 So, with that queue and Dr. Olson being always on time or one minute early, we'll go ahead and start. This is our combined grand rounds slash subspecialty meeting. And today we have some hopefully really good talks from both of our new cornea fellows and then also Mike Murray a resident who may be interested in doing cornea fellowship I think that's still the plan. So, first we're going to hear from Brett Gudgel. Brett's here from Oklahoma, where he did his residency and a lot of his training and growing up. And he's going to talk to us about carrot across theses can give us kind of a broad overview. And then Eric Weinlander, who comes to us most recently from Michigan will be talking to us about an interesting case of inflammatory conjunctivitis and then finally Mike will give us a talk about care to conus and ectasia. After refractive surgery and specifically the detection of that. I'm in a bow out as a modulate moderator a little early for surgery but with that I'll turn it over to Brett. Everyone's nice to meet you. I'm like Dr. Mifflin said I'm Brett Gudgel, one of the cornea fellows. Let me get my screen pulled up here for us. And I did my residency to do McGee Institute in Oklahoma City, but I've really enjoyed being here at Salt Lake it's been a great experience so far. Can you all see my screen okay. Yes, perfect. Today I kind of want to cover a brief, really an update on care across theses and also kind of an overview on some care across theses that we might not be as familiar with and so it's a really big topic. What to cover, hard to cover in such a short time they'll try to do kind of an overview. And I think to get a good appreciation of where we are now, I think it's always important to look back at history and so kind of looking back at the history of care across theses. I think I'm going to be doing an article on kind of the history of this and Dr. Manus's book on the history of corneal transplantation and really the first idea came about in 1789 with a French surgeon I'm going to totally butcher his name I think Yame Piliere. And so he kind of described Dr. Mifflin's laughing at me he's kind of described a his idea of what a care across theses would be like and essentially a piece of glass and a silver frame. The second part is he's talking about fitting it in place and so that the sclera can exactly adapt to it by secreting new juices. So kind of an interesting idea of how the healing process has worked back then. And he also had some interesting tips for the procedure itself some pearls if you will he recommended choosing a clear day for the operation because back then you didn't have a operating microscope you had to kind of operate by the light from the window. I also recommended the lids being held open by assistance and I imagine this is kind of the first role of the cornea fellow back in the 1700s. And then you bandage the eye for eight days and just kind of hope it takes and if it didn't then you just rebandage for another eight days. And I like this little excerpt at the end here one could also for increased security fix the artificial cornea using two or three sutures. So just in case you want a little extra security you could suture in place. And over here you can see he designed you know he's pretty serious about this designed the prosthesis he made some tools for it. And but actually never ended up doing it until a few years later where it just thought that brother actually did the first one in human, which failed. But from that point on there's been many future attempts at care prosthetics and and many complications and failures if you can imagine they're doing this in time without, you know, oxenobiotics without the knowledge of the pathophysiology of glaucoma without anti inflammatory medication so it's just really kind of set up to not do well. And then eventually came the introduction of the penetrating care of plastic and the interest in care prosthesis declined as we started getting better results with penetrating care of plastic. But they're still remained even despite the success of pks and conditions with high risk graph failures that kind of res reignited the interest in care prosthetics. And so that takes us into kind of the modern era, where we are now and so essentially a care prosthesis is indicated in patients who standard penetrating care to plastic is going to perform poorly. Just to name a few indications, you know, limbo stem cell failure and already a chemical injuries, Stevens Johnson syndrome, extensive corneal vascularization repeat graph failures. And there's numerous designs this is not at all an extensive or exhaustive list here, but some of the more commonly used ones is are the Boston type one care prosthesis oftentimes people just call that a K pro for short. The osteodontal care prosthesis which is a little more commonly used in Europe. Some other designs that at least I wasn't initially as familiar with the Moscow I micro surgery complex in Russia, or the my cough, the Alpha core and the care clear. So we're covering some of these. The Boston K protect one is developed in 1960s at Mass Eye and is FDA approved in 1992. And the design has an anterior plate of PMMA with an optical stem, and then there's a snap on titanium back plates and there's a donor corneal that's kind of sandwiched between the two plates and it's sutured into place like a typical care process or care to plastic. Like many care to prosthetics, there's a lot of complications with these just to name a few infection tissue melt necrosis glaucoma you can have lots of inflammation issues retinal issues retro prosthetic membranes and infections like end up the minus as well. So you can see here in the pictures on the right you see some infiltrate around the prosthesis, and then you see some corneal melting in the bottom right picture there. So to address this the Boston K Pro teams done a good job of continually modifying the prosthetic and so some of the modifications that have been made throughout the years are daily topical vancomycin help really decrease the risk of infection. They put holes in the back plate which really helps kind of allow the donor corneal to get nutrition and decrease the rate of melt continues contact lens where to help prevent breakdown that switching from a PMMA back plate which you can see in the top left photo there that was the back plate to titanium back plate helps decrease the risk of retro prosthetic membranes and then they just made simple adjustments like a click on back back plate to try to make it a little easier to assemble. And so in terms of future I guess more recent developments for the K Pro. The Lucia is the newest model is FDA approved in 2019 and so they kind of tried to address several things here one of the big things they want to try to decrease the cost of infection and make it a little more manageable and economically feasible. And then they changed the back plate to one size previously the previous model of K Pro had two different sizes one that you typically use for pediatric cases and one for adult cases but they just kind of split the difference and made one size fits all. They changed the holes from rounds had more of a petaloid radial slits. They say that this is more of a production issue in terms of kind of decreasing the strain on the plate whenever they're actually making it but just looking at it it seems like you'd have maybe more surface contact area with the aqueous onto the cornea so could have an extra clinical benefit to I'm not sure. And one thing that I thought was kind of interesting is they they really address the color specific back plate so now you can actually adjust the color. The first case may seem like a kind of a silly thing to address but you know the cosmesis of this can be really bothersome to some patients sometimes and if you kind of think about on a global health scale. A lot of patients are going to have a darker color iris and so with the titanium back plate it can be a pretty noticeable contrast so they use a kind of an electrochemical process to be able to coat the back plate and change the color. In terms of future developments for the K Pro. There's currently working in rabbit models to make an integrated intraocular pressure sensor and so it's kind of located right by the stem of the optic and they're working on the ways to have contact and non-contact ways to essentially interrogate the device and figure out what the pressure is. They've had some pretty encouraging results of that so far some issues with some stir tissue that maybe limits its durability but hopefully you can get that going and then they're also looking into some new materials to prevent melt particularly around the stem of the optic. So kind of transitioning into the osteodontal care prosthesis or the OOKP. This was actually introduced in 1963. This also has a PMMA optic but interestingly in the first time I saw this procedure and when I was reading about it pretty amazing procedure they anchor it into a tallest tooth and root and alveolar bone. So this is a multi-stage procedure and so in stage one they're actually going to harvest the bone graft and prepare the optic and so you can see them here. That's where they take it and they kind of drill a hole but the PMMA optic in place. And then they're also going to do a mucosal graft over the eye itself and then they'll take this prosthesis and they'll actually implant it into a soft tissue pocket and allow it to sit there for three months and kind of granulate it and get a lot of fibrovascular tissue. And then stage two about two to four months later they're actually going to harvest that opt or that implant and kind of trim it to the appropriate size. And then you trepidate the cornea, you go ahead and take out the lens and you'll also learn that they've kind of made some modifications where they actually take the iris and also do an anti-retractomy and then put that prosthesis in place and then cover it up with a mucosal graft and a mucosal graft for the optic to come out. And so just like the other care prosthetics there's complications for this as well as some of the similar ones and one that's actually unique to this would be kind of resorption of the bone itself. And so in order to do this sometimes you can do some kind of imaging. And I think this is an interesting picture on the right here. This is a radiographic image of a patient who actually had a OKP in place and you can see there and the inferior portion of the prosthetic there's been a significant amount of resorption so you can actually track that with radiographic imaging. Some modifications that they've made over time with this is the correction of the lens, anti-retractomy and iris removal. Those steps are mainly to kind of decrease the formation of the retroprosthetic membrane. And then for some rare situations where patients may not have teeth that are good options for the graft you can actually take tibia fragment, a little quicker resorption rates with that but still work pretty well. In terms of looking into future ideas for this prosthetic there's hope to expand the visual field. It's really a pretty narrow visual field with a really long optic to try to get through all those tissue layers and so trying to widen the optic might give a better field of view. They use some modernized NC to help with anterior membrane formation and also new materials to substitute for bone that would be more accessible like porous ceramics or even coral skeletons I thought was interesting just because of the porous nature that would be a good substitute. And then now briefly just to kind of go over some other prosthetics that we might not be familiar with. This is the mycoph like I mentioned this is a titanium frame with a PMA optic cylinder. And this is also a two stage procedure where the first stage are going to insert the plate into a lamellar pocket and then wait about three months and then you're going to implant the PMA cylinder later. Here's a few pictures of this you can see on the left are actually dissecting out that lamellar pocket and then they slide that titanium plate into the pocket. And then this is the beginning of stage two about three months later you can see that they're first trefinating that top left picture. They're trefinating the cornea there and then they will remove the lens material through that hole actually the video is pretty interesting and then they'll put in the PMA optic on the right there. Afterwards they'll do an anterior vatrectomy through that optic and this is kind of what the final result looks like in the bottom right there. Moving on to the caraclier this one's a little different this is actually a foldable acrylic implant and this is implanted into a corneal pocket. Most typically using femtosecond laser but sometimes they can there's been some studies I've looked in micro care at home as well. And this is actually not a non penetrating implant so you're not ever going to actually go through the posterior decimation post some of the posterior stroma but you do trefinate the anterior three point five millimeters of the cornea. And so some hopeful benefit of not having to actually open the anterior chamber there this is what it looks like on the right. And then finally the alpha core this is a PHEMA material and this is also a two stage procedure. The first stage you're going to make a stromal pocket and so they'll kind of do like a 50% corneal dissection with that plane. And then the first stage you're actually going to trefinate the posterior lamella and make an opening there put the implant in place and you'll close that up let it sit for about three months and then you'll finish with the anterior opening. And so that's kind of a brief overview and looking at this you know, trying to figure out exactly how you compare these is really difficult. The literature on some of these prostheses are as pretty limited and also the indications are so broad the visual potential in these eyes can be so variable. And just the metrics that the different studies actually look at are usually pretty inconsistent and not all studies look at the same things. There really was not one overarching study that could compare these different devices but I was hopeful to get at least a idea of what these type of things or what these devices how they're functioning. So I kind of did a very, very crude and not very accurate literature review and just try to find the best single studies for each of these devices. I could the ones in green here were actually review studies and then the other two were single site just series. If you look here out of all the different highlights here the okp actually have really good visual outcomes compared to the other ones with 52% having 26 year better with a pretty good sample size there. Unfortunately, Cara clear and the Alpha core struggled a little more in the actual and visual potential with the devices and a lot of these different references starting point for almost all these studies was count finger hand motion. Retention rate wise the K pro the okp and the my cough did the best the Cara clear and Alpha core had more difficulties with device retention and that was actually to look to the right due to the higher melt rate often involved most of the time. That was what lost led to the loss of the device was a melt. In terms of retro prosthetic membrane the my cough had the highest complication followed by the Boston K pro. They got Boston K pro though some of those studies were actually done when they had the PMA back plate and that membrane rate has decreased after we switched to titanium glaucoma for the Boston K pro and the okp. Melting like we already talked about the Cara clear and the Alpha core and then infection was highest in the Boston K pro with an ophthalmitis and kind of gradually decreased from there. So kind of in summary, you know, there's multiple options none of them are perfect but it's you know, oftentimes these patients can be better than what they're living with with bilateral corneal blindness, it can be a really beneficial procedure for some patients. And luckily there's continued innovation in the field with the Lucia and then IOP monitoring. And I think there's some future potentials and some desirable changes that we could hopefully see in the future with new biocompatible materials, possible human cell cultures already looking into this within the cell cultures and real kindness inhibitors. Maybe we could do something for, you know, help produce or grow new corneal grafts tissue, xenographs graphs from different species essentially see if we can get something going there. We could have a pressure monitoring and also just increasing cost effectiveness in this new age of medicine, and hopefully something that can be easily produced and it's a tall order a lot of different things to consider but I think we could get there eventually. And so that's all I have here my references. So this is a Dr Olson Brett welcome good to have you're so great summary. It's it's it's very interesting I put in my first character prosthesis. I hate to admit it 45 years ago and it was a person who had been bear like perception for about 15 years. And I'll never forget that it was one of those unusual 2030 uncorrected the day after surgery it was it was just it was just dynamic. And the patient was so incredibly happy and we we ended up in this particular case, having to pull the lids down around it. It was an old Stevens Johnson would still don't do particularly well. And the interesting things that bothered the patient was that she she couldn't close her eyes. So, she, she had to develop kind of a little thing she'd put over when she wanted to, you know to close out the light. I loved it and, as you would expect with Steven Johnson for that early PMMA ended up having a little melt that we didn't see develop endothelitis and lost the eye so the same kind of problems that we talked about and then I get another one not long after that. And it was not being able to monitor and take care of glaucoma. And so these these are the same problems that you know to continue to persist. And it's interesting to see how it's evolved as you as you discuss the field that it's a niche area but for those who need it is very important is that there hasn't really been any dramatic breakthrough, there's just been a, a slow improvement in these different areas, but the same problems as now that existed then adding them all together over a long period of time sadly that still the majority of patients end up if they're going to try to have one for 10 years. Last I reviewed I don't know if you saw a study on this but I think the general consensus is the, you know, over half within 10 years, more like 70% are going to have a significant complication. That's that's kind of where we are. And I like the idea because glaucoma is often still, you know, so hard to monitor these eyes are so aberrant that it's that it's it's hard to know exactly how we measure that pressure. I saw a couple of these odontal character prostheses in Saudi Arabia they were going to Spain to get them. Well I was there they are the weirdest looking thing but it's amazing, one of them had been very successful about eight years and other for about five years so a lot of work and a lot of effort but you know, it, maybe, maybe, you know, using the patients on tooth and on tissue maybe you know that's that's something that you know was relatively viable but boy do they look strange. Absolutely yeah that's great comments and yeah I hopefully we can continue to make some bigger steps it does seem I agree like it's a little step by step progress but hopefully there'll be some kind of material breakthrough or something in the near future. Being able to sense have a sensor there that can tell us what the pressure is so that we really have a good idea and can monitor it and try to control it, rather than just largely it's largely watch the optic nerve. And by the time you can see the changes that are important. Typically you've had some pretty high pressure for a while and it's very hard pressure to control you don't have a lot of good options. Any other comments or not we can move forward with Eric Weinleiners presentation. Sounds great thanks Brett. All right. Okay. Can everyone see the slides okay. Yep. We're good. All right. So shifting gears a little bit. So we'll do a case presentation as a way to discuss this condition a little bit more. So my very creatively titled a contract of a lesion. So centers around a 19 year old woman who came in with redness and discomfort in the right eye for about three months. And she had seen outside ophthalmologist and hadn't improved at all with steroid or antibiotic eye drops. Past medical history is notable for psoriasis and atopic dermatitis and alopecia, as well as a remote history of absence seizures. She's on systemic medications, including an aisle for inhibitor dupexan and methotrexate as well as some anti seizure medications and some topical medications as well for her psoriasis and atopic dermatitis. And interestingly, in addition to the dupexan, she's been on some sort of systemic immunosuppression, starting with cyclosporine from age 16. So for at least the past three years or so. And this issue that she started having with the redness and irritation started a few months ago when she started taking dupexan. There are reports of dupexan associated conjunctivitis has initially chalked up to that. But the symptoms persisted and I'm getting worse and getting worse. So she came to you view for valuation. So this is what she looked like on presentation server acuity in the right house 2060 affected I in 2025 on the left. Normal pressures, normal pupils, motility fields and fundus exam. But this picture demonstrates is sort of the most notable feature of her exam, which is this very large area of injection. And this sort of mass, fleshy mass on the limb is straddling into the cornea as well with some leucoplacic white or lesions parts of it as well. And it was notably somewhat mobile, although she was a little bit difficult to examine. So, sort of stepping back. So normally, we were in the auditorium be the point where I would torture a resident as I myself have been tortured with questions during grand rounds. So the differential is essentially inflammatory and infectious. Conductivitis, sclerosis, scleroceratitis, super broad differential, granulomus disease or phytocellulosis. This really wasn't that likely. It was certainly ruled out in her workup. She did get systemic autoimmune workup, which is negative, some cultures were taken. So this sort of the mass lesion appearance. This is really thought to be more consistent with the neoplastic disorder. And for the differential for Olympus based countertival tumor. It's either a nine squamous papilloma or potentially malignant condition along the OSSN or CIN spectrum. So, in terms of workup next step would be biopsy. So an exceptional biopsy was performed for this patient is using the no touch technique which is reviewed here from 1994 paper. And the idea is that you want to excise the tumor in question in its entirety on block and with only touching normal tissue. So the original description of this technique is applying absolute alcohol to the tumor. Performing epithelial debris of the cornea where you sort of peel back the epithelium and fold it on onto the tumor. And then you take generous four millimeter margins, which cut down the contactiva and then perform a dissection underneath the tumor. And in some cases needing to take a partial thickness sclerotomy as well to ensure that the tumor is excised in its entirety. And again here just grasping only normal tissue. Oftentimes this is paired with a double freeze raw cryotherapy or on the edges and sometimes to the bed, as well as the addition of either a topical chemotherapy or anti metabolite. So this is performed in our patient. And again, another wasted opportunity to to residents. Here's the pathology. So I'll do my best at providing an interpretation. So notable features in the histopathology specimen is a thickened or aconthotic squamous epithelium kind of outline here is keratin pearls here at the black arrows. And then these notable vascular cores as well at the white arrows here. So these features, the acanthotic epithelium and formed around these vascular cores was most consistent with the sessile contactival papilloma. So shifting more into the benign spectrum of the new pleasure that we had considered. So we'll talk a little bit about contractile squamous papilloma. So it's a presentation and current thoughts on management. So these tumors, typically are exophitic, meaning they're either sessile or pedunculated so sessile like ours was were pedunculated where they arise from a central stock. Sometimes you can very rarely they can be inverted more than the government or my car cinema. They're sort of typified, both on histology and on the clinical exam as having spascular cores of the squamous epithelium, which you can see as these fine papillary vessels, which are sometimes called the hairpin vessels who you can kind of make out in this picture here. Importantly, contractile squamous papillomas as benign tumors are mobile over the underlying tissue, in contrast to malignant tumors showing episclerosis, scleral invasion, which tend to be fixed. These tumors, although they are benign, can display some dysplastic features either under the microscope after exceptional biopsy were manifesting clinically. They can be clinically as characterization as an our patient, the carrot pearls and the local plakia kind of go together simple for honor inflammation, and help people involvement, all of which betray some degree of dysplasia. In addition, papillomas can certainly be recurrent, and you can have more than one, which is more common in patients who have HPV as the driving factor, and also multiple conch papillomas are more common in children compared to adults. In terms of demographics, the typical age of presentation is 21 to 40. So our 19 year old patient is sort of right on the fence for, you know, fitting the typical patient. They tend to be slow growing and typically present with foreign body sensation or irritation, although as an our patient you can certainly have significant inflammation. They can present anywhere on the ball bar at Tarasil, people with contractiva, and the only established risk factor is HPV, which in depending on the study that that you read can be, you know, about half to 90% of the papillomas. Personally, our patient has some degree of immunosuppression for several years. There's certainly a thought that for malignant ocular surface squamous, new pleasure that immunosuppression can certainly play a role, especially as seen in patients with HIV. But there's no definitive evidence linking immune dysfunction to an high and comfortable squamous papilloma. The same is said for UV exposure and smoking. In addition, the clinical presentation and behavior of these lesions sort of sequesters almost into two age groups. Although these tumors are much more common in adults, about six times more common children are more likely to have larger lesions, multiple lesions, have treatment failure and then get recurrence. So in terms of diagnosis, sort of, I think a little controversial if these can be diagnosed purely on clinical features and treated as such. But certainly, when in doubt, excisional biopsy is called for, as these lesions can sometimes be difficult to distinguish clinically from a malignant tumor. In addition to clinical diagnosis and excisional biopsy, impression cytology is reported as a way to look at the dysplasia of the cells noninvasively. The high resolution OCT has been a modality that's been really heralded by the folks in Bascom as a way to help to diagnose and parse out the nature of ocular surface tumors. And then it really seems to have its greatest use as an adjunct to quantify and track response to treatment noninvasively. So there's a lot of different options actually for congenital squamous papilloma. So one of the mainstays is excision with cryotherapy around the margins and oftentimes paired either with interferon or anti-metabolite to the tumor bed during the time of surgery. There's certainly reports of cryotherapy alone, just sort of spot cryo to the lesions in question. And then medical options include oral smetidine, which is a histamine antagonist that at high doses can have anti-viral and anti-priliferative effects. Interferon either topically as a drop or intralesionally as an injection and then the anti-metabolites, including mitomycin C and 5-floriurosol. There's also some reports of using photodynamic therapy or even photo coagulation of the lesions, although these are certainly more experimental and are often advocated as an alternative in low resource settings. So given all these options, there's a lot of different ways you can approach it. It seems to me looking at the literature that the standard of care is either a trial of a topical interferon alone. So you make a clinical diagnosis, you say this is a papilloma and you treat the interferon to either shrink or resolve the lesion. Or to just go ahead and proceed with excision of cryotherapy without adjunctive interferon or anti-metabolite at the time of surgery. Then the other options are more, they have a greater role as secondary agent, second line or adjunctive treatments. The oral symmetry is often best used in children or in patients who have multiple papillomas. Interferon, other than as a primary agent, can be used as an adjunct both topically or intralesionally. Downsides are that it's expensive and the intralesional injection tends to have a flu-like symptomatology afterwards. And the anti-metabolites are also tend to be used more as an adjunct or second line for things such as recurrence. And you can run into ocular surface toxicity issues, especially with mydomycin C as compared to 5FU. And similarly for cryotherapy, more so as an adjunct to either interferon monotherapy or excision. And when we think about our topical options, so interferon is sort of the one that is touted as the preferred topical therapy in the literature. It's effective, it's well tolerated, but it's very expensive. And these patients can remain on it for quite some time. So interferon is given as one million international units four times a day until resolution, which tends to be about four months. So that can be quite expensive. So as a second line or alternative, 5FU or urusil, which is much cheaper, but you start to run into toxicity issues. And this is usually given as a cycle of one week on three weeks off and sometimes even one month on three months off. And mydomycin C typically is treated as a third line, similar cycling as 5FU, but much higher risk of toxicity issues, including little stumps of efficiency. In terms of the long term outcome, so these lesions tend to stay benign. So really what you're dealing with is recurrence. And rates of recurrence vary depending on the study, topping out at around 27%, so around a quarter. So close monitoring is certainly called for in these cases. A risk for recurrence, it's higher in children if excision is done alone without any adjunct, so no cryotherapy or chemotherapy at the time of surgery. And if the papillom is located on the bulb or couching type or spreads into the cornea, which unfortunately includes our patient. Interestingly, there's no association with recurrence risk and HPV or HPV subtype, even though HPV is considered to be one of the main drivers of this condition. And similarly, the amount of dysplasia, it's unclear if the more dysplastic lesions tend to occur, although it is known that recurrent lesions tend to be more dysplastic. So, kind of going back to our patient presentation, you know, once on exam, it becomes evident that this is a tumor and an ocular surface, some sort of neoplasia, either benign or cancerous. And then the question becomes, well, okay, now, wheeling towards biopsy is certainly the best way to get a definitive diagnosis, because it can be very difficult to distinguish the two just based on clinical criteria. So we're going to talk a little bit about OSDSN, ocular surface squamous neoplasia, sort of the malignant variety that's adjacent to papilloma. And you're oftentimes considering the two simultaneously when you're seeing a patient. So, ocular surface squamous neoplasia, it's the most common non-pigmented ocular surface tumor. These things do damage by being locally destructive and invasive. They rarely tend to metastasize, but you can certainly cause vision problems if left unchecked. They tend to appear gelatinous or leucoplacic, and it can also be papillary and sometimes difficult to distinguish from papilloma. So, in contrast to papilloma, which is a little bit of a younger crowd, OSDSN tends to be an older crowd in the 50s and up. If it's occurring in a younger patient, you should consider HIV immunosuppression or zero dermal pigmentosa as potential conditions that predispose to this in young patients. Similarly, the OSDSN is a spectrum, so from dysplasia to full-blown invasive squamous cell carcinoma with contratival intraepithelial neoplasia created by how many thirds of the epithelians involved in between the two. Treatment options are very similar to papilloma. We know that in some retrospective studies, excision with cryotherapy has a similar treatment and recurrence rate as merely local chemotherapy. However, this study did not include those who got excision with chemotherapy at the time of surgery. So the newer option of doing excision with cryo plus local chemotherapy, we don't really know how that compares to excision alone or chemotherapy alone. The role of local chemotherapy as an interferon mitomycin 5-a-few has been expanding recently, especially with increased tolerability of interferon. It tends to be used, it's very useful for chemo reduction. It's a large tumor where you cause a bunch of scarring if you excise all of it. It's useful as an intraoperative adjuvant and then also as a postoperative adjuvant, especially if there is positive margins. And importantly, ocular surface squamous neoplasia does carry a relatively high risk of long-term recurrence. Some studies reporting even up to 50%, especially in those with positive margins. So these patients do need to be monitored. And thinking about the medical options, same toolkit as for papilloma where interferon is preferred if the patient is able to afford to do so because it's effective and it's not toxic. Whereas the anti metabolites are more of a second line due to the increased toxicity and perhaps marginally worse success rates, although that hasn't really been borne out. So thinking about the different ways that you can approach a patient with OSSN is certainly reasonable and there's precedent if it's a low risk lesion that's obviously ocular surface squamous neoplasia. You can start with the interferon alone and then if that doesn't resolve it, you can do a salvage excision with topical or intralesional chemotherapy. Or if it's a big lesion, you can do chemo reduction, potentially with interferon or your anti metabolite of choice, and then followed by excision with cryotherapy and interferon. Or you can just proceed straight to excision if it looks like it's a moderately, you know, small to moderate size lesion where you won't cause local tissue destruction by sizing it. And then follow that up by chemo prevention with interferon or anti metabolite after excision. So dialing back into the land of benign counter title lesions and back to our patient. So she underwent excision biopsy of cryotherapy demonstrated that was a squamous pepilloma. So she was monitored afterwards. There was some concern actually for recurrence as can happen up to a quarter of these patients, especially the higher risk features as an our patient. So she's undergone two additional cycles of topical five flurry urus cell, which has resulted in regression of the recurrence, but then she just has some ongoing inflammation which is currently being managed. And then in terms of the lesion itself, she's just undergoing active surveillance plus. So I'd like to thank everybody and especially Dr. Manlis, Dr. Lynn, and I've listed a few of my references. I'm happy to take any questions. Awesome. Thanks Eric. That was a great presentation. Any comments from Dr. Lynn or Dr. Manlis. This Dr. Olson. You know, I've, in the past, some of these that you've had you'll have kind of a relatively larger lesion and multiple smaller lesions. And I don't know, I always felt that it was best. I mean, you try to get four millimeter margins around all of those you've taken a lot of conjuntiva is to just excise the larger one you get your tissue diagnosis. And then you just do a freeze thought freeze to these smaller satellite lesions and not have to excise them also I think, at least in my experience and then and then you watch, and then you've got other therapies and if it recurs and then you know you may have to do something additional But I don't, I just, my experience was you don't always have to excise these it often a freeze thought freeze cycle for these smaller lesions was quite effective I'm curious what, you know, Dr. Manlis, what, you know, Dr. Mifflin or Dr. Lynn, you know, feel about that. I think Dr. Lynn and Dr. Manlis are both co hosts now so I think you can unmute yourself you've got comment. Yeah, so I just, I had a comment that I did not do the four millimeter wide excision because that would be pretty much half her full bar conjuntiva. So I did just probably a one to two millimeter margin in this case. She did have a little bit of involvement of her sclerosis I did have to do a little thin sclerotomy. Most commonly if it's pretty mobile and apart from the sclerot I would not do a sclerotomy. This is Randy what what do you think about where you have a big lesion and you got a one or two small satellite lesions that are sitting next to it, just excising the big lesion and just do cryotherapy to the smaller and not excise them is that acceptable and I used to do that I'm just wondering if that's still reasonable. I haven't had that particular instance, usually I have a smaller focal lesion or I'll have a really, really large I've had very large lesions. My preference is for large lesions to start with topical interferon, if the patient can afford it. And then if there's either no response or insufficient response, then I'll go back in and excise and I've had like very large ball bar conjuntival lesions come down to nothing with interferon. And if there's even just a partial response, you have less of an area to size later on. As far as a large lesion and satellite I haven't done just cryo to satellite lesions. All right, well that was a great case I think we'll introduce time just keep moving and Mike Murray is going to give us a great talk on screening for subclinical care to conus and refractive evals. But before we do Dr. Manlis you've been unmuted so if you want to make your comment you can. Can everyone hear me here. I don't know if we're waiting for Dr. Manlis or not just want to check my sound though. We can hear you. Hey Dr. Manlis you're very quiet we could barely hear you. Just barely. Barely. Why I've got it turned up to 100%. My headphones must not be working. Can you hear me at all if I yell yell yell we can get we can barely make it but we can hear you Nick yell. Okay I'm sorry my headphones just must not be working. I've got them turned up to 100%. The problem with the squamous papillomas is they can have some significant atypia and some features that look displastic because was talked about including the keratinization the keratin pearls they can have nucleoli in them but the critical factor is is the basement membrane is absolutely intact throughout so even though these can look fairly aggressive they're strictly intrapithelial and and even on this one there were some aggressive features when you looked at the pathology and so these patients need to be watched very carefully for possible recurrence. So Nick is making a very good point and that is we like to think of these in specific categories and there's a continuum. And so we've got to recognize that where we've got something that represents continuum then they kind of act halfway between these different categories and they've got to be followed accordingly. Just briefly from a historical I mean the original work on trying to figure all this out in morphology was to categorize in very distinctive small morphological buckets. And as time goes on and we learn more about etiology of these we realize that many of the things we deal with are a spectrum. And there isn't really a clean we still call them in those because it's helpful and how they respond but but to remember that a lot a lot of these different categories are truly a spectrum and have to be recognized as such. Absolutely it's great discussion. All great points. So we'll keep going here with Mike Murray go ahead and get started. My name is Mike Murray I'm a PGI three. I'm glad to be invited by Brett and Eric and Dr. Mifflin to present some information from a review project that I was involved in recently about detecting precaroticonis in refractive surgery screening. So with the advent of a LASIK and PRK in the early 90s to late 90s. There was a spike in post refractive surgery at Asia. The first cases was reported by reports began to increase about this post refractive surgery complications and this has become one of the most important issues in refractive surgery is screening for proper candidates in the surgery. And I'm going to focus in this talk a little bit about caroticonis although there's other conditions such as you know police and marginal degeneration others that could be discussed and a little bit about some of the different screening methods have been developed over the years. So first a little bit about caroticonis. One of the first classification systems was the Anseler Kramer. People on the left there that was developed in the 1960s mainly based on the mean carotometry centrally and then also refraction and then some slit lamp criteria such as scarring. Later on in the 1970s and 80s there was development of the placido disc technology where rings that were concentrically oriented were shown on the cornea with a you know bigger space meaning a flatter area of the cornea and steeper space meaning a thinner area in those placido rings. And over the years some of these indices were developed one of them in the 1990s was called the Kythian compared among other things five points of the superior cornea it's a five points on the inferior cornea and the steep kind of K values between those, as well as the level of astigmatism, and then the SRAX which is a comparison of how irregular astigmatism is compared to and another system that was developed this was by Dr. Randleman was the ERSS, Six Asia risk score system, which went through, you know inferior steepening abnormal thickness, pre-optive kind of manifest spherical equivalent. And all of these were good systems for looking at keratoconus before screening for refractive surgery. In 2015, all of these societies got together the Asia cornea society cornea society of the US the European the pan American in a global consensus on keratoconus and tried to come up with a uniform definition and screening system for keratoconus and they weren't able to do it they didn't agree on a new staging system so unfortunately, just as the background, kind of like Dr. Olson was alluding to keratoconus is a big spectrum and not very well defined, especially the kind of subclinical or preclinical forms of keratoconus. So some of these definitions of keratoconus derived from the fact that it's known to be almost universally a bilateral disease although it may manifest in different levels of severity between eyes. So for improved keratoconus has sometimes been described as the other eye in an eye in a patient, a chronic eye, and as sometimes been compared to normal eyes a keratoconus suspect has often been defined as someone with normal appearing visual acuity and slit lamp findings. And it doesn't have, you know, a retinoscopy, scissoring reflex or any of those, you know, months and lit signs with the lid or the rizuti the corneal conical reflection when you shine nasally, the flesh ring or any of those things but that has abnormal findings on scans, such as topography. And for the purpose of this talk and honestly what we recommended in our review paper was that a lot of these vague terms be just lumped into the category of prekeratoconus. And the difficulty in screening and what I'll kind of talk about is we have historically and with the advent of some new technology, some pretty good methods at determining when an eye is keratoconic and shouldn't undergo refractive surgery. But it's more difficult in determining these prekeratoconic eyes and detecting them or to detect these prekeratoconic eyes as well as the ones with frankeratoconus. So this is a description a little bit about a new technology that was developed in the early kind of 2000s and rolled out in the 2010s shine fluid imaging. And so, instead of just using a direct placebo just image straight on the cornea shine fluid gene uses technology in order to align an image plane and have a subject pain off to an angle. And when you think about looking at the cornea at a slit lamp this is key. The difficulty and I don't know if we have any photographer gurus out there is making sure that you're in focus across an entire image so if you load this train for example. Without shine fluid imaging you could get maybe one of these train cars in focus but you couldn't get the entire training focus and involves kind of a mathematical adjustment of the lens plane such that the image plane the subject plane the lens plane are all able to intersect at a certain point. And what the pen a can which I'll talk about a little bit in detail does is it rotates camera around to get 25,000 data points. Because of these data points that are able to do an analysis not just on the right which would be a topographical image of elevations but instead a tomographical image. So the surface of the front cornea the surface of the back surface of the cornea and also thickness and all technology. So what we did is reviewed all of the studies that had compared these pre cared iconic eyes with normal eyes. We were looking for indices that would provide an area under the curve of point eight or greater. So basically, if you compare true positive to false positive a value of point five basically means that's a wash value one is perfect and a value of point eight is pretty good. This is an example of one of the indices and if you could just see the area under the curve for this and to see which is I'll describe a little bit later, it was pretty. Oh, these were a couple of the indices that we found that were good for pre cared iconic screening. One is the bell and ambrosia and hands dictation display and Roger relational thickness packet metric progression indices and index of vertical symmetry. I'll throw a little bit about these here just briefly. So on the pentacam. This is a corneal thickness spatial profile so basically it compares how thick are things at zero on your left which is central cornea out to the peripheral cornea and the diameter and it should progress and they have kind of mean values and that standard deviation there of a normal cornea and then the bottom one is a percentage thickness increase so how you can see here this is a thin cornea on the left and then a chronic cornea on the right as you can see on the right dips below that corneal thickness, meaning it is getting thinner quicker than you would want to. So one of these indices is the bell and ambrosia enhance the static display. This is kind of a standard deviation from a bunch of different values so mean anterior elevation posterior elevation compared to those that it should be a kind of an ellipsoid shape on the posterior and anterior surface and this packet metric progression, the thinnest corneal thickness and then a value called ambrosia relational thickness. Ambrosia relational thickness is kind of cool it takes a value of how thin the cornea is just a simple packet metric value and then how quickly it's thinning out with this percentage thickness increase and it just divides it so it lets you know how thick and how fast it's getting thick. With these indices, a pretty reliable evaluation of the subclinical care conus is able to be manifest and as we're kind of short on time, these were just kind of like a cheat sheet that we put in our paper of values that are useful to detect both clinical care conus and subclinical care conus. Finally, just a couple conclusions. Advances in corneal tomography such as penicam and then we did some other evaluations like galley information about the posterior corneal surface and help to create these indices that are pretty reliable for not just detecting care conus but these pre care conus patients. Future work needs to be done like we talked about with the standardization of care conus, maybe a global summit or something we'll be able to get that. Obviously screening carefully for pre care conus patients will help us to do the first do no harm and especially needs for refractive surgery patients where at Asia can be really debilitating and tough to deal with. If you want further information. These are the titles of the review. You weren't able to go over the galley and then also some of the corneal biomechanical systems like Corvus that use a puff of air and then analyze. Lastly, big thanks to Dr. Mifflin for helping this presentation and Dr. Mushfar as well as being a mentor and being involved in research here and a couple of my resources and happy to take any questions. Awesome. Thanks, Mike. That was a really good talk. I think, you know, in terms of time we might have time for a comment, but otherwise that we could probably just email Mike if you have any questions or comments. Sorry for going a little bit over today. Technical difficulty there for a second, but I appreciate everyone joining us today.