 We're going to go ahead and get started. Thank you for showing up a little bit early today. There'll probably be some other people that'll be mosing in. So we have four presentations today by some of our visiting medical students. The first one's going to be presented by Anthony Leonard. He's coming here from Storm Eye in South Carolina, and he's going to be presenting, as you can tell, on management and staging of care accounts. So I'll turn it over to you. Thank you for the introduction. So I'm going to present a little bit of work I did today in conjunction with our cornea department, specifically George Wehring, Dr. Wehring. So I have no disclosures, but Dr. Wehring is a consultant to Visiumetrics who makes the double pass scattering device investigated here. So as you know, caroticonis is a primary corneal ectasia or bulging of a cornea that's relatively common. About 1 in 2,000 people will develop caroticonis. It's asymmetric yet bilateral and is characterized as progressive and is not associated with any inflammatory condition. It is, however, associated with Down syndrome, Ternors, as well as Leber's congenital amaurosis, mitral valve prolapse, retinitis pigmentosa, as well as Marfan syndrome, and in those who are chronic eye rubbers, such as those with allergic eye disease. In our interactive slide of the day, hopefully you didn't read that, what physical finding is being demonstrated here in the lower right panel? Anyone can, has to be a resident. So that's correct, this is Munson's sign. So what you should appreciate here is that there is a cone shaped depression of the lower eyelid when the patient is instructed to look down, and this is simply just a deflection of the cone shaped cornea. So ocular double pass light scattering in this instance by an Ocus II instrument, or Optical Quality Analysis System II, uses an infrared laser diode shown through a collimator and then through a pinhole, which then enters through the visual system, reflects off the retina, back through the visual system once more, and then through a second pinhole to a camera, which collects this double pass image. And in doing so, this collects the forward and reverse scattering of light by the patient's visual system. So in essence, you're able to see what the patient's retina sees. Now to contrast this with reverse light scattering, which is a more familiar concept to most of us, in our day to day slit lamp biomicroscopy, reverse light scattering is quite easily observed. You can just shine a light in someone's eye and you'll see it, whereas opposed to forward light scattering, which really you need some sort of instrumentation to observe. Reverse light scattering, as you're well aware, is not representative of how an aberration in the visual system affects the patient's vision. We've all seen this when we look in a patient's eye and we see a really dense cataract that apparently they're able to see fine through and it doesn't seem to bother them that much. This is opposed to forward light scattering, which really defines the quality of that patient's vision. Reverse light scattering is, again, not directly related to the image cast in the retina, but forward light scattering actually has the ability to reconstruct images which are cast on the retina using some mathematical tools. So shown here is an example of an output from an Oculus 2 machine with a reconstruction of a patient's vision alongside their objective scatter index or OSI, which is simply just the ratio of scattered light to the central unscattered light, multiplied times a constant. And you can see here for this patient who has an OSI of 2.5, they do have some blurring of their vision and this is associated with the SNL and I visual acuities of approximately 20 over 30. So the clinical questions we had were, does ocular double pass light scattering increase in keratoconus and can we use a representative of this, the objective scatter index, which I just previously mentioned, as a diagnosis and staging tool. So this was a retrospective study. We included both patients who were being considered for refractive surgery, as well as those who initially presented for keratoconus. We excluded children as well as those who had previous ocular surgery or lens opacities. 43 eyes were included in the study, 22 keratoconics and 21 controls and everyone underwent a clinical exam including evaluation for best corrective visual acuity as well as imaging on the double pass light scattering device, placididus topography by the atlas and shine fluid tomography by the pentakam. These patients were then with just their topography, tomography and clinical exam categorized using the Amzler crew mic scale for keratoconus severity as well as the keratoconus severity scale or KSS. So to jump right into the data, if you look at panel A up here in the top right, you can see that the objective scatter index or OSI is increased in keratoconic patients in comparison to corals. However, there is a large amount of variability within these data. When you split it apart by keratoconus severity score, that is grades one and two which are suspect topography, whereas grades three and four are mild and moderate keratoconics, so frank keratoconus, you can see that really only KSS grades three and four have an elevation in their OSI values. This is to be contrasted with the Amzler crew mic older scale but still clinically used, which has elevations in all grades examined. So the next question was, well, how good of a diagnostic test is this OSI? To answer this, we used receiver operating characteristic studies generated these curves. So for a perfect study, you would expect the line to go all the way up the Y axis and then straight across, whereas for a coin flip, you would get a horizontal line or diagonal line directly across from the origin here. A perfect test has an area under the curve then of 1.0, whereas in imperfect test, a coin flip has an area underneath the curve of 0.5. So anything in between is better or worse depending on how close it gets to one. Just kind of as an example of a good, not perfect test is tear breakup time for predicting dry eye symptoms has an area under the curve of about 0.79, whereas a particularly bad test, prostate specific antigen, quite poorly named if you ask me, to predict progression or presence of prostate cancer has an area under the curve of only 0.68. So just to kind of give you some, rule of thumb type measurements to compare these studies. So what we observe is in comparing controls versus any KSS grade, any keratoconic grade, including the suspects, we get an area under the curve of 0.86, telling us that this is a fairly good test for being able to determine if someone is a suspect or keratoconic. In comparing whether or not, but when we break this apart to looking at just the suspect eyes, KSS grades one and two, we can see that the AUC fall significantly, telling us that really, this test isn't very good at detecting suspect's topography, that is KSS grades one and two. And as expected, if you limit the test to only looking at the mild and moderate keratoconics, this is a great test, you can see it has an AUC of 0.99. But most interestingly, and this is probably the most important piece of data I'll show today, is that when you look at keratoconics or suspect keratoconics, KSS grades one and two, versus people who actually have frank keratoconics and KSS grades three and four, we get an area under the curve of approximately 0.95, which is great. What it's telling us is that we're able to discern suspect topography from people who actually have keratoconics as determined by the KSS scale. Yes, sir? They could develop, that's right. So in the next series of slides, I'm going to display our data where we look at the point spread function, that is the double pass light scattering where a single point of light is then scattered along with the OSI values, the objective scatter index, which again is just the amount of peripheral light intensity versus the amount of central or unscattered light intensity. So higher OSIs mean more scattering. I'm gonna show this in conjunction with Atlas topography, Placidodys topography, as well as Shineplug pentakam tomography on the bottom row. And as you can see here in this control patient, there's a symmetric bow tie type appearance, which is indicative in this case of some against the rule astigmatism, regular astigmatism. When we look at KSS grades one through four, we can see that there is an increasing amount of light scatter as evidenced by increasing widening of this cone. Of the point spread function. So you can see this is wider than the control group, KSS two is wider and more irregular, KSS three and KSS four in actual care to cone. So you can see that there's a significant amount of widening and these are associated with increasing OSI values. Similarly, when we look at the KSS grades one through four, we can see an increasing amount of steepening as evidenced by topography. And as is common in large aberrations, courting elaborations, topography isn't terribly good at picking it up. Where however this is picked up by tomography. You can see that these inferior steepening patterns in KSS one and KSS two progress to even greater amounts of inferior steepening in KSS grades three and four. So in summary, combined with topography and tomography, this objective scatter index provides a decent diagnostic tool. It was found to be significantly increased with KSS grades three and higher and had a significantly large area underneath the curve in comparing controls versus these grades. Double pass light scattering is probably even better as a tool for following care to cone as patients. So when comparing those patients who had KSS grades one and two versus those who had three and higher, we actually got an area underneath the curve of 0.95, which is a phenomenal test. So with that, I'll open the floor. These are my references. I'd like to acknowledge my co-authors including Dr. Waring, the principal investigator on this study, as well as my sources of funding there at the bottom. So with that, I'd like to open the floor to any questions. I don't have that number at the tip of my tongue, but I did note that there was some apical scarring. So one of the criteria for the KSS scale is apical scarring or clinical findings, such as Rezoudi's sign or, I'm blanking on the name of it right now, be a vertical striate, vote striate. So there are, I just don't have that number. I'm sorry. It was a great question. So he's asking, did we follow patients? No, this was just a cross-sectional kind of retrospective type study. I think that's an important study to do to see if this actually becomes a good predictor. So we were able to discern from KSS grades one and two and three and four here, but that doesn't necessarily mean that it's the same as following a patient who had KSS one and two for a period of time. I didn't do that analysis specifically, but there was no significant difference, so I would expect it's a pretty low area underneath the curve. For grades one and two, the area underneath the curve was 0.6, so the clinical utility would be to follow patients who you think might be developing careticoanus or to look at patients with careticoanus or mild careticoanus who you are afraid of might have bad visual quality since this is able to reconstruct the quality of vision that they are able to observe. No, sir. Dr. Petty? You see a lot of new things. Right, in the rare instances where we have nonverbal patients, this would be an excellent way you need to measure their visual acuity. But I will say that you get on a slippery slope when you want to do this for every single patient who's able to tell you that the vision is terrible. I think it's more useful for clinical studies, so if you are doing some sort of optical system intervention in ocular lens implant, in tax, what have you, this would be a great way to tell if to compare interventions, because it then gives you a continuous variable which you can test very readily with statistics. Yes, they've done those studies in the past. Pablo Artal is one of the developers of this technology. Dr. Wehring was actually just at his lab yesterday. They have done a lot of the studies which give those relative correlations of OSI values with BCVA. They haven't looked at it specifically in careticoanus, but they have looked at it extensively with lens opacity. So wavefront aberrometry, if I'm not mistaken, measures the way that the cornea will, it's a ray tracing type tool where you shine a ray and then you see where that ray goes. So that is a form of forward light scattering analysis. What it doesn't pick up is the continuous any aberration continuous in the optical system. So if there's any vitreous or interior chamber opacities or lens opacities for that matter. If there are no further questions, thank you for your attention.