 All right, we're going to go ahead and get started because we have three presentations today. So, first up is Bernoulli Pundu. She is one of the neurosurgery residents that rotated through our neuro-ophemology service. She's going to be presenting on the management of visual threat in a couple of minutes. Hello. So, I'll start off with a case just to kind of set the scene. So, patient EJ, a 22-year-old female who actually presents the ED with visual loss. So, she's actually reports having eight weeks of headaches associated with photophobia and phonophobia. And then three weeks ago, she reported she's having, when she describes a central visual loss, she can't read things, things don't have a lot of detail. She can use her outer vision to look at things, but she's having trouble seeing and that this is getting worse kind of day by day. She's also having just 15 to 30 second blackouts in vision, wishing sound in her ears and double vision on occasion. So, in urgent care, they did an MRI brain, which was read as unremarkable. So, they referred her to actually originally an eye doctor, and the eye doctor then referred her to Moran, Dr. Judith Borner. So, on a past medical history, significant for a 50-pound weight gain in the last year and a half, and though she did manage to lose 20 pounds in the last four weeks, she had an elevated BMI. Family history significant for diabetes, hypertension, thyroid disorder, obesity. Medications were Bpropion, ST-Talipram, Tramdhamidrin for her headaches. Social history is not significant. She's not a smoker. She does not drink cheese versus a janitor. So, while the MRI brain was read as unremarkable, I just wanted to kind of pull it up and point out just a couple of things. So, while this is a normal MRI brain, notice that the back of the globes posterior are kind of flattened, and the optic nerves are a little bit kinked, and this could be normal, but it is present with her. On sagittal view of the MRI, notice that their pituitary is just a little bit squished. It's not totally full. It's not an empty cell. It's partial empty cell, and it could be a normal finding, but she does have that. And then on the coronal view, her optic nerves are fairly full, a little bit distended. Again, could be normal finding, but she does have that on MRI. So, Dr. Werner performed a visual exam. Blood pressure was normal. Heart rate was a little bit elevated. Acuity was 20, 30 in both eyes. Extracular movements were intact. And intracular pressures were on the high side, but normal, measured in two different ways. Pupils were equally reactive. She did not have an APD, and her chambers were clear and quiet. Though on funduscop examination, she did have four-plus optic disc edema bilaterally. And then she did have some mild deficits in color vision. So these are the pictures that were taken of the discs. And you can appreciate their really edematous. There's some torturous vessels in there. Humpery visual fields. The fields aren't great. And granted, I guess she wasn't a great visual field taker, but these look pretty bad. They're actually worse than the records sent from the outside of Tom Truss office. She also did ancillary visual grids. And she did report having wavy lines in the temporal fields of either eye, which could also be early signs of elevated intracranial pressure. So increased ICP, which manifests as papillodina in the eyes, can relate to visual loss. It's associated with visual loss. And there's several theories behind this. One being axonal stasis in the nerve that could cause ischemia, or orbital venous stasis, which then causes hypertension and visual loss. And then there could be structural causes to it, so dilated ventricles causing traction of the optic pathways and then individual loss. So the point of the talk was to kind of go through this protocol. So this is the NCCU Protocol for Management of Vision Threatening Papillodina. It's something that Dr. Warner put together, formalized earlier this year. And this was in collaboration with Dr. Richard Schmidt in Neurosurgery. And it's actually been approved by Neurosurgery, as well as ophthalmology and neurology. So it's a way, a protocol to help formalize how you treat such patients. So the first step, of course, is someone needs to notice that there is optic nerve edema. Could this be due to increased intracranial pressure? So the first step is to get an ophthalmology consult and have someone assess, is this really vision threatening? And that could be based on physical exam, clinical impression combined. And if it is not vision threatening, then that could be managed outpatient using, outpatient treatments. Some of these include acetazolamide. That's been shown in several clinical trials to help with intracranial, idiopathic intracranial hypertension. Chlorothautome, prednisone, some surgical management techniques, orbital inertia, fenestration, as well as even bariatric surgery. This helps these patients with IIH. And then there's some neuro-treatments that are being tested. But if the patient does have some sort of other reason to be inpatient, some other neurological disorder, then of course you go to the next step. So you admit them and decide, is there some sort of immediately treatable cause like intracranial lesion that could be resected? So those things could be some sort of mass lesion into our extra axial lesion, pituitary tumor. And in that case, of course, that the lesion gets taken care of and then they follow up with ophthalmology outpatient. But as in the case for this patient, if the MRI looks good and there's not really anything to treat neurosurgery, then you go to this kind of key piece of the pipeline. Admit the patient and initially you have to do some things to rule out other causes of increased ICP, including things like venous sinus thrombosis or doing a CTA via endocrine abnormalities. Sleep apnea can cause increased ICP. But if after ruling all those out, one would have a lumbar puncture done and the pressure is actually measured. And if the pressures are increased, then consider either doing repeat punctures or placing a lumbar drain. And neurosurgery can do that in the ICU. So while the patient has the drain put in, you would arrange for an optic nerve sheet fenestration, ideally, and have that done as soon as possible. And in the meantime, place the patient on acetazolamide or steroids. Hopefully, through that process, their vision would improve, their headaches would improve. But if you're unable to wean them off the lumbar drain and they continue to have headaches or visual loss, then you might have to consider doing something a little more invasive, like a CSF diversion procedure like a shunt. So this is kind of nicely illustrated in the hospital course of my patient. So day one, she was admitted to the NCCU under Dr. Anasari. CTV was done and did not show venous sinus thrombosis. Their sinuses were patent. Lumbar puncture was performed and unfortunately the pressure was not measured by the resident. I did not do that puncture. But a lumbar drain was placed and there was copious CSF output and the patient did have improved on her headaches afterwards. So that's a good sign. She was started on Acetazolamide, 500 milligrams, Q8 hours. And optic nerve sheet fenestration was arranged with Dr. Krum. So day two, she had this procedure done. Dr. Krum elected to do bilateral fenestration and the opnode said that there was kind of a gush of fluid so presumably the nerve was under a lot of pressure. In the meantime, the lumbar drain was going at 5 to 15 mils per hour output. And so over the first night, she had 80 mils of output. And the second day another 96 mils of output. And so I'm just using the snow and chart. Her visual acuity is actually improved in one eye. So in the left eye it improved from 2030 to 2020. In the other eye it was 2040. But her symptoms improved, which is good. The following day, she had a mild improvement in acuity in the right eye. The lumbar drain was clamped and she was able to tolerate the drain being clamped. So that kind of similar signifies that she's had enough CSF taken out to kind of temporize the symptoms and her Damach's dose was increased. So on the fifth day, she was discharged, followed up an ophthalmology clinic a couple days later. She continued to have discodema but her headaches had resolved, which was great. And then actually at the two week mark, Dr. Warner saw her and her disc edema was three plus bilaterally and at the five week mark, her discodema was one plus bilaterally. So she got better. So I just wanted to kind of bring up this last point here, fenestration versus shunting. So having her sheath fenestration is a really great procedure. A lot, really not much morbidity with it. Our patient had kind of her right eye was swollen shut for a little while but it got better. She was on antibiotics for a little while. There are quite a few studies documenting visual improvements in acuity, visual fields, color perception within the group of optic nerve sheath fenestration. So it's a reasonably low risk procedure and could be repeated if needed. The downsides being that it doesn't usually treat the headache symptoms and it's not usually a permanent fix. Though again the idea is that once you've got, you've done some temporizing the patient can go out, be seen out patient. They can lose some weight and hopefully that would fix the problem on its own. The other procedures being ventricular peritoneal shunting or lumbar peritoneal shunting. These procedures do treat the headaches and the vision loss together so that's kind of nice but unfortunately they do oftentimes require some patients to have numerous revisions. Some patients do really well. There was a recent study done showing that it may be a little more effective at improving visual fields compared to shunting but there are not very many studies comparing the two. And again there's big differences between morbidity comparing the two procedures. So that's all I really have. Those are my references and some questions. So there is a move to, there's actually a study of the difference between shunting and fenestration. And fenestration has been around for a long time. And shunting, I know that there are studies and if you look at the neurosurgery literature it's clear that shunting is the only way to go. But taking care of these patients you know it's really a nightmare because the operations and the complications and sometimes it's going, anyway the NEI is on the verge I'm hopeful of funding a study that actually looks and that would be nice. And our LPVP shut down versus the operation of fenestration and we have submitted our people to the site of the neurosurgery in Bicschmitt and it's done with on the object. That would be great, yeah. So Kathleen, with all your time and experience with your neurosurgery techniques I mean they always, you know, they're all closing their doors, but I have to say that sometimes you use a fenestration and they don't fit better in their own case and still we've been different sometimes we clean this business. Yeah, the protocol is, I mean I am from the neurosurgery so there was a whole bunch of problems to start with with the protocol off the ground. So I mean I think this, for this acute hyperacute visual loss where sometimes people call it malignant. Right, so fall in it, okay. I mean this is where you have to go. But the bigger question because it affects many more patients this happens and it's horrible and it's devastating no matter what you do if hopefully this kind of protocol will save people to visualize. But the bigger issue is what do we do with these other people that are in that kind of in between mode where they're losing vision? It's not a rapid loss like this, please. But I think it's very exciting that we have this protocol and we've got to keep track of our outcome for this because right now. Yeah. Just everyone, when you do the scan how many? I don't know an exact percent. Though I do, I was looking at recent studies have used the stenting procedure on patients that do have thrombosis and it does seem to help with certain percentages. I don't know an actual number. What percentage have a positive CTB? I'm not sure. I mean I think that the day after you add another area you have to have vision and so you'll see I'll leave as they switch over our speaker that I just want to take a moment to introduce one of our international guests, Dr. Frank, if you mind standing. Frank is a good friend. Frank is from Tanzania. He's at the University of Dedema. He's finished his own residency in the past couple of years. Spends a majority of his time teaching at the university and he is the only optimologist. He's our key person and partner and they have to generally teach him more. So next up is Wala Awad. He's going to be resigning on the management of pituitary adenoma. He's another neurosurgery resident. That's for our team here. All right, good morning. You guys are getting hammered with neurosurgery today, huh? So I'm going to present a patient that was all-client with Dr. Warner. This was a 60-year-old male who came in with past malpractices to business and I'm going to be at the left eye who presents with worsening peripheral vision. The patient was initially had a fall while jogging sustained a pretty serious facial laceration and was seen at an ED. They obtained a head CT to route any kind of subarachnoid hemorrhage and they ended up providing an incidental stellar mass. So you can see there that the rest of his history is not contributory. On physical exam, he was trying to have a severe pair of overall achemosis of that left eye and left info-overal laceration that he sustained from the fall. His visual acuity in the right eye was 20 on 20 and 20 over 400 with correction in the left eye and that's his stable eye exam. He also had asymptomatic mesotrophy of the left eye. We obtained visual fields due to the complaints of the peripheral vision loss and you can see them there showing cardinopsia of the lower right and upper left quadrant in the left eye. So this is what the CT head looked like on his initial work up in the ED. And you can see this abnormally large mass in the region of the pituitary and then on the sagittals. You can see that it is in fact a stellar lesion. This is what the MRIs look like with and without. So you can see this large contrast enhancing stellar mass and on the sagittals, once again, you can kind of re-approximate. On the sagittals, you can also make out what could be where the optic chiasm would be so that it's superiorly displaced due to the mass. I just wanna show a quick demonstration. The patient was ultimately admitted to evaluated by neurosurgery and he ended up having a transpeonoidal resection for a presumed pituitary adenoma. These are the speculums that we'll insert into the nears and it helps separate the turbinates laterally. You usually go in and you wanna cauterize and you're bleeding to your encounter in the mucosa. And then the posterior septum is normally fractured off just to increase the working space in that region. So that's the posterior septum coming off there. Eventually you'll make it, so here's the sphenoid sinus, I'm sorry, the sphenoid sinus. You can see how thin it was. You can just usually fracture it off and then immediately you can see this kind of mass protruding. Let's speed this up here a little bit. So next what's inserted is a pituitary retractor, which is just this ring that you see here on this instrument. You place it into the region of the cell and retract and the adenoma tissue tends to be a little bit more friable and so it's easily retracted. And once there's sufficient resection obtained, Dr. Caldwell likes to always pack with a fat graph to reduce the risk of CSF leak postoperatively. So that's what the surgical side of things looks like. I just wanna talk about some of the medical management aspects as well. So pituitary adenomas are actually quite common and they're at 15, 20% of all intracranial tumors with a relatively high prevalence, so you can see they're 77.6 per 100,000. There are two major categories of pituitary adenomas. One is based on size and the other is based on functionality. So micro adenomas are anything less than one centimeter in size. And then the other major category is whether or not the adenoma is functional, so actively secreting hormone versus a non-functional lesion. And many of these lesions will present with symptoms of hypopituitaryism. This is just a quick overview of the region on the anatomy to help us kind of understand some of the visual complaints. You can see the pituitary gland and the cells, it's just inferior to where the optic chiasm would kind of course over. And then in the adjacent region, there's a lot of cranial nerve and vascular structures that could also potentially cause visual deficits. And then patients with pituitary adenomas tend to present with symptoms of headache and by-temporal heminoxyaclassically, but visual deficits can often be subtle because these lesions tend to grow slowly and so patients don't always immediately appreciate them. And this particular patient, he thinks that he's had this kind of peripheral vision loss for possibly over a year just kind of drastically slowly getting worse. And many times we'll find patients present after like a car accident or something where they don't realize that they have loss of their peripheral vision until something like a car accident happens, they still see a car coming out of their periphery and then I'll look up their found to have a pituitary lesion. And as I was mentioning, larger lesions can expand laterally and cause compression of third, fourth and sixth nerves which can cause symptoms of dyphopia. And then because there's endocrine function as the main function of the pituitary, patients will often present with some form of dysfunction either hypersucretion or hyposecretion. So when you're diagnosing these patients, you always want to obtain baseline pituitary function and then as you saw the CT and MRIs for the standard workup. Also obtaining visual fields and a full ophthalmology exams is important. Mainly to establish kind of baseline functions that we can monitor for regression. Sometimes these lesions can't be completely resected and if you're concerned about tumor growth in the future and wondering whether or not this is really causing the patients any symptoms, it would be helpful to have prior visual fields to compare to in patients with subtotal resections which can help guide your decision making. So there are several subtypes. These are the most common prolactinomas depending on the study that you're gonna look at are generally cited as being the most common versus non-functional adenomas being the most common but you can see there, there's a wide range about 22 to 73% of these lesions will hypersucrete prolactin but also a significant portion of these adenomas will be non-functional. So just purely hyperplasia of the tissue but no active secretion of any hormone. And then you can see growth hormone secretion comes in around third and then Cushing's type of syndrome comes in a little bit later. The subtype of the pituitary adenomas are important because a lot of the treatment arguments are kind of, well, you'll get different responses depending on the type of secretion that the tumor's producing. So for prolactinomas, they generally respond pretty well to dopamine agonists and the two classical are the bromocryptine and the carburginine. So both of these act in a similar fashion. They've both been shown to decrease tumor size and hormone secretion but randomized controlled trials demonstrated that carburginine actually is more efficacious. That's usually the first line therapy and in prolactinomas, they're always trialed on a medication or on a dopamine agonist before a surgical resection is considered just because these generally work pretty well. In the case of growth hormone secreting tumors or ACTH secreting tumors, antagonists exist and agonists exist that you can use to treat symptoms but they generally do not respond as well to the prolactinomas. So generally, these lesions are treated surgically and then any kind of symptoms can be managed post-optively with some medications either a somatostatin agonist versus a inhibitor of psoriasynthesis. And dealing with these patients post-operatively, it's pretty standard to get post-operative visual fields for the reason that I mentioned earlier. If you're considering taking a patient back for a second resection due to progressive growth, there's always the decision to be made of the patient really being symptomatic and having something objective like a visual field test is an important guide in that decision making. I did come across a nice review of specifically visual symptoms after transgenital resections for patients with pituitary adenoma. So in the series of 67 patients, all of them had some kind of visual deficit, either a visual field deficit or acuity. And you can see here that at six months of follow-up, the majority of people, 77% cited a improved overall visual field. And surprisingly, 34% went back to their normal state. And in the case of visual acuity, the results were now as dramatic, but still important to consider, 45% improved and 13 were able to go back to their or normal baseline visual acuity. 23 of the patients that were in this series had visual field deficits that were less than a year old. And 82% of them had improvement, just indicating that getting patients to be seen sooner rather than later could have important implications for his visual field function. And then in a sub-analysis of patients who were noted to have optic nerve atrophy, they did a sub-analysis of visual field improvement and acuity. And they found that you did get, again, some significant improvement with 50% having an improved visual field at that six month follow-up. And 23% able to achieve normal visual fields. And likewise with the visual acuity, 22% were able to improve. Obviously not as dramatic. The patients who did have optic nerve atrophy were noted to have symptoms for longer periods of time, notably about two years, two to three years. And so they didn't have as good of a recovery. And then of course, you wanna obtain a panpatuitary panel after all of these resections simply because a lot of times these patients will suffer from panhypertuitary azamine. You'll have to replace some important hormones, notably cortisol function and DDAP for patients who have symptoms of DI. For patients who are unable to obtain complete surgical resection or patients who have particularly aggressive lesions or if they're incredibly small, these types of lesions can benefit from adjuvant radiation therapy. In this particular study, they treated several types of pituitary adenomas. The first one were the non-functional group. You can see there were 60 patients there. And this group was certainly the largest. You can see the average lesion size. And because of that, it received on average the smallest dose of radiation because that was distributed over at a larger area. A relatively small cure rate. So cure rate here means that the pituitary adenoma was completely gone on follow-up imaging. But they all had reacted to the treatment, indicating that they had gone smaller in size. And then control indicates whether or not they had continued progression after treatment. And this indicates that the treatment was actually very efficacious, that 96.7% of these lesions were able to be controlled. The patients that really benefited the most were patients who had ACTH secreting pituitary adenomas. And the reasoning here was these tended to be the smallest types of lesions. And so, per the area treated, they acquired the highest dose of radiation. And so, they had a cure rate of 30% and a control rate of 100%. And then importantly, they were also able to gain hormonal normalization at higher rates than any of the other tumors that were treated or pituitary adenoma subtypes. So in conclusion, pituitary adenomas are relatively common and can often present with visual field deficits. Treatment is largely dependent on the size and the functional status of the tumor. And visual field deficits are more likely to improve compared to visual acuity deficits, just simply because visual acuity deficits are often associated with optic nerve atrophy and longstanding compression. That's all. It was. No, they didn't apply that. It was kind of an older study, but it was the only one that I could find that was specific acid towards looking at visual field and acuity and these types of lesions. So this one was from, I think, 95, so maybe older studies, I don't think they did. So last but not least, I'm Russell, I know most of you. So I'm gonna be presenting some cases for speed's sake. You all got a homework assignment from Alicia. I imagine most of you probably weren't great at doing your homework assignment, but that's okay. Your cases, I printed out some very, the cases, so I'm gonna breeze through the three cases really quick, but during the rest of my presentation, if you'd like to review them, and then we'll have a little discussion about the three cases. At the end, I have no financial disclosures. We'll do the cases and then a discussion of the literature. So the first case is a 28-year-old that presented to Neuro-Oftomology Clinic to Dr. Warner's clinic with complaints of worsening vision in the ride eye over the last eight to nine months. They had been seen by their local optometrists who couldn't find any reason, had ordered an MRI, which was normal, and had referred the patient to Neuro-Oftomology for further evaluation. It works as an IT specialist at a local company. His vision is correctable to 2020 in both eyes, but his manifestor fraction has a little more stigmatism in the ride eye than the left eye, and the rest of his exam was quite unremarkable, including the anterior part of his exam. His visual field, which we had, you can just see there's some generalized impression of the field in the ride eye, particularly essentially, but otherwise relatively unremarkable. And then Dr. Warner astutely got a cortineal topography which shows some asymmetric astigmatism with some radial skew, which would be concerning for possibly some early keratoconus, versus just an asymmetric astigmatism. So the questions to consider during the rest of my presentation is what other tests you might order if you were seeing this patient in follow-up? How frequently would you wanna see this patient in follow-up? And then if you have a patient that has correctable vision to 2020 but has documented progressive keratoconus, what recommendations might you give that patient? Second patient is a older patient with known keratoconus the last six years, worsening visual function over the last year, left greater than right, but has become contact lens intolerant in both eyes, otherwise relatively healthy. His vision is correctable with glasses to 2040 in the ride eye as count fingers in the left eye and no real significant improvement with glasses. Has a Fleischer ring in both eyes and then fairly significant thinning and some scarring in the left eye. His keratometry, so in the right eye you'll see steep case of 60s with astigmatism of close to 10 with the simulated keratometry. And then the steep case in the left eye which is the poorer function visualized up to 87 and 80. So fairly significant. Just an example of the Placido rings which is where you get the topography you can sort of appreciate the displacement of the cone. And then this individual got pentacam imaging which is a really nice way to A map out the astigmatism but also map out both the corneal thickness the corneal thickness here and then also your anterior elevation map. So how elevated the front of the cornea is relative to a controller best fit sphere and the same posteriorly. And importantly just for those who haven't seen a lot of pentacams there's a lot of evidence to suggest that oftentimes if you look at the posterior flow to the back part of the cornea maybe a good way to pick up keratoconus earlier you'll see there's a larger deviation in the back and the front. And a lot of that is due to sort of epithelial remodeling. So you have thinning of the corneal epithelium over the cone which will mask some of the protrusion anteriorly but not posteriorly. The left eye you can see again very significant with very significant both anterior and posterior elevation. So the questions for this would be what options for management would you consider in this patient's right eye and left eye? And then if you're considering a patient with advanced keratoconus with corneal thinning and scarring what would make you maybe decide between a DA, LK and a PKP? And then lastly for all those cataract surgeons out there 68 year old whose status post cataract surgery in the left eye had LRIs done in that eye presented to the VA for cataract surgery in the right eye. His visual acuity is 2060. He refracts to 2025 in the left eye. Has kind of a nuclear cataract with a little bit of PSC. And then this is his topography. Again, sort of this asymmetric appearance to with a sort of inferior steepening. And this is the left eye which has already had cataract surgery. We said he came over to the Moran and got some imaging. And you can see he does have some subtle elevation in the back. This is a ectasia risk factor that's actually used for refractive surgery screening. But you can see there is some signs that he likely probably had at one point maybe has stabilized but has evidence of sort of posterior elevation in keratocons, same with the left eye. His lens star which shows a little bit more astigmatism, 2.31. His IOL master which again shows a little bit more. So about two, I will not go through all the calcs because you have them all in front of you. But the question I would be curious about is what IOL anyone in the room would place. So you have someone which we can't get him to take any astigmatism. He has these levels of astigmatism that are sort of at a relatively consistent axis. But would you consider putting a TORC lens in? Would you not put a TORC lens in? Would you consider doing an LRI? Or would you just put a plano lens in? Or a aspheric lens and then see how he does. So a quick review of keratoconus. So for those of you who are unfamiliar or just want to refresh your. So keratoconus is a non-inflammatory. It's usually bilateral, progressive, thinning and protrusion of the corneum. And in terms of epidemiology, it's a little bit difficult mostly because the diagnostic criteria are not sort of well-defined and agreed upon and they've sort of been evolving over time. But if you look at sort of various literature, you'll get a prevalence rate between 50 and 230 per 100,000. And like I said, primarily bilateral disease. If you're looking with sort of modern topography and tomography, the rates are usually two to 4% for unilateral disease. So it's usually a bilateral process. Starts in puberty will progress over approximately 10 to 20 years and then will typically stabilize. Oftentimes will present with progressive blurring or distortion of the vision similar to the patient that presented to Dr. Warner's clinic. They may have some photophobia glare and monocular dyplopia as well from the asymmetric astigmatism. A quick review of sort of some of the clinical signs. So you have vogue stria, which you'll get some vertical stress lines that you'll be able to see in the cornea. Months and signs, which is if you have the patient look down, you'll be able to see the displacement of the upper eyelid. Rizzuti sign, which is if you're bringing light from a very tangential angle, you can in essence sort of get the reflection of the cone on the nasal iris. Flicer ring, which it's tough to see here, but this patient does have this corneal ring that kind of goes around the area of the cone. Corneal thinning and then you'll get this annular red reflex. And there's great videos. If you haven't seen Scissoring of a Red Reflex, just Google it today. It's pretty unique and I think it's probably, Dr. Tabin would tell us that the VA is a very underutilized test because we don't oftentimes retinoscope our patients, but it's a really nice way to kind of appreciate what the light that's entering the patient's eye is doing. Other testing to consider, contrast sensitivity, like we said, that topography, tomography, which would be like pentakam imaging, and then the pochymetry. So in terms of ideology, this is one of the frustrating things about keratoconus. There's not a great understanding of exactly what causes it and there's lots of opinions and theories about it. Certainly there's lots of people who have found that there's association with keratoconus. Those people of keratoconus that they tend to rub their eyes more than normal people do, but there's people who have postially that this could represent some sort of chronic micro trauma that then may lead to some of the pathologic changes that are seen. There's been documentation of elevated lysozymal enzymes that are expressed in the host epithelium, which could lead to sort of some stromal weakness, and there's been a number of different enzymes that have been postulated. There's also increased IL-1 binding sites have been documented in keratocytes of keratoconic patients, and IL-1 has been shown to induce apoptosis in stromal keratocytes in vitro, so there's some feeling that this may represent a pathway. There's also definitely a strong hereditary or genetic component. If you look at the general prevalence rates and then you look at the inheritance estimates, approximately 6% of those first-degree relatives of patients that have keratoconus will also have keratoconus. So there's obviously some sort of genetic component. There's been a lot of different genes that have been proposed, both by linkage analysis and other processes, but there's no really definitive gene that's been identified yet at this point. And this VizX1 is one of the more promising ones. It's on chromosome 20, but again, there's some reports that say that it's not very strongly associated. Systemic association, I think one of the really important things to consider is that a lot of patients with keratoconus will also have concurrent atopic disease, and this will make them more likely to be rubbing their eyes, which may also lead to increased progression. And so just addressing that as a factor in trying to decrease any aspect of allergic lid disease that they might have to help both improve contact lens tolerance and then also decrease the amount of eye rubbing that they're doing can be really important. There's a number of other associations, Down syndrome, a significant number of people with keratoconus have mitral valve prolapse, and then there's lots of other case reports of all sorts of oftentimes mixed sort of connective tissue disorders, but other things as well. Important sort of considerations when thinking about keratoconus, just a review for the resonance. So corneal hydrops is one of the things that can be a complication of keratoconus, it was first described in 1900. Keratin about 2.5 to 3% of keratoconic patients, so not a huge percentage, but they oftentimes will present with this redness, discomfort, phobia, and then this sort of opaque, edematous cornea, and the treatment is outlined there. The key is that you would not typically do anything acutely in terms of a PK or otherwise you would let them heal, scar down, let the edema resolve before you would potentially do anything typically. Pathologically speaking, the most, the thing that we always talk about when we're with Dr. Mamelis is this sort of breaks in Bowman's membrane, which a lot of people feel may lead to some of the structural instability. There's also the epithelial thinning, compaction of the stromal layers, and then you get these sort of extra decimays and it breaks in decimays where it will scroll up because of its elastic nature, and then you can't have scarring in the epithelium as well, long term. So one of the big areas of frustration is classification of keratoconus, and there's not really a wonderfully unified agreement in my understanding and reading as to how to appropriately classify. The oldest classification is this Amsler classification, which kind of is a grade zero through four based on the severity, with grade four being severe and normal. These were the sort of initial considerations. Those have been adjusted slightly, but you still have this sort of grade zero through four, which people oftentimes refer to. Rebenewitz criteria is sort of classically taught and tested on boards, which is based on corneal topography measurements. But more recently, there's been a lot of these indexes, which I won't go into in depth, but that try to use data from either topography or tomography to better classify those patients that to better sort of risk stratify patients in terms of the severity of their keratoconus. But the problem is a lot of this is based on the structural abnormalities and not necessarily the visual function. And so if you have someone that has a fairly significant structural abnormality without scarring, but they're able to get a really good, like scleral lens fit, they may actually be able to see really well, despite having fairly significant changes on their topography or tomography. We don't have time for that. There's a differential. So I did want to quickly just highlight some of the treatment options. I will cut this short so we can get to the discussion, but I'll send out this PowerPoint so that people have it for their own review. I think the important part to remember is that non-surgical options are a really good option for patients, even after they've oftentimes had some of these surgeries, consideration of glasses, but also importantly, sort of customizable contact lenses, whether that be scleral lenses or other things can be a really good option. So a classification of the different sizes of lenses and the important thing is, a lot of these patients will be in just a corneal RGP. A while ago, a lot of people felt that you should have the lens rest on the cone to try to decrease progression. There's been a number of studies that have shown that that's probably actually not helpful and may lead to hypoxia and maybe some micro-trauma. So generally my understanding, Dr. Olson, you can correct me if I'm wrong, is that more people are going towards this sort of apical clearance or a three point touch, which is where you have this really faint touch on the cone but not significant resting on the cone. The other lenses that are available, a corneal scleral, which is just slightly larger than a corneal RGP and then a mini scleral or a scleral lens where you're in essence resting the lens on the sclera and then vaulting over the entire corneum. There's lots of information about that, but we'll come back to it if we need to. Hybrid lenses provide a nice option. Visually speaking, scleral lenses and hybrid lenses have been shown in studies to have fairly similar visual outcomes, but a lot of patients find these to be more comfortable because they have sort of a soft contact lens skirt. So that's also another option to consider. From a surgical standpoint, so for those patients who have non-progressive care to conus, whose cornea is thick enough, you may consider placing a corneal ring segment in the United States. That would be an Intax. There's some other ones that are available outside the US and are going through FDA clearance, but Intax are currently the only ones that are available. There's two different sizes available in the US. Again, the considerations you ideally probably want to have a non-progressive patient. Oftentimes this is done in patients who are contact lens intolerant in an attempt to maybe make them contact lens tolerant by decreasing their case. And importantly, you want their corneal thickness to be greater than 450 at the seven millimeter optical zone. If they're too thin peripherally, then you're not gonna have, it probably isn't gonna be safe to go ahead and put the Intax because they may either extrude, they have a higher risk of extrusion at that point. This goes over the procedure and the nomogram. I think just importantly, looking at some of the series of it, the benefit of it is that you can have a decent reduction in both the keratometry and the stigmatism, but it's not a cure-all. So I think it's important for patients to realize if they're having Intax, it's not gonna make them independent of their need for glasses or contacts. In most cases, they're still going to need something, but it's an attempt to maybe get them so they can be contact lens tolerant again or have a slight improvement in their uncorrected distance visual acuity. There's mixed data on progression after Intax. Some studies say that you don't progress after Intax. Some studies show that there has been progression after Intax, so we won't go into that. There definitely is associated implantation, so 7% in this study, 23% in this study. So just important to note, not everyone's going to tolerate these or they may extrude, depending on the surgical technique or other things. Some of these were just taken out because they didn't really improve the patient, so there wasn't any refractive improvement. So it's not uncommon to have to explain them. Corneal crosslinking is an option that's not FDA approved yet. If usually you want someone who's thicker than 400 microns, if they're thinner than that, you can use a hypotonic solution to try to swell their corneal. And this just goes through the process. There's both, the classic process is to remove the epithelium similar to PRK and then do it. There's a lot of people who have looked at epi-on techniques. The problem is riboflavin doesn't penetrate quite as well. And the US data on this should be published soon in terms of the biggest study on it. But there's definitely some studies that have shown that there's probably equivalent or slightly less improvement but still fairly good improvement with epi-on crosslinking. A newer technique which some of you may not have heard is Bowman layer transplantation. So the idea being that pathology is a break in Bowman's layer. So there's been a few case reports of people actually transplanting Bowman's layer into a mid-stromal pocket that can either be created with a femto laser or with a manual dissection. And while there's a fairly wide standard deviation, they have shown that there's a reduction in Ks. Again, this would be used in patients that were too thin for crosslinking but had steep corneas and you were trying to maybe make contact lens tolerant as opposed to giving them a transplant. Then there's DALK and PKPs for those patients with severe disease with scarring. I think the important thing to remember is if you look at sort of five-year endothelial loss as well as graft rejection, DALK is probably a better option for most patients. It's a little bit probably more surgically difficult. And so if possible, attempting a DALK is probably a better option because it leaves the patients host endothelium so they're less likely to have a rejection episode. And you're also not entering the eyes so they're less likely to have complications such as cataracts or other stuff long-term. And then there's some people, not many in the States but elsewhere who are doing combination therapy, particularly sort of combined accelerated crosslinking with same-day PRK. Again, an attempt to crosslink and stabilize the cornea but also improve the refractive outcome. And there's fairly good data to support that this is a decent option. You can see they're sort of doing limited ablations so they're trying not to exceed more than 50 microns worth of tissue because you have an eye that has an ectatic process which is why they're crosslinking. So case conclusion, case one has missed three cornea appointments despite me calling and suggesting that he might want to come in. But I would just be curious, is there any other tests from a resident standpoint that you guys would consider getting, again this patient just had a topography? Yeah, so pentakam imaging would be really helpful. And then I was curious from an attending standpoint, I don't know if this patient presented to your clinic how often you would recommend following up on this patient to see if there's documented progression if you would see them every three months, every six months, every year, okay. But if they were younger like 18, 19, 20, would you see them every six months? Okay, aggressive it, yeah. And then the other question for this one is if you have documented progressive keratoconus in a young patient that's still correctable to 2020, obviously ideally if the FDA would approve crosslinking you'd probably crosslink them. So I'm just curious what your sort of recommendation would be at this point, okay. Case two, again there's the questions. This patient ended up having intact placement in the right eye and a PKP in the left eye and sort of post-operatively. I just wanted to show you an important thing when you're looking at these, it can be really difficult, if you're looking at the standard palette which has a set number here, it can be difficult to see if this patient's really improved that significantly with the intact. If you take a sort of auto scale so then it will go to sort of adjust for the highest level of the stigmatism, you can see there's been some improvement in terms of that. So it's just something to consider when you're looking at your topography, what your scale is. Oops, sorry. I guess the question that I wanted to pose in particular was in advanced keratoconus with corneal thinning and scarring, is there considerations that you guys as attendants make in deciding whether to do a doc or PKP or do you attempt to doc in everyone? High drops? Then you wouldn't. And then case three just quickly. So here was your stigmatism. So we put an SN60 lens on this patient and they were 20, 30 post-operatively and he didn't want glasses. He was super happy with his vision as it was. He didn't want contact lenses. He just loved his 20, 30 vision, which is fine. So I guess the question that I was curious is attendants here, if there's what considerations you would possibly do, would you ever put a torque lens in someone who looked like they had stereobole keratoconus with sort of your regular astigmatism? Or would you always put a non-torque lens in? Would you ever consider doing an LRI? So I just opened it up to the floor. Yeah, go. I think the key thing is we're often stabilized and regular. You know, we did not discuss it, but that would have been a good idea probably. Thank you.