 All right, it's seven o'clock, so we'll get started. So I'm Brian Zog. I'm one of the brand new faculty on cornea here. I did my residency here and fellowship here, so I'm a boring Utah guy, but it's a great place to be. So I know most of you, but not everyone, so. I'm Daniel, I'm a business here. I've never seen Nebraska. Nebraska? Okay, Daniel. And who are you working with? I work with Dr. Pettig, I'm a child. Okay, sounds good. Jack, I know. I know, I said I'm not able to do it and it's all Caroline. Okay, great. Who are you working with? Hoffman? Okay, all right. And then I think I met you once in the back, but I can't remember your name. I'm Brian, I'm Daniel. That's right, okay. All right, so we're gonna talk about, yeah, you're Chris, gotcha. We're gonna talk about some of the infections of the cornea. It's a two-part lecture, so we'll have one today and then one next week. Another name for this is keratitis, so that's how you can talk about infections of the cornean sound smart. So we're gonna talk about some of the pathogenesis, some risk factors for infectious keratitis, thinking about how to make a differential diagnosis, what to do in the workup, and then some things to think about as we do treatment. So we'll start off with bacterial keratitis first. So there are some normal bacteria that reside in and around the eye. And so a lot of times you have just normal colonization of bacteria that can cause infections in the right setting. So staff epi is pretty common on all skin flora, but it can cause infections on the eye. Keratobacterium and propionobacterium as well can be just normal flora in and around the eye. So how does the eye actually prevent infections? It uses the tear film initially. The tear film just by washing away bacteria can prevent infection. So if you think about somebody who has dry eye, they don't have a normal tear film. It's not normally turning over the flora. So dry eye patients are at risk of getting keratitis. The tear film has lysozymes and also presents antibodies so the body can respond to infections. You have a good barrier on the surface of the eye to epithelium to try to prevent penetration of organisms to cause infection as well. And then blinking, kind of the same process as the tear film, blinking just kind of moves things around on the surface of the eye helps it turn over. So most cases of infection need some sort of disruption of the epithelium, something that causes it to be susceptible for these organisms to create a home. So common pathogens that can actually go through the epithelium without having any breakdown of it. So Nyseria, Listeria, Cronobacterium, Homophilus, those can all just invade directly through the epithelium without having to have any breakdown. The way that these bacteria work is they have some sort of adherence on them initially, so they'll adhere to the cells on the surface and then they send out toxins to try to break down the epithelium and then they enter and multiply. So the host response is something that we have to modulate in coronial infections as well. It can be a really bad player and cause a lot of problems because the host is trying to kill the bacteria and it also will kill the normal tissue as well because the host uses neutrophils to fight bacteria and it sends out lysozymes and proteases which destroy collagen and so end epithelium. And so that's one of the things that we have to watch out for when we're treating these infections is sometimes the immune response is worse than the infection. So the risk factors, these are things that you're trying to get out of a patient when you see somebody with whitening of their cornea. Obviously the most common cause of infection on the surface of the eyes contact lens related. Homemade solutions used to be common, they're not very common anymore, but probably the most common thing is these extended wear contacts. I don't think there is such a thing. You should take your contacts out every single night. You should make sure that you're changing your cases and not having dirty cases. Contact lenses are very dangerous things that we put in our eyes and people do not use them appropriately. It's pretty rare that somebody doesn't sleep in their contact lenses these days. So trauma to the surface of the eyes, so corneal abrasions are high risk of getting infections. Foreign bodies, especially if they're not removed can have bacterionum and fungus. And then toxic medications is something that we overlook a lot in ophthalmology. We use a lot of medications on the eye to break the skin down and can create kind of Medica Mentosa on the surface of the eye and create a sick epithelium that allows bacteria to grow. Surgery, so we put foreign bodies on the eye. We put sutures in the cornea and the skin and those can have infections that can create big issues. A delin, has anybody seen a delin before? What is a delin usually caused by? What is it? Yes, you've got an elevated spot next to a dry spot, right? So the elevated spot kind of, it almost like prevents tears from really just getting moved around on the surface of the eye. And so you can get little erosions in a low valley next to a high spot. So these are common with Torigia, you can see them quite a bit. We actually had a guy, we did a Torigium surgery and his eye turned black. So he called me and said, my eye's black, like right over the graft where you guys did your surgery and this was like two hours after surgery. And I was like black and he sent me a picture and it was black. I was like, why is your eye black? I don't get it. And he came in and he had a delin, like right over the graft. It was just, there was a little elevated spot next to it and he had a delin. We lubricated, it was just like the reflection that made it look like it was black. It was really odd, lubricated it, it's fine. But a delin can be a big problem. Epithelial defects. So we create epidefacts in cornea surgery a lot, taking off Torigia. We do superficial keratectomies for epithelial basement membrane disease, Salisman's nodules, PRK. There's lots of times that we create epithelial defects. And again, just like an abrasion, it's at high risk of causing an infection. So eyelid issues. So don't overlook these, tracheosis, having a lash rubbing on the surface of the eye, breaking down the epithelium. Can again create a spot where bacteria can get in. Lagophthalmos. So you've got an exposed area of the cornea drying out. Tears are not there, lysozymes are not there to break down the bacteria. And then entropion and nectropion, just malposition of the lids can cause a lot of issues. And especially in VA patients, constantly, right? They all have crappy eyelids. Other things that we deal with on a pretty regular basis, neurotrophic corneas. Again, you just don't have normal sensation. You don't have tears. You don't have all those things and they're helping to fight bacteria. The patients don't really know that something's wrong in some of those cases. And so you have, and then these other issues that are as common, GVHD, SJS, OCP, all those things can cause bolus carotopathy. You got skin sloughing off. Again, just creating an environment where the skin cannot act as a barrier. Epithelium is a huge help in preventing infections. So if you have a healthy cornea, these are some of the bacteria that are pretty common. So meaning somebody who doesn't have like neurotrophic carotopathy or doesn't have basement membrane disease or dry eye, these are some of the things that can just get into a normal healthy cornea, except mostly off the contact lens. This year, I've seen a lot of pseudomonas, obviously, is probably the most common ulcer that we see. But I've seen a lot of more axilla and a couple of enterobactors this year, but mostly pseudomonas stuff. And a compromised cornea, there's not really a lot of difference, but we think about Proteus a little bit more. Some of the strep and staff species come up more commonly and when the cornea is compromised. So when you're talking to a patient on the phone, trying to figure out if they should come in or not, I like to ask them, can you see a white spot on your eye? That's a big deal, right? They can see a white spot. Usually you can see a white spot in the black background, but these are the things to ask them about and to document in the chart when you're talking to them. Pain scales are really annoying to me, but it's important in cornea because when you're talking to somebody on the phone, what's your pain scale now? They're giving a reference to you as to how they felt and how they're feeling now and it can help you understand if they're getting better or worse. So what you're seeing on exam, sometimes you can see an eyelid that isn't even able to open. It's the eyelid so swollen and kemotic, you can't even get it open. You finally get it open, you see this nice big white spot on the cornea, but chemosis and discharge, you've got epithelial defects, stromal infiltrates, so that's where the white comes from. Usually has kind of indistinct borders, you've got white blood cells that are being recruited in. You have to kind of examine all areas of the cornea to figure out where the involvement is. You've got endothelial issues, you can see potentially plaques or circles on the endothelium that can help you understand what's going on. Sometimes you can get pretty bad anterior chamber reactions. So you can see hypopions, lots of cell and flare, and it's hard to tell in a lot of these cases because the cornea is cloudy, so you kind of have them look eccentric and see if there's inflammation going on the anterior chamber. Probably the biggest thing to watch out for is a perforation. So what are things you're looking for, Tara, if somebody has perforated their cornea? Okay, good. So iris is very floppy, flimsy, and it likes to go up and plug areas, so you're looking for a round pupil, it's gotta be round if it's not round, you're suspicious, and compare the chambers on both eyes and see if there's a major difference. Sometimes an ulcer will look really soupy and you can't tell how thick it is, you can't tell if there's thinning of the cornea, so just always sideline, just make sure that there's not an area that's leaky. Why do we care, Chris? Right, we gotta know where the infection is, right? It's gonna really change management if the infection is just in the cornea or if it's behind the lens, right? If you've got vitritus and you've got inflammation back in the retina, you're talking about a completely different beast than just a corneal infection, right? All right, always check their pressure once you've figured out that they're not side-out positive, so do this first, then this. It does metaseal, sometimes people treat it as metaseal lowering the pressure, so putting somebody on some sort of pressure-lowering drop. I find that they're toxic and usually not that helpful, but Timolol's okay on the surface. Cataracts can happen, you can get really bad scarring of the anterior chamber, so PAS, so peripheral anterior, sneaky, and posterior, sneaky. So knowing if there is AC cell and flare is important in preventing somebody's long-term inflammatory consequences of an infection. Okay, so we're gonna go through some of the infectious organisms real quick. So we've got staff, it's a gram-positive coxine clusters, it's a pretty common infection in the peripheral cornea, so you get staff marginal, which is like an overflow of inflammation from staff in the eyelids, so it's not an actual infection on the surface of the eye, but it's usually because there's bacteria in the eyelids from blepharitis. Usually pretty well demarcated, these are kind of what we call dry infections, they don't usually have a lot of discharge, but can have a pretty significant inflammatory reaction. And the lab occasionally will still try to tell you, yeah, it's just staff epi, and then we're not gonna speciate it, it's just a contaminant, but it's not in the eye, right? We know that the staff epi can cause infections. So this is a path slide of ulceration, so you've got thinning of the cornea, absent epithelium, and then you've got a bunch of white blood cells coming in, sorry for the black and white image. Couldn't find a color image for some reason. This is an eye that perforated, so you've got decimates membrane back here, and what it tries to do when it heals after a perforation is it'll, you'll have decimates kind of overlap each other and try to grow in over the top on both sides, so you can get what's called duplication of decimates membrane is a common thing that you'll see on path slides. So this is what a staff or ulcer might look like, you can see a very large hypopia on a very angry eye, and then just kind of this soupy central whitening. This is a suture abscess, not a great photo, but you've got an infection next to a suture. In these cases, we culture it, put them on fortified antibiotics, and remove the sutures if possible. I say if possible because if this shows up right after surgery, you kind of need the sutures, but if it's, if you're two, three months out, you can get those sutures out. The infection will clear a lot quicker with a foreign body gun. In this situation, they actually took the suture out already, right there. Pseudomonas scram negative rod, usually pretty large ulcers with a rapid onset. So some of these staff ulcers, patients will complain that their eyes have been bothering them for a few days. Pseudomonas is like, I woke up and my eye kills and I can't see a thing. And these are more wet ulcers, so really a lot of discharge. Ring infiltrate is kind of a common thing that you watch for. These can thin out very rapidly, and so you wanna try to document how thin the cornea is. Just guess, zero percent thinning, 10% thinning, 50% thinning. Usually contact lens wears. This is what a nasty Pseudomonas ulcer is gonna look like. You just can't really see a lot of the anterior chamber, the IRS details, big hypopion. Sometimes they can be a little bit subtle, just a little bit of whitening. It doesn't look all that bad. I don't know exactly what's going on, but Pseudomonas can present that. Couple more Pseudomonas ulcers. This one's obviously really bad. So this is one that you have to be careful of because any spot in here could potentially be cytopositive because there's so much soupy discharge on the surface you don't know exactly what's going on underneath. And so the areas that I would target is like a thinner area. So you can tell there's a little bit of thinning there, maybe out here, maybe over here, and just kind of paint the surface with the floor seamstrip and just try to tell if anything is positive. Sometimes when I'm doing a Psydel test, I've got my finger on the upper eyelid. I'm wiping and I'm gently, gently pressing on the eye to see if anything will come out. Obviously if you push hard and there's a perforation, it's gonna come out at you. So watch out for the lens. This is what Pseudomonas looks like on an EM. You're obviously not gonna see that very often, but that's a gram-negative rod. This is a confirmed strep infection, bad ulcer in the center, hypopion. Sometimes you just don't know, culture's really gonna help you figure out what to do. Post-RK, we don't see this very often anymore because nobody does RK, but this was fairly common to get infections after RK. It can be very tough to treat. Crystalline keratopathy. So, crystalline keratopathy is kind of interesting. The reason you get this pattern is because you don't have as big of a host immune response. So this is kind of what the bacteria looks like as it starts to spread out and infect the cornea. And so you see kind of these big, little distinct lines essentially of infection. There are some medications that can give you crystals in the cornea. Ciprofloxacin is a very common one. Steroids can sometimes do it. Most commonly, sort of the textbook answer is this is strep with a P, but really anything can give you crystals. So you just have to culture it and see what it is. Usually you want vancomycin on board if you have crystals. This is a confirmed strep and confirmed protease after cornea transplants infection. So you're just not really gonna know unless you culture it. Again, I've seen quite a few of these this year. The problem with moraxel is they take a long time to clear. And so you can have really long, persistent epithelial defects. And because of that, if you have persistent epithelial defects, you can get co-infections and multiple organisms growing in an infection. One of the key buzzwords on tests is that sometimes you'll have a hyphema with a hypopion, it's like a pink hypopion. A lot of times they're not really complaining. They just can't see. There's not a lot of pain with this one. You think about this in immuno-compromised patients, people with cancer, alcoholics for some reason are susceptible to it. It's a gram-negative diplobacillus. Again, very slow to heal. It's kind of painful to take care of these patients because they just don't clear very fast. That's a nasty moraxella. Usually they're a little more subtle, but that's a bad one. How gross those eyelids are. They're just like thick and beefy. So the past clinicians used to say, oh, I can diagnose this just by looking at it. I know what's growing, right? So you've got staph and strep, usually gray, white, they're pretty dry. Usually a pretty severe reaction. Gram-negative rod pseudomonas, wet, mucus, severe AC reaction, common. Really the only way to know is get a lab diagnosis, but a supe ulcer, you gotta think pseudomonas more commonly. So, some things to know. You guys see a lot of patients on call. They're first presenting with the corneal ulcer, and then you don't see them again. It's just how it happens in an academic center. And so you have to document. A lot of times you're actually, sometimes you're seeing patients on call again, right? It's like through the weekend, Thanksgiving's coming up. You've got like Wednesday, there's no triage. So you're seeing them on Wednesday, Thursday, Friday, and they're all different residents, right? So where possible, try to follow up on your own patients, meaning like if you're on on Wednesday, and then on Friday, bring them back then, just so you can tell what's going on with them. But these are the things you need to measure. So, we need a documented measurement of the epithelial defect, and that's different from the infiltrate, right? So you've got the whitening, and then you've got the epithelium that's actually absent. The only way to tell is to put stain in the eye, because sometimes you can't tell if there's an epithelial defect just by looking at a slit lamp. So you always stain an ulcer just to see what the epithelial defect is. I was always painful for me because you can't measure in blue light. There are some slit lamps, I think, at the VA that you can do that, but you can't actually measure the dial and have a blue light in some of the slit lamps. And so you have to kind of like look at it in blue, change it to white, and then measure it, just kind of eyeball it. Corneal thinning, I remember Dr. Crum getting really mad at me one day, because I had seen a patient at the VA document they had a corneal ulcer. He had a Gunderson flap and then ended up with an evisceration. And I never documented how much thinning there was in the cornea. Document it every time you see a patient. Sometimes this can be kind of rapid. 10 versus 60 is a big difference in what we're gonna do. AC reaction, so how much cell is there? How large is the hypopion? Measure those things so we can tell if they're getting better or worse. Again, check side L, pretty much on everybody. Those soupy ulcers are really tough to tell. And probably one of the things that we miss a lot here is if you cannot see the fundus, if you can't get a good view of at least part of the retina, saying the retina is perfectly normal, even if it's 10, 20% of it, you gotta get a B scan, just to see if there's botrytis. If you're trying to look into the retina and you can't get like a good clear view of it, get a B scan just to make sure there's no botrytis, because if they have an ophthalmitis, completely different story, right? So, when do you culture? I pretty much just say, just culture it, right? So, technically, if it's central, you should culture it. If it's bigger than a millimeter, if it's smaller than that, you could get away with it. But it's just always helpful just to culture. The way that I culture ulcers now is much different than I did in residency. Mostly because the lab has requested some differences. They have a new swab called an e-swab that you can just send that, pretty much to cover your bacteria and fungus. There's a few other ones that you'd send if you were worried about other things, but some of these smaller, like if I have a peripheral one millimeter ulcer, I just swab it real quick with the e-swab and send it off. But technically, if it's greater than two millimeters in the periphery, culture it. Yeah, because the e-swab replaces pretty much the blood, chocolate, sap, rhodes, auger. So it gives you all your bacterial stuff. So then you're left with, you know, if you're thinking about chlamydia, you'd want to send that one. The viral transport media gives you chlamydia, gives you the HSV, VZV, PCRs that you can test off of too. So, and then if you're worried about you can't send pages. So there's some things that I tailor, but it was just kind of a normal ulcer looking at just culture with the e-swab. It has a really good bristle on the swab and so you can get a really good scraping deep on it. So I saw a lady on call. She had a one millimeter ulcer in the periphery. She wasn't a contact lens wearer. She didn't have blepharitis, but it was a pretty like dense ulcer. And I was just like, this is weird. Could be staff marginal maybe. So I cultured it, grew pseudomonas in 12 hours. Her ulcer ended up being like three or four millimeters in size by the end of it. Ended up with a PK later. So you just, I think it's better just to culture and just to see what it is. Cause it did change management. I think I put her on Bigamox, but she was still getting worse on Bigamox. So we had to add another antibiotic to cover pseudomonas. So what do you need to culture? I grabbed a quick bag of stuff to culture so you guys can just look at what I usually grab. I think it's pretty typical if you're gonna culture, fully culture an ulcer. And you have to be pretty quick at this on call because when you get the call to culture or you got according ulcer, you've got like five other patients and cultureing takes a while. And so you have to be quick about grabbing stuff and moving on. So these are the things to grab. So the swabs, they come in the culture media usually. The chimera spatulas, 15 blades are pretty good. They're sharp, but they give you a good culture. I don't think I ever had a Gramsene come back positive on a slide. They always just said no organisms, but I would still try to Gramsene it. It's good to circle the area that you put the bacteria with a marker so they can look there. Use topical anesthesia. There's some places where it says, if you're culturing, don't use anesthesia. You gotta use it because you're gonna really hurt the patient and then grab your plates. So you've got your blood, which covers, a canthamoeba technically can grow on blood. It's not the best one for it. A non-nutrient auger with bacterial overlay is kind of the best one for a canthamoeba. Fungi, A-robes, anarobes, and then your chocolate covers your A-robes. Saveroids covers your fungi. So that'll glycolate broth, anarobes, low-enstein gents, an auger, mycobacterias, those are kind of some of the common things. We don't have low-enstein gents and so you just send it in a regular swab and ask for that culture. These are some of the other cultures that you might use in certain situations. You'd have to request them specifically from the lab. So one of the hardest parts about culturing is not contaminating your culture. And so you wanna try not to touch the eyelids with your spatula. So there's two ways to do that. I'd never put an eyelid speculum in, but that's a way to do it. The patients usually squeeze against it and it's a projectile that could come towards you as they're squeezing and it pops out. So I just never wanted to use one. So I usually just hold their eyelid open, scrape really quick, move away, let them blink, scrape again potentially with that same wand or switch out. You technically want a new spatula for each scrape if you're gonna plate them. You definitely have to use a different swab if you're gonna pop it in the tube and send it, but they all come with them. And then what do you do for treatment? Well, your clinical impression is kind of the first line but really the best choice in most cases is just to give them bankantobra. Because it covers, vancomycinol gets your gram positives, MRSA, staff and strep, kind of the main things you're looking for there. And then toberamycinol cover your gram negatives, especially pseudomonas. There's a lot of places around the country that use seftaz and tobra, both, because the most common infection pseudomonas that double covers it. But seftaz doesn't have as good of a gram positive coverage. So I still like bankantobra. And then if it comes back, pseudomonas, I'll get them off the bank, potentially add bigamox, something a little bit more less toxic, I guess I should say. This is something that commonly gets missed. Every time you see a patient you wanna go into the lab and look at the culture results, you can have a positive culture, at least part of a culture that can help you in your clinical management and we're skipping that. So just make sure you check and comment on that in all your notes. Sometimes they won't give you sensitivities. I would always just ask for them. Sometimes I'd call the lab and I'd say, hey, can you run sensitivities on this? And they were like, this is an autism that never is resistant to anything. So in that case, sure, I don't need it, but it's good to tailor your antibiotics if you can. This is another common issue. Have them speciate everything that grows out. So if they're getting some gram positives, they might say one or two colonies of gram negatives and then they don't speciate it. So you have to call them and that's why it's just good to check the culture results and call them. Because sometimes they'll say, well, we don't have that specimen anymore because it's been 10 days since we ran it. So you just have to check it every time you see them. This is an interesting idea. I actually like the idea. You can treat the patient with some beta-dine flushes at the initial presentation. You have to think that it would lower the bacterial load. Obviously you'd have to do this after your culture, right? But that's something that you can try it. I don't care. Give it a go. All right, so antibiotics. So amino glycosides, topomycinamic acid are the ones we use. Gentamycin is not used anymore. Apparently I can't type as an N. These are bactericidal. I remember Dr. Tabin being really big on this. Bacteriostatic versus bactericidal. Antibiotics. He was always big. I can't remember the two combinations. It was like urethromycin and something else that we use a lot. And they were both just bacterial, static. And so they're not technically killing organisms. They're just stopping them from replicating and having the host immune system try to kill the organisms. So there's some ways to think about that. I think it's a little bit more academic than real life, but just some interesting things to make your life more fulfilled. This is a bactericidal. So it kills bacteria by inhibiting their protein synthesis. This has good gram-negative coverage. Pseudomonas is the common one that we use it for and then Proteus that occasionally pops up. The problem with this antibiotic and a lot of the antibiotics we use is they're very toxic to the epithelium. And a lot of these cases, you're trying to get the epithelium to heal and you're causing it to not heal because of how toxic the medications are. And so you wanna back off as quick as you can on these medications, hit them hard initially, and then back off as they're improving to help their epithelium heal. The fortified dosing is 15 milligrams per ml. If you just type in Tobromycin, it'll show up as fortified. So you can get it pretty easily in the computer. Cephalosporins, this is just a common teaching you've learned since medical school. You increase activity on gram negatives as you get the newer generations in weaker gram positive activity. So it doesn't cover MRSA. There's some cross rectivity with penicillins. This is a common one to watch out for. I just don't use Cepthas a lot with Banc and Tobra. You don't really have to worry about the penicillin allergy that you get it commonly. But this is the key is that Cepthas is pretty good against pseudomonas. Fortified dosing is anywhere from 30 to 50 milligrams per ml. That one's not in our system, so you'd have to tell them what concentration you want. So in the real world, fluoroquinolones are probably the most common antibiotic given for accordion ulcers. And the reason is, is because it covers pseudomonas really well. And the other nice thing about Vigamok specifically is it's a preservative-free medication, so it's not toxic to the surface. So it's really nice and safe on the surface to give every hour. All these other medications are also good antibiotics, but again, they're a little bit more toxic to the surface and don't have as good of coverage for pseudomonas. So these are bactericidal, so they don't, they actually do inhibit DNA synthesis within the bacteria. They're good, sorry, I guess not DNA synthesis. Is the gyros more in the protein area? Is they create proteins? It's probably right, is they unfolding the DNA and then, anyway, I don't know. So they kill bacteria. Safe in kids, so don't worry about like that whole tendon rupture or whatever in kids with topical fluoroquinolones. Ciprofloxan, again, this is pretty common. And we have a kind of an interesting patient that keeps on using Ciprofloxan when she gets like a conjunctivitis and she comes in with crystals in her cornea and then it goes away when she stops it. So kind of an interesting one with Cipro. I hate Ciprofloxan, I think it's a terrible medication. There is a good ointment. Ciprofloxan ointment is actually pretty good when you have a pseudomonas infection, but the topical drop is not very good. It's pretty toxic. Vancomycin, bactericidal. So it inhibits cell wall synthesis. It's kind of in a unique class of its own. Really good against MRSA, the fortified dosing's 25 to 50. A lot of people advocate the lower concentration to help with the toxicity of the surface. This one's a painful one, it hurts. Toverycin hurts. The pH is a little bit off on them so they hurt when patients put them in their eyes. So urethromycin commonly used, kills grand positives. Chloramphenicol we don't use very often here. And then sulfa medications are pretty good for grand positives. Even topical sulfa can cause SJS, like symptoms or even cause the full-blown skin reaction. So just watch out for sulfa. We don't use them all that much. So initial treatment options. If I have a small peripheral ulcer, fluoroquine alone's great, just give them a big box. It's more expensive than fortified antibiotics. So it's kind of a catch-22. It's like patients are gonna pay 100 bucks for Vigamox. The combination of vancomycin and Tover is about 50 or $60 for the fortified drop. So some people use Vigamox and Cepthaz. Some people use Tovera Cepthaz. We're probably most commonly Topra Bank on our initial treatment. I think it's pretty good to load patients in the first hour, hit them hard. Four times in the first hour, and then pretty much hourly for the first two days. You don't have a clue what their response is in the first 24 hours. In a lot of cases now, if I see an initial corny ulcer, I see them two days later, unless they're thin, because I'm not gonna really know what's happening the next day. You've got toxic medications, you've got an infection that's ramping up, and you're trying to fight that battle. So you're just not gonna know a lot of times. Again, watch the culture results. Try to taper as quick as you can. And it's really the clinical response that drives the frequency. So I really try to back off quick, but if they're not getting better, then I'm still hourly, sometimes for the first week. Keeping them up at night versus not is kind of a tricky call. I have patients who come in four days after they see you guys, and they've been up every night, and it's pretty miserable for them. So the first 48 hours, I probably keep them up and then let them sleep, and just tell them if they wake up in the night to put them in. This is something that we fight occasionally. Doesn't happen all that often, but you get some of the homeless guys or unreliable patients that need to be admitted. This is a battle with medicine because the frequency of drops that we require is not appropriate for a medicine bed. And so sometimes they end up in a step down ICU area. But you have to sort of fight the battle that this is a very important limb of the patient, their eyeball, and it's a blinding infection. And so if they have an infection in their leg, they're gonna get admitted, but it's easier to take care of that than it is the eye because they're giving frequent drops. So be sensitive to that, but sometimes you have to be pretty forceful about it. So what if they're not improving? This is where things get tricky to figure out. And probably the most common scenario that this happens is in clinic when you're getting a referral from an outside ophthalmologist or a patient's getting a second opinion. That's what happened with the Acanthamoeba patient that I saw, that you guys saw in Grand Rounds yesterday. She came in, had a bunch of different treatments going on and it was just confusing as to what was happening. So I just started at a new baseline and said, okay, I have no clue what's happening. I'm gonna re-culture and just say, this is the first time she's coming in, what's going on? And try to just create a differential diagnosis and go from there. And I think Chris saw her on the weekend. We kind of had to modify our differential diagnosis as things went on as her clinical response. She got worse. And so we started fortified. So I initially just put her on Vigamox because it didn't look all that bad. Stopped with some of her medications thinking they were toxic. And so sometimes you have to take a step back and trial and error. And I just tell the patient straight up, I'm not sure what's happening. We're gonna have to try some things. You're gonna have to be patient. We'll see what happens. This is something that I actually ask pretty much every patient that I see that has some sort of a chronic cordial issue. Do you have any topical for paracaine? Because they ask you for it when you come into clinic. Hey, can you give me one of those numbing drops that gives me good relief? You don't have any of those, do you? It's kind of what I say. Just like straight up, do you have them? And occasionally they'll say yes, because they do have them. The ERs give them out, the instacars give them out. So you have to watch out for this. The other key is do not leave your drop sitting on the counter. I did it a lot as a resident until a patient stole them. And I got them out of their pocket, because I was like, where's my paracaine? And then you have to educate them on how bad it is. Has anybody seen issues from paracaine? You guys have any patients come in yet? I think I've probably seen three or four. And one of them ended up with a transplant because it causes a corneal mel, essentially. It's just very toxic to the surface. The other two actually did okay. They were on them for about 48 hours and we were able to stop them pretty quick. When all else fails, stop their antibiotics for 24 hours, reculture them and see what you get. A lot of times cultures are negative and you're just stuck throwing the gamut at them and trying to get them to respond. So some things that we miss a lot. I see a lot of patients who aren't on cycloplegics but have quite a bit of anterior chamber reaction. Cycloplegics help them feel more comfortable, even just like cyclopenylate once or twice a day or cyclopenylate PRN. If they just throw it in when they're having a lot of licensitivity, it'll help them. It helps with the ciliary spasm that you get with inflammation, but the big thing is preventing posterior synechia. Nothing's worse than having a corneal ulcer clear and having a pupil that's one millimeter in size when you can finally see the anterior chamber. So err on the side of caution and give them one. I don't like atropine because it kind of makes their pupil really big and if they get posterior synechia, it'll just sneak down really big. The nice thing with cyclopenylate is it kind of wears off so their pupil's kind of still moving a little bit but it's moving in a larger range. So if they're gonna get posterior synechia, their pupil's a little bit bigger, but not nine millimeters. So some other common medications that you might see corneal ulcer patients on, if there's any thinning, I give them doxycycline and vitamin C. So they both inhibit collagenases. Vitamin C is an important component in collagen synthesis so it's kind of a battle between creating collagen, breaking down collagen. The initial dosing on doxycycline is 100 milligrams twice a day. I tell them if their stomach is irritated to switch it to once a day, take it with food. You have to watch out for calcium products with tetracycline and minocycline more than doxycycline. They can't take it with milk or dairy but those are common medications you'll see. We'll glue a lot of these patients. Cyanolacrylic glue is actually bactericidal so it'll kill bacteria and it can just create a little bit more stable thinning of the cornea, especially in desmedicill patients. A bandage lens goes over the top of the glue. Less is more with this glue. Has anybody glued a patient? How do you do it? What's the, any secrets? Oh, Mr. Ma, Mr. M? Yeah. Yeah. It worked okay the first time, right? So the way to do this is you take the skin stitch. I've actually used the, I don't know, I can't think of the name of this. What's the glue they use in the ER? It's different. It's not like our skin stitch brand but I can't think of what it's called. Dermabond? Dermabond works. The problem with Dermabond is it just has a really big delivery system so it's kind of hard to deliver a small amount. So I usually get kind of a medium gauge needle, like a 27 gauge needle and put the glue in the end of the needle and just let it slowly drip out. And a lot of times, all you really need is one drop on the cornea surface. I put one drop on there, let it dry for 10 seconds, see how it's distributing and maybe put another drop. You don't want the glue to slide down off onto their conge because then they'll have dried glue that's not covered by the contact lens and you don't want it heaped up too much because you want the contact lens to stay on there. And so less is more in a lot of these situations. In most cases, it's like one or two drops can cover it for you. You can get glue to work in cases where the opening is less than a millimeter or if it's bigger than a millimeter and the iris isn't plugging it and there's not a lot of AC which is kind of not common but because you get an efflux, the efflux of fluid is what creates the difficulty in gluing. And so if you have an AC that's pretty shallow, you can get some glue on bigger areas. A PK is sometimes the treatment that we have to go to. It gives you tissue and sometimes it's therapeutic as well, kind of solves the problem. And then patch grafts occasionally will do that just a smaller corneal transplant to fill in an area of thinning or perforation. Okay, so that's all the bacterial stuff to think about. So fungal keratitis. You think about this in patients who have for sure foreign bodies, especially vegetative foreign bodies. So I got scraped in the eye when I was gardening or poked in the eye with a stick or things like that. You wanna think about this. Clinically, they're gonna have a little bit more indistinct borders. So they'll have kind of a denser ulcer that'll kind of just branch out a little bit different than a bacterial ulcer does. Multifocal is kind of a key buzzword. Diabetics, alcoholics. A lot of times with fungal infections, you'll also have bacteria growing. I don't know if you heard Dr. Mifflin, but we've treated lots of patients with fungus and bacteria growing at the same time. So they come together a lot. So kind of a non-specific corneal infection. You got kind of these borders that aren't very distinct. It just kind of branches out. This one ended up being a fungal ulcer. Or they can look like this and just look like a soupy mess and come back as a fungal ulcer after a PK. So you can actually get, some people culture the rim of the PK tissue because sometimes you can get fungus growing in the donor tissue for a PK. I don't do that. Dr. Lin does. Dr. Mifflin doesn't. But sometimes you can get a really bad infection after PK. Fungi, they come in all different types and styles and it drove me nuts to always try to remember this stuff and it didn't come up that much. But Eucor is the common one. You have to know what it is. But other than that, not really that much. It's what a yeast looks like on EM. They're not very common here. Fungal keratitis is not all that common. I don't see it very often. But it's a lot more common in the Southern U.S. Aspergillus is the most common infection worldwide here in the Northern U.S. Canada and Aspergillus than Fusarium. They ask a lot about for the Southern states. Trauma is a common risk factor, especially with a foreign body vegetative material. Contact lenses obviously. Topical steroids, that's why you can get them after PK. Not all that infrequently. So cornea surgeries, RK, and then these lamellar grafts. Chronic infections. So just things that are kind of smoldering on the surface of the eye. You've got keratoconjectivitis, like allergies and vernal. And then some of these viral infections can give you a susceptible spot for it. So treatment, natomycin, cycloplegics. You can give them oral medications if it's Canada, Amphotericin, PK sometimes. Get rid of the infection. Acanthamoeba we talked a little bit about yesterday. So this is, can be kind of really tricky to diagnose. It's not common. But a lot of times the signs, what you're seeing on the cornea pretty minimal and the patient's miserable. And that's how it was with this patient. It was like her epithelium was a little sick initially. It was white and hazy. But there was no like obvious, dense infiltrate anywhere. But the calcifer white stain is something that the lab will run. The blood auger with E. coli overlay. Sometimes you have to get a biopsy or convochal. Treatment for this, they talked about yesterday again. PHMB, as I don't even know where that came from, PMHM. That was just bad typing. Broline, you have to get that outside the US. Oral atroconazole can help. Neomycin actually does help. But you've got two different forms that you're having to kill. So sometimes they're on antibiotics for months to a year. Some new things, collagen crosslinking is something that's coming out. Being treated in some places, being used to treat Acanthamoeba in some places. PK can kind of get you in a better situation. A lot of times D-bolk give you a tissue diagnosis. Dr. Manlis loves when Acanthamoeba comes through the lab. That's it.