 Well, we'll get started. Welcome to Grand Rounds this morning. Today's presentation is by Jim Bell, one of our chief residents here. Jim, as you know, is a big Louisville fan and has had some success in the last couple of years with basketball and looking forward to this next year. Jim's a great, great chief resident. The biggest black cloud you'll ever meet. And going to talk about one of the crazy patients that you've seen is you've seen basically every crazy patient that has come through the clinic. Usually on call. So his presentation is a bump on the iris. Thanks, Trent. So this patient is surprisingly actually not to call patients, so some regular clinic hours that we're gonna discuss here. So the mass there is just sort of an ode to Halloween around the corner and a small clue as to what the ultimate diagnosis is gonna be. So our patients, a 77-year-old woman who actually didn't start off coming here to the Moran, she went up to see some ophthalmologists in Idaho with a chief complaint of blurry vision in her left eye. She noted that nine days prior to her actually coming in, she had developed some tearing and a pressure sensation in her left eye. This beginning of the history is all from outside clinic notes, but we do know that at that time she'd had a history of chronic bronchitis with a recent flare-up, so she was taking a Budesanide for motorol and haler and an oral flora quinolone. She was also taking chronically albuterol, conjugated estrogen supplementation, daily aspirin and supplemental oxygen at night. That's a little bit of her history. Her vision when she first came in was 20, 20 in the right eye and 20, 30 minus two in the left eye, so a little bit off in the left eye. Pressures were normal in both eyes. Her silt lamp exam was pretty interesting though. She had anterior segment findings of mutton fat Kp leading to a, they noted a difficult view for cells in the anterior chamber although they thought that it was likely that they were there. There were posterior synechia present in the left eye as well. She also had an early cataract. She was noted to have a normal dilated fundus exam although they did point out that again the cornea made the view difficult so they weren't completely confident that that was normal. So they started a workup for this patient that included a quantifier on gold, ACE, FTA, ABS, all of which were negative. Her lysozyme was slightly elevated but again her ACE was normal so they didn't go into that too much. She was started on prednisolone drops in her left eye every two hours along with cyclopenylate drops in her left eye to try to keep her eye or some scarring down anymore. She followed up pretty frequently over the next few days and during one of these follow up visits she was started on acyclovir as well just in case this was a herpetic infection. So nine days later her pressure in her left eye jumped up to 52 so certainly not the nice 16 that we saw in her initial presentation. They thought this could be secondary to all the inflammation going on in her eye so they gave her a subtenons dexamethasone injection and started her on some pressure drops including bronzolamide and bromonidine. They also changed her cyclopenylate to atropine at that point. They gave her a few unknown doses of acetylzolamide that day and the next day her intraocular pressure was eight so she certainly responded to all that they threw at her. As far as her pressure is concerned so they continued her with her acyclovir and all the drops that I just mentioned they switched her prednisolone to dexamethasone drops and in spite of this the keratic precipitates continued to progress across her cornea making the view worse and worse. They did note a small area of neovascularization at the pupil margin in the left iris that they didn't see when she first came in. Her pressure sort of continued to creep up over the next few weeks. It didn't have a spike up to 52 like before but it got up to the 20s. So they started what they called a low dose of acetylzolamide I'm assuming that's 250 milligrams but we don't know for sure. And they went on and got an anterior segment OCT and agonoscopic exam was performed. Again the cornea is not very clear but they were both noted as normal. So around this time she was referred to the Moran because we still don't have an official diagnosis and things don't seem to be getting any better. So just to recap by the time she got to the Moran she was on quite a bit. She's on dexamethasone drops every two hours in the left eye along with homatropine drops, brimonadine drops, benzolamide drops and her acetylzolamide had been increased all the way up to 500 milligrams twice a day. In spite of all that her pressure when she got to the Moran was up to 28 while she's taking all those drops and taking the acetylzolamide at that high of a dose. She still complained of blurry vision in her left eye but still didn't have any pain in her left eye. Vision in the right eye was 20, 20 still. The left eye was 20, 60. So a little bit worse than when she first came in. Her motility was full, visual fields were full to confrontation. Like I mentioned the pressure in her left eye was a little high. The mutton fact KP were still noted and she had for sure she had cells in the interior chamber at this point. Her cataract hadn't really changed much and it was thought that she had some macular edema. So a workup was continued here at the Moran. She was seeing doctor on body at this time and serologies were negative for ANA, Bartonella Hensley, Bartonella Quintana, Lyme, Anka, Rheumatoid Factor RPR and HLAB 27. Those obviously didn't all come back in the same day but as they came back nothing was positive. She wanted to get back up to Idaho to be with her family and be back close to home so she decided that she wanted to follow up with the group in Idaho while these lab results were coming back. Over this time she continued to have pressure issues so she eventually had cataract surgery with an aqueous drainage shunt placed and during that surgery they drew aqueous samples for PCRs for HSV, VZV and CMV all of which were negative. And then she came back to the Moran three months later with a vision in her left eye of 2100 and a pressure of 19. So at this time she was noted to have an obvious iris mass with neovascularization and she still had her anterior chamber cell. This was really the reason I think that she came back. The physicians in Idaho said, look, you know, you need to go back down to Utah and get this worked out and stay until we come up with a better idea of what's going on. So a few more labs were drawn. Some of them were repeated before just to be sure the original results were accurate. CBC, serologies for syphilis, sarcoid and toxoplasmosis and toxochoriasis were all negative and normal. So this is a picture of her eye when she came back three months later. You can tell that the cornea is not clear. There are a lot of keratic precipitates there that have been noted before. But you can also, if you follow that slip beam along the contour of the iris, you can tell it's not a smooth surface and it's not even really just one single mass. It's just sort of a continuous abnormal shape to the iris. You can also note the pupil in this picture is not dilated in spite of the fact that she's taking the dilating drops. So those posts here of Sinecia are there although they're kind of tough to see in this photograph. Yes, see in the pupil? Sure, does anyone want to venture a guess before I have to, mm-hmm, yep. So right here, you can see that's still part of the iris right there. If it's hard for you all to see, you can sort of see the three-dimensional aspect of the mass poking through the pupil. Yes. So that was, yes, it was right along here and it sort of spread back peripherally but this was the area of concentration. It was tough to get a good picture of that just because of those KP. So it was decided to get an ocular ultrasound. Dr. Harry was great and able to help out with this. As far as the posterior segments concerned, on the ultrasound, the retina and coroid appeared normal. It was by this point in time difficult to get a great view of that because of the scar down iris and the KP. But it was noted on ultrasound that she had intravitural opacities and intravitural debris. So that was interesting. That wasn't something that we had necessarily expected. And then as far as her anterior segment was concerned, her ultrasound revealed an iris ancillary body mass in three quadrants. That was most suggestive of an infiltrative process. The differential of which was lymphoproliferative disease and amelanotic melanoma much less likely would be a parasitic process. But Dr. Harry's kind enough to let me use this ultrasound here and we went over it the other day. You can see right along here is the cornea and the interior aspect and this is the posterior chamber and ocular lens that they had placed. And then this enormous thing is the iris and you can tell that it's certainly not a normal shape. But if you look, it is sort of homogenous in its structure. It's not like a distinct well circumscribed mass. So I think that's what was being referred to as an infiltrative process. It's just this homogenously reflective tissue that the iris has become. So we'll talk more about that here in a minute. So the plan at this point was to do a diagnostic of the trectomy along with an iris biopsy. So the patient had an intracular ejection of bevisizumab to try to decrease high intraoperative bleeding during the surgery. And two days later, she had her surgery. During the surgery, a better view of the fundus was obtained and it did look normal with the indirect and the operating room. And the vitreous aspirate was sent for various labs which we'll talk about in a second. So these are some pictures from the surgery. You can see that the trectomy ports are in. The trectomy was done first. And then through some paracentesis wounds, a piece of the iris along where that neovascularization was noted was taken and sent to pathology. This is a picture of some of the vitreous aspirate that was obtained from the eye. You can tell that it's not clear like you would expect. It's more of a turbid appearance. So that's also indicative that something's going on in the vitreous as well as the iris. So she tolerated the procedure while she wasn't in pain afterwards. Her vision did decrease. She had some bleeding and some, as would be expected, some inflammation. And her pressure was 15 the next day. So halfway, she didn't have a big pressure spike. So a lot of words on this slide but I thought they were all important. Dr. Mamoise showed up at the exact right time. So the vitreous aspirate and the iris were both analyzed in pathology. Flow cytometry showed what was described as a posicelular monoclonal specimen. That was CD5 and CD10 negative indicative of a B-cell lymphoproliferative disorder, but that's not terribly specific. The iris biopsy, however, showed a lot of concerning things. So for anyone who's rotated with Dr. Mamoise for path reads, you'd know that we'll just go through each one of these descriptors. So atypical lymphoid cells is a bad sign. A high nuclear to cytoplasmic ratio is not a good sign. Vecicular chromatin and prominent nucleoli with relatively scant cytoplasm, all of those are pointing toward a diagnosis of some sort of a malignancy. And then when we get down to the immunohistochemical studies, these cells were CD20, BCL2, BCL6, and MUM1 positive and CD3 negative, which all point toward a B-cell lymphoma. So unfortunately, that was the diagnosis we were working with at this time. So we're working with an intraocular lymphoma, both in the vitreous and the iris. So it's just, oh, sorry, I'm jumping ahead of myself. So here's a picture of some of the slides. These are all hematoxilin and eosin stained slides of the iris. So this first slide, slide A in the upper left, is 100 times magnification. And again, going back to Dr. Mamelis's path reads, it's just full of blue cells and blue is bad. So that's just a whole lot of lymphocytes that have infiltrated the iris. Slide B is 200 times magnification, just a little bit of a closer view, but you can still see that it's chock full of these lymphocytes everywhere. The third slide, you can see more regularly hyalinized vessels throughout the iris, but you can also see these other abnormal vessels. That's probably some of that neovascularization that we were looking at before. And then slide D is at 1,000 times, a couple of points here. This really is, sorry about this, probably too small for those sitting in the back. But there's a mitotic figure right here, and then up here we have some clumped chromatins. These cells are active in this iris. They're not sitting dormant. So an MRI of the brain was obtained, which we'll talk about why in a little bit, there was bifuronal enhancement involving the corpus callosum along with enhancement at the parietal lobe. This is just one of the cuts through the MRI that showed some of this enhancement. And like I said, we'll discuss this a little further later on. So she was referred to an oncologist who agreed with the diagnosis of intraocular and central nervous system lymphoma. And the question at this point is what sort of a prognosis do we give her and what sort of treatment options do we give her? And that's, well, we'll get to that. That wasn't diagnosed quite yet, but she does have a lesion on her leg later on. So where are we gonna go with treatment? Where are we gonna go as far as what prognosis we're gonna give her? So that's sort of the purpose of the rest of the talk today. It's just briefly touching on masquerade syndromes and then delving more into uveol and iris lymphomas and also vitriol retinal lymphomas. Because they are considered traditionally to be two separate diagnoses. So a bit on masquerade syndromes, you'll note that this patient was followed for a while before she actually had her official diagnosis. These can be tough to diagnose. They're called masquerade syndromes for a reason. They appear as something else a lot of the time. There was a study done in the Netherlands that looked at 828 consecutive patients with an initial diagnosis of uveitis. Out of those patients, 19 ended up with a diagnosis of a malignancy and 13 of those 19 were diagnosed with a lymphoma. So that's just under 5% of these patients. I think that number's fairly high compared to the general population. My guess is this was over referral centers so they got some of the more complicated and less obvious cases but that's still something to keep in mind that if you have a patient with inflammation that you're not getting any tests back that are pointing toward a specific diagnosis and they're not responding to treatment the way you want them to. This should be on your list of possibilities. Another point from this paper was that if you give these patients recent steroids it can decrease the diagnostic yield of cytologic studies. So if you do start to go down the path of a lymphoma and your initial tests are negative that doesn't necessarily rule a diagnosis out. So to touch more on uveal lymphoma these can be divided mainly into primary and secondary lymphomas, meaning they originate in the eye or they originate elsewhere and migrate to the eye. We're gonna focus more on the primary lymphomas today but it should be noted that the most common secondary lymphoma is diffuse large cell B lymphoma or diffuse large B cell lymphoma which is a more aggressive type of tumor so that's a different discussion. But as far as primary uveal lymphomas the most common type is a low grade B cell lymphoma most commonly extra nodal marginal zone B cell lymphomas which are pretty low grade and tend to respond well to treatment. Coroidal lymphomas don't have an official association with central nervous system disease. It's been noted before but it's not common as opposed to vitro retinal lymphomas which have a very strong association with central nervous system disease. So Fuller and colleagues which included Dr. Singh who spoke here in the spring for a resident alumni day went through just a small series of cases of combinations of either just congenitival lymphoma, just coroidal lymphoma or both in the same patient. All of these patients were diagnosed finally with extra nodal marginal zone B cell lymphoma and none of these patients had vitreous cells. All of them were treated with external beam radiation and did very well and sort of the purpose of this article which I think sparks some debate in the literature later on was that maybe these UVL lymphomas, maybe these coroidal lymphomas are sort of an extension of extraocular admexal lymphomas that are found in the orbit and the congenitiva. Maybe they're not two completely separate diagnoses but really just part of a large spectrum and you'll see that more and more in the literature as time goes on and people are thinking that maybe these shouldn't be considered totally separate diseases and we'll talk about that a little bit with our patients. More specific to our patients is iris lymphoma which is much less common than UVL lymphoma. So Dr. Masheyeke and her colleagues looked at a series of 14 eyes and 13 patients with iris lymphoma at the Will's Eye Center over a long period of time. So you can see this is a major referral center for ocular oncology and over that large period of time they only came up with 14 patients with iris lymphoma so it's not that common. Six of these patients were treated with steroids for presumed iris cyclitis which also sort of goes along with our patient but these are not always obvious diagnoses when they first come in. They were thought to have a different diagnosis for at least a significant period of time. Most of the patients were older than 50. I think the youngest patient in the series was 25 and about half of them had previous or concomitant systemic lymphoma meaning that at the time of the diagnosis of lymphoma in the eye there was noted to be lymphoma elsewhere like in our patient there was lymphoma in the brain and about half of them were women so there doesn't seem to be a gender predilection. Out of the patients with lymphoma elsewhere only one of them actually had a concomitant brain involvement all the rest had involvement in other parts of the body. So another point to be made with the patients who'd been diagnosed with lymphoma in other places prior to their diagnosis of intraocular lymphoma is that they were not just going with supportive therapy. They were being aggressive with their treatment with chemotherapy and maybe radiation as well and it's still migrated to the eye. So that's just something else to keep in mind that these can be very aggressive as opposed to the choroidal lymphomas that are more commonly described in the literature. The most common symptom patients came in with was blurry vision which is similar to our patient and then just a few, I think these are important points gained. This is the largest case series that I could find out there for iris lymphomas. All of these patients had anterior chamber cell. So every single one of these patients had inflammation in the anterior chamber and almost all of them had keratic precipitates. So those are two signs that are very common for iris lymphomas at least from this paper. Secondary glaucoma was diagnosed in some of these patients. They weren't specific as to what their criteria for glaucoma was but our patients certainly had an elevated intraocular pressure. And then a number of patients also had posterior synechia, hyfema, pseudo-hypopion. All of them had an iris mass present although it wasn't clear if these were present right from the start. Our patient for instance was not noted to have an iris mass when she first started coming and she just had the anterior chamber inflammation. So but abnormal iris vessels were present in the number of these patients and a number of them ended up being diagnosed with congenitival lymphoma as well although our patient never did develop that diagnosis. So other parts of the eye were involved in a number of these patients. The way a lot of them were diagnosed was with fine needle aspiration biopsies so that can be done. A few of them were diagnosed with incisional, excisional biopsy or enucleation. A point to be made here is that while you can diagnose lymphoma with a fine needle aspiration biopsy you don't get the architectural structure of the actual tumor which can provide help in giving a more specific type of lymphoma diagnosis which can lead to different strategies and treatment and different prognoses to be given. So it sort of depends on how aggressive the patient's planning on being with treatment, how much information they want as far as their prognosis and how much involvement they want as far as their surgery because it's obviously a much larger procedure to get an incisional or an excisional biopsy. So all of these are things to be discussed with the patient prior to them being taken back to the operating room. A number of different types of lymphoma were diagnosed in this series. They sort of ran the gamut as far as not very aggressive tumors to very aggressive tumors. And follow-up was probably the weakness of this study. A number of the patients who were considered to have followed up only followed up for about a month. So as far as who passed away from the lymphoma during the study, I don't know how helpful that number actually is because a number of the patients went back to their hometowns and followed up there and we don't really know what happened with them. One final point from this series of patients before we move on is that three of the cases that had choroidal involvement also had very low-grade lymphomas. Every other case had a more high-grade, aggressive lymphoma in this series. And these patients with the low-grade lymphomas never did develop systemic involvement. And the point was made again that maybe this is more of a continuum as they might have really more had a choroidal lymphoma that spread to the iris because it behaved more like the choroidal lymphoma is another case series. So even though you're looking at a bump in the iris, it might be something that started somewhere else in the eye and then spread to the iris and you might change your treatment regimen accordingly. So we'll jump ship now to vitreo-retinal lymphoma because our patients seem to also have signs of that. So the definition is sort of self-explanatory. It's lymphoma and the vitreous are retina. And it's a subset of primary central nervous system lymphoma. Both of these are considered in general to be very high-grade, aggressive tumors. Up to a quarter of patients with primary central nervous system lymphoma will eventually develop ocular involvement. And up to 90% of patients with primary vitreo-retinal lymphoma will eventually develop central nervous system involvement. So it's a pretty serious diagnosis and you want to follow these patients closely. Most of them again are elderly patients. Median survival time for patients with primary vitreo-retinal lymphoma is about 58 months. And it's rare for these to appear outside the central nervous system according to case series and review papers. They tend to stay within the central nervous system. The diagnosis is also often delayed for these patients. They can be confusing to diagnose as well because they appear as other things and we'll go through an example of that in a minute. Steroids again can decrease inflammation so they can throw someone off the correct trail. And the symptoms like blurred vision and floaters often show up prior to the signs of this disease. So what are the signs? It's typically a quiet interior chamber which obviously was not our patient. There are not often posterior synecias, again not our patient. There are lots of vitreous cells and associated vitreous haze which we suspect was present for our patient just from the ultrasound although we didn't see this at the slitland. And the vitreous cells in haze, this is interesting, are usually in superior locations so they don't conform to gravity. I don't really understand why that happens. I don't think that's been explained but they typically hang out in the superior parts of the vitreous. You can also see cells that grow along Brux membrane creating these little mounds on dilated fundus exam and you can see them on OCT as well. They can lead to a pigment epithelial detachment. These are actually the lymphoma cells that are collecting in that area. So if you see that on OCT that's another thing to keep in mind. So fundus autofluorescence and fluorescein angiography can be helpful for these patients. They have alternating hyper and hypo autofluorescent or fluorescent spots. Mostly in the posterior pole this is the buzz word for this is leopard spot pigmentation. And then late standing around these lesions can show up on FA. And OCT will show nodules like I was just talking about at the RPE. So last year we also had another patient Dr. Vitalli's clinic who ultimately was diagnosed with vitreo retinal lymphoma. And these are just some pictures from her case because we couldn't get pictures from the case I've been talking about just because of the anterior segment problems. So you can see here it looks like a lot of necrotic tissue and a number of hemorrhages. Here's a montage photo of the fundus of the right eye for this patient. You can see that it's sort of geographically located. It's not a completely diffuse process throughout her entire fundus. And this patient was actually thought to have ARN for a long period of time. So again, the diagnosis can be difficult. This looks a lot like a patient with ARN and eventually she wasn't responding to the antiviral treatments she was getting and people took a step back and said, wait, what else could this be? And eventually a vitreous biopsy was done and the diagnosis was made. So here's the FA for this other patient. You can see these hyper and hypopigmented spots and sort of get an idea of where that leopard spot pigmentation description comes from. And you can see them start to leak a little bit more later on these photographs. Finally, here's an OCT of this other patient. I thought this was interesting. You can see in the top picture a cut right through the fovea. That's a fairly normal looking OCT for the patient and it's not going through the area that was affected before. But if you look at the, this is confusing, the bottom pictures of the superior fundus, you can tell that those layers to the retina are just gone and that's just necrotic tissue. So it can do a lot of damage to the fundus. Just not even considering the patient's overall prognosis, their vision can be severely affected with this disease. So that's something to keep in mind just for their daily life. So the gold standard for diagnosis for these patients is to actually get lymphoma cells to be analyzed. A good way to do this is a vitreous biopsy, although those are negative up to 50% of the time. So if at first you don't succeed, try again. Some of these patients though won't have a lot of vitreous cells. It'll be more of a sub-retinal process or an intraretinal process. And for those patients that's also been described that you can even get a retinal biopsy or do a sub-retinal aspiration of fluid if you're not getting anything from your vitreous biopsies. For the people in the room still planning on taking OCAPs or boards, a good number to remember is that a high ratio or greater than one of IL-10 to IL-6 found on the vitreous biopsy is also indicative of vitreo-retinal lymphoma, even if you don't get any actual cells from the aspirin. It's also recommended in a recent focal points, which is really good if you all haven't seen it, to get an MRI of the brain in a lumbar puncture. Up to 75% of these patients, according to the focal points, will have abnormalities on their MRI, specifically paraventricular contrast enhancement. Lymphoma cells are present in the CSF up to a third of the time, according to this focal point. So those can be very helpful in making a diagnosis. So the big question, the big debate in the community is local versus systemic treatment. There aren't any large prospective studies looking at this, but the standard at this time is to go for systemic treatment if they're central nervous system involvement, which makes sense. Local therapy, if it's just one eye that's involved, you can do radiation or intravitrial injections of chemotherapeutic agents. Mostly, methotrexate but buttoxamab can be combined with the methotrexate as well. No studies have been directly performed to compare these two treatment regimens. So as far as the systemic treatment, obviously an oncologist is usually involved. It's often multi-drug and systemically administered, and lots of different regimens have been tried. Most of them involve methotrexate, and there haven't been any large differences in outcome that have been noted up through today. So the median survival if the patient opts to not have aggressive treatment is just two to three months. So that's a pretty dismal prognosis if these patients decide to not go with treatment. If you give them aggressive treatment, the longest reported survival median is 40 months. So this is a different number than what I gave for primary vitro retinal infelmin. These are patients that have active CNS lesions. Obviously, the prognosis gets a little bit worse. Other things that can help you in giving your patient an idea of where they stand is do they have advanced age, which our patient did? Do they have poor neurologic function? That was not very specific in the paper that I was reading, but our patient didn't have any specific neurologic deficits. Do they have more than one central nervous system lesion our patient did? And is it deep nuclei or periventricular lesions that you're looking at as opposed to superficial cerebral or cerebellar and our patient fit the former category, unfortunately? So her prognosis is not too great at this point. So the overall recommendations from this review paper that I was looking at was that if it's localized to one eye, use local therapy. If both eyes are involved, it's sort of debatable as to what approach you can take. And if the central nervous system is involved, then you go with systemic therapy. I know the doctor on body is taking care of a few of these patients. I don't know if anyone else here has. I know Dr. Vitale does. I don't know if anyone else will see them here. It seems to me there's sort of a discussion as to maybe if a patient just has one eye involved, systemic chemotherapy is worth it at the beginning since most of these patients go on to develop central nervous system lesions eventually. Maybe you'd give them a better prognosis overall if you started with very aggressive treatment. There's no data to support this from what I've been able to read. But it seems like that's a debate and that's sort of where the discussion is headed just from what I was reading in preparing for this talk. So we've talked about the two separate diseases. I thought that this was sort of the first time they'd been seen in one patient at the same time but that's not true. There's a couple of patients previously described in the literature. One was a 51 year old woman who was diagnosed right off the bat with vitroretinal lymphoma because of bilateral vitritis. Her lumbar puncture and MRI didn't reveal that the disease had spread elsewhere. So she had brain and eye radiation performed. A year later the vitritus came back and they didn't explain this in the paper. I'm assuming she had an iris mass but for some reason they did an iris biopsy and an aqueous humor biopsy when her vitritus came back and all of these revealed B cell lymphoma. So she underwent systemic and intravitrial chemotherapy and did well initially. Eventually she developed neovascular glaucoma presumably because of the radiation she'd received and needed her eye to be enucleated. On pathology she was not found to have any tumor which is pretty remarkable given the diagnosis she was given initially and she was followed for another six years and had no evidence of tumor recurrence. So this is a patient who had brain radiation at the start even though she didn't have any known tumor there and she seemed to do fairly well for at least the following few years. Our other patient in this series had repeated episodes of vitritus. It was thought that he had chronic endothelmitis secondary to cataract surgery so he actually underwent capsulotomy and lens exchange excuse me with a sulcus sutured IOL and his inflammation persisted so an MRI was performed and it showed an enhancing legion at the caudate consistent with lymphoma unfortunately. So he had an iris biopsy, a diagnostic retractomy because he had iris nodules and a lumbar puncture all of which pointed toward B cell lymphoma. So he underwent systemic and intrathecal chemotherapy and unfortunately continued to have vitreous involvement. It wasn't clear what his ultimate state was but they followed him for a couple of years and his vitritus never did go away. So what are we going to do with our patient given all of this information? Well all these different treatment options were given to her including chemotherapy, radiation, observation. She didn't want very aggressive treatment even though she had systemic involvement. Another point to be made is that these are not benign drugs that we're talking about. They have lots of other side effects and people may decide that they're not worth the side effects that they come with. So she chose to go with intraocular methotrexate injections every couple weeks for six weeks and during this time she was found to have a biopsy proven cutaneous metastatic lymphoma on her ankle so unfortunately there were more lesions that were found. Right after this was diagnosed she moved to the Eastern United States. This was planned from the start for her. This was not related to her recent health issues and there she started with a new oncologist and a different ophthalmologist and she changed her mind and decided that she wanted to have brain and ankle radiation treatment. It sounded like the ankle involvement sort of caused her to change her mind on what she wanted to do as far as treatment was concerned. We do know that her first visit with her new ophthalmologist, the patient's vision was just 2,200 and she still had her keratic precipitates and posterior synechia present. Unfortunately, I just learned from Dr. Umbadi that she did pass away recently. So this visit was months and months ago and presumably she continued with her treatment and unfortunately passed away as a result of her disease. So these are really aggressive tumors and they're hard to control, specifically the vitro retinal tumors although obviously they can present at the same time. So in summary, these diseases can be difficult to diagnose. It should be on the differential for a patient with lots of intraocular inflammation that doesn't seem to be responding the way you want it to where you're not coming up with any definitive diagnosis. It's always something that can be in the back of the mind and it doesn't just have to be elderly patients as we noted in that paper. Most of them are but there can be patients in their 20s who have this as a diagnosis and these patients do respond to steroids. So if it gets better on steroids that doesn't mean that you've cured the patient. You still gotta look for an actual diagnosis. Primary vitro retinal lymphoma and central nervous system lymphoma are different than uveal lymphoma traditionally but they obviously can coexist and it could be that they're just part of a large spectrum. I find it hard to believe that this patient was unlucky enough to develop two different simultaneous tumors in her same eye. They were I think the same process. They just presented in different areas. So it is good to think of them as two different things but it doesn't necessarily mean that they can't show up at the same time. Long-term follow-up is needed for these patients. We saw a number of examples of patients who were treated did better, they got better, everything seemed gone and then they showed up a couple years later with new problems and then a team-based multidisciplinary approach is necessary for these patients. Obviously we're talking about more than just the eye once you're talking about lymphoma so you need other people's involvement. So these are my sources. The first paper up there I would recommend if you're interested in vitro-retinal lymphoma it's a really great sort of review of all literature on vitro-retinal lymphoma and then the focal points recently was also very good. And a special thanks to Dr. Ambati who followed the patient along with Dr. Vitale. Jonathan Harrison was a medical student who worked with us and trying to find all the information on these topics. Dr. Anne Floyd actually put together the path slides that I showed up before. She was one of our pathos last year currently an intern down in Arizona. Dr. Mamelis of course was involved in the pathology for this patient. Dr. Harry was very helpful with the ultrasounds and Dr. Shakur who pretty much has had his hands on most interesting patients at this facility for the last two years. So thanks to all those people are there any questions? Yes. Why didn't you get a really nice job of covering the really salient table? Yeah it was very interesting, sad result but it was obviously pretty rare. I actually didn't know that it had been described previously until I came across that paper with two patients. Yes, Dr. Roscoe, thanks. Thank you, sir. Yeah, I mean that ultrasound really pointed us down the path until then we were sort of floundering. So yes, Dr. Ambati. She did, I didn't see the actual OCT. It was described as normal in their chart. That was also I think prior to when she developed an obvious iris mass but the description in the chart was that it was not abnormal which would go along with what Dr. Harry was describing. Maybe there was something posterior to the iris that they would have seen at that point but they just had this. Did you have something, Dr. Warner? Okay, thank you.