 Good morning. Let's go ahead and get started. We have a couple of our fourth years here today. First is Zak Oki. Interesting fact about Zak is that he's fluent in Armenian. He says that he's going to give his presentation in English. So he's going to be talking to us about Karate Konus. Thanks for that intro, Dan. Very pleasant intro. Yes, I will not be giving this talk in Armenian. I don't know if I remember it well enough to actually be super fluent. So today I'm going to be giving a case presentation first on Karate Konus and then I'm going to describe in some detail the disease, diagnostic criteria, etc. So let's start with the case. So my patient is a 26 year old male. He has a history of Karate Konus that was diagnosed about five years ago. He came into clinic because he said his cornea had ruptured. He said that on May 8th he was at work, got some dirt in his eye, decided to clean out with his hands, and subsequently developed blurry vision and pain. He saw an outside ophthalmologist who essentially said to him, let's observe this or we can do a corneal transplant and wanting a more conservative therapy, decide to visit us and see what we could do for him. As described in the nurses notes, he's a longtime eye rubber. Definitely has pain, a little phobia, and no family history. This is physical examination, excuse me, when we saw him when he came into clinic. His visual acuity, as you can see on the left eye, is quite affected whereas on his right it is not necessarily. He could see though, he could see through this. This is the affected cornea. You can see there's sort of an inferior predominance, white finding. This is his left eye. As I described earlier, you can sort of see the people, everything around his eye was essentially normal, clear cornea and periphery. So we decided to obtain optical coherence tomography. This is technology that's common to the keratoconus and corneal fields. You get a high resolution of corneal thickness by shining infrared light into the cornea and get a high resolution image back at you. Taken at different angles, this is a three-dimensional structure of course. Here we have two-dimensional views. The arrow that I've added to these images denotes decimates membrane, the second to last layer of the cornea. So you can see this normally is a thin structure as we all sort of know. However, in his case it is bulged out. You can see vacuoles of edema. There's one large vacuole just above decimates membrane in his case. This is a close-up view of this top left image. You can see how significant his edema is. In cases of keratoconus, this is known as hydropsyl trial. I'll be discussing in some detail later. So on advisement from my mentor attendings, I would like to get some audience participation if possible. Please any senior residents or any fellows who'd like to inform us on what would be the next best step, please raise your hand if I'd like some help. What would you do? Muro? Okay, that's one option. That's right. So Muro is one option. Any other options? Muro, of course, is a hypertonic saline that can be administered topically. Here are your options. So these are not necessarily discreet. They can be used interchangeably or all in combination. Laser peripheral erotomy in combination with intracameral gas will actually replace decimates membrane back onto the most inferior layers of the stroma, thereby preventing further development of edema and promoting regression. The erotomy is there so that if the gas is for whatever reason displaced, that won't cause a glaucoma. Hypertonic saline, as Tom mentioned, or Muro can be used. Topical antibiotics are also used because there can be a traumatic association with eye rubbing in cases of hydrops, exacerbated keratoconus, cyclopegics, corticosteroids, as well as ocular hypotensives to decrease the fluid inside of the anterior chamber. So these are the options that we had for this patient on our initial visit. We decided to do an LPI as well as sulfahexafluoride gas. The other option of gas is perfluoropropane. Both are readily absorbed. Both are safe. As Tom mentioned, Muro, Durazol, and Acetazolamide, a carotid anhydrase or hypotensive agent. That's what we used. Here's an image of us in the operating room. Here we're injecting sulfahexafluoride into his anterior chamber in the hopes that decimates membrane will stay attached. We instruct the patient after this happens to lie in one degree trendelberg, reverse trendelberg, after the operation so that the gas is nicely maintained on top of the inferior portions of the cornea. So on post op day one we saw this patient and the edema was improving. He still had some pain. His visual acuity was actually worse. He had count fingers then on his initial visit which was 2,300. The bubble, this is my inadequate representation of a bubble inside of an anterior chamber, my apologies, age representing high drops. High drops were still present, 40% SF6 in his anterior chamber. So we decided to start Vigamox discontinue ocular hypotensives and continue Muro and trendelberg and then follow up in nine days. At that visit, his edema was improving. He didn't have any pain which is an excellent indication and his visual acuity improved from his initial visit when we saw him which was so he gained 100 feet and there was no gas. So before we wanted to change our treatment plan we decided to collect more information. We did another OCT and this is his cornea which is quite excellent compared to when he initially came in. So as you can see there's market improvement. Little edema still present, decimates membrane is visible but a definite improvement. This is taken at the same angle. So we decided to reinflate with SF6 gas and continue all other treatments that I previously mentioned. He returned in two weeks. He said he could see some. This patient is a pleasant gentleman. He tends to minimize certain benefits I think from heart therapy. He came in holding his eye and when he came in on this visit he was pleasant and able to sort of look at things around the room. His edema was improving and his pain continued to not be existent and the bubble that we had placed was gone. His high drops opacity had been improving as well. As you can see in this image, definite significant improvement in the opacity that we saw on initial presentation which is this, this is his initial presentation. So by comparison you can see market improvement and this is the OCT that we captured at this last visit which is by my naive medical student eye looks like a normal cornea and this is his OCT on initial presentation. So definitely a large improvement. You can decimate his membrane is right here whereas it's right here on his last visit to us. So let's let's discuss careticonis mildly. Just the disease and we'll touch on management a little bit. So first careticonis it's a non-inflammatory disorder of tecton, corneal stromal tectonic weakness. There are two homarx thinning and a conical deformity that leads to an irregular astigmatism. Typically it will present in the second or third decade but in puberty you can actually see initial thinning associated with the disease. There's some classical features and physical exams, the lamp examination that I'll discuss briefly and the severity of the disease will actually obviously determine therapy. Pathophysiology is an interesting discussion. The literature is full of arguments. There are certain things that we know and there are certain questions that have yet to be answered. One thing is for sure college and content is reduced and I will show some histologic issues excuse me pictures that will I think convince you that this is a very special thinning. The cascade hypothesis states that the keratocytes which are the cells found in the corneal stroma for whatever reason cannot react well to oxidative stress. There are certain enzyme inhibitors that are significant in the reaction to oxide radicals that are formed by light that hit our cornea and for whatever reason in patients with careticonis these enzyme inhibitors tend to be deficient and that leads to a cascade of effects namely corneal thinning. Genetics plays a role both directly because of familial association about 20% of patients with careticonis will have a familial association but there are certain other genetic conditions for example trisomy 21 that will predispose patients to ocular digital stimulation which is another thing that we know is associated with high drops and keratoconis. There are certain inflammatory mediators that have been well described that lead to corneal thinning. But we don't know the hierarchy of excuse me of any of these so we don't know is there one enzyme are there many enzymes that are most responsible excuse me enzyme inhibitors how important is genetics it seems to be important to some but not to others there's a penetrance issue so we still have a lot of questions to answer. As I mentioned I would show a histologic image you can so this is a cross section not excuse me cross section but a flat section of corneal tissue and the periphery there's normal sort of thickness and then as you as you move to the center there's a marked demarcation and then thinning begins. There's a physical exam property associated with that which I will mention momentarily as happened with our patient decimates membrane we can separate from the cornea leading to high drops if untreated with observation. The cornea can develop scarring which is seen in this patient by the significant H&E stain. So this is a disease of the life of the lifetime as I mentioned beginning of puberty presenting in the third and second decade with visually significant symptoms along the way there are all sorts of visual changes most of the pubertal patients are incidentally discovered however along their lifetime with variable penetrance patients can present with different features modified visual changes axes shifts there are different reflexes different physical exam features which I will mention momentarily but some have a temporal significance as a patient progresses. There are different degrees that have been described in the European Journal for that reason visual acuity is described in meters here my apologies but the degrees of care to conus are associated with both curvature visual acuity and thickness of the of the cornea usually pubertal or patients initially present presenting our first degree or zero degree they haven't been diagnosed yet. So these are some external some findings on physical examination that I want to mention only mention a couple of these in our in our discussion here today most prominent among external findings most classic in the textbooks as months in sign this patient is probably a first degree care to conic his left eye is affected for comparison this is a patient probably in the later stage degrees you can see market changes in his cornea V shape classic sign months in sign. Corneal thinning is of course by definition a part of care to conus on slit lamp examination you can see sort of normal cornea and then market thinning in the center and inferior portions of the cornea and then return of normal cornea so to speak vogue stria is important both in the pathophysiology and identification of the disease it's difficult to see here but I mark them with circles this is is a lot physiologically significant because where hydrops occurs hydrops occurs at the vogue stria this is the area of the cornea where there is highest degree of weakness. Flusher's ring is another interesting feature as I mentioned there's a market demarcated thinning and the the tear film aqueous layer of the front part of the cornea will collect iron deposits hemocidrin deposits and will demonstrate this ring shape this is a patient with who had a cornea transplant in the cornea sitting on the OR bench a scissor reflex you shine direct light into the retina and it reflects back to you with an irregular stigmatism interesting physical exam feature there are automated things that you can see inside of the clinic by photo caretoscopy video caretoscopy photo caretoscopy is well well understood we obtain in the in the clinic all the time this is a normal patient this caretoconic patient showing the classic egg shaped mire you'll notice in fear temporal mires are the distance between them is reduced whereas the norm excuse me in a normal patient they're all equidistant video caretoscopy is being used more and more for diagnosis and is associated with formal diagnostic criteria these patients have a normal sort of this is a normal sort of range for any patient coming in whereas a caretoconic will present with this classic video caretoscopic presentation with with a focus as seen in our patient if you remember his just his external physical exam this sort of matches that with in fear predominance video caretoscopy is very important we'll discuss in a moment but this is these are the the signs that we would use to clue in a diagnosis there's a a clinician in UCLA note with the name of Benowitz who is has published greatly on this subject he developed a set of formal criteria they're also modified criteria that you can use in clinic here I'll be talking about the formal extended criteria there are four components of it central corneal steepening as is typical of caretoconics the diopteric asymmetry that we saw in video caretoscopy degree of irregular astigmatism and regular corneal astigmatism we can see in the clinic using these four components Rebenowitz was able to stratify with high certainty different patients in order to say is this a person with caretoconics is this person not those who fell and I will describe how to calculate these numbers but patients who have numbers from 60 to 100% are suspected caretoconics however above 100% definitely have early or and above that advanced those below 60 have normal so how do you develop these numbers this is known as the kiss a number I understand this is sort of a daunting equation there aren't a lot of mathematicians in the room but the k value is well known to central corneal steepening inferior superior value is an interesting way of noting diopteric asymmetry there are different ways you can look at video caretograph which I won't go into detail here but skewed radial axis and a astigmatic index different these three you use video caretograph to find numbers in order to plug into this equation as I mentioned using 60 to 100 as sort of a mid-range above 100 gives us almost a certain diagnosis of caretoconics so management I've already alluded to all this the main goal of high drops is to reduce edema from the corneal stroma there are ways that we can go about that by either putting a hole inside of the iris and then as I mentioned placing decimates membrane to stop diffusion of fluid into the corneal stroma hypertonic solution to extract fluid from the edematous tissue cycloplegics and hypotentives to reduce the fluid burden inside of the anterior chamber and this is my presentation I'd like to acknowledge Dr. Ombody Tom Overg and Steve Christensen who helped me with this presentation and thank you for your attention I will take any questions that you have Yes Dr. Olson thank you for those comments Yes Dr. Tabin thanks guys