 Awesome. You want me to start? Yeah, let's go ahead and get started, please. All right. So I share my screen. Is that what happens? Yes. Awesome. So I thought that I would talk about, um, to regime for the resident part. And then we would talk a little bit about ocular pain for Grand Rounds. Hopefully that's okay with you guys. That's great. We just, I was thinking about things that we have a lot of, you know, it was either infections or to regime because, you know, that's what we're known for in Miami. So, so I'm a cornea, the edus expert. I started kind of doing dry eye. I evolved to ocular pain because I had more people who had pain without dry eye, but I just do the gamut of ocular surface inflammation, um, cancers to regime, high risk corneal transplants. So if at any point you just have a question about anything, feel free. And I'm going to try to make this interactive. So hopefully you guys are into that because I actually see your names and so well hopefully keep you awake. I know it's early for you. Okay. So this first top, we're going to talk about why I think to regime is really, really exciting. I just think it's more than just a growth on the eye. And more than why it happens, the question that always comes up is what to do with it. And there, there are already so many more complexities than you would think of. So I'm going to take a vote. Um, I don't know how to do votes on here. So just do a mental vote. When we see it to regime, what we see is an abnormal tissue growing into the cornea. And it could be two reasons. It could be that there's an area of limbo, some self-deficiency and it just kind of grows in. So that's degenerative or it can be an active process of the cells being abnormal and growing in more cancer like. So how many of you guys think it's degenerative? What about you Abigail? What's your vote degenerative or proliferative? I know it's often associated with UV damage. So I would say degeneration, but maybe also a small component of proliferation as well. I love that. That is totally right. There is a component of both, but actually the proliferation outweighs the degeneration in this case. And you're absolutely right. It all starts with a UV damage that causes DNA mutations that changes a lot of things from the proliferation part. It changes all these, um, these proteins that are involved in growth. And then from a degeneration part, it does many different things, both immunological and a vascular. And so when they've taken the tissue from teritium samples and they've looked, they found all these different genes associated with proliferation and ones that block apoptosis that are changed in these specimens. Now there's always a question of virus that comes up a lot again in Miami or HPV prevalence is really high. But if you look at all the literature, the HPV prevalence in teritium tissue is somewhere around 20%, but the range is zero to a hundred. So it's not really clear if it's necessary, but it may be a cofactor. Now there are really interesting cases like families of the son and the grandfather and the, you know, grandson all come in with teritium. And of course it can all be similar exposures, but when you map it out, it seems to be an autosomal dominant pattern. So maybe hereditary factors associated with limbo genes that are affecting the limbis. Um, it could be part of it. But as we talked about, it's not just the epithelial cells. There's also involvement of the subsistency appropriate. And when you look at these samples, you see both cellular, um, components like T cells and also soluble components of inflammation and you see abnormal vessels with over-expression of VEGF. So you can start seeing that the pathophysiology of this seemingly really simple abnormality is actually quite complex. But what's interesting is we don't really understand what we understand some things, but not all of them. So where do you most often see a teritium, um, Ariana? If you were just gonna, if you were like a bedding woman. I think probably temporal, because I would guess that the nose is walking, but temporal is number two. So you're like super close. So it, you know, in most people it's nasal, although you can absolutely have temporal and it's definitely more, you know, three and nine as opposed to 12 and six. And so there was a really cool study where they actually use computer ray tracing to look at the dynamics of the eye. And what they found out is that there's a 20% 20 times concentration of the UV rays on the nasal limits, maybe explaining that. But then there are things we don't understand because some Teregia are pretty boring. They're just kind of very quiet while others are super, super red, right? So why are some people more likely to have an inflammatory component with abnormal blood vessels? Not abnormal like OSSN abnormal, but an increased density of blood vessels versus others that are not. We also look at the amount of fibro vascular tissue. Sometimes it's very minimal. Sometimes it's a lot. And then again, there's extension, right? If you looked at this Teregium, can you guys see my pointer? Yes. Perfect. So if you look at this one, you would barely look at it at all, right? It's really just right past the limbis. Whereas here you're kind of worried. And the question is why do some stop one millimeter into the cornea? And why do some extend all the way? And even though we understand the different mechanisms, we don't understand what causes the different phenotypes and different patients. Histopathologically though, what we see is solar elastosis. Okay. So the first thing I want you to ask yourself when you see a Teregium is, is it a Teregium or is it something else? Right? You can't just assume that the referral is correct. So I'm going to show you cases of patients that were all referred for Teregium. And we're going to see what you think. So is it Srav? Am I saying that correctly? Yeah. That's right. Srav, tell me about your spider senses when you're looking at these pictures. These are both people that were referred for Teregium. Like, are you feeling good about it? Are you feeling like, I'm not really sure. I'm not really sure. I'm a little suspicious because it looks like gelatinous. Not really like white, like conge and. Right. Yeah, that, that, that would especially as well as thinking about. Right. You see how it's like there's this area here without vessels and then hear the vessels. It just looks funny, right? Right. So what are you thinking about? I'm thinking more like, you know, CIN. I'm thinking more cancerous. Absolutely. So the first thing you have to ask yourself is, am I dealing with them? Illegmancy, right? So how can you tell Srav? Srav. Yeah. So I mean, one of the things is like feeder vessels that can kind of give you a clue sometimes. So feeder vessels are really helpful for melanoma, but for OSSN, you oftentimes don't have feeder vessels, but I agree with you. You have abnormal vessels. So you have these things called hairpin loop vessels, where you're seeing just the dots because they're going up and then back down, or you see vessels that branch like five times or they're twirly. So really looking at the vascular pattern is really important. You're also looking at location right here. This involves all the way down at six o'clock. Like that's weird. You're looking at extension into the cornea. And if you see an opacity that the vessels don't extend all the way, that's weird. You're looking for things like gelatinous or leukoplakia. And all of those things should be kind of tingling your spider senses and saying like something is wrong here. But one of the things that we have been very passionate about is the use of anterior segment OCT to help in the diagnosis. Any of you guys use that in Utah? I don't think I've seen it here. So I'm going to convince you on why you need it. Okay. So Carol carp, who's one of my friends and colleagues is the one who first did this. And she said, you know, Redna people are cannot have all the fun. Like what can we do with this OCT? And it turns out that if you look at the limb this with an answering OCT, this is the cornea. You could see that the epithelium is very thin, like around 50. And it's slightly hypo reflective to the stroma. Okay. So, so you were doing such a good job. How are you feeling about this to region that was referred to you? Why is this just like playing on its own? Stop it. Just like on some loop. Okay. Hopefully this is not going to just play. Go. Yeah, that's very suspicious looking those vessels look. But you're very abnormal for sure. Yeah. Yeah. Yeah. This is playing on its own. I don't know why, but this is the answer. And what you can see here is you can see that you have an abrupt transition. So this is normal. This is abnormal. Stop. And you can see that the area is thickened and hyper reflective. And that is what OSS said looks like. So what you're looking for is three features. You're looking for an abrupt transition. And then you're looking for an abrupt transition between normal and abnormal epithelium. And the epithelium is hyper reflective and thickened. And so who Tyler. OSS said, or no, I said, said. Well, it has a classic location. I don't see any. Significant arborization of the blood vessels. So I would say, you know, oh, and. Yeah. I'd look a plate that can also be vitamin A deficiency. Can also be academic changes. I totally agree. So now that you're an expert. All right. Here's normal. Here's the lesion. What do you think Tyler? This is like C1 do one teach one. So I do see thickening of the epithelium significant with a abrupt transition zone. And it is hyper reflective with blocking in the structures beneath. So you got it tumor. Okay. Who's next? Cole, Cole, you've been so quiet. This is what I'm looking at. This little thing right there. What do you think? Whoops. It doesn't look. Super gelatinous. And the vessels aren't. Crazy concerning. Right. And no leucoplakia, but of course you're not a hundred percent sure. So go ahead and read it for me. This is the epithelium right here. Yeah. I mean, it's. A little bit thickened. But there, it's not significant. There's not that abrupt transition zones. Right. The epithelium is hyper reflective throughout. And it's pretty thin. But what you do see is you see a sub epithelial hyper reflective lesion and you have just nailed the diagnosis of it. Okay. So I don't know that I can see all of you. If any of you feel left out. But, um, Ali, I think I haven't asked you. How do you feel about this one? Um, So. It's definitely more elevated than the last one. The vessels don't look super concerning to me. Um, but this one's kind of hard to tell. Right. So I don't know why. So I need to start using the antigo CT. So I'm going to give it to you. Go ahead, Ali. What do you think? Um, so there is a distinct kind of change in the epithelium. And then it becomes more hyper reflective. And looks a little bit thickened, but then there's also the sub epithelial changes. Ali, it's like my resident forever. There it is. There is the hyper depth, the OSSN. And that's the sub epithelial lesion. And that is an OSSN next to a penguin. And now if you look at this closely, you can see here, these are the abnormal vessels. I didn't want to point it out to you, but you see how these are thin and corkscrew vessels right here. And then right here is the penguin. So the reason it's confusing is because you have this OSSN sitting right next to a penguin. And unless you like really look closely, you could miss it. That's why it's really helpful. And oftentimes, you know, these are called like masqueraders, where you have two different lesions and you're trying to find OSSN within a lesion. So helpful. All right. Okay, last one. 801-803-8642, go. Or did you just like poor thing, just like just enter this and you have no idea what I'm even talking about. I think you might have just entered, but I can. That's like so mean. How about Moran Eye Center? Yes, that's me. So it looks like that. Yeah, it looks like there's a lot of straightened vessels. Right, which is, which is normal, right? Not curly Q. Straighten is just normal. And it doesn't look that gelatinous, but it does kind of go into the cornea. It doesn't look overly concerning, but I would want an anterior segment OCT. Of course, but I agree with you. You're like, I'm not sure, but let's check. So let's do an anterior segment OCT and go ahead. Read it. Yeah, so it does look like the epithelium becomes. I'm just going to, I'm going to just outline the epithelium for you. And just remember the epithelium over a teritium can be hyper reflective. But what you're really looking for is an abrupt transition zone, which is 90 degrees. It has to be parallel. Just kidding. Perpendicular to the, to the cornea. And then the lesion should be thickened and hyper reflective and hyper reflective, not just like a touch. Yeah. It's all, it doesn't look like there's a true abrupt transition zone. No, there is not. And the epithelium here is hyper reflective, but it's thin. So this is what a teritium looks like. You nailed it. But Moran, I sent her. It's confusing. So I'm going to have you look at the lesion again. Okay. And now tell me if there's anywhere in that lesion. That you're like, maybe that looks weird. I left it to you because I knew you were going to like nail it. Yeah. Yeah. Yeah. Yeah. I'm going to get the pinch hitter question. Actually kind of. The blood vessels. Kind of inferiorly. There's maybe a lot in this lump. Right. Right. And so if you don't look at where you're scanning, you're not going to look at it. So let's look at where we're scanning. And tell me about the gelatinous lump. Yeah. That one definitely has a transition zone and then a hyper reflective. Right. Yeah. So I'm going to talk about that. I'm going to talk about that because this is an OSSN tucked right at the edge of a terrarium. And I didn't talk about OSSN, although I could for hours and hours, but you would treat this differently than if you just had a terrarium alone. Right. And so I just showed you images. And of course, son is what's driving both of them. That's why they can coexist. I have a spectralis, which is a Heidelberg, but you can also use the serious. So I'm going to talk about that. I'm going to talk about that. Um, Wait, let's see who we have. Um, who feels left out and feels like they haven't had a chance. Ali, you did such a good job. Go again. Ali, how are you feeling about this? So this one is definitely more concerning to me just because it's so heterogeneous and it has like those white. Lucoplake. It kind of flex in it. I mean, it's weird. I mean, it's so heterogeneous. The downside of a serious is it only gives you three millimeters. But what else, you know, you just use what you can get. So let me help you. And then you tell me how you feel about this lesion. The epithelium. Uh, it's not that impressive to me. The changes in it. Totally not. And then what is this? This is an epithelial lesion. Correct. Yeah. That'd be more consistent with like, you know, So if this was your patient and they were referred for cataract surgery and you certainly don't want to do cataract surgery through a tumor, you can look at this anti-go CT and be like, yeah, you have a weird to regime, but we can go ahead with surgery. So that is why, at least in Miami where literally everyone I see has some sort of a Ditzel. This machine is so helpful and trying to figure out if you're dealing with them. So what do you feel about this to regime that was referred to you? Um, parts of it look very classic, but there are areas particularly inferior that look more concerning. Right. And so this is weird because it's not like a focal point. It's more like a band. And so pseudo to regions. Can look like to regions and call what causes a pseudo to regime. I do not know. It's when your limbo some cells go away. And why do you think this man's limbo some cells went away? I'm going to give you a hint. I put it right up here in the title because I don't want to get radiation or some radiation, but when we remove OSSM and again, that's a different talk. We use cryotherapy, both at the limbis and at the surrounding conjunctiva to decrease the risk of recurrences. And when you cryotherapy, the limbis you're killing limbo some cells. So in someone who's had OSSM, and you remove it surgically, this is a very typical appearance. And the reason it's important is because if someone comes in 30 years later, you don't want to say, like, Oh, this is a to regime. Let me get rid of it for you. You want to make sure you ask about a history of cancer, because this is not the same pathophysiology as a to regime. This is a pseudo to regime due to limbo some cell deficiency that I caused by taking off a tumor. And tell me, Cole, how you feel about this. OCT. I mean, there's not. Really thickened epithelium, or a pseudo to regime looks like a to regime. So you can't use the OCT to tell the difference, but you can use the OCT to make sure there's no cancer hiding in the pseudo to regime. And so that's why it's so that the OCT is helpful for cancer, not cancer. Okay. Cole, you did an amazing job. This is someone who came in for Trigium removal. Anything you want to think about? Talk to me about. There's a lot of injected vessels and they look straight though mostly. Doesn't look particularly gelatinous. It starts here and ends here. It's like the biggest to regime ever. Yeah, it's definitely anything else. I'm giving you a slip beam hoping you're going to pick up on a subtle sign, but I think you're going to be able to do it. Yeah. Yeah. It does like kind of a divot in the center. Like it's more raised inferiorly. I'm hoping that you go the other way. Like hopefully you're noticing that maybe there's a little thinning. Here. Yeah. Anything else that can masquerade as a to regime other things. Yeah. Yeah. Yeah. Yeah. Yeah. Yeah. Scarring. Scarring for sure. But. Entity. Remember that I trained in UV itis. And so my other hat are looking at immunological conditions. Sorry. I'm not trying to give you any. But I'm just saying, like, think about it that way. Yeah. Sure. So as you have like P UK. You have to ask yourself when you see thinning and blood on your skin. Yeah. And in fact, this is a gentleman who ended up with a diagnosis of P. Incovascularitis because he came in for a to regime removal. And my resident was like, this looks funny, not cancer funny, but something else funny. And so I bet you that you're going to guess my next point. That of course the anterior segment OCT is what can help you with this diagnosis, right? Because he'll P UK can look like to a gym. And sometimes it's hard to look for the peripheral thinning which is what I call P. Incovascularitis. And this is what I call P. Incovascularitis. And this is one of my patients, he's 27. And he comes in with a white and quiet eye. But he tells me my eye turns red every once in a while. And someone else put him on topical corticosteroids. And he's been quiet for a year. They did a whole lab work up. He's 2020. He's happy. But if you look at his peripheral cornea, it looks funny. You can't really tell that there are vessels there, And so, of course, what's going on? This definitely doesn't look like a teridium. So the question was, what does it look like? And you can see two things. Number one, the Antsteg OCT clearly shows thinning and it shows you the degree of thinning. So that's a home run. If you're not sure if there's thinning, just scan and look for thinning. But the other thing that you notice here is that there's like this dense band of hyperreflectivity right underneath the epithelium in the area of thinning. And you can see it in multiple cuts. And it was interesting because the very, oh, never mind. So the question is, is this really inflammatory? I never believed things myself. So I stopped the prednisolone and I said, yep, this is definitely inflammatory. Okay, so the same day I had another guy come in, again, not with a teridium, but with peripheral vessels and thinning. Who's next on my list here? I think it was Allie. No, it's Tyler. Tyler. Is this PUK? I don't see significant vascularization at this magnification. So I would say- There's vessels all through here and thinning. This guy's 73, he's never had a red eye. He's coming in for a totally routine eye exam. I'll give you a hint, it's not. It's a degenerative condition. And I want you to just nail it because you look at these pictures and there's nothing else it can be. I don't know. It's a guy's name. Yes, yes. Terian's Marginal Degeneration, of course. Right, so this is what Terian Marginal Degeneration look like, right? They're asymptomatic, they don't have episodes of a red eye. And when you look at the anterior segment OCT, you often see this like, you see the thinning. OCT shows thinning, but you see that the epithelium, the stroma right under the epithelium in the area of thinning is not hyperreflective. So we said, well, let's look at it, right? Case one, case two, hyperreflective band, no hyperreflective band, okay? So we actually looked at our next 10 cases and we found the exact same thing. That in patients who had inflammatory peripheral thinning, we saw a reflective band and people that was degenerative, like Terian's Marginal Degeneration, we didn't. So anyway, anterior segment OCT should be used pretty much for everything. That is my main message. Okay, Allie, to rid you of removal, are you ready to go? I'll do my best. Do you wanna take it off? Should you do surgery on the side? So in this one, the vessels are fairly straight though, like some of them at the end kind of look arborized, but there's some pigment in this one that we haven't really seen in other cases that you've shown. I can tell you, this is a darkly pigmented man and he has bilateral pigment and this is CAM, this is complexion associated melanosis. So you don't have to worry about the pigment. I just wanna know if you wanna remove the turidium or not. And before you say yes or no, kind of notice where the turidium is coming from. Is it coming from the limbo cells like you're used to or is it coming from somewhere else? Just like kind of pay attention to that. No, it looks like it's coming like from inferiorly, like near the, even the fornix. It's definitely atypical in its kind of its growth pattern and where it's coming from. I would not call this- What do you think? No. How you nailed it. This is a Gunderson flap. This is he had a corneal melt and someone took a piece of condom tie bra and like sutured it on. That means there's like a hole underneath that. It may have healed, this was 30 years ago, but if you see something like that, you should definitely stop and say, like, hey, tell me a little bit more because you definitely don't want to go in and then just find a hole in the cornea. Okay, last one. And then we're actually gonna talk about turidium. Abigail, have I talked to you before or is this like our first time? Yeah, I answered your question at the beginning that I can take this one on. So this looks like it's a double headed turidium. Are you ready to do surgery? I would not. Why? It's very broad and it doesn't have that classical wing shaped appearance with straight vessels. And it also looks like it has abnormal vessels as well. And so I probably would image it first to see what it is and I wouldn't quite go for it yet. I'm gonna tell you something. Before you image it, I just want you to have the patient look up and down because I just really want you to like get a sense of what's going on in the eye. And I just want you to tell me if there's anything that's concerning you in any way. It looks like there's 360 adhesions and maybe... I want a better word than adhesions. And it's much more than S. Simblaferan. Thank you. So what do you worry about in this case? He's never had surgery. He's never had cataract surgery. Maybe he has, but a long time ago. An old inflammatory reactive process such as SGS or something that would have... I've never had that. The nice thing about SGS, if they had it, they know it. No SGS. What else is on your differential? Simblaferan that you can't explain. Maybe Pemphagoid. This is Pemphagoid. You do not want to touch this to regimen. This is Pemphagoid. Pemphagoid is a systemic autoimmune disease that needs treatment. Okay. So the idea is before you jump in and you start telling me how you want to treat a to regimen, I want you to really thoughtfully look because there are many, many processes that blood vessels can crawl on the cornea. They're not all teridium. You really need to be thoughtful to make sure you're not missing something like SGS, like OCP, where you want to take a biopathy and then systemically immune to surprise. But let's just say it is a teridium. So Abigail, how do you decide when to remove it? Remove if it is affecting visual acuity. If it's affecting visual access. If there's causing a significant amount of astigmatism, if it has a lot of inflammation associated with it, that's really bothersome to the patient. I love it. I love it. You got them all. You got them all, right? So if the patient's like, I can't live with this, then you're like, okay, that's true. If it's causing a lot of pain, vision, astigmatism. So here, this is one that's going into the pupillary center. And you can see it's causing eight diopters of astigmatism, but this one isn't going into the pupillary center. And it's causing 10 diopters, right? So when you think it's visually significant, it makes sense to remove it. But the controversy comes in what is the best way to remove it to redeem? So Abigail, what's the answer? It's a trick question. If you were the one that said degenerative versus proliferative, like just kind of do the same thing. All right, I'm going to give it to you. No one knows, right? You know what you want. You want a good cosmesis. You want a low risk of recurrence, but you know, people fight about this all the time. How much conjunctivitis to remove? How much tenons to remove? Do I use an autograph or an AMT? Should I use MMC? There are a lot of different techniques out there. And there is not one best technique. So find a technique that works for you, right? One of the problems is oftentimes we can say, well, let's go to the literature and figure out what's best. But the studies aren't great. And this is a really great point by Lori Hurst, who's probably one of the most experienced to regium removals out there. And that's because we don't agree upon the outcomes, right? So many studies say, okay, if any vessels cross the limbis, that's a recurrence. But this is someone who does have vessels that cross the limbis, but he is super happy with his outcome. This is someone where the vessels do not cross the limbis, but you can see all this fibrovascular tissue. So this would be considered success. This would be considered a failure or clinically, like it's the opposite. And so when you're reading these studies, if you can't even agree on the outcome, and how can you figure out what is the best? Now, even more problematic is the idea of this recurrence. We use the word recurrent to regium and primary to regium. And just because the word to regium is in them, we just assume it's the same thing, but a recurrent to regium is not a primary to regium. They're totally different diseases. So we talked about how a primary to regium is solar elastosis. A recurrent to regium is fibrovascular tissue. And the question is, and this is something that Dr. Basu, who's an amazing surgeon in India, talks about, it's probably not more sun, it's probably us. So the idea is, and this is why we're talking about it, is that aberrant wound healing after surgery is what drives recurrences. And so what we need to do is we need to be so thoughtful on how we do surgery so that we don't get aberrant wound healing. So Tyler, who do you think is at risk for aberrant wound healing? Who's at risk for a recurrence after surgery? Oh. And this is hard because, right, you guys are in Utah, you have like no sun. You probably see like one to regium a year, where like all we do, we're like inundated by it. So I just spent a lot of time thinking about this, Tyler, if you haven't, it's okay, just shoot from the hip and just like whatever you think, let's see how many you get. So I think invasions like defects in Bowman's layer could impair healing and lead to poor prognosis. Yeah, I'm actually thinking just like patient, like not your surgery, like you better do a good surgery, Tyler. I'm saying a patient is sitting in front of you and you're looking at them at the pre-op and you're trying to figure out, are you at high risk or not at high risk? Involvement of the visual access. Actually not a risk factor. Oh. That was a good guess. Chronic inflammation, such as like the rosacea. Any inflammation is absolutely a risk factor. The younger you are, the more of an immune response you can mount and darker pigmentation for whatever reason, also higher risk, okay? So those are the three things you're looking at. And so the key is, is we need to minimize the risk of aberrant wound healing and we're going to do it by being very thoughtful about our surgery. And everyone has their own magic combination and here is mine. So here are the principles that I want you to remember. Number one is the congenitiva is the angel. Take only as much as you need. So if I have a tourgium like this, I'm going to go and I'm going to make my cut just behind the limbis and I'm only going to take away that much. And the thing is if you do that, you'll see it'll retract. There's a lot of tension on that. If I take just that amount, it will retract back. Okay? So no more than you need. Step two is you need to remember that tenons is the devil. Okay. So what I do is I just go in with my four steps and I pull and I find these triangles and I cut them off. And I want this entire bed to be nice and clean. Okay. Now, corneal cleanup is important. I was actually my second grader is learning about acute and obtuse angle. So acute is good. I just want you to remember this is an acute angle. Obtuse is bad. So when you're removing things, I need you to always go in the direction of an acute angle. Never an obtuse angle. Oh, now Ali, what happens if I do an obtuse angle? Why don't I like obtuse angles on the cornea? Probably because it causes a bigger defect. It just causes chatter. You get little lines in the stroma, which I don't want to see. So you want to be really thoughtful about your cleanup. And you always want to point in the direction that you're going in acute angle. If I go in, right? So you saw how I flipped. If I go up, then I go, I go towards, if I go the other direction, I flip it so that what I want to see when I look here at the cornea, I don't want to see little lines from your beaver blade. So the reason that you avoid those lines is in the way you hold your instrumentation. Okay. And I always tell my residents, smooth as a baby's bottom. Okay. The reason this is important is because it's very easy to feel really good about yourself and then leave all this tissue behind. And this is all supra bowman. This is just residual tissue that wasn't removed. And this patient has, I can't tell because I'm seeing your blood pressure. 10 diopters of residual acigmatism after his surgery. He is not happy about this. So then after we removed the residual tissue, there was a little recurrence, but we removed the residual tissue. Look what happened. Went back to 1.3. So if you leave a bunch of schmutz on the cornea, your visual outcomes are not going to be as good. Okay. Now there's an exception to the rule. And I really wish I could find this video. If they have a history of Lasik, it's not going to be as good. It's not going to be as good. It's not going to be as good. I leave it alone. And about seven years ago, I forgot to ask. And as I was aggressively trying to clean, I actually tore part of the Lasik flap off. And it was like terrible. So if they have Lasik, you can get into that. And the tourgium is involving the Lasik flap. You can actually de-hiss the flap. And at that point I say, you know what, we're going to do what we can do. And then I'm going to go ahead and go ahead and go ahead and get into the M.M.C. Or not to M.M.C. I have a very low threshold. Okay. So if someone's young, pigmented skin, it's a large to region. It's inflamed. I use it. But my secret is that after I applied the M.M.C. I lift the plunger up. So that the pledges up so that they are just touching the conjugal between other people put like a plastic shield in between, you're trying to avoid MMC touching sclera and only touching conjunctiva. I also harvest thoughtfully. Remember, tenons is the devil. So what you're trying to do, blue is tenons, yellow is conjunctiva, is use a needle to find that potential space between tenons and your conjunctiva and just harvest the conjunctiva. So when you look at your superior bed, you should have a full area of tenons. The tenons should be undisturbed. What happens when you mess with tenon, coal? That looks like a, like a pyrogenic granuloma. But is it, or is it OSSEN? I don't know. I'm sure it's the OCT. This is the answer. It's always the OCT. Let's look at it. Look at the thin epithelium all the way through and this big hyperreflective mess. You're absolutely right. This is a pyrogenic granuloma. This is what happens when you mess with tenons. Coal, don't mess with tenons. It's terrible. Okay, when I reconstruct, I want you to imagine a limbis. Look at this limbis. Do you see that there are no vessels here? So it totally upsets me when someone puts their graft right on here and kind of does a recurrence before it ever started. I want your graft set back about a millimeter and I want the sutures to go into the cornea so it's easy to remove them after a month. So I like conjunctiva. I tried AMT. I felt like my outcomes weren't as good and I actually glue and suture because this is what happened when I only glued. And by the way, I want you to pay attention. These are not what I want. These get buried in and then you're sitting there bleeding at one month trying to get them out. But what I see here is my graft has retracted in and I have this big area of bare sclera and it doesn't heal well. Now this is something that Victor Perez taught me that I don't like to have friction on my autograph. So if I have my autographed, I actually put on a layer of AMT and then a BCL. And that way when people blink, I don't know, 1800 times a day, my autograph can heal really, really nicely in place because it's being buffered by the AMT and the BCL. About five years ago, anti-vegeta agents were like all the range, the studies were not that great. So I do not use them as part of my surgery. Okay, so putting it all together. I do this under topical and I give subconjunctival lidocaine right in the area. And remember conge is the angel. I only remove just a little bit and look how it retracts back. Then I try to find my triangle. This is my tenons, the devil. And I have to say, this is not a nice triangle. You can get a much better triangle, try to find a better video, but you grab it, you find that triangle and you cut it all. Okay, the devil, I don't want it there. So what I end up with is about a six by six by seven area that is totally clean. And then acute angle, baby's bottom. I want a nice cleanup unless they have a lacy flap. And I want all of the abnormal tissue gone. And look at this. How little conge we removed. Look at this big area. Again, more devil. This is all tenons, I want it gone. Mytomycin, you put your pledges in and then you lift up because we're trying to protect our beautiful sclera. So I want the mytomycin on tenons and conge, but not on sclera. All right, now we're gonna harvest thoughtfully. This is, look how much little conge I removed and look at my defect. And it's very nice and clean. So we're gonna harvest a superior autograph, but we are going to only harvest congenitiva because tenons is a devil and we don't wanna deal with tenons. And again, the best way to do it is to use a needle very thoughtfully placed. It takes a while to get there. So you inject a little bit and you see that there is still space and you keep on moving forward until you pop into that right area. And you'll see I'm gonna pop in soon. I'm not there yet. One more nudge in and it's popped. Now I'm in an area where my conge is above me and my tenons is below. That is how you find your potential space. It's all about where you put the needle. So now I'm gonna be able to harvest a very, very thin area of conge and I'm not gonna mess with tenons because tenons is the devil. And you can see how beautifully this is. And what's nice about this, if you look at this patient a month later, you're not even gonna be able to tell that they had an autograph harvested. The conging tibal heals right over tenons and it looks pristine. So if you needed to go in and harvest conging tibal again for another surgery, you still have it. So again, the idea is keeping the anatomy normal and the way to do that is not mess with tenons to harvest a very thin conging tibal graft. All right, so we're cleaning that up. Okay, let's make sure we're good on time. All right. And it's not perfect. There's always gonna be a little bit of tenons in the area but you just try to make it as absolutely thin as possible, right? Now we're gonna put it in my area and you wanna make sure that it's about a millimeter back because you don't want the autograph to be on the cornea. Now my sutures, I use tenon nylon and I wanna make sure that they go into the cornea so that I can easily remove them at a month. And you can see here that I'm about a millimeter back. That gives me a nice one millimeter margin where I can construct my anatomy so that it doesn't look like you have fibrovascular tissue right on the limbus. All right, then I put, I kind of use my thing. You can see how nice this is very, very thin tissue. It kind of stretches really nicely. I put a few vicarals in just to make sure I'm happy with where I am. And then I put a thin layer of glue to fix it into place. And you can see you have a very thin area, no tenons and we left all the tenons above. So this is exactly what I like to see. When you use glue, less is more. You use just a little brushing of the thick solution and then one or two drops of the thin and you're always kind of pushing back so you're not putting the autographed on the cornea. And then I want to avoid friction from my eyelids. So we go ahead and we put on an AMT just to give it a little extra layer of protection. We glue that on, no sutures. And then we put the BCL and this heals beautifully. I tell my patients, you're gonna be in, if you want to, you can be an eye model after this. Now, because I care about ocular pain and you have free nerve endings on the cornea, you just caused an epideffect, be nice. You already have the glue. This is a fibrin bandaid, coats the nerves. They have a little bit less pain from your epideffect. Okay, so that's my secret. But even with this secret, some people heal beautifully and others heal okay. And so that's part of it. Even when you use the same technique, people heal differently. But generally, if you take off these growths, the visual impact is impressive. You can go from eight to 10 diopters to less than one diopter. I always follow them very closely the first year after surgery and I'm looking for any persistent inflammation. So with my teridium exams, the exam starts across the room. This is one I wanted to look like, that I can't tell which eye had surgery. If I see something like this, I see a little redness, then I know I'm not happy. And the reason is, if you're gonna intervene, you have to intervene early. This is my patient who's graphtihist. And I just kept on following him. I'm still not happy. By month two, it just doesn't look great. And so what I do is between month one and three, if I'm not happy with the healing, that's when I use my subconjunctabular vissimab. And I use up to three injections one month apart. I give 0.4, 0.5 cc because you can, it's not like the vitreous, you've got a lot of space. And maybe he would have ended up looking great anyway, but all my patients who I kind of felt like they were going the wrong direction, low anti-vegeta, and they looked great. This is him at a year. Another case, I'm just looking at this healing. I'm not happy with it. Three subconjunctab vissimab generally makes it heal much, much better. So mine isn't the only option for minimizing a barren wound healing. There's this guy, Lori Hurst, who has the perfect technique. He is a much more extensive tenon removal, a very large congenital autographed, but a 0% chance of recurrence, right? So can't mess with success. I call it the good enough technique, you know? I'm not taking a lot of tenons. I mean, he hooks the muscles and takes the tenons off of the muscles, but I get really nice results taking a little less. And so that's kind of what I have found. Now, people continuously try to come up with better options. And so again, Dr. Basu, one of my favorite ophthalmologist, came up with something called the step technique. And he said, if we don't want to mess with tenons, maybe we shouldn't mess with tenons anywhere. So he said, well, let's just remove the congenitiva and do a good cleanup, because cleanup is so important. But instead with messing with the tenons, let's just take a little piece of tissue and put it in its place and just leave it. And the reason this was so exciting is it took like 10 minutes, as opposed to like an hour surgery, right? And so again, his idea, it's called like this supra-tenons. I don't know what the EP was, but the idea is you don't mess with the tenons. And you just harvest this little piece right here. And so when he first presented it, we are all so excited. We were like, now we can do 10-minute tour of gym surgeries. And if you look at his outcomes, they were pretty good, some of them. So this is someone who had this technique and it one year looks amazing. But sometimes the outcomes weren't so great and you got recurrences. And so this technique has since been abandoned, but the idea is there are lots of options out there. I think people have looked at serum tears or maybe injecting mitomycin subconjunctival a month before surgery, or maybe using 5FU instead of mitomycin. We don't know. The bottom line is lots of different techniques out there. But the thing is, is the thing we still worry about is this aberrant wound healing. This is someone who has a recurrence and a restriction. And so the question is, is can I use a non-surgical option so that I can even decrease the risk of this happening? Anti-vegeps, again, modest effects. Doxycycline people looked at for a while, maybe statistically smaller lesion, but not clinically meaningful. Every once in a while, you have like a, wow. This was a case report that showed that, you know, with this, I don't even know what topical di-paritimal is, but it seemed to totally remove this lesion. But that was back in 2014, never to be heard of again. So nothing is ready for prime time. So in the meantime, it's surgery. If you're gonna address it, either leave it alone or do surgery. And if you're gonna do surgery, you really have to respect the teridium. It's a complex process. You need to make sure it is a teridium and not something else. You don't wanna take p-incovascularitis and remove it. You really have to have a very thoughtful surgical technique and good follow-up because you wanna catch the recurrences early before you, you know, while you can still do something about it. We call it an impending recurrence. It's already a recurrence, it's too late. Okay, but anything you do is good because we don't really have an optimal management. That was it. Can you believe that we talked about teridium for an entire hour? Cause it is so interesting. What can I answer for you? Do you, are you careful about not messing with tenons too much because that is the source of fibrovascular? Yeah. If you mess with tenons, it will be so mad at you. I mean, part of the source of recurrences is just tenon manipulation. Don't touch tenons. Remove it in the area you need to but then don't touch anywhere else. You know, especially superiorly, there's no reason to touch tenons. Leave it alone. And then also for the anterior segment OCT, you said that that's not, is that just a mode on any OCT? It's not a special separate machine, huh? No, that's what I'm saying. Like you all have it. Everyone needs to start using it because it is literally the best thing since sliced bread. Any pathology can be helped to understand what's going on with that anterior segment OCT. And I just picked two of the more common ones, right? So thinning and OSSN. But we, like I hug that machine at night. Like we use it all the time. It's amazing. That's awesome. Hey, Dr. Galore, that was just, that was just terrific. Turidium is like, it's almost like a topic that's like not worthy of discussion. I know, it makes me so upset. Is it so interesting? No, no, I had no idea. I mean, and some of the examples that you were showing that turned out to be, you know, cancer. I'm like, I've seen like a hundred of those. Right? That's what I'm saying. You know, the good thing about OSSN is so slow growing that like, whatever, if you miss a few it'll probably be fine, but still, like, that's, and especially, again, I was in Cleveland and it just wasn't such a big deal. But in Miami, it's a big deal. You use so much turidium, so much cancer, like, so you just, we all have been trained at like looking for those things. We had no sun in Cleveland as well. Yeah, my residency was at the University of Iowa and I'm sure that it was pretty safe. Right, it's like not a problem. Like, I can't remember doing more than like a half a dozen turidium removals during, you know, my entire three and a half years of residency. Right, and our residence ends with like 30 or 35. Like, they don't want, they're just like, okay, enough. No more turidium. Turidium, yeah. But it also shows that if you like take the time to like do the surgery right and pay attention to some like core principles, you can really get a nice cosmetic outcome. And that's the problem. Turidia are unforgiving. If you don't do it right the first time, it's awful because the process that happens after that is no longer a turidia. Then it's just aberrant, we call it recurrent turidia but it's not. It's aberrant granulation tissue with scarring and some blepharone and it's awful. So just, this is one of those surgeries that you have to get it right the first time. You know, you asked Tyler a question about, you know, who's at risk for recurrence, you know, before you do the surgery. Isn't that the same group of people that are also at risk for their traps failing? I think it's just the wound healing. No, you know what? That's a great question. I would assume so, but I have to say I haven't done a trap since residency and I'm not gonna tell you how long ago that was. So none of my traps have failed in the past 20 years. I can tell you that much. Those are excellent numbers. So let's just take a quick five minute break. Gives everybody a chance. I'm gonna get a cup of tea and then I'll introduce you like at one minute past the hour. Okay, so I'll just, do you want me to stop sharing and then start sharing again? Yeah, that'd be great. Okay, got it. Thank you so much. That was fantastic. You guys did a fantastic job. Oh, look, now all these people popped up. Susan and Brian, I'm sorry I didn't pick on you. I didn't see you guys. All right, I'll be right back. All right, thank you. The reason that Kathleen and I originally wanted to invite Dr. Galore is that we have a lot of overlapping interests. You might remember that one of our former fellows, Krista Kanard, looked at corneal nerves in patients with chronic migraine and found that they had some very unusual abnormalities in their corneal nerves. We still don't know if it's cause or effect, but there was definitely some differences in innervation of the cornea in patients with chronic migraine. And then, you know, with our work with photophobia and visual quality of life in patients with chronic migraine, we found that the symptom that seemed to be driving decreased visual quality of life in patients with chronic migraine was dry eye. Even though, and a lot of our patients actually in Krista's series, I think like 19 out of 20 of the chronic migraine patients reported dry eye symptoms, and yet none of them had any objective evidence of dry eye. They all had a normal Schermer's test, none of them had, you know, epithelial erosions, none of them had abnormal fluorescein staining. And so we kind of got onto this idea that patients with these dry eye symptoms, our chronic migraine patients, had some sort of neuropathic pain syndrome. And that's exactly the topic that Dr. Galore is super interested in right now is these patients with atypical dry eye, you know, they come in talking about eye pain, light sensitivity, itchy, scratchy, burny, but they're not responding to the usual treatments like plugs and rostasis and artificial tears and flaxseed oil and mybomian gland dysfunction treatments. And she believes that they have a neuropathic pain syndrome not unlike some of the chronic pain syndromes that we see in other parts of the body and patients that have had an injury, for instance, and continue to have pain despite no objective evidence of any ongoing inflammation or injury. And so that's why Kathleen and I wanted to invite her because we have some interest in overlap even though she's a cornea and UVI to specialist. And we of course are neurophthalmologists. We're both interested in how patients can have these abnormalities in their corneal innervation, have light sensitivity, decreased visual quality of life, and these dry eye symptoms that aren't relieved by dry eye treatment. And then Jeff asked her, Jeff Petty asked her to lecture to the residents this morning before Grand Rounds. And she just gave a terrific tour de force one hour lecture on Teridia, which as I was saying is like, at the University of Iowa where I trained was like a topic not even worth discussing. You know, it didn't come up very often because of our location in Iowa. I did very few teridium resections as a resident. And it just seemed a topic not worthy of discussion. But boy, she showed us how like cancers can be hiding in those lesions. And you can use anterior segment OCT to help differentiate between teridia, recurrent teridia, scarring tumors. It was really fantastic. And then she shared with us her surgical technique for teridium removal, which was really, was really cool. And I think, and she did an awesome job engaging the residents, which I really appreciate. So Dr. Galore went to medical school in my hometown at Wash U. She did her residency at Cleveland Clinic and did fellowships at Hopkins and at Baskin Polymer and UBitis and cornea and is now on the cornea service at the University of Miami. And she's really published extensively on this topic of dry eye and neuropathic pain. And that's going to be the topic of her talk today. So Dr. Galore, thanks so much for hanging with us for another hour. Thank you. I'm so excited to be here. So I'm glad, you know, not that many people when I first started really excited about ocular pain. And so it's just the fact that you guys are, makes it so happy for me that I have an audience. So what I'm hoping to convince you is that everyone should care about this topic because it is timely and doesn't only affect a few. So hopefully I'll convince you. I think this is the missing piece of the dry eye puzzle. So just to start off with, I do have a few disclosures. I have grant support from the VA NIH and DOD. I'm a consultant for several companies that make dry eye products. And I will be discussing the use of op-label therapies. Okay, so the reason we're talking about this is because a long, long time ago, there was this disease called chogrens, right? Someone comes in, they have no tear lake, they have interpathopoebral staining. And this is an eye that you just look at and you say, this is dry eye. And the person that had this eye was usually carrying a water bottle, right? This is chogrens. But then we got excited, at least as dry eye specialists because there were these population based studies. And it turns out a lot of people said their eyes felt dry and we got excited. We said, well, we're gonna have all these people to treat. But then when we really looked at these patients, just like Bradley mentioned, many people who said their eyes felt dry didn't actually have dry eye. That's very confusing. So we said, no problem. We're just gonna stop talking about dry eye and we're gonna talk about abnormal tear health. We're gonna talk about evaporation and lid margin disease. And we got a few point of care tests. So we're gonna talk about abnormal osmolarity and inflammation. But it doesn't make sense because those newer metrics also didn't correlate with the eyes feeling dry. So we're still just as confused as we were before. And so to me, I actually hate the word dry eye because to me it's an umbrella term that we put in apples and oranges. And by that I mean symptoms and signs. And if that's not enough, even symptoms I see apples and oranges where some people have pain and other people have visual related symptoms. And hopefully some of you kind of cringed and said, what do you mean pain? I thought we were talking about dryness. But I'm using the definition that pain is an unpleasant sensory and emotional experience. And you're not supposed to feel your eyes. So if your eyes, if you feel them dry burning aching, that's unpleasant. And if you actually ask people they have different words that they use to describe what their eyes feel. Many people use the word dryness but people also use the word burning. Some of you sharp. It doesn't mean that the pain that people experience is the same as the pain from scleritis. It just means when we use the word pain we're thinking no susceptors. There are nerves that are being irritated. And we know that the cornea is the most densely innervated organ in the body. So it makes sense that if the nerves are irritated we feel something. Turns out there's not just one nerve type in the cornea. There are three main categories. One that senses mechanical like someone poking you in the eye. One that senses many different things, polymodal. And then one that senses evaporation. And then there are proteins which are cation channels on these nerves that when they get activated by endogenous or exogenous ligands they send a signal up to the brain. But as most things it's probably a little more complex with a big network. And in fact, there are some studies that show the different types of sensations like dryness may have different pathways than burning. But we're still talking about nerves. Now this is something that ophthalmologists hate because we are trained to believe that we look in the slit lamp and the answer is right in front of us, right? But the problem with symptoms is that they are propagated by nerves and we can't see all the nerves. There's the primary neuron the one that's connected to the cornea but we have central neurons the secondary and tertiary neurons that we can't see. And so the answer is not always lying in front of us and that makes very uncomfortable as eye care providers. So instead of talking about dry eye let's talk about ocular surface pain. And what I want you to see is unhappy nosoceptors and I need you to be a detective and figure out why the nosoceptors are unhappy. So it turns out if the eye is truly dry if you have aqueous tear deficiency that can cause the nerves to be unhappy. But many patients don't have aqueous tear deficiency. So here is my little quiz. So anyone who wants can yell it out or put it in the chat box. But this is one of my patients who came in and said, my eyes feel dry. And what you can see here is you can see an expanded tear lake and you can see these folds in the corner. And this is conjunctiva colases, right? So this is another person who came in my eyes feel so dry. But when you start examining her you can see that her eyelids are really, really lax. So the punchline is any conjunctiva or eyelid issue can give you dry eye symptoms. So do I have any oculoplastic people here to help me figure out why my patient has dry eye? These are all patients that came in with a referral dry eye or any resident who just wants to be nice to me. Anyone see an abnormality? So they won't be able to unmute themselves. Oh, never mind. Our neuro ophthalmology fellow said there's an entropion on the left side. I thank you, a spastic entropion. So it's not there all the time. And the only way to elicit is to have the patient squeeze a few times and then you see it. And all of a sudden you're like, oh, I get it. This is why you're having dry eye. But of course this is not dry eye. All right, what about this one? I guess I'm just gonna give you a second to think and I know all of you are gonna get the right answer. So this was a little challenging. But again, hopefully neuro op, Bradley, hopefully you see that the eyes are a little asymmetrical. And this is someone whose new onset Graves disease was diagnosed because she came in with dry eye. This one, hopefully all cornea people can see that there's a little exposure going on. And this is a picture just showing the location of the corneal staining. And if you see corneal staining inferiorly attached to the limbis, that's a sign of exposure. So if it was aqueous tear deficiency, the staining would be across the interpathal people fissure. So you can look just by the location of staining can help you figure out why this person has dry eye symptoms. Cornea is the same. And you guys didn't, many of you didn't see my first lecture, but the punchline is the anterior segment OCT is the best thing ever. Of course you probably could tell if there's some map basement, mapped up dystrophy changes here, but it really nicely is shown here with the OCT. And this is what EBMD looks like on OCT. You see these little irregularities. And this is another one, someone who came in with a diagnosis of dry eye. And of course, when you look, you see a salvan nodule, which beautifully is displayed here on the anterior segment OCT. So hopefully you can understand that any abnormality of the eyelid conjunctiva cornea can cause someone to be referred with a diagnosis of dry eye and they don't have dry eye. Okay, this is another one of my patients and she comes in and she has only dry eye in her left eye. Kind of weird. And you can see here that there's come in some schmutz on the ocular surface, a little bit of redness. When you look at her, she's using latinoprost only in the left eye. And so this is ocular surface pain caused by toxicity. And so if you have aqueous tear deficiency anatomy, toxicity issues, and you're having ocular surface pain, we call that nociceptic pain because there is something in your environment that is causing the nerves to fire. The part that ophthalmologists don't often think about is that sometimes the nerves themselves are dysfunctional. So if you perform any surgery like refractive surgery or cataract surgery, sometimes those peripheral nerves heal abnormally and they fire spontaneously or they fire at decreased thresholds. And we call that peripheral sensitization. And sometimes the central nerves become abnormal and this happens in patients who have had traumatic brain injury, migraine, fibromyalgia, and so we call that central sensitization. And when people have pain because their nerves are abnormal, peripheral or central, we call that neuropathic pain. Now it seems totally straightforward, but here's the problem. If you have ongoing nociceptive pain like continuous aqueous tear deficiency, eventually the peripheral nerves are gonna become abnormal. And if you have abnormalities in the peripheral nerves, eventually the central nerves can become abnormal. So you can have more than one. It even gets a little more confusing because there are some people who their peripheral nerves don't work very well like in diabetes and they may have a neurotrophic cornea. So you look in and they have totally scratched cornea at the allele disturbances everywhere, but nerves right next door are abnormal. So they can be neurotrophic and have neuropathic pain. And we see that with painful diabetic neuropathy elsewhere. The biggest challenge for ophthalmologist is that someone can come in with a nociceptive cause of pain and they can tell you their eyes feel dry. Someone can come in like Bradley's migraine patients and their ocular surface can look perfect and they tell you their eyes feel dry. So just by listening to the patient complaint, you can't always figure out what's going on. So the whole punchline of my talk is that you have to consider nerve status when you're evaluating your patient with dry eye. And what I can tell you from our research is that nerve status is not equal in individuals with dry eye symptoms. And so what we have a way is we have this thing called the Beaumontes thexiometer, which is super bulky, but it puffs fixed amounts of air on a cornea so we can figure out when people say they feel a puff of air. And the mean detection threshold is about 90, but there's a huge range. 10th percentile is 40, 90th percentile is 145. And when we look at our population, about one out of four is outside this range. So there is a huge threshold of sensation in the cornea. And so I think it's changing, but in the past there was this disconnect where someone came in and said, my eyes feel dry and the eye care provider said, well, you must have a tear problem. But the more we understand about the biology of nerves, we understand that's not the case. And so I think that people are obsessed with tear metrics, but we often see patients who have a shimmers of four and they come in and they say, my eyes feel dry and you say, well, your shimmers is four. And then we have another patient whose shimmers is four and say, I have no symptoms. And then we say, well, we'll just ignore that. I think what happens is people have a shimmers of whatever they have, whether it's four or 10 or 15 and your nerves respond to that amount differently. So some people will have a shimmers of four and will have symptoms, others will not. And so it's not the signs themselves that are driving symptoms. It's how the nerves respond to those signs and nerves are different in different people. Okay. So how do I think about ocular surface pain? I really love math. So I like to try to graph everything. So let's have ocular surface status on the x-axis and nerve status on the y-axis. So you can have someone who's hypersensitive. You can have someone who's hyposensitive. You can have someone who comes in, nerves are totally normal and they have aqueous tear deficiency. You can have someone whose ocular surface is normal but they are hyposensitive or hypersensitive. But the problem is most people come in not on the x or y-axis and it makes our job a little more challenging. So one of the questions you may be asking me is well, why would you even develop neuropathic ocular pain? And I always say, how could you not develop it? Because think about it, we're performing surgery. We live in cities with lots of exposures. We ride on long airplanes while we used to where we have decreased humidity and any insult can damage epithelial cells and corneal nerves. And when cells get damaged they react and when they react, they bring both soluble and cellular mediators. And if you look at kind of the dry eye literature remembering that every dry eye literature is a different type of dry eye, you can see that inflammation is an important component. So people have done really beautiful studies looking at animals. And if you drop an inflammatory soup on the cornea, your pollen modal nerves become very, very unhappy. So what happens is they become sensitized and what I mean by that they start firing spontaneously and they have an increased response to the same stimuli. So if you take out the lacrimal gland and then you look at thermal receptors, they also become unhappy. Remember, those are the ones that are responding to evaporation. So all of a sudden they increase their firing frequency and they respond to a smaller amount of evaporation than before. And when you look at the molecular mechanisms that are driving this, when you have an injury, the corneal epithelial cells release lots of things and peripheral corneal nerve terminals can respond to them. And again, respond by generating their own mediators like CGRP, which then go and recruit cellular inflammatory cells like T cells and macrophages that make inflammatory mediators. And what ends up happening is you actually change the properties of the channels that respond to the environment and make them more sensitive. And the reason you're probably looking at this slide and saying, why do I need to know this is because now we have things that we block some of these processes like we can block CGRP and Novartis is a company that's looking at blocking trip B1 to try to help people who have pain after refractive surgery. So understanding some of these molecules gives us targets for therapeutic intervention. Okay, so it doesn't just happen peripherally if you do something and then you measure centrally like if I remove a lacrimoglobin and then I measure centrally, the central nerves also become unhappy. So they increase their response and you get something called a secondary hyperalgesia where the surrounding tissue like the skin around the eye becomes sensitive. And so things that shouldn't hurt like a feather touching your eye, all of a sudden hurts. We call that botanist aledinia or secondary hyperalgesia. And when you look at the mechanisms here, lots of different things happen centrally. You have interneurons that are inhibitory that go away. So you have amplification of pain signaling and you have these microglia which are supposed to help the nerves. All of a sudden they change and start secreting inflammatory mediators. And in the chronic pain field, people talk about chronic pain as actually being mediated by glial cells or a gliopathy. And again, that has relevance therapeutically because there are different compounds like pentaxiphalin that can be used to treat or to improve the health of the glial cells. So again, trying to understand what's going on in our patients are so important to come up with new treatments. So when we use the word sensitization, we're talking about a lot of different things. We're talking about pathways becoming more sensitive. We're talking about decreased inhibition. We're talking about new pathways. We're talking about sprouting and ectopic generation. These nerves are changing both in anatomy and function. And so we're probably not gonna do this, but we need to understand how do we detect these nerve alterations in humans? And unfortunately, there are no gold standards but I can tell you what I do. I start my exam by looking for specific risk factors like I wanna know if they have a history of effective surgery, migraine, fibromyalgia. And the reason is I know that pain travels together. We did a study where we looked at people who have chronic pain conditions outside the eye and the ones that don't. And what we found out that people with chronic pain have higher AUSD scores and higher evoked pain, but the same dry eye signs. Suggesting again that a shirmers of four and someone who has chronic pain is going to be interpreted in a different way that someone with a shirmers of four without pain elsewhere. And so what this is telling me that dry eye symptoms may actually be a peripheral manifestation of a systemic disease. And that's not something new to us. We're used to trying to see what's happening in the eye and explaining what's happening in the rest of the body. The next thing I do is I look for a specific symptom profile. And so when you're dealing with neuropathic pain, these patients often have hyperalgesia and aledinia. Hyperalgesia means it's something that hurts me a little, will hurt someone with neuropathic pain a lot. And my ocular equivalent is if someone comes in and says I'm so sensitive to wind. Aledinia means it's something that doesn't hurt me at all, hurts someone with neuropathic pain. And when someone comes in and tells me, room life kills me, that's aledinia. They just don't know how to use the word. Then I use a very fancy technique. I prefer dental floss. Some people use a cotton tip to measure a qualitative corneal sensitivity. And I just want to know if it's abnormal. Anything abnormal tells me something. After I'm done with my exam, I use preparacane to try to figure out if they have pain before and then what happens to the pain after I put a drop of preparacane in. I'm also overall looking for a disconnect with symptoms out of proportion to signs of disease. Now it doesn't mean that tear parameters aren't important. I do perform a quick but comprehensive exam. My floor scene allows me with one swoop to look at anatomy, to look at evaporation, to look at epithelial irregularities, but I don't only focus just on what's happening on the ocular surface. I am lucky that I have a confocal microscope. And I do look for alterations in peripheral corneal nerves. This is from a paper kind of showing in general what a healthy peripheral nerve anatomy should look like and what happens in aqueous tear deficiency. And what happens is you have a decreased density of the nerves and an increased number of dendritic cells. These are these kind of like funny looking long shaped cells right next to the nerves. One group has really been focused on this thing called micro neuroma. And we don't know what it is, but what it is is if you look at a nerve and it's hyper reflective and then it ends abruptly with a bulge that looks like a micro neuroma in animals and may represent a micro neuroma in humans. And they have found that this is a very specific sign of peripheral corneal neuropathic pain. The problem is we couldn't replicate this in our population, which was a very different population than theirs. And so the question is, is what are these things? Other groups have looked and said, well, maybe these aren't micro neuromas. Maybe these are just turns in the nerve. And so it could be that we just have to get better at really defining what's abnormal and normal. But it's very difficult in humans to try to figure it out. A turn would occur closer to the stroma or an abrupt transition or abrupt termination would happen closer to the distal terminal. But we haven't been able to really trace it back in a human because they move to try to figure out which is which. So I would say it's out there, but more work needs to be done to figure out how to apply to our patient. One of my main pet peeves though with a confocal is this is actually me. I have occasional dryness, but no pain. And I do maybe have a micro neuroma. My 26 year old, a research fellow who is perfect has a bunch of dendritic cells and I couldn't even find nerves. And so it's very difficult to apply just one picture to an individual patient because we don't have nomograms that tell us what's normal versus abnormal. We don't have built in software to analyze these properties. And so I do love generating these images, but I don't always know what to do with them. One thing that I'm very excited about is trying to image central nerves using fMRI technology in our patients with ocular pain. And this is a project that I've taken on with Eric Moulton, who is both an optometrist and fMRI specialist. And this is from one of his papers showing that he can see activation and trigeminal pathways in someone with a corneal abrasion associated photophobia. So we just started. I don't know what we're gonna find, but we are gonna scan people with photosensitivity and pain, dryness alone and controls and hopefully try to understand centrally what is happening in these cases. So that's kind of our clinical program. What about research? Well, in my research arena, I measure corneal sensitivity, not with a Q-tip, but with my Belmonte scisiometer. And as I said, it's very, very bulky, but I am able to measure detection and pain thresholds. But what I have found is that the more pain you have, the more sensitive you are. And in this study, we excluded patients with chokers and GVHD. In other studies, they have been found to have less sensitivity, but we know that neuropathic pain can manifest with both positive and negative sensory signs, probably different mechanisms, but at least in our population of non-immune associated dry eye, we have found more pain, more sensitivity. One of the problems that's not just unique to the eye is that when we look at how our sensitivity data relates to our anatomy data, it really doesn't. So whatever we're imaging, at least density-wise is not relating to sensitivity. The other thing that we do is we look for effort responses. So once you give a sensation or a stimulus, something happens. People in the past have looked at tear production, they've looked at blink rate. What we are looking at are some novel parameters. So we have this fancy camera that takes videos and then we process the videos and we look at blood flow through the conjunctiva, trying to understand whether if you give a puff, can we measure the blood flow and see changes based on different nerve responses? And then not so fancy, we do this in the clinic, we measure temperature in patients with unilateral pain to look for parasympathetic versus sympathetic contributions based on whether the temperature is higher or lower on the side that they have pain. The other thing that we try to understand is trigeminal responses outside the eye, so in the forehead. And I'm lucky that I have a quantitative sensory testing expert, Elizabeth Felix. So her protocols are that she develops ways to elicit pain and then ask people how they feel about it. But people are really interested in this. They say they've never had, this is part of their dry eye evaluation, this is our room. And what we do is we have a computer that is attached to a probe and we can then ask people when they feel a temperature change and when it feels painful, then that way we're measuring detection and pain thresholds. But what we wanna do really is try to understand dynamic and central abnormalities. And so there's a concept in neuropathic pain called wind up. So if you repeat a stimulus over time in patients who are, their nerves are intact, it stays about the same intensity. In patients who have neuropathic pain, the intensity goes up and up. And so the increase in pain is called wind up. And you can actually do it in humans by applying a hot pain stimulus once, asking people to rate the pain. And then you apply 10 more stimuli on, off and ask them to re-rate it. And you take this second value and subtract it from the first value, the bigger the difference, the more of the wind up, the more abnormal the responses. Another thing that we see in people with central abnormalities is this idea of after sensation. So if I apply a painful stimulus and then I take it away, if you still feel pain in that area 15 seconds later, that's considered abnormal. And so anything greater than zero is abnormal. So what we did is we say, how do these metrics relate to what patients are telling us? And again, if you look at correlation coefficients, they're weak, 0.15 to 0.3. It doesn't mean that all symptoms are explained by these central mechanisms, but it does mean that they're at least contributing in many patients and it's important to consider that. Just so you know when we looked at how the different, the different ocular signs relate to what patients are telling us, it's even worse. There are no significant correlations between your Schoemer test and whether or not you have sensations of dryness. And so as I care providers, the question is how do we treat people who we think have a neuropathic pain component? And the good news is we're all doing the right thing because the first thing we do is we treat all sources of nociceptic pain. And so it's the things that we already hear about in every dry eye lecture, we protect the ocular surface, we treat inflammation, we improve aqueous and lipid health, we address the anatomy and we minimize toxicity. So we're doing the right things, but the part that I think we need to do better on is we need to know when to move on. So in some cases, the pain persists and nerve dysfunction needs to be considered. So I see a patient like this every single week, someone who had pain that started after refractive surgery, saw eight ophthalmologists, diagnosed with dry eye, treated with every dry eye treatment out there. And then number eight said, you know what, this could be a nerve problem. So by the time they come in, they're frustrated, they're frightened, they're anxious, they say, why can someone have recognized this earlier? And so when we start thinking about neuropathic pain, we try to understand, okay, so what type of pain is this? So the first thing we wanna do is try to understand the pain characteristics. When did it start? What's the time course? Is it chronic? Does it persist for a few seconds and then go away? Is it unilateral, bilateral? What are the exacerbating factors? Specifically, we're looking for wind and light. And we're looking at the descriptors. Are they saying that they feel dry, burning, aching? And then what we do is we say, well, we're gonna put you into a category so we figure out how to proceed. And so my general pain categories, and Brad, I hope you're gonna help me with this because they're probably different ones and Catherine, but post-surgical. So generally the pain started after lacy cataract surgery pretty early on within the first three months. There's migraine light. So they may not have a diagnosis of migraine, but they have a family history, they have a headache, they have light sensitivity. The pain started spontaneously and it's typically bilateral. And then we have traumatic. So people who had a TBI had chemo and then their pain started. And then we have this kind of undescribed category of atypical unilateral. And our categories are always changing, but this is kind of where we are right now. And so the other thing I wanna understand is where is the abnormality? And I use my perperacane challenge to understand if it's central or peripheral. So if I give a drop and they had pain before and it goes away, it means that it's either nociceptive or peripheral neuropathic pain. If they had pain and I give a drop and it doesn't totally go away, then it's central or non-ocular. Okay. So the question is, what do I do with the patients? And the first thing is education is key. Because a lot of these patients come in, they've had pain for years, they're very anxious. And the first thing I tell them, there are no magic fixes. So they need to know that. Things happen slowly and years of therapy are often needed. Setting expectations is so important. The goal, I would love to eliminate the pain, but that's often not a reality. So the goal is good enough, you can do what you need to do. So the next thing I tell them is that multimodal therapy is often required. If I think it's peripheral, a neuropathic pain, I often start with otologous serum tears. There's some thoughts that maybe some of the growth factors like nerve growth factors have a positive effect on nerves. People have probably heard that we have a recombinant nerve growth factor available to treat neurotrophic keratitis. People always ask me, should we use it for peripheral neuropathic pain? I don't know. And it's $80,000. So I can't even use it off-label to try. But maybe a different formulation, a different concentration would be beneficial. I just don't have any experience with it. Many of my patients though have central abnormalities. And I try to find an oral medication that decreases their pain and doesn't have a lot of side effects and continue it for one to three years. So I take it up slowly and I tell people, unless you've given me a four week trial at a therapeutic dose, it's not considered a failure. Because I have so many people who come in with a list of 27 medications. And they say I have failed everything. And I'm like, well, how long did you use it for? And they're like one week at a very low dose, right? So I do this really upfront. So expectations are consistent. My step-letter approach, I work with a pain specialist, is that we start with the alpha-2 delta ligands pregabalin and gabapentin. We add an SNRI if there's an anxiety component. If that doesn't work, we consider adding or switching to tricyclic. I don't like that one if there's true aqueous tear deficiency because it does dry you out more than the other ones. If that doesn't work, we go to low-dose no-track zone. And if that doesn't work, we go into pyramid. And we give people this list ahead of time that says this is our current list. We're gonna go through and find one that helps the pain and doesn't have a lot of side effects. So I have had home runs with this success. Remember that 32-year-old I was telling you about? He's had a pain after his Lasik surgery. He was on gabapentin for about three years. We stopped all his other dry eye therapy because he wasn't dry. He's been pain-free for one year and now we're slowly tapering off therapy. And I certainly have patients like this. Not everyone, but I do have some home runs. But in many patients, we can't achieve sufficient pain control with oral medications. And that's when we consider the adjuvants. And we consider adjuvants based on pain type. So what we have found that people who have post-surgical pain or botanist aledinia seem to do well with nerve blocks. And we start by blocking sensory nerves. And if that doesn't work, then we block autonomic pathways. And the idea is, is that non-injured peripheral nerves are involved in pain propagation. And in this case, we're talking about the nerves around the eye, like the super orbital, super trochlear and infer orbital. And we use a combination of methylprednisolone and bupivacane. And the reason I love this is because you don't need any special equipment. You do it by feeling landmarks and you could do it very easily in the office. Here's my home runs. I'm only showing you my home runs, but if you want my disaster stories, I'm also happy to share those. This is a patient. I actually saw him again yesterday. He has had pain since his retinal detachment repair. He has been sitting at home for seven years with extreme photophobia. He wanted his eye taken out. We did nerve blocks and he had immediate pain relief after the first set of injections. The effect lasted for seven months. He got a second set. He's back to work. He's no longer photophobic. He is doing great. He has his life back. If someone has migraine-like pain, we consider therapies that are used in migraine off-label. And the reason is is because we feel like there are shared mechanisms between eye pain and migraine. And Bradley mentioned that in his introduction. And so one of the things we use it is a trigeminal nerve stimulator. Many of my patients don't want to use oral medications. And this is a TENS machine for the trigeminal nerve. It's cleared by the FDA for migraine, both abortive and prophylactic. It's pretty comfortable. And when I wear it, I feel a little bit like Wonder Woman. And so the biggest side effect is that it makes you sleepy, which is perfect for my patients who have insomnia. Just so you know, there are other stimulation options available. I don't know if any of you have followed the story of True Tier, which stimulated the anterior thymoidal nerve. Some people really loved it. Some people told me they're never shoving that thing up their nose again. But it's since been discontinued, but now there's a company called Orster Point that is looking for a spray that stimulates the anterior thymoidal nerve, maybe with the same effect. And so the idea is people are now thinking about using the lateral functional unit nerve pathways to affect both pain and dry eye metrics. So to be continued. Botulinum toxin is used to treat chronic migraine. It's a pretty intensive protocol, 100 to 150 units and 37 sites. It's also been used, photosensitivity outside of migraine. We did a study where we showed that migraine pain, light sensitivity and sensations of dryness were all related. And all the scores improved after Botox, but dryness not so much as migraine pain and photosensitivity, but either way it was independent of tier volume. So people with low tier volume and high tier volume responded the same way. Again, suggesting that it's not tier volume that's driving symptoms. And so we can't get insurance to cover it and patients are not gonna pay for 150 units of Botox. So what we decided was that we would try to modify the protocol. And we got it down to 35 units, it's seven sites. And we use the incobotulinum toxin because it's cheaper. And so far, so good. Our patients like it. I don't know if it's because we're helping their pain or their wrinkles, but this is what we do in patients who don't have a diagnosis of chronic migraine, but have migraine like pain. This is something that I'm sure Bradley can talk a lot more about because this is his passion, but photophobia is a cause of significant morbidity. And it's really important to use tinted lenses. We use FL-41 lenses. I actually don't know what you guys are using, but the idea is you're blocking out the wavelengths of light that these patients are most uncomfortable with without dark-adapting the retina. So anyone who has photophobia leaves with a set of tinted lenses. Now, we have this category of atypical unilateral ocular pain. And there we have found that getting an MRI is very helpful, although we have a low threshold of getting MRIs in patients with chronic ocular pain. So we're looking for trigeminal neuralgia with vascular compression and other abnormalities. The other thing we do is we measure temperature and if it's lower on the side of pain, we think about sympathetic contributions versus higher we think about parasympathetic contributions. This is one of the patients who was diagnosed with a parietal meningioma and actually after resection, her eye pain went away. So my pain specialist under fluoro can block the sphenopalatine ganglion if we think there's a parasympathetic contribution. We generally try peripheral blocks first because they're easier. And you can also block the central, the superior cervical ganglion. That is tricky, don't hit the carotid artery. I'm really glad that my pain specialist does that one and not me. But I do do the periocular blocks. Carotid artery is nowhere near there. So one of the things that ophthalmologists also feel a little uncomfortable with is this idea of the emotional component of pain. And this was really first introduced to me by my pain specialist. Because when you have pain, you have the sensation of pain that goes to your somatosensory cortex, but you also have the emotional component of pain which is found throughout the brain in multiple regions. And he told me, if I see a patient who has eight out of 10 eye pain, they have such a more robust emotional component that 10 out of 10 back pain. For some reason, eye pain elicits a very intense emotional component. And Stu Eicher has done a lot of nice animal work showing that there are pathways to the parabaricule nuclei to the prefrontal cortex, tex, and amygdala. So we just have to acknowledge this that people with eye pain have an emotional component. They have difficulties in coping and they need to be addressed. There's many ways you can address it. Cognitive behavioral therapies, medication, acupuncture, TMS. If you don't need to do it, but the key is, is to find partnerships with someone who can help you address that emotional component. Okay, so the reason I'm giving this talk is because I want people to really rethink the word dry eye. To me, dry eye means aqueous tear deficiency. The patient is dry. Dry eye symptoms is misleading because your eyes can feel dry for so many reasons. And what's driving those symptoms are nerves. So we need to consider nerve status in anyone who has these dry eye symptoms. And we need to remember that it's a nerve activation that causes pain. The nerves are either being activated because there's something they're activating them or they're dysfunctional or both. And so it's up to us to be a detective and figure out why the nerves are being activated. So hopefully you guys are now convinced that this is the most exciting field ever and will apply some of these concepts to some of your patients. So I'd love to hear questions, thoughts. Thank you so much for having me here. Obviously this is a topic I'm very, very passionate about. That was wonderful Anat. It was just super. And you really brought home many of the points that we have been thinking about and studying as well. I'd like to have you just talk a little bit about the inflammatory components in the cornea. And specifically let's talk about CGRP and also some of the inflammatory soup that we generate ourselves with metalloproteins, proteins and things like that. Could you just kind of give us a little tutorial on that? Because I think that's an area that I don't know that we have a complete handle on. Right, so I would say when you look at just the neuropathic pain world, inflammation and sensitization go hand in hand. It happens peripherally and it happens centrally. So if you have inflammation, it can cause the nerves to become abnormal and then the nerves themselves make inflammatory mediators, neurogenic inflammation. So inflammation and nerve abnormalities go together. The problem is it doesn't translate so cleanly as most things don't once you're looking at humans. Okay, so there are two ways clinically that we can look at inflammation on the ocular surface. One of them is with the inflammatory dry which looks for MMP9 on the ocular surface. And even though it's a yes-no test, you can look at the intensity of the pink stripe and grade it qualitatively. We have done a study where we look to see how MMP9 relates to dry eye symptoms and signs and it doesn't. So you could have inflammation and no symptoms and inflammation and symptoms. So we can detect that it's there but it's not necessarily driving symptoms in all individuals. The second thing we can do is we can on our confocal microscope images and this is actually I do feel like useful, we can look at the amount of dendritic cells and then we break it down to whether they're activated or not activated. Activated means that they have these long dendrites and what that tells us is when we see lots of activated dendritic cells, it helps us kind of point to the direction that there's probably a systemic immune issue going on like chogrens or primary or secondary chogrens. And so those are the ways in the clinic that we can look at inflammation. But unfortunately, when I look at those inflammatory markers, they don't correlate with symptoms, including symptoms that I think are more likely indicative of neuropathic pain. So the way I currently use inflammation is my goal is to try to figure out if someone has an immune issue that shows up in their eye because I see patients after they've had chogrens for 25 years and their shimmers are zero and there's no going back. When your lacrimal gland is five roasts, you're done. And so I tell them, I don't want you to get to that point. And the only way I know how to do that is to give you an anti-inflammatory and I want you to use it for years. And those are the people that I use my FDA-approved anti-inflammatory, that's, you know, the cyclosporine products and the Lefitographs with the goal of not like getting rid of their symptoms now but hoping that in 20 years, they'll look better than they did if they had unchecked inflammation. And patients who have acute flare-ups of like MGD, I'll use short-course steroids to try to calm the inflammation but I don't generally use an anti-inflammatory in everyone and especially people who have neuropathic pain, you know, clinically diagnosed, it's a clinical diagnosis, I don't generally use a chronic anti-inflammatory unless I see a reason for it. It could be that we should but I just don't have the data to suggest that that's what I should be doing. But in the experimental world, they're definitely related. Inflammation and nerve unhappiness are related. It just doesn't translate so nicely clinically. And not, you know, there's some literature on using topical lacosamide for some of these neuropathic pain patients. Have you had any luck with that? I've never used it but I would, yeah, yeah. But I mean, certainly, as I said, this is an evolving field and it's not like it's all cut and dry yet. So if you have an idea and please share with me, I'd love to read about it, but I haven't. We used DiClophanac for a while and it didn't seem to have that great of an effect and we're always worried a little bit about corneal melts and long-term NSAID use. Sure. Definitely the Acocyanort pathway, again, has, you know, contributions both to inflammation and pain. We actually worked with a Carsten Gronert at Berkeley trying to look at Acocyanoids in tears and they're definitely there. So I definitely think that that is potential therapeutic target. We just haven't looked at it therapeutically. Dr. Galore, we've got a question from Marisa La Rochelle. She's one of our UVitis specialist comprehensive ophthalmologist and then I have a question after that. Go ahead, Marisa. Can you hear me okay? Yes, audio is great. That was such a great talk. I really appreciate it. I had a question about, you know, inflammation from a sort of a different perspective when I saw that slide with all the inflammatory substrates and pathways, even including TNF, I had a patient I just saw yesterday and she's on methotrexate for UVitis but she hasn't had active UVitis in years and every time I try to taper her off of the methotrexate, she says her eyes are worse but what she's talking about is her dry eye and her APMD, you know, she comes in, she says my eyes are worse and I look, there's definitely no UVitis but I wonder, is it, I thought she was kind of like cuckoo. She's right, but the methotrexate is having some kind of overall anti-inflammatory effect that is helping those pathways in acornia as far as dry eye symptoms. Have you seen that with any? Absolutely, and so this is again, one of the problems is if you look at the therapeutic pathways, therapeutic, the regulatory pathways to get a dry eye product through, they have said you have to have an improvement in a symptom and a sign and that's crazy because those aren't totally, they're not related. So like trying to like force something that's not related to work is pretty crazy. So they've actually tried, they've tried IO1, they've tried TNF alpha, like if you look at the therapy of failed dry eye therapies, they can't hit a symptom and a sign because that's really challenging because they're not related, but it doesn't mean that they wouldn't hit one or the other. And so that's part of the problem that you don't even have to go systemic. Like you could take some of these anti-inflammatories on the ocular surface, but regulatory wise, people need to think of different ways to get through. And so now people are, there are some companies that are saying forget dry eye, we're going to go for pain and trying to see can we get through based on pain alone? But that is a new turn for like the past like 15 years, many anti-inflammatories have tried the dry eye route and they just can't, they can't cross the regulatory hurdles. And then Dr. Guller, a clinical approach question. So after we've addressed no susceptive causes again to the best we can, or if someone it just clearly only has a neuropathic component, are you trying to then differentiate between peripheral neuropathy versus central neuropathy? And if so clinically, how it seems like there is a divergence in treatment, but I'm still not clear exactly on how I can determine peripheral versus central neuropathy. I agree. I think our diagnostics are terrible, but this is what I do. I use my properacane challenge, which only works if they have pain when you see them. If they have pain and you give a drop and the pain goes away, then it's either no susceptive or peripheral neuropathic. If the pain gets better but doesn't go away completely or doesn't go away at all, then you're thinking it's central or non-ocular. Like it could still be peripheral afference from around the eye. It doesn't have to be central. So that's number one. Number two, I look for botanist aledinia, which is like super not fancy. I press on their eye and I say, does it hurt when I touch the skin? If it does, I consider that a central component because I consider that secondary hyperalgesia. And third, I ask about photosensitivity. This to me, photosensitivity implies central mechanisms. So those are like my three really crude ways. However, anyone can do it. They don't require any special equipment beyond what we have. So I would say even though they're not perfect and I hope that some company will be interested in like developing it in a more refined way, we all have the same capabilities to try to differentiate based on the tools we have. Thank you, that's incredibly helpful. So then again, for the rest of us, before we refer to Brad and we've identified, okay, this seems a little more central. What is your first step? Are you going straight to a systemic medication in most cases? So it depends. And again, my problem is I have a really tertiary based clinic. So like generally by the time I get them, they come to me with a list of 27 peripheral therapies that have in work. Like they've gone through all the quote, dry eye therapy. So it's helpful, just like less work for me to do. Plus my population tends to have a lot of comorbid systemic pain conditions, which means the threshold of just adding something oral is super low. If I have someone who this nociceptive components have been addressed and I think it's peripheral, neuropathic, my go-to is some sort of plasma based product. I have autologous serum tears. I also have PRP, platelet enriched plasma. But once I think there's a central component, I wouldn't say I necessarily always go oral, but I will try something that can modulate. So also I use a lot of TENS, the trigeminal nerve stimulation, that's not oral. If it's post refractive, I'll often block the nerves around the eye to see if there's a component. And what's nice about that, it's diagnostic and therapeutic. I mean, if the pain goes away or is modulated, then you know there is a contribution by the peripheral afference around the eye. So you kind of get a quick response. There it's not so much, it's either gonna work or it's not gonna work. You're gonna know it by the time they leave the clinic. It's just how long will it last if it does work. So I find that really helpful. But I have found that in patients who have like migraine-like pain, that doesn't work well. So I don't try it anymore. I did in the beginning and then I had a bunch of unhappy patients. So I've kind of figured that works best after post-surgical issues. But again, Botox and periocular injections were set up. And so the idea is I really think that we don't even realize how many tools we have ready to go. There's like zero upfront cost to try to get it. We have everything we need. It's just about doing the right diagnostics and being set up to just change our therapeutics a little bit. But especially for uveitis, we give oral steroids all the time. I would say if we feel comfortable with oral steroids, probably a whiff of Lyrica is not gonna kill anyone. So I feel like ophthalmologists shouldn't be worried. We already have the tools to do all of this. Nat, this is a Randy Olson, an outstanding lecture by the way, and spot on. One thing, just once a comment and then the other one, a question. I wonder how much also is associated with what I see as abnormal suppression. I mean, we're inundated with all kinds of signals and throughout our body with all kinds of things that we've just learned to ignore, the body suppresses that. And I think a good example of that, where some people just seem to have an abnormal ability not to suppress would be dysphotopsia, for instance. Clearly that's a very, very weak signal that everybody has. Those people suppress it, they can't. We also see that with asteroid hyalosis where some people have horrendous and they don't see a thing. And others have, even after it's vitrectomized can still see three or four of these things and they're driving them crazy. So there's some element of abnormal suppression in that whole thing that's going on. But the other one is, is that when I try to talk to these people and I'll often get them like you and they've come a long ways. And I'm trying to talk to them about that to maybe it's not so much the eye, you'll get a few of them who suddenly get anger and it says, you think I'm crazy, don't you? You don't think this is any, you think that, I need to see this psychiatrist. How do you handle where they won't even listen, that outburst of anger and then- Yeah, I just keep it to biology. Like I literally have a picture of the brain and then I have a picture of pathways and I say, when you have a stimulus, this is where it goes and when you have eye pain, the pathway goes here and it stimulates your amygdala. Like I keep it very, very scientific. There's nothing like crazy or emotional. I'm like, this is the biology. We need to figure out a way to make these pathways less sensitive. And I'm generally like, all right. All of a sudden you think I'm crazy. You're saying I'm crazy, aren't you? Like no, no. Yeah. They're a tough group. I'm glad there are people like you willing to get in because they can be really, really difficult to deal with. Yeah. Yeah. I mean, it is. It's a lot of TLC. I think what really helps though is having a team. Like I never feel like I can go at it alone because I have a pain specialist who I co-manage the challenging ones. And whenever I feel like I'm up and like I don't feel comfortable, he's like, no, no, no, no. Just combine these two, do this, do that. And so I feel like I've been doing like a pain fellowship the past few years and it's made me a lot more comfortable doing a lot more on my own. But so A, I never, I didn't start it alone and we've just added more and more people to the team. So now we have a psychiatrist who's really interested in TMS and setting up a TMS center. So that's transmagnetic stimulation which is used both to treat depression and neuropathic pain. And so, you know, as this expands people outside of the eye world are like, oh, I want, this is cool, right? And so, you know, once we have a team then it makes it a lot easier than trying to go at it alone. Fantastic. Sadly, I got to check off here for another meeting but anyway, that was great. It's getting done, but yeah, this is way more than my bomean gland dysfunction and, you know, insufficient tears. Thank you, thank you. Absolutely. So we're just coming up on the hour and so I'm gonna wrap up grand rounds. Dr. Galore has graciously agreed to stick around for about another 30 minutes and then she has surgery starting at noon her time, 10 a.m., our time. So we wanna make sure that we let her go in 30 minutes. And the purpose of this followup talk was to have a chance for her to get to know some of the neuro-ophthalmology and cornea team here at Utah. Like we would if she was here visiting in person. So if anybody needs to sign off cause they've got other things to do, please do so. And if you wanna stick around for a Q and A with Dr. Galore for just another 30 minutes, anybody is welcome to stay. It's, you know, it was set up for neuro-ophthalmology and cornea but anybody that's interested is welcome to hang about and we can go into a little bit more of the details. So Dr. Galore, there's a couple of questions that have popped up, one from my neuro-ophthalmology colleague Dr. Warner about the blocks that you described for the super trochlear, super orbital and infra orbital nerve. Do you always block all three spots when you're trying that technique or do you just pick one or two? I generally just, if I'm already gonna do it and I'm set up, I just do all three. And so it's three different injections. I find the notch, I go up, you go straight in until you feel bone and then go out, just a little bit, pull up so you make sure you're not in artery and then you inject and I inject a total of four CC. So I go here, then I go one over and then I go down and then I kind of point in to get to the nasal one. So with one penetration, you can get kind of two spots, one right under and one closer to the nose. And so we're just trying to hit all the periocular nerves saying that, you know if any of them are involved in propagating the pain, we wanna quiet them immediately with, we use bupivocaine and then, you know, corticosteroids have lots of long-term effects. And so again, that is saying like if there are inflammatory clinical or subclinical factors, we wanna address those. And really it's once you get used to it, it's very, the technique is easy and it's tolerable for the patient. Cool, and I'm sorry. So it's bupivocaine. We use bupivocaine and methylprednisolone. We use one CC of methylprednisolone and four CC of bupivocaine. We mix it in one syringe and then we re-inject it in four spots, one CC in each spot. And the four spots are where again? So we find a notch and go up right there to try to hit like the offshoots of the superior orbital. Then we go a little medial for superior trochlear and then inferior orbital. And then from the same point, we just kind of go a little bit in to hit inferior trochlear. So we're trying to get all the branches. Awesome. And we have pictures, we have two papers on it and they both have pictures of, you know where we inject. So it's all published. Neurolytacane? So bupivocaine is longer acting lidocaine. So we're gonna do it, we just wanna really. Okay, all right, cool. And then we actually have a physician's assistant, Irina Krikova, who works in our neuro ophthalmology clinic. And she had a question about using CGRP inhibitors for anything. I am so disappointed with CGRP. Like when they came out, I was just like I'm so excited. But when I looked at the data, the effect on migraine is pretty modest, you know and I have found that the effect on photophobia, again they're expensive, so I can't use them off-label. So my only experience are people who got them any way for chronic migraine and then I see them to see is it doing anything? And it just, it's modest, it's a modest effect. I wanted it to be an amazing effect. So, you know, I know there are different types and I don't know if one would be better than the other but so far it's just hasn't been the wow that I had hoped for. Okay, cool. And let me see, there are some other, some other questions. Yeah, I think somebody would like to know if you have flow charts, rubrics, guidelines for diagnostic and treatment options. Probably, I mean, I have lots of papers that we have published talking about all of this and I will have to try to find out if one of them has a flow chart. If not, maybe I should write a paper and put a flow chart in it. Yeah, we do have a flow chart that we developed for photophobia and eye pain and it's very similar to exactly what you've been doing. And it's kind of reassuring that what we're doing and what you're doing are very, very close and similar and you're coming at it from a different point of view from the corneal point of view and we've been trying to come at it from the neuroaphthalmic kind of brain point of view and headache point of view. Yeah, no, I agree with you in the sense that we kind of developed this and what I was really hoping from you guys is to say like, hey, are we on or we off? Where should we tweak? And so it's interesting that you guys from the neuroap point of view came to a similar pathway. Exactly the same. And we've studied the emotional impact of photophobia and found exactly the anxiety level, the depression levels are elevated in people with chronic migraine and chronic photophobia, chronic photophobia. So you could have episodic migraine versus chronic migraine with chronic photophobia. And if you've got photophobia chronically, you're gonna have elevated anxiety and depression level. So it's kind of an interesting connection. I have a- Anything specific though, like in terms of is there something that seems to work better in modulating? Like so for us, medically kind of we've been through a bunch and deloxatine, which is an SNRI seems to be better in our hands. In terms of like, I just don't have experience with TMS yet because we haven't started it. But I just didn't know like, is there something that works for you in your hands to deal with the emotional component? You know, SSRIs, SNRIs is what we've been going with. And once, well, really I think cognitive behavioral therapy is also really important here because there's a certain element that people need to come to terms with emotionally. And it's not like a magic pill is gonna stop everything as you said. I mean, that's just, we just don't see that. Yeah. And again, that's the first thing. The first thing we do is we give them our like, we don't have a magic pill, it's gonna take years. You gotta stick with us. And I do feel like compliance is better when we have that first conversation. Yeah, exactly. I wanna make sure everybody gets their questions answered before I ask on mine. So Dr. Shoredkoff, can you tell us about trigeminal nerve stimulator? Yeah, so TENS is a therapy that's used for chronic pain. They're like a bazillion different machines that are used. And we wanted to use one that was specific for the trigeminal nerve. And so I have no financial interest in any company, but the Cephaly is a device that stimulates the trigeminal nerve and it was cleared for migraine. And so we use one that's like a dual Cephaly, which means it has two different buttons, well, one button that you press either once or twice. And there are different algorithms, one for abortive. So they're having a migraine and they press it and they use it to try to stop the migraine. It's a longer treatment or prophylactic to try to reduce the number of migraine days. That's a 20 minute treatment that they're supposed to use right before they go to bed at night. We generally use it as a prophylactic right before they go to bed. Although I always tell them, hey, you have the machine. If you have a day where your pain is really bad, try it as an abortive treatment. And the good news about it, I mean, if you don't have a pacemaker, there are no side effects, right? It's not gonna, it's either just not gonna work, but it doesn't hurt. And so many of my patients like it because they wanna try non-pharmacological options before they jump into oral medications. If you look at the migraine data, the curve separated at three months. And so it's one of those things that we, again, we tell them like it's not gonna be immediate. You have to use it for a few months to figure out if it's gonna do something for you. And when we looked at our population, symptom scores got better in everyone, except for two people, but they got better if you had migraine. So in people who have migraine, the symptom of improvement in their eye pain is much more robust than people who have eye pain without migraine. And again, that's, it's so, it's people are a little discouraged because we keep on saying, well, dry eye isn't one thing, but neither is pain. So it seems like even within eye pain, there are different types of eye pain that respond different to different treatments. And so that's how we're trying to figure out how do we categorize them? And we find that the people that do best with the cephaly are people who have eye pain in the setting of migraine or chronic headache. It's not that you can't try it in someone who doesn't, it just seems like it doesn't work as well. And the cool thing about the cephaly is if it doesn't work after three months, you can send it back and get your money back. And not only that, now they don't even need a doctor's prescription. It's clear, you can just buy it yourself and try it. So again, like $500, most of my patients with chronic eye pain are super happy to try it. And then, you know, if it works, it works. But some of them really say that even if it doesn't help their pain, they use it to help with sleep. So. Yeah. Yeah, that's great. I don't want to monopolize this. So if anybody has some questions, guys, in terms of tinted lenses, I know there are a bunch out there. I don't even know why I did FL-41 because that's what Byron did. But like, what are you guys using? What are the different? Well, we told Byron Lamb about FL-41. So we've been using FL-41 for over 20 years. In fact, you know, the story behind that is that the article came out in the journal Headache. And it was used by a couple researchers who did, you know, an experiment and a orphanage on people with migraine and put them in different lenses and then saw how their migraines responded. And the FL-41 was this combination of kind of blue, yellow blocking type of blue blocking lens, kind of a pink tint. And then we came back to our ocular, we have an optical shop here at the Moran and actually asked them to make it up. This was what, 25 years ago? And they, so they contacted the guys in Great Britain, made it back up and it's a, you know, it's kind of a generic formula. And so we've been using a lot. And Brad, you've got a lot of experience. You might even talk to her about some of the contact lens work and some of the other work you've been doing. Yeah, so not, you showed a graph during your talk saying how FL-41 blocks the wavelengths of light that are most associated with migraine. That's our graph. Oh, good. I know where I got it. So now I'll get her proper. Yeah, that's really funny. Yeah, and actually there's been so much demand for FL-41, not only for migraine and photophobia, but also for traumatic brain injury patients and blepharospasm patients. Well, if you ever go to a blepharospasm patient conference like everybody's wearing FL-41 and we got so many calls for it that I actually started an online company called Axon Optics that makes, that sells, you know, our own sort of version of FL-41. And we've started putting it into contact lenses and then, and it's actually, we sort of tried to develop something that's even better. And so we're still working on different ways, you know, using tints or thin films, other ways to block those wavelengths of light without making a lens that's pink because some people find that cosmetically unacceptable and they don't like the way that it affects their color perception. So we are working on a version that doesn't pink and that, but still blocks the wavelengths of light that seem to make people uncomfortable. And it'll just, time will tell if it's effective. It's great, because I have to tell you that, you know, it seems so easy, but when I get this to my patients, they're like so grateful. They're like, why couldn't someone have just given me that a long time ago? Which is these really easy things that sometimes we don't think about that makes such a big difference. Yeah, we have a pair in our clinic and every resident who rotates through neuro-optimology knows about FL-41. So, yeah, and I do think it's really going to be important to use those wavelengths for some people. For some people, it doesn't work. It's, you know, doesn't have a side effect, right? It's easy. I get the same way about the tints. You know, there are just some things that you should just do automatically. Like if you've got migraine-like pain, you're at least with tinted lenses and tints. And then we can talk about the rest. Now, I'm reminded of your article that has the great big pads around the eyes. I hate you. So that's the thing. We had to start somewhere. Right. But I wanted to know if those were working differently than the cephalae device. You know what, maybe, but like the minute we found out that there was something for trigeminal and we didn't have to modify it, we were like done, you know? And so I just, we're just, again, we're not connected to any one company. We just want the best for our patients. Yeah, that's what we do too. One question I have is, what do you think the role of the autonomic nervous system is to dry eye, dry eye symptoms, and the whole lacrimal tear unit? Where do you think the autonomic nervous system- So we're still trying to understand it. But I would say every single time I do a study, it shows up. So for example, we did the blood flow study where we're looking at the amount of blood flow and we're also looking at dilation, right? And what we found out is that if you have, I have to look, it's been a long time, but tear production was related to the sympathetic system. And I don't remember why, but that was the conclusion while pain was related to the parasympathetic system. Now that was kind of our conclusion. So every time we've looked, we always find that there's some sort of correlation and that the correlation of symptoms is different than signs. And so again, one of my pet peeves in quote, the dry eye world is this linking of symptoms and signs, like it's all part of one process. And to me, everything I do shows that the contributors to symptoms and the contributors to signs are different. And that's, it's pretty much impossible to try to detach that. And that's been the challenge in talking to cornea people, but you have to think about them differently. Like it's not good to have a shimmers of zero. I'm not trying to minimize signs, but I'm saying you can't link them to symptoms and think that those are the only things that are important. Yeah. Have you had luck with some of the scleral contact lenses and putting medications into scleral contact lens? I have to say, we haven't been as aggressive with putting medications in it. Sometimes we put serum tears, like dilute serum tears in it, but I have to say that I use more not for my neuropathic pain patients, but for my neurotrophic keratitis patients. So someone who has a history of VZV and they keep on breaking down or end stage GVHD and their shimmers are zero and we're just trying to maintain a healthy ocular surface. I find that that is kind of where I use my sclerals most often. Yeah, because we've had a lot of these really difficult dry eye patients that get horrible photophobia and then you're just trying to come up with some treatment that might work. Yeah, I think what you said about setting expectations is so important not only in this field, but like it's the same thing in cataract surgery, right? It's all about the patient's satisfaction is all gonna be based on how you set the expectations at the beginning. And I think it kind of gets to Randy Olson's question as well. It's just sort of explained to people like, hey, if you had something that was easy, like this would have gotten figured out six doctors ago, but you have something that's difficult, we're gonna work together, you're not crazy, we're gonna help you, you're gonna have to stick with it and nothing's gonna work right away and it's gonna be trial and error and that's so helpful when patients have a more realistic expectation about how long it's gonna take to make them feel better and how much they're gonna feel better and the treatment that's administered by ear is so important. It's just as important, it really is. And I find that my patients, they come in really anxious and once they get it, they're like, fine, I'll talk to you every four weeks, every four weeks we check in because I'm not gonna call you like panic, like my pain's really bad today because I just know that there's nothing to happen. So I find that once we kind of get going and the patient buys in, it's not any more challenging than anything else. We have an outline, they know the outline, I know the outline and we check in at intervals that makes sense. And so I think that's one of the things is that they come in, they're like, well, my doctor tried Gabapentin, I was on 300 twice a day and it didn't work. And I'm like, that's not a therapeutic dose. That doesn't count. So we literally give them the sheet that says like, these are the therapeutic doses. This is how fast we're gonna get there. This is when we check in and then they know like, okay, I'm not even gonna bother you until I have something to report. And so that's kind of, we do that. Our first session is always the longest because we wanna kind of lay out the whole path. Yeah, no, that's really great. And then I also like the fact that you're also using some treatments that are not systemic medications because the longer I'm in the business, the more patients I meet who are either unwilling or unable to try systemic medications because of side effects or fears about side effects. And so the more treatments that I have in my armamentarium like TENS units and CVT and drops like the better. Yeah, and I have to say Botox, like especially 35 units, it's $150. So it's much more affordable than if you were gonna do 150 units like the migraine protocol. They do have to pay out of pocket because insurance doesn't cover off-label Botox but it's not break the bank and it's right where the wrinkle line is. So if nothing else, my patients seem to really love that one also. Yeah, we've actually written a couple of papers about using Botox and Botoacilidinia, which I think has a lot of overlap with what you're talking about. But I've never tried Xiumen, so it's cheaper. It's just cheaper. Okay. It's just cheaper. And again, it's not to say this as effective because I've never done a head-to-head study. Sure. But I'm just saying like, it is cheaper. Take it for what that is, so. Yeah, no, that's fine. And then in your lecture, you showed like the injection sites that you use. Is that also in one of your papers? Yeah, it's published. I can send you. Yeah, we do try like, that's a thing. We just, we do a few, we publish it just so that it's out there. I can't tell you that it won't change but at least you know what we're doing. So, yes. Right, yeah. And I'm also glad you brought up the topic about how the FDA regulates and approves drugs for dry eye treatment. It's so frustrating. It's crazy. It just doesn't work with the biology of the disease. Right. And we don't go along with the signs and symptoms never correlate with this disease. And so why they would insist on the signs and symptoms improving is really puzzling. Yeah, no, I agree. And I think that is changing. And that's why, for example, Novartis is going for a trip V1 agonist. Just kidding, antagonist. And going after pain. They're like post-lasic pain orphan indication. So companies are trying to modulate nerves and they're trying to do it in a way that's not like the dry eye pathway. I have no idea if it'll be more successful or not but at least it's something different. We already know that that one is not successful. So listen, if it gives new treatments to my patients, I'd be thrilled. Yeah. So I have a chicken and egg question. In people who've got this eye pain related to migraine and we found these corneal nerve changes and you've seen that too. Brad, are you, do you have your hand up? No, no, I just... Oh, okay. I thought, oh, you have a question. So in people with migraine, do you think that the migraine is changing the corneal nerves or do you think the corneal nerves are playing a role in migraine? All right. Or is there like an underlying process that's happening in both compartments? So I think it's really hard to know because I've never met someone where it was like a cute onset. Like by the time I get them, all these processes have been going on for years and then it's really hard to tell. But I'll tell you what is interesting to me is when you read the, the dural inflammatory microscopic changes in the dura, it's the same as what's going on in the cornea with the metalloproteases and the CGRP and all that kind of stuff. So the same inflammatory things are happening in both places and it's all served by the first division of one. So the dura and the cornea are one. And so I just think it's so interesting that could we use the cornea as sort of a microcosm of understanding migraine better? Because it's visible, you can measure it. Those dendritic cells are typical, there are similar cells in the dura and that are playing a role also in this picture. And it just seems to me like there should be a parallel pathway here. I agree. I mean, I am a big proponent of like the eye is like the best model for so many diseases. My pet peeve though is that I just wish my confocal was a little more sophisticated. You look at the OCT, you take a picture and then you get this nice printout with red and green and yellow. I look at these confocal images. We can't scan at the exact same place over time. So when I scan, I'm scanning such a small area. I don't know if it's representative of everything. I see one area that's abnormal but maybe it's there and the others and I just don't see it. So like I love the photos. I just think that we just need more. We need age-adjusted nomograms. We need software, we need more because it's very challenging to find the signal through the noise. Yeah, we had the same experience. I mentioned at the beginning that one of our previous fellows used confocal microscopy in patients with chronic migraine and found some really interesting changes but we've bumped up against the same frustration. It's very hard to figure out what's abnormal, what's normal, and then to find some sort of like reliable software that can analyze the images and sort of a readout. So we've kind of dropped it. We really haven't followed up on that work at all just because of that frustration. Yeah, and I'm getting close. I haven't done that yet. We just keep on plowing away hoping that the next version will be better but it's very frustrating. Did you know more about your esthesiometer setup thing? Yeah, it's terrible. I mean, I love Jean-Marie Perrell. He's the one who built it for me but the thing takes up like half the room. You're sitting there with a cylinder like four millimeters from someone's cornea and then we do the ascending method to try to find threshold. So we start at 10 and we do 15 second breaks and then we detect when they first feel the pop and then when it feels painful. Can you imagine just sitting there like this uncomfortable thing with like a cylinder like looking at you? I mean, it's painful for the operator. We're like, please don't give this person the corneal abrasion. It's painful for the person being tested. I mean, we do it because we care but I mean, I just, I hope something better comes along. Like I want to be able to capture your function not structure because again, function and structure don't go together. And I just feel like my functional tests are terrible. Koshu Ibonne, you know, it's a limited range. So, you know, unless you're hypo, it doesn't really measure hyper because most people feel it at six and they won't let us use it because you can't sterilize it properly and now they're big on reusable medical equipment. So even still, we can't even use it. We're not allowed. I didn't really like it that much anyway. Yeah, we have one of those and a same problem. So, and we wish we could test for hyperesthesia and it really just doesn't and- Right, you just, they can't. My Balmante can for sure. It's just a pain. Yeah. That's all we got. So we use it. And that's a custom instrument that you- But he built it. He built it for me. He's amazing. You know, he also built the OPA. So we have a DOD funded study trying to diagnose photosensitivity. So it's a machine that starts at zero lux and it goes up and people again click when it first feels painful to try to, and then we use different tins, including FL 41 to try to understand in TBI which tins can actually, not just the person says they feel better but actually improve your visual sensitivity thresholds. And he built that machine. So, I mean, it's amazing, you know, the guy's 82 and we're like, I have a problem. He's like, yeah, let's build you something for it, you know? Oh my gosh. That's amazing. He's so great. We built- I had a chance to work with him, I was just amazing. Oh, Brad built a machine on light sensitivity exactly like that. Oh really? Well, only it was, yeah, he's an engineer by training too. So I didn't know that. So yeah, so he's really easy. He's wonderful to work with but it was kind of a clumsy thing too. It wasn't easy. This one's smaller than my Bel Monte. So I'm not complaining. Like my expectations are super low. This one doesn't take half of the room. So, but yeah. And then we have a colleague in neurology, Melissa Cortez, who has like a autonomic nervous system measuring laboratory that we've been collaborating with too. That's cool. So what have you found? The same things, you know, people that have, you know, other bodily pain syndromes have abnormalities in their autonomic nervous system that are multiple and quantifiable. And, you know, so I think we're all on the right track in terms of, you know, where the underlying path of physiology is but like how to make it better for people that, yeah, that's really proved more frustrating. Yeah, but it's interesting that it keeps on coming up. There's autonomic contributions to pain. I think to me it's a fascinating field. Yeah, and we really, and we need to explore it more for eye pain and photophobia because I- Well, the nice thing you can do is you can block the parasympathetic and the sympathetic ganglion and get an immediate response to say yes or no. It's just that, did you see one, one you shove it up the nose and the other one you're like one millimeter from our carotid artery. So every time my pain specialist is like, let's do that. I'm like, oh my God. Do you know, no, we've been using the stellate blocks, not the, we wrote a paper initially on photo oculodinia with superior cervical ganglion block and it was in blepharospasm. It's right by the carotid artery but most of the anesthesiologists that we've been working with have been doing stellate blocks and I don't know if there is effective as the superior cervical ganglion block. I just don't know that. I don't know. I still think that the carotid artery is really close to that one too. That's here. Well, the stellate is a little bit more accessible but it's close but it's definitely a block that they're much more comfortable doing than the superior cervical ganglion block. Absolutely. And it's, so then I think that the more we do it, the more we'll get to understand really on how much, because then I think about the blocks that you get immediate answer on what's being driven. And it's so crude, but we literally, we measure temperature. It only works if it's unilateral pain and if the temperature is lower and they failed everything, we block the superior cervical ganglion and if it's higher, we block the phenogalatin ganglion. I'm like, there's gotta be a better method other than thermography to try to look at these. So maybe I should talk to this lady. Maybe she has some better ideas. Like if you have a patient with unilateral eye pain, can something in her lab help point out whether it's parasympathetic or sympathetic, you know, driving the pain? And that's how we choose which ganglion to block. I will ask. We can ask her. We can ask her. Thermometer, I bought a CVS. So I'm feeling like probably something else would be good. You're using a thermometer? Yeah, we do a thermograph and we keep on going back and forth. We're looking for even a small change. The temperature is lower on the side of pain. We block the sympathetic. If it's higher, we block the parasympathetic. Not the most sophisticated technology. Yeah, well, there are these cameras that are infrared cameras too. Those are $35,000. Oh, okay. CVS has a $70 thermometer. Yeah, yeah, yeah. Well, that's great. Well, it's 9.30 and I did promise to give you. Yeah, oh. Thank you. They're actually calling me. Not this was absolutely wonderful. It was wonderful. We may have to have eye pain, photophobia rounds. I would love it. I would love it. Because we are actually as interested as you are. And I follow every single paper you write and I love the one from that you worked with, the Iowa folks, a wonderful eye resident there. I actually was there doing a talk and I met him and he was so excited about what he was working with you. And of course, Randy Cardin has been interested in a photophobia and traumatic brain injury. And he was, I was at Iowa. That's where I did my neurology and neuro-ophthalmology training. And Randy was in my medical school class. So we've been colleagues for many years. And I'm just so glad there are actually people interested in this topic because when I started this 25 years ago or whatever it was, I thought I was going to get tart and feathered. And my mentor just said, Kathleen, you're really barking up the wrong tree. Photophobia, that's a crazy idea. Forget it. Don't even think about, and I went, well, people aren't crazy. They don't make this stuff up. So we just have to understand it better, you know? You know what I would really love? I mean, if we ever travel again, I would love to put in like a course with the Academy that is about photophobia and try to get neuro-op and cornea people to get in the same room. Because I think that's the way to move the field forward. That would move the, have you talked to the cornea meeting? I was invited once, maybe 10 years ago to the cornea meeting in Boston. Have you ever gone to that meeting? No, I don't ever go to that one. Well, that one is, it was really interesting because it was all those cornea gurus. And so I went with my data and told, they kind of went, ah, and then Perry Rosenthal was still alive at that point. And he was very excited that I had come to that meeting. But people just have to start thinking a little bit more creatively about these problems. I want cornea and neuro-op together. And I just think we should do something. We should really think, I don't think that the deadline has passed. If you want to put it in for next year, we can do that. Let's talk about that. I think that would be really cool. Yeah, I would love it. And it's something one of our, I'll email you about it later, but it's actually one of our fellows currently is working on a curriculum for I-Pain. And that's Amanda Redfern. And she's getting a curriculum together for I-Pain and maybe you can be a part of our curriculum development for I-Pain and Photophobia. Yeah, we would love it. So that would be awesome. And maybe we can develop another little meeting like this and come together. We don't want to keep you from your surgery, but- No, absolutely. But I would love to meet this lady who does autonomic testing. Like I want to know what she's doing if she uses a $90 CVS thermometer. No, she doesn't. She's got an infrared camera. And she does, but she does other sympathetic and parasympathetic testing. So- I just want to see what she's doing to see if there's anything that we could do that's not really expensive. Yeah, so maybe we could do another meeting and invite Melissa to it. And then maybe we can have some kind of joint project going on which would like even just working on this curriculum together what I think would be awesome, you know? I would love it. Well, we would love to be with you anyway. So that's great. That's really great. Thank you so much for inviting me. I'm sorry that I have to run to the operating room. Okay, thanks again. Thank you so much. Thanks, Dr. Ruler. And thanks for an excellent resident lecture this morning. It was so great. Thank you. You guys are awesome. Absolutely. All right, thank you so much. Bye-bye.