John J. Chen, M.D., Ph.D. , is a neuro-ophthalmologist at Mayo Clinic in Minnesota. Dr. Chen joins our podcast to discuss papilledema, including his collaborations with NASA, papilledema in astronauts and the role artificial intelligence (AI) is playing in evaluation of the optic nerve.
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Welcome to the Mayo Clinic Ophthalmology podcast, a weekly podcast on All things ophthalmology brought to you by Mayo Clinic. I'm your host, Doctor Andrea Tooley and I'm Doctor Eric Ban. We're here to bring you the latest and greatest in ophthalmology medicine. And more today, we're joined by Doctor John Chen, a professor of neuro ophthalmology and neurology here at Mayo Clinic. We're talking all things papy edema, how to tell pil edema in conditions like IIH versus other more atypical causes of pil edema. We're also talking about the role of A I artificial intelligence looking at the optic nerve. Finally, we'll test it on astronauts and conditions their optic nerve may suffer while they're in space. John Chen is an MD PhD and Professor of Ophthalmology and Neurology here at the Mayo Clinic in Rochester, Minnesota. He serves as president of the Minnesota, a Academy of Ophthalmology, Chairman of the Upper Midwest Neuroth Theology Group and is an editorial board member of neuro opthalmic. We frequently see his editorials on neuropathology through a AO. Additionally, John Chen was just awarded an RO one for his work with invest it worked to investigate structural changes in eyes with Pil edema. Welcome Dr Chen. Well, thanks for having me. Excited to be here. We're excited to have you. So we're talking piled today and whenever I think of piled Dema, I immediately think of iih idiopathic intracranial hypertension. So, could you just quickly take us through the traditional pil edema we see with IIH versus other more atypical types of pil edema? Oh, absolutely. Um So in a scenario when you have a patient with bilateral swollen opt nerves with intact vision, that's typically going to be paloma from raised intracranial pressure. I think the first thing you have to do is determine is it truly paloma because some patients can come in with nerves that look elevated from optic ruin or other cause in that pseudo paloma. So that's my first branch. Is this paloma. Is this pseudo paloma. Once you determine its papilloma, then you've got to go and truly investigate to make sure it's truly idiopathic intracranial hypertension. So I was getting an MRI and MRV and if that's normal other than indirect signs of race pressure, then you proceed with a lumbar puncture to confirm, you've got an elevated opening pressure, make sure the fluid shows no signs of infection or inflammation. Then you can make your diagnosis of idiopathic intracranial hypertension. Of course, some of these other causes of raise pressure may have neurologic deficits other than just a vision. So if they've got problems with balance or you know, weakness in the arm obviously you're not thinking this is gonna be idiopathic intracranial hypertension. But sometimes you don't know. Um you know, we had a patient a month ago who was a female in her thirties who came in with, you know, headaches, bilateral swan up nerves looked like it was gonna be idiopathic inr hypertension. Got an MRI and there was a massive tumor there causing midline shift and you know, that was, that was a mass that was doing that. So just looking at a patient alone isn't enough, you really have to do that imaging to make sure everything looks ok, the lumbar puncture to make sure there's no signs of inflammation or other things like that when such patients come in and they're complicated. And I think most of us as ophthalmologists can recognize there's something potentially more going on. It's so critical to stop and think about what you're referring to as other signs and symptoms to help us in diagnostically, you bring in a phenomenal skill set, not just as an ophthalmologist, but also as a neurologist. So help the rest of us in terms of giving us a quick and dirty list of things we should do. That would be a neurological examination in our eye clinics to help us evaluate patients. That's great. I I think a lot of it's going to come from the history. And so oftentimes with patients, you know, I'll just kind of rattle off some symptoms to see if they have any, I'll say, do you have any numbness, tingling, weakness, imbalance? I just kind of rattle that off on almost every patient. I see. And, um, so that's, that's one thing that's helpful. I, I just see them walk in the room because, you know, you're looking for problems with imbalance, ataxia problems with in coordinations, you can see that in their gate. And then, you know, if they do say they have problems with co ordination, just a simple finger nose to finger, kind of test to kind of look for kind of crude um problems with coordinations. Kind of some of the main things I do. The great thing about being at the Mayo clinic is we have some phenomenal neurologists. And so, you know, I often refer our patients to our colleagues in neurology if they have any of these symptoms or any of these signs of any deficits. And so it's, it's great to have colleagues that have expertise uh beyond what we have. And again, um it, it's good to build those relationships no matter where you are. There's been a lot of talk about A I and grading disc edema and how that's kind of the new frontier. What do you see with the role of A I in terms of how we look at the optic nerve, how we grade edema and how would that kind of fit into your practice? Artificial intelligence is pretty amazing and I do think it's going to be having a large impact. Uh We actually had a collaborative study with uh Dan Milia in Singapore. And he's got this amazing setup to look at A I for looking at swollen optic nerves versus not swollen optic nerves. And so he has this train algorithm to differentiate paloma from pseudo paloma. And then AAA group of us sent in uh photographs of optic nerves, some that have Pablo, some that have ischemic opt gray, some that are normal, some that are druze and tested this algorithm essentially blindly. So essentially, it was trained on these other photographs and we sent them 1500 photos that it had never seen before. And essentially, it was 90% accurate in being able to detect papilloma versus non papilloma. So it's just gonna, I think revolution is the way of being able to pick things up. And then what was exciting even beyond that is we then sent two of the best neuropathologist in the US. Uh uh Valerie um P and Nancy Newman sent them to Singapore to challenge the A I computer. It was sort of like the chess versus chess master computer and the results were striking essentially, they were about the same. And the time it took the A I to do the analysis was 25 seconds. And our experts, it took over an hour and this was the best of the best and still ended up with about 90% accuracy based on the funnest photos and then we've got a future study looking at A I versus non neurop themost. So, ophthalmologist, uh, neurologists, optometrists, er, physicians and essentially A I is, is, is, is beating them. So, you know, I see a I, you know, potentially being in, in the, er, so if we've got a funnest camera in the, er, a patient comes in with headaches, blurred vision, take a non meia, non dilated picture of the funnest photo and then just run it through the A I and the A I is gonna be able to pick up papilloma and alert, what's, what's important or not. So, I think it's exciting. It's right around the corner and I think we'll uh revolutionize the way uh we care for these patients and avoid uh missing patients that could have significant problems. Yeah, it's such a condition that pattern recognition of subtleties are, are so valuable. So, it's wonderful to think about some of these tools helping us because I think most of us that look at a swollen optic nerve get nervous because we don't have the expertise and pattern recognition built up like um neurop do. So you make a diagnosis of IAH based on your own expertise and, or teamwork and, or A I tell us just, you know, over the last 10 years, what's changed in the classic paradigms or treatment of IAH for a patient, then you once diagnosed. Yeah, actually a lot. And we've known about IH for a long time. Um but, you know, some things have changed. Um we've always treated with acetaZOLAMIDE and, you know, clinically, we knew it worked. But in 2014, uh we actually had a randomized clinical trial showing that acetaZOLAMIDE is superior than diet alone and not only led to faster recovery of the papilloma, but also actually ended up with better visual outcomes. So it's really nice to have that clinical trial data showing that things that we've done for a while does work. And so it just proves that these treatments are effective. It allowed us to know what dose we can go to patients. A lot of patients can tolerate as high as 2000 mg twice a day. So 4000 mg of acetaZOLAMIDE a day and again, outcomes were excellent. The other large shift is um there's been in terms of surgery, you know, traditionally, we reserved surgery for vision threatening disease and our options were optic nursery penetration and a VP shunt. Uh over the past, you know, five years or so, there's been a little bit more exploration of another surgery called venous sinus stenting. So patients with IIH typically have um a stenosis or squishing of their transverse venous sinus. And with this surgery, uh endovascular surgery there, we're able to put in a stent to open up that stenosis and allows the blood to uh e essentially escape the brain. And it has been working very, very well, we've done about 100 cases of venous sinus stenting at the mayo clinic. And essentially, I don't think there's really been any patient who had normal iih who did not respond in terms of the PLO Demi grade to the venus sinus stenting. Uh and, and complications rates are quite low. So I think that's been a large paradigm shift is how much more venous sinus stenting we are doing compared to a VP shunt and some of these other surgical options, again, it still remains a medical disease. But if you need surgery, it's nice to have that extra treatment. And then most recently this was done actually at the UK, they did a randomized clinical trial comparing bariatric surgery to weight loss alone and its response in patients with IH. And this was just published in the summer and they found that patients who underwent bariatric surgery, of course, had more weight loss, but they also had lower intracranial pressure, faster resolution of pap edema. Obviously, you're not gonna do that in a patient who comes in with Foman at Iah, who's gonna be blind in a week, that's gonna take time. But it's nice to know that that is an option. Uh We know weight loss works and, and pediatric surgery certainly helps with that. So a lot of um a lot of new treatments, a lot of new data and I'm sure in the future we'll probably have randomized data on venous sinus stenting as well, but I am very confident that it's gonna work. Yeah, it's amazing. The new treatment options that we can offer our patients is terrific. This is clearly a passion of yours and a research interest of yours. You actually just got an ro one. Congratulations. Looking at structural changes in the, in eyes with pil edema. Can you tell us about your research and your ro one? Yeah, of course. It's, it's, I find very fascinating. One of the most fascinating things is the fact that it's so variable. You know, you'll, you'll see a patient who's got an opening pressure of 35 which is high and they've got grade four pap edema. You'll see another patient who has an opening pressure of 50 which is two times normal and they've got grade one pap edema. So why, why is there not a direct correlation between how much pressure you have in your head and the amount of swelling? And even sometimes we'll see a patient with paloma in one eye, none in the other. And obviously, again, the pressure is high everywhere in the brain and yet one nervous one, one's not. So there has to be something that either predisposes an eye to paloma or something that um prevents the PLOM from happening. And one of our theories is that there may be structural differences within the eye itself. And so in collaboration with Xiao Ming Jian and Ar Arthur sit, we're using this technology called ultrasound elastography. So essentially, it's an ultrasound that we typically kind of see. But on top of that, we have something called a shaker that actually just gently vibrates the eye and kind of moves it a little bit. And then what the, what it does is it causes little waves of propagation through the eye. And depending on how fast the tissue moves, you can actually determine how stiff it is using ultrasound elastography. And what we did is we measured the posterior sclera of eyes and this was a uh uh mini grant through the Mayo Clinic ultrasound um team. And we found that the posterior sclera was actually stiffer eyes with paloma compared to normal controls and in eyes with unilateral paloma, the eye with the paloma was stiffer than the other eyes. So they almost had an internal control. And so essentially, there's two theories in terms of what might be going on. One is you've got a stiff posterior sclera and we can't measure the lamic curves where the actual pressure is being transmitted. But if you've got a stiff posterior SCLE, you could see that there's less flexibility there. So all that pressure is getting transmitted to the Lamin curbs and then you've got a more swollen up nerve. And then if you had a softer posture sclera, pretty much, if you've got pressure going in the back of the eye, the entire area can move up and that may kind of protect you so that stiffer sclera may predispose you to papilloma. The other option is that what we're measuring is there's more pressure getting to the eye with more paloma. And that's why it's different because everything is just kind of pressing on the eye. I think both of those explanations will be helpful. One, we could potentially predict which eyes are predisposed to paloma or two. We can actually detect that there's pressure getting to the eyes. So we can help differentiate papilloma from pseudo papilloma. So with the ro one, we've got funding now to enroll about 50 to 100 patients with IH to confirm our finding. And also what's great is we're gonna get baseline measurements while there's pap edema. We're gonna treat them medically or surgically if they need it. And when the papilloma is gone, we're gonna remeasure those exact same eyes and see what happens to that stiffness. And then we'll be able to answer. Is this secondary to pressure getting transmitted the eye or is this that predisposition that allows that eye to develop more pap edema? That's fascinating kind of a chicken or an egg situation. But I think both answers are going to be helpful clinically. Yeah, I really like it. And you're also looking into um structural changes in the optic nerve in astronauts or types of changes that we see in space flight. Yes. Yes, absolutely. So, it's, it's really fascinating. So astronauts when they go to space will actually develop some of them will develop Paloma corals. It will look like our terrestrial IH. But these are not your demographics of. Ih. So, Iih is going to be typically females, 90% are going to be obese or overweight. Our astronauts are the fittest men and women we've got and yet they develop these structural changes that look like. Iih, and it's going to be from the microgravity essentially, you know, on earth, we've got gravity kind of pull that blood back down to our heart in micro gravity that doesn't exist. So that's how I think they developed the PLO Dema in IH. We've been collaborating with a group in NASA um Scott Smith and Sarah Zord and they're using, what they found is that astronauts to de develop more Patil tend to have a polymorph morphism in the one carbon metabolism pathway. And so um what we're doing now is we're looking at our patients with IIH. Um And to see if they may potentially have those polymorphisms as well because that may be a shared phenotype that predisposes to pap edema. They are also uh in Germany, there's this amazing cohort, we're trying to come up with some kind of on earth, I guess mechanism of, of, of mimicking PLO demon space. So, in Germany, they have normal healthy volunteers that lie six degrees head down for a month at a time. And actually within one or two weeks, they start developing paloma and chloral fats. So that's our terrestrial model of space flight is people just six degrees head down. And, um, Scott Smith and Zar looked at the ones that develop more PLO Dema and they had the same polymorphisms in there. And so we're now going to extend ultrasound ela geography to see if we can predict and help predict which of the astronauts that might develop pama or some of these patients that are six degrees head down. Uh They're looking at the one carbon metabolism pathways to see if we could potentially alter this by diet. Uh We're looking at O CTO CT angiography in both astronauts and these, these healthy volunteers in Germany. So, you know, it's exciting to try and be able to get this sorted out. Um This is important because we think that there's more papilloma the longer you're out in space. So if we do want to send our astronauts to Mars, we've got to get this figured out because the last thing we wanna do, it's have astronauts unable to see while they're piloting these incredibly intricate space shuttles. It's fascinating. Well, thank you so much for the tour, both uh locally, nationally, globally and and uh outer space through um optic nerve or swollen optic nerves and paloma. Of course. Happy to be here. Yeah. Thanks so much. Wonderful. Thanks, everyone. You can find all episodes of the mayo clinic ophthalmology podcast on our website. Thank you for listening and we definitely look forward to sharing more next week.
