 So, of course, that are more based on the anatomy and things that our chief gave us videos a couple years ago to learn from. So, this is just for anyone to... Oh, you turned it back on? Yes. Got it. This is not a layer of the mantaire poster, if you've got it. Which layer of the Irish is absent at an Irish crypt? So that's the crisp form on the anterior border of the layer. It's not there and allows the indentation to form. This is the Irish dilator muscle travels. But I thought my dilator was the creole nerve 5. And then the sphincter muscle is the creole nerve 3. Unless I mix them up, which couldn't be possible. And then the nerves that interface the sphincter muscle kind of has talked about. Synapse at ciliary gangling, adding a Westphal nucleus. The ciliary spinal center budge or the superior cervical gangling. Just killing it. The ciliary gangling. It does go through the adding a Westphal nucleus, but does not synapse there. And the other two are sympathetic pathways. Which two drugs diagnose that one or syndrome and which one helps local isolation? All of these cause anisocoriograe in bright light. Except for which one? See. These structures are involved in pupillary constriction, except... Kind of wondering. Goes to the short ciliary nucleus. Not the long ones. And the last one, which pharmacologic agent best used to diagnose or syndrome in the acute phase? I think it's... Sorry. So we're going to go over a few cases. As illustrative points in terms of just things to know in a neurophthalmology clinic and on call and in general. So this first case here is someone who... I saw in clinic fairly recently. She's a 68-year-old woman. She has a history of breast cancer. She had a mastectomy for that. She had been seen by Yuveitis Clinic because she had an episode of nodular scleritis in the right eye. And she had laboratory workup for that. Nothing had come back and she had been treated and it had gotten a lot better. She had a history of convergence and sufficiency. And so she was referred because she's had this anizocorrhea that's been pretty persistent, but it has recently, or more recently, the clinic has become a little bit more pronounced. So when she's telling me about her history, she says that I was a grad student in Paris and I couldn't read really well and they diagnosed me with convergence insufficiency and they gave me some exercises to work on. And it got better and I've only seen an orthopedist once since then and I haven't had to do anything else for it. But that's what she wants to resolve. And then in the past month or so, she's had double vision. She says she gets her phone out in the middle of the night to read it and when she's trying to read it, it takes her five to ten minutes to be able to focus on her phone. It's really hard for her to focus on that. She also says that she had a neck injury during judo practice and she was 18 and she's had multiple chiropractories sessions since then because she's had chronic neck pain. So on exam, she has 20-20 vision in both eyes when she's corrected. Her pupils are two millimeters and we couldn't get them to be different in light or in dark. So they're around the same in dark and light. And she has about minus one restriction on up gaze in her right eye, nothing on the left eye. And then she's got a like a four-diopter, exotropia, that is slightly more pronounced on left gaze and less pronounced on down gaze. And on convergist testing or when looking at her convergence, she heard your point of diplopia was about eight centimeters. She was pretty good. So exotropia or exophoria? Exophoria. She was able to use everything as part. But she was having double vision, so this was likely the cause of that. And so on examination, she had... I wish I had a picture because I didn't take people's pictures of her. So to my best description, she had... She had dermatocles on the left side, but she had a little bit of mitosis on the right side. It was about a millimeter different than the left. And it was her... her sulcus was up a little bit as well. And the iris had some anisocorrhea. You can see below there that her levator function was normal on both sides. She was strong orbicularis. And the funnest exam was she had elevated disc ratio. So the thought about this case... So in a patient who has anisocorrhea, right grade to the left, she has maybe a little bit of ptosis on that side. Hard to really tell. And she's had this exophoria that's, you know, a little bit better on down gaze and worse on left gaze. So it wasn't like a slammed-on case for this is a cranial third nerve palsy because they were all very subtle findings. But she had all three signs of it. And so, of course, in that case, you have to go for the imaging just to be sure that's not the case. Before you go, can you guess that one slide? Because you've measured the exo and you're saying she's got an elevation deficit of the right eye, but you didn't measure a vertical deviation? I didn't remember. I didn't see it documented. So I don't think we did document a vertical deviation. You don't know for sure that she's got an elevation deficit unless there's actually a deviation because if she's got ptosis there, then it can be really like subtle limitations, can be hard because even though you know that's not what you're supposed to do, you can use the lid to judge the eyeball movement. That's probably true. So you're right, we should have looked at that. So the way you confirm if there really is an elevation deficit is by looking for a vertical deviation in up gaze. Exactly. She didn't say that she had any difficulty. So our thinking was, it's very possible she has like a, she has physiologic, well it's somewhat possible, she has physiologic anasporia, she has a little bit of asymmetric ptosis due just to the motion and disinsertion of the right side and where the left and maybe her convergence efficiency explains her exophoria. But more likely she's got a cranial third nerve palsy. So she did get an MRI, M-R-A. And on imaging, this was like a few days later, you can see on the right side that she's got, this is more than the neck of the aneurysm right there, the posterior communicating artery, and it measured like 11 millimeters in greatest diameter in total and it was kind of like inferior, but it actually displaced just on the right side. So they did reconstructed imaging, it does look pretty sizable there, so it's coming off where the ICA, PECOM, sorry, I'm not used to this. So she was referred to neurosurgery, she had a pipeline embolization, coil embolization of the aneurysm and she was discharged in aspirin and prostagrilla. We're going to be seeing her back in a week or two, it's just this only happened recently. But that went pretty well. So the, what I took out of this is that she had two millimeters of anisocorrhea and that's not physiologic. If it's more than one, that merits a workup for anything else that could be causing an anisocorrhea from a deficit, from a deficiency reason. And also an exodibiation of any sort that's for some contralateral gaze, potentially on improved on down gaze part of a cranial third nerve palsy without having a full blown motility deficit as you were talking about earlier. So, and the reason that I didn't put this in here and the reason that we get the pupillary involvement in cranial third nerve palsy is because those pupillary fibers are falling along the community aspect of the outside of the cranial third nerve where it like runs up right against the posterior community artery. So just, I know we look out for these aneurysms a lot and they're not always positive, but this was a case that was really interesting because it was a little more, it took a little more piecing it together than some of the other ones. Any questions about that case? All right. Well, I didn't remember any pupil cases that I've had in the past month. So for those of you who watched all of DR's video, Shay won you because we only said to watch the first four minutes so this is just going to be... But I think it's good that we go over this. Okay. So, and like I said, I don't know this man so I'm going to talk like I examined him but I didn't. This is thanks to DR. So he's a 34-year-old male. He was referred for a right-blown pupil. So this is in a neuro-ophthalmology clinic but apparently in the middle of Saturday his vision was a little blurry. So he walked into the mirror and he had this very dilated right pupil. And so here's a picture of not him but what I imagined it would look like except on the right side. So you can see the left pupil is significantly enlarged than the right pupil. So he walked into the ED that Saturday. They got an MRA head, neck, and MRI brain which was all negative. He was referred to neuro-ophthalmology non-urgently but was really freaked out by the fact that this could be an aneurysm. People were telling him all sorts of things and so he got in pretty quickly to neuro-op clinic. As you can see, his exam was pretty unremarkable. Vision was fine. His movements were full. Visual field was full. His pupils... Oh man, that looks really bad. You can't really see. Well... Okay, so who can see that? Anyone still to describe it to me? Sir Av, what do you see? Can you see the pupils or no? Is that unfair? Yes. What does RLF stand for? And why is it important that it's far? Yeah, exactly. I think it gets bigger at second. Yep, yep, exactly. So with that, would you say then... So the difference in pupil sizes in greater and lighter dark? The difference in pupil sizes? I can't tell. Well, it's greater in light. So they become more equal in dim light. And sorry, DR actually had like little circles which I should have done but I didn't want to completely copy everything he had so I thought I would just do this but obviously that was the wrong choice. I should have done that. But yeah, so that's... I mean, I feel like that's really good to just when you're going through your different... or your exam for anisecoria, it's really important to look at the pupils in light and dark and basically the question you're asking is where are the pupil sizes... The difference is the greatest. Is it in light and dark? I'm going to send you down two different pathways which I have here which is like a super simple diagram. So basically in this gentleman's case the difference was greater in light. So this is going to be a parasympathetic lesion and then if it's greater in dark then that's going to be a sympathetic lesion, okay? So this is a really cool table that I actually found off of an anesthesia website which looks like really complex but I think at least for me when I'm on call I think I'm going to print this out and kind of put it in my pocket because once you... you could go down the list and it basically gives you your differential so when you actually give somebody a call and you're calling Dr. C in the middle of the night you could have sound semi-intelligent kind of go down this. But for this gentleman the unequal pupils are greater in bright, right? So then you kind of go through are his movements okay? Does he have any ptosis, papillodema? You know, go down the list. I don't need to go through this but basically you should print this out and put it in your pocket. So the differential diagnosis what do we think the differential diagnosis for unequal pupils that is greater in light than dark I see all some things out without looking at that. Pharmacologic, yep, exactly. What else? Eighty's, yep. And then what's like the... scary, yeah, yeah, third neuro-policy, exactly. So, and I think eye trauma of course as well so that's something that's really important to keep in mind. So this gentleman ended up having you know, if you guys actually listened to the lecture, ginsengweed which... That's not ginsengweed. This isn't it? That is ginsengweed. That's J-I-M-S-O-N. Wait, this is not that. That's the flower. But it's what it's called as ginsengweed. Oh okay, well you get what I'm getting at. It's... The picture of the plant is not that important. Okay. It's a picture of a flower, okay? I just thought it was nice, but the point of this... It's the right flower. It's the correct flower, the drug they call it. Oh, the drug. Oh yeah, yeah, there it is right there, ginseng. Yeah. Ginseng does not cause any pupil problems. Okay, thank you. That was my point. Alright, it's both. Have you drunk any ginseng tea? No, I haven't. Have you drunk any ginseng tea? So, I think this is important to go... Just remember that there are different drugs that can cause pharmacological medriasis, and I mean this is a busy list, but I think in terms of the most common that you will see maybe in the hospital is diphenhydramine. You could have also, you know, any sort of atropine, which is actually what causes the medriasis in ginseng weed. And so, just something to keep in mind, I think that oftentimes when it is drug-induced, we think it would be bilateral, but there are also a lot of reports, case reports of unilateral medriasis, and so I thought it was a good case to go over just to keep in mind when you're on call or when you see somebody. So guys, in addition to that, it's a very good list, but what's the drug that they use all the time for inhalation treatments? Oh, the nebulizers in the ICU. Atropine. Yeah, I mean, in the hospital, that's going to be the big one. And these, they can cause bilateral medriasis if you're taking systemically, but the point of the unilateral is usually its top. Yeah, in this case... I actually saw this patient, he was outside gardening, and he took his gloves off, it was hot, and he kind of wiped his eye, and they didn't even ask him any history of the year, and they just sent him straight for scans, so don't forget to ask history. Hand out history. All right, well, I have no plant pictures in my presentation, so I'm just going to turn on the lights. Because we have some photos to look at. So, we'll talk about encyclopedia. So, this is a gentleman who was in clinic, a 69-year-old guy who was referred from an outside ophthalmologist for evaluation of unequal pupils and a droopy lid on the left. He'd seen a general ophthalmologist for cataract evaluation, and there he noticed an ophthalmologist noted encyclopedia, and his wife noticed that his left eyelid had been droopy for years, but really hadn't paid attention to any unequal pupil sizes. Initially, he told us, you know, you don't have any changes in vision. Then his wife reminded him, oh, you know, actually, you know, you have these episodes a few times a year where you get, your lid gets really droopy and you have these bad headaches and your eye gets a little bit red, you get a little teary, but he didn't really think it was important to bring that up. So, it's important to have collateral when you're taking history. His exam was otherwise pretty unremarkable. Acuity was normal, motility was full, visual fields were full, and his pupils will take a look at here. So, that's him. And they don't want to tell me what they see in this picture. It's not a trick question. Anybody? Yeah, yeah, so there is unequal pupil sizes. The left is smaller than the right, and what do you notice about his lids? Higher lid crease on the left. Yeah, so there's a bit of ptosis on the left. Exactly, exactly. So, Brad kind of took us to... I'm not sure I can actually see the lid crease, per se. You can see the fold, but, you know, the creases are actually looking at the lid itself, sort of open up. Like, if his eyes were closed, you'd be able to see the lid crease. Do you know what I mean? Yeah, okay. So, there is ptosis on the left, and a smaller pupil or a matted pupil on the left. And Brad kind of took us through, you know, the pathway to try to figure out what's going on, but what's the next question we should be asking ourselves is, you know, we see these difference in pupils, but is it greater in the light or the dark? And so, thankfully, we have these photos. And it's a little subtle, but, you know, his ptosis is not resolved, he's opening his eyes there, but what you can see is that the difference, it's a little bit hard to say here, but for the sake of argument, the difference is a little bit greater in the dark than the light. And so, the next question is, you know, did the differential for things that are greater in the light or the dark, Brad kind of went through that, specifically for the differential for things in the dark, we want to decide between, I mean, obviously, you know, we're leaning towards is this something like a Horner syndrome, or could this be something simple, like physiologic and a psychoria, and what can help us differentiate, just on the physical exam before we do any kind of, you know, drop test or anything else, what can help us differentiate between physiologic and a psychoria and a Horner syndrome? Any ideas? There's a dilation lag. Exactly, exactly. And so, the way we look for that is here, we have his pupils here at five seconds and then on the left at 15 seconds. And you can see it's a little subtle, and again, for the sake of argument, go with me here, but you can say that you can see that here at five seconds compared to 15 seconds, the encycloria is a little bit different, maybe half a millimeter to a millimeter, but it is different at five seconds compared to 15 seconds. So, we would say this is a positive dilation lag. And so, the next step would be to do pharmacologic testing. And so, here, we can see what do we notice here? This is 30 minutes after giving aproclonidine. What do we notice here? Exactly, yeah. So, this is, you're exactly right. We see reversal of encycloria. We see reversal of histosis. And so, this is diagnostic of a Horner syndrome. So, Horner syndrome is something that we see fairly frequently and it's important to remember and talk about. Horner syndrome is a dysfunction of the sympathetic pathway to the eye. So, the classic triad, we all learn in medical school is ptosis, meiosis, and anhydrosis. The ptosis is a result of loss of innervation to Mueller's muscle. The meiosis is a result of unchecked action of the iris sphincter due to that loss of sympathetic innervation to the dilator. And then the anhydrosis, so the textbooks say that depending on where the lesion happens, you can see anhydrosis. So, if it's the first or second order lesion, you'll see anhydrosis of that entire side of the face. Whereas, if it's the third order or a poskin-leonic lesion, you'll see EAC anhydrosis just of the forehead. I don't know how often that's seen clinically, but that's what the textbooks say and that's what we remember for ROCAPs. So, this is a diagram of the pathway. So, the sympathetic pathway starts up here in the hypothalamus. You can see the first one, the neuron then that goes up. It synapses again. And the third order neuron then goes out to the face and to the eye. And you can have a lesion anywhere along this pathway that can result in a hornar syndrome. So, the differential diagnosis for hornar syndrome is pretty long. And depending on where the lesion is, can help you, you know, there could be associated symptoms that will help you decide where the problem is. A couple to be aware of here. So, first for lesions, you can have this you know, we learned about it in medical school for step one and everything. The classic Wallenberg syndrome and the lateral medullary syndrome. Here you'll see so on the face you see this lateral impairment of pain and temperature sensation over the face with contralateral pain and temperature impairment over the trunk and limbs. You'll see ipsilateral ataxia. And you'll see this you can see this ipsilateral hornar syndrome. The one that we always remember is this Pianco's tumor. So, if you have an apical lung tumor, that can certainly cause it. And then in third order problems can certainly be listed right there. Crad artery dissections one that we don't want to miss. So, pharmacologic testing just to walk through it, a review from the video that we had. So, cocaine is used at blackberry uptake of norepinephrine and in a normal functioning eye, right, that doesn't have a hornar syndrome, it should result in dilation. Now, post-cocaine and sequoia of greater than one millimeter is diagnostic of a hornar syndrome because in a hornar's eye there's no norepinephrine, there's no synthetic innervation. So, it's not going to dilate like a normal eye would. The other drug we use frequently is apriclonidine or iopidine is the other name for it. It's an alpha-2 agonist and a very weak alpha-1 agonist and it will result in dilation of a hornar's pupil due to denervation hypersensitivity. So, reverse sequoia like we saw in our patient is diagnostic of a hornar syndrome, but there's a couple limitations to using apriclonidine. One of them was in one of the questions at the beginning of the lecture. It takes time to develop denervation hypersensitivity. So, in the acute setting if someone comes in with a hornar syndrome and you give them apriclonidine, you may not see the expected result if it's within the first couple days because it takes time to develop this hypersensitivity. And then, apriclonidine really isn't to be used in children for the same reason that bromonidine isn't used in children. It can cause them to become apnic which is something we'd like to avoid in our pediatric population. And then hydroxyamphetamine is another drug that can help us localize. This has been used historically in them. I think the issue is with supply and getting this, we don't really use it that often anymore, but the idea is that it enhances the release of presynaptic norepinephrine. So, depending on where the lesion is, it can help you localize that. So, if you give hydroxyamphetamine and there is no dilation, then that tells you that the issue is on that third-order neuron. However, if you have dilation after giving hydroxyamphetamine, that tells you that the third-order neuron is intact and you've got a first or second-order horners issue going on. A couple special cases to be aware of. Horners associated with pain, especially cervical pain, is a carotid dissection until proven otherwise. This is something that we really wouldn't want to miss and this patient wouldn't need imaging. Another case that may have been the case for our patient, he actually has been lost to follow-up. He never really came back. But, horners associated with headaches is another known phenomenon as well. And autonomics of phalges could certainly result in this. There's a specific syndrome specifically seen in men called Raider prayer trigeminal phenomenon, which is a syndrome of headaches associated with horners. And actually over time, if that happens frequently in the ptosis and can become more permanent. And then in pediatric patients, if you see a hornar syndrome, we always have to think about neuroblastoma. Now, a hornar skin and pediatric patient can be caused by trauma, so birth trauma specifically. So if there was a traumatic birth, if there brachial plexus was stretched, or if there was a traumatic delivery, that could certainly be a cause of hornars. But if it was an atraumatic birth and this patient has a new hornar syndrome, we have to think about a neuroblastoma, the sympathetic chain, and that patient probably deserves some imaging there. So, that's a quick overview of hornar syndrome. Any questions about that? Okay, awesome. Can I add? Yeah. I don't know if this is going to be covered, but the other thing you want to think about is other things that, other than horners, it would cause the pupil that failed to dilate the amphetamine and or hydroxyamphetamine. Sure. So traumatic pupils, things that cause anache, can give you a false amphetamine result in that case. That's why a good salt lab exam can be really helpful. Yeah. Indeed, another case of anisoporia. I also borrowed from DR just for her completeness in the cases that we were presenting. So, it modified it a little bit, but we have a 35-year-old woman, and she presents to the emergency room because her friend noticed all of a sudden that her pupils were unequal. She had some associated blurriness of the vision in her right eye, and she has never had anything like this before. Actually, it's going to be her left eye based on my measurements from below. Her visual acuity was 20-20 in both eyes. Her left eye was known to be larger than her right eye. And, sorry, this is all switched up. I didn't realize this until last night. So, it's going to be unresponsive to light with decreased accommodation. Her extracular movements are full and painless. Her visual fields are full of confrontation bilaterally. And then, because you're a great neuro-opemology student, you carry around your reflex camera and note that the patient also has a reflexy of the knees and ankles bilaterally. So, just to clarify, so let's say the affected side is larger, and then it has, the affected side is unresponsive to light with decreased accommodation. So, what are you guys thinking? So, you have a large, I think an abnormal people is the large people. That's unresponsive to light with decreased accommodation. So, then you go do a slit lamp exam. And so, there's a really great, I watched this video last night on the ran quarry from Dr. Degree. And so, what do you guys see here, other than the arrow sign? Yeah, what do you call that? Psectoral. Psectoral Palsy. There are talks about churning this lamp on and off and on and off and watching the pupil actually move, and there's like some areas where it's slower, and not as quick. And so, it was, the gentleman in the video actually has a bilateral 80s, and it's really, it was really subtle, and actually, I want to go back and watch it again. And then they watch him look at near and watch his pupil movement as well. So, then you find a Psectoral Palsy on exam. So, this is an 80s tonic pupil. So, this is a benign idiopathic syndrome. It's thought to be due to damage in the ciliary ganglion, and so there's when histologic studies are shown to have reduced ganglion cells, and you lose this post-ganglionic parasympathetic innervation. So, the causes can be pretty broad, but in addition to being idiopathic, so surgery, trauma, viral infection, or phasospasm due to migraine, and then in addition, it can be associated with a more general neuropathy or pharmacologic blockade. So, this is important. So, whenever you have a patient with this right or enlarged pupil, you want to think about their past medical history. So, for example, do they have really bad diabetes and like really terrible neuropathy, and then you want to examine their medications because as Brad talked about, all those things that can cause an enlarged pupil and the anticholinergic medications could give you also a clue to the diagnosis. And then basically, the other associations think about really peripheral neuropathies. So, chronic alcoholism, sarcomery tooth, sarcoidosis, things like that. It tends to be 70% women, usually in the middle ages, and it's unilateral and 80%, but this can be bilateral. Second pupil is involved at a rate of 4% per year. And then if you have diminished deep tendon reflexes and orthostatic hypotension, then that's home's ED syndrome. And generally, you don't need any additional imaging. And so, a lot of the symptoms that they have will be in relation to accommodation, which can usually resolve within a few months, but can be difficult to treat. So, you can try pilocarpine multiple times a day to constrict the pupil, and then prescription reading glasses to correct impaired vision. And so, of course, the treatment is also how you can help diagnose it. And there's kind of a timeline of the findings, particularly with an ED pupil. If you have a diminished day, you'll have this large pupil in the light and dark. It's unresponsive to light and near, and then you note the sectoral palsy on slow lip examination. And about a week later is when you develop the denervation sensitivity. And so that time is when you can start doing your pilocarpine testing. And so then, months later, you can see the light near dissociation. The light near dissociation is that as the pupil redialates after constriction very slowly, that's where the term tonic comes from because of the slow redialation after pupillary constriction. And then years later, so DR has this in his video. So this is a gentleman who, whenever they were first diagnosed, I could see that he wouldn't know which one's abnormal pupil on the top. Which one looks bigger? Right? And then years later, so you can tell that he's aged quite a bit. You notice that the right pupil is smaller, and it looks like he even has a little bit of ptosis as well on the right side. So this would look like a right-sided hornar syndrome years and years later. But this could be also actually just him with a little old 80s pupil. It's kind of a timeline of findings. So an unreactive pupil in a conscious patient also a large unreactive pupil in a conscious patient. Your slit lamp exam is really important and the sectoral palsies can be really subtle. And then after a week, then you can treat or you can test with dilute pilocarpine. So basically put your dilute pilocarpine in both eyes, you wait an hour and then the affected pupil should constrict more than the normal pupil. And then 80% of these patients will show colonerject innervation super sensitivity. It can be bilateral, check your reflexes. And then two points that DR had in his teaching points as well is that you can't have super sensitivity to a cranial nerve 3 palsy and then he talks about also a midbrain corectopias where you can have oval pupils due to rostral midbrain disease or intrinsic compression.