Lecture: Current Management of Acid and Alkali Burns in the Short Term and Long Term

DR DJALILIAN: Good morning, everyone. My name is Ali Djalilian. It’s my pleasure to be here with you all this morning. For us this morning, and night for some of you. So wherever you are, I hope you’re all doing well. So this morning I’m gonna share with you some thoughts and a review, basically, on the current thought process and management of chemical injuries, both for short-term and long-term. I have no financial disclosures related to this talk. So, again, as you know, chemical injuries can lead to severe destruction on the surface of the eye. And it’s one of the true medical emergencies in the eye, immediately after it takes place. So interventions are necessary to try to minimize the complications, both in immediate and short and long term. And obviously, as you know, epidemiologically, this is more common in males age 20 to 40, but obviously it can happen at any age. So the common offending agents: Chemicals that are used for cleaning, they’re a common cause, both at home and in industrial settings. This one is, for instance, sulfuric acid. But battery explosions — I’ve seen patients. Alkali, acids, both can be quite destructive. As we’ll talk about in a minute. And the severity of the destruction, obviously, depends on a number of factors. The pH, and the concentration, the volume, the temperature, the time the surface gets exposed to these chemicals. All of these can affect the severity of the damage to the surface of the eye. So again, a quick word about alkaline injuries versus acid injuries. Alkali in general, as you all know, can cause much more severe damage, because they can penetrate the tissues more. While acidic substances won’t be able to penetrate as much, given that it causes coagulation of the proteins. However, having said that, a point to remember is: Both acid and alkali can cause very severe damage. So in the acute setting, really, you treat them both the same. And I’ve seen just as bad things happen with acidic injuries. But the good part is that the penetration is less with acid. But nonetheless, the surface complications are pretty comparable. So acutely — this is one of my patients. This is actually a combined chemical and thermal injury, and this actually came up — it’s off the screen here — but it’s from a fireworks injury. Not too long ago here in the US, we have an annual fireworks festival. But the findings — this is a pretty severe injury, again, which also affected the skin and periorbital area, which can happen in these settings, but often in severe injury, there’s quite a bit of chemosis here. You can see a lot of white tissue, basically white ischemic tissue here. The cornea is quite hazy and edematous. And you can’t really see much further here. But there can be other findings inside the eye. There can be sometimes cataract, and a very severe injury that penetrates the eye further. So this patient, again, when you stain this patient, you see no epithelium. A total loss of epithelium. So these are severe grade injuries. But again, you can have varying degrees of epithelial defects. So some of the findings, like we said: Cataract could indicate penetration of the chemical. High IOP — again, this sometimes can be, again, through damage or inflammation in trabecular meshwork. We’ll talk more about the IOP. And then in very severe cases, there can be damage to the retina. It’s mostly immune mediated. So in those very severe alkali injuries, you can have posterior damage. Okay, so a quick question: What is the most most important prognostic factor immediately after ocular chemical injury? Corneal and conjunctival, chemosis, conjunctival inflammation, and limbal ischemia? I guess I’ll submit my answer also. Okay. Great. All right, so… 95%, limbal ischemia. That’s great. Good, good, so we do have a very experienced group here. So we can go through some of the basics more quickly. All right, so again, the severity of limbal ischemia — and this will be basically whitening of the tissue. Because of all the vessels and all the structures of the vessels — have been destroyed at part of the injury. That ischemia is a major prognostic factor. And that’s really — again, here, you can see quite extensive limbal ischemia here. We’ll talk about grading in a second. So that degree of limbal ischemia really forms the basis of these grading schemes, to determine the severity of injury. Grade I has no limbal ischemia. And just limited corneal epithelial damage. Grade II has a little bit of corneal haze, and less than one third limbal ischemia. Grade III has total loss of the epithelium, stromal haze, and one third to one half limbal ischemia, and then grade IV, which has a poor prognosis, the cornea is mostly opaque, and more than half limbal ischemia. And that’s the Roper-Hall classification. Dr. Dua also has come up with another classification, which goes up to number VI. Basically it breaks down the limbal involvement into the number of clock hours. One to two, two to three, three to four, or four. And that is just — since there is a bigger jump in the other classification. But I still tend to use that original one, grade I to IV, for most of my patients. So a typical example: This would be a grade II type injury. We can see the ischemia here. It’s less than a third. There’s some corneal haze. And this would be probably more, I think, grade III, or possibly IV, depending on what’s happening superiorly. Okay, so in terms of pathophysiology, there are different types of events that are taking place. In the acute setting, there’s the acute phase, in the first seven days. Then there’s an early repair phase, 7 to 21 days, and then late repair, beyond 21 days. I mean, these days are somewhat arbitrary. Plus or minus 10% or 20% on each of those numbers. So we divide the management and how we’re gonna discuss today in the talk… Into immediate, acute, and chronic. And acute being the first six weeks and chronic being beyond six weeks. So, again, it looks like we have an experienced group here, mostly. So the management of the immediate phase goes without saying. That it’s irrigation, as quickly as possible. With an aqueous solution that can be obtained as quickly as possible, and oftentimes that’s gonna be water, tap water. Followed by, obviously, irrigation, when they present to the emergency room, or to the clinic setting. So these patients, again, we have, again, an experienced group here, but this protocol for treating patients with chemical injury, when they walk through the door, should already be established. They should have everything ready. You shouldn’t have to scramble to find everything. You should get started immediately. Not waste time taking history. You put an anesthetic in and start irrigating right away. This should be “can use”, instead of “us”. Can use a Morgan Lens. I’ll show you what that looks like. You can irrigate at least a couple liters, checking pH, until you get to 7.5. So this slide, again, is from the Morgan Lens manufacturers. There could be other variations of this. Obviously no financial interest in this, but basically it’s a plastic lens type that sits on the eye, and it gets hooked to an IV bag, and you can irrigate continuously. And it facilitates the process. Makes it easier. Again, as you know, it’s important to sweep the fornices, both lower and upper, for any particulate matter or pockets of chemicals there. If the patient is wearing a contact lens, remove their contact lens, which could also be another reservoir with chemical. So the management of the immediate phase, like we said, really tap water as quickly — or water as quickly as you can in the field. It’s hypotonic, so it does cause some corneal swelling. Probably the most readily available are gonna be these isotonic solutions that are used for IV fluids, normal saline or lactated ringer’s. Lactated ringer’s is probably preferred, because it has some buffering capacity. So that probably is our first choice. Buffered solutions are probably not the ideal, especially if you have this. And then these amphoteric solutions that have higher buffering capacity have been developed. There’s some data that these might have some slight advantage over the lactated ringer’s, but probably in the long run doesn’t make much difference. But the probably is that these are not readily available. If it’s right away available, then obviously you can use this, rather than the other options. Okay. Now, I’m gonna move on to the acute phase, beyond the immediate phase. So this is the question beforehand. Which one is not one of the main objectives during the acute phase, after the immediate phase, in the management of chemical ocular injury? Decrease inflammation, avoid further epithelial and stromal breakdown, foster re-epithelialization, and copious irrigation? Okay. I didn’t phrase this question properly. I wanted to know: Which one of these is not part of acute management, following immediate? Immediate, the treatment is copious irrigation, then following that, starting immediately in the first couple weeks, these first three are what we’re gonna do. So this was not a very well worded question. But anyway, we’re gonna discuss these here. Okay, so during the acute phase, starting after the immediate, to the first six weeks or so, where the major goal of our treatments are to decrease inflammation, avoid further epithelial loss and stromal breakdown, and foster re-epithelialization. So we published an algorithm, in a review paper. I can share that with the audience later on, if they like. After irrigation, these are the steps we’re gonna take to control inflammation, promote reepithelialization, prevent infection, and prevent stromal breakdown. We’re gonna talk about all the components here, basically what are involved. So okay… So I saw that steroid really is a key question that a lot of people also had a question about steroids. We’re gonna spend some time talking about steroids. Which timing and regimen is most appropriate after chemical injury? Immediately before irrigation, start with mild steroid drops. Start after irrigation, steroid drops every hour for the first 10, 14 days, wait until the cornea is re-epithelialized, then use it four times a day, start steroids only if there is inflammation, and start with the lowest dose. So which of these sound to be most appropriate? Okay, great, perfect. That’s the one that I had in mind. Start after irrigation. So why are we using so much steroids? What’s the rationale? And the rationale obviously is that when you have such massive tissue destruction, you’re gonna have massive inflammation. And that inflammation itself is gonna cause even more destruction. So what we’re trying to do is stop or reduce that surge of inflammation, particularly neutrophils. You get a massive infiltration with neutrophils within that first week. So you really give very intense steroids. And here we use prednisolone acetate, is our strong steroid that’s easily available. But any other equivalent potent steroid, dexamethasone, or something like that, is fine. And you use them every hour, for an injury that’s grade II or higher. So now the question about the steroids — as you know, they’re a great medication, but they come at a cost. And the problems here that we run into are that steroids can inhibit epithelialization, they can inhibit collagen synthesis, and because of that, they can help contribute to melts. So the standard teaching is to stop the steroids, after the first 10 to 14 days. And I would say… So a key determining factor here is the epithelial defect. So if you still have an epithelial defect at two weeks, and those are gonna be the more severe injuries, then definitely you have to back off your steroids considerably. However, if your epithelium has healed by two weeks, then really you’re safe to continue using steroids, as much as you think it’s indicated. And I would be hitting them pretty hard with steroids. Maybe not every hour, but you can back off to every two or three hours. But once you have an epithelial defect that’s persistent, beyond two weeks, then you have to back off your steroids, and I typically back off to probably no more than three or four times a day. That’s just because the risks of contributing to a melt… And that has been shown in previous studies. So other things that we can do to sort of augment our antiinflammatory therapy is systemic steroids. With severe injuries, I’ll start with one milligram per kilogram, right away, that first day. On presentation. And keep them at this level for at least a week or two. Then start to bring it down, taper over that first month or so. Again, just a minor point, that again, patients are gonna have chronic, prolonged inflammation, and I have these agents, such as Azathioprine or mycophenolate. But generally the longer you can use these, the more you can reduce sequelae. And why would you get melts in this setting? Because there’s been so much destruction on the surface, there’s much viable cells in the stroma. You have hardly any living keratocytes in the stroma. And when you have such massive infiltration of inflammatory cells, such as neutrophils, who are dumping a lot of matrix metalloproteinases, they’re gonna start digesting the tissues, and there are no cells there to start repair. So that’s why in this setting we try to do anything we can also, things like tetracyclines, which have MMP-inhibiting activity, ascorbic acid or vitamin C, to help promote collagen synthesis, these two for sure I do use. We’ll talk about doses in a minute. And then these — citrate or acetylcysteine, cysteine, aprotinin I don’t use in this setting. But this citrate certainly some people use. It’s just not as easy to get. So tetracycline — class of drugs. Whether it’s tetracycline itself, or doxycycline, or minocycline. That we’ll start in all these chemical injury patients. Vitamin C, 1 to 2 grams a day. Like I said, citrate also some people use. But I haven’t used it. It’s not easy to get. So promoting epithelialization. That was controlling inflammation. Now we have to try to promote epithelialization. And obviously that’s critical. The faster you can get the epithelium to heal, the faster you’ll stop the risk of melts and other potential complications. So prophylactic antibiotics I use, but we don’t have to use the most potent antibiotics. I like like to use something like erythromycin ointment, several times a day. These other agents like chloramphenicol, which might be available to some of you, probably just as good. I would avoid medications that are a little bit toxic to the epithelium, like gentamicin. We use a soft bandage lens in pretty much all these patients to help with epithelialization. Now, if you have a persistent defect that’s not healing, then scleral lenses may be an option to think about. Once you get into that sort of chronic phase. Large diameter scleral lenses. But again, this depends on this being available. Just because it requires expertise to fit these. So it does require some time to get the right fit, but also have a good enough fornix to get this into the eye. Either way, I think this has a role in the chronic phase. Acutely, soft bandage lens. So amniotic membrane… I think most of you are probably familiar with this. It acts like biological bandage contact lens. Sort of an alternative to using a hydrogel contact lens. So this is one sort of contact lens-like device and again, I have no financial interest in the ProKera, but this just makes it easier to put in and out. It does offer advantages here. In that amniotic membrane also does have antiinflammatory effects as well. So basically it’s acting like a sponge, let’s say, for trapping neutrophils, and other inflammatory cytokines. And I would say for injuries up to grade III, for sure it can improve… Or let’s say it can accelerate your epithelialization and that’s been studied, and it can also reduce pain in these patients. But for the very severe grade, grade IV, probably doesn’t make much difference. Because so much tissue has been lost, and destroyed, so it probably doesn’t… It still cannot lead to epithelialization during that one or two weeks that this membrane lasts. That’s still not long enough for epithelium to heal. Or epithelium to start to come back in these patients. Anyway, so I would say… The most appropriate place to use it would be in a severe grade II or grade III injury. And basically for most of you, something like this would not be available. This is a persistent epithelial defect. This is a little bit different. This is more in the chronic phase. A patch graft was placed here. Or I should say a graft was placed here. Then the membrane was placed over the whole cornea, as a patch. And some people would even go and line the rest of the epithelial surfaces, the conj and bulbar surface. There’s not much downside to it, but I’m not sure it really makes a big difference. Anyway, we can talk more about this through questions at the end. Other things people can use to try to speed up epithelialization… Again, we don’t routinely use these right away, but for a defect that’s persistent several weeks, we’ll start the patient on autologous serum, PRP, or platelet rich plasma, is another alternative. Really no studies comparing these head to head to say which one is better than the other, but maybe the PRP has more rich growth factors. But either way, both are good options, and really very little downside to them, other than that they’re difficult to get, or to get someone to make it for you. There was a question on tarsorrhaphy. I threw a slide in on it here. Tarsorrhaphy doesn’t have much of a role in the acute phase. But definitely in the chronic phase, we have a persistent epithelial defect that persisted for two or three months, for sure it has a role. But if I have a patient that has adequate fornix, and scleral lens is available, I would probably try that before tarsorrhaphy. But nonetheless, I’ve dealt with epithelial defects that have persisted for three, four, five months after the injury, and finally the only thing that got it to heal was a tarsorrhaphy. So another question on the management here during the acute phase. Which one of the following pitfalls, or, let’s say, mistakes, if we should call it, or oversights is more serious during the management of a chemical injury during the acute phase? Not using artificial tears or lubricants, not following the IOP, intraocular pressure, not using amniotic membrane, or not using a bandage contact lens? Which of these could be the most serious oversight, let’s say? Yeah. Great. So, again, not following the IOP really is definitely an important part of our management in these patients. And it’s easy to overlook that, because you’re so focused on the surface that you lose sight of the fact that the IOP could be going up. So these patients need their IOP checked every single visit. Usually you’re seeing these patients at least twice or three times a week during these first couple weeks. So that’s just so we don’t forget that that. Again, I have to myself also about that. So Tenonplasty. Basically the idea here is that when you have so much necrotic tissue, including necrotic Tenon’s, and really not much in this picture — I’ll discuss this in a minute — in those cases, you want to excise a lot of that necrotic tissue. When there’s extensive limbal ischemia, a lot of your Tenon’s tissue could become necrotic. Not here. This tissue is obviously nice and viable. But again, if this whole area looked like this, you would have some necrotic Tenon’s there. So excising that may help reduce inflammation, and then you can pull healthier tissue over it. So the idea is to try to, if you can, bring vessels up to the cornea, bring tissue, bring some viable tissue closer to the cornea. In all those necrotic or ischemic areas to help promote healing. And you can combine it with amniotic membrane transplant, if you want it, or patch grafting. So I’ll tell you — what we did in this patient, actually, this area persisted as a defect, for… I can’t remember exactly, but at least a month or six weeks out still had a persistent conjunctival defect. And we were worried about a melt or something like that. So basically we went and any sort of necrotic tissue that was there was removed, and then we advanced tissue surrounding area, to try to help close that defect, and bring viable tissue here. So we basically brought some conj and Tenon’s, and the patient did quite well. They basically healed within a week or two after that. So to sum up our summary of our management in the acute phase, and this just shows the sort of level of evidence in terms of studies. It’s tough to do randomized controlled studies for these conditions. Not enough patients and too variable. But there’s good evidence from different studies to support many of the things that we’re doing. So steroids, tetracycline, vitamin C. Many of these studies really support those. Bandage lens, I think, goes without saying. It can help with epithelialization. Amniotic membrane, as we talked about, if you’re going for the antiinflammatory effect, then you want to do it in that first week, for sure. But otherwise, if you’re doing it to promote epithelialization, that can be done later as well. Just because it takes while for that epithelium to start moving. Autologous serum, Tenon’s, and then high IOP. Okay. Now we’re going on to the management of the chronic phase. Which one is the last surgical intervention that should be performed in the chronic phase of ocular chemical injury? Keratoplasty, correction of eyelid abnormalities, management of glaucoma, or ocular surface reconstruction or transplantation? Okay. Great. Again, probably not the best-designed question here. What I was going for here was keratoplasty. In other words, not to jump to keratoplasty, but again, the reason… So the idea was to correct eyelids and glaucoma and surface reconstruction before you do keratoplasty for vision. I should have corrected that. But you may have to do a tectonic keratoplasty, because it’s melting. So again, if you didn’t get keratoplasty, it was more my fault for not phrasing this question right. Okay. So the chronic phase can be challenging. And it requires, often, multiple procedures to try to rehabilitate these surfaces, these eyes. But typically the order that we go with is we start with correcting eyelid issues, address the glaucoma, then you do surface reconstructions, limbal transplantation, or conjunctival restoration. Finally, keratoplasty for vision. And this is a patient who, again… This patient only required just a limbal autograft. Actually, first required a one-step procedure for amniotic membrane and fornix reconstruction, followed later with an autograft, and did quite well. But didn’t require anything else. It was due to a battery explosion. So here is, again, this is the same thing. We published this algorithm in the Ocular Surface Journal. But I can share this, or that whole review, with anyone who would like it. Basically, talking about all the steps that we talk about, but specifically focusing more on the limbal stem cell deficiency, whether it’s partial or total, and it’s unilateral or bilateral. And then stepwise, which procedures we consider. So we’re gonna talk about all these steps. So really the first step to think about is to address their eyelid and conjunctiva, basically. They go hand in hand. So frequently they’re gonna have extensive scarring and symblepharon, and before you can do anything for the cornea, you have to address those. And a good rule of thumb is that you want to wait for these eyes to quiet down. Doing surgery on a hot eye will often lead to recurrent inflammation and scarring. So you want to quiet them down. And in fact, what I do sometimes in the patients — I start them on something, start them on a systemic agent, to help quiet them down. The agent I typically like to use is mycophenolate, and have them on it for a couple of months. But I know one colleague, Dr. Charlie Bouchard, in severe injuries, to try to suppress inflammation, has put them on cyclophosphamide, which is a pretty… It’s a major intervention. That drug is a serious drug. Anyway, so controlling their immune system is definitely part of the picture. Part of the management. Okay, so for mild to moderate symblepharon, which this really is not… This one looks like it has a nice lower fornix here, but this part is really shut… So the main steps of the surgery — again, we’ll show a quick video here. You excise Tenon’s, but preserve conj. And in mild to moderate cases, just amniotic membrane to cover the defect, and definitely in all of these cases you have to use mitomycin C. Let’s see if this works here. So again, you can see here the symblepharon, coming all the way up to the cornea. You start your incision at the most anterior edge. Sorry that this goes quickly here. So after this dissection is complete, then you really — and I don’t show this in this video. It’s edited too much. But there’s extensive Tenon’s that has to be excised from here. So any Tenon’s in that subconjunctival space you have to excise. You relax this conj, you have to let it fall back as much as you can, then you take mitomycin C and you place it in that subconjunctival space, deep towards the fornix, but it’s in the subconjunctival space, basically treating any residual Tenon’s that you did not excise. So typically… Actually, you put several pledgets of mitomycin C, 0.03 or 0.04%. For a good three or four minutes. So then you cover your defect with amniotic membrane, and we use… For our amniotic membrane, we use fibrin glue. But you could suture these membranes. There’s no difference. And you try to get the membrane to basically cover that bulbar surface deep, as much as you can. And I don’t show it here, but you also throw in a symblepharon ring. That’s very important for these fornix reconstructions. And I like to keep that ring in as long as possible. Minimum, six weeks, but my preferred length of time is three to four months. Because I think keeping that ring in definitely does help. But the patients often don’t like it. So you’re forced to take it out earlier. Now, in the most severe cases, then really you don’t have enough conj, and that patient that we just showed, that patient did extremely well. Sorry I don’t have postop photos. But again, that patient had partial limbal stem cell deficiency, so I ended up not doing a limbal transplant. Even though the other eye was healthy. And I just went in with a keratoplasty, and the patient did quite well. There was enough reserve in that eye. But going back to fornix reconstruction, for the most severe cases, you really need to bring new tissue, and in this case, obviously, if it’s a unilateral injury, you could get some conj tissue from the other eye. But for bilateral injury, a mucous membrane graft. Buccal or labial mucosa. It’s hard to reconstruct a severe symblepharon without that. Once you have sort of gotten a better fornix, you want to address — if they have glaucoma, they’re on multiple medications, then you want to think about trying to address their glaucoma surgically. If there’s enough conj tissue and the glaucoma surgeon feels comfortable putting a tube, that’s great. If not, sort of cyclodestructive procedures. Either way, this would be a good time to address the glaucoma surgically. So we’ll spend the rest of the talk, the next 10, 15 minutes, talking about limbal stem cell deficiency, which is really my area of interest. And many of you are familiar with the manifestations, but the bottom line is: Conjunctiva ends up growing over the cornea. And you get neovascularization, epithelial breakdown, stromal opacification. These are very visually devastating consequences of severe limbal stem cell deficiency. This patient’s not a chemical injury patient. This is a different patient. This actually has some type of… It’s actually a keratitis ichthyosis syndrome. But these are chemical patients. Once you’re here, we’ll talk about how you diagnose limbal stem cell deficiency. Sometimes it’s obvious. This vascularized pannus growing over the cornea. Vessels are superficial as well as deep. But that’s important, because it highlights the conjunctiva. Stromal neovascularization by itself is not sign of limbal stem cell deficiency. Like, in a case like this, it’s hard for me to know: Is there true limbal stem cell deficiency or not? Here it’s pretty obvious. This is a clear limbal stem cell deficiency case. This one also. But again, even with this, it would be hard to know for sure how much… There could be some limbal stem cells here. Low possibility in this one. But really also this one, without… Sometimes it’s hard to tell. And so the most useful tests for diagnosing limbal stem cell deficiency for me is fluorescein staining. And the fluorescein staining really helps to bring out the conjunctival-type epithelium, versus corneal epithelium. So in this case, this is not a chemical injury patient. This is a contact lens-induced limbal stem cell deficiency here. This part of the cornea is staining differently from here. And you can see this nice demarcation line here. If you’re really zoomed in here, you would see a little bit of whorl pattern to this staining here. So this late staining epithelium — here you can see it more clearly. This is also contact lens-induced. Just easier to see in these patients. So clearly corneal epithelium. Clearly conjunctival epithelium. And the conjunctival epithelium is a little more opaque, so it’s a patient with a chronic limbal inflammation, that had limbal stem cell deficiency — so again, you can see areas of opaque epithelium, areas of clear epithelium. So if you stain these patients, this would stain. This area would not stain. So staining is the most useful. And once you start looking at these patients, after a while it will become more clear. But again, Palisades, superficial vascularization, and these are all evidence of superficial stem cell deficiency but if you really cannot determine, you can take some cells from the surface, or you can do cytology. Those are some ways you can confirm it. So in this setting or in general, it depends on how severe it is, or whether it’s unilateral or bilateral. For partial stem cell deficiency, not uncommon in the setting of chemical injury, parts of the cornea are protected by the lids, you might not get total loss of limbal stem cells. In those cases, it depends on, again, whether the central cornea is involved. If it’s not, obviously you just… You just observe it. Lubrication, serum, vitamin A, some steroids. These are the kinds of things. So this combination, this number one, two, three here — this is what I use in any kind of partial limbal stem cell deficiency, where I’m trying to help support the limbus and those remaining limbal stem cells, the way we help them expand or proliferate some more. This is pretty much all we have right now to offer those patients. But again, same thing. If you have central corneal involvement, I would still start with this first, but if this is not doing it, then you can think of a surgical intervention, but often you’re not going for something very major. So this was described by Dr. Dua, where you can scrape that epithelium away, that conjunctival epithelium, which comes off very easily. You don’t have to really scrape it. You just take a Weck-Cel sponge, and it just sort of comes off, just by gentle brushing. So that’s a good way to distinguish conjunctiva from corneal epithelial sheets on the cornea. You remove that, and you just keep doing that multiple times, and try to give a chance for the other healthier corneal epithelium to grow in. Or you can do this in the setting of surgery, where you do a peritomy. This is a patient where we did peritomy, almost 360. Not quite, but we basically let all this conj fall back, removed all this, then placed amniotic membrane over this whole area. But you have, again, some improvement. But still… I mean, the patient really had at most just a couple clock hours of limbus left here. And even this wasn’t that healthy either. So you still have some limbal stem cell deficiency up top here. But it’s improved them to the point that they can see better through that eye. So obviously the other alternative — we’ll talk about it in terms of these unilateral partial cases — is to actually redistribute the remaining stem cells. The remaining limbal stem cells here — you could try to take some piece, move it up top, or do a SLET-type technique, which we’ll talk about in a minute. So these are all the procedures we have available. Unilateral disease, you can take an autograft two from the other eye. The cultured limbal epithelial cells are not readily available. And the SLET technique we’ll talk about in a minute. And bilateral disease, you can get tissue from a relative, cadaver, and these other procedures — we won’t talk too much about them. So again, like we said before, before you start doing limbal transplantation, you definitely want to address all eyelid problems beforehand. You have to get a good fornix and symblepharon repair. Sometimes we could combine some symblepharon repair when you’re doing conjunctival limbal grafts. Again, this patient did have some symblepharon, which we addressed as part of their limbal autograft from the other eye. And you can still see some parts of the graft here. But when you let the conj fall back, you help reconstruct the fornix for them. This patient has done well, more than 12 years out. But this is the basic technique. You’re taking two pieces of about two clock hours from the fellow eye, and we use basically just glue to secure these. We’ll suture them, combining them. So SLET. I’m sorry I don’t have a schematic or a diagram here, but basically the idea — this is another unilateral chemical injury. Limbal stem cell deficiency. You can see some of the injury also caused some iris damage and ischemia here. This patient took a good five, six months for the epithelium to heal. This patient had had a LASIK beforehand. That flap got necrotic. Anyway, this patient did a SLET procedure with pieces of tissue from the other cornea. I set the tissues a little more peripheral, so that it can leave the central cornea a little more — basically the idea is to take one clock hour from the healthy eye, cut it into pieces, amniotic membrane over the whole eye, cut it up into pieces, put it on there with glue. This was developed by the people at LV Prasad, as an alternative to a conjunctival-limbal autograft. So I think it’s a good technique, but some disadvantages over an autograft, a traditional autograft that you do… Bring some conjunctiva with you, and helps reconstruct the fornix, when you have a fornix issue. So if you have fornix issues, I would probably prefer to do a traditional limbal autograft. This patient didn’t have much fornix issues. The stromas were relatively clear. Again, if the patient does not have enough clear stroma, and you’re bound to require keratoplasty, my preference is to go with the autograft, because I’m worried about removing these pieces of graft with the keratoplasty, although they’ve shown that the midterm results, three to four years out, seem to be doing okay, even after a keratoplasty. So anyway, I’m gonna be answering some more questions about SLET at the end. Moving on to bilateral disease, you really do need to get tissue from someone else. Let’s see if this movie will start playing here. So again, this is not a chemical injury patient. This is a patient with aniridia, so we don’t need as much conj here, for this patient with aniridia. I took smaller grafts, and these grafts were taken from her sister. So that’s basically the idea. But again, with a chemical injury patient, you’re gonna have a much bigger graft, because you want to bring as much conj with you to try to reconstruct the surface with that additional live conjunctiva. Because there are not many ways to really get conjunctival allograft tissue, other than getting it from a living donor. The conjunctiva on the cadaver tissue is often not viable anyway, so these have to be ABO matched and HLA matched as much as possible, depending on what’s available. But a sibling that’s tissue matched is the ideal. If not, then we go to a parent or child. Okay, and then limbal allografts, using cadaver tissue, I think this uses the Ed Hollis technique of using three pieces of tissue. But I now just use one single graft. But I do cut it right in one space, and that allows me to sort of dissect that tissue. And again, I can share videos with people who are interested in learning more about this technique. But the key to success with this procedure is that you have to have systemic immunosuppression. Otherwise this or even the other living related allograft… They require systemic immunosuppression, steroids for a couple months, long-term, use tacrolimus or cyclosporine. Orally, mycophenolate or azathioprine. Again, these have been published. I can share these with people who would like to know. The problem you’re trying to avoid here is rejection. Here you can see rejection lines, the patient several years out, they can develop rejection. Okay. Another question here. Which of the following is not an important factor in preventing complications after limbal stem cell transplantation? You have good tear film status, keratoplasty before any ocular surface reconstruction, full correction of adnexal abnormalities, proper handling and dissection of limbal grafts, and adequate immunosuppression. So which of these is not an important factor to improve the success rate of limbal stem cell transplantation? In preventing complications? Yeah, perfect. So basically, yeah. Keratoplasty is typically done afterwards, unless you need it for tectonic purposes. But good tear film makes a big difference. The really dry patients you can’t really fix with limbal transplantation. So we talked about all of these. I’ll keep going here. So for optical reasons, these patients can benefit from transplantation with a penetrating keratoplasty lamellar. If their endothelium is healthy. And in some cases, like I said earlier, if they just have partial limbal stem cell deficiency that’s not too extensive, you may, if you just get a healthy epithelium with a graft, and do a keratoplasty, that may be enough. They may not need additional surface procedures. So I have sometimes done that, and I’ve just said: Okay, if they have problems, I can always address that later on, with an additional limbal graft procedure. But when you have near total limbal stem cell deficiency, then really you have to do limbal transplantation, and get a healthy surface before you do graft. And we would definitely like to not do these as combined procedures if we don’t have to. I like to separate them out by several months. So keratoprosthesis — actually the last couple slides here. As you all know, the Boston keratoprosthesis, Boston type I here, shown in the picture, is now the main KPro that’s available, although there are now other models that are becoming available. But the one with the longest track record is this one. And this is really… I think it can be a great alternative to limbal transplantation, or sometimes combined together. And here’s a quick question on this too. Which of the following is an ideal case for Boston type 1Kpro placement? And these answers are not absolute, but this gives my thought process. A 32-year-old male without systemic disease and unilateral limbal stem cell deficiency. 32-year-old female with type I diabetes and bilateral limbal stem cell deficiency. 75-year-old male without any systemic disease and unilateral disease. And 75-year-old with type II and bilateral limbal stem cell deficiency. Which would be the best case scenario? The kind of patient that I feel comfortable putting in a KPro. Feel most comfortable with, let’s say. None of these is a contraindication, but… Okay, so I think I have to explain my thought process here. Basically I think the answer that most of you chose, that first one, is reasonable. Someone without systemic disease and unilateral limbal stem cell deficiency, to put in a Boston KPro for that. That’s not unreasonable. And many patients who are hesitant to having the other eye touched for getting any kind of limbal autograft for that eye… In which case this would be a good, reasonable option. However, that’s not the one that I was going for. The one that I was going for is this one, the 75-year-old female. And the reason is because this 32-year-old male is gonna… First of all, it’s a unilateral disease, so you have to argue whether it’s appropriate to do a KPro in a patient who already has one seeing eye. And there’s nothing wrong with it, but it’s patient choice whether they want to do that or not. But they’re already a seeing patient. This is a patient, bilateral disease, can’t see. The other thing is this 32-year-old is gonna have to deal with the KPro for the rest of their life, which is gonna be another 60 or 70 years of keeping that KPro in the eye. The 75-year-old should have less, let’s say. It would be on the order of 20, 25 years, in that range, at most. So this would be a time frame that I think is reasonable to think about a KPro staying in the eye. Again, 60 years to keep a KPro in the eye is long. We don’t know if anyone has ever kept a KPro that long. It hasn’t been around that long. So younger patients I wouldn’t push towards a KPro. Older patients, it’s more appropriate. You might not do it or you might think about doing some cadaver-based tissue, if they’re open to it. But it depends on how comfortable they are with procedures. So the patient must understand long-term risks, long-term follow-up, antibiotic prophylaxis. There’s a lot to talk about with the KPro. I won’t go into it too much. Patients with chemical injury are not the best candidates, because they’re prone to melts and extrusion. The tissue is not so viable. They don’t have healthy tissue surrounding the area. So that’s why our preferred approach is to sort of often do a surface reconstructive procedure, obviously, as part of their fornix reconstruction. So bring some healthier tissue to the surface before you would consider doing an intervention, like a KPro. So I’ve never jumped to KPro as a first procedure, unless it’s really necessary. Unless I feel very confident in the health of their surface. But for sure, they need to get fornix reconstruction first, because they have to put the contact lens in. So a lot of complications. Fortunately not… I mean, they’re less common. But they happen. If you do enough KPros, you’ll be seeing complications for sure. The glaucoma obviously needs to be addressed in these patients as well. Finally, just the last one or two slides. For the very severe dry patients, the surface is keratinized, none of the procedures we talked about really can work, and the osteo-odonto-keratoprosthesis or type 2 Boston prosthesis are the only options, but both of these have issues and complications. So we’re trying to get better at managing these patients. So just to sum up everything we talked about, for the chronic phase, the fornix and eyelid disease, glaucoma, limbal stem cell deficiency, the different procedures, and keratoplasty and keratoprosthesis. Okay, just want to leave you with a couple new ideas here. I think this is our last slide. So the toughest patients are these grade 4, this Roper-Hall or Dua grade 5, grade 6 patients. So much destruction on the surface. Really, these patients are at high risk for even getting perforations and melts, even in the first several months. So what can you do to try to help these patients? So some new ideas. This idea really was published by Geetha Iyer. The idea is to use some cadaver tissue, or a living relative, take a biopsy, one clock hour, but basically doing an allo-SLET, an allograft-based SLET, over the whole limbal surface. With cadaver, you can get lots of tissue, but if don’t have access to tissue, living related would not be unreasonable either. Although they didn’t use this. I think they used mainly this cadaver tissue. And try to get… So basically the idea is you have to bring some viable cells to the surface. And help repopulate… At least get some epithelium to grow over… And you know that epithelium is gonna get rejected. The tissue is gonna get rejected, but it just buys you some time, so the tissue doesn’t melt. So this, I think, is one good idea. Or also I’ve heard Dr. Dua talk about taking a free conjunctival graft from the other eye to put it over the cornea. That’s not unreasonable. Again, some patients may not be open to touching their other eye, if it’s available, in unilateral disease. But this allo-SLET — I would never do an auto-SLET in an acute setting. That’s bound to fail. None of these procedures should be done in an acute, hot eye. That’s bound to fail. Another idea — just throwing out ideas — this hasn’t really been published, but I think it’s worth trying, if some of you want to think about it. In very severe grade 4 injuries, if you want to try taking some oral mucosa and using a SLET-like technique, to get those tissues to adhere. And mesenchymal stem cells is an area that we’re actively looking at, potentially starting a clinical trial, and Dr. Basu and some people elsewhere are looking into putting this on the eye, and I think this is really exciting. These are my acknowledgments. I want to thank Dr. Medi Eslani, who helped with the slides, as well as the grant funding in the research that I do. This is my email. Definitely email me with questions later on. We’ll go through some questions now, but feel free to email me with patient-related questions for the future. If I can help.

>> So Dr. Djalilian, you can stop sharing your screen and open up the QA box. We have five questions.

DR DJALILIAN: All right. So here’s the first question. It’s asking: Is there any difference in the management if the chemical agent is powder, gas, or liquid? And no, not really. The main thing to remember with things like powder, you’re gonna have particulate matter, so you really have to be quite vigilant and aggressive in trying to find those residual particulate matter and get them off the surface. But otherwise, acutely — chronically for sure, there’s no difference, but acutely, they’re pretty much the same. Okay, next question. How do we recognize necrotizing conjunctiva, and when is the best time to do surgery such as necrotomy and AMT for large cornea epithelial defect? So there are two different procedures here. One is a reconstructive procedure. Those are the ones we want to delay as much as possible. For the eye to quiet down. The surface reconstruction. But then you have surface stabilization procedures, procedures you have to do to stabilize the eye, prevent further loss of tissue and further damage. Those you can do in the acute setting. No problem. You can do AMT as early as a few days after the injury. That’s no problem. But a necrotomy… I would say, again, I don’t jump into it. I would give it maybe a week or two, just to see where this eye is going, but probably usually sometime in the first two weeks or so. If it’s pretty clear to you on exam that there’s quite a bit of necrotic Tenon’s and subconjunctival tissue that you have to excise, then I think in that first couple weeks is probably the right time. You don’t have to do it immediately. But yeah. So I hope that answers that question. Okay, good, good. So another question: How do you identify normal corneal limbus at the slit lamp? And can you speak about your way of identifying limbal ischemia? Okay, great question. So normal limbus… So again, I’ll answer this question more generally, and then more specific to this presentation. So in general, you have some normal limbal landmarks that you can look for. Those Palisades of Vogt. Those are lines at the limbus that you probably have all seen. But that’s not… You don’t see this all the way around the limbus. You don’t see that 360, usually. But any time you see it, that’s a pretty good indication that you have a pretty normal limbus. Often this becomes important in the setting of… A patient that had a unilateral injury — I have to look at their other eye to make sure the limbus is completely healthy. Again, something I neglected to mention here. If there’s even partial injury to the other eye, I think you’re better off not touching the other eye, or at best, maybe you could take just that one clock hour, really, just for a SLET-like technique. But I would be very, very careful about touching the good eye of a patient that had had a previous limbal injury. Because you don’t want to compromise and tip over that eye. So a standard kind of autograft is not something I would do in that patient. So looking for limbal Palisades of Vogt, looking at the vessels in the limbus, if you see the superficial vessels coming out into the cornea, that’s a sign that the limbus is not as healthy. A staining pattern can be helpful. Especially if conj is starting to grow over that area, you’re gonna see a different staining pattern. A normal limbus should stain just like the rest of the cornea. And limbal ischemia — basically just look for white limbus. We saw some examples of it. The vessels have died, have been destroyed. So it’s basically white. If the whole eye is so white and quiet, the eye almost looks normal to us, because we’re used to seeing a red, hot eye as part of a severe disease. But the most severe injuries, when there’s total ischemia, the eye looks white, because there’s no vessels. Nothing left. How can we measure IOP in a KPro patient? Okay, going on to the next question. That’s a great question, and it’s a problem. Really, there’s no good way. Really, the best… So one of our residents did a study a few years ago on basically using one of these handheld tonometers, and tried to measure it over the sclera and tried to correlate that with a cornea-based IOP, and it was not a great correlation. But it still gives you some sort of ballpark numbers. But basically what we’re down to — I mean, that’s what I do in every KPro patient. I just feel it by fingers. You just have to do it by finger. That’s the only way we have available right now. All right, next question. What is the indication of AMT early in the course of chemical burns? We talked about this, and really I would say… You know, in a grade 2, grade 3 injury, if you’re trying to get faster epithelialization, and you want to do everything possible, then I think it’s reasonable to do an AMT. I would say in grade 4, those most severe injuries, where there’s so much tissue loss and ischemia, really it’s not gonna do you a whole lot of good, because really that membrane will last you a week at most. A week or two. And that’s still not enough for the surface to epithelialize. But I would say grade 2, grade 3 injuries — it’s reasonable to think about them. And here we have… It’s easy for us, just because we have access to the ProKera, the self-retaining membranes that go in just like a contact lens. But the added advantage is not that great. It’s not like you are really altering the course of the disease. When you look at long-term outcomes, I don’t think anybody has shown that AMT clearly changed the long-term outcomes, especially in the more severe injuries. In the short term, for sure, I think in the milder injuries, it helps, but long-term, you’re probably not altering the course of the disease too much. I hope I answered that question. It’s tough to say. Since there are no good studies, I think people have different opinions on this. But I just told you my opinion. So what kind of medical… Okay, yeah. Is there a role for AMT in large conjunctival epithelial defect only? In the setting of fornix reconstruction, yes. That’s one of the most common places that I use AMT. Is a large conjunctival epithelial defect, after trying to do a fornix reconstruction. Again, in a severe injury in the acute setting, you’re gonna have total loss of epithelium in the conjunctiva as well. Again, I don’t think amniotic membrane is gonna do a whole lot of good in those acute settings. You put this tissue there, a week later, it’s gone. Still there’s no epithelium. You’re gonna wait a long time for the epithelium to work its way to start to come to the surface. But other indications for AMT in general… Where else do we use it? The most common place I use it is really in fornix reconstruction. Another good indication for it is acute Stevens-Johnson syndrome. That clearly I think there’s good evidence to support that, in that first week, for sure. In those severe cases. And then persistent epithelial defects to help those heal by putting a graft inside the defect area. That also helps. So those are my main indications. What kind of medical therapy can we use to treat secondary glaucoma? Is it also the same with non-chemical traumatic etiology? So medical therapy — drops. And you hate to use drops on surfaces that are compromised already. But oral agents — almost all of these patients we’ll put on acetazolamide or methazolamide, if they have IOP issues, and drops, as much as necessary, to keep their pressure in a safe range. But if you’re really maxed out on drops, I’m pushing towards getting a glaucoma procedure, just because gonna be hard to rehabilitate their surfaces when they’re on so many drops. So again, before you do any limbal transplant procedure on a patient that’s on multiple drops, for sure they should have a glaucoma procedure and get them off the drops as much as possible. What’s the ideal time for bandage contact lens or AMT after chemical injury? What are the signs to look for? So BCL, depending on your injury… There has to be some epithelium on the cornea or some indication that there’s healing. So it depends on the grade of injury. But if there’s epithelium there, I would start pretty early. I wouldn’t do it right away. I would try to maybe let your steroids get in a little bit better, just because I worry about having a bandage lens there. Maybe not letting my steroids penetrate. But I would say after a week or so, when I really give them a good amount of steroids, for that first week, a BCL is reasonable. AMT, again, like we said earlier, it’s up to you. If you’re gonna do it, probably that first week seems reasonable. But if you’re gonna do it for its antiinflammatory effects… Long-term, I mean, for epithelial defects any time. But in the acute setting, probably I would say the first week or two is the best time, if you’re trying to get the antiinflammatory effects. Can we use medroxyprogesterone? I have not used it. I know basically it doesn’t cause as much stromal melting, and it’s reasonable. I mean, I think it may have some advantages. But I’m not sure. Yeah, since I don’t have personal experience, I don’t want to speculate too much. But my guess is that it probably doesn’t make much difference. But you certainly want to hit them hard with intense, potent steroids that first week or two, but then this can be second one, after you switch from prednisolone. What analgesic do you prefer after chemical burns so a cycloplegic agent. I think I didn’t mention that. Something like atropine helps once a day in that sort of acute setting. The most severe patients, the most severe chemical burns, actually may not be that symptomatic, because you’ve destroyed the nerves as well. At least on the surface. But in the patients who still have some viable nerves and are feeling pain, obviously I wouldn’t use anything topical, but if they want something… Oral agents for pain control, that’s not unreasonable for that first week. But a cycloplegic agent certainly helps them as well. All right, it seems like that was the last question that I got. So I want to wish you… Okay, one last question here. How about the use of EDTA? I’m not sure. I guess for calcium chelation? That’s not unreasonable. If they up with a lot of calcium on the surface, that’s not bad. I’m not familiar with it as a therapeutic agent, using it as a drop, but EDTA for calcium chelation, as a one-time, strip the surface, get the calcium off, it’s not unreasonable. But I worry about a stable surface that has a healthy epithelium, you de-epithelialize it, and it gets unstable. What about paracentesis? I don’t do paracentesis, but it’s not unreasonable. I don’t have personal experience with it. But it takes time to do that. I would spend that time irrigating the eye and trying to normalize the pH. But in a severe injury that’s already penetrated the eye, I guess it’s not unreasonable. That aqueous gets turned over pretty quickly. So I don’t know. I don’t have that much personal experience. I guess I won’t say much. Vitamin C… Yes. So vitamin C definitely we give them. Again, I don’t know the evidence, how much difference it makes. But it’s a safe, readily available medication. As you know, it helps promote collagen synthesis, so it can help reduce stromal melting. Theoretically. The data in animal models supports it. Clinically, it’s hard to know how much difference it’s making. But that’s not unreasonable. All right. So I guess that brings us to the end. Okay. Scleral melting happens with chemical burns? Yes, yes, of course. When you have necrotic sclera, they definitely can melt. For sure that’s a complication. That’s why sometimes advancing some Tenon’s tissue that’s healthier from surrounding areas can help reduce that risk. Anticollagenase agents… Really, when talking about anticollagenase, basically collagenase is a form of matrix metalloproteinase. So we talked about matrix metalloproteinase inhibitors. The main ones we do use are the doxycycline or tetracycline class of drugs. For sure, we use that in every patient with chemical injury, and then other things… Like I, vitamin C helps promote collagen synthesis. Citrate probably has some anticollagenase-related activity. That’s not unreasonable. I think, again, these drugs… If they’re readily available to you, I think yeah, there’s no downside to it. But I can’t say that they are critical, that you must, no matter… You’ll find citrate somehow to use it for this patient. I don’t think it makes a big difference, that you have to go out your way to find it.

>> All right. Thank you, Dr. Djalilian.

DR DJALILIAN: Yeah, thank you. Thanks, everyone. Thank you, Lawrence, and Cybersight, for this opportunity. And definitely for those of you who have follow-up questions that you didn’t get to here, feel free to email me, and I’ll try to get back to you within a week or two. Pain killer for oral? Okay, so I guess really… I haven’t used it that much. But here you have to use something with some narcotic strength, if they’re really in pain, and your typical pain medications like acetaminophen or NSAIDs are not helping. So you have to go with something more… Stronger. Some narcotic strength in the short term. Not unreasonable. All right. Very good.

>> Thank you again.

DR DJALILIAN: Yeah, thanks.