Corneal Dystrophies I

(soft piano music) - Hello, welcome to Eyes for Years, our off the Mology OCAPS and Border View podcast. This is your host, Ben Young. Andrew Powell is out of the country today, so I'd like to introduce my co-resident and guest host, Amanda Redford. - Thanks Ben, I'm excited to be here today. Please keep in mind that these podcasts are for medical education only, not to diagnose that weird thing on your eye. - We are off the Mology residents who figured reviewing for clinic, OCAPS, or boards. It's better when you don't have to do it alone. Each week, review a high-ealtopic and flush out the Y and the Howe. - Today, we're reviewing everyone's favorite topic, Cornell Districties. As you know, there are too many of them, so we're actually breaking it up into two episodes. Today will be the first half. - Wait, what's a Cornell Districtie? - Excellent question. So a Cornell Districtie is generally a bilateral, symmetric inherited condition of the Cornell with little known relationship to any environmental or systemic factors. - Oh, okay. So that means it's not things like, like, ban care atop it, or something, where there's a clear and siding factor that causes it. - Correct. - So for anyone who's started studying for OCAPS already, you know that there are many, many different Cornell Districties. We'll try to organize them in a reasonable way that is also the way it's organized in BCSC, so that it's hopefully easier to organize and remembering, remember, and we'll do that anatomically from anterior to posterior. So we'll go through the epithelial, bone is membrane, stroma, and some of the posterior Cornell Districties in that order. - So starting with the epithelium, Ben, can you name an epithelial Cornell Districtie? - Oh my God. Are you tempting me? Hold on. - Heck yes. - So there's the one that has the word epithelial in it. There's epithelial basement membrane and Districtie. There's a couple other names that you've probably heard of. There's map dot fingerprint dystrophy, which is just another name for the same disease. And there's ABMD, which is anterior basement membrane dystrophy. Again, it's all the same thing. What gene is this again, Amanda? Do you remember? - So it's TGF beta one, in some cases that is. - Yeah, I think a lot of the time it can be sporadic or they don't find a clear genetic cause. And you know, it's also probably the most common of the Cornell Districties. It's present in between six to 18% of the population. Usually it's in older people. People older, the 30 is typically where presents no inferior can present in younger people as well. Then above age 50, it actually increases in frequency by quite a bit. The appearance of it clinically is just as one of the names describes maps, dots, and fingerprints. There's essentially these gray subipithelial patterns that look like maps, fingerprints, or dots. There's also a quote, "blebipadern" which looks more like pebbled glasses. It doesn't really look like any one of the map dots or fingerprints specifically, but that's just another way that it can present. What are some of the symptoms that patients can get when they have EMD, Amanda? - Patients can get recurrent erotions, mild visual changes, such as blurring ghost images, or even monocular diplopia. - Right. On pathology, you can see exactly what we just described. You can see these sheets or extensions or pseudosis, which represents the maps, the fingerprints that dots respectively of the basal laminar material. So, Amanda, you mentioned recurrent erotions, recurrent abrasions. Is this the main thing that would cause a recurrent abrasion? - Actually, there are a lot of things that can cause recurrent erotions or abrasions. So things you should think about are recent traumatic abrasion, EMD, which we're already talking about. History of herpetic caratitis and other epithelial discharfies that we'll get to in a few minutes. Most commonly, the differential diagnosis is between trauma and EMD to tell the difference examin' the fellow I. Remember, discharfies happen in both eyes, whereas trauma could just happen in one eye. So if you only see it in one eye, it would lead you to consider trauma as the most likely cause. - Right, and if you look at one eye with an abrasion and the other eye has my dot fingerprint discharfee, then perhaps it wasn't trauma or a past trauma that caused it, but rather the EMD. So to remind you about why traumatic abrasions can cause recurrent abrasions is that the traumatic abrasions is that when you have a traumatic abrasion, your epithelium has to regrow quickly to cover where the abrasion was, especially if it was a larger abrasion. And because it grows quickly, it isn't necessarily adhered to the underlying moments of stroma. As a result, it's not tightly adhered and there can also even be epithelial gildema in that area, which also can interfere with that adherence. Thus, if it hasn't adhered, it's easy for it to have an abrasion again. And it can take time, it can take months, sometimes even a year or more for the problem to go away. And if you have another abrasion in that time, then you're starting from ground zero basically again. So it shares a similar path of physiology to epithelial basement membrane dystrophy that both have a poor adhesion of the underlying epithelium to the underlying moments and stroma, but obviously the mechanism for that happening is very different. - So as a fun clinical parlor, it's really important to look at the superior cordia when you're looking for EBMD because it generally starts there underneath where the eyelid would be rubbing against the cornea over and over again. - Okay, I think that's good. So we can move on to the next dystrophy that affects the epithelium as well. It's a much rarer one than EBMD and it's called Miesman's corneal dystrophy. - One might even say it's the most peculiar of the corneal dystrophies. - Peculiar, why do you say that, Amanda? - Well, because there's something in the cornea that we call peculiar substance, really mysterious, huh? - Right, those are those epithelial cysts that are PAS positive when you stain them. And on the pathology, they can also, they're surrounded by this peculiar substance which is a common buzz word that we'll see in the OCAPs. - In terms of genetics, it's an autosomal dominant dystrophy and it's related to the genes KRT3 and KRT12. - Right, and clinically, the appearance is related to the pathology that we just talked about. You'll see these epithelial vesicles, they can be very small and they're more obvious and retro-illumination. It's a disease that starts very early in life and usually has pretty mild symptoms. They will have mild irritation, they have mild changes in their vision, but in general, Miesman does not progress a ton of it, it comes very severe. There's another disease that's really similar to Miesman's, isn't there, Amanda? - Yeah, it's not what feather you one, leash, leash corneal dystrophy? - Lish corneal dystrophy. - Yeah, sorry. (laughing) - Lish, where's the heck up after this? (laughing) - So, leash corneal dystrophy, they're discrete feathery gray sub-epithelial lesions. They're densely crowded microsys, similar to Miesman, but instead of diffuse microsys, they are concentrated any feathery or world pattern. - Great, so when you think of these epithelial dystrophies, you can really think of these three, the epithelial basement membrane dystrophy, Miesmans and Lish, where Miesmans and Lish have those cysts, whether they're diffuse its Miesmans or concentrated and feather pattern is elitious. And then if it's, you see these sub-epithelial lesions that are more like MAP, Dr. Fingerprints, then you know what it is, MAP, Dr. Fingerprint dystrophy. Let's move a little bit more posteriorly into Bowman's membrane. What are two dystrophies that affect the Bowman's membrane, Amanda? - These are the two that I always get confused. There's rice bucklers, re-spucklers? - I'll respect a Dr. Reese or rice. We're gonna call it re-spucklers. And dear listener, if you wanna tweet us a correction, we'd love to hear it. - The other one is teal-benky. I can't hear, I'm pretty. - I'll respect a Dr. Keele and Dr. Benke. - With all due respect, we're gonna go with teal-benky. - Teal-benky. - So what's the difference between these two? - Yeah, you know, as you allude to, they're pretty similar diseases. They're both these that affect that anterior stroma, really Bowman's membrane, which to remind you, is not a true membrane, it's condensed anterior stroma. Basically, there's two ways to tell the difference between them. One is on pathology. On pathology, re-spucklers is sheet-like. So it's just like a plain sheet of dystrophy compared to teal-benky, where it has a more of a sawtooth pattern. As you can imagine, the clinical result of this is that re-spucklers can leave people more prone to recurrent abrasions because that smooth sheet-like dystrophy allows the epithelium to slide off more easily. Compared to a sawtooth pattern like in teal-benky, which means the epithelium will adhere more tightly because of the more corrugated surface from the teal-benky. There's another difference with another imaging modality that we don't really often use, right Amanda? Yes, but it always comes up on boards. On electron microscopy, re-spuckler looks like rod-shaped bodies, whereas teal-benky looks like curly fibers. To help you remember which is rod and which is curly fibers, rod-shaped bodies are re-spooklers. So, are for rod and are for re-sp. And then crew. fibers or the other one. If someone has a clever mnemonic to help remember that we'd love to hear that too. One thing to remind you is that they both actually feature the same gene. TGF beta-1, which to remind you, is the gene responsible for producing carotopethelian, carotopethelian, which is common to a number of these cranial discharfees and we'll help you remember them with a mnemonic at the end, but that's another thing that's in common between them and it must be a different variation of the genetic abnormality that manifests as a different conditions. Okay, well that's the wonder twins of Reese Bucleus and Theo Pankey. Is there another thing that affects the anterior stroma in particular? Why, yes, there is Benito, there's Gillatin, his drop-like corneal distrophy. And then right, another name for that is primary familial amyloidosis. So that name can remind you that this is an amyloid deposition in the anterior stroma and that's reflecting the pathology where you have amyloid deposition that reportedly deposits due to disruption of the epithelial tight junction, which is probably where the genetic abnormality is. Remember that amyloid can deposit in any condition that we have chronic inflammation or chronic exposure or breakdown of the epithelium or the anterior aspect of the cornea. This is just a congenital version of that where they just are born with this abnormality. So this one actually has a unique gene that we haven't talked about yet and it's T-A-C-S-T-D-2. Oh, S-T-D-S-A-B-E. You said S-T-D on air. You're never going to become president. Which stands for tumor-associated calcium signal transducer 2. So what does it look like? Yeah, this one has pretty colorful descriptions. There's three variations. One is a mulberry-shaped gelatinous mass, which are kind of smaller lesions where there's still a visual potential through it. Then they look apparently look like mulberries. Actually, before learning about this, I did not know what a mulberry looked like, but now I do. There's also the band-care topathy type. So it'll look very similar to band-care topathy and deposit in a similar pattern. And then finally, there's a very severe, cum-quat gelatinous drop-like corneal dystrophy where the front of the eye looks just like a cum-quat. If you didn't know what a cum-quat was, and I can't element, I didn't. It's an orange. It's like a tiny orange. Is that basically it? No. It's a tiny orange, right? No, it's way more bitter. It's more. It's like the size of a date. Right, but it's like a tiny orange. It's a date-sized. But it's very bitter. Oh, okay. So it's like a bad orange, so the front of your eye will look like a bad orange. To be honest, I've never tasted it. I've just been told that. Stay posted for the after credits to find out more about cum-quats. So clinically, these patients will have the vision decrease depending on the degree or the type of gelatinous drop-like dysstrophy that they have. They can have pain from erosions, because remember, this is affecting anteriorly, so that it will affect the adherence of that epithelium. It typically starts at a young age, and it frequently recurs if transplanted. So there's really not many management options that are super helpful, apparently contacts can be helpful. Luckily, it's a rare disease. Okay. So moving on to just the stromal distrophies. There's a macular. Let's start there. Macular. Zeta. Is that an acronym for something? That's that. Dr. Rudfern, would you say that macular may be its own mnemonic? Maybe in your world. Check it out. If you spell out macular, the M is concerned for a muco-polis acryte, which is what deposits in macular. The A stands for Alcyn blue, which is the stain that you can use to find a muco-polis acryte. The C can stand for either CHST6, which is the gene. It's the only distrophy that caused by CHT6, or can stand for colloidal iron, which is another stain that is used for muco-polis acryte. The L can stand for limbis to limbis. IE, this is a disease, even though it's called macular, and that may make you think it's only going to affect the central cornea. It really can affect from one end of the limbis to the other end of the limbis, IE, the whole cornea, and the A stands for autosomal recessive. Because this is one of the few distrophies that's autosomal recessive. Many of the others are autosomal dominated as we're covering a bit. So I was really listing most of the features of macular corneal distrophy. You'll see that it causes these, you know, whitish deposits in the deeper stroma, but, and again, it can cover from limbis to limbis. What's another stromal corneal distrophy, Amanda? Well, granular is actually kind of similar looking to macular, so why don't we go there next? This one, however, is a TGF beta-1 corneal distrophy. I think you're probably noticing a theme by now. So with granular corneal distrophy, what you see is Highland deposited in the stroma, and you use MASSON trichrom stain to help visualize that Highland. It can also have this crushed bread-crumb appearance, and there's space in between the lesions, which is different from macular, which we were talking about earlier, which is just one big sheet of badness. And then to kind of finish off the trio that, because these three are often talked about together, is lattice degeneration. The associated gene is also TGF beta-1, and here the pathology is, and this is another amyloid deposition distrophy, though this is also pretty interior, though it doesn't manifest at all like gelatinous drop-like distrophy. To remind you, amyloid can stain with hunger, red, or crystal violet. Both may show up on on exams, and are both important to know about. Just as a side note, there's a lattice corneal distrophy type 2 out there, but that's no longer considered part of the corneal distrophies, because a systemic manifestation is due to the systemic amyloidosis. So you won't go into a detail here, but it may show up on past questions and such. So now that we've discussed those, we can start talking about avaleno, which is also known as type 2 granular. It's essentially a combination of both lattice and granular corneal distrophy, as both highland deposits and amyloid deposits. Interestingly, it's called avaleno, because it was first described in a group of families that were found to have this disorder in avaleno-Italy. Okay, so. Now I'd be a good time to talk about Marilyn Monroe. Oh, who's Marilyn Monroe? Wow, some like it hot. Come on Ben, you need to stop studying and watch the more movies. Okay, I think I'd have editorial pattern. It's actually one of the few companies that won an Academy Award for Best Picture. What's this Marilyn Monroe business? Marilyn Monroe was one of the most beautiful, most out and I was just kidding. I mean, she was pretty cool, but. Welcome to Monroe for years. I'm Marilyn Monroe focus podcast. So there's a very famous mnemonic for OCAS review that has to do with macular lattice and granular corneal distrophy, and it's about Marilyn Monroe. Marilyn Monroe always gets her men in LA County. First one is Marilyn, which stands for macular. Monroe for mucopali sacri, always I'll see him blue, which is what you use to stain to see be mucopali sacri. Gets is for granular, her is for highland, man is for mass and trichrome, which is what you use to see the highland when you're staining it, and then LA County is lattice, amyloid and cago red, or crystal violet if that helps you remember. Okay, that's pretty good. So what's next? There's another one that affects a stroma called schniders corneal distrophy. It's specifically due to a vocal lipid metabolism problem. So it's essentially where lipid deposits in the stroma and that lipid stains with oil red O or Sudan black. Those are the two that stain. So this usually appears very early in life, and what you may see on exam first is very dense arcus, but usually we see arcus in our, you know, Medicare population. And this time, if you're seeing it in someone who's much younger and in both eyes, you should be thinking about schniders. Now, classically, it tends to affect the central cornea, and as a result, there's this classic presentation where patients will have poor vision in bright light conditions because if people will be constricted, so it's hard for them to see around the central corneal opacity. And that's in contrast to in dim light conditions when their people is more dilated, they'll be able to see around their central corneal opacity and see, honestly, surprisingly well given how significant their opacity can appear. How does that go with the arcus? I think the arcus is purple enough that it doesn't. And it's like doesn't get a visual. So does it not classically have arcus too? No, it does have arcus too. So it's arcus plus central catch. Yeah. Yeah. You know, to that point, someone with early arcus should tip you off to look for something like schniders corneal dystrophy. But if someone has, is it's who's older has only unilateral arcus that actually can be an indication that the on the unaffected side, either side without arcus, they may have significant crowded disease because enough blood flow is getting to the cornea on that side to deposit the normal lipid that is seen in Arcusinolis. So patient walks into your office and you see all these lipid deposition in that cornea. What you need to do is check for the lipid levels or get a lipid panel. Though controlling the lipids doesn't really affect the progression of the disease, it's important to monitor that and remember that you are a doctor first. Right. Interestingly, in patients with Schneiders, you know, some they don't have to have lipid, you know, systemic lipid metabolism problems. But when they do have lipid metabolism problems, sometimes unaffected family members may also have markedly elevated lipids. So, you know, that suggests there is some kind of systemic association with it, but this is still a local lipid metabolism problem to the cornea. One last note is that Schneiders used to be called Schneiders crystalline dystrophy. The reason for that is when the lipid deposits in epithelium deposits as a crystal. So, you know, people thought of this as a crystal disease. However, the epithelial deposits only happen 50% of the time. So, that's why they generalize the name now to just Schneiders corneal dystrophy to make it more general, which in the case of epithelium and dystroma. Well, okay. There's only like a few more weird ones to go over, right? Yeah, I think it is because there are already too many. There's so many. So, the next one is congenital stromal corneal dystrophy. This is an autozomal dominant disorder and it's associated with the gene decorin, decorin, decorin. So, as the name suggests, it's congenital and it's a diffuse stromal dystrophy that presents with a thickened cornea with flake-like opacities. So, even though it looks kind of bad and it starts from birth, it is actually not that bad of a prognosis because it is either non-progressive or slowly progressive. And one last thing is that it is extremely rare. There's only a few families that have been noted to have it and it's only been reported a couple times in the literature. This will come up because it can be on the differential when looking at someone who you think has seen HED, which will cover in next week's episode. Okay. Wait a thread, a cliffhanger. Oh, you'll have to go to it next time, dear listener. But before we end it, let's talk about flake dystrophy. What is flake dystrophy? It's a dystrophy with flex. There's-- How? Yeah, I know. It has these discrete danger of flake lesions. It's another word that's associated with it. It's usually not very symptomatic. It doesn't require any additional management in general. So it doesn't really cause increased pain. It doesn't cause-- Usually minimal to no vision changes. And it's not very anti-erstromal, which is why it doesn't typically cause abrasions or pain. So the next one is poster amorphous corneal dystrophy. And it presents as a poster, she like opacity. So the corneus thin and flat. And the opacity that you see in this dystrophy actually indent decimates membrane. And then finally, there's one that's-- You know, can be seen as fairly similar, called predesimase corneal dystrophy. Here, the caratocytes that live in the corneal stroma are actually enlarged with a lipid-like material. There's some, you know, studies that show that that lipid-like material is a lipofusion. So just thought that it's degenerative matter. But, you know, I don't think that really makes much of a difference clinically. But it will appear like focal fine grail capacities just interior to decimase. And they'll, you know, usually have normal vision because they aren't very dense. So the difference between poster amorphous corneal dystrophy and predesimase corneal dystrophy is poster amorphous tends to look more like a sheet-like thing. And pre-decemase corneal dystrophy tend to look more like fine focal grail capacities from those enlarged caratocytes. So Ben, any mnemonics to help us remember all this stuff? No, we're done. This, thank you for listening to "I'm Joking." There's a couple more mnemonics that, you know, I find helpful for me to remember some orders of things with respect to corneal dystrophies. One of them is to help you remember which dystrophies tend to recur if you attempt to transplant to fix them. So one of them is really likes to grow more. So that stands for really which is Reese Booklers likes which is lattice, grow which is granular and M which is macular. So that's in decreasing order of how often they'll have a recurrence after a transplant. Another mnemonic is mini large grand. That just tells you at what age they tend to present. So mini is macular. So it tends to start early. Latest will start early like tends to be during childhood, sometimes before 20. And then granular for grand is tends to occur the latest in between these three. So they remind you that's mini large grand. Macular lattice granular. Okay, so one last mnemonic for you and that is large genes. So these are the corneal dystrophies that are associated with TGF beta one. So TGF beta one is located on chromosome five and there are five letters in the word large which stands for lattice, avalinos, Reese Booklers, granular and sometimes EBMD. And that's all we have. There's a few more dystrophies we'll talk about. Post your dystrophies like FUX and PPMD and we also want to talk about it tages in association with these diseases and you can check those out in next week's episode which will be part two of the corneal dystrophies plastic tages. If you like what you heard, you can follow us on Twitter at i's for years with the number four. You can also leave us any questions, comments or corrections we'd love to hear them. It also helps to rate and review us on iTunes, Google Play or wherever you listen to your podcasts. And thank you for supporting us by listening. Bye! [Music] Welcome to the podcast Food for Years where we review different types of fruit. Today we review the co-pots. Wow they say it's much sweeter than you think. Maybe we have really bad co-pots. One fun fact for about co-pots is apparently you eat the skin. Maybe that's why it's so bitter. Perhaps. What is a co-pots? Where's the part where it says what it tastes like? Another fun fact is that the bitterness of an orange actually comes from the peel so when you squeeze an orange, what? The skin is sweet for a co-pots. That's why you eat the skin. It's to help make the, so why you eat the juice even? Okay, eat the skin because it's sweet and that overpowers the sourness of the juice. There you go. I wonder if there's a satisfying cum clot cuts. It's also, I don't like saying the word cum clot. Why not? I'm like kind of disappointed I'm saying in an air like listen to yourself cum clot. I like saying like cum clot. Moist cum clot? Yeah okay. So, clinically these patients. Oh we're still recording. We're still recording every second of this.