 So the fish I'm presenting is a 74-year-old male. He originally came in with complaints of itchy, watery eyes while he was in Island Park. And he was having trouble with his vision-wise fly fishing. Came in, had a history of my Bowman gland dysfunction, had some dry eyes. Was noted to have a bilateral nasolabial cirrhigia. He denied any chemical or thermal burns to his eyes. He was started on artificial tears, given a new prescription. And as follow-up, I encourage you to do several things here. His redness and tearing was initially stable as vision was doing good. But he started developing terrarium, both inferiorly. And then at his last appointment before being referred to Dr. Zog, he was starting to have some congenitalization inferiorly in bilateral eyes. When he presented to Dr. Zog, he also had a nasal cirrhigium. Here's his exam. His visual acuity was preserved as pupillary reflux was still intact. And the congenitalization was never pulled in inferiorly by the eye. They had some, no, cataracts. These are images taken from that first appointment with Dr. Zog. These two stacked closer to me are his right eye and these two on the far side are his left eye. You can see the cirrhigium pretty well there. And inferiorly, you can kind of start to see some congenitalization and neobascularization. So what he was diagnosed based on his clinical signs and symptoms with limbal stem cell deficiency. So I wanted to review a little bit of limbal stem cell deficiency, go over some of the key studies or at least some of the interesting studies that I found that helped localize the corneal stem cells to the limbus and a few other anatomical landmarks that are important both diagnostically and with the pathophysiology. So one of the earliest studies I was able to find was in 1942 by Maun and Poinger. They were studying the effects of mustard gas on the cornea of rabbits. The first thing that they noticed was that there was a dose-dependent relationship between the amount of exposure to mustard gas and damage to the rabbit's cornea. They also noticed that with that damage, they would get migration of melon and pigment, more essentially, onto the cornea. And then in 1971, when their first paper was published for Davenger and Edinson, they were studying guinea pigs. Later went on to study humanized as well. But a couple of very interesting things that they noticed is they would remove areas of the corneal epithelium just central to the limbal ring in the guinea pigs and then watch them. And within the first 24 hours, they would notice that in the limbal ring, exactly adjacent to their corneal erosion, that it was slightly lighter in pigmentation. And then they found pigment overlying those corneal erosions. And then following those guinea pigs after five days, they would see a complete resolution of the pigment that they found over the cornea. And then a return of the color, the appropriate color in the limbal ring. They also noticed that within those first 24 hours, they found an increased rate of arrested cells of myctosis. And so that was interesting. Then in the early 80s, Thaft and Friend, they came up with the XYZ hypothesis, which is kind of what this picture on the far side takes a little bit, although perfectly incorrect. But I appreciated the different views in correlating with the views of the corneal. So their thought was the stem cells in the limbus represented by ax were dividing and multiplying. And then as they continued to divide and differentiate and migrate superiorly and are superficially and vertically, they would continue to divide. That's why those are the trans-amplifying cells. And both the sum of both of those divisions were equal Z, or amount of corneal mature, corneal epithelial cells that were lost and something out from the tear film. Their hypothesis was later confirmed in 89 by Sharma. And then Consorellus in 89 also had that experiment that I thought was very interesting. They used a tritiated thymidine to label the cells in the corneal. And they noticed a region in the limbus that the cells were very quiescent. But they would increase their mitotic rate after injury to the corneal. And then the policy of the vote, these are anatomical structure. They're papilla-like structures in the limbus with densely packed basal cells at the bottom of the papillae surrounded with connective tissue, good blood supply and nerves. Of the basal cells in the policy of the vote, they would think about 10% to 15%, or maybe stem cells. And the most concentrated area of policy of the vote are in the superior inferior limbus, more so than the horizontal meridians. And then interesting, the corneal obviously plays a very important function as a barrier. And the corneal epithelium specifically has tight junctions that help make up that barrier, which are lost in limbal stem cell deficiency, which kind of helps potentiate the inflammatory cycle of limbal stem cell deficiency as the tear field breaks down, increased permeability to leukocytes and other white blood cells in the corneal stroma. So I have a couple of slides on the ideologies. Not necessarily listed in order of most common, but idiopathic obviously probably one of the most common is chemical or thermal burns, especially alkali, so cement, mortar, things like that. Acidic burns from clean air or strained clean air as car batteries. They can also be iatrogenic, macular surgery, conduct use, radiotherapy. The autoimmune causes, I found to be very interesting. They have the highest rate of transplant rejection, with obviously there being systemic diseases, so it's hard to control the implant or response, which is pro-epoptotic on the limbal stem cells. Steven Johnson syndrome specifically seems to affect the lids more so. Destroys the myobovine glands and some of the other accessory glands, which can lead to severe dry eye and corneal curatidization. Bocular secretarcial pimpagoi, usually found in women over 50. I think the average age of diagnosis was around 65. Commonly seen with simplethoron and shortening of the forex. Important for both of those, I guess, diagnostically really quick before I forget, they can have a complete absence of goblet cells, which, when we talk here in a second about some of the methods that are used to confirm the diagnosis of limbal stem cell deficiency, that can create some difficulty. There's a whole list of eye diseases there that you can see one unifying factor in that list under number five is kind of the effect of inflammation and then knocking out limbal stem cells. Congenital causes, aniridia is probably one of the most common. I thought it was interesting that it spans the whole gamut of aniridia. You can still get limbal stem cell deficiency both from complete absence of the iris or to just mild stroke hypoplasia. About 90% of people with aniridia will have a scarotopathy. It's been linked with a PAC-6 deficiency. PAC-6, they've shown, is important for the up-regulation or is up-regulated when the cornea is injured. And further downstream will up-regulate. It's like cytokiratin 12, MMP9, a few cell adhesion molecules, which are all, in summary, kind of all very important for corneal health. So moving to some clinical signs and symptoms. There's obviously pain, teres, photophobia, corneal neurovascularization. Conjunctable ingrass is probably the most reliable or considered the most reliable sign of disease clinically. You can also see with topical forcing some wave-like irregularity, kind of in a vortex pattern, on the cortex, and increased ophthaloformability, kind of like I mentioned, with the loss of those tight junctions. And you can see the stromal body line a little bit more. Here's a picture of that. You can see the wave-like abnormality there. Like I mentioned with our patient, if it's kind of classic with clinical signs and symptoms, that is enough to establish the diagnosis. And if you're looking to confirm it, one of the other more conventional techniques is Impression Cytology. The goal of Impression Cytology is to identify goblet cells, or mucin. Use a cellular acidity paper put on the corneal and dry them, periodic acid shifts thing. I'm pronouncing that correctly. You look for the goblet cells, or like you're seeing here, mucin, agarates, and pink. It has a really good ability to identify the disease and confirm the disease, but a negative result with Impression Cytology. Not necessarily rule out the disease. As I mentioned, there can be an absence of goblet cells or an element of disease, or lay down disease, like in those all immune conditions, there can be a complete absence of goblet cells as well. So people have been looking into several different diagnostic techniques to try and confirm this disease. So they've used indigo confocal microscopy, OCT. These are confocal images here with three columns by A are from the centropornia, and the two columns by B are from the limbis. That far corner picture is a normal cornea, and those are the policies to vote. You can see as disease progresses, a lot of these anatomical landmarks are lost, or destroyed in both locations. The confocal microscopy, they found a 90% concordance rate with Impression Cytology, has some limitations, obviously that it's expensive equipment, takes a lot of technical expertise to use it, a very cooperative patient, as it does require a contact with the cornea. OCT, if you have a high resolution OCT with the actual resolution of like three millimeters, you can diagnose or identify some of these anatomical landmarks. Papers that I was able to find, they haven't shown any diagnostic evidence of OCT for this disease, but they're rising that it could be helpful as you can identify all those landmarks. Histological markers are having use or being used and studied in common accordance with Impression Cytology. So the set of cares in three is found in the cornea and 19 on the conjunctiva. More recently, they've found cytokinesia 713, a little bit more specific for the conjunctiva. So they've done studies and looked at using both together with Impression Cytology alone. They found a job of selling like 56% of samples and using Cytokinesia 319 that jumped up to around 86%. So increased the cash there a little bit. And then Mach 5 AC is just a goblet cells, secreted mucin. We're a way to identify that. Has some of the same problems. It can increase the catch. I think that was even more dramatic from like 30% or so up to 89%, or no, 94%. The problem with these is the specificity and getting more specific markers. So moving to magic really quick. If it's mild or focal, you can just focus on controlling inflammation, removing any incited factors, topical steroids or stasis. If it's kind of sectoral mod, you can do it right around normal, of that normal epithelium. More extensive disease. So if it's unilateral, diffuse, you can use this conjunctival, or autograffin technique. We either kind of ordered more recent techniques, a simple emboled epithelial transplantation. I think the first paper was in 2011. The culture of the emboled epithelial transplantation benefit with those, if you're using autograffin, you don't have to use systemic immunosuppression. If the disease is bi-level, diffuse, though, living relative autograffs or donor, categorical donor autograffs are possible. And they have had a really good success when they use systemic immunosuppression. These are some diagrams that I thought were interesting, really helped me visualize the surgical process. So these ones on the left is the conjunctival limbo autograff. And the living relative autograff is kind of the same process, just where you're getting your donor sites from. You take the donor sites from the superficial, or the superior and inferior meridians there, kind of like we talked about the most dense location of the palisades of Boe. Do the 360 career to me and the superficial career type to me. Sewing your grafts, kind of similar with the, so the one on the far side is the carotidolimbo autograff. And then in the middle, I guess I forgot to mention, there's the Cincinnati procedure, which kind of combines the conjunctival limbo autograff and the carotidolimbo autograff. I was able to see, although not on our patient with Dr. Zog, simple limbo autogransplant, one of the benefits of that specific surgery is you can take less donor sites. So instead of taking two and A on this close side, you can just take one sample, pretty much complete the rest of the steps the same. And then instead of D, you cut that sample into eight to 10 pieces, arrange it around the cornea while avoiding the central visual access and place amniotic membranes below and above to kind of help protect the cornea and give a lot of growth factors there. One of the benefits, I don't have a good picture here of the culture transplantation, but compared to these, you get a full, a complete coverage of the cornea and the lindus, which is one of the benefits and you're kind of sitting there. So kind of returning to our patient. When he followed up in Dr. Zog's clinic, he was stable, doing well, no further progression of the disease, so we just continued the current treatment plan. These are some of my references. And any questions? Thanks.