 So I'm Christopher Ricks, I'm one of the first-year residents. I'm going to talk about active fever, visual pathway, and glaucoma. So a quick question I want to address is how extensive is neurological damage from glaucoma? Is it end of the optic nerve with a large cup to disc ratio? Or does it go farther back and how far back? So to start with the case, 87-year-old woman referred to both retina and glaucoma, past medical history of glaucoma, hypertension, diabetes, hyperecademia, as well as a few other things. Her past doctorial history, so glaucoma has been very well treated. Diagnosed back in the 1980s, astute exfoliation glaucoma. She had feco-travel and right eye, SLT in the left eye, 713. There may have been more things that happened in between there and when the epic records started kicking in. We had a trav done. And the left eye says 14, SLT in the right eye, blood revision in the right eye. A lot of different drop regimens over the 30-plus years she'd been treated for glaucoma. And in April 2016, it was felt that her visual acuity and her visual fields were stable. Vision was 20 over 30 and 20 over 20, and IOP was well-controlled. Then in December, she started feeling that her visual was worsening, so she was referred to both retina and neurochromology. So you can see her visual fields from 2013 when we first had access to the visual version. And then in 2016, some minor changes, specifically the left eye and the super nasal field and then centrally in the right eye. So she was seen in retina in April 2017 and it was felt that she had macular degeneration, very, very mild, not enough to explain the changes. And they agreed with the neurochromology referral. You can see her OCT vermiculitis, generalized thinning of the entire macula. So then in May, she was seen in the neurochromology clinic. Chief complaint was that her vision was worse. She would say her own self-visual acuity check, which she'd walk out every morning and she'd see the mountains from her front porch. And I felt like the tops were sort of blurry and that was kind of the main thing she had noticed. So visual acuity had dropped to 20, 15, 30. IOP was still well-controlled and no APD. Color vision was not good at all. And then stereo vision was poor. Enter your segment was relatively normal. She had cataract surgery. Post-ear segments, she had quite a bit of cupping in her optic nerves and then some RPE changes throughout the retina. She can see the visual field that was done. Regression of that superior nasal field and then the central area in the right eye. And OCT of the RNFL was done. It showed generalized thinning as we'd expect. And in neurochromology service, like we said, we'd lift the MRIs, could always do. And we noticed that her chiasm was very, very small compared to a normal patient's optic chiasm. You can see quite a bit of thinning there. So if you can see the optic tract, what a very, very thin and tenuated versus the normal optic tract is quite a bit more robust than in the normal control patient. So our impression was that she had atrophy of the visual pathway secondary to her chronic glaucoma. We recommend to continue to treat the glaucoma and then also managing her vascular risk factors. Remember, she had all of them essentially. So what does the literature say about this? In a paper by Kashiwagi et al. in Journal of Glaucoma 2004, they did a study on 31 patients with advanced glaucoma, 26 healthy controls, the age and gender matched. And their conclusion was that MRI and the anterior visual pathway may be a good tool to for evaluating glaucoma and its damage objectively. Specifically, they measured smaller optic nerves in glaucoma patients. The height of the optic chiasm was thinner in glaucoma patients. Although they did say in their study that the height of the optic chiasm had a low correlation with the cup-to-disc ratio. In the British Journal of Radiology study by Kitsos et al. 26 patients with advanced glaucoma, 26 controls. Their conclusions were that PoEG leads to optic nerve atrophy and degeneration of the entire optic pathway. The finding of increased numbers of white matter and hyperintensities in the brain of patients with PoEG suggests that hypoprefusion due to microangiopathy may play a role, basically suggesting that maybe there's other things besides just increased the eye findings attributing to this atrophy of the entire pathway, including the optic nerve. So they found optic nerve atrophy, degeneration of the chiasm, and they even found degeneration of the occipital cortex, white matter, and then all the microvascular changes. In a study done by Zeng et al. They found that patients with normal pressure glaucoma have an HGestive reduced optic nerve diameter, optic chiasm height, and LGN volume as measured at MRI, and this correlates with the reduced RNFL thickness. So you can see a graph here of some of their data showing 15 millimeters behind the optic nerve. There's a great correlation between the RNFL thickness. And then different measurements, 5, 10, and 15 millimeters behind the eye. There's quite a bit of difference in the optic nerve diameter. They suggested even that MRI may be applied to examine the optic nerve in patients with glaucoma with opaque optic cancer, suggesting that's another way to monitor their glaucoma. In a way at all, it suggested that they saw widespread CNS abnormalities based on the diffusion tensor imaging. Basically, all these studies are coming to the conclusion there's damage throughout the whole entire system of the optic, the visual system. So a few questions that I want to address and to quite a few experts in the room. First one is what role does glaucoma play in actually the visual pathway behind the optic nerve? I'd be curious to hear some of your thoughts. I know Dr. Roscoff talks about how glaucoma is felt to be a vascular disease in some patients. I mean, I think your level of damage will be proportional to the amount of, the gain in the cell goes a little bit to the body. So we've always kind of had this theory that in the nervous system that if the disease is in cell system packs, that everything else kind of stays there. I call it the light socket theory of vision. The bulb is gone and everything else is ready. You just screw the bulb back in there and it's fine. And frankly, the core work that's been done on this, that the Saint Peter Manchin recognizes our own brother Mark and Brian Jones who sat there and shown, no, the wreckages doesn't sit there. If you knock out Bob Rods and Combs, the wreckages say, okay, all right, we're ready for some of the Rods and Combs. It generates extensively, and it continues to do so. It works itself into an atrial-fig, self-stimulating series of cycles. And the very work now done shown that that continues on through the process, the visual process, that the nervous system likes to be stimulated, and I'm part of an example of that is why patients with macrogenerations get these formal hallucinations. Those are self-stimulatory type processes that are ongoing, and that's part of the whole system. So I think, again, it's amazing how that still is out there. And there's still people pushing that room-nice pigmentosa that the retinas otherwise just say, ready to be wired up. And yeah, you can get it. First sex, you can stimulate with enough energy to get something, but you don't just have the system sitting there ready to go. And that work now is for those who understand core physiology is not well accepted. One of his first proposed by Robert Markey was roundly excoriated as being a horrible thought and not possible. And the rest, I remember Jean Duvall, when that was first presented, I was sitting next to him and he just said, well, I find that very offensive. And there is, there isn't. So we gotta be careful about how we get involved. So I don't see this as any problem. I, here's my thought in regards to this work about the fact that umber scan is a good way to tell the virus to glaucoma. It's about the same as saying, death correlates very well with big deal. If you need an MR scan to know, you've got glaucoma. You've been missing some really serious things for a long time. And so, you know, is there enough damage done if you're knocking on the gang in the cell as you can probably see after the award? I'm sure. And that's, that shouldn't surprise anybody. If you're knocking on the entire stimulatory pathway from the eye, that results in changes. I think from Brian, from Grodner, Mark, from Landry, the answer to that is yes. That the visual pathway itself is gonna be impacted. So I don't, you know, I think it's a kind of, what would you expect more than, well, this is a head scratcher. And it's amazing how continuing people don't realize how the nervous system responds in a very aberrant way. It's not getting the stimulation. I was just gonna say, it also is very interesting because it shows the presence of cell-cell interactions. So there's the neural to neural or probably the questions I get for you, and would you find any evidence to the treatment of it? I didn't find anything about that, no. It's a good question, no. Well, there are certain conditions like, for example, diabetes is metabolic memory. You have where if glucose is out of whack for a long time, then even when you get it back into control that there was damage done, it doesn't seem to be the treatment of it. So it would be interesting to know what happens if there is an ability to sort of reverse some of it. Yeah. Just got to my friend, he's going to just kind of prefer this about the MRI, it's kind of a call combination. I could say, typical situation, the nerves don't follow my book. It feels like there's a pretty straightforward, so $2,000 MRI scan, but where are you going to give us the same indication or? If I remember right, she'd had a fall, I think, and so it wasn't done for this. We just happened to have access to it. Sorry, this is the very beginning of your case, but this has become a not terribly uncommon neuro ophthalmology consult request. That somebody gets a scan for some of the reason and the radiologist says this person looks like they might have high internal pressure or this person has dilated nerve sheath or the optic nerves are asymmetric. And so the person who ordered the scan gets that report and it causes somewhat of a hullabaloo and then nobody puts all the pieces together and says, well, could somebody just sort of think about how this might actually just be the case? Yes, they had a traumatic optic neuropathy 30 years ago and their right optic nerve is atrophic and thank you very much radiologists for letting us know, but we kind of knew about that. Thanks a lot. It's like when the radiologist calls to tell me that somebody's got papillodema and I say, thank you, that's very helpful, that's kind of why I ordered the scan, but yes, thank you very much, I'm glad you can see that. But there's been this intersection of radiology has improved phenomenally in the last 10 years and they can actually see this now. I mean, you wouldn't have gotten any calls like this 10 years ago because they wouldn't have been able to see the subtle finding and so now it's just something that we're having to kind of understand as almost like a technological advance. This is not, obviously, how you diagnose glaucoma at all, at all, because it's completely nonspecific. Every optic atrophy will cause the optic nerve to look small, but in case you want to... And it's an advanced finding, I mean, this is something that happens after one thing. And I answered one of these questions, by the time the optic nerves are looking small in the MRI scan, I don't think that anybody in the glaucoma world at current treatment capacity feels like that's anything even close to reversible. What you would hope is perhaps that you could stop it from getting worse. I put that to the key there is current, because there's a lot of research in this area and I think there's holes in the future. I don't think anybody's got any good optic nerve regeneration stuff yet, but boy, that would be nice. So, kind of the fall-up for question is, what about from the other direction? Is a lot of microvascular disease and quadratrophy play a role in what we're calling just pure glaucoma? Any specific thoughts on that? I think we definitely will see the atrophy of the whole visual pathway and is that going to correlate with what we consider glaucoma as changes? A retrograde atrophy, I guess. Well, the regeneration work that Robert Martin had shown definitively in the rep and now starting to show elsewhere through the system would seem to be something that you generally can expect. The interesting thing is how severe that degeneration continues down along the system, which is really relevant, because quietly there's been a group working here for a long, long time. Alessandra's not here, but Alessandra Angelucci and others and we are going to have, I've heard this before, but I'm pretty confident, the first of the Moran cordillus array implanted in the visual cortex in humans this summer. And we're going to find out, it's a place where you can actually get very robust, heavy density. They already have an array that'll stimulate 625 points. The original one's going to be 100. And this is going to be the first time we're going to answer. And those who have had normal vision lost their eyes. The ones they're looking for, that they've wind up with people who then had trauma and lost all vision, but have had a fully formed system but they've lost their vision within a period of a few years, is that a time where you don't have enough, you don't have so much atrophy in the cortex to get usable vision. Theoretically, you could get excellent vision, you get better vision there than you can certainly in retina. And in the optic nerve, the optic nerve is so tight that you get crossover signals, you've got room for it to potentially get some very usable vision. So we're going to start answering that question about what's left of the circumstances. But if you give it enough time, obviously this rewiring is important. If there is microvascular disease that is beyond just what's happening in the optic nerve and scatters you there, then I think we would have seen more obvious signs of it in regards to elsewhere now. Imagine anything, just the visual system, not the rest of the brain, that just has not popped up as a clinical entity. So I think that that's unlikely. That would be, I just think it's unlikely that we would not have picked up on that in some other clinical signs in regards to all the glaucoma patients. Thank you. And then the last question, MR imaging playing a role in glaucoma research versus patient care. I think it's pretty clear that it's not a useful measure for monitoring patients. When that one study suggests if someone has opaque optic media, but in research it could be something interesting down the road. I want to thank Dr. DeGree for helping this presentation. And thank you.