Infectious Keratitis

Hello! Welcome to Eyes for Ears, our Optimology OCAPS and Board of View podcast. We're your host Ben Young and Andrew Powell. Please keep in mind that these podcasts are for medical education only, not to diagnose that weird thing on your eye. We're Optimology residents who figured that reviewing for clinic, OCAPS and boards is better when you don't have to do it alone. Each week we review a high-yield topic, flesh out the lie and the how. Today we're reviewing infectious care at Titus. Oh my god, that sounds awful. There's just what bacterial, right? Most of the time it's probably going to be a bacterial caratitis, but there's also all the other fun branches of the microbial ecosystem out there. So we'll talk about bacterial caratitis and I'm also touch based on fungal, protozoan and viral caratitis. Let's start with bacterial caratitis. Alright Ben, here on call. Cornea looser comes in from the ER and what you think can before you even go see them. What do you know about how bacteria can affect the poor cornea? The things that we would think about are some risk factors for bacterial caratitis. So it can be contact lens wares, really common or trauma or form bodies in the eye or abrasions that aren't healing wall and were treated. Chronic steroid use. But after I've gotten the history, what are some things I want to look for on exam, Andrew? So in general, these are focal areas of infiltrate in the stroma with really sharp demarcation of their epithelial edges. Oftentimes it'll be edema surrounding the actual inflammatory infiltrate. Sometimes it's hard to tell whether the stuff you're seeing is truly active or is an old stromal scar. Truly active ulcers will look a little more yellow and they won't be as quite consolidated looking. Right, and you know, if you're going to take away something, the key to differentiate something that's just a simple abrasion versus something that's actual caratitis, actually ulcer is whether the cornea looks clear or not clear. An abrasion will just be clear and the epithelial will be gone. But with the caratitis, you should have something opaque or something white or something a little off yellow in there. I saw in the ED the other day that there was a patient who had, you know, they had definitely an ulcer, but then I also saw this endothelial stuff in AC chamber cell, hypopeon. And you know, I called my senior and they told me to not tap and inject it. Like, why wouldn't I? It's a Doppler mitis, isn't it? They were right, actually, because you can get that stuff and it wouldn't actually be endopter mitis just yet. That stuff can all be just reactive inflammation. So let's talk about some particular bugs. You know, there's the common kind of infections that can cause my cure, caratitis, like staff and common strep species. We can talk about some caratitis that have unique factors associated with them. Like. I've never seen that word, caratitis. Soodomonas. Soodomonas is particularly present in contact lens related corneal ulcers because they tend to enjoy or grow on the biofilms that can develop on contact lenses. What's the longest corneal ulcer patient has ever told you they kept their contact lenses in? What's my record? Yeah. I think my record was two and a half months, like 10 weeks, what's your record? Six months. Six months. My God. That is too long. Interesting fact actually about biofilms, especially for things like pseudomonas, is that it can take around 24 to 48 hours for that biofilm to develop. You know, the bacteria actually that make dental caries like cavities and such, you can take around 12 to 24 hours itself also to form a biofilm. That's actually why dentists tell you to brush your teeth twice a day as you try to disrupt the formation of that biofilm. Similarly, that's why it's important to watch your contacts at least daily to prevent the formation of the biofilm from something like pseudomonas. And on the topic of biofilms, there's another entity of caratitis where the bacteria makes its own biofilm called infectious crystalline carotopathy. Some of the risk factors associated with it are chronic corticosteroid use, such as in patients who have corneal transplants who are chronically on pred4tay or something. What's unique about infectious crystalline carotopathy is that the crystalline part is actually a biofilm made by the host bacteria such as strawberry dance, is the most common kind, an alpha-chimolytic star species. Because it is biofilm, there's a minimal host response. So, I might not be as red, they might not have as much, you know, stormolidema or it might not be as necrotizing, but it will have this nice crystalline structure that the bacteria can hide in. There's also just a highlight something that can be tested on on boards or OCAPs is a group of bugs that are known to be able to infect through intact epithelium. Usually you have some kind of enzyme or some way to degrade intact epithelium to tunnel through. Or should I say channel through, because that's our favorite nivonic. To remember what group bacteria this is, the channel semonic is CHANLS channels. And that's used for chorin bacteria, CHANLS, HEMOFLOUS EGEPTIS. That's H&A, CHANLS, NISERIA, LISTERIA, and CHIGELA. Channels. So, once you've found a thing like this and ultimately you'll just try to figure out what's growing exactly. So, get a culture. You should get a culture. You should try to be as sterile or as clean as you can, at least, so that you don't contaminate anything. In fact, we used to have issues with our plates having condensation and being stored kind of wrong way up. So, try to make sure the petri dishes you're using with the egg ars as dry as possible. Condensation's gone. And as a side note, you don't need to culture every corneal ulcer. I'd refer you to the Will's eye manual. They have a good little checklist about what to culture and when you don't need to culture. The basic summary of it is that if it's less than one to two millimeters or so, if it's not within the visual axis, and if you don't suspect an unusual organism, then you don't have to culture it. Then you can just start in pure therapy. But again, I would just look at the Will's eye manual before deciding not to culture someone who is a corneal ulcer. Another thing to consider is if your caretidus has a lot of thinning or dermal melt, a lot of practitioners will start a patient environment and see that with collagen synthesis, or Dr. Cyclone, for its reported inhibition of matrix-metalloprotonase, which is a key enzyme in the dermal melting process. We can also talk a little bit about one specific bacteria that also pops up a lot in different contexts, which is the atypical micro-bacteria. That one's going to pop up on more specific media, like acid fast stains or culturing on low-instein-gents in media. But that also can be really popping up a lot after the refractive surgeries, too, like LASIC. At least in terms of questions, this mostly will come up with LASIC related carotopathy, so keeping your back pocket for those kinds of questions or clinical scenarios. And to be a bit more specific about post-refractive surgery bacterial carotidus, for atypical micro-bacteria, they typically would occur 10 days or more after refractive laser surgery, along with fungal infections. So to review, if someone has a bacterial carotidus within 10 days after a refractive surgery, then you would suspect your normal bacterial carotidus. If it's after more than 10 days, then it's more likely to be an atypical micro-bacteria or a fungal carotidus, which we'll get into later in this podcast. So, Andrew, what do we do if these treatments aren't working? You know what happens. You follow this patient along that you saw in the year for a long time. You've been blasting the heck out of their poor cornea with a bunch of really heavy-duty, strong, fortified antibiotics, and it's not budging at all. Now, could you go back and say, "Huh, look at these feathery edges. I knew a long that was actually fungal. I should have cultured that, or you should have, uncharidably speaking, sure." But truthfully, even cornea specialists can't really tell apart a feathery edge of a fungal ulcer from a bacterial one. So, usually the course is just if they're not getting better with your antibiotics, then start thinking about fungal reasons why their cornea might be infected. Now, why would somebody be more at risk for a fungal carotidus? Common risk factors for fungal carotidus include plant or vegetable matter related trauma. Contact lens wear. A fungal species love to grow on the contact lenses as well. Frequent hotosteroid use of a patient's immunocompromised. And they're going to be particularly painful or feeling a lot of pain, like we said, nothing's getting better. Those feathery edges have always been talked about, but you can't really hang your hat on them. And the foliality of the infiltrate might not be as just singly focused as it might be for bacteria. You might have multifocal infiltrates, so then satellite infiltrates into some other places. Right. A way I like to remember that is think about how mold, you know, when you see it on your ceiling tile, how it grows. It often isn't just one big clump, but a bunch of little clumps that grow. Those are basically satellite lesions as well. So that can help you remember, oh, if you see a satellite lesion, what was that correlate to? It's probably a fungal theory. or Titus. All right, and usually these fungal, these fungi themselves, it's usually Candido or Physarium. You can expect to find these on Sabarode Agar, or Blood Agar, and then Confocal Microscopy can show you whether these, the filaments are septar branching or not, which can also assist in differentiation. And knowing what kind of treatment you got to use, right? So if you're dealing with Physarium, then Natamycin is usually your go-to treatment. But if Candido or even Aspergillus pop up, then you have to be a little more intense with amphotericin or voreconousol. This gets even more kind of intense. Sometimes some people are trialing out interest-stroma injection of antifungal agents for some really recalcitrant fungal caretide disease with varying results. So don't jump right ahead to jab that needle right into the stroma, but talk to someone first. And then Classically Physarium is more common in the human southern US. What else is the-- No, that's it. We did it. We've talked about all causes of infectious keratitis. Benjamin, if you insist that we're finished, then I'm going to push you into a pool or a lake where you'll just have to cross your fingers that you don't get a catamoeba. Fresh water or salt water? All right, I'll go find a freshwater pool. And then we'll try this out. So why is a catamoeba so difficult to eradicate? What's so special about it? Well, it's a really resilient, stoic little guy, because it can exist in a dormant cyst form and then pop right out into its other form. It's trophazoid form. And it has a particular pattern of spread where it can spread along the nerves. You can have parinural inflammation, which you can give patients various of your ocular pain. Besides parinural infiltrate, it can also classically present as a ring infiltrate, though it doesn't have to. It grows on other agar. It grows on non-nutrient agar. And then in the same fashion, it'll grow along with e. coli and enterobacter. That's because it's got to have some kind of food supply, since your agar is not providing anything. So it eats the e. coli that grows there. And it has to be that the e. gar provides no nutrition for the e. coli. Otherwise, you're just going to have a petri dish full of e. coli. If you also look under a confocal microscope, you should be able to see the cysts of the organism. To treat it, you can use a b iguanide. That's the class that includes chlorhexidine, which we all know and love, because we use this scrubber hands before surgery or polyhexanide. It-- the reason you like b iguanides is you're going to kill both the trophazoid and that difficult to treat cystic form. There's also moving topics again to a different bacteria, one that is relatively less seen in the immunocompetent population is microsporidiosis. So who does microsporidiosis carotitis usually affect men? Classically, it was an immunocompromised patient, especially during the heat wave aids. While it can still pop up under an immunocompromised scenarios, it apparently has been popping up more in Southeast Asia in immunocompetent patients. So this, too, for patients like that, will be a very painful carotitis. And you also see a punctate epithelialiopathy. And you might even see the small tiny cysts in that area of epithelialiopathy then. So it doesn't really make as much of a big confluent ulcer or a penitentiary deepened astral mitle, just look like a really recalcitrant punctate epithelialiopathy. The treatment for it is if you can restore their immune function, that typically is what you need to help the microsporidiosis go away. But Fumigilin has also been shown to be effective in some cases, though not all. There's one more group. There's one more group of infectious carotitis that we need to know about, isn't there? We can't get away from it. It's herpes. So how can herpes, like a primary herpes infection, present? - Mayna might as well go from front to back. It can present as a follicular blepharoconjunctiveitis. So every time you stand in there, minding your own business, clinics seems to be going well. And suddenly a rogue attending pops out around the corner and goes, what's the differential for follicles? Go. You're scared stiff, right? You can probably mumble out herpatic, saucer, simplex. And then pass that. Do you know anything else? Sure you do. Just remember, moloscomes always gonna be there. And that might be the easiest to remember because it's so exotic. But don't forget about, of course, your more bread and butter herpes of viruses that we talked about, but also the video. I don't know virus can do it too. Could also just be medicmentosa. Can't do anything else. What the hell is MCM? - That's the differential. - This moloscom, colomedia, herpes, and other virus. - And then in the monic and I didn't even know it. - We were deep in the monic, my friend. - I feel so used. - Moloscom, colomedia, herpes, and then a virus. And I just remember it's like any kind of viral contactivitis and medicmentosa can give you a follicular conjuctivitis. - I've been used for a teaching point. So there you go, your follicles, MC hammer. Is that what we were going for? - Yeah, but it's like, you can remember it because it's like, it's like a pig, you know, like a little cute little pig, but it's gonna say it's like MCHAM. See that image? You can't get it out now. It's stuck there. - In my fournics? - Just like herpes. So another way you can present, so that's how it presents on like the contactivitis. And we all know that herpes can present on the skin as vesicles. So we know what vesicles look like. On the cornea, it looks kind of different, but it still looks like injured. - The cornea you've got your dendrites, as often talked about, your dendrites can come in real dendrites or pseudo dendrites, but we'll just kind of ignore that for now, just dendrites. What else looks like a dendrite? What else could it be besides herpes? You know, try this on and off riff band. - Yeah. - I'll take herpes, you'll take Zoster, I assume. - Uh-huh. - And then past that, you could actually just have a weird looking healing epithelial abrasion that just go figure, looks like a dendrite as it heals. But what else more, a little more exotic could it be then? - Yeah, you know, we talked about a can't do meepa before and that can, it's been known to start appearing as a dendrite. And then the weird one to remember is tyrosinemia type two, which is a genetic problem. So if you have a child who has bilateral dendrites that are recurrent and doesn't seem to be responding therapy, you couldn't remember that tyrosinemia type two, which, you know, the life they bring up on the boards can cause that kind of a dendrite. So to review, we have herpesimplex, herpesoster, healing or recurrent epithelial abrasions as it's coming together. Tyrosinemia type two and a can't do meepa. If you want, you can remember the navonic hats with two A's and a Z at the end. - So that's H for healing abrasion? - H for herpes? - H for herpes. - H for abrasion? - Abrajan, a can't them meepa, tyrosinemia and zoster. - That's it, hats. - Okay. - That's for your dendrites. - Herpes, herpes, abrasion. And a can't them meepa, tyrosinemia and zoster. - So, hot. - Hot. So, - How could you prove that any of these is whatever it is we just said. If you've got a handy little vesicle to culture, you can send that along and see whether it's one of these fun things in your two nomonas or not. - In addition, zoster carotitis is known to have more of a pseudo dendrite. That's another thing that can help you differentiate zoster carotitis. A pseudo dendrite doesn't stain like a, your typical herpesymplex dendrite. Whereas a herpesymplex dendrite will have fluorescing staining in the center of it. A pseudo dendrite is more of this kind of stuck on thing onto the cornea. Some people describe it as like you took a bit of paint and splattered it on the wall, then you'd have to have a raised area where the paint splattered. As a result, fluorescing won't stain onto that raised plaque, but rather it'll pool around it, leaving a negative staining pattern. - When it gets to just epithelial involvement for herpetic lesions though, and we're going back to just simplex, herpesymplex here. It's been ascertained that various antiviral eye drop therapies will help. Now, people have their different preferences among them. Some of the older agents like trifluridine are very toxic and you have to apply it so many times, like nine times a day, and it's really rough on the eye because they've got thymarousol for one in your trifluridine. It's really kind of rough. It'd be much preferable if you're in an area that's got it on formulae to use GAN cyclovir, topical GAN cyclovir, because it doesn't have all that as much toxic effect on your cordia. - Studies have also found that one can do orally cyclovir or valley cyclovir, and that's a purportedly equally effective as topical therapy, so some providers are moving in that direction her BCL. one thing with vali-psychovere. One thing to remember is you have to be careful and immunocompromised patients are patients with significant liver problems because one of the known side effects of vali-psychovere is to develop TTP or HUS, chimolytic uremic syndrome and as an eye-providing you don't want to do that so keep that in mind if you're gonna put some on a vali-psychovere. So we always have this debate then and we always revisit the head study and try to remember and don't but when do you use steroids for a herpetic viral keratitis? Not for just keratitis, it has to be stromal keratitis. Yeah so if you see the dendrites and the epithelial problems but you see no stromal infiltrate you're probably gonna keep the steroids in your back pocket you're not gonna bring them out just yet right? Right but if you see some like whitish haze the stroma or overlying corneal neovascularization over the stroma then you really have to think about stroma keratitis. You also have to think about dyscaform keratitis which is really an endothelialitis where you have the circulatory area of endothelial KP and overlying that because the endothelial cells aren't working you'll have a overlying stromal and even epithelial epithelialema over that circle. And in both cases of endothelialitis and stromal infiltrate steroids can't be helpful. Hey, hey Andrew. Yes, Ben. Heads up. We have to do the head study now. Heads up. Get it? So the head's trial had. My head is hanging down right now. The head's trial had a couple of conclusions. We'll just highlight some of the more important ones especially when managing stroma keratitis. One is that the topical steroids reduces the length of stroma inflammation and resulted in better visual outcomes. So most providers will start their patients who have stroma keratitis on topical prednisone. They also found that oral acyclovir reduces recurrence over a 12 to 18 months span after the initial. after the initial episode of stroma keratitis. They actually found that oral acyclovir does not treat the help reduce the length of the average episode of active stroma keratitis but most providers will still start the patient on it because it helps reduce the recurrence rate. If a patient is multiple recurrence, most providers will start the patient on lifelong acyclovir assuming no side effects. Finally, another significant finding of the head's trial is that there's no clear risk factors that precipitated attacks. Classically, we think things like stress or an initiation of steroids or lifestyle risk factors may trigger the onset of an episode of stroma keratitis but that's not proven and was not shown in the head's trial. And that's all we have for infectious keratitis this time. We did an Andrew. We stamped out disease. If you liked what you heard, you can follow us on Twitter at i's four years with the number four. You can also leave us any questions, comments or corrections. We'd love to hear them. And it helps us to rate and review us on iTunes. And a big thank you to Dr. Jessica Chao, our cornea tending and director of the cornea service at Yale who taught us so much of the material that we learned this podcast. And a big thank you to you for supporting us by listening. See you next time. Bye. [BLANK_AUDIO]