 Okay, so our next presenter will be Sherif Rauf and he's presenting on peripapillary retinal perfusion in papillodema, a pilot study using OCT angiography, and he's a fourth-year medical student from Stony Brook. All right, everybody, thank you very much for the introduction. This is our talk, let's get right to it, no disclosures to share with you all. All right, so OCTA, what are we talking about here? This is a promising new optical imaging modality that uses motion contrast. Its fundamental premise is the same as OCT, except with the variation of how the data is processed by the software. Volumetric scans are acquired and segmented. The nice thing that we'll hopefully give to this is that you can acquire qualitative as well as quantitative data. So the technology that distinguishes OCTA from OCT that we're all familiar with is called Split Spectrum Amplitude Decorrelation, or SSADA, essentially allows the machinery to distinguish between static and non-static tissue due to the fact that non-static vessels will produce signals of larger or more varying amplitudes over time. That is, particles that move faster across the light beam will cause a higher decorrelation and can be distinguished in that way. The hope is that with this you can distinguish perfused vessels which should be more highly decorrelated from more static tissue. So this is kind of what you get with an SSADA, you get an on-face angiogram. The important point to take home here is that vessels must be perfused and kinetic in order to be seen. It can be useful in assessing the perfused retinal capillary network in the macula as well as retinal peripapillary capillaries. So those we'll just call RPCs from now on retinal peripapillary capillaries. A bit of the anatomy, depending on the depth of focus that you opt for, OCTA can image various vascular beds in the retina, including the coriocapillaries, which is not depicted in this diagram. Until recently the RPC network has been mostly visualized through histopathology, analysis ex vivo, as demonstrated here with this indian preparation. Advanced optics scanning has also been able to capture the fine details of this capillary network, but it can be somewhat limited. A recent study demonstrated a comparison between OCTA and adaptive optics. We can talk about the relative strengths and weaknesses of those, but the thinking is that OCTA will allow for better visualization of this network, while perhaps being a little bit easier on the health care provider and the patient. Short description of the kind of data that we'll get. So here I'm going to show you we're going to have a visual representation of areas that are well perfused as well as areas of dropout. In terms of the quantitative data, which affords significant advantage, we'd like to get mean perfusion values for different segments surrounding the optic disc as well as inside the disc. The analysis fundamentally begins with determining where the layer of interest is. This is just an example of the automated segmentation highlighting the NFL layer between the red and green lines. For a given image, you can then calculate what's called the mean perfused vessel density. Essentially, this is basically a calculation of the total number of voxels or pixels within a given sector that correspond to perfused anatomy divided by the total number of pixels in that anatomy. And then we can subset each of the areas that we're referring to and determine whether or not there's a spatial relationship, etc. So the basis for the sectors that you're seeing around these, and we'll refer to these throughout this, are the work that Garway Heath did in determining where RFL defects and prominent bundles kind of converged on the optic disc. So the parapapillary ring is thus divided into six sectors that were the basis for their work. So that's OCTA. This is a bit about the processing. Here on the left most, you see the image that we've viewed over and over. This is a skeletonized OCTA, which just takes every vessel that you'll see, regardless of its width, and assigns a uniform one unit width. This allows for better visualizations, various dropout, and also prevents us from perhaps overestimating the effect of large vessels on the perfused vessel density calculation. And the last two maps are simply color maps where colors assigned to each pixel in the frame based on the density in that area. Density of greater than 50% perfusion is assigned the color of red, zero is blue, and then intermediate colors are accordingly assigned. And then you can kind of see how illuminating that the overlay of the two can be. This is just a quick overview of some of the work that's already been done. A prominent paper showed that in normal discs, the dense microvascular network was visible with OCTA and that it was visibly attenuated in colcomitus eyes. So this is our fundamental question. Can this provide any new information about peripapillary retinal perfusion in papillodeminus eyes? This is our purpose. We had two hypotheses that there was a difference between our patient and control groups and that patient eyes would have lower peripiricine of the RPCs. This is our methods, all done at the same place. A bit about our control and patient numbers and their breakdowns. This is the equipment that was used and a bit about the analysis that we did. So the parametricity of the data was examined. There were some departures from it, but not enough to preclude us from using an ANOVA. And then a comparison was also performed between low and high grade. It was not found to be statistically significant, but will limit our remarks to the former comparison. Again, this is just a bit of the qualitative. Here we have color map representations of control and low and high grade papillodemus subjects. And so you can see even subjectively that there are increased blue areas of non-perfusion and papillodemidus subjects as compared to controls. These are the perfusion density values that we referred to earlier. You'll see that across the board, each of the six sectors as well as the entire peripapillary region taken together, there is significantly increased perfusion for controls. The inside disk is notably the only one that is increased in patients versus controls and we're going to get into why that might be the case. This is just an example of control in a high grade. And so you see here that for these comparison high grade papillodemus versus our controls, there was a statistically significant decrease in RPC perfusion. And this is highlighting just some of the areas of dropout. So I guess the take home result that there was really one to be taken home is that there was overall peripapillary decrease of 5.7% decrease in peripapillary perfusion between the papillodemidus and control optic nerves. So just a bit about the pathophysiology. While this isn't completely elucidated, there's very much informed way we're thinking about our results and how we might interpret what was happening. So the idea is that papillodema in increased intracranial pressure is not entirely a vascular phenomenon. Hyra has done a lot of work that's been really useful on this. The pathogenesis is not one of initial leakage of fluid into the interstitial space but rather it's thought to be caused by intrinsic swelling of the ganglion cell layer due to stasis of axoplasmic flow. The initial edema then can cause compression of low pressure venules and then venous stasis can give rise to leakage of venous blood into the extracellular space. The thinking is that low pressure venules and peripapillary capillars would be most subject to this kind of compression. So it's kind of easy to see how this might cause some kind of ischemic damage as the RPCs become progressively obstructed. The venous stasis could lead to hyperprofusion. That in turn could lead to dilation of superficial capillars at the nerve head. And ischemia is possible. Ischemic damage to the RFL is what we're worried about. And we would be very remiss if we didn't think that this could be able to predict RFL bundle loss and visual field loss in papillodema. While we haven't correlated the deficit in perfusion density with that functional loss, that's something that we would aspire to do. So there were lots of real limitations. This was the first time study that we'd done with OCTA. There are lots of artifacts in acquiring the data. A lot of good data that we would have to keep had to be thrown out. You rely quite heavily on the automated segmentation. The machine doesn't always do that well, especially in highly demented disks or very tilted disks. We often had to manually adjust the delineation of where brux membrane was opening. And then we worry about vessels where perfusion hasn't ceased entirely, but it was very slow. The concern is that the decorrelation algorithm may not be robust enough to detect those as perfused. So it becomes a matter of thresholds, and that's something I think everybody is still trying to figure out. This is an example of a notable part of me, a notable lousy image due to artifact. Again, like I mentioned, we didn't have any bases to make structure function assessments. Also, there's no normative database for us to work with while collecting the data. This is something I think that is going to be a really promising avenue for OCTA analysis. And we want to see whether changes, particularly in the perfusion of the RPC network, can be associated with bundle loss and visual field testing, and whether or not that will be robust enough to be detected. So I think OCTA is really exciting. The more I got familiar with it, the more I'm kind of convinced of its potential with the few caveats that we've discussed. I think it's a very fast, non-invasive way to image the capillary networks. I think it's, once well used, could be exquisitely sensitive to identifying changes in perfusion levels and might elucidate some of the functional losses that we see as like the capillary team that I'm indebted to. And I'll take any questions or comments. We'll talk about this more. Were all the patients either dilated or undilated? And was the illumination in the room where the OCTA testing was done controlled in all patients? Yeah, the room was, again, and patients were not only dilated, but the technician who did the scans did seem to think that that mattered. But the room was always very... Some were dilated, some were not. No, they were not dilated. All were not? Yeah. Do you think they all took it, or...? Well, just with corocatillary perfusion, I mean, you can definitely get changes in non-mount blood, perfusion with changes in, you know, lighting conditions and dilation status. No, I don't think it matters as long as it's... Yes. Any correlation to the ethnicity of Prasadena? How long you've had it? Do you have more chronic changes? Stasis changes after the OCTA? So, I think that might be a shortcoming of our analysis. You know, we didn't have very many of the high-grade, I'm going to show you the qualitative comparison, but we didn't adjust for a time of syncytagnosis. I suppose that's the best thing we could have done. We tried to do comparison by grades, I'm sure, but I think that would be interesting to pursue once our dataset was more robust, there would be more subjects with a longer span of databases. How do you know that you're seeing reduced perfusion due to papillodema versus reduced ability to detect perfusion because of the papillodema itself obscuring vasculature? I don't think that we do. We tried and we're trying to address this. I think the skeletonized version of the OCTA analysis might address that. So that was the picture where every vessel, regardless of its width, was assigned the same dimension and the same threshold was used to declare it was either perfused or not perfused. The thinking is that if you have a compression of very small vessels, but also the analogous dilation of medium or larger vessels in papillodema, that you might be overestimating the contribution from dilated vessels. So we were worried that that was going to obscure the compression of the vessels we were interested in. Beyond that, that's a difficult question to address and that was the way that we came up with to alleviate that concern in our minds, but I think that's a question we're struggling with. Thank you very much.