 Good morning, everyone. It's about eight o'clock. My name is Lee Ferguson. I'm the new first year resident here at the John A. Moran Center. I have the distinct pleasure of introducing the three presenters for this morning's grand rounds. The first presenter is Dr. Brent Betts, and his talk will be about unknown corneal lesion. First off, I want to thank our patient for coming in early this morning, and she's also here today to hopefully hear some discussion that we have about this interesting case that we have. So this is a case that has seen most of the corneal service. The chief complaint presenting was there was a bump on the patient's left eye. In history, she's 26-year-old female. Lesion started as a white dot about a year and a half ago now. She did have surgery to remove the lesion, which I'll go into a little bit later a year ago, but in the past six months, it's growing back with a vengeance. Her vision, she reports, has been blurring her left eye during the last three months. She denies any eye pain, any redness, removal irritation. She does have difficulty wearing contacts, and like I said, that were the fourth opinion that she sought for this lesion. Passable chemistry is pretty insignificant when you see her eye issue. Examination, she's 23-year-old right eye, 25-year-old left eye. She's a contact lens wearer. You can see she's a high myode. She does have some irregular stigmatism in the left eye, limiting her vision. But everything else is pretty unremarkable, including her IOP. Anteris segment examination with Siltland. You'll see a photo of her left cornea, but everything else was unremarkable. We did not do a fundus exam on her visit. So here's the Siltland photos. She did have her contact lens in, so you can't appreciate fully, but I'll try to explain some pertinent points here. But you can see here she has this lesion of her inferonazle quadrant. Measures about 5 millimeters vertically by 4 millimeters into the visual, near the visual axis. You can kind of see there might be, you know, a little bit more prominent vasculature at the limbis where the lesion is growing. And here's a close-up shot, but you can see it's kind of this yellowish color at the leading edge. It appears that there's some kind of crystalline or lipid deposition. One thing that it's hard to appreciate because she has her contact lens in, but actually when you get into the cornea there's actually clear cornea over the top of the lesion, so you can appreciate that's fairly deep into the stroma. You can appreciate the lipid cartopathy here. And then here again. We did enter a segment OCT and you can kind of see here it looks like the anterior stroma and the epithelium is intact and fairly normal over the deep stroma lesion. I actually, when she came this morning to Gonioscopy on her and the lesion is either full thickness or it bows in the peripheral cornea, but it's not invading the angle at all. Here's some tomography. You can appreciate she has quite a bit of a stigmatism centrally and you can see her posterior float is really bowed in where the lesion is located. So for past OCT history we got great notes from where she was treated in San Diego by a prominent cornea specialist. She was evaluated first in May 2015 down there. There's kind of this described as like a red spot by her cornea for two months previously and felt that sometimes it was hitting her lower lid. She was treated with medications over the next two months and you can see she had topocleroids, oral NSAIDs, oral corticosteroids, none of which changed the size or shape of the lesion. And then she was also treated with valicycabir due to concern for maybe some kind of her pettic process. Nothing changed me of that. So it was decided to do a full laboratory work out. Everything was within normal limits. And so kind of the working diagnosis through most of her visits down to see this cornea specialist was nodular scleritis interstitial carotidus. I'm not saying that's what it is, but just kind of as an idea of what they were thinking. So they decided to do a biopsy of it. So they did about 10 weeks after she presented, after she had tried all these oral and topical therapies. And then postoperatively and I'll go through the operative report next, but she was on Durazol twice a day, a lever daily and then a best advance for the first week. She did a long Durazol tapering was on it for about six weeks to two months after the procedure was performed. But this is, I basically copied this straight from the operative report. The contractile was pulled back. The lesion was resected with a crescent blade till it was flushed with surrounded cornea scleritis. And then, you know, he said it seemed that there was some kind of yellowish lipid mat underneath and this was taken in its entirety. But you can see the patient provided a postoperative photo. Oh, and here's the pathology report. This is once again taken. It was not read by an ophthalmic trained pathologist. But there was this benign screen is up feeling with sebacellular nodular clestinal lymphocytes, histocytes and ethereal cells and stromal cells. There were some markers that were that were done. Some of the markers, I didn't include them in here, but everything was negative. Any kind of markers they did. Post-reception, you can actually appreciate it's kind of blurry because it's a cell phone photo. But you can see here, it's a lot different looking than what we're seeing today. There is still this yellowish material at the limbis partially onto the cornea. But, you know, compared to today, that's quite a bit different. This is about a year later. And so we're bringing it today because we don't really know what this is. There's some things that are differential diagnosis, infectious things we were thinking about. We do know that she was on Durazol for two months postoperatively, never had any kind of, you know, infectious appearing thing going on. So we think that's pretty low. Congenital, you know, when we first looked at it, I thought, was this a limbo-dermoid? Those typically don't occur like this. And it really only started a year and a half ago. Inflammatory things all going to a couple, one diagnosis that I'm not proposing that this is, but just food for thought. And then neoplastic, there has been a, I didn't include photos because I couldn't get permission, but there was a, there was a case report of benign lymphocliferative hyperplasia, baryngoactive lymphocliferative hyperplasia with corneal involvement. And it did have a fairly, you know, kind of similar to a parent star patient. But that patient also had follicles, kind of classic for lymphocliferative hyperplasia. And had completely opaque corneas and required keratoplasty. And when they did pathology, there were there were germinal centers and all kinds of things suggestive of that. But we also, you know, thought as this, sometimes you can get CIN that looks like this. Not quite like this, but you know, we're, this was all in our differential. One thing I just wanted to bring up, because Dr. Lin actually had a recent case, is this thing called epi-bolver nodular fasciitis, sometimes just called nodular fasciitis, the cornea, but it's benign fibroplastic growth. There are only about 23 cases total in eight case series published in the literature. It's thought to be associated with trauma and inflammation. A lot of the case reports are associated with floppy eyelid syndrome, which our patient doesn't have. But the thing that is kind of classic is you have this really rapid growth. A lot of times people the treating physicians were concerned about some kind of malignant thing. But it's almost always just this kind of mixed, a mild fibroblastic tissue on pathology. I was fortunate enough to know two people who provided case reports. The top one is kind of a really striking example out of Cleveland Clinic, but you can see this is a huge nodule on the cornea that was resected multiple times. And once again, pathology didn't show anything really, it was just kind of my eryfibroblastic growth. And this is our case that was about a year and a half ago. But you can see here at the limit, there's this elevated lesion. This patient didn't really have any pain with it. Just kind of showed up. No history of trauma in this case. But you can kind of appreciate it's hard to see on here, but it is a little bit yellow, you know, kind of same as yellow color as our patient at the limbis. But, but like I said, we really, you know, include this in our differential. But once again, our patient has no history of trauma. She has a chronic contact lens wear, but wears them appropriately. But they are the very high correction soft contact lenses. So our kind of we thought about treatment options because it is nearing visual access and it's inducing a lot of stigmatism. Number one is observation. It seems like it got worse after she had an incisional biopsy. We thought about doing cryotherapy at the limbis to shut off maybe if there's some feeder vessels. More extreme things would be a complete incisional biopsy. You'd want to get ultrasound before we even consider that to see how deep this actually is. And then we thought about doing maybe like a partial repeat biopsy and using mydomycin C afterwards. But we just wanted to bring it to here to get some expert opinion because like I said, we just are not entirely sure what we think this thing is. So appreciating the comments or thoughts if anyone hasn't any. I'll just show the lesion again. Oh, this is a, you know, obviously a fascinating lesion. Very concerning. See where some of the residents so so first of all, as you look at a care for the sitlamp and where is most of this change occurring? Tara, where's most of this change occurring in the cornea now? Is it superficial? Is it deep? In fact, the superficial cornea as you get out towards the head looks looks really normal as the epithelium. And so this is something that you can follow as you get along to the front of it. I mean, this is right at decimation. So you've got to tell me that this is going, this is mainly posterior cornea where these changes occurring. And this is going right down to get it. So I know Francis Miles, he's a good friend and an outstanding corneal specialist. I mean, I have a feeling as what he was removing was some of this thicker superficial change, which I think is likely secondary. And so the pathology may not really have gotten that, you know, to where this is. But I've learned, I mean, those are the kinds of reports you see from a, you know, a non ophthalmic pathologist. And often that kind of stuff is just almost meaningless. And nothing should be done until we get the slides and we get the specimens and have Nick look at this in detail and try to give us a better idea of what we're dealing with on this. But that's the problem. And most of the things we deal with, be it be at CIN or be it, you know, stem cell failure or the rest isn't deep in the cornea. Something you can use these superficially take out, whereas most of this change is coming in extremely deep. And if you're and if we know it's a lesion that somehow scary and otherwise can be treated, and this is going to require a full thickness corneal resection in order to get rid of all of them. So the other important thing is, is we keep talking about it, it's yellow. What does it what does it mean that it's yellow? You see something like that. I mean, what, what does that tell you? Yeah, yeah. So don't mean anything that's causing new vessels to grow that are not fully formed and fully mature will leak lipid. And that causes a yellow change. So that's, that's a non specific. And all, all it's telling you is, is that you've got immature new vessels that are growing. And that crystalline stuff you see right along the edge. That's, that's what it looks like. And it gets thicker. It turns around into yellow in that particular area. So often what you do on these tough ones is you try to, first of all, decide, you know, what this isn't. And you know, obviously, the big thing we deal with all the time is infectious. And the one area that you think of an infectious is some form of interstitial keratitis, which is really not infectious. It's almost for sure type of immune reaction associated and what's what would be the most common cause of an interstitial keratitis in association with an infectious agent? Was that chickenpox? You know, chickenpox a deep deep interstitial keratitis would be number one herpes can do a bit of everything you can always through that differential. So, you know, we got to think about that any of that Ikea associated those is a form, however, of an inflammatory reaction. It's not infectious at that point. So, out and out infectious, extremely unlikely. We're not seeing any other signs of that. Typically, that is going on a lot faster. You're going to see a lot of vessels that are engorged. So I think we can kind of rule that out. Some type of neoplastic, some lymph. I mean, if it is, it's most likely some type of a lymph or proliferative, my guess. And Nick, don't you agree? That's got to be sitting on that list pretty well. Some type of a lymph or proliferative. You know, I'd love to see the pathology on this because I haven't seen anything like this before. This is very interesting. And, you know, it certainly doesn't look like a superficial pathology that's invaded deep. But so it doesn't look like CIN or variants of CIN before just doesn't look that way. And, you know, with the deep, that's definitely deep right there. If they did just the superficial biopsy, we may have missed the path completely. So it'd be good to look at it and see. But, you know, with the deep lesion like this, you know, the differential that Doug Rolson was talking about, some kind of infectious or inflammatory reaction secondary to that, in terms of lymph or proliferative, I've not seen a lymph or proliferative lesion in the deep corneal stroma before. We're in uncharted territory. This is definitely a neat-looking lesion. I've never seen nodular fasciitis of the cornea either. There was, like I said, one case before, he's out in Malaysia and this lady had bilateral corneal infiltration from lymph or proliferative. And they actually had anterior segment OCT that showed, you know, kind of full thickness evasion. But there wasn't, it didn't spare the anterior cornea. So it had that classic salmon patch appearance too. So it was, you know, this doesn't fit in any category. No, no. I mean, the kinds of things I've seen that are somewhat like it, you know, in Saudi Arabia, we quite commonly see pyogenic granulomas and they can come in really deep. But it was pretty obvious that, you know, there've been some preceding lesion. They tend to really heap up and be huge on the surface. The other thing that you could see growing that's quite deep would be some variation on the dikteoma. That's why I ask really strongly, was there anything there beforehand? Was there any change? And really, you know, just no evidence that there was some really small germoid or something that was sitting there. I mean, that's an area that I have. So I think the key for right now is to find out exactly what it is. And relatively rapidly, because this is growing and it's already affecting vision and it could soon be in the visual axis. So, I mean, I think we got to get that, all of those slides and the rest and Nick's got to look through to see if we can come up with at least some area. And if not, then it looks like it's a little thicker and a little easier to get to out of the limbus is to get, you know, a punch biopsy where we can get down relatively deep to get it out. And then Nick, you know, work with pathology about maybe some stains. We'd like to know, is this in the immuno category? Is this in lymphoproliferative? Is this in the, you know, some unusual form? I mean, if it is some type of an unusual malignancy, and this will be the first reported case. I mean, I've never, but it's got to be in one of those categories, for sure. And one way or the other, we've got to find out. Because, I mean, this could be something that should be treated with low dose radiation rather than trying to do surgery. Or this needs a definitive excisional biopsy, which I think has got to be a full thickness, and you got to get out and you've got to try to remove all of its there. Certainly a doable surgery and something we've done before, but you know, this can result in a lot of irregular stigmatism and other issues or problems. But better that than, you know, this thing grow through the visual axis, which it looks like it could be doing relatively quickly. Amy, what do you think? Any of that help with your thoughts? Yeah, so, I mean, in that case, I have a fear that people are not really fasciitis, and people with my arm are not. So, I took half sclerolusia at all. It was, you couldn't really define where the lesion was, where normal scleroma was. So, what I did was I kind of shaved it off and maybe went a little bit thinner. Right. But I didn't, I couldn't really tell how deep it was going. So, it might have a full thickness, but in that patient, it did not occur at all. Interesting. You see how deep this is? I mean, you can see this right at decimally. So, you get this here. You really got to go full thickness. I, and I think we need to report back, obviously, but the first thing is, is let's ASAP get what pathology we have and, you know, let Nick take a look at it. For those of you who are out and around, I don't want to knock general pathologists, I mean, they do a good job, but you know what we say when there's an exam done by, you know, in family practice or by internist friends, when they put down W-E-N-T-W with W-N-L, you know what that really means? We never really looked. They don't have a clue what's happening in the eye. And general pathologists, I mean, they'll put it in categories, but by and large, they just, you know, don't, don't have a sense. So, it's a very, always a good thing. I mean, they'll tell you, they can sit there and tell you, well, this is cancer and superficial, but there's a really good lesson for you. You know, you've got to get this to an ophthalmic pathologist. And the ophthalmic pathologist, the other great thing, once you get it to one, I mean, you're, you're kind of tied into a group. I mean, Nick, you guys share, I know you share stuff all the time with each other, and it, it, it is, it has its own separate area and separate nation. And we, we got to figure out exactly what this is. So, before we can decide just how to treat it. But, having a general pathologist read IPATH is equivalent to me looking at a liver biopsy. You know, I mean, you can look it up in the book and say, it looks like this, but it really isn't just a different, it's just a different group of, of lesions. And so, you'll often get a vague, you know, a vague report that says infiltrate with chronic inflammatory cells or something like that, but it really isn't helpful. So, if we get the slides right away and blocked too, if you can get that in case we need to do some special schemes with that. I fear they're too superficial. I fear they're probably, they were getting secondary changes and they weren't getting right down into where the lesion is. But, but let's, let's determine that first. And if, if we go for a biopsy, you know, out of the lumbus and got to get pretty deep, I think, to make sure we know just where, and that, that's where it started. I mean, that's, that's a problem where the money is. But this is, this is, I've seen a lot of weird stuff, but this is, this is out there in the fascinoma area. So, let's, let's find out what we're dealing with before we try to treat it. Thank you everyone. Thanks for our patient for coming in today too.