 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 coriorentinal 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 intravitral clindamycin to cover toxo, as well as phosphocarnate to cover viral etiologies. These are the labs that were checked, and they were started on valtrex and Bactrum. 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 buzzwords for ocular toxoplasmosis, so he was treated as such for presumed ocular toxoplasmosis. He received Bactrum, 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. Vision's mildly affected. Pressure's 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 buzzwords, focal area of retinal whitening adjacent to a hyperpigmented scar, so all 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 workup. It looked really classic. We just did a very limited lab workup, 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 that 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, so you can assume some anterior chamber reaction, redness and pain. The vision was 2,400 at the time. They noticed a diffuse vitritis, and then diffuse retinal thickening on the OCT, which they were saying was consistent with macular edema. So their plan was to do a workup for pan-uvidus and see her back a few days later. Vision was unchanged. This was the workup they did for the pan-uvidus, so they ruled out syphilis. She 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 positive for the retinitis. So at this point, they felt it was non-infectious and injected intravitural triampsin alone. So they thought, oh, it improved initially. She went from 2,400 to 2,200 for a few weeks, and then a couple months later, she comes back with worsening vision again, now has mutton fat KP, a diffuse vitritis, and so they re-inject triampsin 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 vitritis. 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 toxoplasma is an 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 vitritus because sometimes it's not a diffuse vitritus, but just a clump of vitrious cells overlying the areas of activity. Or if they're immunocompromised, there can be a lack of vitritus. So vascular sheathing, as we saw in the flourishing 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 a 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 and 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 macula, or sorry, 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 are 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. In classic treatments, triple therapy, so sulfidizing, pyrimethamine, and fulinic acid. The pyrimethamine causes decreased platelets in white blood cells. That's why we use the fulinic 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 of 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-uvietus in an exposed patient population rather than assuming it's an autoimmune process. And then there is some appropriate way to use intravitural steroids. There's reports of using dexamethasone intraviturally, which is much shorter acting, concurrently with clindamycin, intraviturally 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 vitritis. 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 aviitis.