 Welcome, everyone, to our subspecialty grand rounds. We're very excited to have Jason in the back and Dr. Mushfar in the back to provide some cornea expertise as well as our presenter. I don't want to forget Joe Hatch, who is the original cornea surgeon of the Intermountain West as well, who's in the room. So a big thanks to Carl. Carl is a current cornea fellow. He came to us via medical school at Drexel University and then did his residency in New York. What I like to say is in Jamaica in New York, and he can explain what that actually means. But again, we'd like to thank Dr. Mushfar again for helping get these cases together. Yes, Jamaica was an interesting place. I'd like to thank everyone for allowing me to be here this morning. I'd like to present intriguing corneal cases. I'd like to thank Dr. Mushfar for providing these for us. And I thought I'd start with two more simple cases that we can have a little discussion about, and then a third one that's more of an interactive case that's a little longer and a little more interesting. So the first case is a 63-year-old female who presented originally to Dr. Bernstein with headaches and poor vision in the left eye. And she has a past medical history of non-insulin-dependent diabetes, mellitus, asthma, depression, and migraine. And she has no past surgical history, no trauma, and no real known or unknown conditions of the eye in her family. And really no ocular history in the past. She really has had a couple of eye exams with optometrists, but nothing significant in her history. Her vision was 2020 in the right eye, 2250 in the left eye, and four millimeter pupils, no APD, full EOMs, full visual fields, normal pressures, normal lids, lashes, white and quiet. Interestingly enough, she had full stromal thickness, well-delineated ring-shaped opacities in both of her corneas. And these didn't involve epithelium, decimates, or the endothelium. And we're pretty symmetric about two to three millimeters in both eyes. And deep and quiet, one to two plus NS, one plus cortical in both eyes for cataracts. And a posterior exam was significant for a pretty large macular hole in the left eye, no subretinal fluid, but everything else posteriorly was normal. So we saw her for this corneal finding. Obviously, there was a more important thing going on, which was the retinal hole. But this is what we initially saw. You can see that there's this central corneal ring right here. It's stromal. It's full thickness from anterior to posterior stroma. And kind of outlines the pupil right here. Before we looked into that any further, she had a vitrectomy and ILM peel. She had C3FA gas placed. And we did a cataract extraction with a posterior chamber intraocular lens. And then we kind of looked further into these strange corneal rings that we had never seen before. This is the right eye. This is the left eye. You can see they're very symmetric. Outline both pupils. Again, this is the right eye. You can see here, the cross section of the rings that goes pretty much full thickness. It's hard to tell here whether it really involves epithelium and the endothelium. Here again, you can see full thickness, stromal opacities. Here's a vasante anterior segment OCT. You can see with this cross section right here. Again, you can see this hyperreflectivity right here that shows it goes. It doesn't involve the epithelium. It's hard to say here whether it involves the endothelium, but we don't think so, or decimates membrane, but you can see these definite areas of the opacity right there. And she didn't have any history of elevated lipids, no antirhythmic, antimalarial, antiromatic drug use, no deficiency in mucopolysaccharide or amino acids in the patient's family or herself. So we were trying to figure out what this was because we had never seen anything like this before. And we looked in the literature. And whenever we see any type of corneal opacities, we go through the differential. And obviously a Kaiser Fleischer ring is something that comes to mind, but this patient don't have Wilson's disease. Juvenile arches is a possibility as she was younger, but much more peripheral. We went through the dystrophies, something like central cloudy dystrophy of Francois or shag green, but these don't really look like that at all. Even those can be central. Arcus furrow degeneration, Terian's marginal degeneration, these are all peripheral findings that can form sort of a ring shape, but not high on our differential for this case. Herpetic discoform keratitis can be ring shape, but it looks completely different than this. And then you can think about immune rings, coats rings, PUK, but a lot of these are unilateral or at least asymmetric. And with those two rings, they show some sort of nitus for that immune response of that immune infiltration. And when we looked into the literature, one of the main we saw was one by Mellis, who in 1998 in the British Journal of Ophthalmology described in a 25 year old male. And this was a little bit different. It was eight millimeters in diameter. And, but this similarly had no medical or surgical history that was pertinent, no involvement of Bowman's, Decimazer, endothelium. And he had some pretty extensive testing, hematologic general medical testing, and they didn't really find anything for him. And similarly, he did not have any symptoms. He had no glare, no halo, no blurry vision. And this you can see is the larger eight millimeter ring in this 25 year old male that is pretty insignificant. You'd be surprised that that did cause some sort of glare, halo or blurry vision. You know, kind of similar in the fact that it's symmetric and that the patient doesn't have any reason to have it. They also described in that same article in 1998 that they had found five other cases where patients either had a unilateral or bilateral. Three were unilateral, two were bilateral. Stromo rings that they didn't know why they had this. There were no findings there at all. It was hard for me to review that literature because it was all in German. I haven't brushed up on that in a while. But you know, there hasn't really been a lot in the literature and we don't really know what this is. That's one of the reasons why we wanted to present it. See if anybody else had any ideas of what this could be. We contacted a couple other corneal specialists from different universities and they had noted they had seen things similar to this before. Maybe a little larger, maybe a little bit smaller. Bilateral, but they had not found any reason for these findings as well. And you know, for this lady, she's 63, she has no symptoms, she has good vision at least in the right out of the left eye had the macular hole. You know, should we put this lady through a million dollar work up to try to figure out what this is? Or should we just let things be and kind of let her live her life and monitor her and make sure things don't get worse? I don't know if anybody has any thoughts. That's a great point, thank you. So we're not really sure. We know that she went to an optometrist two to three years before. She had been evaluated by Dr. Bernstein and they had mentioned something to her. They didn't really make a big deal of it. She wasn't referred anywhere else, but she knows that it had been around for a couple of years, but again, hadn't had an eye exam in 20, 30 years before that. Between rings and high myopia. You know, I didn't come over anything like that in the literature, but that's a good point. I'll have to take a look at that. Great, let's move along to case number two. This is a 73 year old female who presented as a referral from an optometrist on the outside for just a corneal opacity and multiple corneal opacities and the patient was asymptomatic when she presented. She had 20, 20 vision in both eyes, no APD, full EOMs, normal visual fields, normal pressures. And lids and lashes were normal, white and quiet, corneal and congenit sclera and she had these numerous scattered and variably confluence anterior stromal opacities in both eyes, the left more than the right. Normal iris, normally anterior chamber lens and fairly normal posterior exam as well. So this is the right eye. As you can see, she's nicely white and quiet, a little bit of vasculature right there, but you can see these anterior stromal one to two millimeter here, opacities smaller here, but they're a little bit confluent. Kind of patches, kind of fluffy, maybe crystalline in the right eye. Left eye, a little more significant, a little closer to the visual axis, more confluent, but that same fluffiness could almost call some of these satellite lesions when you're looking at them. Nice cross-section, you can really see how these stromal opacities are in the anterior stroma. This is a good example right here. So as far as these opacities, we're wondering exactly what they are. We don't have a great history on this lady. She's not a great historian. Could be infectious, unlikely, no injection, but could fungal has areas of fluffy white, has satellite lesions, but doesn't typically look like that. Herpetic, maybe not an active infection, but oftentimes patients have these anterior stromal opacities that can be scattered across the cornea. Maybe a dystrophy, macular, granular doesn't really look like it at all, but you gotta think about the dystrophies. Could it possibly be a lipid deposition or some sort of crystalline deposition? Or could there be, have been in the past, some sort of chronic epithelial defect in both eyes? Patients who have these epithelial defects over time, if it stays that way, can develop these anterior stromal opacities. Usually it's more diffuse in one localized area and not as scattered as that, but these are all possibilities. So we dug a little deeper and did find out that the patient had been seeing a hematologist and had had a recent diagnosis of monoclonal comopathy of undetermined significance or MGUS. And this is a condition that involves 6% of the people in our population, 60 to 80 years. And it's a slight elevation of a monoclonal para protein. And these patients must have normal plasma cell counts because we need to rule out multiple myeloma if they become elevated and they are transferred to that diagnosis. And it's thought to be a precursor of multiple myeloma. And the low percentage is one to 3% can transfer their diagnosis from this to multiple myeloma every year. And these patients are yearly monitored with serum electrophoresis to specifically screen for that. What other hematologic disorders have corneal findings? Well, chronic lymphocytic leukemia, there's been some case reports, have talked about circular superficial stromal infiltrates. Some of them, there's been a couple in virgin corneas, a couple in actual graphs of patients who've had penetrating keratoplasties. But the most significant one that we see is in patients with multiple myeloma where they have these crystalline, either anterior stromal crystalline deposits or they can have copper deposits on decimates membrane and sometimes they're diffuse and central and sometimes they can be peripheral and patchy. And the reason for this is they can have hypercupremia related to their multiple myeloma. They can also have lens capsid deposits as well. Also, Waldenstrom's macroglobulinemia can have a carot conjunctivitis but not necessarily deposits of stroma. This is an example of the crystalline deposits in multiple myeloma. It looks similar to our patient but not as patchy, not as fluffy, much more crystalline as I was describing. So what should we do for this patient? The vast majority of these patients are not treated for their problem. They have a slight elevation, they're monitored by cerebral electrophoresis but they're not given any treatment and in fact it can be pretty toxic at times depending on which one is used. So generally no treatment is necessary. They're generally asymptomatic and for this lady, even though she had an area in the left eye that was kind of encroaching on the visual axis, she did not complain of any glare, halo or blurry vision. So I think that for her monitoring progression of these deposits and also it would have to be a discussion between the ophthalmologist and hematologist if it did become a problem, whether systemic treatment might be an issue because in patients who have multiple myeloma and have these findings, there's regression of the corneal findings when the systemic disease is treated. Any questions or comments? Yes, Dr. Olson. So well. That's a great point. And maybe you could, by alerting whoever's taking care of that patient, systemically you could prevent them from having to have dialysis because maybe you catch them going right into renal failure. So something that we can really help the patients with other than the ophthalmic findings. In case this is a little bit more in-depth and I'd like a little bit of interaction with this. This is a 67-year-old male who presented the Moran Eye Center for worsening vision. The right a little worse than the left who has a history of hypertension, hypercoronial. And he had a pretty extensive ocular surgical history. Lasik in both eyes 15 years before presentation. An enhancement in the right eye only about seven years before presentation. He had a single intact placed in the left eye three years before presentation. Then he had conductive care toplasty two years before presentation in both eyes. And then he had a posterior chamber intraocular lens in the right eye. One and a half years of presentation. So we didn't have a lot of details on a lot of the back and forth between the surgeons and the patient for these surgeries and enhancements. But as you can tell, we have a certain type of patient population who demands perfect vision and wants continual treatment. And this is one of those types of people. And stringently enough, the patient didn't have too much of stigmatism on presentation. About 2.25 in the right eye, 3.5 in the left. But the vision, regardless, was not great. 2070 in the right eye, 2050 in the left eye. You can understand why he's not happy, especially having all these procedures. So Liz and Lash's were normal, white and quiet, conscience Clara. He had LASIK flaps as we know, nasal hinges in both eyes, CK in both eyes, and the intax in the left as we discussed. PCIO on the right, one plus NS in the left. And pretty normal posterior segment, no macular findings that could explain why his vision is poor. So unfortunately, we didn't have any photos, but I thought these drawings would be very valuable in explaining what this cornea's looked like. So you can see in the right, they had a PCIOL and the nasal hinge here with the LASIK flap. And CK was done in both eyes superiorly, I guess in an attempt to try to steep in that area, that must have been a significant flattening. And then you can see the single intax segment here. This deposition is just cholesterol deposition that can happen in the more central area of the intax. So the right eye, the topography shows definitely some significantly irregular stigmatism. You can see very steep area right here. Not a tremendous amount, only 3.12, but definitely very irregular. Left eye is more regular. Understandable why his vision is better than the left eye. So what's our diagnosis? We diagnosed him with a regular stigmatism in the right eye as some of the regular stigmatism in the left eye, but what should we do in this situation? This patient comes to us, he's had all these surgeries before. Honestly, we'd rather not have to do another surgery on him because the options now are not great. He's not gonna have 20-20 vision. And I don't know, so what does everyone think? What should we do first for this patient? That's a great point, yeah. And then if it doesn't work, we should probably try it again. And then maybe even try a hybrid lens with a rigid center and a peripheral skirt. That's a great point. So rigid gas permeable lens, yeah. You know, I listed a couple of other things that are possible on our list of surgical interventions, but something that we'd rather not do. Another single intact in that eye, an astigmatic caretotomy, maybe a piggyback twerk lens, but probably not. And our last line of defense is the penetrating caretoplasty. Some of these patients cannot tolerate these lenses, so that's the only other option. And we'll just talk about the left eye real quickly here, but this is the last slide, we'll really address the left eye. Since it was more regular, I think maybe could have benefited from the astigmatic caretotomy, or maybe even a cataract extraction with a twerk intraocular lens in that eye. So yeah, we decided to do a rigid gas permeable contact lens, or maybe a synergized hybrid lens in that eye. And he did try once, he made a good effort, failed the trial of the lens. He had painful, painful one that contact was in the eye. He had poor vision. And the exam was very similar as to what it was when we saw him four months prior, five months prior, excuse me. A little bit, yeah. He did have some vision, he did some improvement in his vision, but he could only keep it in for a brief period of time. He couldn't even make it out of the office with that contact lens in. So he actually tried it again, which was nice. Tried a little bit different fitting, but failed the second time. So we decided that we would try penetrating caretoplasty. We talked to him extensively that his vision may not improve, he might have this penetrating caretoplasty, he might have irregular stigmatism, he might have exactly the same problems that he's having right now, but he was extremely adamant in having another surgical procedure. So we decided to do a penetrating caretoplasty, a millimeter graft in that right eye. And we used 16 interrupted 10-0 nylon sutures. And then we followed him for three and a half months and began taking out those sutures. We used our topography to guide us, taking out the sutures at the steep axis every time. And by eight months, all the sutures were removed, but he had irregular stigmatism again. And a lot of it, 10.68. So we went from 3.1 something diopters of stigmatism to 10.68, and his visual acuity actually decreased to 27. On his manifest, he had 8.5 diopters of stigmatism. So, you know, this is a tremendous amount of stigmatism, you can see it here on the plethora rings, the shortening in the axis of the steepening. So, you know, again, does anybody have any ideas what we should do here? Dr. Olson. So what? That's a great point. So what? That's a great point. What do you think about doing larger grafts? I know we found that doing larger grafts, making the edges closer to the limbis, even though it increases the chances of rejection actually decreases the chances of stigmatism in those patients. That's not a great situation. Excuse me. Thank you. Dr. Mushford, Dr. Werner. Dr. Hash, yep. It was the degree of stigmatism? It was 10 point, about 10, like 10.3 or 10.4 diopters. 10.3 or 4 diopters. That's a great point. We'll talk about a couple of those things in a second. Dr. Olson. All right, so that's, we have a lot of options now. A couple of them that I'm gonna talk about are astigmatic keratotomy, wedge resection, which you talked a little bit about, Dr. Hatch. LASIK, or PRK. And I know it sounds crazy, but depending on what modality you use, it's, they're viable options. So what about astigmatic keratotomy? Well, it might be a good idea in this patient, has fairly regular stigmatism. The pros are you can actually do it at the slit lamp or a minor room, and it doesn't take that long for these incisions to stabilize about three to six weeks, sometimes longer, depending on how large you make them. And depending on which literature you read, you can use them to try to correct as large of a amount of astigmatism as 15 diopters. But the only problem is for patients who have penetrating keratoplasty, they're very unpredictable. And you know, where do you make these incisions? Do you make them in the graft? Do you make them in the host? Do you make them in the graft host junction? So to show you a little bit about what I mean, if this is the axis of astigmatism right there, you can put them in the host, you can put them in the graft host junction. And this is a little more complicated. It's not simply creating an incision with a guarded blade. We take these patients to the operating room and we open the epithelium with a 15 degree blade, and then we actually spread the tissue to reopen those incisions with a .12 or a colibri or a Kohan, rather than just making another incision right in that area. Or you can do it in the graft. So what are the advantages and disadvantages of those three modalities? So host, you know, no one really does this. It's minimally effective compared to graft and graft host junction, AKs. And you know, the source of astigmatism is actually at the junction of the graft in the host. So you're really not addressing that at all. And let's say you wanna do another graft in the future and you have these AKs in the peripheral host. Number one, you might actually hinder yourself and you might actually have a problem with making the next, with creating the tree fine groove for the next penetrating careplasty. Or it just might create more irregular astigmatism that you have to deal with that you can't really, it's much more complex at that point. What about the graft? Well, like I said, it's more effective than the host, but you can't really use traditional nomograms. Usually we look at incision length, incision depth and the proximity of the incision to the central cornea to try to titrate the amount of astigmatism that we're gonna treat. But this doesn't really work. They've done a lot of studies and they found that rather than by altering the incision parameters, the amount of reduction that people get is usually proportional to the amount of preoperative astigmatism. So patients with larger amount of preoperative astigmatism get numerically a larger amount of decrease of their astigmatism afterwards. There also have been reports of actually doing multiple graft AKs circumferentially and then at intervals .5 millimeters inside each other to get more of an effect. What about the graft obstruction? I talked a little bit about the procedure that we used to do that. And the results for these are very similar to those of the graft. And like I said before, the length of the incision doesn't really correlate with the amount of astigmatism reduction that you get. And really what we try to do is we try to center our AKs around the axis of astigmatism. And a lot of times it's not necessarily 180 degrees apart. Sometimes you have one axis here and one axis here and we center them right around those areas. And I'll show an example of that in a second. Right here, you have a very asymmetric amount of astigmatism. Well, you could argue that this in both sides it's about 180 degrees. We would make the incision smaller for that area and larger for that area. And if this was rotated over here, we'd make the incision here. What about femtosecond? That's a great point. They're great for making really accurate length, depth and curvature incisions. But like we just talked about, that doesn't really matter for these patients. So they've done some studies. They haven't really compared femtosecond versus manual, but as far as the reduction of astigmatism, they've been comparable. What about regrosection? So instead of actually making incisions like AKs of the steep axis, for regrosection you make them at the flat axis. And the problem with these is they take a long time to stabilize and a long time to heal. And you can actually titrate them. You get a diopter or two of correction for every 0.1 millimeter of tissue removed. And they're nice because you can actually correct a larger amount of astigmatism. So let's say a patient is 10, 15, 20 diopters of astigmatism, 10's kind of the low end. You can use these if you don't think the AKs are really gonna make a dent in that astigmatism. And there's been different studies that have shown as much as 70% astigmatism reduction when these have been used by themselves. So here's an example. You can see there's basically two incisions being made. The first one is more central. And it's perpendicular or maybe a little bit angular towards the periphery. And then the second incision and the distance from each other is depending on how much astigmatism you wanna correct. It's angled towards the base of that first incision and then you remove the tissue. Usually about three clock hours is the measurement that people use. And then you suture them together. Usually they're paired. What about Lasik? We'll talk briefly about that. People use microkeratomes for a long time to try to correct post-keratoplasty but the problem was as soon as you go over that grass-tooth junction, it throws everything out of whack. And a lot of times the calculations from before were completely off and they did these in two instaged procedures. They would do the incision with the blade first to create the flap and then they would wait and then they would do the treatment. Well with femtosecond, you can actually just do it within the graft. And some of what Dr. Moshevar was talking about before there's more and more people outside the United States are using topographical guidance of eczema laser for this and that would be a great option for these patients. Similar thing for PRK, topoguided PRK for these patients. And the only issue for this is that there's a high risk of haze so you gotta make sure you use mydomycin C in these patients. Start it rolling. Tell you too, I don't know, but I would think that yes, it probably can make the cornea more susceptible to a derejection episode. So I wanna show that pre-AK topography one more time. 10.68 diopter of the stigmatism, you can see it's fairly regular more inferior lengths than superiorly. So the AKs were performed post-operatively two weeks, went from 10.68 to 7.79. It's a reduction, not tremendous. Five weeks, 8.09 diopters, a little bit higher. Three months, 7.89, kinda stabilizing high sevens, low eights. Still a large amount of stigmatism. Best corrective visual acuity, 2080, worse than them when they started. Lower amount of stigmatism, now it was 8.5 before the AK on the MR. Now it's 7.5, but not really what we're looking for. My trolls. Yeah, that's a great point, thanks, yeah. You know, I didn't mention it, but this was done in the seven millimeter optical zone. And obviously, like you said, you get more effect the further in you go, but they've done a lot of studies. And once you go within that five millimeter zone, you start, not only you start having issues with vision, but their regular stigmatism can kind of go crazy. So. Just inside the graph, but you don't have to create. All right, so now what are we gonna do? Does anybody have any ideas? Now we kind of threw out a lot of ideas already. That's a great point, yeah. That's definitely an option here. So we could do the AK again, and deepen and lengthen it. Sometimes just can't go deep enough and long enough that you can really get the effect that you need. You can't go deeper than what you need. Yeah, so compression sutures are a great option. And that involves the meridian 90 degrees away from where you're making these incisions. So that's a great option. What about conductive care deplasty? It has a similar effect as compression sutures. It steepens the corny in that area. Or you could do some sort of combination of the two. So this is a different patient, but just kind of shows you someone who intraoperatively is having AK as well as compression sutures 90 degrees away. And you can see here are the graftose junction reopened incisions from the original care deplasty. And here are the compression sutures. And you can actually see the striae. You want it to be tight. You want to see the striae. You want to have some fish-mouthing of those incisions. That epithelium kind of moves in and allows it to stay and have a greater effect. Care deplasty. This is basically, for those of you who don't know, thermocotery that causes a controlled shrinkage of the collagen lamellae, steepening the corny in that meridian. And in general, it's used to treat low myopia, but as you saw with this patient initially, you can use it in focal areas to cause some sort of steepening for regular or irregular stigmatism. And this is generally the positions that people put the conductive care deplasty spots for general hyperopia without correcting stigmatism. They usually put anywhere from eight to 24 spots, a single spot for eight. And then the more you go up, the more correction you get. But for us, we didn't really want to cause a general steepening. We wanted to cause a focal steepening. So we put six spots on each side in the area of the flattest meridian. And this is just a picture of that patient. It'll give you another view so you can actually see, but here you can see the AK incisions within the graft. So like I said before here, the AK incisions. And here, if you look closely, you can actually see the conductive deplasty spots right there. So here's a topography of the seven days post-op period for this patient. And it's pretty amazing. Went to 2.11 diopters with stigmatism. You don't really see that regular stigmatism pattern in the 90 degree meridian. Fortunately, his time went by post-op month one, increased a little bit to 3.66 diopters. At that time, the visual acuity was 2060, which was better than before, which was, it was 2080. You can see four diopters of a stigmatism on the MRX, which is significantly better than it was. Three months, increased a little bit more to 4.66. Similar best corrected visual acuity of 2060. 4.5 diopters of a stigmatism. Five months, went to 5.19. Still 2060, and you know, if you're wondering the graft is clear-center, there's no gaping of the wounds. There's no other abnormalities here. So, you know, what do we do from here? We could repeat the AK. We could do additional CK. We could do compression sutures. Maybe a piggyback TORQ IOL, now that the stigmatism is more regular. What about a variceis lens? They have, in Europe, they have the foldable variflex TORQ lens. Or should we really go anywhere for this patient? I mean, we took this patient over a long period of time with many surgeries, many procedures from 2070 to 2060. Realistically, as we've been speaking, this patient's not gonna get that much better, and it's a result of the peripheral cornea, or whatever else is involved here. So, you know, at this point for us, we've recommended and told the patient that there's not much else we can do for you. And we don't think it's a good idea. I mean, you never know what terrible things can happen if you keep going at this pace. And the vision could just, they could be 2200 or 2400. You know, at this point, they should just try to contact lens again, see if that helps them, and unfortunately have to live with this type of vision. Any questions or comments?