 So we're going to switch gears a little bit. Thank you so much, Dr. Hurley. I'm going to introduce our next speaker, which is one of our phenomenal cornea fellows, Dr. Daliwal, who's going to be speaking to us about a review of Respookler's corneal dystrophy. So a little bit of a gear switch, and I'll let her just take a few seconds to pull up her slides. Good morning guys. My name is Shug and Daliwal. I'm one of the cornea fellows here. And today I'll be switching topics. We'll be going to the front of the eye and presenting a review of Respookler's corneal dystrophy, which is also going to include a presentation of a case that was managed and treated here. So Respookler's corneal dystrophy is an entity that we don't often see in clinics. So I'd like to start off by just presenting an overall review of what this disease is, how it came to be identified. So this was initially described by Wilhelm Reiss in 1917. He described a 20-year-old patient who had intermittent attacks of ocular irritation. Initially he thought this was just a recurrent herpetic keratitis, but when he examined the family pedigree he noted that several other family members also had similar attacks. So ultimately he determined that this was in fact a separate disease, that this was a dominantly inherited condition characterized by recurrent corneal erosions and superficial corneal scarring. But obviously this isn't the whole picture. About 30 years later, Max Buckler examined the same condition in greater detail. He looked at the same family actually that Wilhelm Reiss examined, and he noticed that in four successive generations this same entity presented itself. So he determined that this was an autosomely dominant heron condition that was, you know, as Wilhelm Reiss suggested it was characterized by recurrent painful erosions in childhood. He added that there was corneal opacities present at Bowman's lair in these patients, and as this dystrophy progressed, these patients would have a progressive decrease in visual acuity. And this essentially is the foundation of our present-day understanding. Obviously we've built upon this more, but the basics of it are about the same. We understand this disease to be autosomely dominant inherited. It's a bilateral central corneal dystrophy that primarily affects Bowman's lair. The clinical course is pretty much about the same as what they described back in 1917 and 1949. At birth, these patients have normal corneas, and within the first decade of life they present with painful, frequent, recurrent erosions. And by age 30 the erosions have remitted, and now they develop superficial corneal opacification and surface irregularity, which is a true cause of visual acuity declining in these patients. And in that picture you see there that's an image of a four-year-old patient. And essentially the cornea, on first glance, looks the same, but if you look closely at the pupillary margin, you can notice some fine, reticular opacities there. And this is what this entity looks like in the advanced stages. You can see that superficial opacification. You can see some haze and scarring. The genetic basis has also been elucidated in this disease. As we all know from our boards and OCAPs, this is one of the TGF-beta-1 gene-associated corneal dystrophies. It's autosomally dominantly inherited. That gene is responsible for an extracellular matrix protein that mediates binding of other extracellular matrix proteins to integrins for cell proliferation, adhesion, and migration. Its further molecular analysis has revealed that this is specifically an arginine elucine mutation at codon 124, which leads to this deposition of dystrophic proteins. There's some controversy as to which corneal cell actually causes this dystrophic protein deposition, whether it's keratocytes versus epithelial cells versus both. Ultimately, this manifests on histopathology as atrophic epithelial cells. Work done by Rice and Ikea in the late 60s, early 70s revealed that nearly all epithelial cells are affected in these corneas. You notice degenerative changes such as swollen mitochondria, large vacuoles, and swelling and disruption of the endoplasmic reticulum across these corneas. Of course, Bowman's membrane tends to be completely replaced by collagen fibers in these patients. With the advent of newer technologies such as anterior segment OCT and confocal microscopy, our understanding of this disease has expanded. In 2016, Q et al. pursued further evaluation of this dystrophy. He examined these patients' corneas with anterior segment OCT. He noted that there was thin bands of hyperreflective signals present at the level of Bowman's layer. This is assumed to be those dystrophic proteins that are visible on anterior segment OCT. In these images, you'll see that those top two images, A and B, are slit-lamp photos of patients with Rheismogler's dystrophy. The anterior segment photos corresponding to those images are C and D, and there you can see that layer of hyperreflective signal in the anterior cornea that corresponds to Bowman's layer, or the previous known as Bowman's layer. E and F are normal corneas for comparison, and you can see that you don't see that same hyperreflective signal. We also notice that in children, there is that same hyperreflective signal present, which corresponds with the onset of this disease early in life. However, that thickness of that hyperreflective layer is far less than in adults. He also examined these patients with confocal microscopy, and this is fairly interesting. He noted that there's changes that occur into the mid-stroma in these patients, and that's not something that was apparent to us in histopathology or on clinical exam. So in this little grid of pictures, the top two rows are of dystrophic corneas and the bottom rows of the normal cornea, and then you have the corresponding depth as it marches along the columns. You'll notice that there's hyperreflective granule aggregates, and that was the characteristic feature on confocal microscopy of these diseases. And that's present in both of the top two dystrophic corneas. But for a few patients, that's present into the mid-stroma. It extends from the epithelial basal layer to the anterior stroma into the mid-stroma in that second row patient. There's also a notable decrease in the subbasal nerve flexuses. It's delineated by the white arrows, and you'll notice in both the top two rows there's none present. The diagnosis of this disease can still be confusing, however. Our traditional method of diagnosing dystrophies with clinical or histopathologic examination is not sufficient at times for this disease. It's often confused with another Bowman's layer dystrophy, the ill-banked corneal dystrophy. But it's important to be able to distinguish these two because visual acuity is worse in Reisbuckler's corneal dystrophy, and prognosis is poorer in Reisbuckler's corneal dystrophy. There's a far higher rate of recurrence in Reisbuckler's corneal dystrophy. Significant work has been done in order to delineate these two diseases. Kukl et al published a fairly extensive paper in which he stated that we should in fact change the names of these dystrophies. Reisbuckler's dystrophy should instead be known as corneal dystrophy of the Bowman layer type 1, and Thiel Bankie should be known as corneal dystrophy of Bowman layer type 2, so that you can understand them as essentially a spectrum of disease. However, it's still important to delineate the difference between these two and identify which group your patient belongs in so you can more appropriately choose a method of treatment. You recognize that when just examining symptoms and inheritance, these diseases are very similar. They're both autosomally dominant, they're both characterized by recurrent erosion starting in childhood, and clinically they both manifest with opacities at Bowman's layer. But light microscopy and electron microscopy per Kukl's work were the most efficient ways to establish a diagnosis. So you can see here two light microscopy images that in Reisbuckler's corneal dystrophy, the Bowman's layer is replaced by superficial stromal fibrosis, whereas in Thiel Bankie it's replaced by a thick area of panacea, and it's overlaid by that characteristic sawtooth undulation of the epithelial tissue. Transmission electron microscopy is also fairly helpful in delineating these diseases. Reisbuckler's corneal dystrophy is known to have this electron-dense, rod-shaped bodies present on transmission electron microscopy, and that's highlighted by those white asterisks, whereas Thiel Bankie has the characteristic curly fibers that are often tested on our exams in Bowman's region. Genetics and molecular analysis has also come into play as a new way of distinguishing these two diseases. They're both, both of them are a result of mis-sense mutations, but at different codons in the genome. So as we said before, the Reisbuckler's corneal dystrophy is due to an arginine delucine mutation at codon 124, whereas Thiel Bankie is due to an arginine deglutamine mutation at codon 555. Management for both of these antiracornial dystrophies is fairly similar. It's essentially, once again on a spectrum, you have your conservative therapies which include lubricants, gels, ointments, and you have your surgical options. And in the middle you have laser ablation, which came into play in the 90s, and has now sort of emerged as a standard of care for this disease. Just to briefly touch on our surgical options, superficial care tectomy is an option that was previously fairly popular for this disease. There were reports that during, in the post-op recovery process of this, patients would develop increased astigmatism from pre-op. Lamella keratoplasty is also a possible treatment option, micro keratome and femtosecond-assisted lamella keratoplasty has been described, and of course penetrating keratoplasty, which has the benefit of being able to remove those opacities at all layers, but the possibility of recurrence can be kind of, we had a little devastating for a patient who underwent penetrating keratoplasty. But now moving into laser ablation. As I said, with the advent of the eczema laser in the 1980s and 1990s, this has become the most popular treatment option. Just to briefly review, the eczema laser is a 193 nanometer wavelength light, and it's capable of ablating tissue in a very controlled and precise manner. That ability to control and precisely titrate this laser is what makes it perfect for antiracornial dystrophies. And you can see that picture there, it's a picture of a human hair that's actually been etched by eczema laser. Obviously there are certain contraindications to this. If the cornea is already toothed in, and there's going to be insufficient residual stromal bed, laser ablation is not advised, deep corneal pathology would not be ideal for this disease, and there are complications, nothing is without complications. The biggest thing that we worry about is, obviously recurrence, as we stated with all the issues, but specifically haze, scarring, and induced refractive air after PTK. But despite all those, it is still the standard of care currently. There's a few things to note when you're performing PTK for this type of disease. You want to make sure that you have a large ablation zone, and this is different from what we would do for refractive treatment. You would want an ablation zone that's over six millimeters, because this isn't disease that extends into the peripheral cornea. And it's important to have some level of assessment of the depth of this pathology. You can do that at the slit lamp with bimicroscopy, or you can have more precise measures with anterior segment OCT or UVM. There are a few big concerns that were more prevalent in the early days of PTK for anterior corneal dystrophy. One of the big issues was a hyperopics shift. In these early cases, patients were found to have significant hyperopics shifts after PTK was performed up to five to 15 diopters of induced hyperopia. The way this was prevented, first off, physicians tried to prevent having a deep ablation. They would ablate, then they would check the patient, see if they'd gotten a sufficient amount of opacities ablated, and then they would go back and do it again if needed. And then, more recently, what we try to do now is a myopic and then a hyperopic treatment, where you would ablate the central cornea and then also ablate the peripheral cornea to have a refractively neutral result. Another major concern is recurrence. So initially, PTK, that was the major issue with PTK. Some studies show that at least 50% of patients had recurrence following PTK within the first two years of treatment. And really, although PTK lets you have repeat rounds, it's not like penetrating core keratoplasty where there's perhaps a limit on how many times it can be done. There is still a limit on how many times you can ablate a person's tissue and how much residual tissue they're gonna have left. But with the introduction of topical mitomycin C, that has become far less of an issue. Miller, in fact, reported a case of refractory rice buckler's corneal dystrophy in which a patient underwent two rounds of PTK without mitomycin, had quick recurrence of the rice bucklers. But with the addition of mitomycin in the third round, he, I think it was a female patient, showed no recurrence of one year. There are new frontiers for PTK as well. We haven't quite figured everything out. There is a description of a technique known as sequential customized therapeutic keratectomy. And essentially what this is is topography guided custom ablation, which means exactly what it sounds. Where the laser ablation is guided by the topography present in the patient and the refraction. And that you perform multiple rounds of this in between every round. You'll assess the topography. You'll assess the chemistry. You can even assess visual acuity and you'll repeat rounds. Of course you're gonna use mitomycin because that is now sort of standard of care with this disease. And this has shown fairly good effect. Very limited recurrence on this small sample size of 14 eyes, only two patients had recurrence and that was past five years. And following retreatment, no recurrence. And nearly everyone, about 99% of patients showed improved visual acuity with nearly three quarters of patients showing two or more lines of improvement. So now that we have an idea of what rice bucklers is, how you diagnose it, our imaging possibilities, and management, I wanna move into the patient that we saw in our department. So our patient was a 61 year old male who was referred to us with rice bucklers corneal dystrophy. He was complaining of decreased vision, severe irritation and severe photosensitivity. He described to us a gritty sensation that persists despite the use of frequent tears and lubricating women at night. And he also told us that when he was a child, he would wake up with his eyes very sore. But that was not really something that happened to him much anymore. We had the benefit of knowing his family history. His mother also had rice bucklers corneal dystrophy, and she underwent corneal transplants in both eyes here at the Moran, actually. His vision on presentation was fairly poor, 21, 25 in the right eye, 20, 70 minus a few in the left eye. And he was noted of a hyperopic prescription with mildest stigmatism. We re-refracted him, but the best we could get him to was 20, 50 in the right eye and 20, 30 in the left eye, with still a fairly hyperopic prescription. Slit lamp exam initially was very difficult. The patient had extreme light sensitivity. But we were able to identify that he had diffusely scattered superficial reticular opacities that were great, essentially, and in the mid periphery. That external exam picture is a picture of our patient. We weren't able to get slit lamp photos on him because of his light sensitivity. But you can see there at the nasal edge of the pupil that there is this fine, reticular stippling of Bowman's layer. And that is what the whole cornea looked like. Here's another picture that I included of another patient, which is a slit lamp photo of what Bowman's dystrophy should look like. Just for comparison. So we decided to proceed with PTK. We used our Wavelight EX laser, and our treatment involved alcohol-assisted epithelial removal. We did proceed with mechanical debridement and diamond burr polishing for this patient. And then we performed that consecutive treatment method where we did a myopic central treatment and then a hyperopic peripheral treatment, followed by 30 seconds of vitamin C. And this is actually a video of the procedure. So at this point, we're starting in the middle of the procedure. A large diameter well has already been placed on the cornea, which was filled with alcohol. That was left to sit on the cornea for about 40 seconds to loosen the epithelial bonds, and now the epithelium is being scraped off. Once the epithelium is scraped off, we'll proceed with the mechanical debridement. And you can see that here, well, this is just smoothing of the cornea. And then with a greasher blade, we'll proceed with the mechanical debridement, fairly aggressive mechanical debridement, so we can make sure to get as much of the irregularity smoothed out as possible. And now the diamond burr polish as well. And this is followed with the ablation treatment. And you can see here, initially we'll do a central myopic treatment, followed by a peripheral hyperopic treatment. Following these two treatments, we placed a corneal light shield soaked in mitomycin C over the cornea, let that sit, and then the treatment's complete. Put a bandage contact lens on the patient and let them go. Here's actually the treatment sheet that we performed, and I just want to show these to point out that we did with the combination of the central myopic treatment and peripheral hyperopic treatment, you can essentially treat the whole cornea in a refractively neutral way. And you'll also notice the ablation zone size that we used is far bigger than the typical six millimeter size that you use for your refractive treatments. This is our standard post-op regimen for the patient, and I'll speed through some of these since I think we're reaching our time. At one week post-op, we noted our patient already had improved uncorrected vision, which continued to improve at the one month post-op. We assumed at this point that he had achieved his stable final refraction. But when we saw him at the four month post-op visit, we noted that he was far closer to Plano in both eyes and was best corrected to 2020. This was interesting to us because he started out with a hyperopic refraction, and we performed a refractively neutral treatment, but he ended up better than we expected. His main complaint at this point, he was happy with his vision, but his eyes were significantly dried. So we've placed punctal plugs and then we got a message two days later that he was very happy with his vision. The dryness was essentially an audio issue, and he's been doing well since. So that is just a quick review of Rice Buckwheat, hopefully it's been helpful.