 Here's her abnormal head position, a left turn, left tilt. She came mainly because vertical prism in her glasses was failing to give relief from her diplopia because that was also part of her symptomology. If you look at her measurements first, you can see she has a fairly large left hypertropia in primary gaze with alternate cover testing. A left hypertropia that built, if you look at the photograph of her in primary gaze, the photo doesn't reflect that, but with alternate cover testing it does build. If you look at the measurements once again, her left hypertropia is about the same into left gaze, but if she looks up and left, it increases a bit. And she has no hypertropia, I apologize, she has a lesser hypertropia in left gaze, and she also has an esotropian primary gaze that increases in left gaze with an abduction deficit, an ABduction deficit. If I could direct your attention to the photos, you can see that she may have some globetraction here when she looks into adduction, which is typical for Duane syndrome with co-contraction of the medial lateral rectus. But look what happens when she looks into left gaze. Her left hypertropia actually increases along with her abduction deficit, and that's quite unusual with Duane syndrome. Now, if you're confused a little bit right now, that's okay. I would expect you to be a little bit confused. You've heard of upshoots in Duane syndrome, but they don't happen when a patient looks into abduction. They happen when a patient looks into adduction towards the nose, usually because of restriction of the lateral rectus. And if you could look up here at this boy, he has bilateral Duane syndrome, and if you could look at his left eye in primary gaze, and when he looks into adduction in that eye with Duane syndrome, he does have elevation of that eye. And in particular, when he looks up and right, he has quite a bit of elevation. That we consider an upshoot in Duane syndrome, and that's a typical upshoot that we see with restriction of the lateral rectus. And contrast that, please, to this patient. She actually has an upshoot when she looks into ABduction. And it's really very unusual with Duane syndrome. So here's a video. I'm going to try to fast forward this a little bit. Watch her left eye as she looks into ABduction. It's right at the tip of my finger. Goes up when she looks into ABduction. So I'm going to advance here. And here's her exam again. And in the clinic, she seemed to have decreased force generations of the left lateral rectus. Well, what does that mean? Well, her lateral rectus doesn't pull very hard. How do we figure that out in the clinic? Give some alkane, make the eye numb, have the patient put their eye in primary gaze. I rest a Q-tip against the temporal limbis, and then have the patient look into left gaze. And if I can push the eye into ABduction, there really isn't much pull in that muscle. So she had poor force generations. And she seemed to have restriction of the meteor rectus. Again, Q-tip on the limbis, but this time on the nasal side, have her look into ABduction and try to push her eye into ABduction. And it didn't go into ABduction easily pushing on a Q-tip. So it seems that she has poor function of the lateral rectus with restriction of the meteor rectus. And so I took her to the operating room because I wanted to help her with the double vision in the abnormal head position and ended up finding that both the meteor rectus and the superior rectus were restricted with force suction testing in the operating room. And so the surgery ended up being just the right amount of six millimeters recession on both muscles. That was enough recession to release restriction in both muscles. And worked well. Here's her abnormal head position preoperatively. Here's her head position postoperatively pretty much resolved the turn in the tilt. And here's her exam. Her esotropia is a controlled intermittent exotropia, the hypertrophy is decreased both in primary gaze as well as into left gaze. And if you look at her photos, you can see that that up shoot in ABduction is improved. If you look at this eye as it goes into ABduction, that's also improved. And here's her postoperative video. I'm going to back that up a little bit. Watch her left eye as it goes into ABduction. You can see your finger. The up shoot is much improved. So just a, just a couple of points. This is an unusual presentation and up shoot in ABduction in Duane syndrome rather than an up shoot in a deduction. I can't find that this has been reported in the literature. And I think it's a variant of the cranial disinnovation syndromes. Think of it as a Duane's variant. The reason I'm presenting it is that an advance in our field has been transposition of the vertical rectus muscles in the presence of Duane syndrome, which is better than a meteorrectus recession alone. In the sense that it gives you better, a better field of single binocular vision. Look, what am I talking about? Well, a more outdated, more traditional way of treating Duane syndrome is to assess the meteorrectus only. And that will help you with, with an abnormal head position. But the problem with it is that you do reduce a deduction quite a bit when that procedure is done. And if you look at our patient here, her esotropia and primary gaze is a well controlled, small exotropia, but look in right gaze. She develops an exotropia. So she does have an imus alignment looking into right gaze. And with vertical rectus transposition, that's minimized. So that's the advance of that procedure. So it's not, it's a good procedure. But in this particular patient, a vertical rectus transposition clearly wouldn't have ended well. We probably would have ended up with some bizarre vertical deviations afterwards. So it's something to watch for in children with Duane syndrome. Children, of course, are notoriously difficult to examine. And finding these sorts of subtle variants might be difficult. So keep an eye out for in children. One child was referred to me in that situation, I believe in retrospect. It was 15 years ago referred in after a vertical rectus transposition for Duane syndrome with a terrible hypertropia. I actually referred that patient on to Los Angeles. Ground zero for that procedure where Arthur Rosenbaum practiced and that child did okay in the end after an additional four surgeries. Finally, again, this is a rare variant of Duane syndrome. Just keep an eye out for it in children before you operate. And thank you very much for your time this morning. Again, I hope that was calm and soothing. And I'm all done. Thanks, David. Can everybody hear me again now? You okay? You hear me? Great. We're going to move on. And I do need to say that I feel much luckier to be moderating this session than to have been Chris Wallace last evening. That would have been a different sort of moderator job. Next up, we have Dr. Griffin Jardine who is going to speak to us about treatments for progressive myopia, wondering whether they are too short-sighted. Dr. Jardine. Thanks, Bob. Let's see. Let me just get this pulled up. Great. Everybody can everybody see my screen? Yes. Yeah, we can see it. Perfect. So. The, uh, yeah, forgive the play on words. I, um, I'm not very, uh, not typically very clever with titles, but I tried to do a little play on words here. So, um, I'm going to start with a case presentation of a five year old who had a failed vision screen sent to us from Idaho and they, uh, had an otherwise normal exam, except they were already minus two, which would be a pretty young age to be already myopic. Most kids start off hyper-opic as they move towards and metropization. So talk to the family said that we would just start with glasses, but then watch this. And within a year, they'd already progressed to minus three and a quarter. And if myopia in childhood progresses over a diopter a year, it is considered, uh, rapidly progressive. And, and so, uh, I had a conversation with this parent about, uh, whether we should start a treatment to slow myopic progression. And in the end, they, they couldn't come down frequently for contact lens fittings. And they didn't have a compounding pharmacy to make dilute atropine available. So the decision was made that we're just going to watch it. Um, and I, I was totally fine. So this is a natural history, uh, case, uh, a couple of years saw them a year later and they jumped even more and then had a little bit of a lapse and saw them at four years and they were already minus seven. Uh, and so this is a case. I just think illustrates this issue of early myopia and childhood and how rapidly progressive it can be. Um, so. And speaking of myopia, uh, you know, we're focusing on the myopia that's related to axial elongation. Um, you know, in contrast to other forms of myopia, for instance, an ROP where we see Orban anterior segment, um, alteration driving the myopia, but. Or I should say laser after ROP, but, you know, my myopia is the most common. I pathology in the world at nearly half a billion people. Um, who are suffering and qualified as visual visually impaired due to that my myopia being uncorrected. What's more concerning is that myopia is on the rise. Um, this is a study that, uh, you know, future, uh, forecasting is, is almost never perfect. But if you look at here in 2000. The global estimated rate of myopia was about 23%. To 28. So jumped about. Five or six percentage points. And then again in 2020. So, uh, So this is a, this is a really big, um, meta analysis study that looked at, uh, over a hundred studies of, of getting these prevalence rates and. Put it into a future prediction model and, and estimated that in 2050, we're heading towards about 50% of the population being. Um, myopic. Uh, and you can see the differences in. Um, in various parts of the world in North America and you know, we're maybe middle of the road. Whereas you see in some of the Asia East Asia and Southeast Asia, that they're already at. You know that, you know, that, well, they're already above the 50% mark. Um, in some places they're at 90% of the population is myopic. So myopia in and of itself is, for the directly proportional increase in risk with the increase in myopia. And this is, I pulled a couple of studies that showed some of these relative risks. You can see as you get into the minus six to eight range, the cataract risk is five-fold increased. The retinal detachment risk is a 21-fold increase. And then myopic maculopathy has a 40-fold increase in risk in that myopic range. And in Japan, in certain parts again of Asia, myopic maculopathy is becoming one of the leading causes of visual impairment where myopic rates are really high. So I know this is a pretty common topic. I think we've all heard about this. This is really caught fire in, again, parts of the world where this is already seeing causing a lot of problems. So one question is, why is myopia on the rise? I think this is a complicated question and it's certainly multifactorial, but most studies are showing that it's predominantly environmentally driven. So one of these studies that I thought was really interesting to capture this point was it took families, Chinese families, families or children from Chinese ethnicity who were living in Singapore versus Sydney and just did a prevalence of myopia study. So just a snapshot in time, but they found that children in Singapore, which would, in terms of lifestyle, represent Asia and Southeast Asia would mirror those lifestyles more. The prevalence rate of myopia, this is again children six to seven, it's like first to second grade. Their prevalence rate was 30% compared to just almost 3% in Sydney. And of all the factors they looked at, the one that stuck out the most as the difference between these two cohorts was that the children in Sydney were spending 14 hours a week outdoors compared to only three in Singapore. Pretty drastic difference. No significant difference in the parents myopia speaking to the genetic cause. Ironically, children in Sydney reported having actually more total near work activity. So the amount of time we're spending on screens, the amount of time kids are spending accommodating is thought to be a risk factor, but in this study it was really much more so the time spent outdoors. So just to talk about this, what are the mechanisms behind outdoor time and the arrest or decreased incidence of myopia? And the leading hypothesis is this light dopamine theory, which is that UV radiation and not all forms of light really made the UV radiation, stimulates dopamine release in the retina which slows axial growth. The absence of which causes axial elongation. A couple other theories. One of them is pupillary constriction causing less blur on the retina. And we'll talk a little bit about that later. And another one is just the idea that when we're outside we're not accommodating as much. So again, probably multifactorial, but I think the light dopamine theory has the most robust data behind it and it's been proven in several animal models. Just to share another study, I'm gonna try to just share as much data as possible to shed more light on this topic, but there was a randomized control trial in Guangzhou, China of a thousand kids, about a thousand kids who the intervention was giving half of this group that were randomized an additional 40 minute outdoor recess at the end of school. And that extra time outdoors reduced the incidence of myopia by about 9%, which ended up being about a quarter in terms of the relative risk reduction. So my first question is, do we encourage young children to spend more time outdoors to curb the incidence rate of myopia? And I think with all the data out there this seems to be a pretty strong yes. The next question is, what if somebody is myopic? What if a child is myopic? Should we tell them to spend more time outdoors as to slow the rate of progressive myopia? And that is sure, but that's probably not enough in its own because the mechanism is actually changing in what's driving actual elongation once a child is already myopic. So let me talk about that. So if a child is diagnosed with myopia, what we see is starting here on the left, so an uncorrected myopia, the myopic eye, the line kind of the focus distribution here, it doesn't actually correspond to the curvature of the elongated eye. And when you put traditional correction, namely glasses and or contact lenses, you do get the central retina, the central vision in focus, but the peripheral retina is out of focus and it's a hyperopic defocus. It's focusing behind the retina. What we're finding that this hyperopic defocus is another stimulus for axial elongation or myopic growth and that's driving some of the progressive myopia and again, children who are already myopic. So this is an image pulled from a recent study out of JAMA called the blink study that talked about multifocal contact lenses to slow myopic progression. As you see here, so this is just a traditional contact lens and these peripheral light rays are coming into focus again behind the retina, so hyperopic defocus. When you compare that to a multifocal contact lens, so the ad power is not central, but it's in this mid peripheral part of the contact. It's causing myopic defocus on the peripheral retina. And that is the kind of proposed mechanism of theory behind a couple of these treatments to slow myopic progression. So again, to look at the data in this study, this is a really well designed double mass randomized clinical trial here in the United States that was done in children seven to 11 and a decent size. So they tried three different study arms. The single vision contacts with a medium ad power versus a high ad power in the multifocal contact lens. And these are actually soft contacts, interestingly. So the three are myopic progression and a single vision contact was only minus one. And I think that's probably, I think contacts have been shown to slow myopic progression as compared to glasses. So that's already probably a somewhat slowed down intervention, but when you went to the 2.5 multifocal contact, your myopic progression was about 40% less. Probably more important is the axial elongation since that's where most of the pathology of high myopia is linked to. And here we saw nearly a third, a 33% reduction in axial elongation over three years. So actually I think this is quite a sound study with support for multifocal contact lenses in this context. Another treatment is ortho keratology for slowing down myopic progression. So I don't think I fully understood ortho keratology in its mechanism in this context. And in continuing this theme of trying to create peripheral retina, hyperopic defocus with ortho keratology, this is on the left supposed to simulate the corneal curvature. What we're doing with these lenses, we're trying to flatten the central cornea. And in so doing, as we know about the cornea, if you're gonna flatten one part of the cornea, you're distributing that curvature elsewhere. So by flattening the central cornea, what we're actually doing is steepening the peripheral cornea. And that is gonna cause, again, a hyperopic shift of the peripheral cornea, not too dissimilar from the same concept that the multifocal contact lenses were doing. And just again, as a review ortho keratology is where these contacts that are inducing central flattening their contacts that you sleep in overnight and then you don't wear during the day to change the shape of the cornea. And it can make patients independent of spectacle or contact lens wear who are myopic. You're limited in range, I spoke with David Meyer and Dick Spetty, both of whom offer ortho keratology to interested patients. They don't really push it much beyond minus five to minus six, but short of that, this was another good randomized controlled trial. This is back from 2012. It showed that the axial elongation was the only outcome because the refractive air in these patients is altered by the ortho keratology lenses, but they saw nearly a 50% reduction in axial elongation over two years. And just when they, again, to point out the importance of addressing this in younger ages, when they divided their cohort into those who were younger, seven to eight, those in the control group who fell into the category of rapid myopic progression in that they're progressing over a doctor a year was about 65% in the control group compared to 20% in ortho-K group. So really curbing those who are the most problematic, those who are rapid myopic progressors. So the third intervention I wanted to cover is talking about dilute atropine. So dilute atropine has really been hot in the press and in the literature and especially in China, they've been looking at this really carefully. Again, this is already a public health issue for them. So they've put together some really well-designed randomized controlled trial. And the Atom study were the first two big studies that looked at this. And Atom one study looked at 1% atropine, which is represented here by this line compared to the control group. So in the Atom study, 1% atropine actually showed an early hyperopic shift, which is pretty impressive. And then it kind of tailored off. And over two years showed that it definitely slowed myopic progression. As you can imagine, 1% atropine was nearly intolerable. This was one drop a day. The amount of photophobia and near blur meant that most of these patients needed progressive lenses or bifocal. So Atom two study was kicked off to look at a diluted concentration of atropine and to see its effectiveness in both slowing myopic progression, but that hopefully finding an improved tolerance of the drop. And I love the study because this just goes to show how when you really good rigorous science and these randomized controlled trials can sometimes reveal unexpected outcomes. So the 0.01% was even debated as whether or not it would be valuable in this study. They thought maybe it can even be near a placebo effect. But as you looked at the study, it was there was a dose dependent rate of arrest of myopic progression. So the dilute atropine here in the white circle was the least effective at two years in slowing myopic progression of the four different concentrations, but they did a washout period for a year and the rebound phenomena in the other three arms was profound. And in the dilute atropine group, their rebound phenomena was actually the was the least. So at three years, they restarted all the groups on what was thought to be the leading contender of the four choices, which ended up being the dilute atropine. So they restarted on and they saw again, a slowed progression. And in this study, after five years, the dilute atropine group showed an average of minus 1.4 diopters of myopic progression. And that same number was hit in the control group in 30 months, about half the time. So again, a really interesting study. The mechanism here is not really that well understood as to why this atropine drop does this. But there's an ongoing study called the LAMP study, which is essentially a continuation of the LAMP study. But now we're looking at, could we do different variations of this dilute atropine to see which is most effective? So they're comparing 0.01 to 0.025 and 0.05. And here you see that there is again, this dose dependent slowing of myopic progression in that the higher concentration of 0.05% is seeming to be the most effective. So even though I'm using 0.01% in a lot of my patients right now, I think as this study continues, we may be switching to a point to one of these two other concentrations. We're still waiting for the washout period. So the jury's out as to whether or not the higher concentration will have a bigger rebound phenomenon like it did in the first study, but hopefully not since these are all lower. And the 0.05% was well tolerated, still did not have a significant incidence of photophobia or near blur requiring glasses. So again, most importantly, the change in axial length is really the data point we care most about. And again, this was shown to be slowed in the atropine groups as compared to the control group. The control group right here at one year was switched to what was determined to be the most effective of the three concentrations. So it was switched to 0.05. And in a year, it actually passes the 0.01%. So again, the next phase, it's a four phase study, the next phase is the washout period. So that will be again enlightening on what is going to be the leading contender for dilute atropine. So let me end with another case presentation. This is a sweet two-year-old boy referring to me for high myopia. He was put in a pair of glasses, but on my exam, the psychophagic refraction was about double what they had estimated. He was nearly minus eight in both eyes with some oblique astigmatism. And this is pretty unusual. I'm often surprised at how many patients I see who are even double digits in their myopia under the age of five. And when we see this high degree of myopia, this early in age, I typically refer for genetic testing. And this child unfortunately came back positive for congenital stationary night blindness, which is associated with early high myopia. The other things that we see fairly commonly are fever and stickler and less commonly Wagner. So we're so fortunate to have Emily Spothier who does navigate the genetic testing and then the complex interpretation of the genetic results. I wanted to show a video of this sweet boy. The first time he put his glasses on, sometimes I tell parents it's sometimes it's worth filming because it's interesting to see their reaction. So I want to ask you what you think the reaction is of this little boy here? What's different? What the optical properties are of his reaction? I feel weird. Does it feel weird walking with it? Or not weird? It's a little bit of an adjustment, Emily. It's going to take some time to adjust. And you can just tell his depth perception is way off the glasses. Good job. I'm just going to pause it for a second. Any thoughts on what would be the driving factor there? Why would he have such a difficult depth perception adjustment? I don't know. I don't know. I don't know. I don't know. I don't know. I don't know. I don't know. I don't know. Depth perception adjustment to those glasses. I actually lost my chat to pull up. But while you're thinking about that, I unfortunately can't see the chat. I'm almost done here, and then we'll open it up for questions. But my thought was that minus eight has a potent minification effect where things would look further away. You can see him looking in his hands in front of his face and not being able to see exactly where his hands are. So I think within thankfully a couple of days he was cruising and functioning much better than he was before the glasses. But that adjustment video, I thought was quite interesting. Again, the optics of myopia. So take comes here. To get back to that original question, I'm going to unfortunately belabor the play on words. But I think actually it would be foolishly myopic to ignore this growing problem. So I think the treatments have really good data to support them. Ortho caretology, we're so worried about this idea of sleeping in contacts and the risk of microbial keratitis and the incidence rate in the studies where there was patients were really well instructed and how to take care of it. It was about one per thousand of corneal ulcers. And we're so fortunate to have David Meyer and Dick Speddy that at least amongst, there may be other optometrists in our group, but I know those two specifically do offer all of those contact lens options for patients who fall into this category of being high risk for progressive myopia. I think the UV exposure in early childhood is definitely something that we need to be thinking about. Pediatricians are pushing for kids to have more time outdoors for dozens of health reasons. And I think we're at a public health crisis where the amount of programmed busyness that children are facing and the kind of early aggressive academics that we're seeing are causing them to have all sorts of issues, including increased depression and anxiety that I'm gonna let out my own personal parenting philosophy here, but I think we do need to let kids be kids and have a lot of unstructured free play time, especially outdoors where that UV exposure has a lot of health benefits to them. With some block as a redhead, I have to speak on that. So lastly, if a child is myopic out of the age of nine and especially if it looks to be progressive, we ought to think about offering one of these interventions. There's other ones, these were the three that I really thought stuck out and had the best and most supportive data. And I do use a lot of dilute atropine, but I just think it's a conversation worth having with parents. And here are my references, it's really a pretty, you know, there are just hundreds of thousands of studies on this right now being done, especially in the parts of the world where it is an issue. So on that note, let me stop my screen share and just open up for any questions. You're welcome to chat and write into the chat if you have any questions. If you wanna be unmuted, raise your hand or say in the chat and we can unmute you as well. Griffin, I'm not hearing a lot of questions. I think you must have made the issue very clearly in focus. Perfect, thanks Bob. So I think we'll go ahead and move on our third presentation. Wait, I have a question. You have a question, well, you better ask it. So I have two questions. Griffin, what's your thought on why atropine works? I mean, I guess there are several theories on that and I think the leading one is they don't really know, but just kinda curious what you found looking in that. And my second question is like those kids with congenital stationary night blindness or things like that, you know, do you treat those kids? Just curious on when they have other pathology, what's your thought on myopic progression when they've got other things going on? Yeah, great question to be me. To the first question, I actually, the theories are all over the place and they don't really have much support on any of them. I think there's a biochemical theory that atropine is having some effect on the eye. There's the other theory is causing, is there some way that it's potentially decreasing that peripheral retinal blur and that doesn't really pan out either. So I think it's one of these things that works, but for reasons that are unclear. I didn't come across any compelling theory that really made sense or that I thought was very supported, well supported. To your second question, the challenge with these patients that have and another reason to be myopic is that the exclusion criteria and all these studies was all these genetic conditions and ROP and so we don't have any data to really answer the question about what to do in patients that have, for instance, ROP and that's probably a different mechanism. They don't actually have elongation or again, RP with laser or like a stickler's patient. So I've been pretty conservative because I don't know if there's, I don't think there'd be much risk of doing dilute atropine in almost anybody. I think you could discuss it with family and just mention that there's not enough data to answer whether or not it applies to their specific child, but it's likely safe enough that you could try it. That's probably where I stand on that. Yeah, no, just curious. Great, great review, thanks. Yeah, thank you Mimi. Are there other questions? Griffin, great review. One quick question within kind of the Moran system. Are we then, if we're seeing these patients or having acquaintances, et cetera, are we supposed to send everyone to you directly? Are there others who are doing this? And is this the sort of thing where you'd feel comfortable with our optometrist comprehensive ophthalmologists prescribing this and moving forward with dilute atropine? Yeah, Jeff, I think this is thankfully fairly straightforward and I know everyone in our division is open to using it and I know the optometrist are really ones who have been the, I think the predominant leaders in driving a lot of these really well-designed randomized control trials. So our optometrist are perfectly capable in managing this. I think you do need to have a really careful and a good-readable exam initially. If it's a really high myope, you got to think about genetic testing and maybe even an exam at anesthesia looking for fever or doing a forcing angiogram or peripheral breaks. If they're sticklers, sometimes we pre-treat those with laser or cryo. So once you've kind of thought about those things, if it's just a young kid under the age of nine and they're myopic, to any degree, I typically see them back in six months, sometimes even less, but I watched to see if their myopia looks like it's progressing quickly. If it is, then I just have a conversation with the family and the Moran is about the best compounding pharmacy with the cheapest price for prescribing diluted atropine and it's in the, it's an epic. I actually went to the pharmacy committee and had them add 0.01%. So it pulls up. You don't have to write anything about compounding or diluting it a special way. So I think this is really, this should be feasible for anybody who is seeing kids and interested. All right, other questions? Bob, could I make a quick comment? Yes, you can. A very basic point, but important, cycloplegic refraction on children is important because kids accommodate readily and you might make a diagnosis of high myopia where there actually isn't any, it's just a accommodating child or progression without cycloplegic refractions could be diagnosed. Cycloplegic refractions for the trainees, medical students, that's really the gold standard to diagnose high myopia. Go ahead, Mimi. There's a couple of questions in the chat, but why don't you go first, Mimi? Oh, Mimi looks like you're muted again. Can we unmute Mimi? I'm sorry, I think it's a safe treatment as well and I've got kids on it and even considering putting my own daughter on it because I'm quite myopic myself. It got muted again, I think somehow. So I... Did you hear what I said? The last thing we heard was you're continuing, you're putting your daughter on it because you're myopic yourself. Brian Stack has a question too if you look in the chat. So, looking at Stack's question. So in teenagers and older kids, I think the highest, one of the leading risk factors for the rapidly progressive myopia is being under the age of nine. So if they're older than nine, they're at a lower risk for the, again, the real rapid progressive myopia which is gonna take them into that minus seven plus range or minus, you know, more than minus seven. So, but I think it would be totally reasonable if you're seeing a teenager to just recheck it in six months and try to get a trajectory of where they're heading. And to David's point, I think you wanna do both of those as psychoplegic refractions just to be absolutely sure that you're getting the absolute measurement of the... But I think, I mean, to add to that, yeah, teenagers, you can for sure put them on it. This isn't just to prevent, you know, pathologic myopia, it's just to prevent any kind of myopia. So I think it's a pretty low risk treatment and if parents are interested, yeah, I think you could definitely put teenagers on it. Agreed. I was gonna add one other, or answer one other question from, looks like from Roger about how much pupil dilation is there with dilute atropine? Very minimal, almost none. So I think if we go to the 0.05%, maybe we'll see a little bit more, but these patients rarely have any difficulty with photophobia again or near blur. I'm not, well, better turn the time over while we have to Catherine to finish off and then we can answer maybe any questions if there's time left at the end. Great. Catherine, who's gonna talk to us about neurotrophic keratitis? Doctor, who? You're up. All right, can everybody see my screen here? Yeah, we can. Okay, perfect. All right, so today I'm gonna be presenting a pretty memorable case to our service. So this was a two-year-old Navajo boy admitted for poor weight gain in malnutrition. This was in May 2018 and it was pretty striking. He was in the 0th percentile for weight and had only gained about 0.15 kilos over the past two years. He also had gained less than half a centimeter in growth and length in the last year. And so we were actually consulted for aid and management of a known non-healing corneal ulcer in the left eye for which he was previously followed by a provider and ophthalmologist in New Mexico. So the parents said that they first noticed about like a small white dot in his left eye with redness, irritation, as well as eye rubbing. And this was starting in January 2018, which was about five months prior to this presentation. And so he had been initially managed with a big amox every Q2 hours and then had been tapered down as he started erythromycin ointment as well as autologous serum tears six times daily. Some additional history, he was born full-term and healthy. Interestingly enough, he did have also a five-year-old sister with failure to thrive, but otherwise his family history was non-contributory. And he does live in Monument Valley in Utah in Navajo Nation. And we had actually seen him on prior outreach trips and he had normal exams at that time. So he was admitted with elevated liver function enzymes and also a whole host of other vitamin and electrolyte and nutrition derangements. And interestingly enough on his neurologic exam, he had absent reflexes as well as a wide base gate. So on our initial bedside exam, he was alert interactive and he didn't really appear to be in that much discomfort. His vision, pupils, pressure and motility were all normal and appropriate for his age. But most notable, he had a 0.5 millimeter paracentral corneal ulcer at five o'clock with about 30% central thinning. And he was noted to have decreased corneal sensation on that side compared to the right. And his dilated exam was normal. So unfortunately, he did have worsening appearance of his corneal ulcer despite aggressive topical treatment. So he underwent an EUA with Dr. Jardine and was found to have an increased size of the epithelial defect. Now about two millimeters from the original 0.5 millimeters we saw on initial exam, as well as increased erosion and thinning. And his ulcer had this very striking kind of excavated appearance, almost looks like a divot in the cornea with a very minimal to no infiltrate and minimal stromal haze. So because of this, we elected to proceed with an amniotic membrane graph with a contour lens. And we used a double layer technique AMT to slow disintegration and promote healing. We also use a contour lens, which is essentially a large 18 millimeter diameter bandage contact lens. And this can be good to use in the pediatric population since it is so big, it stays in a little bit better. It kind of tucks in and prevents irritation from those adovipral sutures. And it also concentrates the AMT to the cornea for full effective in promotion of healing. So this is kind of a timeline of this very stubborn non-healing corneal ulcer all the way from first presentation in January to when he went to the provider in New Mexico. And then all the way to, it was about five or six months when he underwent surgical intervention with us. So on post-op day, I'm just gonna move this screen over here. So on post-op day five, when he saw Dr. Dardin in clinic for follow-up, the amniotic membrane had mostly dissolved, but the left eye definitely appeared dramatically more quiet and there was decreased thinning of that two millimeter corneal ulcer. So he was instructed to continue Vigamox as well as the serum, the autologous serum tears every two hours. And unfortunately when he came back two weeks later for follow-up, the two millimeter ulcer had again increased thinning to about 50% and he was taken the next day for a repeat AMT. So again, he underwent an EUA and we did elect again to perform the double layered AMT technique and also the contour lens. So about one month later after the second AMT, he still had a pretty, the size of the ulcer didn't really go down, but he still had pretty significant thinning, but it had started to re-epithelialize and kind of become more of a scar. And so he was actually supposed to follow-up one month afterwards, but was somewhat lost to follow-up. So about six months later, he came back for a follow-up in December, 2018 and miraculously actually the epithelial defect had completely healed and the thinning had near resolved. And at this time, he was just really using artificial tears for lubrication, but what had really, really changed in terms of his, in terms of his systemic health was that he had significant improvement of his nutrition status and caloric intake with a G-tube and supplementary enteral feeds as closely followed by GI and also the liver clinic. So this is a slit line photo that was taken at that time and you can see that there is a well-healed corneal scar just inferior to the visual access and significant improvement of thinning as well as kind of more fill in or distribution of that prior corneal ulcer site. So in summary, we have a two-year-old who has a non-here, who had a non-healing neurotrophic corneal ulcer in the setting of failure to thrive in severe malnutrition. And if you recall, in addition to his ophthalmic findings on initial presentation, he was also noted to have liver dysfunction and absent reflexes, as well as a broad base gate on neurologic exam. So on a very thorough workup, our patient was diagnosed with a rare condition and that is known as Navajo neurohepatopathy. This is also known as hepatocerebral mitochondrial depletion syndrome and it is almost exclusively seen in children and young infants and children of Navajo Native American descent. An incidence is estimated to be about one in 1,600 live births in the Western Navajo Reservation. And so it is an autosomal recessive disorder and they have found that it is caused by a mutation in this MPV17 gene. And this codes for a protein on the inner mitochondrial membrane that has helped to maintain mitochondrial DNA that is crucial for liable production of energy. And it has been postulated actually that this mutation is closely linked to the high concentration of uranium in the drinking water of the Navajo Reservations. And they have identified this genetic defect by blood samples and homozygosity mapping, which have been published in case reports and literature. So clinical presentations of Navajo neurohepatopathy, they include liver disease, corneal anesthesia and subsequent ulcers, of course failure to thrive, as well as peripheral neuropathy and acral mutilation and acral mutilation being injury to hands and feet and limbs due to loss of sensation, as well as cerebral leukoencephalopathy and recurrent metabolic acidosis and also recurrent infections due to poor healing and again failure to thrive. There are three major phenotypes described for this disorder based on presenting age and that is infantile childhood and classic. So for the infantile phenotype, this is a presentation prior to six months and the patients usually present with jaundice and also peripheral and CNSD myelination. They also have unfortunately very severe liver disease and a result of this is liver failure and death prior to age two. The childhood phenotype is actually very similar to the presentation of the infantile phenotype, just that the age of presentation is one to five years. They also have jaundice and also peripheral and CNSD myelination as well as pretty profound liver disease and death within six months of their initial presentation. And this last form, the classic form is progressive and not really associated with any disease, rather sorry, any age group, but it's more progressive and classically associated with this moderate liver damage and characterized by a more progressive neuropathy. And so peripheral and CNSD myelination can present in any three of these phenotypes and the peripheral neuropathy, of course, is thought to be played a major part in the pathogenesis of their neurotrophic corneal sensation in corneal keratography. So some additional history in our patients. So he does have a confirmed genetic mutation of that MPV17 mutation. He also, a convenient part of the history that I left out is that when he was four months old, he presented with jaundice and hyperbillirubinemia and he underwent a liver biopsy and the microscopic findings of his liver biopsy at that time were suggestive of a mitochondrial disease and that's kind of what kicked off this workup. For his neurologic workup, he has fortunately had normal MRIs without leukoencephalopathy and his sister also has a confirmed genetic mutation of that same MPV17 mutation. He is considered to have a mild and moderate involvement without evidence of portal hypertension, spinal megalitis, or thermobocytopenia. And aside from a mild motor delay, our patient is doing very well with maximizing his nutritional status and replacement environment in mineral deficiencies. So I know as residents, most of us are familiar with causes of neurotrophic keratopathy in adults, including classically topical anesthetics, iotrogenic injury after surgery, and herpetic infections. But I wanted to take some time to discuss the differential of congenital neurotrophic keratopathy as these can be more rare entities that we don't really encounter as much. So the first one is Riley Day or familial dysautonomia. This is autosomal recessive and seen almost exclusively in patients of Eastern European Jewish descent. You can see here with congenitalization of the cornea as well as a dense stromal scar in a patient with Riley Day. Another one is golden har, which we classically learned from Dr. Mamelis is associated with a limbal dermoid as well as a pre-irricular skin tag. And these are associated with embryologic kind of defects in facial and facial development and also the ear. But these patients can have corneal pathology due to decreased tear film production as well as some postulate that there is a hypo development of the trigeminal nuclei. And then the last one on this that I was going to discuss is Mobius Corneal Hypocesia, which is a very, very rare disease entity. And it's not to be due to a non-progressive paralysis, congenital paralysis of cranial nerve six and seven, so the facial and abducens nerve. So corneal pathology in this disease entity is more thought to be exposure keratopathy, though some have also postulated that there could be maldevelopment of the of cranial nerve five as well. So our patient was actually just seen two months ago follow up in July, 2020. He's now five years old and he's doing quite well. He just started reading the vision chart and his vision is 2030 in the right eye and 2040 in the left eye. And everything in terms of his exam is pretty stable with the cornea. Aside from some anisomatropia and a regular astigmatism in the left eye that we were following in treating with glasses, he's actually doing very well. And just reading his liver and GI notes, he's also continuing to do very well with G-tube feeds and they're transitioning him to NG tube for his supplemental feeds. So some takeaway points that I wanted to just highlight on Navajo neurohypotopathy. Overall, it is a very rare disease entity caused by this MPV17 mutation. However, because we see these patients on outreach trips or even in Salt Lake City, any patient with failure to thrive, kind of a non-specific liver failure or liver disease in neuropathy, as well as of course any corneal findings should raise suspicion. And patients with mild involvement can actually do very well with maximal survival benefit and quality of life by addressing their nutrition status and promotion of healing and things like that. Though a lot of these patients will unfortunately have a poor prognosis requiring either liver transplantation or significant rehabilitation. So with that, I'd like to wrap up. I'd like to thank Dr. Dardin and also Dr. Tina Mamelis. She was, I think, the resident that had done a lot of work on this case and also was the first console resident who saw him initially. And so I'd gladly take any questions. These are my references and I'll open it up to questions. Thank you. Catherine, that was a great presentation and kind of underscores the plight of the Navajo particularly Monument Valley where a lot of the uranium mining occurred and uranium is in groundwater in food sources and mine slag was used for house foundations. Interesting to me in that you look at this Navajo neurohepatopathy, the genetic component, whether that all was caused by uranium exposure and then continues to be a heritable defect that these people are saddled with. Interesting that your patient came from Monument Valley which was ground zero for uranium mining is also I think very significant part of their plight. Great presentation and bringing this issue up. It's an important one. Thank you. Other questions, comments? If not, well, thank you all for joining us today and let everybody get on. Now let's just look here at the anything in the chat that we need to pass on here. I think we're okay. Okay, I think we're set as well. One quick comment from Ashley Bernhaisel if you see that Dr. Hopman. Oh, yeah. And actually I think that actually what Dr. Bernhaisel raised was that vitamin A deficiency may actually have been involved. And that was I think corneal zirosis with vitamin A deficiency, very rare to see in the US. But I agree. I think that may have been a strong component here in terms of the nutritional improvement. It really takes a lot of work to become vitamin A deficient in the US but this child may have been a setup for that. Thank you, Ashley. All right, thanks everybody. Have a great day. Remember to claim your credit. Thank you. Okay.