 All right, so just because we always seem to go late, I think I'm going to get started on these case days. So some of you may have met this patient upstairs already. For the rest of you, I'll go through her history. But a big thank you to her and her husband, because I didn't realize this, but when I called them to come in this morning, they were vacationing in Hawaii. And they got here at midnight last night. And they still showed up at 7 30 this morning. So thank you. And they're here. So they might have questions in addition to everyone else. So our patient at the time that she presented, or not that she presented, but at the time that I'm going to start was 74 years old. She had a history of open-angle glaucoma. She had a cataract surgery done in her left eye in 2008 at another facility. We don't have those records. And she has a history of aortic stenosis, thyroid disease, GERD and asthma. She takes Taflopros for her glaucoma in both eyes, cosopt and restasis. And those are the medications she's on. So her vision is 2050 in the right eye and 2030 in the left eye at this point in time. Her pressures were 24 in the right eye and 13 in the left eye. She had a moderate cataract with what was described as a fakeomorphic effect in the right eye. Again, she's pseudophakic in the left eye. She's got asteroid hyalosis in the left eye. And she's very cupped. She has a cup to disk of 0.9 in the right eye and 0.85 in the left eye. In the left eye, it was described as having a normal fundus exam. So on May 30 of 2014, she had a combined cataract surgery with trabeculectomy in the right eye. Because her pressures are high, she's continuing to have progressive glaucoma. So it's time to get the pressure down more definitively. Post-op day one, she was 2200 in the right eye. This is after the fecotrab for those who just got here. Her pressure was 28. Her blood was massaged to drop down to 13. Interior segment exam described a low blood and the fundus exam just said that the periphery was flat. She was started on Vigamox prednisolone and preservative-free post-opt. And essentially, everything was described as normal for post-op day one and things were the way they were supposed to be. So two days later, post-op day three, she woke up and had progressively decreasing vision in the right eye, in the surgical eye. She had no pain associated with this. She came in that day and her vision had dropped to hand motion from 2200 a couple of days before. Her pressure now is 24. And her anterior chamber had rare cell, presumably consistent with the recent surgery she'd had. So that's a picture of her fundus on this day. You can see the vessels are fairly tortuous at this point, which they weren't before. She's got diffuse hemorrhages in the retina, in all quadrants. This is just for the sake of showing a photograph of her left fundus. Again, the asteroid hyalosis is there that was known. And the fundus exam is essentially normal, even though it's kinda hard to see it in the photograph. But the vessels aren't tortuous, there are no hemorrhages, nothing else like that. So we'll go through the FA here briefly, but I just wanna point out in this frame that we're 30 seconds in and there's no evidence of fluorescein in this picture, other than in the coroid in the background, but not in the retinal circulation. All the way up to 48 seconds is when you get the arterial circulation, so it's quite delayed. You can see, up at a minute, we're still not filling the veins. Left eye essentially looks pretty normal. The right eye late, still not great perfusion. The OCT shows some distortion of the foveal architecture, but you can still see the layers of the retina fairly well in that picture. The left eye, the OCT is fairly normal. So we move on later, her vision's count fingers, starting to be some concern about neovascularization, so she gets lucentus in her right eye. The hemorrhages are progressing at this point, and I'm intentionally not talking about a differential right now, cause we'll go through that in a minute. Move on months into the future. Her vision's now light perception. Her vision's not getting any better. She keeps getting anti-veg-f injections because she keeps developing neovascularization of her fundus, and she's getting it in her iris as well. And now she's really sclerosed in the posterior segment. So this is pretty profound at this point. It's certainly not improving. The OCT shows further thinning of the retina, more loss of the retinal architecture. We're almost a year out now. She's still getting a vast and still very sclerosed vessels. And then this FA I just wanted to show cause I think it's pretty impressive. There's just a little bit of perfusion of her fundus. And the part that is perfused is certainly not normal architecture of her vasculature. Those vessels are all leaking. And that's pretty much the only blood supply going to her retina at this point. Significant edema at this point that's just not going away even with persistent injections. So she stays at light perception. October of last year she had PRP, very heavy PRP that was done to try to get rid of the NVI that she was having. Her IOP had not increased in spite of this neovascularization but obviously there was concern that it would. She continued to receive Avastin, continued to have edema. So March, it was thought things were fairly stable. They'd gotten her off the Avastin. We were going to see her in four months. But then she went to NLP. Her pressure went up to 62 with the NVI. And she was on max meds. So in May of this year, she had a diode laser to that eye to try to get the pressure down, which helped last visit. She had a hyphaema although today for those who saw her, the hyphaema is gone now. She's no longer in pain. Her pressure was 35 at the last measurement. And as this says, she had a new hemorrhage but it seems to be clearing up. So I was going to open it up to what people think may have happened after this surgery. There are common things, not common things. We can start with the people in the back, my back left if no one else has any suggestions. Dr. Feist, what are you thinking may have happened after this surgery? Any other ideas as to what this may be? And we're, to be clear, we don't have an exact diagnosis for this patient. I don't know if there's a perfect answer to this question. That's partly why I didn't want to say what we were thinking right away because somebody out there may have an idea we haven't thought of yet. So, yes, Eileen? So that? Yeah, no, that's right, Eileen. I mean, that got us thinking as well. So CRVO, CRAO was what we were calling this right at the start. And that might end up being what it actually was but it seemed pretty aggressive and it seemed progressive. It didn't seem to stop just after the first day, which is sort of what you would expect with something like that. So there's another diagnosis out there that we've at least considered. It's called postoperative hemorrhagic occlusive retinal vasculitis. If you haven't heard of this, it's because it was made up in the last year. So there was a paper published on this about a year ago and it's with 11 eyes from six patients from six institutions. And the common link that the authors have found with all these patients is they all had uncomplicated cataract surgery. So they didn't get fecotraps like our patient did. They had uncomplicated cataract surgery. All of them received viscoelastic and all of them received intracameral vancomycin. All of these patients had good vision on post-op day one and then they all had profound painless vision loss between post-op days one and days 14. They were all treated with systemic and topical steroids and people didn't know what was going on with these patients. These aren't all at the same institution so they weren't seeing a pattern. Each of these physicians, this is the only thing like this that they'd ever seen and ultimately they all pulled their data. But some people thought it was a viral problem so they were treated with a cyclovir. Some people thought it was an infectious endothomitis so they were treated with antibiotics but all of the PCRs and cultures, everything, these patients were really worked up thoroughly. Everything came back negative on all of them. They did not have an infection, at least if you believe the labs that they did. Some of them got vitrectomies. Seven out of 11 eyes developed neovascular glaucoma that was pretty profound, similar to our patients that was hard to control. The final vision was less than 2,108 of the 11 eyes and four eyes went to NLP. These were really nightmare cases. A lot of these patients had one eye done and not a lot but some of them had one eye done. They were doing great. They had the second eye done and then both eyes would go to NLP in the next week. So these were patients who were 20, 30 in both eyes and then they were NLP a couple weeks later and people didn't know what was going on. So all of these patients received vancomycid at a concentration of one milligram per 0.1 cc. Interestingly, no one ever in the paper mentions the total dose that they got so I don't know if they were injecting a total of one milligram of vancomycin into the interior chamber or if they were taking a one cc syringe and just injecting the whole thing. That's not clear from what was written because we friend of the Midas will inject one milligram of vancomycin routinely but I don't know if there's a limit to the amount that the eye can handle if there can be a reaction if you put too much in. The authors of this paper said that there is an entity previously described called leukocytoclastic vasculitis induced by vancomycin and that's basically a type three reaction. People can get rashes and fevers and they can feel really sick. It's not Redman syndrome for those who remember that. This is a different entity. So they started testing these patients for that. Three patients who were tested for skin sensitivities tested negative but this is more for types one and four reactions so people were kind of wondering if maybe this is related to this other systemic condition that some people have been found to have. So these are just some pictures from that paper of what these patients looked like postoperatively. There's some variety in the way they looked. This patient had more hemorrhages than some of the others certainly more hemorrhages than our patient had. Profound vascular dropout in the right eye and some hyper fluorescence of the peripheral vessels in the left eye. This one had more vascular sheathing than our patient had. Certainly macular edema was present. This patient I think looked a little bit more like our patient especially in figure B, which is a little further down the road. They had a lot of dropout and then this patient as well down the road they had more vascular dropout after that first inflammatory period. So that was this condition that would be on our differential. Yes, Dr. Mamelos. This condition has sent a shudder through the entire ophthalmic community right now. I have the displeasure of being on the committee for mascaras' side working with the retina people to put together a formal announcement about this which will be coming out really soon, simultaneously without my SCRS and the retina folks on this. What's really scary about this as you said is it's thought to be a phase three immune reaction. There's really no way to predict that the cases were when we dug further into it did not receive a toxic dose of ankylomysine. Okay. It really was just the one milligram in the .1CC. We put together a questionnaire that was sent out and since then there have been a couple of other cases that are possible for this that are being looked into. But the reason this is so scary, there's very big groups that are now using vancomycin, routine when it's your camera, the prophylaxis against endoplamitis and the Kaiser Group in California has used this in literally 100,000 people without having a reaction like this. But now that this is out and in the literature and the fact that it occurs, you can do one eye and have no complications and then a week later they're fine, you do the second eye and then they get this. People could go by that early fine and so that is scared people so much that this may actually kill vancomycin as a prophylaxis and your camera against endoplamitis and so that announcement is gonna be coming out very soon and we're gonna be very careful how to work that because of potential legal issues involved because if this does happen to happen and it comes out, I mean lawyers will jump all over this and you know about this and use this material anyway. So I'm not sure if this case you have fits into this. I mean I don't really have all the classic criteria but it certainly is a potential case. So along those lines, the biggest classic criteria is it doesn't have, thank you for the segue, is that vancomycin was never used on this patient. So that certainly would raise a red flag as to this being the diagnosis but at the same time, and it sounds like Dr. Mamelis, you may know of more cases than I do, I've been emailing a couple times with Dr. Jumper whom he mentioned out in California who at the time that I sent him this case really felt like it fit other than the lack of vancomycin and it hasn't been definitively shown that vancomycin really is the cause. Certainly vancomycin's a common link between all the cases that have been put in that report and I don't know if you all have more information than I know at this time, but there are lots of things about cataract surgery that were common between all these patients. You know, they all had viscoelastic, they all had presumably high pressures during the case. There are lots of similarities between these cases in addition to the vancomycin. Certainly the vancomycin is one of the more relatively recent additions to cataract surgery that would make it reasonable to assume that it's the cause and that's the reason that this has never been seen before the last few years, but, you know. I think we've seen it similar to this and this was many years ago, probably a decade and a half ago. There was a study we were doing with an extended release pellet that was going to be used for cataract surgery that was in a dissolvable polymer that would elude the steroid after surgery. You just put it in the eye and there were several people in this study that had a reaction very, very similar to this that was tracked down to something wrong with an immune reaction to the actual plastic vehicle that was dissolving this stuff, but again it had a reaction very, very similar. Weird stuff in the vancomycin. Right, so, that's, yes. That's a great question, yeah. And we actually had a journal club on this topic I don't know, six months ago or so in retina and we talked about that exact thing and that was something we discussed. We, I don't think that there is any published entity like this from an end of the minus, but that is the question is did this happen and we just blamed it on the infection, which is possible because we don't even see the retina for three, four weeks after those cases sometimes. But that's possible that maybe this has been going on. It's also reasonable to think about the fact that it's never been seen before because we do it routinely. Again, we always inject at least at this institution one milligram total, but Dr. Manwest was just saying that's really what these patients were getting. So that was one of the things I was wondering, but I guess that's not really up for debate. I spoke with Dr. Zabriski, he wanted to be here this morning. This is his patient and he is of the feeling that this was a sick eye to begin with with bad progressive glaucoma and she had a vascular event after high pressure fluctuations from the surgery and this is where she ended up, which is certainly still on the table. So just to combine CRVO, CRAO is another option and it's in a lot of ways more reasonable to think of it that way, but with this paper published we didn't want to ignore this. The final thing to think about would be minomycin C toxicity, because that was used in this case and that's not something that's used in regular FACOs. And there's really not a lot out there about minomycin C toxicity of the posterior segment other than causing straightforward central retinal vein occlusions. This report came out in 1994 of a combined CRVO, CRAO and a 45 year old five days after needling of a trabeculectomy with minomycin C. So it's certainly reasonable to think that this got into the eye. There was already a nice connection from the bleb to inside the eye during the needling procedure. I was texting with Dr. Zabriski last night. He had not entered the eye yet and he did the same thing he does on all of his other cases the way he's never had this happen. So his words were it's possible, but it's extremely unlikely seeing as how it hasn't happened on a single other one of my cases and I use minomycin on every one of them. So he thinks it's more of a combined CRVO, CRAO picture. But anyway, I thought this case raised interesting questions to my knowledge. I don't know, Dr. Mamelis, are they maybe you know this case already because it was sent to Dr. Jumper, but I don't know if they're still considering it. So they're two separate groups. They're doing it together, but we, as you know, we did a formal submission of this. They're aware of our case and their only comment, their comment was basically it looks like this. They said it looks like the definition of the case except it doesn't have any response. Right. At the end, there's maybe only one other that they have. Everything else is with my mind, with thank my son. So I'm gonna say thank my son. So, any other questions? And you know we did just to talk about, my first thought was this was an ocular ischemic syndrome for some, right? So she had her products worked up right away. I think, you know, we also ruled out during some of our writers a few other things, but it just, to me, it was very profound how bad this looked and how bad it went so quickly. Yeah, Rhys. So I'm not sure you didn't get the main question, but if you were gonna say that it was really FBA, why was there just such delay-filling like, because that was more like something. Right. And that's part of the debate. We don't have a great answer to that. But that, I think that they described that, I don't remember the specifics of every case, but in the paper they go through all 11 eyes and I think that that was actually mentioned in a couple of these eyes. They did have delayed-filling. So, I don't have a great answer for you. I don't know if whatever this reaction is of, whatever it's reacting to, if it's the vancomycin or something else, if it's able to diffuse posteriorly a little bit and cause inflammation, just posterior to lamina crebrosa, I don't know. Yes, Brian. In the paper, did all the patients who had it both eyes? All of them had it in both eyes. So the only people who had it in one eye were just dead in that surgery. Hers was only one eye, but her cataract surgery was long ago. Yeah. You know, there's, I mean, we've seen reactions to toxicity of too much antibiotic with it. And there've been cases of a severe task which then spilled over into a vasculitis when the pharmacy had mismixed the vancomycin. You know, people got 10 times the dose that they should have. And they got a reaction like this. We saw reactions like this in the past when people were using gemycin, intracamalase. Again, someone confused it and they got 10 times the dose and you can get a reaction of that. As far as I know, they couldn't track it down to the fact that this was toxicity due to too much vancomycin, at least in the case that they looked at. I mean, you didn't have the bottle there to analyze it afterward, but as far as they know there wasn't a toxicity from your 10 times the dose or something, this was supposedly the proper dose in each of these cases. All right. Anyway, well thank you all. Thanks for coming. Thank you.