 Let's go ahead and get started. Welcome to, this is Pediatric Ophthalmology, Stout ran around. We're gonna do case presentations. And first up is Dr. Dries, who's lately become quite the expert on superior oblique dysfunction, surgery and everything associated with it. He's gonna share some of the wisdom that he's gathered. Thank you, Bob, and good morning, everyone. This morning, I'm trying to present something that will interest you with quite a bit of information and fairly quickly. So, what if I told you that the superior oblique muscle was not just one muscle, but rather two? And indeed, it kind of is. There are muscle compartments in multiple extraocular muscles. And this morning, I'd like to talk about the compartments of the superior oblique and what that means clinically for diagnosis and surgical management. Thank you to Dr. Joseph Deemert, UCLA, and Steve Archer, the University of Michigan, for helping me with figures and multiple discussions over the more recent years. Here, you're looking at the histology of the superior oblique muscle belly with multiple cuts starting posteriorly and then the cuts march anteriorly. And the two colors correspond to two branches of the trochlear nerve. This green color innervates here, purple-ish color here, and here's a reconstruction of selective, separate innervation of the two compartments of the superior oblique. Separate innervation makes sure that it has a totally separate oblique. Yes. So, what does that mean clinically for diagnosis and surgical management? Well, we do need to talk just a bit about motor physiology at the superior oblique. As we all know about the axes of rotation, the superior oblique is an in-torter, an abductor, and a depressor. So, here are a few diagrams. This is the vertical axis about which the eye rotates horizontally that gets you oriented as to the position of the superior oblique tendon with regard to that axis, and you'll have to think about the other axes, sagittal and horizontal as well. This is in primary gaze, and it makes sense that this muscle has those three functions. What about in down gaze? Well, it does change a bit. It's a better in-torter, an abductor in down gaze, and that's in large part because, simply put, the muscle just pulls harder, but the superior oblique does have this unique anatomy we all know with an origin at the apex of the orbit, coursing anteriorly and curving around the trachelea and then tendon fibers fanning out in the globe, and in down gaze, here, actually here, this is the eye in down gaze. You can't see the cornea very well, and it's kind of hard to understand why the muscle's a better in-torter and abductor. So, let's view the eye in down gaze 30 degrees forward. If you saw the movie, The Matrix, they were fighting and they would freeze and then the camera would pan over to a different perspective. That's what this view is like here. So, the eye is in down gaze. Look what happens to the relationship between the belly, the superior oblique, and the tendon. This is more or less perpendicular. Here, it's more acute, and if you look at the vertical axis, you can see the position of the tendon has changed with regard to that axis, making it a better abductor in down gaze, and the tendon is more at the equatorial position, giving it better in-torsion in down gaze. The contribution from this unique anatomy is only about five to 15% increased in-torsion and abduction. Mostly, it's that the muscle's just pulling harder. So, what does this mean clinically? Well, what's it like to have torsional diplopia? This is what it's like to have torsional diplopia. This is a 55-year-old photographer who supplied this photo shot, photo of what it's like to walk down stairs at an apartment complex. And I would just like to show you in this diagram the compartments of the muscle. There's a lateral compartment of the superior bleak and a medial compartment. The lateral compartment, its tendons insert on the posterior fibers of the tendon and the medial compartments inserts on the more equatorial anterior fibers. So, the lateral compartment has more depression, and the medial compartment has more in-torsion. The case here is a lady, mainly with tons of torsion, okay? So you think, maybe this is a selective medial compartment peresis. One could speculate. She has lots of torsion, eight degrees in primary gaze, much more in down gaze, 15 degrees. Really makes sense that those anterior fibers are affected, right, in the medial compartment. And look at her vertical deviation. It's really not that big. It's really quite small, and there's not much incomitance in down gaze. So the posterior fibers of the tendon probably are less affected. Probably the lateral compartment is less affected. So what surgery would help her? Because she's suffering. Prism isn't gonna work. Well, let's go back to the 20th century and talk about the Harada Ito procedure. Initially devised by Japanese Dr. Harada Dr. Ito just to anteriorize the front tendons of the superior bleak, but later fells modified it by splitting the tendon and transposing these fibers temporarily and anteriorly on the globe, giving them a better mechanical advantage to in torsion. How did it work? Well, quite well. Her extorsion is two in primary gaze, six in down gaze. She still has her hypertropia. Initially she fused two weeks out, but three months later, she did have trouble controlling her dyplopia again, especially in down gaze. Luckily, a small amount of vertical prism and she was fusing and she liked spectacles in the first place and she's happy. So does she have a selective medial compartment superior bleak peresis? One can speculate, but we really don't have dynamic MRI that will really tell us this in these patients at this point. Let me just talk about one more case. I think this is bilateral and maybe even a bilateral medial compartment trochlear peresis, a 60 year old female director of medical directors at the University of Utah, torsional and vertical dyplopia with a small head tilt going back to the teenage years, but a worsen recently after she had cataract surgery, which often happens with clarity of vision in patients with preexisting strabismus. She had dyplopia when driving and when reading. Let's look at her exam. Bit more complex than the last one, but look at how much torsion there is. 15 degrees in primary gaze, 16 degrees in down gaze. That is a lot of torsion. And let's look at her exam. Again, a hypertrophy that's not large without much incompetence, which would argue that the posterior tendon fibers at the superior bleak and the lateral compartment probably are not as affected. She does have a V pattern in an esotropian primary gaze. She doesn't have classic three-step Park-Spielczowski testing for superior bleak peresis, but I think she probably has a mass bilateral superior bleak peresis. When patients are this complex, you gotta break down the deviation. You gotta treat their extortion, their esotropia with their V pattern and their hypertropia. A superior bleak tuck might have been a good choice, but it chose not to do that because she had such little incompetence of her hypertropia and her hypertropia was small in down gaze. So instead for her hypertropia, a contralateral inferior rectus recession is my procedure of choice, the yolk muscle of the predic superior bleak. She also has the esotropia with the V pattern. She needed a meteor rectus recession, one half tendon with infra placement for the V pattern, but keep in mind, when you transpose recti muscles, you induce torsion and if you infraplace the meteor recti, you're going to make her extortion worse. So she had a bilateral herata ego, bilateral with the goal of creating 15 to 20 degrees of mechanical encyclotorgen under general anesthesia, which we can do with a Mendez ring. The refractive surgeons know what that is and the stupasma surgeons are beginning to learn about it because you can mark the lid, mark the limbis, do your surgery, change torsion and measure how much you got mechanically. There are other ways to do this, but this seems to be the most convenient easiest for me. So how does she do? She was fusing in all gaze positions except for extreme down gaze. Her extortion was five degrees in primary gaze, five in down gaze. So she did very well and mainly the point here is, could she have a bilateral medial compartment superior oblique peresis? So what if I asked you, does the superior oblique muscle have two compartments? Well, you'd probably say yes. Thank you. Next, Terahan, resident currently on the PDF got home initially about our next patient and then I'm gonna have some comments as well. So this is an 18 month old boy who at birth developed infantile spasms and was noted to have unilateral hemimegalencephaly, which is an enlargement of one cerebral hemisphere. He had a left hemispherectomy, but despite this he had persistent seizures. After a vagal nerve stimulator and starting the ketogenic diet, this helped, but he still has about 20 seizures per day, which is better than about a hundred that he was having before. His mother had a normal pregnancy, normal ultrasounds, no known infections during pregnancy and he was born full term. There's no family history of seizures, no neurodevelopmental or genetic diseases that run in the family. And his developmental history, as you would expect, he's developmentally delayed. He's able to sit with support, he can throw objects and he likes toys that have lighted buttons. He can't say any words, but does communicate his likes and dislikes with sounds. This is a list of the medications that he's on. As you can see, he's on Sabral or by Gabbatron and we'll be talking more about that. Because of his use of Sabral, it was recommended that he get eye exams. Unfortunately, the first exam that he got was just VEP and ERG without an EUA. So the first time that we're seeing him is in April of 2018. In the clinic, he has wandering eye movements and XT and then for his EUA, his pressure is 712 and this is a cycloplegic retinoscopy. And so as I said, in 2017 he had a VEP and ERG without the associated EUA. So we do have a comparison point and that you can see that his P100 amplitude is slightly better back in 2017, but this wasn't under anesthesia, so probably pretty comparable. And this is single flash ERG and you can see that he has decreased B wave amplitude. And this is 30 Hertz testing the cones and he has a very poor cone response bilaterally as he did back in 2017. All right, so this issue of Vigabit, the question at this point with his child when he came down here from Montana was, is there evidence of Vigabit or toxicity? And we typically do an exam under anesthesia, do electrophysiology. It turns out that many years ago when this drug was studied, Don Creel and I were among the investigators that participated in gathering data that brought to the fore the issue of Vigabit or toxicity in children. And in this child, that is definitely an issue. And the thing that was striking with our exam under anesthesia was these changes depigmented areas from mid peripheral retina out to the periphery. The optic nerve notably looks healthy. We, because of issues getting test accomplished did not get an OCT during our recent exam under anesthesia. And what we did do the electrophysiology that you saw and the thing that struck me with that electrophysiology was that the cone ERG, the flicker response, which is predominantly a cone response, all we saw were stimulus spikes. That was a grossly abnormal electroretinogram. The manufacturer of Sabral has recommended that testing be done every three months, including electrophysiology and all children on the medication. We have held the line in doing it here every six months recently incorporated doing OCT. It turns out that retinal nerve fiber layer thinning has been identified as another component of this toxicity. In looking into this, there are a couple of things with this kit and I wanna show you some of the pictures. These are these areas of depigmentation that are present and fortunately the posterior pole looks relatively normal. One of the questions here is, is this Sabral toxicity? And I apologize for the flashing. I have no idea how to operate this when it works, let alone how to troubleshoot it. So if anyone has a clue, please jump in. Any of the residents, as far as is, if we were to consider other things, what else should we consider? You've got an abnormal electroretinogram in an infant who's got borderline poor vision and some pigmentary retinal changes. RP could be some sort of retinal dystrophy. The other question in a child who's got abnormal neurologic function is, in my mind, was is there some evidence of a metabolic disease? It turns out that we have him scheduled to see Dr. Longo, who is our pediatric geneticist metabolic specialist. So we will hopefully have answers on that. In the interim, the plan, quite forcefully to pediatric neurology, was let's taper him off of Vicabatron while we were sorting this out. We are going to bring him back at our next exam. We will do an OCT and we'll have more information. In terms of looking into this, what have we learned and what have I learned in putting this together for you? It turns out that Vicabatron is an irreversible inhibitor of GABA aminotransferase. And when you have increased GABA, you have decreased seizure activity. Where is it most frequently used? At least 90% of the patients that I see this medication used in have tuberous sclerosis. Why is it the magic bullet for seizures and T.S.? That is an unknown. Now, the ERG changes that Dr. Creel identified years ago include a decrease in the cone B wave, decreased in flicker amplitude. And the thing that most people remember is absence of oscillatory potentials, those little spikes you see on the elevated portion of the B wave in the electroretinogram. Nasal optic atrophy and nasal retinal, kind of segmental retinal atrophy were described by Ray Bunsik at hospital for sick kids in Toronto back in 2004 for monitoring, again, electroretinogram, fundus photos and OCT. Now, one thing I learned that I was not aware of is this has been associated with a cumulative dose greater than 1500 grams of drug. So we're going to need to start recording that when we see kids. We've not been doing that. The other issue is question of does this have long-term implications? And there are at least two papers suggesting that it indeed does. In adolescence, with documented sabral toxicity early in childhood, when they were seen later, when one could do a goldmine visual field and do OCT, looking carefully at nerve fiber layer thickness, there are abnormalities seen in adolescence from documented toxicity early in childhood. This is years off. Years down the road. And this is really opening a can of worms. And then the other issue is these authors, and this is a French group of investigators published in pediatric neurology presented VEP and ERG stimuli to selected parts of the retina. And what they found were that there were issues in the peripheral parts of the retina that they were abnormal when presenting these flashes, both VEP and ERG in school-aged children who had been exposed years earlier. And these were school-aged children who had been on the medication that did not have documented toxicity. So there's real question about this and reason for us to be following these kids closely. And so, now, setting that aside, I wanted to think, you're in clinic, it's very busy, you get a text. And the text is from one of your radiology colleagues. And the text basically just says, what is this and do you need to see the patient today? And here is the scan. And this is the only image I got. And yes, it was this fuzzy on my cell phone. And you see what looks like a lens here and not much of an anterior chamber. And so I'm wondering, is this a child with anterior segment dysgenesis that they've discovered? Say, tell me more about the patient. It turns out that the patient is a healthy 12-year-old girl head injured CT from an outside hospital reported to have perfectly normal eye exams, good visual acuity by mom. And this was an artifact. And I don't know in retrospect whether he sent this to me as a joke or seriously asking a question. But when things don't look right, you wanna wonder about the source of the information. And back to the first case, questions, comments particularly from our retina colleagues in neuro-othemology as far as this issue of bi-gabatron toxicity. What percentage of all patients on this medication do you think end up having toxicity? We talked and this is an extremely rare occurrence. This is a rare occurrence. It's a rare occurrence. When we were doing, they're doing the initial treatment trials and we were doing electrophysiology, they were using much higher doses. The doses they're using now are much lower. And I have, this is the first patient in recent memory that I have recommended that they stop the medication. Almost all the other patients we've been on have had good electrophysiology and we've had good stable electrophysiology. And again, the issue with this first ERG to understand is when you put a patient under general anesthesia, it suppresses the EEG. When you suppress the EEG, you decrease the response that you're gonna get with electoretogram and particularly with the VEP. So that anesthesia can alter it. So comparing an awake study to an asleep study is not necessarily a good thing to do and draw firm conclusions. Yes, not that I am aware of. Clearly the RPE looks like it's being impacted. Yeah, this is, if this is due to Vygabitrin, this looks like RPE. The other thing I'm gonna do when we go back next with this child and they've gotta come down from Montana and we have to coordinate care is I think it'd be wise to do an FA. We can easily do that now with a RETCAM. And Glenn Jenkins has been very good about coming to do FA's for us and helping us through that, both with PEDS Retina and Pediatric Ophthalmology Services. And doing an FA I think would help sort out where this is. The other thing I thought, as far as the metabolic disease of this, could it be gyrate atrophy or something like that? And, but there you've got loss of Choroid. This does not look to me like loss of Choroid. It looks like simple loss of RPE. I've never seen anything look just like this in any of the patients that I've either seen in person or published with Vygabitrin toxicity. So I think the important thing is the finding that this indeed can be a permanent change from a permanent loss of Daner. So, who knows how advanced that could be if somebody doesn't pick this up and then just could extend it very well. Well, the other plea I would make is that rather than having someone order the test, I think that having someone look at the eyes carefully and thoughtfully is highly desirable in terms of trying to sort these things out. Yes? I mean, the hard thing I think about Sable is it's an amazing drug for a lot of kids. And so it's not like, I mean, in some cases you have to have the discussion with parents. Would you like to take them off this drug which is the only drug that can control their seizures or the trouble I've had with this drug is that when I put them under anesthesia and do these repeat ERGs, sometimes they'll get a little lower, sometimes they're a little higher. And some of it a lot of it has to do with under anesthesia, they're a little bit different and it depends on how light the anesthesia is. And so I have trouble sorting that out and these are usually very delayed children that you can't get much of an exam in clinic. And so it's hard to know that, but it is, you know, it's really getting lower and you look at their exam in clinic and is it really worth putting these kids under anesthesia because these are kids with lots of other developmental problems. But this is the only drug that controls their seizures. It's a very difficult drug to deal with. What I said, I'm impressed how kids with uncontrolled seizures just are developmentally stalled or regressed, they're in a vegetative state. And if you can't get the seizures under control, their life expectancy goes to the teens. So this is often the option that parents have. So I find that the parents are often very comfortable with the risks of vision loss because their child for the first time is developing their brain, is not seizing and they're starting to hit milestones. So it is, it's a very complicated situation. But then they say, but you can put glasses on and fix that. Right? And that's the issue because this issue of having a brain that functions is important and it is a night and day difference. Dr. Warner. At the analyst last year, one presentation discussed a prospective trial of by Geltrin and doing baseline prior to taking medication and a very high percentage of the patients had abnormalities on RFL, on electrophysiology, visual fields, and. Prior to. Prior to. Exactly. And they had the study go on for a couple of years and they didn't see any statistically significant changes in the visual fields or RFL. Maybe the RFL actually increased a little bit and no patient had lost immunity. One patient developed visual field constriction. So I mean, I think that that's sort of called into question because a lot of the studies are done way later after the exposure. Yes. And it's, you know, understandably a lot of patients were very young at enrollment and couldn't have done a pre-treatment extensive testing. Right. But it's been somewhat controversial as to the really frequency of how often this really occurs compared to the potential benefit of the drug. It's a tough call. We try to get pre-treatment testing, you know, whenever possible. And this situation we're in here unusual for me where I've never seen the child and the very first time I see them, they've been on it for a long time, supposedly been tested and things don't look good. And we're trying to sort out whether it's old or new, which is exactly the case. And I also think of the point of the syndrome kids who, you know, there's often a reason why they have intractable epilepsy and end up on pre-treatment. That may definitely include a potential retinal issue that's related to their own disorder rather than their drugs. I'll bring additional info back. Dr. Bernstein. Yeah, just as a plug, we do have a genetic counselor that we're hiring as of July 1st. You need to do genetic testing on a patient like this because you're bringing up the idea could this be a retinal disc repeat? Yes. A retinal disc repeat plus a toxic drug and all sorts of disorders, so to say. And the genetic testing prices are coming down, so compared to a lot of other testing you're doing. It's, they're plugged into genetics already and hopefully we'll get some sort of answer in terms of an overall, better overall diagnosis. All right, next, moving on. Number three, oh, Dr. Young. Dr. Young's gonna talk to us about a very interesting patient that led both of us, I think, initially. So I'm gonna present a case of a kid I actually just saw in clinic last week, Tuesday, and the kid came in and I kind of started to discuss it quickly with Bob and he said, oh, you should present that case. So this is a six-month-old kid who was in my 930 slot last Tuesday, came in because he had some left orbital swelling. He had been treated by his primary care doctor with a course of augmentin. After he'd been on that about two days, mom felt like it got worse and she went to the emergency department where they saw him and said he has a little bit of injection of his conjectiva, some swelling with erythema of the upper lid, thought the pupils were equal and reactive to light. They thought he looked around, looked fine, told him to go home and come back and see his primary care doctor in two days or follow up with them if things got worse. But nothing got better and so they were a little bit concerned and talked to their primary care doctor and decided that they needed to come see ophthalmology. His past history is pretty insignificant. He was born full term. There was no family history of any eye problems, no past medical history. On exam in the clinic, he would follow things with his right eye but would not follow anything with his left eye and got mad when you covered his right eye. His pupil on the right was round and reacted. The left, I had a hard time seeing but it certainly didn't seem to move at all. His pressure was normal in each eye which I was able to get with the eye care. He had pretty small palpibral fissures. He was a half Asian kid so he didn't open either eye a lot but the left eye barely opened at all. The anterior segment exam on the right eye was clear. When I could get the left eye open, he had a very, not a very, but he had a hazy central cornea there and it was difficult for me to look at the anterior chamber. So at this point, I was a little bit concerned that he had kind of a fuller, it didn't look so much like a swollen orbit to me but it made me concerned that mom was saying that it was swollen. What's going on here? That in addition to an eye with a cloudy cornea that I can't see to the back, couldn't really dilate the pupil and the pupil was unresponsive. The bad thing that I was really worried about was is this retinoblastoma with extracular extension and that's why he's got some orbital changes. Mom said it kind of comes and goes. I looked at her phone and it didn't look like it, she said it wasn't there right after birth but had come later and I was wondering if maybe this could be something like a lymph angioma which has kind of a course that comes and goes but that didn't really go with the cloudy cornea. Could this be a tumor like a rhabdomyosarcoma? Something else that's very worrisome but always thinking of. Dermoid cyst, we see these commonly but that also wouldn't go with the cloudy cornea norwood congenital ptosis. Always think about congenital glaucoma in any infant you see with the cloudy cornea but his pressures were normal and that kind of rules that out in a kid. Or is this a retinal detachment with the pretisical eye and that maybe it's not really a swollen orbit, maybe it's just a small eye that doesn't open up as much. I was thinking about those things while I was letting the kid dilate and I took a brief look at the dilated exam in that right eye and thought it looked pretty normal but was quite concerned about the left eye. I couldn't get a view at all, couldn't get that pupil to dilate at all and fortunately that day I was at primary so I was able to send him over to see Dr. Harry for an ultrasound which showed a total retinal detachment and interestingly an axial length in the normal eye of 20 millimeters and an axial length in the left eye of 14 millimeters so I thought, oh, this is PHPV. This is a smaller eye with the retinal detachment. You know, it just, maybe a little bit of a and the eye is smaller so it just doesn't open as much. This, you know, doesn't have anything to do with it being swollen at all and kind of started to talk to the family a little bit about it. They were understandably quite upset but I also recommended that we do an exam under anesthesia just to get a really good look at the right eye to make sure we weren't missing anything else but I was pretty sure this was what was going on. They were quite concerned that we, you know, although there was a retinal detachment here that I didn't think we could fix that retinal detachment but I said, let's just get an EUA. I have OR time tomorrow and then we can have a better idea of things. So we put the kit under anesthesia here and these aren't the greatest photos but the right eye has a nice clear cordia. The left eye and a normal anterior segment. The left eye here, there's a haze here in the middle. The pupil is, you know, about a millimeter big and the iris is all the way up to the endothelium and I think that's why the cornea is cloudy. It's just starting to. The anterior segment doesn't look particularly, doesn't probably look like corneal. No, no. The anterior segment actually looks pretty normal. It's just that the, there's no, there's no AC. It's about a half millimeter difference in corneal diameter in the OR. Yeah, no. It's attracted to pressure, 17. Yeah, it was 17, normal. Yeah, pressures were normal. And we rechecked it in the OR and it was, it was even less, it was like 13 and 11 or something like that, very normal. I took a picture of the kit under anesthesia and you can see that this was at the end of the case but apart from the lid speculum marks, it doesn't really look like a swollen eye. It more looks like, you know, it's, the orbital swelling was just kind of a red herring. This is just a smaller eye that doesn't open as much. We also did some electrophysiology and electro ERGs here and you can see that in the right eye looks pretty normal. Single flash here in the left eye, almost nothing. And VEP is, you know, very abnormal as well. So at this point, we were, you know, I was, we kind of looked around inside the eye and taking a little closer look now that the kids are under anesthesia and, you know, Bob and I both took a look here and we could see that there was this depigmented area here which made us a little bit, take a little pause and think a little bit more about what's going on with the retina. Also, if you look, you know, a little more closely here, you can see that the vessels don't seem to completely go all the way out to the edge but at this point, we were, you know, still kind of thinking about it and kind of still thought it was a PHPV until we got in the floor scene. Glenn was nice enough to come over at the very last minute and do a floor scene for us but you can see very nicely which, I don't know, you can't, the lights are on a little bit here but this showed up much better on my computer. Yeah, if we can hit those lights off here. Oh, this picture up at all. It shows up much better on my screen here but the vascular retina ends right here. And this all branches out into fans which showed up much nicer on my computer here but pretty, and as well down here, you can see a little bit. It just adds a little bit of a... Very dramatic. Very dramatic. The vascular areas in that eye. So pretty clearly looks like something like fever now which we were completely thrown off until we, you know, did this under anesthesia. There's no leak, you know, these are the later frames here at two minutes. There doesn't seem to be any leakage. It's just all peripheral abasca retina here. You can see it just kind of fans here into a, you know, ear pattern. Looking here. So, very glad, you know, you can also see it from here as well. We put this kid under anesthesia to kind of answer that question a little bit better. So just to talk a little bit about fever which is something I didn't see so much in residency or fellowship but have seen a couple of cases and picked up on a few cases as in attending. It's characterized by peripheral abasca retina in patients without a history of retinopathy and prematurity really kind of looks like ROP. Can be very asymmetric and has variable patterns of inheritance and penetrance. This is actually one of my patients here who had kind of a similar story born with retinal detachment in the other eye. This I actually was initially doing much better and then, you know, just suddenly took a turn for the worse. You know, when the kid was a couple of years old and started pulling more and more and more although she had many times been lasered. So certainly can have a course that's very unpredictable and can change very, very rapidly. There's a paper in Ophthalmology in 2014 done by Mike Tracy's group that suggests that the prevalence of fever is quite underestimated. They looked at 74 subjects of 17 families and found that 58% of asymptomatic family members had stage one or two fever and 21% had stage three, four or five. So our patient would be a stage one just because they just have peripheral vascular, avascular retina. Stage two is, you know, when they start to have, you know, can start to have some exudate and a little bit more concerning. So 35% of these asymptomatic people had stage two which is kind of that stage that can really take a turn and start causing a lot of problems in terms of retinal detachment and macular dragging and things like that. So the question for me is how do you pick up on these kids, you know, when you see them in clinic and when can you identify them? I mean, this is one of the few retinal dystrophies that we can do something about and we can prevent vision loss. So what are things we look for? We can look for straightened vessels. We can ask about a family history but that's not always so helpful unless it's positive. If it's negative, it doesn't really help rule this out. We can look for some vitreous opacities or things. This is actually one of my other patients who was seen by another pediatric ophthalmologist in town. He had a little bit of nystagmus, had a Chiari I malformation, had actually seen neuropa at one time for his nystagmus and his Chiari and questions about whether they wanted to decompress that. He came to my clinic because the other pediatric, he had a head turn and they were considering doing a Kestin bomb so they came to me for a question of whether we should do surgery for the Kestin bomb and I said, well, what is your ophthalmologist or what have people said in the past about that tough to vitreous that's in this, you know, right over as an optic nerve and the family said, well, we don't know what you're talking about. And I sent this patient up to Emmy and it turns out this kid has fever and the nystagmus was probably due to the Chiari and he probably had both things but he ended up getting some laser in the periphery. Vertical stribismus, I have a couple of fever kids that have kind of funny vertical stribismus but we often see that too in kids who are dragged in RLP. So these are kind of some things that I kind of think about when I'm looking for these kids. The other thing that, you know, is a huge part of our exam, sometimes the biggest part of our exam is the retinoscopy and so I always kind of think about when I see kids with really high refractor, oh, sorry, this should be mine, yeah. Do these kids have fever? I have a couple of kids with fever who have really asymmetric, you know, this is a case report that was actually written by my mentor, Boston Children's, where they was published in 99 but looking at, you know, this kid who had some anisomatropia and this is actually the eye with the worst fever and they conjectured that maybe the disease could be associated with this axiomyopia. I have seen this in a few cases. I have at least one kid who's a minus nine with fever and one eye and nothing in the other eye but I also, you know, this other kid here is that I showed as a, you know, Plano in each eye. So certainly doesn't always have to be that. Also high myopia, kids with really high myopia, I kind of wonder about that as well. This is, there was a Taiwanese study that was published in 2002 that looked at kids and said that all of them had, they looked at nine patients actually with fever that they saw consecutively in their clinic and all of them had myopia greater than five diopters by age eight. This is another kid I saw who came into my clinic just after failing a vision screening and maybe a little bit of straightening. This is from his first EUA but he was 19 months old and had this refractive error. Also had a little bit of exudate here and I sent this kid up to Emmy and ended up having fever as well. So bottom line is I think it's a lot more common and I think sometimes we miss it and I think it is something that we can do something about some of these really sad cases like it can cause devastating vision loss but I think we're missing some of these cases. It's good, you know, this is the, one of the reasons I'm so glad we have our pediatric retinocerous with Dr. Hartnett, I mean the issue with this case that she presented is that without knowing the diagnosis, this child's only eye is a significant risk of vision loss. We're gonna go back and do a combined EUA for pediatric retinocerous. That I will probably get laser treatment to the abascular retina. So this is making a big difference and these are cases, it was tough to sort this out that we likely would have missed years ago and so I think that this is a clear case we're having a pediatric retina specialist that has brought this disorder into our consciousness and made us a lot more aware of it. So the question is, in the left eye? Yes. Is it feeding, this was bilateral fever? Yes, yes. Or was there a PHPB in the other eye? No, I think it's. So is fever sometimes associated with that mark difference in regards to overall globe size? I don't know the answer to that. If, I mean once you have the, this is an eye that probably didn't thrive and had retinal detachment very, very on. So, okay. And in vascular development. We know that can affect globe growth. And that's what I attributed the very short eye to was that it probably, if we don't have a prenatal ultrasound, what would be fascinating is that they had one to go back and look and see at what point in development. So this thing could have been attached potentially even to the uterus? Oh I think it did. Yeah, oh it did. I think it did. So that's what we would, I think it's a size difference too. I think it's a pretty tight funnel in there. I think it's been there a long time. So the other thing you're telling is you look at these signs but it sounds like in these mild cases, the only way you can know for sure is a fluorescent angiography. Am I not right? No you're correct. That's right. And if you hadn't had a fluorescent angiography. No, and I almost didn't. Cause to me it looked pretty like a, like it looked like a PHPV to me. You know, and that with, especially with the globe size, I almost didn't do one. But then I just kind of been thinking and I've seen kind of, I have a collection of these fever kids now and I'm thinking about it more and more. So yeah. You're right. Cause even in the or looking at the peripheral retina, she and I agreed, something isn't quite right here. Let's get an F.A. And the F.A. night and day difference. So. It was just that one depigmented area. And then the vessel, it just looked a little funny, but not really straightened. I mean, you can, it didn't, it's not advanced enough. It was just themselves. Okay. Sorry. I wish the advantage. You're not better. This is great. Thank you very much. Next, we're going to hear from Dr. Owen, who's going to talk to us about new onset esotropia. Sorry. Lost on the list. No, that's okay. We only have a few minutes. So I'll just go through kind of quickly. I don't want to delay anybody today. The patient that I'm presenting was a previously healthy two year old girl. She was born full term, no prior medical problems, not a patient of our clinic previously. She was initially presenting to the pediatric ophthalmology clinics from the primary children's ER. And she was seen there after a chair fell on her head. And the chief complaint in the ER, she had new right eye crossing with a face turn. And it was after this unwitness blunt trauma to the head. She did not lose consciousness when she was evaluated in the ED, which was initially the day after her trauma, she was sent home without intervention. She then represented to the ER several days later because her parents were concerned that her eye was still crossing, her face was still turning. They didn't understand why this was the case. At that time, we were consulted. We documented a right esotropia, but a normal dilated exam and the recommendation was made just to follow up as an outpatient. And so I saw this child six days after the initial injury in my clinic. And to highlight some of the pertinent parts of the exam, this was a two-year-old child, not reading the eye chart, but did have normal tracking abilities in each eye. But on her strabismus exam, you can hopefully see, it's a little small, I apologize. She has a right esotropia that is greater at distance. It's 25 at near, but 35 at distance. It's also incommitant on my exam, which is probably why she has at least a 30-degree head turn to get her eyes into the left gaze position where you can see she no longer has a right ET. And I did document aduction limitation in the ER, our evaluation felt like there was no adduction limitation, but she did have the face turn at that time, which is kind of a red flag for an incommitant esotropia or eye misalignment of any kind. Because generally a new onset face turn, why would anyone do that? To keep their eyes straight. And so that must mean there's some position where their eyes are straight, and by definition that means it's not incommitant. Because in a incommitant deviation, the eye misalignment is the same in all directions of gaze, therefore there would not be a position, a head position that would be advantageous at least to give you binocular vision. So these things were concerning to me. The rest of her exam was fairly non-focal. She didn't have optic nerve edema. Her dilated exam, I agreed, was normal. And she really didn't have a significant refractive error. She wasn't a high hyper-op. So I recommended that we scan her and the radiologist read is gonna be most informative, more so than my impressions. But essentially, this is the computer, that the radiologist was coming to us. All right, so they found these flare hyper-intensities that were bilateral. They had a specific pattern in the white matter. They didn't notice volume loss, but they essentially called this a picture of Luko Malaysia, but they weren't quite sure. It didn't look like anything that they could call specifically from the MRI, but it wasn't normal. The other thing that was really interesting to me is that they didn't feel like it looked very acute. I mean, we were imaging her because this all happened after what I found out from the mom was that a chair that was sitting up on a table, she pulled it off onto herself in the kitchen. So I expected to maybe see an acute finding, but this didn't seem acute. So it was really interesting and perplexing, and I thought a neurologist would be better able to evaluate it. So I referred them to neurology and their findings, they did find a right six cranial nerve palsy, which is what prompted everything in the first place. She was maintaining her head position when she saw them in clinic, but they didn't notice any other neurologic deficits in their clinic. They were specifically looking, it sounds like, for things like spasticity that they didn't find. They felt that they were in agreement with her pediatrician and her parents that she'd been meeting all of her developmental milestones. They really could find no clinical evidence that would coincide with her MRI findings. And they also said they can't tell if the white matter injury to her brain is old or new. So it was really kind of perplexing. Their plan was to watch her carefully. They're gonna repeat a brain MRI in three months. It has not yet been three months since this was done. Sooner if she develops any other motor deficits. And then they're also doing some blood analysis to look for things associated with different leukodystrophies because their main concern was this thing called vanishing white matter disease that I had not previously heard of. So we'll talk a little bit more about that, but I think the salient points and the reason I wanted to present this is that when we see new esotropia in a child, we never know if they had a tendency previously that was unrecognized and that their disease process has worsened and this is just a manifestation of something that was already present or if this is truly a new phenomenon. And it has implications for what the cause is and if we should image the child, if we should look for any concerning underlying etiologies. So some things to watch out for if it's an incombitant esotropia, that's a big red flag that this should be imaged. And it can be difficult in a two-year-old child to ensure that all of their ductions are completely full especially in an ER setting. And so some things that can, it's certainly a induction limitation is going to help you determine if it's incombitant but a new head posture as we discussed earlier is also a sign even if you can't fully evaluate the ductions or feel like you might not be getting a true picture. If they have a new gaze position, a preferred gaze position, that is a red flag. In the setting of eye misalignment, it's a red flag for an incombitant eye misalignment. But if there is no eye misalignment but they still have a new gaze preference, that's still worrisome. They could have a new homonymous hemianopsia or something like that. So any time a child has a new head posture, it should be a cause for concern. And especially in the setting of trauma, even if you feel like the parents are poor historians, they don't know what they're talking about. This probably has been going on forever. In the setting of a trauma, you have to give the benefit of the doubt to the parents, I think. And so what if this was actually a incombitant esotropias I think was initially thought? Well, there's some guidelines for this, which we don't need to go into in depth, but people have studied this. And even a new onset, a comitant esotropia can be cause for concern. And they found in their study that out of these 48 children that presented with an acute comitant esotropia that about 6% did have an intracranial process that would account for that. And the things that were red flagged in a comitant deviation were larger angle at distance than near, which really suggests possibly a cranial nerve 6 etiology that's really a notice because that pattern because the lateral rectus muscles, which are innervated by the 6 cranial nerve are more important at distance and have more activity, we think. So common because it's bilateral? Comitant meaning it's the same in all gaze directions. The reason why a 6 would be comitant is because you've got one. I think it might have been missed. If there's truly a distance near disparity, it may be a missed 6th. And they may be calling it comitant when it might be, yeah. But obviously if the child has neurologic sign symptoms, they included optic nerve edema in this. If they have recurrence, like it gets better and then it comes back. Or if they're older than six years of age at the time they present, those are the things that correlated in their study with intracranial pathology causing the deviation. So even in a comitant esotropia that's new, there can be a reason to image those kids and those are some of the things to look for. So what do we know about vanishing white matter disease and why would that be causing this 6 nerve palsy and how is it related to the chair falling on her head? Well, we don't know for certain that she has this, but I think the reason neurology suspects it is that it is a stress-induced leukomalacia. And the MRI was substantiating the fact that this child had a leukomalacia. The chair, they feel like, could have been the stress that caused this chain of events. You can see here that there is, we won't go into detail, but there is a molecular rationale for why stress could potentiate this disease process. But essentially these children, like our patient, if this is an early childhood onset form of the disease, they do tend to develop normally. They may have some mild motor or speech delays, but they can be completely normal until you see evidence after a trauma of something like any neurologic deficit. In ours it was the 6 nerve, but it can be a taxia or spasticity. And you can see that there is some concern for life expectancy. It's an awful disease, you should read that. Yeah, we won't go, it is an awful disease, and it's really hard to fathom considering that she's a cute, normal two-year-old right now. And so for me, this is a conundrum because how do I treat her? Her head is like this. And so that is not sustainable. You know, for long-term. But it is allowing her to maintain binocularity, which is one of our goals. So I like that. I don't know how she would respond to strabismus surgery for a couple of reasons. Would strabismus surgery stress her in a way that could potentiate her disease progression? Otherwise, I don't know. And I wouldn't want, and it might not just be relative to the eyes, it could potentiate other manifestations of the disease, which I would not want to do. I mean, she's currently binocular, even though she's got this giant head turn. I don't want to make things worse for her. And then would she respond normally to our traditional strabismus dosing and techniques because her neurologic system is not normal and that's what's causing this. Often in our accommodate abyssal tropes or partially accommodated abyssal tropes, if we're doing surgery on them, we feel like the innervation is fairly normal, the muscles are fairly normal. So we have some framework to believe that they're gonna predictably or somewhat predictably respond to our surgical dosage, but in circumstances where the muscles are abnormal, the innervation's abnormal, they don't respond as reliably and would a surgery be able to allow her to maintain a straight eye position? Would it be worth it to do that? I don't know. So we're kind of working through this now with neurology and with the family, but any thoughts would be appreciated.