 Okay, so we're going to get started here. So I'm talking to you guys about immune-related disorders of the N-nexa and ocular surface, and there are a lot of them. This is the list. This is not even the full list. I took off some like real zebras that I didn't think were as important, but I'm not going to spend a whole huge amount of time on each of them, but there's a few that I will spend a little bit of more time on, but we'll go through the rest pretty quickly. So this is the order I think they were in in BCSC, so it's kind of random to me. It's not even by severity, but we are starting with something not so severe, contact dermatitis, so this can be a type one reaction if it is occurring within minutes, and that is considered anaphylactic. I think more commonly it's a type four reaction, which is T-cell mediated, which is about 24 to 72 hours after exposure to the allergic agent. Symptoms are eyelid redness, swelling, severe itching. Signs will be erythema and scaling of the eyelids. Treatment is discontinuing the offending agent if we know what it is. Unfortunately, I think most of the time we don't know what they are, just because there's a lot of possibilities for things that touch your face if you think about it. But even if we can't really identify what the offending agent is, I recommend cool compresses and then some sort of topical steroid ointment or topical antibiotic and steroid ointment for a week or two. Atopic dermatitis is similar, but this is chronic and it does begin in childhood, and this is a type four hypersensitivity with increased IGE hypersensitivity and increased histamine release. Symptoms are itching. There are usually lesions on the eyelids as well as other locations such as arms and legs. And there's a history of other atopic disorders such as asthma and allergic rhinitis. Symptoms are scaling of the skin, some periorbital darkening, which is shown in the picture, and also some exaggerated eyelid folds. Treatment is minimizing environmental allergens and also food allergens, using moisturizing lotions. The acute lesions can be treated with topical steroids, but you don't want to use those long term because there's side effect of skin thinning. Long term, you might consider a tachrylimus ointment because that has fewer side effects. Consider oral antihistamines and then consulting a allergist. Allergic conjunctivitis, very common, this is an IGE mediated hypersensitivity reaction. Typically, this is going to be something airborne, so pollen, weeds, something in the environment, usually seasonal. Symptoms are itching, swelling, redness, and kind of a mucoid discharge. You can also see a chemosis, which is seen in the bottom picture, but the most common finding is going to be a papillary conjunctivitis. So treatment, again, decreasing exposure to allergens. Consider doing some massive cleaning of bedding, carpets, air filters, cool compresses, artificial tears, topical antihistamines or mast cell. Stabilizers, but you do have to warn people that if they do have concurrent dry eyes, that can worsen their dry eyes. You could consider a short-term course of steroids. You might consider topical cyclosporine like rostasis and systemic antihistamines, but again, warn patients about worsening dry eye. Next is vernal keratoconjunctivitis, which is bilateral, seasonal, most often in male children, but it could be year-round in tropical climates. This is type one and type four hypersensitivity. Symptoms, again, itching, photophobia. They can also have blurred vision and they can have a copious mucoid discharge, and the appearance is rather striking. So on the paleopubrolconge, they'll be pretty much almost like a GPC look on their upper tarsal congenitiva. They may have some hemosis present. And then along the limbis, you'll see this in usually in kids of African or Asian descent, where the limbis has this kind of gelatinous, nodular appearance, and hornartrantus dots is kind of a buzzword that you'll see on tests. So these are a little white areas of degenerated eosinophils and epithelial cells. So you'll see this typically on the superior limbis, but you'll see this all the way around 360. So for mild disease, topical antihistamines, mass cell stabilizers, usually, they do need more intensive therapy than this. So usually, topical steroids, they do respond quite well to topical steroids, but I usually like to start at a high dose and then rapidly taper down. If it seems like they're still flaring, you might consider topical cyclosporin 2% or tachrylimus ointment as well. You might also consider supertarsal injection of steroid. Haven't done this, because usually this occurs in kids who are not gonna be kind of sitting still for this as an outpatient, but that's something that could be considered for very recalcitrant cases. Atopic keratoconjunctivitis. So this occurs in 1-3 patients with atopic dermatitis. Again, this is type 4 reaction. It is depressal mediated immunity. They are susceptible to HSV and colonization of their lids with the staff. The patients who get atopic disease are gonna be typically older than those with vernal keratoconjunctivitis. It is your round. The papillae are smaller than what you see in vernal. And I'll show some pictures of all this later on, but they'll have kind of a milky congenitival, edema look with some sub-epithelial fibrosis. They can get congenitival scarring and simblaferos. So this is not a benign disease. They can also get PSC cataracts, shield ulcers on the cornea, which are kind of usually a response to the papillae on the upper tarsal conge. They can get cornea neovascularization. And there are associations of this with curatoconus and pollucid. So this is kind of showing some sub-epithelial fibrosis here and also papillae. This is some massive corneal neovascularization, very thickened eyelids, and there may be some simblaferon going here. And then this is an example of a shield ulcer, which is gonna be like a chronic corneal epithelial defect usually found superiorly. Treatment is again allergen avoidance. It's the same treatment as with vernal, so topical allergy medication, topical steroids typically. You do wanna watch for secondary herpes or staph infections. In very severe cases, they may actually need systemic immunosuppression like oral cyclosporin. Okay, I'll spend a little bit more time on Stevens-Joneson syndrome and toxic epidermal necrolysis. Just because this is one of the, if you see this acutely and you diagnose it, it's something that you can actually treat to prevent further complications on the ocular surface. So this is a rare, potentially life-threatening immune complex hypersensitivity disorder that's triggered by medications or infectious organisms. It's quite rare. The incidence is one to seven cases per million, but you will see it here at the burning occasionally. You'll have sloughing of the skin and mucous membranes, and they actually simulate partial thickness burns, which is why patients get transferred to burn centers. It can affect anyone of any age. Usually it's caused by medication, and sulfa is a, and like Bactrum are a big culprit, but also anti-epileptic meds, allopurinol, even something as benign as NSAIDs or Tylenol has also been in etiology. And 15% of the time it's from an infectious cause, the most common being microplasma pneumoniae, also HSV, adenovirus, and histoplasma. So when it first starts out, it's actually a very non-specific set of symptoms for up to two weeks. So there's malaise, fevers, a big thing that happens, and they have chills, they have headaches, and then usually at this time they'll get exposed to medication as well. So it's hard to really know, pinpoint what the exact etiology is. Is it a medication that they take because of brewing Stevens-Johnson or was it from something else? And then after this two week period, then they get a very diffused progressive rash. They'll get erythematous macules, that progress to baleian vesicles, and the epidermis is very easily separated from the underlying dermis. And then mucosal erosions affect 90% and affects all mucosal areas, oropharyngeal mucosa, ocular surface, GI tract, and GU tract. And so this is actually a spectrum of disease, depending on how widespread it spreads. So first is erythema multiforme, which is a detachment of less than 10% of total body surface area, and they may have localized typical target lesions. The definition of SJS, Stevens-Johnson syndrome, is detachment of less than 10% body surface area, plus widespread erythematous and propraric macules. Mortality rate is only 5%, but that goes up quite high with more progression of the disease. So SJS and toxic epidermonic analysis overlap is 10% to 30% total body surface area involvement. And then full-blown TENS is greater than 30% surface area involvement. And the mortality rate of that is actually 35% to 40%. So this is what patients will look like. They'll be sick, they're in the burn unit, they're on oxygen. This is a woman who, I mean, when you look at her picture on the left, and for some reason my mouse is not here, but when you look at the picture on the left, it looks like there's kind of blood all over her face, and that's actually cause she has no skin. So that is her dermis that you're looking at over her whole face. On the right, this woman hasn't sloughed off too much of her face, but she actually has pretty severe oropharyngeal involvement. So her eyes are involved, and also her mouth is pretty involved. Acute eye findings. So there are ocular surface findings involved in 67 to 81% of patients. So we believe that pretty much all patients should be screened for ocular symptoms if they are diagnosed with Stevens-Johnson. But there can be variable presentation. Some people may not have any ocular signs. Some may have only mild, or they have a little bit of contractivitis, maybe a little bit of redness, and it can progress to severe, which is diffuse, extensive mucosal inflammation, pseudomembrane formation, which are these kind of membranes here, which are, it's basically their tarsal conventiva separating and sloughing off. They'll have epithelial sloughing of their eyelids and also lash loss. The late ocular complications are what we really kind of fear with Stevens-Johnson syndrome. They can have very extensive sim blepharone formation, eyelid deformities, ankle blepharone, where basically the eyelids kind of almost fuse together. Very severe dry eye, because you have destruction of the goblet cells and also the mybomian glands. There's limbal stem cell deficiency, corneal neobascularization, that can lead to thinning and perforation. Keratinization along the eyelid margins is something that happens a lot, as well as scarring of their tarsal conventiva. And if they have severe corneal involvement and you wanna do something like a transplant, it's a very high risk transplant because it's prone to rejection and failure. Even a cure to prosthesis or an artificial cornea is very prone to thinning, perforation, just because the ocular surface is so dry. So in mild disease, the medical management, there's actually medical management, so we recommend frequent preservative free artificial tears and ointment. Depending on how the eye looks, you could consider sweeping the foreign aces for pseudo membranes. I use a cotton tip. I mean, classically, they say use a glass rod, which I don't know where you find one of those, but cotton tip and just run it along the foreign aces to sweep for pseudo membranes. If there's large corneal epithelial defects putting an advantage contact lens, and then I'm using topical prednisolone and or rostasis. But then what's recommended, if there's more severe disease, is actually urgent amniotic membrane transplantation. So amniotic membrane is from the innermost layer of the placenta, and there are different forms of it. It can be dried or it can be cryopreserved. So when it's cryopreserved, we feel that it's really a lot more beneficial for these people, these patients. So it's actually acting as a substitute for the ocular surface. So these patients have sloughed their entire ocular mucosa, and we're trying to replace it. But we're not only replacing it, we're trying to get some anti-inflammatory treatment directly to the ocular surface. There are growth factors, anti-inflammatory cytokines found within the amniotic membrane, and there's various methods of actually applying the amniotic membrane to the ocular surface. Most commonly for these cases, it's sutured, could consider gluing it. There are not, there are suture-less ways to apply it to certain areas of the ocular surface as well. And it promotes re-epithelialization of the ocular surface, reduces inflammation, prevents symplophrone formation, and it naturally does degrade over one to two weeks, and depending how severe it is, after the amniotic membrane degrades, it may have to be repeated if there's still significant inflammation. So it's typically performed if there are corneal epithelial defects, if there are pseudomembranes, and if there's moderate or severe contactival injection. Perform within two weeks of the onset of symptoms, and I would recommend performing within one week if possible, just because the earlier you intervene, the better the outcomes are. Post-operatively, doing some topical antibiotics, prednisolone, rostasis, turbidex, ointment at night, and we also recommend QH saline flushes just to kind of flush everything off the ocular surface. And again, the amniotic membrane transplantation can be repeated later on. Actually, it was part of a study when I was at Loyola, where we looked at, it was a chart review of 128 Stevens-Johnson patients who were admitted and they were biopsy proven. And we had graded their ocular surface as mild, moderate, severe, and then these patients were either treated medically or with the amniotic membrane. And amniotic membrane hasn't really been used maybe only in the past, I think 10 years ago is when we first started doing it. So it was kind of a nice way to see how, compare how patients were, how patients did before amniotic membrane was employed versus after. And then the patients were graded as good, fair, or poor as far as outcomes. I'm not gonna go over all the results of the study, but this is one result that we had which was looking at patients with moderate to severe inflammation. And there were actually 23 eyes who were treated at the amniotic membrane and 23 eyes that were medically managed. And we found that the patients who had early amniotic membrane transplant, most patients had the good or fair outcome. So there was only one eye that had a poor outcome after amniotic membrane, whereas patients who had no amniotic membrane transplant, there were eight eyes who did not do as well. So it would be these, were the eight eyes in the poor category. And this was within three months. And then after three months, the results were not as statistically significant. There was a higher P value, but the results were similar. But actually in, I think it was the last month's ophthalmology, there was a new grading system that came out for Stevens-Johnson. And it was a nice way to kind of help see what to do for certain grading diagnoses. Diagnoses. So mild SJS was defined as pretty much no staining of the lid margin, no staining of the cornea, hyperemia of the conjunctiva with no stain, and the treatment recommendation there is medical. Moderate disease was defined as staining of less than one third of the lid margin, no staining on the cornea, and then small staining was okay on the conjunctiva less than one centimeter. And this could also be observed and treated medically. And then there were severe and extremely severe, and both of these required urgent amniotic membrane transplants. So for both severe and extremely severe, it was greater than one third of a lid margin. Any epithelial defect, more than punctate staining, automatically put patients in the severe or extremely severe category. Staining greater than one centimeter puts you in the severe category. Multiple areas of staining greater than one centimeter was considered extremely severe. So again, both of these categories required urgent amniotic membrane transplantation, and the extremely severe may require repeat surgery. Do you like follow that, would you follow that treatment recommendation like that? I think so, I mean I, the way we had graded things at Loyola was we a lot, we would observe if there was a small cornea epithelial defect of less than 25% of the cornea we would observe. But with Darren Gregory, he's not out of Denver, he felt that you needed to be a lot more aggressive. So I may follow this now, that this is kind of the newer treatment guideline. So you really wouldn't consider doing like amnion until like, until they've got corneal staining? Yeah, corneal staining or extensive lid margin staining. This one doesn't really talk about pseudo membranes, but I think by the time you get to pseudo membranes, you are having massive staining of the conditiva. And then I'm starting to think it's like mostly conjunctival. Like would you, I don't know, I had a kid that's here this past week that had like a mycoplasma mechocytus and like had no corneal staining, but had like a decent amount of like conching. And so it would be like monitoring based on this definition, like would you ever do like a prokera for that? I don't know what would happen. No, cause prokera, prokera only covers cornea and like a little bit of the conch. So if their problem is mostly contantival, like probably have to do the full thing or you could watch them and then if they have any sign of any corneal involvement then jump to amniotic membrane. Okay, I think treatment guidelines we talked about, mild and moderate disease can be managed medically, severe or very severe should undergo amniotic membrane. And this new study that had come out, the severe cases all had outcomes the best corrective visual acuity of 2020 and mild or no dry eye symptoms. And then the very severe cases still did really well. Nine out of 10 had 2020 vision, seven out of 10 had mild or no dry eye symptoms. Three out of 10 had, did have moderate lid margin scarring and dry eyes and severe photophobia. So they weren't completely normal but they were a lot better than the patients who have very severe some blepharone who don't see well. So this shows that the treatment actually works. Yeah. I think once, so once the amniotic membrane dissolves or gets incorporated and if they're still, if they still like say fit into the severe or very severe inflammation category then retreat. But if they are calmed down where they're now like mild or moderate then you can observe. Okay, so that was SJS. So we're going to move to mucus membrane Pemphagoid. So this was formerly known as oculosicrificial Pemphagoid or OCP but I think a lot of people still refer to it as OCP because no one knows what you're talking about when you say MMP. So this represents a type two cytotoxic hypersensitivity reaction and it's a chronic psychotrizing conjunctivitis of autoimmune etiology. And it frequently affects other mucosal membranes, mouth or pharynx and genitalia. Difficulty swallowing is an early symptom. It affects women more than men in a two to one ratio and usually you'll see this in elderly patients. So the stages of mucus membrane Pemphagoid. So stage one is sub-epithelial fibrosis, which you see here. Stage two is fornoceal foreshortening. So if you only pull down their lid you'll notice that the fornox doesn't go down as far as normal because you'll see some scarring along the fornox. Stage three, there's simple forno formation and stage four there's extensive adhesions to the eyelid and globe. So this patient is stage four. She's got some blepharone. She's got some adhesions to the globe here from her eyelid to the globe. And she also has corneal scarring. So the diagnosis is to do a conjunctival biopsy. And ideally you want to take this from a non-scarred area. So what looks to be a non-effective area. So not a some blepharone area. When you send this off for direct immunofluorescent staining there's a special media they have to place the tissue in. And then you'll see basement membrane staining of IgG, IgM, IgA, and or a complement three to see along here. And then you do want to work with either dermatology and or rheumatology for systemic treatment. For mild cases this is just oral dapsone. For more severe cases this could involve psychophosphamide, rituxin, or other immunosuppressive agents. You want to really delay surgical repair until the disease is quiescent because it, because there's so much scarring that if you were to aggressively try and repair them surgically they're just gonna scar up more and end up being worse. Eyelid repair is often needed. These patients don't do well with any sort of transplant, they may need lumbel stem cell transplant even then they don't do well and they might need a carrot across thesis. And those also have a high rate of failure. Next is graft versus host disease. So this occurs in patients who have undergone allogeneic hematologic stem cell transplant. Ocular disease is the more common form in chronic forms of GVHD. And what happens is that the donor lymphocytes start to attack host histocompatibility complexes. And 40 to 90%, depending on the study, of patients with GVHD will have ocular involvement. So this is a T cell mediated process that leads to infiltration and inflammation of the lacrimal gland, congenitiva, and ocular surface. So they typically have very severe dry eye because of this. So that leads to decreased goblet cell density, scarring of the lacrimal gland and congenitiva, myobomine gland dysfunction in scarring and limbal stem cell deficiency. So these are just some examples. I mean, there's very kind of dry eye. You can see the diffuse punctate epithelial staining. Their ocular surface is very inflamed. And when it's chronic, it can lead to some extensive new corneal neubascularization. So treatment is gonna be just very, very aggressive dry eye treatment, very aggressive lubrication, punctal occlusion, topical cyclosporin, topical steroids. And then working with their hematologist or oncologist for increased systemic immunosuppression may be needed. Next is Tigason superficial punctate keratitis. So this is of unknown etiology and there are recurring episodes of touring, foreign body sensation, photophobia and blurred vision. And it affects kind of people of a very wide age range. It's usually bilateral, but it may be very asymmetric. And the signs are gonna be these small, kind of slightly elevated, corneal epithelial lesions that will stain with fluorescein and rosebangle with minimal conjuntival inflammation. So I've got some pictures here. So when we talk about SPK, depending on who you talk to, I mean really, to me, SPK really refers to this. So I was taught that SPK shouldn't really be applied to kind of dry eye in general because it's more specific for this particular syndrome. So you'll see these multiple very small dots in the epithelium that do stain with fluorescein. And sometimes you can have a little bit of haze around the dots as well. So it looks different than the dry eye punctate epithelial lesions because these are a little wider. They're a little kind of more elevated because in dry eye you'll see kind of excavation of punctate epithelial lesions whereas here they're a little bit elevated. They typically respond very well to topical steroids and you could also consider topical cyclosporine. However, it tends to recur multiple times over several years. So it's kind of something that keeps happening and people have kind of looked into viral etiologies but nothing's really panned out for sure. Interstitial keratitis is a non-supertive inflammation of the corneal stroma and it usually has neovascularization without involvement of the epithelium or endothelium. And it usually results from a type four hypersensitivity response to some sort of infectious agent or other antigens in the corneal stroma. Most commonly you'll see this in HSV, also Zoster, syphilis, and there are a lot of other rare causes such as TB and Lyme. But most cases you actually see it with syphilis and it will be with congenital syphilis. And this is kind of a later immune-mediated manifestation of congenital syphilis and it develops late in the first decade of life. And there's a stroma keratitis that lasts for several weeks. It's usually bilateral. If you have acquired syphilis, it rarely develops but if it does, it's typically unilateral. Symptoms will be pain-tiering, photophobia, some peri-limbal injection. You'll see some sectoral stroma inflammation and KP's. There will be a deep stroma new vasculatization seen later in the course and the cornea may appear pink and it's termed a salmon patch, just kind of another buzzword that you'll see on tests. Inflammation spreads centrally with a pacification edema and the sequelae are corneal scarring, thinning and ghost vessels in a deep stroma. So this is showing some extensive corneal neovascularization and scarring and then on the right, you'll see ghost vessels. So there were a lot of vessels there and then when they regress, you'll see the remnants of the prior vessels. Diagnosis and treatment, so you want to test for syphilis with blood tests. In the acute phase, you also want to apply topical steroids and cycloplegics. If it's untreated, the disease actually does burn out on its own but after several weeks. Systemic syphilis should be treated with penicillin as a neurosyphilis and you want to work with your infectious disease specialist for that. Next is Kogan syndrome. This is a rare syndrome but it's an autoimmune disorder that's characterized by stromal characteritis over to go and hearing loss. This is again, something that has an unknown etiology but it does share some features of polyarteritis nodosa and it typically occurs in young adults one to two weeks after a upper respiratory infection. So the signs will be, early on there'll be some bilateral faint whites of epithelial infiltrates in the periphery and later on there'll be some multifocal nodular infiltrates in the posterior cornea and then some patients develop a systemic vasculitis that presents as polyarteritis nodosa and there's no real specific diagnostic test for this. This is a diagnosis of exclusion. Treatment was with steroids for the vestibular auditory symptoms, oral steroids can enhance prognosis for normal hearing for very severe cases they might require some systemic immunosuppression. This is a very common thing that you'll see, marginal corneal infiltrates. So like I said, this is a very random order but this is what it was in BCSC. So marginal corneal infiltrates occur in the peripheral cornea where the basically areas where the eyelid margin intersects the cornea. So like at 10 and two and eight o'clock and four o'clock and they're typically very well-defined gray white anterior stromal infiltrates have a little bit of a clear zone from the limbis and there may or may not be an epithelial defect. The treatment is gonna be a combination of topical antibiotics and steroids. And here are some kind of classic appearances. This is pretty classic for a staff marginal infiltrate. This one is not as classic because there's so many but you can have multiple ones like this and you can have variable, I guess, distances of a clear zone. This one may be a little bit more central than typical and these may be just a little bit more peripheral than what is typical. Next is peripheral ulcerative carotidus or PUK. So this occurs in autoimmune disease. Most often with rheumatoid arthritis but it can occur with Wegener's lupus, polyarderitis nodosa and ulcerative colitis. You do need to work these up if there's no known autoimmune disease. It's usually unilateral but they can be bilateral. You can have paracentral thinning so it doesn't have to be peripheral but with rheumatoid arthritis it's actually I think more common to have paracentral thinning than it is to have peripheral thinning. And it's usually painless or they mainly just have mild discomfort. So this is pretty severe PUK that you can see in the periphery here. In this case there's some chronic PUK that's occurred inferiorly. You can see a lot of blood vessels growing in and then this is the area of paracentral thinning. So the treatment is they're gonna need some more aggressive systemic immunosuppression so work with their rheumatologists to do that. Increased lubrication, drops, ointment, puncto plugs. Oral, tetracycline, class antibiotics such as minocycline and doxycycline can inhibit collagenases and kind of prevent further thinning of the corneal stroma. Typically, classically you're not supposed to put on topical steroids because that can exacerbate thinning and delay epithelial healing. If you're getting to a point where there's a dysmedicine or a small perforation they may need to be glued and they may need a patch graft if they're perforated or if there's a larger perforation of corneal transplant but they typically don't do as well unless they have very, very aggressive systemic immunosuppression after their transplant. The Morin ulcer is a type of PUK but it's of unknown origin. It's a diagnosis of exclusion. There are some factors that might make you think that you have a Morin ulcer but the precipitating factors are going to be prior trauma exposure to parasitic infections because there's thought to be some cross-reactivity of the immune reaction to parasites with corneal auto-engines. In some cases may have an association with hepatitis C. So the signs are going to be a painful red eye and it usually is going to be starting in the corneal periphery and then spread circumferentially and then spread kind of more centrally and the classic sign, which I'll show you a picture of later is a leading overhanging edge in the cornea and it can be unilateral or it can be bilateral. So when it's unilateral, you'll typically see in older patients it's slowly progressive. You'll see an equal distribution between male and female. The bilateral type is more common in African males. It's rapidly progressive. It responds very poorly to treatment and perforations can occur. So it's a lot more aggressive. So here are a couple examples of Morin ulcers. So this is that overhanging edge and it'll be a very kind of well-defined kind of white edge and it's really seen here. I mean, here you can see it's like a cliff and then kind of this excavated area underneath. So there's very little success with topical steroids, cyclosporine, bandage contact lens. Patients may need to undergo a limbo-conjunctival excision kind of in the area where the disease is occurring. So excising the limbo-conjunctival area and then allowing that to recess. They often do need, or they might need a lamellar periodoplasty as well. They often do need systemic immunosuppression and consider systemic interferon if associated with hepatitis C. So again, this is something you'd have to consult your infectious disease specialist. Corneal transplant rejection. So this is something that can occur greater than one month after a transplant and up to 20 years after a transplant. And 80% of cases can be reversed with intense topical subconjunctival and or oral steroids. So this is why patients do need some sort of immunosuppression for their corneal transplant. So it's usually gonna be topical steroids but for very high-risk patients who are prone to rejection, they may need systemic immunosuppression. Corneal neovascular vascularization does increase the risk of rejection up to greater than 50%. And you could consider some topical and subconjunctival anti-vigorous agents. There are a few types of corneal transplant rejections. There is epithelial where there's an elevated kind of epithelial ridge that's caused by lymphocytes. Usually it's in the first year after a PK and this is more uncommon. Subepithelial, there'll be subepithelial infiltrates. Stromal rejection, not as common but there'll be stromal infiltrates. Some thinning of the stroma and that may need to necrosis. Endothelial is the most common and it's the most serious form because that can lead to a loss of endothelial cells which can lead to chronic corneal edema or graft failure. And the buzzword here is the kudaduce line which is inflammatory precipitates on the endothelial surface and it may be in a line under corneal edema and enter chamber cell is common. So I'll show a picture here. So this is a picture of a kudaduce line. This is in the endothelial surface and this is showing some stromal and subepithelial kind of diffuse haziness of the cornea. So there are different ways to prevent rejection. At the time of surgery, you can consider putting in a smaller graft that's further away from the limbis. I typically will recommend the patients are on topical steroids forever after the corneal transplant. However, you'll see a lot of people who are no longer taking topical steroids because they're, you know, they had their transplant like 10, 15 years ago. For those patients, I usually won't restart them if they've been doing well but if they ever have any sort of rejection then I tell people they need to be on steroids for life. You do want to remove any broken or loose sutures because that irritation can induce not only infection but also rejection. Okay, next is episcleritis. Common condition is usually self-limited. It's a benign inflammation of episcleral tissues. The minority of cases are associated with a systemic cause. So I don't usually work up patients with episcleritis unless they're coming in with like very recurrent episcleritis and I'll do a full workup. The symptoms will be some redness, usually not very irritated. There may or may not be any tenderness. That's very slight. It can be diffuse or it can be nodular. It's bright red in natural light and the redness actually blanches five minutes after the installation of topical phenyliferin. So that's a nice kind of diagnostic tool to differentiate between episcleritis and scleritis. So like I said, consider a workup if the condition is recurrent. There are some systemic associations but they're all less than 10%. So it can be associated with herpes zoster, collagen vascular disease, gout or syphilis. Episcleritis is something that will actually resolve without treatment. So even if you don't really do anything, it's gonna get better on its own. But if you do do something, you could consider a short course of topical steroids and oral NSAIDs to speed the resolution. Okay, so you wanna differentiate episcleritis from scleritis. So scleritis is severe ocular inflammation that's gonna have a high association with systemic autoimmune or infectious disease and it can lead to a destruction of scleral tissue in certain cases. Half of cases of scleritis are bilateral at some point during the course and this is not gonna get better if you don't do anything. It has to be treated to achieve resolution. So the symptoms are gonna be severe pain and redness. This will be a pain that's so severe that it often awakens people from sleep. And instead of that bright red that you'll see with episcleritis, this is kind of more of a purplish hue and it's got this deep, volatious hue and natural light. The globe is very tender to touch. So you can see this is very inflamed. So there are different types of scleritis. This is non-necrotizing scleritis and this can be diffuse or nodular. So it can be sectoral or it can be involving the whole entire segment. It can be nodular where there's actually a scleral nodule present. Necrotizing scleritis without inflammation and the other name for this is scleromalacia perforans. So this is a painless type of scleritis and there's a white, quiet eye but there's thin sclera and you'll see this in elderly patients. It's typically bilateral. 50% of these are from rheumatoid arthritis and scleral rupture is rare in these cases and it rarely needs surgical repair. Whereas necrotizing scleritis with inflammation is a lot more serious. This is painful. It's bilateral in most cases. It is highly destructive with vision loss in 40%. There's high association with systemic vasculitis such as Wegener's. The mortality rate is actually 20% at five years if you do see necrotizing scleritis with inflammation. So you can see this little photo montage of different very severe cases of necrotizing scleritis with inflammation. So very thin sclera and a lot of inflammation. Post-ear scleritis can occur in isolation or with anterior scleritis. However, with post-ear scleritis often even after a full workup, no systemic disease can be found. The symptoms will be pain, which may be referred pain. There may be some proptosis, tenderness, vision loss, and restricted motility. And the signs are coroidal folds on dilated exam. They can't have an exudative RD and they can also have papillodema. And then the T sign on B scan ultrasound is the classic sign in post-ear scleritis. So this is, I'm trying to get my mouse here, the T sign here. So this results from kind of a severely thickened sclera and then you'll see kind of the optic nerve coming back. This one is showing some coroidal detachment there. And complications of scleritis, whether it is anterior or posterior, can be significant. So you can get a peripheral keratitis, you can get uveitis, glaucoma, cataract, sclerothinning, a scleroceratitis, where you have actual opacification of your peripheral cornea that's associated with a neighboring area of scleritis. And scleroceratitis is more common in zoster scleritis. So the workup may have to be tailored according to the review of SIP systems. So you can check a CBC, ESRCRP, ANA rheumatoid factor in incas, uric acid, check for syphilis, check for TB, and check for sarcoid. So the treatment, some mild anterior scleritis may be treated with just oral NSAIDs. Usually though you want to use oral steroids and then refer to a rheumatologist for treatment for systemic immunosuppression. And they may start them on a variety of different agents depending on what the etiology is. And that is it.