 Good morning, everyone. It is 8 o'clock and we'll go ahead and get started. I am happy to see you all. Just an update. We are working on getting us all back together in person for Grand Rounds. If not, I anticipate it'll be for the first Grand Rounds of March, but stay tuned if that ends up being sooner. We'll certainly communicate that out to everyone. Beyond that, R&11 is both presenting and moderating, so I'm going to go ahead and just do an introduction for her. R&11 came to us by way of Cornell. She's been an extraordinary resident with her hands in many things. She's been very productive both in education realm and in her research as well. Something you don't know about Ariana is for someone who didn't grow up here or hasn't lived here for over five years, she has the most comprehensive listing and descriptions of things to do within various distances from Moran. That could be three hours, five hours, eight hours. If you have any planned road trips, I highly suggest you connect with her and somehow she's managed to know our state better than a lot of people have lived here our whole lives. Without further ado, Ariana, I'll turn the time over to you and let you take it. Thanks, Dr. Petty. I had not prepared such extravagant introductions for me or Marshall, but I guess I got to give Marshall one now too. So I can wing it. As Dr. Petty said, R&11, I'm here with Marshall Huang, we're both PGY4 residents. Marshall Huang, like me, came to Moran from first Connecticut and then Cornell, and we are both applying to glaucoma. Marshall, let's see. Marshall also has traveled the state of Utah, he got me my first ski setup from Costco and has since shown me the mountains. So next year I'll be at Wash U St. Louis for Glaucoma Fellowship and Marshall will be at Minnesota Eye Consultants for Glaucoma Fellowship. And today we're going to take you through some glaucoma. We'll start in the 1960s with an overview of steroid induced ocular hypertension and glaucoma, where we've come from, where we are now. And we'll move forward to present day with a review of Meg's outcomes. Let me share my screen. Okay, so starting with an overview of steroid induced glaucoma, our consult resident was called recently for consult on blurry vision headache and halos. Let me just change this. And this was in a pediatric patient with a diagnosis of ALL who had started chemotherapy and IV dexamethasone eight days prior to the consult. On exam the patient was 20-20 in each eye with an intraocular pressure over 60 in each eye and the exam was otherwise normal with deep angles, no cupping of the optic nerve. The patient was started on maximum IOP lowering therapy and at follow up the next day the pressure was 45 in the right eye and 35 in the left eye. A few days later the pressure had come back up above 50 in each eye and the patient went to the operating room for IOP lowering surgery. Glaucoma history overall is really recent. For example, the ocular hypertension treatment study OATS, which determined that lowering intraocular pressure reduces the risk of glaucoma came out in 2002, which is probably within the lifetime of everyone in this room. This is one of the exciting things about glaucoma. And also recent in the 1950s and 1960s, Dr. Armalee was doing a lot of the early work at University of Iowa. One of his earliest projects, the Des Moines population study of glaucoma measured characteristics of eyes and the population and described crucial basics like normal ranges of intraocular pressure. His collaborative glaucoma study which defined the cup to disc ratio that we use now. And his early work also included steroid induced ocular hypertension and glaucoma. So shown here is one of his important early studies titled effective corticosteroids and intraocular pressure and fluid dynamics the effect of dexamethasone in the glaucoma this eye. This was a prospective study with 19 eyes with primary open angle glaucoma. Pressures ranged from 25 to 30, and also 15 eyes with normal intensive glaucoma with pressures ranging from 13 to 20. The eyes were to be treated with steroid. Now one of the interesting points about the study design is that he already knew that steroid could cause huge increases in pressure like the case we started with today. So in fact in this study he set an upper limit of the baseline intraocular pressure in his inclusion criteria, so that he would not induce huge spikes in treating the eyes in this study with steroid. In this study, antihypertensive were stopped in the right eye with the left eye as a control and topical dexamethasone 0.1% three times a day was applied to the right eye. The graph that we're looking at here shows one example I from the study intraocular pressure is on the y axis and on the x axis there's a dark bar indicating when dexamethasone was started and then stopped. The intraocular pressure in the right eye is shown on the dotted line and we see a big spike in the baseline pressure from about 26 up to 40 millimeters of mercury. This coincides with dexamethasone application and then that spike resolves when the dex is discontinued. The left eye is the solid line the control I below and we see that there's not much change there and then on the right side of the graph, the eyes are treated with pilot carpet in addition to dexamethasone and we still see a spike with the dexamethasone, but the pilot carpet dampens this spike. This study additionally showed that steroids reduced outflow facility in these eyes and that primary open angle glaucoma and normal intensive glaucoma were both eyes with both of these were both affected by the dexamethasone. Now the incidence of steroid induced elevations and intraocular pressure varies in studies and studies on this topic are heterogeneous because we use steroid in so many different clinical scenarios. We use it after surgery for hyphema for uveitis, but overall review papers state that the incidence might be as high as 40%. We're looking at a few clinical examples here so first we have a paper that measured intraocular pressure after tourgium surgery. This paper was prospective with 62 patients who are on a long dexamethasone taper for three months. Six of the patients which was just under 10% had an intraocular pressure rise greater than 10 millimeters of mercury above their baseline and 45% had a peak intraocular pressure occurring one month after surgery. The second paper shown here looked at eyes following DSEC it was retrospective with 81 eyes. The eyes got subconjunctival dexamethasone, then also one dose of acetazolamide 500 immediately after surgery, and then we're on a dexamethasone drop taper for three months. In this group almost 20% of eyes developed a high intraocular pressure, which was defined as greater than 21 millimeters of mercury or six above baseline. Those are common measurements that are used in papers, and these eyes had the IOP spike resolve after steroids were withdrawn. The time to stare it induced ocular hypertension in this paper range from one week to 16 months. The third paper shown here looked at intravisual triumcinolone for vein occlusion. This was a randomized controlled trial. It was not randomized for steroids it was randomized for other treatment for vein occlusion, but they did assess the effect of the steroid on intraocular pressure in the randomized controlled trial. The incidence of a pressure greater than 10 above baseline at 36 months so at three years was just 2% in the control group, 9% with one milligram dose of intravisual triumcinolone and 45% with the four milligram dose. In this paper established that there was a dose dependent relationship in studies of intraocular pressure and glaucoma and eyes receiving injections for retinal pathology, it can be really tough to tease out what the effect of the steroid on intraocular pressure is versus the effect of the injections themselves because there is good information in published studies to suggest that intravitual injections themselves can elevate intraocular pressure chronically in some eyes, even without steroid. And also to compare these versus the effects of the underlying retinal pathology like new vascularization on the pressure. This study here the long term incidents and timing of intraocular hypertension after intravitual triumcinolone injection is a retrospective study of 929 eyes that received at least one Paris planet injection of triumcinolone and the mean number of injections was 1.6. In the graph on the why access. We're looking at the need for the need for IOP lowering medications and so all the way at the top though which is 1.0 that would be 100% of eyes. And then the x axis is the time in months after the first trimcinolone injection. The history of glaucoma are indicated with the dotted line, and then eyes without glaucoma are the solid line. And in this study, 13% of eyes overall needed IOP lowering medications, six months after injection. 34% which is a quarter of the eyes needed IOP lowering medication at two years and three eyes required IOP lowering surgery and we see that eyes with a history of glaucoma are at higher risk and that's true throughout studies of steroid induced cancer hypertension and glaucoma. As I said though it can be tough in these studies to tease out what is the effect of the steroid versus underlying pathology related to injection or retinal pathology or the natural course of glaucoma in the glaucoma So what we really need in this kind of study is a control group without steroids. Now what about the difference between routes of administration or doses or types of steroids in the OR these days for example some of our surgeons have replaced topical prednisolone with subconjunctival injection immediately post-op or with dextenza which is shown in the bottom an intra-canalicular steroid implant. Does the steroid dosage or the proximity to the outflow system make a difference in the effect on IOP? There are some studies that have compared steroid strengths and routes. I don't have data on dextenza for you today but the chart that we're looking at here is from a prospective study of 155 eyes newly diagnosed with uveitis. They could receive steroids by any route and eyes with glaucoma already on IOP lowering treatment were excluded from this study. In this study a steroid induced IOP elevation was reported in 8%, that's in the first highlighted line there, 8% of the eyes on topical steroids and 37% of the eyes treated with oral steroids. To our point earlier, the authors in this study do distinguish between steroid induced intraocular pressurized separate from IOP rise that's likely due to other causes like synechiae. And then it's also important in this study to recognize that there might be inherent differences in the eyes that are treated with topical versus oral steroids that would predispose them to a high IOP. For example, the eyes treated with oral steroids might be sicker at baseline. This chart is from a review paper and summarizes the published effects of different topical preparations in red circle dexamethasone, prednisolone, FML, the topicals that we often use here, and the range in intraocular pressure increases is shown in the second column. The highest rises are shown with dexamethasone and the lowest with FML, but there's quite a bit of a range, and this possibly is demonstrating that IOP elevations are more severe in some eyes compared with others, even with the same drug. And we'll talk in a moment about steroid responders versus non responders. On the right, the proportion of patients in each group in which IOP rises also ranges quite a bit. So for example, with FML published studies show that IOP is elevated in a range from 0% of patients to 88% of patients. So that's a pathophysiology, and what's going on in the eye when treated with steroids. Recall that in the conventional outflow pathway, the aqueous drains from the anterior chamber through the trabecular mesh work into Schlump's canal. Steroids have been shown to decrease outflow and to increase intraocular pressure via trabecular mesh work remodeling. The effect of steroid on the trabecular mesh work has been shown well in cultured eyes. So in the study that we're looking at here, anterior segments from donor eyes were mounted that's shown in the illustration on the upper left and exposed to dexamethasone in culture. And then the eyes were examined under an electron microscope for changes in the TM. The graph on the right is showing intraocular pressure on the y-axis and days on the x-axis. Some eyes were determined to be steroid responders and these were analyzed separately from eyes that were determined not to be. The white bars are the control eyes without dexamethasone exposure and the intraocular pressure does not change from 0 to 12 eyes, 12 days in these control eyes. The gray bars were the eyes treated with dexamethasone and we see a large increase in the intraocular pressure in the subset of eyes that was determined to be steroid responders. The gray bars on the right where we don't see a change are the non-responders. Under the electron microscope, the dex responders had increased density of trabecular meshwork structures, loss of TM cells, increased TM extracellular material and decreased outflow facility. Several papers have shown changes specifically in the cytoskeleton of trabecular meshwork exposed to steroid. We're looking at a representative image here from a paper that's titled dexamethasone alters F actin architecture and promotes cross-linked actin network formation in human TM tissue. And the circled structures are cross-linked actin networks in steroid exposed eyes. Finally, I'll make a quick comment on a few of the protein signaling pathways that have been studied. Many genes have been examined for possible roles in steroid induced ocular hypertension and these are just a few of them. So the myosilin and TIGR gene is really interesting because it was first reported, it was the first reported disease causing mutation in primary open-angle glaucoma in a publication in 1997. Coincidentally, it was also identified as a trabecular meshwork inducible glucocorticoid response protein in cell culture the same year. And so the protein was shown to be induced by the glucocorticoid signaling pathway. However, there's still no known causal link between myosilin and specifically steroid induced ocular hypertension or glaucoma. Alkaline phosphatase has been shown to be elevated and matrix G1A protein has been shown to be low in eyes with a steroid response. And there's a hypothesis that these markers of calcification are indicating stiffness in the tissues. Similarly, the TGF beta and Wnt signaling pathways have been studied also as indication of tissue stiffness and fibrosis leading to increased intraocular pressure with steroid signaling. And then IL-1 has also been looked at as having inflammatory effects that may decrease outflow in these eyes. So in conclusion, steroid induced ocular hypertension can occur in up to 40% of patients and can occur as early as one week. Now, one week is a difficult time point for us to see a patient and so it may be that the steroid response is occurring earlier and we're not catching it before one week. There are steroid responders and non-responders. Increased density of cytoskeletal components of the trabecular mesh work have been well described. And the underlying genetics is not completely elucidated, but many signaling pathways have been hypothesized to play a role. Thank you. We have time to take some questions now otherwise I'll turn it over to Marshall. So I'm looking at question in the chat, are children more likely to get steroid response? That's an interesting question because I think that in the early studies like Dr. Armley's studies older age looked like it was a risk factor, but in more of the recent studies, younger ages identified as a risk factor. And these studies are looking at younger adults. So I'm not sure how children compare to adults. Just a reminder for anyone that wants to be unmuted just go ahead and raise your hand we can unmute you or you can ask questions in the chat. That's an impressive, impressive review and amount of information looks like. I'm not asking Kaiser or rather stating Kaiser showed a subconge kind of log after cataract surgery to increase risk for ocular hypertension, the closer to the limbis it was injected. Thanks Dr. Jai for that comment. I think that's also something for us to think about as we consider even what to use after cataract surgery, whether you're doing topicals or subconge injection or intracanitlicular. We have different proximity to the drainage system, at the same time different ability to get them out of the eye, if needed. And I think we just don't have great data for everything and some of what we talked about today. The complexity the comorbidities with retinal pathology all these things can make the effects kind of hard to study, but I do think the proximity as I said is something important to think about as we treat our patients. Dr. Mamelis, why don't you go ahead and make your comment and then we'll read Dr. Shortcuff's question next. Kariana that's that's a great review of a very complex topic and I think we understand the reason why the steroid effects that you're making a measure and why we get the steroid responders but the bottom line is in spite of all we've looked at the genetics and everything we still don't know who's a responder and who's not a responder to actually try it. And what's going to be critical in this topic is if we know ahead of time, who's a responder who should we avoid the steroids on because the scary part of this is again I've seen people have a response in a week. And so it's it's a very difficult, you know, very difficult to issue not knowing who that responder is going to be and who that responder is not going to be. So I think that's that's where the money is going to be in doing this kind of research is to see how we can predict the responders ahead of time before we get into trouble. And by the way, before I go on, you've been in Utah now for for two and a half years, and you've already learned learned to drop your tea and you say mountain now so we've made you a Utah and that's very good. Thank you Dr. Malis that's a big compliment. That was not a compliment by the way so that's And then we have a few comments from Dr. Chia Dr. Simpson talking about the distal outflow system that eyes that have goniotomy can still get a steroid response. And I think that's important as well something I didn't touch on completely, but I don't know completely what the literature on it is but I do know that here at Miranda's been some discussion again about which pathways could be affecting that distal outflow system, even for example, could pathway play a role or also when we're using these drops and seeing like the eyes get so red and seeing dilation of vessels what kind of constriction and dilation throughout the system is having an effect here. So the short answer is I don't know the specifics but it's really important also to think about the outflow system distally. I have a question from Susan short cough and what did you find out about other routes of administration inhaled injections or other areas. Also a good question. I did not. I'm not sure. I think that the steroids in all forms, maybe have the same effect but I can't speak to the literature on it. A clinical question you know when we come across a lot in our post call patients who've been put on steroids they may have other reasons kind of this multifactorial glaucoma. Do you have any tips for teasing out the steroid response among things such as trauma or other, you know, factors that could be contributing. We often cite the timeline of the of the pressure rise but any pearls for teasing that out and whether or not we need to adjust our steroid treatments. Yeah, I'm sure I'm not the best person in the room to give clinical pearls but I had two patients recently with hyphemis who I who had very high pressure and I thought it was steroid response or maybe I just wanted it to be. And it was more likely from all the cell and hypema and inflammation in their eyes and I think that it maybe makes sense to withdraw steroid as quickly or switch to a less offensive dose or drug as best as you can and if the pressure is not coming down. Maybe it's something else at the same time like the case we started with. At the with a really high pressure I think it doesn't necessarily come down so immediately as the steroids are withdrawn and so could be combination of things as well. Spinal comment from Marisa Laura shell, we find Urus all to be extremely hyper intensive in kids. I will pass it over to Marshall. All right. So, thanks Arianna for the excellent presentation. We will go ahead and continue with our glaucoma grand rounds. Again, my name is Marshall Hong I'm a PGY for here at the ran and I'll be presenting on long term makes outcomes. And we'll start with glaucoma so why do we care. Well globally it is one of the most common causes of blindness. It causes 2.1 million. Oh, my view. Okay. So it causes 2.1 million case of blindness worldwide about 6.6% of blindness total, and that's a 62% increase from 1990. It also causes 4.2 million cases of moderate or severe vision impairment defined as worse than 2060 vision, and that's actually an 83% increase from 1990. Overall there are about 65 million people that have glaucoma of any stage and that's globally. In the United States, also kind of mixed in with high income North America so Canada, we find that 50,000 people are blind from glaucoma, that's a 20% increase and then about double that with moderate to severe vision impairment, also an increase from 1990. We have about 2.7 million in the United States overall, and about half of those cases are estimated to be undiagnosed so definitely a problem with a large burden for our society. In terms of glaucoma, all it is is a pressure related damage to the optic nerve there are more complex definitions but I think that generally covers it and decreasing the pressure has been shown to decrease progression in numerous studies and that makes it easy for us as glaucoma because basically all of our all of our treatments work to do that one thing decrease the pressure. Just as a brief overview. This is a chart that separates the surgical glaucoma options into their mechanisms of action, as well as their surgical approach. So starting on the left here we have subconjunctival ranges and for the ab external options that's basically our traditional glaucoma surgery so tribeculectomies and tube shunts. They now do have an ab internal version that Zen gel stent, but as many people found the outcomes can often be better if it's implanted ab external. And also there's a pressure flow which is similar that's will be designed to be implanted ab external. In terms of the trabecular drainage, we will be mostly focusing on the ab internal versions of that you can do an ab external version of canal ostomy and canal plastic. But those are less common especially for our adult open angle glaucomas. The ab internal tribe particular drainage devices that includes most of our mix so that includes the ice stance hydras. And then all the goniotomies so tribectom co hook dual blade gat omni, as well as ab internal canal plastic so that's the eye track and not me. For the super curio drainage systems, we do not have any in America that are currently available. The jet was recently approved in Europe in 2019 I believe to be implanted I sense super was had a C mark in Europe but is not being used clinically per se. The side passage you might know was previously available but has now been has been recalled in terms of the inflow modifying procedures we have ab external CPC as well as internal e Cp. I will not be focusing on those. Those techniques for the sake of time. So we'll first start with a definition of mix. This was coined by Dr. Ahmed in 2009. Initially and it's either minimally or micro invasive glaucoma surgery and it's the first. And I call it qualifications that's an ab internal micro incisional approach on that has been changed a little bit over time, especially with the Zen gel stand and the pressure flow coming out where there may be starting to allow an ab external approach for some mix procedures depending on how you define it. Generally it's minimally traumatic and being mostly ab internal generally was just conch. There is a IP lowering efficacy to warrant the procedure itself. There should be a high safety profile because these are used mostly for mild and moderate cases of glaucoma. And there should be rapid recovery basically similar to recovery on that you'd expect in cataract surgery. So going back to this chart. Again, we will focus here on the particular drainage devices on the ab internal particular drainage devices in this talk. As those are the ones are available in the US. So we'll start with the ice stance. The ice tent was first developed back in 1999 it was first implanted in a human 2001. It was an extrebecular micro bypass stent that was implanted in a human is finally approved in 2012 with the first generation ice stent. That's often described as a snorkel you can see it's an L shaped device that is open on one end on the, that will be on the posterior aspect of some canal and has retention arches in order to keep it in place. In 2018 they updated it to the ice and inject so that's the second generation. They made it a bit easier to implant or you just go straight into the trabecular mesh work. And they basically found that there's not, it's easier because there's not a right side and the left side associated with it. So here, they updated that again to the ice that inject w and you can see they're basically the same thing. The only difference is really the wider flange which is what the w stands for. That's to help hold it in place and prevent it from going too far into the trabecular mesh work. Most of our studies that I'm going to be citing are going to be talking about the G one and the G two ice stents. So those of ice and outcomes I'll start with the randomized control trials that we have available. Particularly the ones that have over two year follow up because that's what we'll be focusing on just the long term outcomes. Samuelson presented a paper in 2019 that compared 387 FAKO ice stents to ice stents versus FAKO alone and had 24 month follow up. They did do a washout and found that the unmedicated IOP reduction was about seven for the FAKO ice stent group compared to five and a half for the FAKO alone group. And then they noticed a medication reduction of 1.2 drops for the FAKO ice stent group versus 0.8 for the control group. And overall they found that 76% of patients had an unmedicated IOP reduction greater than 20% which they considered a success. And here's just a few charts from the paper that summarizes that. And this is another RCT that basically compared ice stents with itself. So they used first generation ice stents comparing one ice stent to two ice stents to three ice stents. And they had up to 42 months of follow up. Overall they found that the unmedicated again with a washout IOP reduction was 7.6 for one ice stent 9.2 for two and 10.9 for three. And the unmedicated IOP reduction was greater than 20% and 61% of people with the first generation ice stent but 91% patients for both two and three ice stents implanted. And you can see here that especially here the survival curve in terms of percentage of people taking no medications. You can see that the curve is essentially identical for the two and the three ice stents but significantly lower for the one ice stents suggesting that two ice stents might be the sweet spot in terms of long term pressure control with the ice stent. Here are a couple other randomized controlled trials I don't want to focus on them too much because they're not as good quality as the previous ones. They're smaller sample sizes but just briefly a bold here compared to ice stents to just that travel process alone, basically showing a similar IOP reduction and unmedicated IOP reduction between the two. And the FAYA did a smaller study here comparing a single ice stent with FAKO also showing that the ice stents was more effective at maintaining the pre-off washed out IOP whereas in the FAKO only group it rose above the pre-off baseline IOP. They also showed that the FAKO ice stent group did have a decrease in eye drops compared to control also. So here are a couple more studies that are longer term follow-ups but not randomized controlled studies. So here it was a prospective study with a planned five year follow-up comparing FAKO ice stents, the second generation and that's just one ice stents compared to one ice stent alone so without FAKO. Overall, they saw a medication reduction of about nine millimeters of mercury versus about 11 millimeters of mercury. So just slightly more with the ice stent alone group. They also noted a drop reduction of 1.7 versus 2.2. Overall, they defined success as IOP less than 15 millimeters of mercury which they found in 86% of people in the combined group versus 71% in the ice stent alone group. And you can see here preoperatively only 2% and 1% met those qualifications. So here we have, like I said, five years of follow-up data. You can see that the mean pressure remains fairly consistent from years two to four. And again, this is showing the percentage of the amount of reduction rather, showing a 39% reduction in the combined group and a 42 reduction in the standalone group. There's another study to kind of corroborate that. This is a ice stent first generation versus an ice stent second generation, basically showing that they're pretty comparable. So we don't have to worry that there's a decrease in efficacy with the second generation ice stent. And here, these are some retrospective trials. Again, look at longer term follow-up. Here there are 35 patients at five years showing a decrease in IOP from a baseline of about 18 and a half to a five year post of a 14 and a half. And 62% of people had greater than 20% IOP reduction in that study. And this study is showing a follow-up to eight years. And again, the pressure remains fairly consistent, dropping from 19 to 14 and staying at around 14 or so for the duration of the study up to eight years. So overall, we can expect a mean IOP reduction of five to 10 millimeters of mercury on average of their washed out IOPs, whether that's implanted with a standalone device or when combined with cataract surgery. When you compare it just to cataract surgery, the difference may be as low as one and a half millimeters of mercury, but still a significant difference statistically. On average, we see a mean drop of about a half a eyedrop per patient. And the study suggests that the effects are likely to persist for five or even eight years at least. And then I present a study showing that two eye scents seem definitely better than one, but three eye scents are not convincingly better. And with all these studies, there are virtually no significant adverse events. The next one I'll be talking about is the Hydrus. So that is by Ivantis and approved in 2019. It's an eight millimeter crescent shaped device that covers about 90 degrees of slimes canal. So if you have a hand raise, Dr. Gobi will go back if there's no question. So here again, another study by Samuelson in 2019 very similar. This is a study designed as this other study with the with the eye scents. Here's he's combined comparing 369 Faco Hydrus eyes to 187 Faco's Faco only eyes. And again, he does a 24 month follow up. They see a 7.6 point decrease in the combined group compared to a 4.2 point decrease in the Faco group, a significant difference but also a significant decrease in both. In both groups. For the drop reduction, similar to the ice then we see about 1.4 drops on average reduced for the Faco Hydrus combination versus a one drop less for the Faco alone. And we also see 77% versus about 60% for IOP reduction for the Faco Hydrus versus the Faco alone. And here you see good stability from the one month mark up until the two year mark suggesting that it's stable at least the two years based on this study. So in terms of RCTs that over the two year follow up, Pfeiffer et al did one in 2015 with a slightly smaller sample size but also showed a greater decrease in the Faco Hydrus eyes compared to the Faco only eyes and also a significant difference was about, you know, one to two millimeters of mercury as seen previously, IOP reduction success was similar, 80% on versus 46% for decrease of over 20%. Just recently at AO and ash I was presented by Dr. I got med, looking at the five year horizon data for the Faco Hydrus versus the Faco trial. And this is not published in a peer review journal but this is at least from his slide that he's presented. They found that 66% versus 46% were medication free at the end of five years, and one of the bigger findings was that far less of the Faco Hydrus group required glaucoma surgery, after five years and factors 2.8 times less likely to success of glaucoma surgery, after having the highest ice that they also presented that on the end of the cell counts were stable at five years for, for both these groups. There was one randomized controlled trial directly comparing I sent with Hydrus, unlike some of the other randomized controlled trials presented this was not a completely washed out comparison. They had a medicated IOP reduction they showed was one millimeter mercury versus 1.7. They also showed a drop reduction of one versus 1.6 and a greater than 20% decrease in IOP from the washed out baseline medications of 13.3 versus 40% or so. That's showing a relatively small difference in the IOP reduction. But if you look at the, the change in the medication amount that is a more significant difference. So the ice then, the ice then times two group, I'll require significantly more medications to maintain their IRP goal compared to the Hydrus suggesting the Hydrus was a little bit more effective and maintaining the pressure. So overall, I conclude that the mean IOP reduction from the Hydrus is similar to ice then expecting maybe five to 10 millimeters of mercury. If you're looking at a washed out IOP decrease and IOP reduction if you're comparing this just standard IOP, maybe as low as two millimeters of mercury. The drop reduction is a little bit increased around one drop on average per person. And again, we expect the effect lasts for at least five years. We do not have any data beyond five years so can't claim that it lasts as long as ice then. Overall, there were, there's a theoretical benefit of ice that's being safer being that's a smaller device but based on the studies, both had very little adverse events and it's hard to really claim that one is safer than the other. So the next group of procedures I want to talk about is removal of trapeculum mesh work. And there are a few terms I want to just clarify because it can be a little bit confusing. With goniotomy, you expect just based on how it's written that it's defined as an opening of the TM, goniectomy you might expect as excision of the trapeculum mesh work, trapeculotomy again opening and trapeculectomy and excision of the TM. But it's not really clear how these are categorized just based on their names. So, overall goniotomy is the most preferred preferred word for the device for the mix devices that remove trapeculum mesh work, particularly through an app internal technique. It's all coded by the same CPT code. So whether that's Trebectom, KDB, GAT, Omni, iTrack, all of those if approached from an ab internal technique to remove the trapeculum mesh work are all going to be coded the same and all would be termed a goniotomy. Certainly, you could call say like a Trebectoma goniectomy, but it's rarely used and goniotomy is more preferred. Another option would be the ab internal trapeculectomy or an ab internal trapeculotomy. There is a theoretical distinction between the Trebectom and KDB because they actually excise tissue versus something like a GAT which just opens the tissue. But again the CPT code is the same and there's not necessarily a clear difference in the outcomes clinically. So in the case of the Trebectomy, it's generally defined as an ab external technique, and it's often used for kogenital glaucoma, especially when there's a pacified cornea. So we can't do an ab internal technique. And then Trebectomy is our traditional trap that we think of, though in reality we don't necessarily need to excise the TM and maybe a more accurate term would be a garbysclerocherectomy just because of how the flap is made. So now that we've gone through some of the definitions there, I'll start with the Trebectom. Originally it was created by Neomedix and then was bought by MST. It was originally released in 2006. And what it involves is a electrocutory tip with a foot plate that prevents any disruption of tissue posterior to the foot plate. And there is a device that it connects to and then there's a disposable handpiece that you use for it. So not too many randomized controlled trials available for the Trebectom, but here is one of the few. This is comparing Faco-Trebectom with Faco-Trebectomy and there's just a 12 month follow up. Overall they do show that the Trebectomy is more effective as you might expect with six millimeters mercury decrease versus 3.2. There's also a significantly, excuse me, there is however a less of a drop reduction with the Trebectomy group compared to the Trebectom group. Overall in terms of medication-free IOP reduction greater than 20%, you have 20% of the Trebectomy group versus 50% of the Trebectomy group. In terms of the non-randomized controlled trials, we do have a few with some larger sample sizes. Here, one by U7 2020, they looked at 39 Faco-Trebectom versus 39 Faco-I-Stent, one of the generation 2 I-Stents. They show that there's a significant IOP reduction in the Faco-Trebectomy group, but really not much at all in the Faco-I-Stent group. And again, a greater drop reduction in the Trebectomy group compared to the I-Stent group. This next study is a 90-month retrospective study where they seem to show a really good sustained effect of IOP reduction from the Trebectom from 23 to 16. This is a drop reduction of 2 to 6. However, if you look at the numbers here, the number of patients that make it past even 72 months is pretty minimal compared to the original sample size. So definitely at risk for some bias errors with this study. And moving forward to the Cahook dual blade. This was first developed or approved in 2015 and sold by New World Medical. It has a foot plate that elevates the Trebectom mesh work and then brings the Trebectom mesh work into two parallel blades that excise the tissue. And the idea is to decrease the amount of potential scarring that might happen if you leave some of the Trebectom mesh work around. The best randomized control trial I found was by Falcon Bear in 2020 where they compared Faco KDB to Faco I-Stent with a 12-month follow-up. The medication reduction in the Faco KDB group was greater, 3.2 versus 2.4 in the I-Stent group. The drop reduction was the same at 1 and about the same number of patients achieved an IOP of less than 18, which was their target for success in this study. Here you can see the Faco Goniotomy versus the Faco I-Stent. The curves of the charts match pretty well from the one-week point and there's no significant difference at the one-year point. And similarly, this is kind of just showing the proportions of patients with less than 18 millimeters of mercury here. And then in a 24-month prospective but non-randomized control trial, they do show medication or a Medicaid IOP reduction of 7.7 at the end of the two years, as you can see here, as well as a drop reduction of 1.9. However, you can see that the number of drops needed really start to creep up as you get past the six-month point. There's definitely a question of how long living this effect is, and we don't really have much data beyond that. There's a few more shorter-term follow-ups. Here they compare Faco KDB again to Faco I-Stent, but here there is a significant ethnicity difference between the two groups, 76 percent versus 42 percent African-American. And again, you see Faco KDB being more effective, but the significant baseline population difference certainly brings the question how reliable that finding is. In this study by Almelea and as well as it also shows a significant ethnicity difference of 38 percent to 64 percent Caucasians. Again, while it does show a difference between the two groups, it's hard to necessarily trust this information. So overall, I found that the evidence for goniotomy was relatively low quality, especially compared to the I-Stent and the hydrostata. There's really minimal randomized control studies, and there's really minimal studies that show outcomes after two years. Overall, from what we see, it's likely that it has a similar efficacy to an I-Stent over the one to two-year time point, but it's really unclear if it's able to maintain that over a greater period of time. In addition, one of the potential downsides is that it is a destructive procedure, and it can't necessarily be repeated in the same location. So here's the I-Track provided NOVA-I Medical in 2008. What this is is a catheter with a light on the end that's 250 microns that's threaded through the slimmest canal, 360 degrees, followed by viscoelastic, about 100 microliters of viscoelastic that's pushed through the cannula as you withdraw it. If you like, you can also do a 360 degree goniotomy while doing that procedure, but for the purposes of this talk, I'm keeping them relatively separate. So not too many good, not really any randomized controlled trials for the I-Track, but there is a good study in 2012 by Gallardo looking at Faco I-Track versus I-Track alone with 24 months of follow up. And you can actually find that the Faco I-Track decreases pressure by 6.6 versus the I-Track alone decreases by a 7.8. So a little bit more with the I-Track alone versus the Faco I-Track. Drop reduction was similar, about one drop in both groups, and IOP reduction was also similar, about 72% versus 80% hitting that 25% IOP decrease that they were targeting. So this study by Hyami, again, is a retrospective review, but up to 36 months here. Drop reduction was the same between the Faco I-Track and the I-Track alone group. And they also showed in this study that actually baseline IOP remains stable. So they weren't really targeting a IOP decrease because the baseline IOPs are so low, about 14 and 15. And they do show that the mean number of medications over time has decreased. But as you go from about 24 months to 36 months, you can see that the number of medications required does start to creep up in both the standalone group and the Faco group. I'm suggesting that maybe this effect is not as long lived. So here is the Omni, created by Sight Sciences in 2018, as a competitor to the I-Track, and it's kind of a evolution of their VSCO 360 device. So with the Omni, it pushes a catheter through 180 degrees, and then as you withdraw, it releases VSCO elastic automatically. It releases much less than the I-Track, about 10 microliters, about 10 times less. And you can also go back in to do a 180-degree goniotomy or even a 360-degree goniotomy if you go into the other side. Most people in these studies did a 360-degree canaloplasty with a 180-degree goniotomy, if a goniotomy was performed. So here there are again no randomized control studies for the Omni or the VSCO 360. But VOLD did present a paper in 2020 that was a retrospective review with 12 months of follow-up, looking at the outcomes of 48 patients that had the Omni-ABIC with goniotomy. And again, that's a 180-degree goniotomy for most patients. They found about a 20% decrease in IOP. And they also found that 73% of patients had an IOP reduction of greater than 20% while also on fewer medications, which is what they defined as a success. They also separated the subgroups into group one and two, one for patients above 18 millimeters mercury as a baseline versus patients with below 18 millimeters mercury. You can see the two groups here. The upper group has a much more significant decrease in their IOP compared to the lower group, which has been shown in numerous studies with glaucoma surgeries where the higher starting IOP allows you to get a lower or a greater change in your IOP. And here this is this graph which they created this prediction model for predicting your IOP reduction, and you can see your pre-op pressure is directly correlated with your likely percentage reduction. And here in another study we have the FACO Omni VSCO 360 canal plastic device versus the ABIC alone. And here they show a more significant decrease in the patients who got the eye track, so the ABIC versus the FACO Omni device. The drop reduction was about the same, and they also didn't find any difference between the 360 versus the 180 goniotomy. There was a trend towards more effectiveness for the 360, but overall it's not statistically significant. So overall I would say there's low quality evidence for the canal plasticities and there's not good long term data. They do show good IOP reduction, but it's unclear whether or not the effect is persist after two years. And just for time I'll be skipping through this last for ELT which is not done here, less common than some of the other procedures, and also does not come with really many retrospective clinical trials. The only one they had was ELT versus SLT with a small group. So overall take on points for me is that with the eye stent and the high just as good evidence of IOP lowering effect lasting at least five years, maybe up to eight years for the eye stent. There's likely good IOP reduction of over 20% in about 80% of patients, and there's some moderate evidence of the high just might be slightly more effective than the eye stent. For the goniotomy, there's not good evidence that one version of the goniotomy is better than the other, but there is good evidence that it's at least effective in the first one to two years. And the effect size is similar to eye stent high just maybe even a little bit larger. However, there's not good data, like I said to show persistence over two years. One of the theoretical disadvantages is that it's a destructive process and might prohibit you from doing something in the future such as an ab internal canal capacity if you remove too much of the regular mesh work. And with the ABICS, again, good, good efficacy, but no good data over two years, but it is nice that you can repeat it so even if the effect doesn't last beyond two years it's possible to repeat it and that is approved. You can do ABIC alone without doing cataract surgery. Again, I skipped over the ELT today, but just wanted to clarify that all procedures had minimally significant adverse events and they were shown to be safe. And thanks to Dr. Chia for clarifying a few terms for me. And here are my references, thank you. Really impressive present Marshall and Arianna we are at time there was no we have I see a few comments so from Dr. Nakatsuka. I'm gonna says. Oh, this is a steroid versus others. Well, at least for Dr. Nakatsuka he's mentioning that he had a young girl with trauma retina surgery subtenance catalog and IOP. She was in her 30s with max drops 60 after she took off the drops that 360 vacuum like to me and she dropped to the teens when they were dropped. Yeah, so you felt that could be trauma related but with a big drop it feels that's probably steroid response instead of the TM was removed. Also mentions another interesting point that some people are doing goniotomy at the same time as to to blunt the steroid response, especially for valve was tubes. Very interesting for those comments.