 Should we get started? So Steve, actually, do you want to introduce yourself? Actually, they all know it, because I've been coming and learning, sitting right alongside them, and hopefully learning as much as they're learning. Okay, good, good, good. Yeah, I think they all know me. Let's see if I can get this to advance this way. Oh, maybe not. That's okay. Okay, that's okay. So this is supposed to be very, very interactive. So I want you guys to think about questions, okay? And you do need to know landmark studies for the boards. So that's, you know, you need to know the key takeaway. So we're going to try to think about why these studies were conducted and basically what questions were being asked. So one thing I always ask, what are our current topical eye drops that we use for glaucoma? What are they actually indicated for? Okay, decreasing pressure. Decreasing pressure or decreasing, and this is kind of a nuance, decreasing elevated pressure. Elevated pressure. And why do you say that? Teresa, what do you think? Correct. So lower the pressure, because that's the only thing that we know that works. And it really based on what the clinical trial design showed us. So when the current glaucoma medications that we have were approved, the patients were randomized with higher IOP. So they had to have at least 21, 22, or 23 millimeters of mercury to actually be included in the clinical trial. The only study recently that did not do that was by Zalta. So if you look at the label for all our current glaucoma medications, they are not indicated for glaucoma. They're indicated for IOP elevated lowering of interocular pressure, except for by Zalta. By Zalta is indicated for lowering of interocular pressure. The reason being is they had one clinical trial where the baseline IOP was 19. So technically that was not elevated. So again, when you think about a clinical trial and where some of these trials were conducted, it really is around who was put into the clinical trial. We'll talk a little bit about PO AG, Normal Tension Glaucoma, what defines it, and what makes these studies and landmarks. Also, how do they impact our care and our approach? What are the takeaways and why should you care as a resident? And that really is the way the OCAPs, when you're quizzed on them, that's what they want to know. So PO AG, so define for me, what is PO AG? What does it stand for? Why? Why is that primary? Not secondary to anything else. Correct, not secondary to anything else. So when you examine the patient, what do you not see? So all the pertinent negatives, steroid use, trauma, right? Congenital juvenile, those would be considered different, although there are... Well, juvenile is a little bit of primary, but more and more we're thinking of it separately. What constitutes it? How do patients present? Why is it painless? If they have pain, what would you think? Secondary cost. Secondary cost, sudden, right? So it's slow, it's insidious, it's a progressive optic neuropathy, and what is to date still the biggest risk factor? Age is good, but can you treat age? No. So I correct myself, I should have said, what's the most or the modifiable risk factor? What's the strongest modifiable risk factor? There's pressure, but you're right, age, absolutely. So let's think about what are the other risk factors? Age? Is corneal thickness a risk factor? We use it all the time. I ask you all the time, what's the corneal thickness? You don't have to answer me yet, that'll come up in one of our landmark studies. So the question is, is corneal thickness actually a risk factor? IOP is a risk factor, right? We show that if you lower IOP, you can slow down progression. How do we know that? How do you know that? Studies have shown it. These studies, these landmark studies, these are what basis our treatment paradigm. What are some of the secondary causes? You had mentioned it, Ariana. Uvascularization. Uvascularization. Medication is good. Trauma. Uveitis. Uveitis. There's a whole list. Okay. Why do we care about their history? There's been genes that have been linked. We still can't look at them, but that's where the studies are going. In fact, I'm going to mention one of the studies that's actually looking at the genetics. But also, family history is important. Because again, if there's a strong family history, especially at a younger age, that can indicate one of the genetic predispositions. How about medical history? We talked a little bit about it. You could push it towards looking for secondary causes. Okay. Like what? As long as you have diabetes, is diabetes associated? Is that a risk factor? If you have new vascularization. If you have new vascularization. Okay. But how about primary diabetic? Are they going to increase risk for POAG? So Steve says yes. They wouldn't have to deal with their vascular supply in length there. Partly. Yes. You just said something. Did some studies say yes? Correct. You know, and it depends upon the study, and the way the study was conducted. So basically, I think it was, was it oats where they actually did a questionnaire? The problem there is that it was secondhand reporting. So the patient had to report whether or not. And a lot of times patients weren't even sure if maybe they were prediabetic. The jury's out. But yes, if you're thinking about an ischemic cause, for sure. So we say the totality of the data. You know, it's the IOP, it's the medical history, the family history, the ophthalmic exam, the structural loss and the functional loss. So when I see a patient in my clinic, and they say to me, do I have glaucoma? And when I'm seeing them for a second opinion, I look at the whole patient and I look at the whole story. And sometimes you can't tell them, do you in fact have damage, or do you in fact have glaucoma? It's suspicious. But I usually tell them it's not just pressure. Pressure is one piece. But it's also the structure and the function of the nerve. Ask about steroid use. In fact, I was talking to Ariana yesterday and I had a patient that we had been following, Chai and I, and he's had, his eye looks like a hardware store at this point. Really, really bad Parkinson's, volatile IOP, volatile blood pressure to the point where he will stand up and his pressure will go to, you know, 90 over 40. And then he'll get a little nervous and he'll be 210 over 170. I mean, it's insane. He's got really bad vascular endothelial regulation. His pressures have been spiking. His blood pressure was uncontrollable. And I, you know, I'm always like, okay, what's new? We see him all the time. We follow him really closely. He had been getting steroid injections in his back. And he didn't think to tell me. And we had talked to him about medications, but he didn't associate these steroid injections with medications. Now, could this be impacting him as possible? He's actually a very interesting patient because he's actually now on CBD oil. Actually, he's on THC and CBD in a mixed combination. And he came in and he was really relaxed. And he said he feels like he's stoned all the time. He's 78. His Parkinson's. He has less of a tremor. And his pressure actually was in the low to mid teens. And he had been running in the high 20s. So it'll be interesting. I told him to stay on it. Don't change anything. Don't get any steroid injections in your back and come back in a month. So Chai and I were corresponding about him. But very, very interesting patient. He also is ENOS deficient. So I checked him for a genetic marker for endothelial nitric oxide. Synthase. And he is homozygous deficient. So he's got another respect. But ask about normal tension predisposing factors. We talked a little bit about that. You guys have mentioned it. So what, again, we talk about it at the VA all the time. What do you want to know about that normal tension glaucoma patient? And when are they taking their blood pressure meds? When are they taking their blood pressure meds? Why? Because they have maternal hypotension. They take it at night. And what do you think is worse? Think it's worse to have high blood pressure or too low? That's kind of a trick question. Depends upon how high and how low. Exactly. And if you read the studies, if you look at some of the studies now coming out, it's variable. In fact, what we're thinking that the biggest concerning factor is the change. It's the big swings. We'd rather have a patient that runs consistently lower or consistently higher, but it's those big changes, especially at night. We're all at secondary causes. We talked a little bit about that. Ischemia. If somebody has ocular ischemia and they're not in angle closure, how do you think they would present? High pressure or low pressure? Low. Why? They increase. Yeah, exactly. So again, if you're seeing asymmetry, glaucoma tends to be, can be asymmetric, but usually both eyes have it, except for what's the leading cause of asymmetric glaucoma? Besides ocular. Secondary. Besides trauma. My passion. Psydux. Psydux. Yes. We'll present asymmetrically. So if you see asymmetric glaucoma, think about these other causes. And if you're really high, if you've normal to high pressure in one eye and the other eye is low in a diabetic, cardiovascular disease, which is the abnormal eye? The low one. So don't always think about the high eye being the pathologic eye. Put the whole patient into the picture. And go neo, right? Because if you see some NVI in that eye that has lower pressure, that could be an indication of ocular ischemia. I actually, as a resident, operated on a patient like that. And brunesse and cataract, gentlemen with prostate cancer, and I was with my retina attending at the time. And we were doing extra caps back then, did an extra cap, and suddenly the lens comes out, but all this whitish material. And my retina doctor didn't even know what it was. He was like, this looks really strange. Turns out it was all just a vascular retina. And he had just, you know, a very ischemic eye. So we'll never forget that patient. Your patients always teach you. 30 to 50% of patients with POAG have IOP less than 22 on initial exam. The other thing to think about, variability, diurnal variability. I will still bring patients in and do diurnal curves. When's pressure the highest? First thing in the morning. And there's some great monkey studies. I was just at ICER for four days, and it was all about glaucoma. And it was all preclinical for the most part. And they've got some really great monkey tracings now of normal healthy monkeys that upon weakening, I mean, there are dramatic increases in IOP, with constant IOP moderating, monitoring. You know, and they can go up into like the high 20s and then slowly come down. So always first thing in the morning upon waking. And it can be as much as 10 points, which is really, you know, that's crazy when you think about it. So you could be seeing a patient in the afternoon and their pressure could be 14, but it could actually have been 24 in the morning. So always think about when the pressure's the highest and that's the pressure you want to try to reduce. You want to go from the highest point. What are some other risk factors? I think we talked pretty much about that, right? Anything else that we did not cover? How about lying on one side? What about elevated episcopal menus pressure? We don't talk about that very often. You guys remember the patient I presented? So she actually responded very nicely to Ropressa, which vasodilates. So pressure came down to about 12 from 17. So this is a patient that has a unilateral elevated episcopal menus pressure. What we think is a low flow fistula from strabismus surgery when she was 14. She's now in her early 50s. So I've been trying to get her an OCTA to see where that anastomosis is. Mastomoses is. I haven't had much luck. And trauma. Think about trauma. Yes. Sleep apnea. Sleep apnea. Sleep apnea, yes. How many patients do we send for sleep apnea at the VA? All of them. That I actually have on another slide. Yep, right there. I really think we're at higher incidence here in Utah because of the elevation. It just seems that we have a lot of patients with sleep apnea. Okay. But also what people don't realize with sleep apnea is after the end of each apneic episode, or high apneic episode, your oxygen levels low, so your retinal blood vessels are dilated like crazy, and then you have this what's called reprise, which is this massive bang increase in the blood pressure at the very end. And on people with CPAP, I always ask about elevated episclerol venous pressure because of the elevated thoracic venous pressure. But nobody's ever studied this. That's a great point. That's a very good point. I'm sorry. I didn't mean to interrupt you. No. Just to think about this whole process. Because I actually will ask patients with more severe glaucoma on one side what side they sleep on. Exactly because of that point with the elevated episclerol venous pressure. And we're still thinking too that patients in a supine position also have elevated episclerol venous pressure. And we don't even think about that piece. Yeah, I'm still right there with you. There's so much more that we don't really understand. Normal tension glaucoma. So we think about sleep apnea and normal tension glaucoma, but I think it's playing a bigger role actually in all our glaucoma patients, especially those that have these volatile blood pressure changes and venous congestion for everything that Dr. Sinclair just said. 90% of Asians, very, very high. Actually upwards of 9% in Japan. A little bit lower in Korea and other sort of Southeast Asians. But think high in Asian population. And is it really a distinct entity? More and more we sort of say that glaucoma is the spectrum. So we're not thinking of it as separate as we would with Poet, but we end up working them up much more aggressively also from a neurologic standpoint. Phasospastic disease, rainouts, migraines, low blood pressure, over-medicated, hypertensive patients, hypotensive, autoimmune, low salt, exercise, nocturnal variability. Very interesting patient population in Park City. You've got a lot of your ex-athletes that are aggressive with their exercise. They're worried about their health, so they purposely take in less salt. So their electrolytes tend to run low, their blood pressure tends to run low, and especially in women, they tend to be very thin. And it's amazing how many of them have what looks like normal tension glaucoma. And what I'll do is I'll do a 24-hour blood pressure monitor on them, a 48-hour blood pressure monitor, and look at the variability, and sometimes I don't find anything. A lot of times, too, they will have history of standing up and becoming dizzy, their blood pressure runs low, so then I'll put them on salt. They want a salt diet before they go to bed. So I say, please increase your salt intake. We need to get your blood pressure up. And they'll come in and they're like, yeah, I'm running like 100 over 60. That's great. Keep eating your pretzels. Recreational, getting to that point. Ask what the patients do. We've got a really interesting gentleman at the VA who is a young... He's a doctor. He's on staff at the University of Utah. I don't know if any of you have seen him with me and I can't think of his name. I want to say he's in his 50s, early 50s, maybe 40s still. Has been worked up for normal tension. He's had the gamut of everything. He used to play wind instruments as a youngster, high school and college. Supposedly it increases venous congestion. Could it cause episodes of increased interocular pressure? It's been reported. His brother also has glaucoma and his brother also played wind instruments. So for what it's worth. A patient of mine is a pilot and he's been having progression. Multiple medications does not want surgery. He's had laser. He flies back and forth to Las Vegas. He lives here in Las Vegas and he is a private pilot. So it turns out he has sleep apnea. So I asked him, I said, well, what do you do when you fly? Do you wear oxygen? He's like, no. Mike, have you ever monitored your O2 sat while you're flying? So he did. Sure enough, it drops. So he now wears oxygen when he flies. I don't know if it's going to help him or not. But when you're dealing with a pressure of 12 and you've got fixation losses or actually you've got losses close to fixation and you're on maximum medication and you're trying to do everything possible, just keep thinking outside the box. Area of controversy? How much is IOP playing a role? Think about vascular dysregulation. Nitric oxides become a very interesting topic. You can have mutations and not make enough of nitric oxide. You tend to run higher though, usually. And also a lot of discussion around the laminar carousa and CSF. So that tension on the laminar carousa, there's a lot of conversation, a lot of interest at ICER on that. That's a whole full day conference lecture. All the other things that can cause normal tension glaucoma in the differential. So basically things that can change or cause damage to the optic nerve head. So things to think about. In fact, my gentleman with Parkinson's I actually thought he may have had a posterior ischemic optic neuropathy and I thought he had an infarct. His optic nerve didn't look different but he went from having almost no visual field to a dense hemispheric scatoma. But his pressures are running low 20s and he's got all these other autonomic vascular abnormalities. I'm sure he's got a schemia going on and I'm sure more and more so many of us think that yes glaucoma has a strong schema component to it. So ophthalmic signs. Peripapillary atrophy. There is loss of photoreceptors there. There's also damage and changes to the fine capillary beds that are actually within the optic nerve head. And this is where a lot of the conversation at ICER was around is actually what happens to the optic nerve head. And even with just subtle movement, I think you guys have heard me mention this, now a lot of the engineers in ophthalmology are focusing right at that optic nerve head because there is so much stress even with just normal eye movement. And you've got all these little vascular capillaries that are running up through the optic nerve head and if you pinch them, if you squeeze them, if you have extreme changes in vascular blood flow, vascular congestion, is that what's giving you your nerve fibrolet or hemorrhages? Is that perhaps what's giving you that peripapillary atrophy? Challenge with peripapillary atrophy and tilted optic nerves is it can also give you visual field defects and it can also give you changes on your nerve fibrolet. The other thing that I thought was interesting because this is right out of the AAO.org web page is, this works, yes. So what they wanted to demonstrate here was a notch. So the conversation on this web page was about visual field fixation and focal notches, more so in normal tension glaucoma. I think you can also see this in regular poetic. But anyway, the point was, is that be suspicious for a notch. And this was the contralateral eye that they demonstrated and as I was looking at this, I was like, you know, what about the vasculature here? It's very narrowed. And here, there's almost AV nicking. And look at this. Would you agree, Steve? The vasculature is not normal. And this was their representative case on AAO for normal tension glaucoma. So again, I'm like, hmm. Look at the blood vessels also in these patients. Look at the asymmetry between the blood vessels in these patients in your normal tension because a lot of it, again, may be partly ischemic. And then again here, what would you want to do for this patient the next time they come in? This is something, again, I hound you at the VA on. 10-2. 10-2. Because what you want to try to do is preserve that central vision. And that's going to encroach. And that's going to change your treatment. Gratitude. So ages. This is not yet in the landmark studies, but I thought this was an important paper to call out. There's been, it's an ongoing study. And basically they wanted to look at the differences in glaucoma onset and the rate of progression between individuals with African descent and European descent. They looked at patients that actually had no glaucoma and also those with POAC. So it's somewhat a natural history study as well, right? They found that patients with African descent had thinner corneas across all diagnostic groups. They had a higher percentage of reported diabetes and high blood pressure and a lower percent of reported heart disease. They also had worse pattern standard deviation on visual fields than patients with the European descent. No difference with mean intraocular pressure. Significant baseline differences were found in a number of clinical findings between patients of African descent and European descent. Again, patients. So these are patients with POAC. Logitunal data will be important for determining baseline features. So they collected all these patients. They said, okay, some of you've got glaucoma already. Some of you are age match controls. Let's follow you moving forward. Here was the breakdown. They found that African descent patients were significantly younger, as we would expect, right? We tend to think about our African patients. After adjusting for age, they also had different phenotypic characteristics compared to Europeans. Higher interocular pressure, worse visual cutie, and worse visual field mean deviation and thinner corneas. So again, we talk about when we look at those visual fields, look at the mean deviation as well. I know we look at pattern standard deviation and the focal defect, but look at the mean deviation because even a change in mean deviation over time with no focal defect can also be representative of early glaucoma's change. So look at the mean deviation. And I thought this was interesting. Family history didn't differ. So we sort of knew we always thought African Americans were at a higher risk. Multivariant analysis revealed that at higher mean IOP during follow-up, individuals of African descent were more likely to develop visual field damage. So they've got higher IOP, they've got thinner corneas. So back to the question, is thinner cornea a risk factor? Or are we just missing true IOP measurements? So we haven't yet determined if thinner corneas in and of themselves are risk factors. But we know to look for it because it's going to influence our IOP measurement. In addition, older age, higher baseline visual field, pattern standard deviation, glaucoma's optic disc, increased risk of future visual field loss. What study does this sound like? You guys know which landmark study talked about a lot of the same things. Higher baseline IOP, older age, larger optic nerve. Keep that in your mind. Older age, higher baseline visual field changes, glaucoma's optic nerve at baseline, older age. For the study for the patients that didn't have glaucoma, was there any difference in the baselines? There's still going on with this. So this is this with different regions. No, that's not that. I take that back. So it's still going on so that cohort of glaucoma subjects, those were the controls. So it's the same. The higher mean IOP. So those were glaucoma suspects. So they were considered controls at entry point. They did not have yet glaucoma and they found the same, the higher IOP. So everyone was at least a glaucoma suspect. No one was completely normal? No, no one was completely normal. And the next step, they're continuing to follow these, they're continuing to follow these patients and now they're doing genetics to help try to understand the clinical phenotype and the difference between clinical phenotypes. Landmark studies. So what do we, why do we even care about these landmark studies? Because they influence how we treat patients and they were set up at a time where there were questions. So for instance, kind of back to your point, you know, what was, what happens with patients with elevated IOP? And should we even treat them? Who's going to go on to develop glaucoma? And that's sort of what the AGES study, right? The AGES study is sort of asking the same thing. They're looking at these patients, they're following everything, much more than we did in the other studies, but they're really trying to find out who's progressing to identify the factors accounting for differences glaucoma onset and rate of progression. And they're finding older age, higher baseline IOP and suspicious optic nerves. They are confirming the OAT study. That was the OAT study. So the OAT study says, does reducing IOP have other hypertensive eyes for patients with high IOP? Should we reduce their IOP? Should we even treat them? This was a noon, you know, 15, 20 years ago. In fact, they just reported on their 20-year data. And it's kind of frustrating because if you take a step back, I was with my colleague when they were presenting it at ADO on glaucoma day. And basically the takeaway is patients still progress. But wait and see when the paper gets published. The other thing is, what are the identifying features in ocular hypertensives that predict who is at a higher risk for progressing? So two things. OAT is important. You will get asked about OATs. OATs was ocular hypertensive patients. Did we need to treat them? And if we did, who progressed? So what did that patient look like? And there was a calculator that actually came out of the OAT study. Do you remember that calculator, Steve? I never ended up, I used it a little bit, but it's fallen by the wayside. But there was a calculator to help try to predict. So the OATs. 1,636 participants, no evidence of glaucoma's damage. They were age 40 to 80, and they had elevated IOP. One eye had to have 24 to 32. The other had to have 21. Keep in mind they did not know about corneal thickness at this point. So they were measuring IOP, and the goal was to reduce the pressure by 20%. It wasn't a huge, huge drop in IOP, because these were patients who only had elevated IOP. They had no other symptoms. No other signs. They treated them with medications versus no meds. Back then, predominantly the medications that were available were beta blockers, and they were decreasing IOP by 20%. What is, when you put a patient on a beta blocker, how much, what drop, what percent drop do they generally get with beta blockers? 20. They get about 20%. 20 to 25%. So they were as effective as the drops were at that time, and they found that 4.4% of patients progressed over a five-year period despite lowering their IOP by 20%. 10% progressed with visual field or optic nerve damage with no treatment. So you were at a two-time higher risk of progressing if you were not treated over five years if you had elevated IOP. That was basically the takeaway. Topical medications were shown to reduce the risk of progression. One millimeter of mercury, if you had for every, every one millimeter of mercury elevation, you were at an increased risk by 10%. That was another key takeaway. Same risk factors, right? Is adage is finding. Older age, higher IOP, thinner corneas, suspicious visual, suspicious optic nerve. The other key takeaway was they found out that patients who had optic nerve hemorrhages, trans hemorrhages, flame hemorrhages were at a risk, increased risk for progression. So the OATS study was the first study to prospectively follow these patients and say, yes, if you've got an optic nerve, disc hemorrhage, you are at an increased risk of developing glaucoma damage. So that's another key thing. So OATS, treat patients, disc hemorrhage, older age, higher IOP, and it was the first study to look at corneal thickness. It didn't call it a risk factor, but they did find that the African American patients in this study had lower corneal thickness and higher IOP at entry. They didn't call it a risk factor, but they did make that, they did note that finding. And again, I just think it's interesting that ages is actually reconfirming a lot of this. But asking the question in a different way. Let's go back to, I realized I should have repeated this slide. So now we know we have patients without glaucoma and we know we should treat them. What about if they have glaucoma? Let's take it the next step. So now the patient walks in, they have glaucoma damage, how aggressively are you going to treat them? Are you going to put them on one medication? Are you going to put them on four? Are you going to take them to surgery? Those with the next series of studies that were done. So we established the fact that we should treat them. Now what happens if you treat? Or you just follow those early patients? This was one of the first natural history studies for glaucoma. And I had the pleasure of meeting at dinner, Anders Hiles, who did the EMGTS study. And it was really neat to be among somebody who was really so paramount in the field from Sweden. Also what happens if you treat or do surgery on these early patients? So think about it stepwise. We wanted to know how to treat these patients. We're talking about early glaucoma. What about if they're advanced? What do you do for patients that are more advanced? Are you more aggressive? Do you treat them more aggressively? They're more advanced? Why? They have more to lose. But yes, you treat them more aggressively. And again, a lot of it came from this study. What? Yes, they don't have much remaining visual field. Exactly. And then also then the whole question around the normal tension glaucoma. Because as we're following these patients we're realizing that we've got some patients that have glaucoma that don't have elevated IOP. Does that kind of make sense? As you guys think about the landmark studies, think about where you're at in terms of glaucoma. Because you know what the other thing that's interesting is, I mean, now we've got so many glaucoma meds to work with. But back when we were residents in early attendings we had nothing. We had pilot carbine. We had timalol. I mean, the PGA's did not come available until I was a resident fellow. So a lot of these studies were done with very basic bone meditation. Okay, so EMGTS Early Manifest Glaucoma Clinical Trial Anders Heil, 1999. The study was designed in the early 1990s when the controversy existed regarding the timing and the appropriate degree of aggressiveness of treatment. Do you do laser? Do you do medication? And when the practitioners were openly discussing the uncertainty of treatment, was it actually doing anything for these patients? It evaluated the effectiveness of reducing IOP in early, previously untreated glaucoma. Primary, compare the effect of immediate therapy to lower IOP versus late or no treatment on the progression of newly-detected opening glaucoma. And they looked at visual fields and or dischanges. And then secondary to determine the extent of IOP reduction attained by treatment. Newly diagnosed patients ages 50 to 80, early visual field defects was conducted in Sweden. It wasn't a very large study. It's 255 patients. And they were randomized between 1993 and 97. They followed for four years, although this says six years. Mean age was roughly just under 70. 66% were women and at baseline the mean IOP was 20. That's not very high. Right? 80% of eyes had IOP less than 25. So again, not very high IOP. They lowered IOP by 25%. A little bit more aggressively. And they also found that was interesting. I thought, is that even the patients that were not treated, their IOP was still about the same. So you didn't have these huge swings, but again, they weren't measuring numerous times during the day, but there weren't any obvious large increases in IOP. But they did lower the IOP to 15 in the treatment arm. They found progression risk decreased by 10% with every one millimeter of mercury reduction. What did I just tell you Oates showed? Same thing. Same thing, but reversed, right? Oates showed you that for every millimeter of mercury that you went up your risk of progression increased by 10%. Here they're showing you essentially the same. If you lower IOP by one millimeter you decrease the risk by 10%. So when your patient asks your doctor how important is that one millimeter you can quote the studies. So basically the takeaway was yes, you should intervene and you should start to treat patients, even with early block-comatous damage. Risk of progression increased by 5% with each millimeter of higher baseline and then they go on to say 3% by one decibel and 1% by one year of age. So again, same thing, age. We're seeing the same risk factors. SIGIS collaborative initial block-coma treatment study was a randomized control clinical trial designated to determine whether patients with newly diagnosed open-angle block-coma they included pseudo-exfoliation and pigmentary. So it's not primary, it's just open-angle on this study. We're better treated by initial treatment with medications or surgery. So now we're going one step further. Okay, we know we're going to treat our open-angle block-coma patients but are we going to do medications or are we going to do surgery? 607 patients open-angle block-coma were enrolled and monitored for 5 to 9 years depending upon the patient. They either had initial medications in a stepped regiment or they were randomized to surgery and they underwent traps. And there was no they could actually use whatever was available in terms of IOP lowering agents as well. They weren't restricted. Progression and visual field loss constitutes the study of primary outcome variable. Secondary outcomes include health-related quality of life, visual acuity, and trochanal pressure. Randomized assignment resulted in a balanced distribution between the treatment group. They were very similar based on demographic and clinical phenotypes. More males than females in this study by little percentage and more Afro-Americans, more blacks. Most enrollees were diagnosed with primary open-angle block-coma. The others had exfoliation and pigmentary. This is interesting. Does anybody know what in the U.S. the epidemiology studies report for exfoliation? It varies. I mean there's some countries outwards of 15 to 20 percent. 30, 35 percent in Sweden and Iceland. But in the U.S., it's about anywhere between 3 and 5 percent. So in our database, we've seen about 3, 3.5 percent of patients with exfoliation. So I just note that that's pretty consistent. So what did they find? Well, both the Trab and the medical therapy were able to lower IOP significantly. Trab's were more effective as we would suspect. SIDGETS, a key take away, they were the first study to use a questionnaire to assess quality of life. They are now using PROSE, which are patient-reported outcomes more and more in drug and device studies. But it was really to ask the patients how are you doing? The medically treated patients report slightly more ocular symptoms than the patients in the Trab group would suspect. SIDGETS set an aggressive target IOP for each patient according to baseline characteristics. Substantial sustained IOP reduction was achieved in both treatment arms 35 percent and upwards of 50 with surgery. We're getting more progressive. We're getting more aggressive with our IOP lowering. We're going from 20, 30. Now we're at 35 and 48 percent. IOP more. Medication arm uses step regiment, single agent, continue to add on. If they serve visual field progression and in the surgical arm, trial to perform in either arm if the treatment failed, they went to a laser. Key learnings, patients with moderate or advanced disease at the time of diagnosis had better results with surgery than with medications, specifically those who had pretty significant mean deviation loss in the visual field. More likely to show progression if you're treated with medicine. What do we think about with medications? Compliance is one. What's another thing that gets thought about with surgery and or laser versus medications in terms of IOP? The stability of the IOP. The stability of the IOP. There's more fluctuation with medications and a lot of the medications actually don't work at night. There's studies where they've actually looked at Wine Ribs Lab down in Doheny or San Diego, actually San Diego. He's looked at IOP and Carol Torres has done a lot of this work as well out in Nebraska but they show that certain medications actually don't work well at night. It could be because they're not affecting episcleral venous pressure and when you're sleeping, the thought is your episcleral venous pressure goes up but your traps are lowering IOP because they're not going through that outflow system. They're going outside of the eye. So there's this thought that with surgery you get a more stable IOP effect over 24 hours. Ages. Another landmark study that comes up a lot. Advanced Glaucoma Intervention Study and this was around the sequence in procedures. I could never remember the details of this and every time I hear it or talk about it I've got to go back and look but they looked at two different sequences of treatments. So now again, medication, we've got oats, we know we want to treat. We've got EMGTS we know we want to treat. Now we're moving to SIDGITS and we say okay maybe we want to do surgery. Now the question is well do we do surgery? What is the order of surgery? Now we've got lasers. So where do we do the surgery and the laser? How do we combine them? And that's what ages was meant to show but it was in advanced patients. So again, think about the patients. Oats was ocular hypertensives, right? EMGTS was early glaucoma, SIDGITS earlier glaucoma. Some a little bit more advanced. Now we're moving on to advanced. Key finding reducing IOP slows visual field loss. So when I come back to you guys and I say so why do we lower IOP? You're gonna say it's because of oats, EMGTS SIDGITS, normal tension and ages. They all showed that if you lower visual field you slow down progression. One millimeter by how much? Ten percent. Good. Different sequences. So they randomized patients to ALT trabeculectomy, trabeculectomy versus trabeculectomy, ALT trabeculectomy. So you guys don't even know what argon laser, trabeculoplasty is anymore, but it's the same essentially as SLT. So we used to use the argon laser. You had a higher risk of IOP spikes. Patients with advanced glaucoma were defined as those with visual field losses enrollment who failed to achieve adequate IOP reduction despite the use of maximum effective accepted and tolerated medications. So all these patients were already on medications and they said okay they're going to surgery but should we do laser first or should we do surgery first? Think of it that way. And most had pressures greater than 18 millimeters of mercury at entrance. 591 patients large disparity between age. I thought this was kind of surprising. 35 is young. Advanced POAG and they were followed for 8 to 11 years. They had to be a maximum tolerated medical therapy randomized to either the ATT or the TAT main outcomes were again visual field. So most of these were visual fields right? They did not look at optic nerve this one looked at visual field. Votes also looked at the optic nerve. Sustained decrease in visual acuity showed that the Caucasians did slightly worse. Afro-Americans did markedly worse if they were randomized to trabeculate to me trabeculoplasty rather than laser trap trap. That's easier to say. So when we treat our patients what do we do first? If we don't go straight to surgery we try laser, right? Sort of from this study. Think about when you're treating your patients you're going to start off with one medication you're going to lower IOP about 20 to 25% they're more advanced we want to get their pressure higher we want to get their pressure lower 50% right? You hear us throw around 50% well that prior study showed us 48% with traps was effective. Here we're going to try a laser first and then we're going to try a trap. The other thing that AGES showed was that people who had pressures lower consistently lower than 18mm of mercury had slower progression. So if you don't remember the whole thing about the surgery piece and what arm did what what arm did worse 18mm of mercury. So now when you look at drugs and they go to get approvals they say by Zolta does this Ropressa does this. Certain percent of patients were consistently maintained at an IOP of 18mm of mercury or lower because of this study. Last one collaborative normal tension glaucoma study does IOP, lowering IOP have any effect on normal tension glaucoma? And what in my slide do that? Yes So 30% So if you lowered IOP by 30% you were able to reduce the visual field loss over five years from 35% to 12%. And these were 65% of patients progressed without treatment 12% progressed even despite treatment. So again thinking about blood pressure sleep apnea vasospasm the key takeaway was you treat normal tension glaucoma patients. Normal tension again visual field optic nerve progression threatening fixation disc hemorrhages the SIDGETS trial was there for instrumental in demonstrating the role of IOP. So again 30%. So sort of when we think about if you look at the European Glaucoma Society's recommendations and the U.S. or A.A.O.'s recommendations we usually say sort of it's stepwise. 20 to 25% from mild 30 to 35% from moderate and then 50% for advanced. Again kind of from these studies. Quickly we did a tube versus shunt study this was published in 2008 so more recent and it basically made people rethink the purpose of the tube and be a more aggressive tube. You can use tubes in younger or earlier patients that was the key takeaway. So with that a minute to go. So as you guys hear it may always say preserve vision but do no harm think about the patient think about the age of the patient think about their lifestyle think about their needs that's a really key thing especially at the VA our low vision facility is amazing and I think we do not send patients to low vision early enough. There was an editorial in one of our journals that spoke about actually getting patients with glaucoma to low vision centers earlier. We think about macular degeneration patients all the time because it's fixation it's main vision but these patients are bothered. They see constriction. Yes. I testified at the FDA when they were saying look we really need to do more 10-2s because we are underestimating the reduction in central vision with glaucoma to sentry. We're really underestimating again. We've got to do a better job at this. I agree I absolutely agree and the other thing too that the agit study found was that if you have a disc hemorrhage and you do a 24-2 you will miss the the defect. You have to do a 10-2 for patients with disc hemorrhages. The 24-2 is not sensitive enough. Was this helpful? Yes.