 Okay, so she had no significant past history, except she had this pituitary adenoma, which had never affected her vision. And she was a bit unclear about how long the vision loss had been going on, but the best I could tell, it had been like kind of brewing for about six months. I first saw her on June 16th. She was 21, 25 in the right eye, 20, 40 in the left. Her pressures were good. Her optic nerves were very cupped. And you can't see it. I don't have any disc photos. You can kind of see it in the red free photos. Her right eye, especially the 20 over 125 eye, was like just completely cupped out. And the left eye wasn't much better. And I got a nerve fiber layer scan. And although her nerve fiber layer was pretty beat up, like you would expect, like maybe moderately bad glaucoma, I didn't think that that explained her acuity loss. This is what her visual fields looked like. Her visual fields look pretty much like glaucoma, except for the central scatomas. You can see her foveal threshold and the more severely affected right eye is 28. And that's not terrible, but it's definitely not normal. She'd already had an MRI of her pituitary because of the adenoma. That's everybody kind of jumped to the conclusion that the adenoma had grown, but it hadn't, the adenoma was stable. So I made her get an MRI of her orbits with contrast, which turned out to be normal. And so I thought, you know, she's got some sort of an acute optic neuropathy that's affecting her acuity on top of chronic optic neuropathy, which I figured was most likely low tension glaucoma. And we, you know, we worked, I did all kinds of laboratory evaluations for vitamins and heavy metals and inflammatory markers and NMO and MOG and all kinds of stuff. I mean, her CRP was one or a sedrate was normal. She had no symptoms of giant salarteritis. She saw Dr. Zabriski on July 19th. I'd sent her to him for treatment of her glaucoma. Her vision had deteriorated to 20 over 300 in the right eye. Her pressures were still good. I'd started her on some drops. And Norm agreed that this doesn't just look like glaucoma. There's some sort of acute optic neuropathy on top of her low tension glaucoma that, you know, explains her acuity loss. He got a 10-2 that day, which he thought, you know, looked like her optic neuropathy was on the move. And the thing that bothered me was that she's now got some optic nerve swelling in the right eye. You can see, especially here in the kind of temporal superior area here, that she's kind of perked up into the purple zone, whereas before that was a trophic. So I put her in the hospital and she got high dose IV steroids for, you know, a presumed inflammatory optic neuropathy. Dr. Patel did a temporal artery biopsy, which turned out to be negative. And she seemed to kind of stabilize. So she left the hospital, but then while I was on vacation, she called Norm and said, you know, I think I'm worse. She came back in, she deteriorated, to count fingers in the right eye and 2100 in the left eye, her pressures were still good. And so this time, Dr. C saw her and, you know, we decided to readmit her for plasmapheresis and IVIG, just because we didn't know what the hell else to do. And like we knew that there was something happening. We weren't quite sure what. This is what her Goldman fields looked like after she got out of the hospital. You know, it kind of just looks like central scatomas with generalized constriction, not really a glaucoma look, but it didn't really fit the picture of really anything, except, you know, we did entertain the thought that this was a maculopathy. And although I didn't show those things, her OCT of the macula looked pristine. We did a multifocal ERG twice, I think, that looked pristine. So even though it looked like it could be a retinal problem, her retina actually looked like it was working pretty well. And then one of the diagnostic tests that I had ordered way back in June, finally became available. And that showed that she had a G2A mutation at the 11778 position on her mitochondrial DNA. So this is a pathogenic variant for labor's hereditary optic neuropathy. Now, we usually don't think about labor's hereditary optic neuropathy in 70-year-old women, but apparently it can happen. This is an atypical case. A lot of people walk around with this mutation and never get labor's hereditary optic neuropathy. So, and that's kind of alluded to in the report. But in this case, it did, for some reason, suddenly become a case of labor's there. It turns out, I can't remember if it's in my notes or on my slide. Yeah, so if you do a literature search about atypical labor's hereditary optic neuropathy, there's some case reports of women popping up in their 20s and 30s with labor's hereditary optic neuropathy. There is just some scattered reports of people with low tension glaucoma walking around with these mutations. It's not clear if it's pathogenic in that case or just incidental. There's also a lot of talk in the literature that I reviewed about environmental triggers. And the ones that we think about typically are alcohol and tobacco. And in my patient's case, she does not drink and does not smoke. There's also talk about, let's see, this is all in my notes. Other triggers. Oh, antiretroviral therapy for people that either have HIV or at risk for HIV, those can be triggers for people that walk around with labor's mutations. And I think I feel like there's one other one that I'm not remembering, but she just didn't have any of those triggers. Again, we went back through her family history, you know, his family history of blindness. So I just think this was a very unusual case. It's really, we're really lucky to have genetic testing available. Like when I was doing my residency, this was only available as a research test. And at least now it's commercially available, but it's still very slow to get results. And in the meantime, this lady, you know, had two hospital admissions, high dose IV steroids. She had to have a port put in for plasma exchange and IVIG. We did all these tests and treatments were in retrospect unnecessary. It'd be nice if these commercial tests would be a little bit quicker in turnaround. I think that's all I had about this. Yeah, that's it. Dr. Warner. Oh, I did not remember that. Okay, so for our home audience, Dr. Warner was pointing out that I sold around his use for alcohol, abuse prevention, can be a trigger. And off the top of my head, like amiodarone, but it's also a mitochondrial toxin, although I've not seen any sophistication reports. Dr. Diggory. Yeah, so in Europe, treatment has been, I did have a known and I did only treatment that we know of right now for laborers. In this country to get it, you have to do, you have to go online and buy it online. Dr. Diggory is pointing out that Idevanone is the only effective therapy. It's more popular in Europe than it is here. Like you can print it online. And that's actually what my meeting did. She's taking Idevanone. Idevanone is a Coenzyme Q10 analog and it's not the support and PTP production in the mitochondria. And but it's really in some people, it seems like it makes it better and other people it doesn't do anything. It's not fair if that's a natural history of the disease. So some people do small things to get better labor, which we usually do, but she is taking Idevanone. Is that a hard to say? Yeah. Yeah, you know, as a glaucoma person, this is like super stressful, cases like this. This is like what we hate to see, you know, because glaucoma is really like a diagnosis of exclusion in the end for us. And so, especially these normal tension cases are so hard. And so I just was thinking for the residents, maybe like, I have, so I have a bunch of questions about it, but one, like thinking through what made us feel confident this isn't glaucoma. So the early acuity loss, but you can get that, but then it was really progressive, right? It went through the line. Yes, for the home audience, this Dr. Stag is pointing out that, you know, these types of cases are also a source of heartburn for glaucoma specialists because the attention glaucoma especially is a diagnosis of exclusion. And then the thing that really took Dr. Zabrisky and I off was that OCT where her optic nerve was swelling. And, you know, with, with labors, you can get swelling of the optic nerve as part of the disease pathogenesis. It's mild. But I think that's when Tick decided to the fact that there was something on top of what appeared to be low tension glaucoma. Was the swelling there from the very beginning? Or was that? No, I will show you. Although you could argue that there was pseudonormalization of that optic nerve initially because I mean, it looked terrible with the OCT with normal, which is, or almost normal, which is kind of like you think, how is it? But the swelling in the presence of thinning can be really, Like that, like there, you know, you could look over at the left-hand side there. I can't tell, I think that might be superior. But, you know, there shouldn't be anywhere in that nerve based on just the picture. Right, right. Where it's coming out as normal. So in retrospect, you could say, well, maybe that what, maybe it really was a little bit swollen. Yeah, my, it was too nice. Yeah, so if you look right here at this, I think it was the superior centipural area or maybe the nasal inferior area, but if you just kind of keep that in your head. And also if you look at like the, it's just the scan of her retinal nerve fibro layer here. And then I'm gonna go down to the slide where she came back into norm. You can see that area is definitely, I mean, there's no question there's swelling going on here now. So I think in this case, it was a little more dramatic. I mean, that's really what tipped us off. Right, yeah. Really interesting case. And then, you know, one question is what to do with her eye pressure going forward too? Yes. And that's, you know, just from a glaucoma side, that's like, we worry about, because I think she probably has normal tension glaucoma too. And then do we need to keep like the, you know, get single digits pressure just for the sake of that? So I mean, that's not her case to know what to do going forward. Yeah, you know what she, you know, because she was so, you know, well, she asked for a second opinion and I sent her to operators to do like a labor's made at USC. And he agreed with the diagnosis, but he actually didn't want her pressure to be in the single digits, which is where we didn't put her. He felt like that, like there's some controversy about, you know, about it not being just a matter of intraocular pressure, but the mismatch between intracranial and intraocular pressure. And he wanted her more like around 10, 11, 12. He felt that having her pressure super low like that could very slow the optic nerve maybe cause her labor to progress, but it's just so that they can weigh in her. Yeah, so while I'm at it, I'm going to do it later and drive her from here, I'm just going to put up race. It's nice to have someone to take that. Yeah, yeah. Okay, and this will go to Dr. Warner. One other thing, I think that, I think that we can all recognize labor's often in retrospect when it happens in the classic situation. Yes. I don't think we have good ways of recognizing labor's when it's presenting really atypically like this. I mean, it just doesn't spring to your head immediately. And I also think that the clinical features of these labor's plus maybe or labor's weird are well described. So I think it's entirely possible that the slowly progressive operability that she had before, which manifests by her severe cupping, that could also be a manifestation of labor's. We just don't know it and recognize it yet, which brings us to this problem. It's coming up later. It was a really interesting question. Yes, for the home audience, Dr. Warner was just pointing out that these atypical cases like it wasn't happening in women or that happened later in time, but when there's no environmental trigger and may not have the typical clinical features that we're accustomed to, like the demographics, but also like the visual field effects of the optic nerve of parents. And it's possible that her optic nerve cupping is just another atypical amount of stage labor's is not low-tentable. I'm actually not sure how it will ever I don't know the difference. There is in one study, I didn't see where they took like, I can't remember like a handful of low-tentable opoma and tested them all for labor's mutations and they all came out to normal. You know, for what it's worth. Dr. Sagan. So our case is said to have opoma and labor's. There are, yes, there are cases where patients have both opoma and labor's and it's not clear if the labor's mutation is anything to do with their opoma. Dr. Sagan, have a comment. Yes, sir. One more question. So, I'm just thinking of other things on the differential and like a CNS lymphoma or something, would that have shown up on the MRI? Or would you, is that, I'm trying to think, would you need like a, did you do a lumbar puncture? Were you worried about anything with that with the, like the nerve swelling like that? Yes. Dr. Sagan is asking if CNS lymphoma will be on the different bone, you know, an optic or, you know, a acute on chronic optic neuropathy and a lot of the top of my head and almost like we did worry about that. It doesn't always show up on an MRI and I'm almost certain that we did a spinal tap during her second admission. Pretty sure, because we were just, you know, so desperate. Yes. I see that's the, maybe you did the glaucoma module premium addition. Did you get a ganglion cell layer of that? Did you get an image of that? That might be interesting to see if it looks in a classic glaucoma test pattern. Right. I'm not, I don't. That would be fun to look at. I guess the norm did for ganglion cell layer. It's probably in there. You have to sometimes pull out that report. Yeah. So it might be really good to look at that. And then how is she doing? That was the other thing. She's stable. She's about, I count figures in the right eye at 2,000. It's a lot better. Her pressures are good and her feel is stunned. She's not, she hasn't progressed. She still does. No, I don't think she'll be, she's a, well, I don't want to say too much. There would be like PHI, but I guess we're all in a contained room. She's a neonatologist. I don't know. She'll be able to go on and on and on and on. Very receiver-oriented spectrum. So I think I encouraged her to go on and on and on. Okay, this is a good segue to Dr. Viginta's presentation about glaucoma. How long has this been on for us? All right. So you and I are sitting on the edge of our seats. I found the cure started about seven, eight weeks ago and every case I see I'm just like, am I right? Do I get it right? So there's a lot of things that happened on the edge of my seat, but I figured like this would be an interesting topic to talk about. It's segueing from Dr. Katz's topic about, you know, was this glaucoma, whether it's not glaucoma when you see pretty severe optic neuropathy in patients. And so this topic came up when we were discussing in our morning meeting about how we do get referrals in neuro-ophthalmology regarding like end stage glaucoma passively that continues to progress or is difficult to treat or has quickly progressed in one eye. And we wonder, is this just glaucoma or is there something else going on in addition to glaucoma that's causing non-glaucoma this optic actually. So we have a patient who presents like this when we have this end stage, sort of very severe atrophy of both eyes. This is our Brooksman brain minimum rim width scan here showing pretty severe atrophy in both eyes. And you have this periapapillary atrophy, this nasalization of the vessels, but then this patient, you know, is referred from glaucoma because maybe they're not responding to treatment in the way that we usually expect. We're not sure if they should be, we should consider surgery for them. Maybe they have some neurological symptom that they're also presenting with this time around. So then they're referred over to neuro-ophthalmology and then that's what this presentation is about. What kind of workup do we do and what is the pathophysiology maybe of this cupping versus a pallor that we see? So the question is that we came up with in our meeting in the morning, our usual morning meeting is should we have some sort of protocol for these referrals because they do seem to come in regularly. This is just a picture from Dr. Degrees' book which I thought was really cool. So we have protocols in neuro-ophthalmology because we love protocols. We have a CRAO protocol, I have an IIH protocol. There's a newer one that's been released since I was last year, which was trying to figure out the difference between optic neuro-pipoplasia and some patients in pediatric patients versus optic atrophy. So maybe we can come up with something that helps streamline this process for these patients as well. We ultimately wanna know for these patients, do we have the diagnosis correctly? Are we missing something and how can we preserve their vision? What is the proper intervention also? There's also this thing lingering in some people's minds in the back where are there medical legal issues of missing a diagnosis, right? So in this 15-year study that was published in 2013 as a UK study, but the largest mean payout, so the largest payouts for medical legal insurance claims was due to poorly followed intracranial tumors that were causing visual field changes. I mean, the largest chunk of payouts were still due to retinal or knee cataract surgery issues, things like that, but individual payouts, this was the largest group. And there's also the possibility to think about when these patients are referred is there more than one pathophysiology going on here? So is there normal tension, glaucoma and labors, for example, or are those on the same spectrum? So it's clear for us, in general thinking and our teaching that non-glaucoma issues usually present with like pallor, usually they're younger patients who have poor acuity, centrally poor color vision. And then on the other end of the spectrum we have the glaucoma patients who have clear cupping, maybe they're older age, they have preserved acuity, that's more, they have some asymmetric cup to disc disease, things like that. But there's all these patients in between that we don't always know if there's more than one pathophysiology of their disease or if there's something else going on neurologically, it's causing non-glaucoma is optic atrophy. And the differential for what we look at is pretty broad, for non-glaucoma is optic atrophy. So we think about ischemic causes and this is more acute changes that we see or in radiation more chronic changes. Retinal disease when patients present with severe retinal disease because of ischemia to the retinal or coroid can eventually lead to optic nerve pallor and optic atrophy. Of course there's de-melanating issues, eubiotic causes, retinal dystrophies, inherited ones themselves can result in optic atrophy. Infectious causes, infiltrative, so we do like CSF studies to look for this as well in imaging. There's compressive issues, and of course trauma nutritional toxic. We've talked about a couple of medicines already that are more susceptible to affecting the mitochondrial function. And there's a long list of toxic medicines that can result in optic atrophy. Genetic causes, of course we don't, we always cannot keep that at the end of our list because we wanna make sure we rule out all these other things that are probably easier or possibly things where we can actually intervene, but we don't wanna forget about genetic causes. And of course there's always, I always think about congenital as well because these patients sometimes they're always this way, have always been this way, but they're just interacting with the medical care system for the first time and someone's like, oh, that's pathology one that has always been that way for them. So you have a lot of clues. So of course, a glaucoma initial visit is very extensive and neuro-ophthalmology visit is very extensive, but we ask different questions usually. So the history is a little bit different, the examination, what we do next as far as testing is different. So one thing, I saw most of the, I saw patients with who were referred for this issue mostly as a resident and a neuro-ophthalmologist. I haven't had personally like any referral sent to me yet, but I've reviewed about four cases that were sent to me from the our neuro-ophthalmology attendants. So history of vision loss, it's important to ask if there's been any sudden or painful vision loss that can be a clue. Any associated neurological symptoms, of course that can be a clue as well. Especially when you're thinking about any sort of like Spino, Cerebellar, Ataxia, things like that and looking for that as well. Other corneal neuropathies help to figure out if there's any localized lesion somewhere else. Digging into their vascular risk factors is important. Looking into family history, personal history of autoimmune diseases. Anemia or surgery with history of hypotension can lead to like a posterior ischemic optic neuropathy. Bariatric surgery is something that I don't always remember to ask about, but I was making this list of like, if you remember to ask about this because of again, nutritional issues and deficiencies or poor absorption. Any history of radiation because delayed optic neuropathy can present, even of course like years, two, three years after radiation exposure to the head. Trauma and infection. So these are just again, more things we ask about. So in medications, we do a very extensive review of their medications. So when I have a patient coming in with disc swelling or atrophy, I'm not quite sure I have a diagnosis. I literally have to do PubMed searches of every single one of their medications they're on just to make sure there hasn't been something reported or an association with optic atrophy because it's just so extensive. Social history is important as well. I sometimes ask, sometimes our patients also are from the boonies or other remote beautiful areas around here. So they have exposure to well water so it's important to ask about that. And then family history of color vision loss and other ocular diseases or autoimmune diseases can be helpful. So we know that cupping is obviously associated with glaucoma but there are many exceptions to cupping being associated with other types of non-glaucoma disoptic atrophy, including labors that is on the list and compressive optic neuropathy. So like meningiomas can sometimes cause cupping in addition to pallor. For some reason, we don't know exactly why unless someone else has another thought here it can explain. Areridic ischemic optic neuropathy rather than non-areridic seems to cause cupping more often. And then congenital optic disc anomalies are important to keep in mind. So does this patient already have some cupping at baseline and then now they have an optic neuropathy something to consider? Now my optic atrophy as well can present with cupping. And then this is a picture right here of methanol poisoning. So this is a pretty severe cupping that you're seeing here in addition to pallor. I can really see that laminar really nicely. So we know why pallor happens and this is again from Dr. Degrees' book I just put a picture of her from a front stage here instead of putting this ideation but I think it's a really nice picture of why we see a pink optic nerve. Initially, which is, you know as you see in this picture this is a normal optic nerve up here the nerve fiber layer and the vessels when light is shine on them it gets to appear pink. And then as there is death of the fiber layer that area is replaced with these astrocytes and glial cells that actually are opaque. So you have that white reflective appearance of the nerve rather or opaque appearance of the nerve rather than a nice pink color. But do you really know why cupping happens? Especially since there are so many different pathophysiologies of patients ending up with cupping. You know, the theory is when someone has high pressures we think maybe that intraocular pressure is compressing the posterior ciliary arteries especially at the lamina and maybe there are some connective tissue issues where, you know which is why we measure like corneal hysteresis. But don't really know exactly why cupping happens especially when there's normal intraocular pressure. In the, in looking at the optic nerve when these patients present there are many features that we typically learn that are related to glaucoma essentially. So we look at the nerve fiber layer defect the pattern of the nerve fiber layer defects. We know that when we're looking at the neurorentinal rim that's probably the most useful area to look at and the most specific area that's affected in glaucoma. So obliteration of that rim is very specific for glaucoma. Thinning is not as specific as still important. You see that typical nasalization of the blood vessels that long vertical cup and backward bowing of the lamina. And then of course asymmetry in the cup to disc is something we're taught early on. Hemorrhages at the disc, small hemorrhages usually and that peripapillary atrophy that we also see like in myopic eyes as well. The visual fields are also of course very helpful. So again, the classic teaching is that we see in non glaucoma this optic atrophy or in non glaucoma this visual field defects that there is like visual field defects that are approaching the vertical midline. And especially if there's something homonymous of course we wanna do some imaging to look into that. Altitudinal defects, so like we see in NAION are also more typical of non glaucoma this having an enlarged blind spot, a central scotoma or a secosentral scotoma, having severe loss of color vision in one eye especially and then a more significant pupillary defect a fan pupillary defect in one eye is also more of a clue. But even as you know in glaucoma there can be asymmetric RNFL loss and a fan pupillary defects. Some glaucoma we feel that like the RNFL is preserved at the papillomacular bundle whereas in non glaucoma this or direct like mitochondrial issues with the optic nerve we see the papillomacular bundle which is a high energy use area is often affected causing those like secosentral and central scotoma. So now I wanna move into here what do we know that's new? What are some new clues that can help us with the diagnosis? This isn't necessarily like mind blowing by means but this is what's been published recently. So it's always fun to look at how new tools can help us, right? So we have these Brooks membrane opening minimum rim width scan that actually Dr. Stag introduced me to when I was a PGU I4 and we started using it in neuro ophthalmology as well. So when someone has a very, very thin neuro retinal rim or when they have myopic eye then it's hard to tell like, is there a significant atrophy or is there a preserved rim? It helps to get the scan and there have been studies comparing what does that rim look like when we do a ratio of the rim thickness to generalize like peripapillary RNFL thickness we do that ratio we find that the rim of course is as I was saying more preserved in patients with non glaucoma this optic atrophy like an NAION and it is thinner in patients with like normal tension glaucoma. I'm gonna show you a picture of that. And then the other thing I'll talk about is OCTA as well. So in this study that was published in the neuro ophthalmology journal back in back in 2020 they looked at, I had edited this image so it's just a little easier to follow here. So we have in this column Brooks membrane minimum rim width reduction and then the peripapillary retinal nerve fiber layer thickness reduction and the patterns that they each had an NAION and open angle glaucoma. So in these patients there was a pattern to where the thinning occurred and it was similar in their rim and in their peripapillary RNFL. So as we expected in glaucoma superior in your thinning and then in NAION a little bit more of a maybe a little bit more autitudinal like it's more in the superior and then a little bit nasal as well. When we see these really helpful graphs I felt from that from that article where they compared again this is you can't see it over there when it's over but this is a GMRW meaning the global minimum rim width. So when they looked at the global minimum rim width for NAION patients we'll just compare this section with the opening of glaucoma. This is compressive optic neuropathy which was they felt like was not as useful of a measure. So we ignore that right now but the minimum rim width was preserved in the NAION patients where it was significantly like more lost in the opening of glaucoma patients. And when you look at their peripapillary RNFL thickness there's quite a bit of thinning of the RNFL thickness and again thinning in opening of glaucoma and NAION. So you can see the ratio here would be different where the minimum rim width is higher and preserved in NAION compared to opening glaucoma. So that's a very important area for us to look at. And this is an example case from one of my colleagues. So this is a patient who was referred for do they have glaucoma or something on top of glaucoma that's also causing their optic atrophy. In this scan, this is their minimum rim width scan and this is their RNFL thickness. You can see again just by the colors just wanna just generally give you an idea quite a bit of thinning of the minimum rim width more in comparison to the RNFL here. So it's just one example case. Another study looking at OCTA these investigators looked at the coroidal micro vasculature right around the optic nerve. And so in this picture, I want you to try to focus in on this area. It was hard to see, I had to zoom in pretty a lot when I was trying to look at this but they're highlighting in this picture that in a patient, this is the top column as an NAION patient, the bottom column is a normal tension glaucoma patient. Sorry, bottom row. This right here is outlined in the red is showing that there is some coroidal micro vasculature thinning here on OCTA more in the NAION patient more so that then there is in the normal tension glaucoma patient. So now they looked at just a small sample size overall but they thought that that was significant in this study. But it's not a slam dunk always. These are just studies that look didn't necessarily and the problem with both of these studies is that they didn't have a control for like how severe was the glaucoma and the patients with glaucoma. A lot of variability there still. So once we've looked at the optic nerve in detail, then we think about, okay, looked at the history of the optic nerve in detail, what other testing can we do? There is a lot of potential testing we can do in neurophthalmology. So it's important to try to focus it and not put the patient, you know, drain them of all their blood and CSF. But the things to look at are if there's any symptoms like a ladies' infection, autoimmune, serum protein electrophoresis, vitamin levels especially, like even we think about vitamin A and vitamin E, B12, B6, but also niacin has been associated with optic atrophy, heavy metal. We can test for perineal plastic antibodies. Again, that's like something that is worth testing and someone who fits the right demographic a little bit older, maybe may or may not have a history of cancer, but we're concerned about it. We can do, you know, evaluation by scanning the appropriate area, sending them for appropriate cancer screening. And if there's still, if there isn't another cause that we're finding it's worthwhile testing for perineal plastic antibodies in these patients. Lumbar puncture can also be used to test for multiple things, including cytology and cytometry, especially if we're thinking this patient might have an infiltrative lesion like multiple myeloma or lymphoma leukemia. And of course, I wanna talk about genetic testing briefly. This is one of the last things I'll touch on. I talked to Emily Spoth, our genetic counselor about how she recommends that we approach this. And she always has great, like different tricks and tools to help make the testing more affordable for patients. So one of the things she suggested is that if there's no paternal inheritance of vision loss as far as we know, then a great place to start is with the Spark retinal dystrophy panel. So as you know, it's like 330 gene panel that is free until about January 2023. It includes some optic atrophy genes or genes that have been associated with it. And if that comes back negative, then for free we can add on with in vitay testing can add on additional, like an additional optic atrophy panel. So that's a great little trick that she's found. If there is a possible paternal inheritance or we don't really know and we're interested in looking at mitochondrial inheritance then blueprints, genetics, optic atrophy panel cover 76 genes that can be captured, labors and other mitochondrial issues, dystrophies. And then there's also blueprints also has a neuro-othemology panel as well as covers even more genes. So considering again, back to the idea of maybe a protocol as you can see, there's quite a variety of things we have to try to cover for our patients if we're thinking about why could they be developing some non-glocomatos optic atrophy but oftentimes we can find like maybe they were referred for a particular reason and we can dive into that history of get those relevant labs and then neuro-othemology referral is helps to kind of piece everything together spend the extra time needed to coordinate all that testing and lab work. That's where I'm gonna end right now but any questions or any thoughts on? Yeah, Dr. Dag. Yeah, I was just gonna say I think a protocol is a great idea. We should maybe talk more about it but these are really, really stressful cases for us and there is a lot of normal tension glaucoma. I think maybe in a way they're didn't used to be but like we see a lot of normal tension glaucoma and it's a lot of it's really severe. And so yeah, coming up with some sort of protocol or the best way to handle it because a lot of times our question what's stressful with normal tension patients is a lot of times our question is whether or not to do a big surgery like a trabeculectomy or something else. And so, and those are like risky surgeries and so there's, we don't wanna do it for someone who doesn't need it. So yeah, I think that would be really helpful. Absolutely, yeah. I'd love to talk about that too and we can discuss with you and bring it back to where you're at and get some ideas together on our protocol. Could be a great QI project for somebody. I'm gonna work with you. All right, well, I'll step down and then Dr. C's next. So this is gonna be just a quick update on an upcoming clinical trial that we're gonna be participating on the IAH evolved trial. So as most of you know, IAH has significant morbidity, reduced quality of life and both the headache and vision standpoint. We've gotta see those all the way which does have evidence for it but can be quite intolerable. People get the nummies and tinglies, some loose stool. So some people end up not taking it and not good for their IAH. You know, we have surgeries but we reserve this for people with severe vision loss due to complications, high failure rate. So bottom line is we need better treatments for IAH. And I know you all are wondering why aren't we using these gut neuropeptides to treat IAH? Well, we are. So the GLP-1 which is glucaon like peptide-1 is known to stimulate insulin release, helps control glucose in patients with diabetes, also helps weight and appetite control which is very important for IAH. However, it's also believed to act on the coroid plexus to reduce DSF secretion, hence lowering ICP. So potentially many benefits from this medication for patients with IAH. So xenotide is an example of a GLP-1 receptor agonist medication has been shown to lead to weight loss in patients either with or without diabetes. It's actually been around since 2005. So we have a lot of experience knowing its safety profile. Precendent is a formulation of xenotide that's been developed for IAH. It's different because it's extended release which creates a lot of more convenience with dosing. And that's why Precendent is gonna be used in this trial which is going to assess the advocacy and safety of Precendent in IAH. So the primary objective of the study is really looking at intracranial pressure after 24 weeks of being on this medication. However, there's many secondary objectives such as Humphrey visual field, mean deviation, the degree of their optic discadema is measured by OCT, their headaches, their acuity and then how many patients have treatment failure. So this is a randomized placebo-controlled double-blind multi-center trial. Goal is to enroll 240 patients with IAH and they'll be split into placebo versus those receiving Precendent. Goes for 24 weeks and then the outcomes are measured. Inclusion of patients, so these are adults over 18. These are newly diagnosed IAH patients and they have to come in within four weeks of their screening lumbar puncture. They gotta have bilateral optic discadema. And importantly, this is mild IAH because you'll know that there's that placebo-controlled arm so we don't want people losing vision on placebo. They gotta have headaches and then not be pregnant. Some exclusions, so they can't have secondary causes of elevator pressure like masses or venous sinus embossies. And then they have to not have been on treatment to lower their pressure within a week of screening. Can't have any other ocular diseases and they can't be on any other glucose lowering medications since this is a glucose lowering medication. And they have to be able to perform subcutaneous injections because this is a once weekly injection that they do themselves or someone else does for them. So very brief highlights, but not yet enrolling. Not exactly sure when but in the next coming months hopefully. Questions about this? Dr. Warner. Yeah, I'd have to, right. Yeah, I need to, so the question is how many of our patients can't do assign medications? Can they be stopped for a week and then enrolled? I do need to double check that but the exclusion criteria does stay within a week of a lower punctured sign. I think, yes, but I double check. Yes. I'm not very familiar with these medications but are they the ones that are also being used for weight loss? Yes, the question was are these medications being used for weight loss? Yes, they're being used for diabetes or weight loss in general. But like I said, there aren't animal studies that show that they lower ICPs so potentially they're very beneficial for IH. So a patient report, they said that their doctor was trying to get it approved for weight loss. And so I think that by inference they're quite expensive and the insurance companies are not psyched about them being used for weight loss. So they create sort of burdens of criteria. Yeah. My friend who's a pharmacist has said there's like a huge black market almost for these. They said they're like, you know, it's like more than opioids, people are like forging prescriptions for them now. Forging prescriptions. Wow. For those wanting to gossip, there's due to insurance problems for weight loss, that they need these for weight loss alone. Apparently there's a black market for this. So, be on the level. Is that a question from Chad? So the question is, why did they decide to use C-book control rather than non-imperiority? I think that's compared to that C-book control line. So they, I don't recall the exact reason for why they're not comparing it to C-book control line. I think they just want to see if it's working for IH. But it was felt to be safe to have a placebo-controlled arm because it's mild IH. Just like the IH treatment trial had a treatment arm and then a placebo arm and that was mild IH. So we do have the option of treating patients' headaches in the placebo-controlled arms with any migraine medication, or they start to deteriorate. We obviously take them out of the trial and treat them as they normally would.