vision in a vision threatening lesion or in which there's a lot of vitritis and also to limit the size of the scar so treatment is recommended for lesions that are approximate to obstructures that are responsible for good vision macular optic nerve visually significant for tritis an immunocompromised host has to be treated and usually with maintenance prophylaxis and of course congenital disease the standard of treatment for congenital disease is antiparasitic therapy for a year this is the patient that presented the evolution of their scar with the consolidation of their scar the classic regimen is with three agents that work by different mechanisms pyrimethamine sulfa-diasing and then fulinic acid it is important to remember that pyrimethamine can suppress the marrow so patients need to have their CBC tested on a weekly basis sulfa-diasing 10% of the population is allergic to sulfa it's also hard to obtain and then corticosteroids can be used with severe vitritis usually at about half the dose that we use for severe uveitis at about 0.5 mg per kg there are some alternative regimens clindamycin can be added on to that triple therapy for what is called quadruple therapy but clindamycin and sulfa-diasing can be used together again you have to remember that clindamycin can produce pseudomembranous colitis is actually very useful and can be used frequently in patients with peripheral lesions that are not affecting the center of vision it's cheap, it's easy to administer in other patients where there is vision threatening lesions in which pyrimethamine and sulfa-diasing may be difficult to obtain for that patient because again they may be poor azithromycin is effective it has good penetration to the eye atovacwone and then of course intervitral clindamycin in patients with really macular threatening lesions or in patients that for example are pregnant that can't take these medications just so you know that there is no consensus among uveitis specialists when there is no really randomized controlled data to suggest efficacy of one regimen over the other and there's really no clear cut benefit for the short-term use of antibiotics other than maybe limiting the size of the scar itself I'm going to stop here and we'll talk about some of these other infectious diseases in the context of pediatric disease I'm sorry about the technical issues but I think that should give you the heavy hitters and infectious diseases you're welcome