 Good morning, everyone. If you can all quiet down and take your seats, we're going to get started. We have a really exciting full Grand Rounds Day full of four of our visiting medical students, fourth years all here who've done excellent work over the last month. Our first medical student, Austin Bonner, is actually from Salt Lake City or from Utah. He comes to us by way of the University of Utah School of Medicine. Interesting fact to know about Austin is that he was in the bike race. I don't know if you guys have heard of this, the Logan to Jackson or what's the abbreviation, Loda Ja. Loda Ja. OK, I'm not cool enough to know this. In which case, you ride your bike from Logan through four mountain passes all the way to Jackson Hole. And his time was just under 10 hours, is that right? Which is pretty remarkable. So Austin's going to be talking to us, giving to a case presentation this morning. Thanks, Austin. Thanks, Tina, for the introduction. So I'm just going to jump right in. So this is a patient that I saw in follow up in UVI's clinic. So patient was a 66-year-old female. She was referred to UVI's clinic by an outside ophthalmologist for possible vitritus OS. Patient's main complaint was this sort of large cloud in her left vision that she felt like she first noticed after she had cataract surgery the prior year. Past medical history was mostly insignificant. As far as the eye, no other ocular history other than that single surgery. No family history of eye conditions and other medical conditions. Had some diabetes, arthritis, fatty liver disease, and this remote history of seizures, but mostly non-contributory. On review of systems, she had this recent history of fatigue and then had some chronic constipation that she felt like had recently changed diarrhea. But she denied all other review systems. Exposers, she stated that she had previously worked as a nursing assistant and had been exposed multiple times to TV, but had had prior negative testing. As far as other exposures, she denied any travel pets, IV, drug use, tobacco, STIs, and insect bites. So on initial exam, the right eye looked pretty good, but she was count fingers at the face and the left eye. And then she had this APD on the left, but pressure and extranocular motility looked good. So on initial slit lamp exam, the anterior segment looked pretty good. She had the PCI well and the left eye, early cataract and the right eye, and then kind of this really significant vitritis and like thick cell with three plus haze and the left eye that was sort of obscuring the view to the back of the eye. We thought we saw a little bit of pallor and sort of these sub-retinal, retinal sort of nodule things and the right eye looked pretty good. So this is, I don't have imaging of the right eye, but this is the left eye, kind of what we saw. So like I said, we kind of saw some nerve pallor here and a little bit of whitening along the superior arcade and then this sort of multifocal diffuse sort of retinal sub-retinal infiltrate. And this is kind of a more zoomed in view of those infiltrates. On FA, so this is a late phase imaging about five minutes. The right eye looked pretty good and then we saw even more multifocal, more diffuse, hypo and hyper fluorescence. These lesions are about a hundred microns each. So kind of very distinct presentation. On OCT again, the right eye looks pretty good. On the left eye, you can kind of note the poor quality of the images due to the significant haze and cell that was in the vitreous. I see kind of some thickening here, maybe some fluid here and then again these infiltrates. So assessment at that time, we thought the patient had intermediate and posterior uveitis, OS, much greater than OD. Differential given the patient's exposures thought maybe ocular tuberculosis, syphilis, sarcoidosis, Whipple's disease, intracrofoamphoma and idiopathic. So further workup that we did, ended up doing a retrectomy, gave the patient intravitral immune modulators, antibiotics, antifungals and antivirals. Labs, kind of to rule out our differential looked pretty good. CBC, CNP were normal and ruled out sort of all our other things. And then interestingly from the vitreous we saw these highly atypical cells and like this small population of CD5 and CD10 negative B cells with a bunch of lambda chains and suggestive of a possible B cell neoplasm. So ultimately the patient was diagnosed with primary vitreal retinol lymphoma or PBRL. This is the focus of my talk. So PBRL, it's a subcategory of primary intraocular lymphoma, closely related to primary CNS lymphoma and maybe thought of as like a precursor lesion or precursor cancer to primary CNS involvement. This is an aggressive malignancy compared to other primary intraocular lymphomas such as UVL lymphoma, which is usually indolent. It's a non-Hodgkin lymphoma. Most commonly is a few large B cell but T cells have, T cell lymphomas have been reported. It's still relatively rare and this makes studying this cancer really hard to do. Represents about four to six percent of primary brain tumors in one to two of action-available lymphomas. Most commonly presents as bilateral but unilateral can be seen such as the patient that we saw and mean age of presentation is in the fifth and sixth decade of life. So common presenting symptoms like the patient that we saw had are very vague, not specific floaters, blurred vision and cloudiness. This is actually the picture that we initially took. That really nice color picture was after the vitrectomy. So you can kind of see a little bit of power but really significant haze and cell. And this is secondary to a bunch of the lymphoid cells sort of floating in the vitreous. I mean, that's important to know that 38% of patients are asymptomatic. PBRL is known as like a masquerade syndrome because of the vagueness of the symptoms can really look like a lot of these other things, sarcoid, viral infections, vascular diseases, a bunch of others. And this often leads to misdiagnosis and delayed diagnosis. So common signs in the vitreous like I already talked about, you see these like thick clumps of strands of cells, lymphoid cells in the vitreous and then you can see pretty mild to moderate haze. In the RPE, you see the characteristic or buzzword leopard skin pigmentation. This is a really good picture I found online. You can kind of see the leopardy pigmenty stuff here. And this represents older areas of lesion where the pigment started to come back. And then the retina, you can kind of see these more creamy orange yellow infiltrates kind of more like here and this represents more active areas of lesion. You can kind of see some here too. You can see macular edema, although that's a rare finding. Most patients don't have macular edema. And actually, if you can, after they've attracted me to that pretty good vision. An optic nerve is very involved. Anterior segment is usually quiet with the patient who we saw. So diagnosis is made histologically from the samples that you can collect. So you usually see these sort of large lymphoid cells, low cytoplasm, kind of your regular nucleoli, dense chromatin. And then you can stain for B cell markers like CD20 and immunohistochemical staining. So there's a couple of ways to collect cells from the vitreous. You can do fine needle aspiration or the protractomy like we did, the fine needle aspiration, although that's the convenient thing is that you could do that in clinic. You really don't get very much of the vitreous. So making a diagnosis is difficult. It's difficult even with the protractomy to get enough cells to definitively make the diagnosis. So the fine needle aspiration may help you sort of rule up broadly between inflammatory malignant infectious processes if you're lucky. But protractomy is much more highly sensitive. And then you can do sort of direct sampling with the retinotomy. And then use PCR and full cytometry to get a better analysis of the cells. So additional important workup, like I stated before, the PBRL is a closed cousin or possibly precursor lesion to primary CNS lymphoma. So imaging of the CNS is really important. MRIs, your best modality of viewing lymphoma is changing the CNS. Both are limited, however, in actually diagnosing and viewing lymphoma is changed within the eye. So this isn't gonna help you as far as your diagnosis of PBRL in the eye. Other important things to check are the blood tests, sort of a broad range or broad net of lab tests to sort of rule out other, those masquerader syndromes like we did in this patient. And then CBC effort blood counts and also HIV status given that lymphoma is more common in HIV patients. Then you can do lumbar puncture and CSF cytology to sort of catch any early CNS involvement that may not be picked up on the MRI. Treatments, so PBRL is actually highly radio and chemotherapy sensitive. Chemotherapy is usually centered around methotrexate or satarabine. High dose methotrexate, given systemically, actually has pretty good remission rates, 72%, or when used in combination, you can get you up to 94 to 100. And then other routes of administration are intrathecal and intravitral. Intravitral for early CNS involvement and intravitral for unilateral disease like the patient we had or in relapse or uses combination. Another interesting option is the Rituximab given intravitral, which is attacks CD28 monoclonal, or is a CD28 monoclonal antibody. So prognosis, really poor visual prognosis without quick treatment. So that's why catching this early is really important. Mortality, again, this is a really rare condition. And so the mortality range is quite broad, nine to 81% on follow-up periods with average survival time between 12 and 35 months. I did note that improved survival has been seen without CNS involvement and uterilateral disease usually again has improved prognosis possibly because this is maybe considered an early lesion that hasn't progressed to bilateral or CNS involvement. And then bilateral more commonly progresses to primary CNS lymphoma and T cell lymphoma again gives the worst prognosis. However, ocular currents even with treatment does come back in about 22% of patients. So big takeaways in why I felt like this case was both really interesting and important. Primary ocular lymphoma incidents in the U.S. has tripled over the last 15 years. Why that is, I don't know, maybe you guys have a better idea. It's a masquerade syndrome so can present and look like a lot of different things. And actually I found one case report that did say that it often partially responds to steroid treatment so can look better and this often sort of out in the community can be misdiagnosed and look like maybe it's getting better often delaying treatment. So because of its rarity, this is again a very difficult thing to study. And while sort of broad treatments have been outlined in broad ways to diagnose it, there really isn't a clear, concise way or protocol to follow in monitoring or giving therapy. And then optimal treatment is a multidisciplinary approach through ophthalmologist, radiologist, pathologist, and oncologist. So these are my references. Do you have a haswin-chacor review? And then I just wanted to say thank you. Thanks for letting me present and rotating through. Appreciate it. So what did we find in regards to systemic disease presentation for this patient? I mean, was there signs elsewhere? Was there a CNS? When this patient, Dr. Chacor can correct me if I'm wrong, but this patient presented with unilateral and at presentation didn't have any other CNS involvement or bilateral disease. Because now it looks like it's we're about a year out now. That's prognosis. It's essentially one eye and no CNS. And even with that, the median survival was only about three years. That's what I found maybe Dr. Chacor knows better. And they don't go systemic either. So what you're telling us is really the prognosis for this patient is fairly good. So I guess she's had an interfecal treatment. Just one other comment, and that is you're talking about how we're seeing a lot more of this. I think a lot of it is is we were just treating this as non-specific uveitis and we didn't know what the heck. And all of a sudden the phoma came. Well, my gosh, this patient has a phoma. So I just think there's much better appreciation of how this presents and what it is and much better diagnostic attempts to figure out. I mean, in my day, is Roger Harry here? Roger? I mean, almost all the stuff just got treated with steroids. And we called most of it idiopathic. We had a few things we checked. You usually rule out syphilis and TB in a few, but nothing to the extent like we're doing today. Give steroids and help with the bus. A case years ago, we published about a patient presented his papillodema. That makes sense with CNS involvement. Yeah. Papillodema. I didn't see that as a presenting sign. I don't know if Dr. Chacor's seeing that or not. Papillodema, but not with ocular involvement.