 Okay, so we'll go ahead and get started. So we have some fourth year medical students that'll be presenting to us today. We're gonna start with Kevin Garf, and he's a medical student here at the University of Utah. He's here from Salt Lake, and he's gonna be talking about measuring ocular blood flow in glaucoma. Thanks, Brian. Good morning. Before I get started, I'd like to thank Dr. Orozco for helping me get this presentation ready and helping with my slides. So I'll be talking about ocular blood flow in glaucoma. So glaucoma is often referred to as the sneakleaf of sight because it has an insidious onset. It starts in periphery of the vision, the vision loss, and kind of like you've seen this picture here, presentation of what someone with glaucoma, advanced glaucoma would see. It's an optic neuropathy that is characterized by loss of the retinal ganglion, nerve cells, and optic nerve axons. With glaucoma, the vision loss is irreversible and permanent. So patients are often asymptomatic, don't notice disease until it can be advanced. The irreversible damages already occurred. Multiple studies have shown that elevated intraocular pressure is correlated with the vision loss in glaucoma. It's thought to be via direct compression on the optic nerve, the laminar crevosa, axonal flow leading to the death of the retinal ganglion cells. And studies have shown that reducing ILPs is shown to slow vision loss, but not reverse vision loss. But there's a subset of patients that even if you are able to reduce the intraocular pressure, they will continue to progress. And there's also a subset of patients known as normal tension glaucoma who really never develop elevated intraocular pressure, but still have the typical peripheral vision loss and optic nerve changes. So there's more going on than just ILPs. So I'd like to talk a little bit about possible vascular components. So studies have found a higher prevalence of ischemic lesions in the heart, eyes, and brain in glaucoma patients and additionally diseases of the blood vessels and blood pressure, both hypertension and hypotension have been associated with glaucoma along with diabetes, peripheral artery disease. These are normal tension glaucoma as I was mentioning that glaucoma patients with that never seem to have an elevated IOP. That form of glaucoma has been associated with vasospacic disease such as renotes, low systemic blood pressure, but in particular something called ocular perfusion pressuring. The in the last few years, the American Academy of Ophthalmology has actually identified ocular perfusion pressure as a risk factor for glaucoma. So what is ocular perfusion pressure? Just going back to blood flow to any organ, so Q flow is equal to the difference in pressure over resistance. So our delta P is also known as the perfusion pressure and in the most simplistic terms, that's just the difference in pressure between the arterial system and the venous system, but in the eye you can't directly measure those pressures. So ocular perfusion pressure is measured using the main arterial pressure to estimate the arterial pressure in the eye and then IOP to estimate venous pressure. That two thirds basically accounts for the drop in pressure from the brachial artery from typical blood pressure reading up to the ophthalmic artery, but that is just obviously an estimate that can change if a patient's laying down or even sitting and the IOP is not an exact measurement of venous pressure. Venous pressure is obviously a little higher to allow flow, but a general estimate for venous pressure and then our resistance, I'm not gonna really talk about much today, but the biggest factor affecting resistance is diameter. If you remember the equation, it's radius to the fourth. So the diameter of the vessel plays a huge part in that. So a little bit about ocular perfusion pressure in glaucoma. I just wanted to highlight a few studies that have looked at ocular perfusion pressure in glaucoma patients. And the main point here is that ocular perfusion pressure, low ocular perfusion pressure has been associated both with increased incidence and more advanced progression of glaucoma and really the strongest evidence has been for a low diastolic ocular perfusion pressure. So the equation I presented in the last slide, which is just looking at the mean ocular perfusion pressure, but I can be broken down into systolic and diastolic. And so as I mentioned, so it's increased with or associated with increased incidence and progression of glaucoma. And these were some of the bigger studies that have been done. So as we think about that, ocular perfusion pressure is really an estimate. So how can we actually measure ocular perfusion in the eye? My interest has been particularly in the coroid. So coroid derives its blood supply from the posterior, ciliary arteries and it accounts for the vast majority of blood flow to the eye. It's one of the most vascular areas in the entire human body. And it actually supplies the preliminary area of the optic nerve, which has been implicated in glaucoma. So the first myth that I wanna talk about, possibly a way to measure ocular perfusion in the coroid is called dynamic contour tonometry. So this is a tonometer, pictures across the top. It's similar to the goldmine, except the actual tip of the tonometer is curved to fit the eye rather than a flat replanation. Another difference is, it's actually able to measure the waveform of IOP. So just like blood pressure, IOP is dynamic. And when we're taking it, we're measuring it at one point in time, but it changes just as blood pressure does. So this is kind of a typical reading that the dynamic contour tonometer shows. This is an example from a machine called the Pascal. And you can see there's this waveform particularly it gives you a measurement called OPA or ocular pulse amplitude. And all that means is it's the difference between the maximum IOP during systole and the minimum IOP during diastole. And there's been a lot of interest in how ocular pulse amplitude could be related to blood flow. And so it's thought to indirectly represent the coroidal perfusion because it gives you that pulsed-out component of blood flow. And a lot of studies, I just wanna kinda highlight a couple. A lot of studies looked at this in glaucoma and Schwann suggested that it could be an independent risk factor for the presence of normal tension glaucoma and especially when they compared it to just a primary angle, primary open angle glaucoma and patients that did have elevated pressures and ocular hypertension. Additionally, it's actually been found to correlate with severity of the disease as defined by a cup to disc ratios and visual fields. So another method that I wanna talk about is coroidal thickness. So early histological studies back in the 60s and 70s looked at coroids, postmortem, found that they were thinner and had a reduced density of vessels. But really, they weren't able to get a good in vivo look. I told a few years ago, Dr. Spade published from papers about what he called enhanced step imaging. And that is a mode used on the OCT that actually allows visualization of the anterian posterior boundary of the coroid. And he used enhanced imaging to actually measure coroidal thickness. And his studies mainly looked in healthy patients and they found in healthy patients that coroidal thickness was strongly correlated with age and axial length. Interestingly, axial length has also been correlated to intraocular pressure. So this is kind of an example of an image acquired from enhanced step imaging on OCT. And these red lines are just delineating the borders of the coroid for a measurement. So here's the anterior borders below the retinal epithelium and then the border between the coroid and the sclera. And you can really actually get a pretty good view on most patients of the coroid. So a little bit about some studies that have looked at coroidal thickness and glaucoma. There's been some disagreement over whether there actually is a relationship between glaucoma via incidents or severity and the coroidal thickness. I'm highlighting a few studies that identified some differences, although there were that did not find any difference. And really it's hard to compare the studies side to side because most of these studies had different groups. So once that he looked at glaucoma suspects versus glaucoma patients in general, most did not differentiate between glaucoma patients with elevated intracular pressure and normal tension glaucoma patients. And most of these studies were cross-sectional. There was this one by Cara that actually looked at patients before and after trapeculectomy and found that the decrease in IOP corresponded with an increase in coroidal thickness. But really where the best evidence seems to be if there is a difference would be in the parapapillary region, which would make sense around the optic disc, although some did find a difference in the sub macular sub foveal coroid. So a little about my interest in research. So I've been working with Dr. Roscoe and Dr. Petty and we have an ongoing study here at Moran where we are looking at both ocular pulse amplitude and portal thickness. And we're looking to compare it to known risk factors for glaucoma and indicators of disease severity. We're actually splitting patients into three groups, primary opening glaucoma patients with elevated intraocular pressures at time of diagnosis, normal tension glaucoma patients. So patients who have never in their medical record had elevated intraocular pressure and then healthy controls. We think that will best allow us to detect a difference. And we're comparing parapapillary and sub foveal coroidal thickness as demonstrating these two pictures in patients, comparing that both with ocular pulse amplitude, ocular perfusion pressure, visual fields, and IOP, just various indicators of glaucoma patients and hoping to better identify if there is a relationship both between severity of glaucoma, ocular perfusion pressure and these two new methods of possibly majoring of ocular pulse amplitude. And coroidal thickness. So here are my references. Are there any questions? Yeah, that's a great question. So I mean, that's been the problem with a lot of cross-sectional studies. You can identify possible risk factors, but really hard to identify is this actually a causative? Is it just associated? So, I mean, ideally, if you're able to identify a difference in a cross-sectional study, would be to follow these patients forward in time and see if you can correlate changes in the pulse amplitude and coroidal thickness which actually changes in the disease. Does that answer your question? Dr. Olsen. So, and really as we do all... Yeah, I think one of the, the Heruca study, they actually identified a normal tension. So those patients did not have interocular elevated pressures and they were still able to find a difference. But that's a good point. A lot of the studies lost their significance when they actually controlled for IOP.