 All right, so I'm gonna get started because I've got a longer lecture today. So we were talking about surgical treatment of ocular surface disorders, and these are the procedures I'll be going over. I'll be spending a little more time on limb bull stem cell transplantation, kind of more about the background rather than just the surgical procedure. So first, congenital biopsy, this is pretty straightforward. So is this helpful for diagnosing congenitival tumors for the most part, such as CIN or pigmented lesions, but it's also useful in diagnosing conditions such as ocular secretarial pump for void where you do need some immunofluorescent staining to diagnose. So typically if there's like a discrete lesion, you do wanna mark the borders, even if it is obvious, because once you inject some subconjunctival lidocaine that can obscure the borders. If you are very suspicious for melanoma, the books talk about a very wide margin, like four millimeter wide margin with a no-touch technique to remove lesion suspicious for melanoma. And anytime there's any sort of suspicious lesion, whether it's CIN, usually it's kind of CIN related, I will perform a chirotherapy of the cut congenitival edge after the lesions removed. And there's something called a double freestyle technique which I'll just show a few seconds of. Or basically you use a cryoprobe to freeze off an area of the conge edge and then kind of go on to the second section, kind of just barely overlapping what had just been frozen. And so the purpose of this is to freeze off any possible areas of any suspicious cells that may be beyond that cut edge. And so you just kind of keep going around once and then you go around one more time just to make sure you got everything. So that's enough of that. All right, any questions on congenitival biopsies? Next I'll talk about tarsorophy. So this is for non-healing epithelial defects that fail other treatments and other treatments being lubrication, bandage contact lenses, or even prokera. You might also do a tarsorphy in the absence of an epithelial defect if there is ligophthalmos and a high chance for recurrent epidefics. And tarsorophys can be temporary or permanent. And the permanent tarsorophys you do have to take off the kind of the lid margin epithelium to get the lid margins to stay together. And tarsorophys can be medial, central, or temporal in the lids. And tarsorophys are usually performed with suture. Like I mentioned, they can be temporary or permanent. You can also do something called a glue tarsorophy where you use cyan or acrylate glue to literally kind of glue the eyelashes together. That's usually very temporary. I might resort to this if there was some reason why I wasn't able to suture maybe because of patient movement issues and kind of, if you're doing this at the bedside, you could do a glue tarsorophy. And then there's Botox Tarsorophy where you inject Botox into the lid to drop, basically causatosis, which is nice, but just know that that does last three months. But it can be an effective technique. Next, we'll talk about teridium excision. And the indications for removing a teridium are kind of listed here. So one is the most obvious one. Any progressive growth towards the visual axis. If you've got a teridium, which is causing decreased vision or significant astigmatism. Or you may have a relatively small teridium, but if it's causing persistent redness and discomfort that's not relief by topical drops, that would be an indication for a teridium excision. Can we shut the door and just make sure it's unlocked on the other side too? Thanks. So here's an example of a teridium that is causing flattening on topography in this area. So it's gonna flatten here and it can cause some astigmatism 90 degrees away. When removing a teridium, it's important to remove the underlying tenons layer, not just the congenitiva. And you wanna always send the specimens to path just because I've come across the occasional teridium that's turned out to be CIN. There are a few techniques about what to do afterwards. There's bear sclera, which we don't recommend because there's a very high recurrence rate. So that just means removing the teridium and just leaving everything bare. So super, super high recurrence rate. It's like at least 50%. You could do primary closure of that defect with suture, but that can be difficult if it's rather large. So if it's a really teeny, tiny teridium, I might consider primary closure. But typically I will use a congenitival autographed, which is a, I guess you could call it like a congenitival transplantation. When you take the congenitiva, usually from the superior bulb or conge and apply it to the defect, you could also cover the defect with amniotic membrane. And congenitival autographed is my preferred technique because it has the lowest rate of recurrence, about two to 5%. And also it has the best cosmetic result, I think even better than amniotic membrane. And so again, free graph from the superior bulb or congenitiva. You leave that superior congenitival defect open, that can kind of heal in just primarily. And then to stick that autographed down, I will apply some fiber and glue such as to seal. And I usually put down a couple dissolvable sutures as well. And it's important to seal the congenitival graph to the congenitival edge so that kind of decreased rate of scarring and recurrence. Amniotic membrane I'll use if the superior congenitiva is not available for a graft, like let's say there's a lot of scarring, there's a trap there, or let's say you've got a nasal and a temporal turidium at the same time. And so I'll typically harvest the superior graft for the larger turidium and then use amniotic membrane of the other turidium. And just like with congenitival autographs, you can secure the amniotic membrane down with fiber and glue or sutures. I'll use mitomycin C interoperatively if I'm taking a patient back for a reop turidium. And this is to prevent recurrence. So after the turidriums are moved, I'll have some soaked sponges of mitomycin C tucked underneath the congenitival edge for a couple minutes and then rinse off really well and then move forward with either congenitival autographed or amniotic membrane. With any use of mitomycin, there's always a concern for long-term complications, scleral melt and infectious scleritis are two of which are possible. Okay, so next I'm gonna go to limbel stem cell deficiency which will be next several slides and limbel stem cell deficiency may be partial or complete. And typically on exam, you'll see congenitivalization of the cornea. You'll see a thickened vascularized irregular surface and kind of an irregular epithelium. There may be chronic inflammation. There can be persistent epithelial defects, stromal ulceration, scarring or even corneal perforation. So here's an example of, I'd say probably near total limbel stem cell deficiency. There might be some semi-healthy limbis down here but there's extensive neovascularization as well as scarring. Here's another example of probably this is 360 limbel stem cell deficiency. And this is an example of 360 limbel stem cell deficiency with stromal ulceration and probably an epithelial defect there. So stem cells are cells that are defined by the capacity for unlimited or prolonged cell free neural to produce at least one type of highly differentiated progeny and they're defined by their niche where there's contact with surrounding cells. There are interactions of those cells with the extracellular matrix as well as local growth factors. And stem cells are a major target of gene therapies to change entire cell populations and limbel stem cells are not embryonic stem cells. So this is kind of a little diagram showing the limbis being the border between the congenitival and the cornea. And so the limbel stem cells or the corneal stem cells reside here and they are able to regenerate corneal cells. When you have limbel stem cell deficiency and you get congenitivalization, there's actually goblet cells within the congenitiva which are visible on pathology. These kind of bright magenta dots are the goblet cells that are seen within the congenitiva. I think this is showing an epithelial defect and this is showing kind of the edge of some irregular epithelium that you can see which you'll see with limbel stem cell deficiency. So there are many causes of limbel stem cell deficiency. They can be congenital, traumatic, iatrogenic, autoimmune, neoplastic or eopathic and so we'll go over all the causes. The most common congenital cause is aniridia. So aniridia means no iris but it's more than just that. Patients who have aniridia do have a pretty profound limbel stem cell deficiency. Other congenital causes include ectodermal dysplasia and keratitis ichthyosis deafness syndrome. There are several causes of traumatic limbel stem cell deficiency. Chemical injury and thermal injury are one. Contact lenses can actually induce a slow limbel stem cell deficiency. A severe infection that extends to the limbis could kill off limbel stem cells. Neurotrophic keratopathy can lead to limbel stem cell deficiency as well as even chronic, bullish keratopathy. If you have someone with a chemical injury, the prognosis depends on the extent of ocular surface involved and more particularly the amount of limbel ischemia. So there is a table here called the Roper Hall Classifications System which kind of predicts prognosis based on the amount of limbel ischemia from grade one to four and this is kind of what you'll see typically on a corneal exam. So here's an example of an acid burn. There's maybe some limbel stem cell deficiency. You have some vessels so it's not complete. Lumbel stem cell deficiency here but it's just a little bit maybe wider than we would like. The cornea is a little bit hazy but it's clear enough where you could see the iris. So I would probably classify this as maybe a grade two. Here's an example of kind of more severe limbel stem cell deficiency where you see some whiteness but there is good vascular blood supply here and let me just show you an example. It's a lot more obvious. So this is an example of acute limbel stem cell deficiency from alkali burn. So it's just really, really white. So it's very, very striking when you see complete limbel stem cell deficiency. So this is an important finding to see like when you're on call and you have someone who's admitted with burns or if you're on consult service and you're consulted to the burn unit you would do want to look for this finding. Very striking kind of later on, subacutely. You see everything around is pretty red and then this area is just kind of dead. This is an example of yeah, pretty severe limbel stem cell deficiency. You can see the whitening kind of around here and a very, very opaque cornea. So this is a poor prognosis. Moving on to the next category of limbel stem cell deficiency causes. Iatrogenic can occur with multiple eye surgeries which involve the limbis, which can kill off limbel stem cells or multiple cryotherapies to the limbis. Long-term topical medications like some glaucoma medications with a lot of preservatives can lead to limbel stem cell deficiency. Musa 5ifu or mitomycin can also kill off limbel stem cells as well as radiation. Autoimmune, we've got many causes here including SJS, secretorciplemphagoid, any sort of chronic limbitis from A to P or limbel vernal, as well as a morons ulcer can lead to limbel stem cell deficiency. Neoplastic, atoridium is kind of a very focal limbel stem cell deficiency as well as CIN and other neoplasias on the limbis can lead to stem cell deficiency and then lastly there's always idiopathic as being a kind of an unknown cause. With transplantation of the oculosurface or with limbel stem cells, there's kind of different classifications. We've got autographs which use autologous tissue which is harvested from the same or fellow eye and allografts which are typically harvested from cadaver eyes or can be harvested from a living relative with HLA matching. And here's kind of the alphabet soup of some of the more common limbel stem cell transplants that are done. There's a congenitival limbel autographed or CLAU where the fellow eye is used to transplant limbel stem cells. There's living related congenitival limbel allografts. There's carotolimbal allografts. These are from Categrinveric donors. So that's a CLAU or a K-L-A-L. These last two are not performed in the U.S. but these are using kind of taking limbel stem cells and expanding them in the lab and then transplanting back in either from a fellow eye or a living related relative. So this is kind of the basics of what's done. The patient has their kind of abnormal limbel tissue removed and then there's a donor from cadaver or fellow eye or a relative where sections of limbis are sutured on. And that's kind of the basics of limbel stem cell transplantation. With the congenitival limbel autographs from the same patient, this is indicated in unilateral limbel stem cell deficiency or there can be kind of a primary unilateral limbel surgery. So a teridium with a congenitival autographed is technically a congenitival limbel autographed or CLAU. No one ever calls it that. We just call it a teridium excision with a congenitival autographed but it's technically a limbel stem cell transplant. Let's see. We've got, yeah, so sores from the same eye or unaffected fellow eye and you can take up to six clock hours of donor tissue from the healthy fellow eye without much risk. The nice thing about same patient limbel stem cell transplant is there's not gonna be graft rejection so you don't need to have any sort of systemic immunosuppression. Living-related congenitival limbel autographs are indicated in bilateral limbel stem cell deficiency. Again, a source from a living-related donor with an optimal HLA match. You still do need systemic immunosuppression and having a living-related donor can improve the prognosis over a cataviric donor. So what's done, this is the, I guess, living-related donor where sections of congenitiva are harvested. This is the recipient where the bed is kind of all cleared, the vascular panacea over the epithelium is removed and then these sections here are sutured down there and there. Yeah. Do the donors have any trouble with like healing if they get... I don't think so, not if you take less than six then, six clock hours, yeah. I mean they lose some limbel stem cells but I don't think you get... I guess you technically have a partial limbel stem cell deficiency but the rest of the limbis can heal over. So this is a picture showing harvesting of this section of limbis. KLA-ALs, these are limbel stem cell transplants from cataviric donors. So again, indicated in usually bilateral disease. Systemic immunosuppression is required and usually we do the limbel stem cell transplant first and then see whether or not a PK is needed later and so doing the limbel stem cell transplant will improve the prognosis over just doing a PK primarily without a stem cell transplant. So again, this allows for healing of persistent epithelial defects, stabilizes the ocular surface and can cause regression of neovascularization and chronic inflammation. So this is one technique so you can mark the recipient congenitiva first just to get the borders there then peel off the vasculopanis seen here. So then you've got a clear bed of kind of taking off all the corneal epithelium and kind of cleared off the limbel area there. And then you have cataviric corneal scleral rim. You punch out like a 7.5 millimeter opening in the middle and then you wanna take off the posterior two thirds of the donor so you have just the superficial one third to use. And so this is kind of a diagram here showing what's done and you typically do need three halves just cause things kind of stretch out so you do need two rims typically but you're using three halves and then this is showing the three sections here so even though they're halves when you kind of stretch them out two halves don't really cover one eye so you do need three sections. And these sections are all sutured down and this is showing a post-surgical I think not immediately a post-op but post-surgical section where you can see a suture holding down the section of limbis here. And I think this is showing that there are some sutures immediately after. So it's kind of a mess afterwards but kind of give things time to heal and then see how much the cornea can clear afterwards. This is a procedure I'm just putting one slide in on. It's kind of a newer procedure called simple limbo epithelial transplantation or SLIT. So instead of harvesting these big chunks of limbo tissue, you actually take a small chunk of limbo tissue that's like literally two millimeters long and cut it up into little pieces and that small amount of limbo tissue can come from patient's fellow eye or it can come from, I suppose, a cadaveric tissue. So you take these little chunks of limbo tissue and you take the patient, de-epithelialize their cornea, put on amniac membrane, sprinkle like literally sprinkle these pieces of limbo tissue on. Used to seal the gloom down and put another layer of amniac membrane. So the thought is the little pieces of limbo tissue can kind of propagate around and heal on the surface of the eye. I haven't done this. I've heard that the results can be good but may not be quite as good as a traditional limbo stem cell transplant surgery. Okay, lastly, kind of a few slides on ex vivo stem cell expansion. So this is not something that's available in the U.S. But what's done is stem cells are actually kind of grown on a carrier of amniac membrane. And amniac membrane, again, is from the innermost layer of the placenta. It's an epithelial monolayer with a thick basement membrane. It's not immunogenic and there's no systemic immunosuppition required with amniac membrane. So there's limbo stem cells that are placed on the amniac membrane and are kind of grown on top and then that tissue is transplanted into our recipient. But again, not available in the U.S. but I think they're doing it in Japan. Postoperatively, after a limbo stem cell transplant, you wanna use topical medications, topical steroids. You can also consider topical cyclosporin. You wanna really lubricate the surface of the eye as much as you can with punctal occlusion, lots of artificial tears. You might consider a tersorphy. And then you may plan on a subsequent penetrating PK at least, I think at least three months after a limbo stem cell transplant. And systemic immunosuppition does need to be employed for at least 12 to 18 months. There are a few, I guess, systemic immunosuppression regimens that are used, so topical steroids are always used. And then you can consider either systemic cyclosporin or tachylimus and also azithioprene or mycophenolate. So that's limbo stem cell transplants. Any questions as far? Okay. Next, we'll talk about curatoprosthesis. So this is also used in cases of limbo stem cell failure. Also used when there's been multiple PK graft rejections. It's kind of a surgery of last resort because there are complications such as glaucoma and infection that can be difficult to control. So the Boston curatoprosthesis is what's typically used. There's an older design, which we'll go over first because then I'll kind of translate what the newer design is. So with the older design, there was a front kind of plastic window to look through. And that goes through, it gets thread to kind of a donut punch of a corneal graft. There was a PMMA back plate and then everything locked together with a titanium locking ring. And this would be assembled kind of outside the eye. And then it sutured into the eye by suturing the corneal graft to the patient. So it's kind of like a PK, but it's got extra literal hardware attached to it. Now there's a newer design of the Boston K-Pro. It's called the click on design where there's still a front plastic optic and it's still threaded through a corneal graft. But instead of a kind of two portions here, the back plate here is made of titanium. And then the back plate kind of has a way of locking in place. So you don't need a separate locking ring. So it's a little easier to put together. And the thought is that the titanium may have less of a risk for the development of retro corneal membranes, which can occur, especially with the PMMA design. I think that finding has yet to be proven, but that's kind of the impetus for the development of the newer type of Boston character prosthesis. So this is what these look like. This is the older PMMA version. And this is the newer titanium version, which because it's titanium, it's a lot more visible than with PMMA, which is clear. So the purpose of the corneal graft is literally a carrier to suture something into the cornea. So that's kind of the purpose. And then the cornea is just left, it's vascularized in. So this is one that's kind of vascularized in. So all that's left that the patient can look through is the middle PMMA clear optic window. The holes that are here, and there's kind of little holes they can see here, that that's just allowing for nutrients to kind of flow in and out. So that's the purpose of that. So the holes are not really, we're not using the holes to pass the sutures through. They're just there. The sutures are only going through the cornea. So that's curative prosthesis, yeah. It fails, is it possible to go back and do a PK after that? I can usually do it. Yeah, no, you can go back. So you can, I mean, I didn't go into all the complications of CAPRO. I mean, I mentioned glaucoma and infection, but extrusion of the curative prosthesis is also something that can happen. So if there's an issue of where the CAPRO just can't be retained, then it can be implanted and then just do a regular PK, which will probably fail, but at least keeps the eye intact. Next, congenitival flap. So this is like Gundersen flaps. This is for a chronic sterile ulcer, patient with maybe very painful belay with poor visual potential, or an unstable cornea, such as progressive thinning. It's not used for corneal perforation. It can be a partial flap versus a complete flap, which is a Gundersen flap, and I'll go over what this is. You do need to take off the entire corneal epithelium to get the congenitival flap to stick on. So it's literally used to cover the cornea, but it is gonna, because the congenitiva is semi-opaque, it decreases vision, but it's kind of like almost like a last resort, like just something to cover the cornea because nothing else is working. So this is a schematic of a Gundersen flap. So what you do is you go way back, like 14 millimeters behind the limbus up superiorly and then size the congenitiva. You try and leave tenons behind, so you're just separating congenitiva from tenons, and you kind of make a big dissection all the way around. You have to do a 360 degree pyritomy, so all the way around here. And then after that's done, and there's more dissection that has to happen all around, you slide this section kind of down over the cornea, and then this is sutured down in this fashion. So it completely covers the cornea, and this is meant to be a permanent thing. Would be really hard to reverse. I suppose, I mean, I've done a PK on top of kind of through a Gundersen flap unknowingly, but that's kind of what a Gundersen flap is. So it's a pretty bloody cornea surgery-wise, kind of a bloody surgery, just because you have to dissect kind of a very large area subcontinitivally and kind of put this over the whole cornea. Mucus membrane grafting, so this is for the reconstruction of contrientival mucosa in inactive secretarial contrientival disease, such as Stevens-Johnson syndrome, or ocular secretarial pinfagoid, and it achieves a better ocular surface lubrication by improving to your film distribution eyelid movement. This would be something that's partnered up with typically plastics. The buccal mucosa is usually used. It's nice that you have a nice kind of new ocular surface, but it does not replace stem cells. So it's not for lumbar stem cell deficiency. Next, we'll talk about amniotic membrane transplantation for severe SJS, and hopefully you guys have the, this is available, I believe, on the resident box file. So this is kind of the chart that we use to decide whether or not a patient with acute SJS needs amniotic membrane transplantation. So if you look, you have to look at the lid margin, the cornea and congenitiva. So whether or not there's staining, you know, the degree of staining of the lid margin will dictate whether or not an amniotic membrane transplant needs to be performed. Also, if there's any staining of the cornea that would lead to surgical treatment. Sorry. Do you need to look at the congenitiva and how prebro congenitiva also for staining defects? If there, I guess, is less than, basically if there's less than one third staining of the lid margin, no staining on the cornea and kind of small staining on the congenitiva, we can go medical. Any more than that, you wanna do amniotic membrane transplant. So the technique is you take a large, the largest piece of amniotic membrane, which is a five by five centimeter piece and you cut it in half, trim the patient's lashes to the base and then you suture the amniotic membrane kind of anterior to the lash line with a running suture and then you tuck in the amniotic membrane kind of under the lid and then secure the amniotic membrane to the lid with 6-0 proline that goes in the furnaces and suture it to bolsters. So that's what these are. These are 6-0 prolines going through the lid. So then you have the upper lid. Do the upper lid, do the lower lid and then to cover the cornea, place a prokera, which is amniotic membrane that's attached to a kind of a hard plastic ring. And so that's what's done in the oar. This might be my last procedure. Superficial caretectomy. This is a simple removal of the cornea epithelium without replacing it with anything. So you might do that. I mean, I guess we kind of do that with a theridium surgery. We're not replacing the theridium tissue off the cornea with anything, even though we're doing a congenital autographed on the conge. You can do that with Salisman nodule. You just peel off the nodule, let things heal in. Epithelial basement membrane dystrophy. So taking off the abnormal epithelium, letting that heal in. Very, very superficial kind of epithelial scarring. You could do a superficial caretectomy. If there is suspected corneal CIN, you can send the epithelium off to pathology. Let's see, you can also, oh yeah, if there's a retained superficial foreign body, that technically is, and you're removing that, that technically could be a superficial caretectomy. Manual superficial caretectomy is performed with a blade. You can also peel it off with forceps. Then afterwards, you can consider kind of polishing down the epithelial basement membrane with Diamond Burr, which I'll use in the case of recurrent erosion syndrome. And I'm taking off kind of loose epithelium due to Diamond Burr polishing of the base. So the hope is that what heals over can heal over a bit more smoothly. You can do a laser superficial caretectomy, which is called PTK or phototherapeutic caretectomy. And this is where the eczema laser, so the eczema laser is used with Lasik and PRK. The eczema laser is used to ablate tissue, not for the purpose of correcting refractive error, but for removing abnormal epithelium as well as kind of abnormal anterior stroma. Our laser here doesn't have a PTK setting. So what we do is we'll typically just do PRK. So we're programming in some sort of refractive error correction for the purpose of PTK. But there's another laser that's commonly used called the Visix Laser made by AMO, which has a PTK setting. And what that means is instead of having, with PRK, there's tiny little spots that we use to ablate tiny little areas of the corneal stroma with PTK setting. It's just one large diameter, like a 6.5 millimeter diameter of laser beam that's used to just ablate away tissue. So PTK is used to smooth superficial anterior stroma irregularities. The problem though is that scar tissue can ablate differently than normal tissue and can result in an uneven surface. So if you're using like actual PTK and you're doing large diameter laser ablation, what you have to do is because you've got this irregular kind of stromal surface, you use what's called a masking agent, which is typically like a kind of a artificial tier with a little bit of viscosity like refresh plus, apply a thin layer so it fills in all the valleys of your irregular stromal tissue. And then you can use PTK to kind of ablate off the peaks. You can do PTK in granular dystrophy. It's not gonna take off all the chunks of abnormal tissue with granular dystrophy, but it can take off kind of the anterior portion and smooth that out. It's been used with post-lase X-GREA. PTK is not good for anything deeper than 100 microns though, because you don't wanna ablate so much tissue that there's kind of not much left. It may not work as well in post-tropetic scars or traumatic scars, but PTK is an option for kind of very superficial pathologies. That's it. Any questions? I mean, I feel like on call in the acute setting when we have these patients whose lids, the skin is sloughing and they're so inflamed and in pain, it's kind of hard to flip the lids and get a good assessment of the conge underneath. What are your suggestions for how to do it? So I don't think you necessarily need to flip the upper lids, but you can do sweeping with a cotton tip. And if you have pseudo membranes coming off, like that's not normal, so that would be... What about when it's not an SJS patient, so I think we'll see the burn patients and then we'll see the Pemphiboid patients and I guess the purpose is to assess how much P-world conge is involved and really the extent of disease. Is it important to get a good look under there? I would say that's not as important. I mean, because with Pemphiboid, you can look at the fournesses. You'll see if they're a symbol of wrong formation. And you can tell that just even by raising up the eyelid, you can tell if you like, sometimes you have the lid kind of scarred down where you can't raise it. And you know, okay, there's gotta be some blepharone down there kind of tacking the lid down even if you can't see it. With burns, I mean, you can tell just by looking at the pelvic roll, congenitiva. I don't think you need to know like how much tarsal epithex there are. I think that's more important with SJS you can tell by sweeping the fournesses. Any other questions? Okay, well, I guess that is it.