 First of all, actually I have to admit that the idea to ask the residents for their career aspirations came from Cally Nelson and not from me. And not only with this but also with many, many other things she already proved to be a very valuable and creative co-worker. So we now all know Elaine's shoes are very large but you already did a great job and thank you so much, Kelly, to be with us. So our next speaker, Tony Mai, here he is, he will talk to us, he actually has the longest title. The Gonioscopy Assisted Transluminal Chavegalectomy, three to four year outcome data in correlation with pre-operative Humphrey visual field and OCT retinal nerve fiber layers. And he wanted to become an astronaut or a train driver. Take it away. There was actually one more, Dr. Hoffman reminded me, Dr. Hoffman said he wanted to be a garbage disposal man, a garbage collector and I had to say that I actually dreamed of that too. So wide variety of things. Let me just pull up my presentation. All right, do I need to start, screen share it all back there. So again, my name is Tony. I'm a third year resident here at Moran or PGY three and we're just going to be looking at some long term data of the gap procedure. The Gonioscopy Assisted Transluminal Chavegalectomy and I have no financial disclosures. Today we'll just be going over first the background of the gap procedure and why this has led to this current study. What our aims are for this study, the design of it, what we're currently doing in our next steps and this is because this study I started on just over the past year we're still just in the process of data collection. And so this is more just an introductory project and presentation where hopefully we'll have some more work to present to you next year. So first going over the background of the gap. What is the gap procedure and this is a good segue after the previous presentation by Cole Swiston, and this procedure was first described just a little over under a decade ago by Grover 2014. It is considered a minimally invasive glaucoma procedure does fall under that category. And what it does is that it decreases the intraocular pressure of the eye by increasing aqueous outflow, and it does so by cleaving the 360 degrees all the way around the angle. This is performed AB internal and this is as compared to AB external which is the traditional trabecuilotomy approach and I'll show you a picture of that later. So this AB internal approach is done with the help of agonioscope and hence that's why it's in the name. So how does this work, how does the procedure work, we first make small incisions in the cornea and in the trabecular mesh work, then a suture or a catheters and threaded into the cornea into the anterior chamber through that incision we made in the trabecular mesh work into Schlem's canal and then it's threaded all the way around, and then it's grasped with a micro forceps once it's threaded through that's pulled and then that cleaves the trabecular mesh work so we'll just be showing some pictures here. This is a video but I only took some snapshots of the video. And this is first a keratomic in a clear corneal incision. And this is just an animation of the trabecular mesh work with Schlem's canal behind there so we have to cut through trabecular mesh work in order to access that canal. And so you can see that blade doing that in the angle. Then this is a proline suture it's being threaded through, and then micro forceps is being used to thread that suture into Schlem's canal through the opening that we made previously. This is an animation. This is not a suture this is a catheter here that's being put through the canal. That's, and it goes all the way around, and under the gonioscope you can see how it comes out right around where the other suture entered and you can grasp that. And then on the outside there's another larger forceps, you hold one end, hold on the other, and then it rips through the entire trabecular mesh work. And immediately after that commonly there is some AC high FEMA and blood which a lot of times is not a poor indicator this is a pretty common thing and results. And so how has the gap procedure performed over the past decade this is a relatively new procedure, especially with the makes revolution. And it's been shown to be pretty comparable to the prior traditional trabecu lot of me. And what is the traditional trabecu lot of me. Well for this is an ab external approach so you're actually going under conscientiva and under sclera. And there have been many ways described previously this here is a picture showing the use of a trabecu lotome a metal one. And so you would access it ab external and then work in the slums canal and in the interior chamber from the access point. So that's as opposed to our approach now, which is through the cornea and you're not disturbing the conch or the sclera. So the get since its inception 2014 has been shown to be very useful for a wide variety of procedures. There's been an explosion of research showing that can be used for hoag primary closed angle glaucoma congenital glaucoma juvenile open angle pseudo x glaucoma can be used even you via the glaucoma. So many things that's been found useful for. And what we found through the studies is that there is an IOP lowering of about 35 to 40% only while the effects last. So now the question is how long does the get last for. And so we've had a lot of studies going up just to your point. And that's why our project was initiated to see, can we get data further than just two years. And actually there was just a recent data or recent study published just earlier this year, having four year data. And this is actually really interesting to be showing in the next slide, but the failure rate really starts to climb after those two years. So for the data sorry this got cut off a little bit right there but for the first study, I included from Grover 2014 that's the one that first came out showing one year data after the gap procedure. Grover then followed up in 2018 having two year data and the newest study that I found to be really important came out early this year by Lou showing four year data after the gap. For the patients whose effect this had lasted for you can see after one year is about 40% IOP lowering 37 for two years and still run 46 for four years so they stay pretty consistent. And this trend was pretty similar to the number of eye drops decrease 1.1 at one year 1.4 at two years and 1.0 at four years. Well what I found to be very significant is a percent of failure. So over the four years, the percent of failure actually increased all the way up to around 52% of patients, and they had a specific definition of failure that I won't really get into but it's something like greater than IOP of 21 IOP not being controlled one single instance of very high IOP. So what we can see here the trend is that the failure rate goes up to 52% at four years. For those people who it works for it works well and it stays so for those that don't, there definitely is this trend going up. And so they included this Kaplan-Meier survival curve here, where you can see where there's a sharp increase up in failure over the first six months after the procedure and that's pretty expected. So then it levels off for a while up around until the two-year mark and then there's a steady climb for both primary and secondary open-angle glaucoma. And so because of these failures, now we're wondering to ourselves, is there somewhere we can risk stratify these patients, use their testing to figure out if they are a good candidate for this procedure or whether they're going to fail pretty quickly after we do it. One of the most common things that we use are the HumperVisual Field testing and the OCT-RNFL scan. And so can we take this data or relate it to their survival rates in terms of the success of this gap procedure and then see if we can come up with some better idea of who will do well and who won't. And so looking at the pre-op HumperVisual Field, Grover at the two-year data actually did this and was able to show that there was significant increase in failure for eyes with mean deviation on the HumperVisual Field of worse than negative 15 decibels. What we can see over here that those patients, this is in the dark black line here, had this huge increase all the way up to over 80% failed just at six months, whereas everyone below that they did relatively well. And so this was a great way to risk stratify these patients. What we haven't seen yet is similar data for the RNFL scan. No studies have looked at that. And we use the scan all the time, and especially as these procedures are being done for patients who have more mild glaucoma who might not have a lot of findings in their visual fields. This might also be a good way to assess them. So this leads to our study aims, which is to first extend our follow-up data all the way up to four years, but hopefully even more than that, and just preliminary looking at the data that we're getting back. We have patients all the way from 2015-16. So this is actually going to be a good amount of follow-up data that we're going to get. And then we're going to try to correlate their success with the pre-op HumperVisual Field and OCT RNFL. So for this follow-up, we're going to be looking at their intraocular pressure, the number of medications are on, their failure rate and their re-operation rates. And then for both pre-op HumperVisual Field and RNFL, we're going to try to do the similar survival curve over at least four years of data. So for our study design, this is an IRB approved for a retrospective review. The timeframe is going to be from the first GAP procedure done here at the Moran, so anywhere from Moran 2012. And we're going to collect data all the way up until this year. The GAP procedure, it's going to be performed anywhere through 2019, so at least they'll have four years of follow-up from 2019 until now. For inclusion, we're actually going to be looking at just the adult patients who have had uncontrolled IOP, and that's why they needed the procedure. There's a lot of exclusion criteria on here, but basically just patients who have good follow-up, who aren't using steroids before or during around the GAP procedure, who have pretty open angles and don't have any other, like, big coromabidities like neobascular glaucoma. So this is actually a project that we're doing together with Iowa, and we are collecting data from both sites, and we're going to be pulling our data together. And just going over who's involved in the project, so this is led by Dr. Chia here, and then John Moosar and I have been on the project along with two medical students. On the Iowa side, this is Dr. Pow, and my friend also a PGY III Dr. Mansour. And so currently we are still just undergoing the data collection. We're actually doing a big revamp of our data collection where I'm actually going back using some more CPT codes to really try to capture more patients, more eyes, and then we're going to be cleaning through our data this summer, hopefully getting analysis in by the end of it, and then writing and submitting by September. And so just acknowledgments here, and I apologize, some of the format here got messed up when the transfer of the PowerPoint, but just to acknowledge everyone involved. People I didn't mention yet, Benjamin Brintz, Hunter Fogg, who also have been helping with this project. So, still a lot to be worked on and hopefully next year we'll be having some good data to present to everyone about this project. Any questions. Nice job Tony. I was wondering, I noticed in your inclusion criteria you mentioned on controlled IOP is one of the inclusion criteria do you guys know yet how you'll define on controlled IOP for these patients. Thanks. Yes, so it's for patients who are on maximal medical therapy already, and I have to remind myself and look at the paper but I think it's above 21 where they cannot get lower than that with the medications and therefore they needed to go for the gap procedure. So, you know, as I remember talking to Alan Crandall about this procedure a long time ago. And I just said, you know, inherently the body doesn't like tearing disruption, and it will tend to want to repair it or change it and repair mechanisms in the eye notoriously are not good. I mean, we understand the body does it elsewhere. I just suggest that because we've got such amazing electron microscopy capabilities with Brian Jones he's always looking for these unusual. If we get any of these patients in whom we have to go back and reoperate and we can get some area of tobacco mesh work to look to see how it's changed and evolve because there's really not much in the literature of looking to see what what down to the ultra structural level in the fine cellular level because he's got ways of branding so we can look at what types of cells are there. You know what the remodeling has occurred. I think it's almost for sure that's got to be what's happening. I think, and actually to this point in my literature review. Part of what I found was that there has been some studies not on the electron level or imaging level at all but there's been a lot of suspicion that a lot of make things makes things fail because of the scarring and remodeling in that area and so these things just block up again after we tear them open. The Schlemz Canal surgery is really a relatively new thing that we've been doing. I mean people knew about Schlemz Canal many years ago but it's only been the last couple of decades that people are looking at Schlemz Canal and looking at surgery in the canal itself. And Rob Stegman from South Africa was really the modern person who pioneered working Schlemz Canal externally though not internally, but for the residency, you can find his videos he's got some amazing videos of putting light devices through Schlemz Canal and putting things through Schlemz Canal. The problem is is he was working externally and anytime we work externally it scars even more than internally. So I do think that there's inherent advantages of working internally because you do at least eliminate the scarring that takes place in the Schlemz Canal in the area and Episcopal area and externally. All right, thank you everyone. Our next speaker is Lydia Zawa, and she will talk about retinal vascularization following intra vitriol and TVGF for RLP. And when Lydia was young or younger, she's still young. And she wanted to become the anchor woman of the mini playback show. So this was an extremely fancy and renowned television show in Europe. And it was actually that there were children who wanted to mimic their stars. Usually these were US stars of course, Whitney Houston and Madonna. And so there they put on their clothes, you know, looking like their idols, and then they did a playback show and mimic these superstars. And so she wanted to be the anchor woman. So today, the stage is yours. Thank you so much for that introduction. Yeah, I'm going to present some very new data that I'm actually very excited about ever since I got unmasked about a week ago. And I'm going to start with a pomegranate. And I'm not going to start with a pomegranate because the kids that used to be dressed up as stars went through kind of this magic bowl that almost looked like a big pomegranate. But I'm going to start with a pomegranate because at week 22, your baby is going to be about the size of a pomegranate. And the youngest child that is known to survive was born at 20 weeks of gestation. And the incidence of these young children that are born prematurely to survive is increasing. And about 11 to 13% of pregnancies in the United States, and in premature birth, and birth is considered preterm when the child is born before 37 weeks of gestation. The survival rates of the very young premature infants is increasing constantly. And that also means that the incidence of retinopathy of prematurely is increasing. And our P remains a major cause of preventable vision loss in premature children. It occurs in children that are born at 30 weeks or less, and with a birth rate of 500 grams or less. And the incidence of our P in premature infants within the United States has nearly doubled from 4.1% in 2003 to 8.1% in 2019. The treatment of our P includes laser ablation of the a vascular retina, as well as intervital injections of anti VGF agents, specifically by the system up and individual in anti VGF was found to be beneficial in the known V drop study that was published in 2011 so almost 15 over than 15 years ago, and it is still largely unknown how VGF and anti VGF alters the development of retinal vasculature. So my big research question for this study is how is retinal vascularization affected by anti VGF injections. And the hypothesis is that the vascularization of the peripheral retina differs in infants who received an anti VGF injection compares to those who did not. So motivation as I mentioned before the incidence of our P is increasing, and it is poorly understood how anti VGF affects the vascular growth in premature infants. And there's really not a lot of quantitative data available to compare the vascularization differences between treated and observed patients. All of this study is really to quantitatively investigate how the retinal vascularization changes or progresses after a single injection of anti VGF compared to a group of patients that were observed and did not receive injections or any treatment. This is a retrospective analysis of patients treated at the moran from 2019 to 2021. All patients were examined and treated by the same pediatric retinal specialist list which is Dr. Hartnett. I have included patients with our P type one that require treatment, and they received a single low dose of interveteral beaver season map. And then the control group was a group of closely observed type to our P patients. And all patients needed to have photographs pre and post treatment. And I was a blinded reader and received the identified photos from Mel. To investigate the retinal vasculature. The big challenge in the beginning was to find a way on how to reliably analyze these images and find something or find a way to reproducibly get data on the vasculature. So I came up with the idea to choose a marking line on vessel be vocations which you can see here as the black line that I included in both the posterior pole image as well as the temporal image, and it had to have the same marking points at baseline and follow up and those had to be visible in both pictures. And then I measured the vascular extent at a 90 degree angle from the optic nerve to that marking point and from the marking point to the periphery where the vasculature ends. And the same angle was used in all of these pictures at baseline and follow up as a control measurement, the optic nerve diameter was analyzed as well. The images that were excluded were images like this where it is impossible to tell where the vasculature really ends or where it is impossible to find reliable points to set these marks. As well as pictures where at one of the at one of the visits no optic nerve image was available. And considering that we looked at three years of patients, we were only able to get seven patients that matched our criteria which was a fairly low number. And we included seven patients that were observed that were birth rate and age matched. There was no significant difference in those two groups between as I mentioned birth rate, the week that they were born, the days between the visits that they were analyzed and the optic nerve size. Initially I was very skeptical about these numbers, but when I got unmasked and saw that there's a significant difference in a couple of areas, I got a little excited about it. As we expected the vasculature, the vasculature extent was different significantly different in the observation versus the treatment group, because the treatment group is so one hour P and the observation group is so two hour P. And interestingly, the vascular extent or the acceleration of vasculature was much faster in the treatment group at the follow up visit. And those patients actually caught up in the vascular extent at the, at the follow up after treatment. So there was no significant difference in the vascular extent at the second visit. As shown in this graph here, the difference in the vascular extent is significantly different between those two groups. And it is also different if we kind of divided by the days in between visit one and visit two, we can say that on average the observation group had an extent of about 14 pixels. And the treatment group had an extent of about 52 pixels, which again was significant. This just kind of shows how the vascular extent increased in the treatment and the control group on the left side. And then for each individual patient on the right side, the treatment patients depicted here and the controls over on this side showing a clear difference between those two groups. Furthermore, we looked at how what area of the temporal periphery experience that growth. So I looked at the area from the optic nerve to the mark versus the area from the marking line to the end of the vasculature. And it turns out that the vasculature seems to extend most significantly in that area B. Here's the difference in the table. So in area B is where the vascular growth happens. And that's also where we can see a significant difference between visit one and visit two in observation versus treatment group. And this is depicted again in this chart. Finally, we also looked at vertical changes and it's a little bit more difficult to assess how the vertical diameter is changed over time. But since we have the marking line with known points that we looked at, we were wondering if the marking lines changed at all. And there was actually a decrease in the marking line that was significant for the observation group, but not significant in the treatment group. There was no significant difference between the two groups overall. So what that means is that the vertical diameter got slightly smaller, which might be just the normal growth of the eye. But this did not have any relation to whether or not patients got anti VGF injections. So, in discussion, there are a couple of laboratory studies that have shown that anti VGF has a favorable effect on the vessel elongation in the retina. And that is thought to be due to the fact that anti VGF causes a favorable orientation of the endothelium mitosis cleavage planes. And those are responsible for the elongation of vessels. And there's also a clinical study, the only one that really showed quantitative data that showed that in patients who had received intervital bivacism up. The increase in temporal retinal vascularization was greatest at the short term visit at 7.3 weeks and less at the long term visit. But those patients were again not compared to control groups. In terms of long term follow up for these patients, there are no adverse side effects medically or neurodevelopment neurodevelopmentally that were found for the patients treated in the B2OP study, or in other studies that also looked at long term follow up for these patients. There's one big discussion going on about peripheral vascular retina which is frequently found in patients that have RP and it often requires additional treatment. However, a study that looked at patients who were screened for RP and did not receive treatment with anti VGF 91% of these patients also had a vascular retina. So this is something that's likely not related to the anti VGF injections, but related to RP itself. However, future studies are really needed to investigate the long term effects of anti VGF and what it does to the vasculature of the babies. But in conclusion, this study found that the vasculature length increases with anti VGF injections, and the increase in healthy retina vasculature is really accelerated with one single dose or low dose of vivicism up. And that the patients actually catch up with the controls at their one week follow up with only that one single injection. So what might be the case is that regulating abnormally increased VGF signaling may promote the physiological vascular development and future prospective studies would be needed to kind of quantify this effect for longer term follow up intervals. Here are my references. And with that I would like to thank especially Dr. Amy Hartnett who is really the brains behind a lot of this and I think this study is kind of a proof of concept clinical proof of concept of a lot of her laboratory work up work that she has published. And then also Mel who got a lot of these images for us Maria Maria Margarita and Dr. Jacobi. And thank you all for your attention. Yeah, thank you so much for this very impressive data. Dr. Hoffman. Yeah, this is great work. You know the more we hear things like this more. I realize that we don't understand everything we need to understand about RLP because my clinical standpoint concerns about failure to develop peripheral vasculature and recurrence of RLP is been the big thing that leads to many of these children, particularly those that come to us from disparate areas, Montana, northern Wyoming, getting laser treatment prior to discharge. But you're also showing that there is increased vascular development. Putting those together is is going to be key. This is really good work. Very impressive. And you know I mean in my practice career I've seen things go from kids with severe RLP were simply sent to the blind school. There was no treatment. And then we had cryo at laser, various anti VGF treatments and all the subtleties of that are being sorted out. This is this is good work and look forward to good things from you. Thank you so much. I think the benefit of using anti VGF injections might also be that if the vasculature the healthy vasculature increases patients could see in those areas versus as they were if they receive early laser, those areas would be visual field defects. I think investigating whether even the children from like northern Idaho who take hours to come here, whether they would benefit from a single injection and then doing laser, if it fails to develop further might be a good point of thought. Hello. Thank you. Other questions. Okay, our next speaker. I'm a Curie, and he's talking about leveraging the site outcomes research collaborative repository also the source repository to identify patients with RPG are related ready 90s pigmentosa. And you wanted to become a teacher and basketball coach. I think, you know, being a physician allows you to teach a component and luckily for me, having Jordan in my in my class, I think there's still hope to the coach them up and be that basketball coach in the future. So, so like she said the title my presentation today is all leveraging the sites outcomes research collaborative repository to identify patients with RPG are related retinitis pigmentosa. Thankfully, we've kind of already touched on this briefly. Dr efforts did a fantastic job of laying the groundwork and Dr stag added some comments as well. But I'll specifically talk about how it has helped us with the specific inherited retinal disease. So just a brief overview on retinitis pigmentosa. It's the most common cause of inherited blindness in the US affects about one and a half million people worldwide with the prevalence of one in 3000 to one in 5000 per year. It's clinically and genetically diverse with inherited retinal disease, predominantly affecting rods with later degeneration of cones. It can be also more excessive dominant or excellent, and its inheritance pattern correlates with disease severity. And so on to some of the symptoms that we will typically see in this disease because it's rather predominant. You can have Nick tilopia or night vision issues, as well as tunnel vision. And, but later on you start to notice some for the topsy is for the phobia and gradual onset of vision loss. So, in terms of the classic findings when we get tested on and one might see in the periphery you can see clumps of pigment dispersed in a pattern that's been previously expressed as a bone spicula retinal pigmentation. I'll be honest before this project I had no idea what a bone spicula was. I think still afterwards I'm still not sure how it correlates. But here's an image that I found online and and what we typically see on a funnest photograph so hopefully maybe someone can make that connection for me. Please reach out again. Other findings you might see arteriolar attenuation optics optic disc pallor, commonly described as waxy. You can also see vitreous cell retinal pigmentary epithelium changes, as well as posterior subcaps or cataracts being a fairly common complication of this disease. In terms of additional findings, specifically with female carry carriers that are symptomatic. The periphery changes are commonly described as mild. And that's what the top funnest photograph is supposed to be, which was a little bit more zoomed out apologize for that. And the bottom ones, specifically focusing on the macula so it's commonly described as a petal petal reflex that we can see in canines. Here is a picture of a topidum and kind of the same thing present but I think I can better hallucinate here and see how this might correlate a little bit better. So in terms of the causes of red nice pigmentosa it's it's due to mutations in rhodopsin protein genes. The most common and severe form of which is the RPG are related excellent for it nice pigmentosa about 10 to 20% of cases in our RP is excellent 70% of which is localized to mutation that the RPG are gene. And because all caps is 330 days away I just thought I would put a picture make sure everyone's preparing of some of the differential diagnosis for retinitis pigmentosa. I will go into much detail here but I just wanted to show you how broad it can be. In terms of that diagnosis so there's multiple modalities with which we can utilize to better assess and track these patients full field ERG is particularly sensitive. Early on it can show scope topic changes so reduced a and b ways and eventually you can become undetectable. And this is an EDA, an EOG which helps you look at specifically RPE abnormalities. This will be sub normal or you won't see a light rise in this specific disease pattern visual fields will commonly show mid peripheral scatomas that eventually will coalesce and ultimately leading to this tiny central island of vision. And that's because of the rapid changes rapid expansion outward and kind of slower expansion inward. So we can utilize OCT look for macular edema and of course genetic testing to confirm the presence of the disease. And in terms of treatment. Currently there's no approved treatment for excellent retinitis pigmentosa but there are retinitis pigmentosa in general but there are some new exciting potential therapies on the horizon. One of the biggest challenges with studying and expanding this is upon this is the fact that there aren't ICD 10 billable codes for retinitis pigmentosa so it's hard to get a large enough population size to really dive into research whether it be finding the correct patient population to do gene therapy on or just looking to these in general. And then of course there are symptomatic treatments for cataracts or just low vision in general that will pop up in these patients. Often very early. And so I kind of briefly touched on this but the question back in how do we expand our research capabilities. How do we better attack therapies in the future. It's not as complicated as I think that one of the first steps we need is just to increase our sample size and of course here's a picture of two of our students. So the objective of my specific research was again to leverage that new repository source to obtain a better appreciation of the demographics, the clinical findings and really a patient's journey with their disease and disease process. On some materials and methods. So what is source. It's a consortium of an academic ophthalmology centers utilizing the same HR submitting the identified data from these various institutions. Again we can capture demographics capture exam findings capture diagnoses procedures labs surgeries medications. Of course, like Dr said mentioned earlier we're not capturing. We're not seeing the full chart, we're not seeing the full progress, no to report, and this is from multi variety of different centers so it's going to be very different with which in terms of the visual fields we're using and a whole bunch of other different things but the source allows us to essentially clean aggregate this data to better harmonize it and use it for research and quality improvement projects in the future. And so this is a graphic just to show you which sites are currently involved so about 12 or 13 sites are currently active and that's depicted on the right, and then all the sites that are either planning or in the process of becoming involved on the left. So right now there's about 4 million patients in that repository. And the patients specifically I'm going to present on today are actually from about three or so the sites that are currently active. So the number. Well, actually I'll discuss that later. And so in terms of the methods. Once again, it's de identified data so I'm just this slide really just to show you an example of that chart review that we did specifically at the Moran ice center. On the left, we just have an ERG again removing patient data on same thing on the right with the visual field. All right and then in terms of results so actually before I dive into that we I want to describe a little bit more about how we classified our patient population. So we have four main categories. The first of which is definite cases which are males with the clinical phenotype, as well as RPG are confirmed genetic testing. And I really want to focus on that in particular it's incredibly important for us can really help us narrow down any variability that is really inevitable with small sample sizes. So effectively we can increase our power in future studies by increasing this specific portion of our data set. Probable cases include males with perhaps the clinical phenotype and a relative with RPG are confirmed retinitis pigmentosa. And it needs to also be consistent with an excellent pattern of inheritance or males with clinical phenotypes and reported genetic testing that confirmed RPG are but we just didn't have access to that currently. And then possible cases are when we had males with the phenotypes, but variants of unknown significance. And in terms of symptomatic carriers as kind of self explanatory but essentially females that were confirmed to be symptomatic carries either by genetic testing or excellent someone in the family, having the same pedigree and testing. And so, one of the focal points of perhaps the most important kind of thing that my specific research is touching on is the fact that even in our infancy source that we were able to the patient that we're able to accumulate really does do a good job of. As compared to recently published literature on XLRP. So we found that it stacks up very favorably to any single center capability, and I just include this for absolutely no reason and I'll continue. Further on with results for demographics, the majority of which were non Hispanic white individuals about two to 4% fit and other racial demographics. We have about 8% unknowns or undisclosed. And I kind of touched on this briefly before but clinical management varies across all these sites and first I thought that was a limitation but I really just think that's a result in general. There's no clear distinguishing factor to say that it's a limitation quite yet it can actually be a benefit depending on maybe what quality improvement factors that we end up finding from this. Not every patient underwent the same assessment so as we all know visual fields can be quite different from center to center so the specific visual field is going to be different type of visual field might be different etc. This is just a figure showing the age at first I encounter. That was fairly consistent between the different types of patients we had. So around 25 years old. And then we had a figure showing the visual QT at the first I visit as well as the most recent I visit. This is a difficult, I think, bigger overall because we're not showing. Well, patients were not seen that over the same time periods right so it's not really going to encompass whether or not we have a patient who was seen five times or over the span of five years or 10 years etc. But as expected it's showing that visual QT does worsen with time and that can be again, confounded by a whole variety of different things we talked about PSEs we talked about other complications that one can expect from just aging. And then this is specific to the Moran eye center comparing RPG are related retinitis pigmentosa as to our P2 at the Moran. Our goal is to really replicate this research that we did use with source and see how it compares to our specific patient population. About 90% of these patients were male 90% of which were also have the RPG are mutation in green we see the combination of both RPG are an RPG to lose the RPG are and then the red is that RPG two minute mutation. The average age was very similar across both the groups, but specifically when it came to the average age that legal blindness represent on the right hand side. You can see that RPG two patients became legally blind a lot sooner than RPG are patients and this is just one of those data points that we can kind of look at. Examine I think source gives us that opportunity to to explore more. So ultimately sources a novel database that offers comprehensive clinical data for rare disease populations, like those with XLRP, but also like glaucoma and a variety of different sources as Dr. Stagg and Dr. Ethridge mentioned earlier without specific ICD 10 billion codes. It really can be difficult to locate these patients and other data sets so this is the huge advantage with source and multi centered studies in general. Once again permits us the or provides us the opportunity to really better understand. XLRP compared to other genetic field types, etc. And so I wanted to acknowledge some of the people who helped make this research possible, starting with the research to prevent blindness and New York, the Carl and Joan Moscow family, Jansen or Johnson Johnson company, as well as Arx Foundation. And further acknowledgements include Dr. Joshua Stein and Michigan doctors Barbara Roscoe and Brian Stagg here, and special thanks to our medical students who did a ton of chart review and a ton of really hard work. Dennis Jensen a third year medical student here and Taylor Johnson a second year medical student here. A picture above is a presentation Arvo was fortunate to present this a couple of weeks ago. Already any questions. This is probably a question more for Dr. Stagg, Brian. I know that these big data sets have to be de identified in order to use them. Is it possible to pierce that and then identify who these individuals are just thinking of ways that because often our problem has to do with numbers and they're not having enough in different data set to be able to do really detailed analysis and and if you can go back and for instance any of our Utah group, almost for sure you can get them in Utah population database and start getting pedigrees and others and and I'm just so I'm just curious or it in order to make it as usable it you really this data is de identified. So, that's a good question I've actually gone through like a few different things with that like, like this, like getting this data has been a huge process, like I started working on this in 2019. And we're just like getting the data now it's like, you know, Christmas finally came and but so we're, we'd like to do a link so that we could reverse it. So right now, so we know all of our patients with so it's not a huge issue for this we know who are who our patients are, but for future work, we're right now once we send it from there you can't go back to our data. And that's how we've set it up. We're, we're working with like our, our institutional, you know, legal and advisors here, we'd like to create a link so that potentially we could go backwards. So we're working on that. But right now, once we send it it's completely de identified, but we do know all of our for these patients we would be able to connect them with the Utah, Utah population database. And for studies though too as well you know you, you have these you say, what if we could do x that may be helpful, and if you can't go back and and for many of the areas, it may not be that easy indeed if they if it's totally de identified. I'm just, yeah, I know I know that it's the pluses and minuses and the privacy and all of the others. But I think in the end it would be really safe, because we would keep that on a secure thing so someone would have to like pack the data in Michigan. And then independently hack our system. And by that point they would have hacked a lot more stuff that would be a lot more useful. And so I think, like, I think that like like credit card numbers. Yeah, exactly. So I think that I think that we'll be able to get approval for it, and it'll be our plan is to keep it like behind like behind an IRB firewall you know so you'd have to have an IRB to use that reverse link. And we'd have to demonstrate you know the the normal IRB things like the patients would get a benefit from it they'd have an. And so I think it would be really safe. It's just a matter of getting approval on that and so I'm working through that process. So if you support it that's really helpful. You've got my support. I guess just a quick comment on that. So that is one of the goals for at least Janssen's involvement with this. They want to essentially find the right patient population to starts a lot of these clinical trials and gene therapy. So ultimately it would be hugely beneficial for future studies to be able to work our way backwards. And we can easily do that with the Marani center data that we have, but, especially when this grows and really expands. If we find out a critical time period with which we want to perform gene therapy in the future be great if we can work our way back and, you know, find those patients to get them involved. Hey Nana I'm sorry if you mentioned this at the beginning but if you take your garden variety excellent RP patient what percent of them have that RPG our mutation. So 60 to 70% at least in some of the later trials looking at 60 to 70% of retinitis pigmentosa was RPGR. So it was the most common and also the most severe form of course as well. And so it's significant enough for us to hopefully find enough data and make a huge impact in the future. Given the processes that we talked about earlier. The other questions. Thank you. Thank you so much and I do not only see a huge value for rare disease but also for, you know, certain sub types of age related macular degeneration and response to upcoming therapies and dry AMD so Brian thank you so much for this initiative. I think we can all benefit a lot from this. Okay, so our next speaker is Jordan desautols I'm sorry I certainly pronounced it. And Jordan will talk about orbital implants receiving pre market approval. And I very much like what you wanted to be when you was young. You wanted to be a street crossing guard. This is solid this is reliable and I think these are the most important character. Is this lapel mic working I'm debuting the lapel for biomechanical reasons. So hi, I'm going to be talking a little bit about orbital implants that received FBA pre market approval or what we call FBA pre market notification. As you'll see in the title I was going to originally talk about another case series on awakening ptosis but it was a little busy so we're just going to talk about orbital implants today. And this is a project that was published in the ophthalmic plastic reconstructive surgery in the fall of this year I worked on this with a mentor from medical school Dr. Miliore. I'd be remiss not to mention Dr. Corcoran Ruiz who's a resident at University of Pennsylvania who spearheaded a lot of the efforts for this project. This study is really more qualitative than anything but I think it's a useful background for us as ophthalmologists as we interact with technology daily, we're in a high technological use field we put in a lot of implants and things like that so it's kind of an insight into how these devices are brought to market and some of the potential inherent flaws in that process and I will specifically talk about that process with respect to orbital implants. So, I'll start off talking about kind of just some background on how the FDA classifies medical devices and the FDA clearance or approval pathways that are relevant to those different classes. And then I will discuss some pitfalls of the system and present data from the US marketing of orbital implants that showcases some of these pitfalls. So the class that the FDA designates to a medical device before it is considered able to be marketed in the United States is based on both intended use but also indications for use. So class one devices, for example, Band-Aids with only some exceptions are subject to a series of controls that we call general controls. These are just basic production safety guidelines that apply to all US marketed medical devices. In class two devices, for example, orbital implants and a vast majority of the devices that we use every day in ophthalmology are given a designation of quote FDA cleared through something called the 510K pathway. And there's also some nuance to that which I'll discuss in a moment. One specific exception that is given to class two devices is called the pre-amendment exception, which allows any device that was marketed before 1976 when the FDA passed the Medical Device Amendments Act to essentially be given grandfather status. So it never had to undergo additional clinical testing to actually remain on the market. So if you were selling an orbital implant in 1975, you were allowed to continue marketing that device without any additional approval after the passage of this act. And then class three devices, of course, such as pacemakers, these are high risk products, they have life sustaining functions, and they require rigorous clinical studies showing safety data prior to being placed on the market. And at the end of that process, they are given the designation of FDA approved. So when you hear FDA approved that is the result of a actual safety trial. So I'll talk a little bit more about the 510K clearance pathway, also known as pre-market notification. And this is a notification that is essentially filed by a company to the FDA, at least three months in advance of marketing a device that allows the FDA to determine if the device you are trying to sell is what they call substantially equivalent to a device that is already on the market, so called predicate device. So substantial equivalence itself means that the characteristics of the new device that you're trying to bring to market are deemed similar enough. The characteristics of a predicate device as to be considered safe to market without any additional testing. There's no additional safety testing. And this is really the only real way you could bring a product to market. And it's a good thing because if you had to do a clinical trial every single time, you wanted to make an iterative improvement on a new orbital implant or any new device, you would essentially get nowhere in terms of bringing devices to patients, the time expenditure would just be unacceptable. But there are several inherent flaws with the 510K system. And in our study, we essentially demonstrate this by looking at orbital implants brought to market, but the logic holds essentially for any product that we use on a daily basis. So the first problem is that an orbital implant can be cleared and deemed substantially equivalent to a pre 1976 device that was not subjected to any safety data and was sort of just grandfathered in. And the second is that you can prove substantial equivalence by being compared to a device that was also cleared by being substantially equivalent to a device prior to it. And there's no limitation on how many generations that can go back so the original predicate device that was actually studied and approved, maybe so many generations removed from the product at hand, as to be, you know, really and if at any point in that chain of substantial equivalence claims, if one of those products is determined to be flawed has complications has safety issues and is pulled off the market. There is no formalized process by which subsequently cleared devices that were substantially equivalent to that device undergo review. So they are essentially remaining on the market, having been cleared by being substantially equivalent to a device that is now not allowed to be marketed to any device anymore. So what we did is we actually utilize the FDA is publicly available 510 k pre market notification database for all FDA cleared orbital implants going back to the laws inception in 1976 to try to trace these chains of substantial costs as best we could. And ultimately we identified 29 orbital implants brought to market over this time period, and only nine of those implants so about a third anywhere in that available pre market application, even list a predicate device anywhere in that information. So a lot of that is actually done behind closed doors with the FDA, and a total of four of 29 of these orbital implants were recalled for various safety reasons like extrusion infection rates that were considered unacceptable. And only nine of those implants like I said listed a predicate device. Of those nine implants that did list a predicate device, three of them were cleared by being deemed substantially equivalent to an orbital implant that was subsequently recalled is taken off the market. Those implants essentially just remain free floating being put in orbits all over the United States. And so, kind of some of our conclusions, while none of the orbital implants with a recalled predicate device went on to be recalled at least thus far. When you see these late night commercials of, you know, have you are a loved one had an abdominal mesh that extruded through your abdomen. Those kinds of things that this is how that happens is through this kind of series of substantial equivalents claims. It's really shocking when we went through all the data only 1% of devices that you see on the market today are actually FDA approved meaning that they undergo clinical safety trial data, and these labels that say FDA cleared may give false evidence both to consumers, but also to doctors who are using these products every day, and you're going to put in an implant, and you say this is FDA cleared that may not be as meaningful as you have originally thought. There are some positive things in 2022 the FDA pass an act, which is called the medical device user the act and they essentially tighten the definition of substantial equivalents and they put in a post market studies program called the 522 program, specifically other class two devices like the ones we use today, where essentially devices that get flagged in some way either through clinical trial data or through public comment data can be subject to additional controls and require additional approval and regulation. This is yet to be applied to any orbital implant currently on the market. And so just all, I'll finish here with just a small public service announcement, if you are noticing complications with devices that seem to be disproportionate maybe to what is published in the literature or is being claimed by a company. The FDA has a public database called medwatch where doctors and patients can essentially report safety issues, and then that allows for this flagging process and some post market regulation to essentially occur. And thank you for your time I'll take any questions. This goes back to a time when there was no devices act, and it wasn't a drug you could essentially do anything. And we had people making intraocular lenses in their garages and putting inside a vice to disastrous impact so. The devices act largely occurred, because two companies using what's called what sterilization, in which you use sodium hydroxide to have the lens sterilized and then you would put it in bicarbonate of soda afterwards to, you know, to make it safer than rinse it. Their bicarbonate of soda in one case had a fungal infection through all of them, and cause devastating impact that was one of my first papers I wrote about that series. Then right after that another company had their sodium, you know bicarbonate of soda contaminates to the bonus you can imagine how that went. And those two cause the outcry that resulted in the devices act, but you point out the very real holes that exist. And there's always this cry about the fact that you know we're too restrictive, but even though I think at times it is too difficult when you're doing the full formal process that the loopholes that still exist today cause problems that would otherwise be avoid them. Thank you. Wonderful talk I am wondering, and I'm not as familiar with that. How many of the ocular implants that we implant at the more and I center our FDA cleared versus FDA approved and do you know if there's a price difference between those. I'm not sure if there's a price difference. All the orbital implants that we use at the Moran as far as I'm aware our FDA cleared. So like the med poor, for example, those are those all came through the 510 K program, rather than initial clinical trial data. How about if you have a device that is delivering medication, it does that fall under medications or the devices like the insurable steroid. I also did something like that. I'm, I would imagine that that would. I don't know exactly I would imagine it fall. So they can't hear you online really quick. I'm going to let Deborah or resident expert may comment summarize any comments that were made today. I will just say that, you know, something like a drug delivery device implant is regulated as a combination product as Dr Hoffman said but they're held to the drug standards for their FDA trials, rather than the device clearance. And just for those online that was Deborah Harrison would you tell us your full title if you would as well. Yes, my full title is associate director of research. Associate director of research just just for those who haven't met her yet. And Dr Warner a little bit more to your point so it is, it is both integer upon the intended use but also the indication kind of what if you have to be cleared or approved through a study. If the intended use of a scalpel say is to make an incision that might give you one class designation, but if the indication for use what you actually put on the label is to make corneal incisions, then that will upclassify you and require you to undergo more formalize safety. If anyone wants to lapel this is this is nice. Thank you so much. Our next speaker, Mubarak Mohammed, and he will talk about systemic review of the diagnostic approach to non glaucomatous optic atrophy. And when he was young he wanted to become a professional soccer player. I get this I have two boys in this age. One wants to be a professional soccer player the other one a professional basketball player. I still hope that. Thank you so much approach to non glaucomatous optic atrophy and this is kind of born out of both kind of being on the neuro ophthalmology service and then you know with glaucoma. A lot of the referrals are for kind of these atypical cases of glaucoma where they don't have kind of, you know, the family history, you know the IOP is kind of normal maybe normal to glaucoma and then the visual field they're a little abnormal so it's very common, as far as kind of this patient population and very commonly seen in neuro ophthalmology. So just a little bit of a background. It's the most glaucomatous optic neuropathy is the most commonly acquired optic neuropathy encountered in clinical practice. The definition is a progressive optic neuropathy characterized by typical changes in the optic nerve head, including a large vertical cup to disk ratio no retinal rim loss disc hemorrhages, and that correlate with visual field loss as far as the although elevated intraocular pressure is the most important risk factor for glaucoma significant portion of patients may present with a normal IOP and I'm sure that was kind of all in question that we're asking medical school as far as like what's the actual definition of glaucoma. Yeah, such a definitive diagnosis is not always simple, and it's not straightforward because I would be talking about pressure is not a criteria for diagnosis, and there's a high possibility of misdiagnosing various non glaucomatoscopic neuropathies. You know, the kind of differential is very broad as a lot of the, I guess, PGY to first year residents know working in our neuro ophthalmology clinic so kind of the main one is you know not missing kind of an extrinsic compression but certainly a congenital optic neuropathies such as as well can also presented as an optic neuropathies such as RP and kind of not as talk, certainly intrinsic tumors such as ophthalmokneomas extrinsic compression vascular disease, ophthalmic neuropathy inflammatory disease toxicity trauma. Just a lot of unpack and I'm sure certainly I've been in the case where you know you're presenting to an attending and always seem to miss one of these they always get it right so see if I can go back. In literature there are varying opinions in the utility of neurological and neurophthalmal evaluation of atypical glaucoma explained optic atrophy. Certainly from kind of our research, you know there's been kind of over the years, certainly ending Lee has published several articles looking at these utility as far as a laboratory and imaging work up several folks out in Israel as well have produced some results which are a little mixed some folks you know advocate for a kind of an extensive laboratory work of other was other folks, you know, say more so just kind of get a brain scan and make sure that you don't roll out a or you will add a tumor compression. But with these varying opinions in regards to the imaging and laboratory evaluation. There's a need for a directed approach in regards to their initial diagnostic evaluation. And certainly this is a kind of a need for such research in the literature because it's lacking. So, I did not realize that prior to starting residency that you have kind of a year by year contract, and I just recently reviewed my contract for PG Y3. Thank you Dr. Simpson and Dr. petty for letting me say at least one more year. But one thing I also realize is you know systemic literature reviews take a while. You know, as someone told me about 18 months and working with the, the librarian and kind of the folks at Apple South Sciences. So certainly my research project is not completed in the sense but I felt like it was a good opportunity to use for the junior residents and some of the other residents here to kind of go over systemic literature review and how to kind of go in a kind of a, literally a systemic way. So you can kind of get the answer that you would like. So as far as kind of a basic definition. It's a rigorous and structured approach to identifying and analyzing synthesizing all available evidence. The goal is to provide a comprehensive and most notably unbiased summary of the distance evidence of a particular topic. And this includes retrieving and identifying all relevant studies assessing their quality. And most importantly, there are several steps and I'll be brief and not for you too much but it is important to just kind of go over. This is kind of a process that I've at least seen in the Cochrane review. And first half is just obvious. I have a research question, I developed a review protocol development review protocol involves creating a detailed review of protocol that outlines methodology and procedures to be followed. So defining inclusion exclusion criteria for the studies, search strategies as well that extraction methods analysis techniques. Certainly literature search also involves using a comprehensive or relevant database. Most often people use things we're aware of such a method of med web science and scopus and then certainly that extraction part is obvious. In terms of quality assessment. Each systematic review has to include is assessed for the quality and the risk of bias. There are various tools and checklists that are used to evaluate the study designs and methodology and official sources of bias as well as the reliability of the results. In terms of publication bias and activity analysis, the potential for publication bias where positive or statistically significant results are more likely to be published is also assessed. In our kind of initial assessment we work with the folks at the Eccles Health Sciences Library and University of Utah. I don't know what kind of a library specialist did it was kind of when I explained that I was going to ophthalmology for my mom like she was just quizzical like all the L that training for just the eyes, like you couldn't learn anything else. And then I told her like, um, yeah, what a way so I have four years and then I told her I was interested in fellowship. And she answered segment is like, for four years you're studying the eyes and you can't learn anything else. But it's the same way like, you know, as we kind of talked about with the stomach, the cinematic review it's very complex you certainly it's a very regimented approach and folks know go to school and have very, very good to be to formulate, you know, these questions that are help us form in the questions and kind of go about it the right way as far as making an unbiased review of the available literature so just wanted to shout out. Mary at the Eccles Health Sciences Library is helping us perform this literature review and kind of collating the data. It's going to be kind of an extensive process that takes about, you know, a year and a half to kind of fully complete, but just wanted to let you guys know that's available resource and those folks are very smart and very good at what they do. This is just kind of a template as far as a protocol. It's called the diagnostic text accuracy and it's literally. It's very nice. It's a protocol in a sense we just kind of fill out all the required information and as a researcher, your goal is to not only come up with a research question as far as other participants and index testing and the target condition. If you want to go out to the background and rationale and objectives, those folks at Eccles will then help you kind of do a study selection, a section of the risk of methodology quality as local analysis as well as integration and sensitivity analysis in regards to that review. We are kind of in the early stages as far as this systematic review. We have come up with kind of a background and rationale as well as the objectives and looking at the available literature, but it is pretty extensive and we hope to have kind of the initial results of the systematic review for next year's research day. Kind of switching gears. There are kind of, it was kind of a two phase project in a sense where number one, we wanted to do a systematic review of kind of the available evidence but you know for a lot of our global providers, it's also nice to kind of have a kind of a handy sheet or quick and dirty method of just assessing a lot of these patients in the quick clinical setting. And certainly, you know, as PG Y twos we are always trained in the broad differential for optic neuropathy and with kind of the help of Dr. We developed this typical optic neuropathy kind of in a sense like worksheet that just highlights kind of the different types of optic neuropathy, the associated visual field losses on certain risk factors. We're hoping to be able to disseminate this a little bit further in regards to just any general provider or glaucoma doctor would like it. Certainly a lot of what's on here is pretty basic you get that in your residency training but it's also nice to have that as just a quick reference in regards to the decision to refer or not to refer. So these are my references I would like to thank everyone for their attention and we'd be happy to have any questions taken I would like to think the neurophthalmology department and then especially shopping things been very patient and helpful in regards to getting this project started. Awesome. No questions. I think Brian, did you raise your hand. Yeah. Yeah, I just wanted to say great work and thank you for working on this this is a it's a big issue. And I think, you know, also an issue that's maybe increasing I feel like we're getting a lot more normal tension glaucoma patients than we used to. And I don't know if that's because of iPhones or not but I think it is I think it is true and it's just something that we face really often in in clinic. So, this is super helpful. One of the reasons this subject came up in our morning report was because we, we do see this sort of back and forth referral between glaucoma neurophthalmology is this is typical glaucoma or is this not do how far do we need to go and working this up. But specifically, what about genetic causes. And of course that's the big news in in all areas of care these days. But I don't know that that's something that in optic atrophy and glaucoma that we really use enough, because I think you can really potentially answer a lot of questions and halt a lot of extraneous problems if you've established that there is truly an underlying genetic cause be very helpful. Other questions. Okay, so we go on our next speaker is Ashley Polsky. There she is, and she will talk about the incident glaucoma after peri ocula and individual steroid injections claims based analysis. And Ashley wanted to become a horse, veterinary and and I know that Bob wanted to comment on this. Your mic travel with Alan Crandon line to Ghana number of times, who did become an equine vet. And so, I can put you in touch with her, she probably like to work together study glaucoma and. That sounds awesome. Thanks, Dr. All right. Sorry, I know I'm the last talk before lunch so thanks everyone for sticking around. So I'm going to talk about the general conflicts of interest to disclose. And I'll start with just a bit of background. So in recent decades, regional administration of corticosteroids via peri ocula or intravitrile injections has become increasingly prevalent in the treatment of various ocular conditions. The regional administration includes subconjunctival sub teen on retro bull bar approaches, whereas intravitrile injections deliver the steroid directly into the vitreous chamber. The advances in technology have also led to the development of sustained release steroid implants such as ozard and alluvian, which are injected intravitrile and red assert which is anchored to the sclera and allows for prolonged release of steroid into the posterior chamber. So ocular hypertension and glaucoma are well known potential complications of steroid administration and in some cases even require topical or even surgical intervention to treat. And this slide shows a very simplified schematic of the pathophysiology of steroid induced glaucoma. In general, steroids are thought to interact with various enzymes and cytoskeletal components within the trabecular mesh work to cause increased aqueous outflow resistance and therefore elevated intraocular pressure. While many studies have demonstrated the association between steroid administration and intraocular pressure elevation. In fact, a few studies have actually directly compared the risk of glaucoma development between different types and routes of steroid injections. And additionally, no studies to our knowledge have utilized insurance claims data to investigate this topic. The purpose of this study was to determine the incidence of new glaucoma following periocular and intravitrile steroid injections using a large insurance claims database, and to assess the impact of various demographics and treatment characteristics on the risk of developing post injection glaucoma. In this study we performed a 10 year retrospective review of the IBM market scan database, and is just a little background of this database. It's a de identified database, and it's one of the longest running and largest collections of privately and publicly administered patients, including more than 260 million individuals and containing both inpatient and outpatient procedure and prescription drug information. So we searched this database for all patients who had received periocular or intravitrile steroid injections between 2011 to 2020. To ensure that we were measuring new glaucoma development, we excluded all patients who had a prior history of glaucoma within two years before their first steroid injection. We also excluded patients under the age of 18 to ensure that we had an adult cohort for this study. Another measure was the development of glaucoma, which we defined as a new diagnosis of glaucoma or ocular hypertension, the initiation of IOP lowering drops, or laser or surgical glaucoma procedures. And we then used a series of Cox proportional hazards models to determine the risk of glaucoma development within five years after the first steroid injection. A total of 50,112 patients received steroid injections in or around the eye during the study period. 26,459 patients did not have an adequate enrollment period prior to their first injection, so they were excluded. Additional 593 patients were under the age of 18 and then 3904 patients had a prior history of glaucoma, so we're excluded. So this left us with a final study cohort of 19,156 patients. Overall, about 26.8% of patients developed glaucoma within five years after their first steroid injection. And more specifically, 20.5% were newly diagnosed with glaucoma or ocular hypertension, 17.5% were started on IOP lowering drops, and about 2.3% required a laser or surgical procedure to treat glaucoma. We did not find any significant association between age or sex and the risk of post injection glaucoma development within this cohort. So this graph shows the risk of glaucoma development represented by hazard ratios, according to the steroid type and route of administration, which you can see listed along the bottom of the graph. And just to clarify, a hazard ratio of one indicates a lack of association, a hazard ratio greater than one suggests an increased risk, and then a hazard ratio of below one suggested decreased risk of glaucoma. So we found that subconjunctival trimestinal loan injections were associated with a significantly lower risk of glaucoma development, compared to all the other types of regional steroid administration that we looked at with 6.4% of patients being started on IOP lowering drops, and only about 1% of patients requiring a laser or a surgical procedure to treat glaucoma. On the other hand, the red assert intravitrile implant was associated with the highest risk of glaucoma development with over half of patients being started on IOP lowering drops, and over 35% of patients requiring additional laser or surgery to treat glaucoma. We also looked at glaucoma development relative to the total number of steroid injections received over time. And we found that the risk of glaucoma was significantly higher for patients who received more than one steroid injection. The largest increase in risk of glaucoma occurred after the third steroid injection, after which the risk of glaucoma development started to level off after four or more injections. So to summarize, this study was the first to our knowledge to utilize a large claims based data set to characterize the incidence and risk factors of post injection glaucoma over a multi-year period. And this highlights the potential for utilizing a large scale insurance claims data set like this to investigate population patterns in steroid related glaucoma development. We found that the risk of glaucoma development was particularly high for patients receiving intravitrile steroid injections and implants. And previous studies have demonstrated that a high intraocular concentration of steroid is achievable, even after just a single intravitrile injection of steroid. We found that the medication can persist at significant concentrations for multiple months or even years for some sustained release implants. So this could explain the higher incidence of glaucoma development in these patients compared to the subconjunctival and other routes of administration. And again, the risk of glaucoma development was higher for patients receiving multiple steroid injections over time. And interestingly, the largest increase in glaucoma risk occurred after the third injection. So this could be indicative of a cumulative effect of steroid injections on the risk of glaucoma development. I think this finding is also possibly reflective of the potential delay that can occur between steroid administration and subsequent IOP elevation, which can be as long as multiple months according to some studies. We additionally found that the increase in glaucoma risk began to kind of level off following four or more steroid injections, which could be influenced by the fact that typically clinicians tend to avoid repeated steroid injections in patients who demonstrate IOP elevation initially, which effectively prevents higher risk patients from receiving very large numbers of steroid injections. As we come to a close, I just wanted to highlight some of the more clinically relevant points of this study. First of all, we showed that glaucoma is a considerable risk of periocular and intravitral steroid injections, despite these patients having no prior history of glaucoma or ocular hypertension, which I think is an important distinction to make. Because of a potential delay between initial steroid administration and the development of glaucoma, it's also important to maintain long-term vigilance in monitoring for glaucoma in patients receiving repeated steroid injections, even if there's no IOP elevation after the first one or two injections. And finally, having a better understanding of these risk factors for steroid induced glaucoma could be really useful, not only for providing individualized counseling for patients who are receiving steroid injections, but also for potentially determining how closely these patients should be followed to monitor for glaucoma over time. Of course, there are some limitations that are inherent with using an insurance claims database, including a pretty heavy dependence on provider coding accuracy, rather than having direct access to eye exams or intraocular pressure measurements. And in order to address some of these limitations, I'm, I think, like the fourth person to talk about this awesome database, but we hope to replicate our findings using the source database, which, as you know, Dr. Stagg is really closely affiliated with. And this database contains over 220 million eye exam findings, which could provide us access to more specific IOP measurements that the IBM Market Scan Database fact. And I'm currently in the process of putting together a research proposal for source so that we can take this next step. So here's a list of my references. And I just want to especially thank Dr. Stagg who's been an awesome mentor throughout this process, as well as the ARCS Foundation for funding my research over the past year. We also had a really incredible group of collaborators from the Duke Eye Center who have contributed their time and their ideas to this project, so I'm really grateful for them. I had the really fun experience of presenting this project as one of the selected top posters for the American Glock homeless society meeting this year. So, thanks. So, I'm really excited to submit this as a manuscript for peer review soon and continue my research next year as a PG Y3. So thank you for listening happy to take any questions. Thank you for this work. Did you look at any of the comorbidities that people have. I mean, not just migraine of course but others like diabetes and and other metabolic problem. Yeah, that's a good question. We, we did look at visions with diabetes, we looked at a few of the, what's been previously reported in the literature is potential risk factors for steroid induced glaucoma. We also noted things like diabetes. I think like a family history of glaucoma and then a history of PK as well. I think the history of PK was the only one that seemed like maybe there was an association there in our cohort. But as far as other metabolic problems we didn't look too much into that so that would be an interesting thing. We, I'm so sorry, Dr. Yeah, that's a really good point. Thank you. Thank you. Quick question. Good job, Dr. Palski. So, since you guys identified like the risk factors and some of the different injections like use of the intravitral injections the sustained release. You think there's any utility in like prophylactic SLT these patients to prevent the onset of star induced glaucoma I know can treat it but yeah that's there's research out there about that. That's a really good question. I would have to look further to see if there is I was just having a chat with Dr. Roscoe the other day about how low risk SLT is and she I know she's a huge fan of it so but that would be really interesting to look to see if there are any papers on that. So I think you'd have a hard time insurance companies even at a 50% incidence as a prophylactic measure but I just in my career as I look back. I think some of the most many of the most tragic cases are steroid induced glaucoma that have not been recognized where the treatment's been given by ophthalmologists and they don't recognize what's happening so just briefly one. A patient with that you know vernal character conjunctivitis well treated with steroids nobody ever measured the pressure. They came to me because they're worried about decreasing vision and there's a steroid cataract but both nerves were almost burned out pressures 3839 this has been going on for years. Big malpractice suit and correctly so I mean that that's just shouldn't happen another one was a neighbor who'd had a corneal transplant had had a rejection. And they keep was told that it's getting better and better. Over time but he said my vision is getting worse and worse as well let's take a look. So I just came in to see him as a friend you know actually brought him in over the weekend and his, his pressure was extremely high, the nerve was burned out. And indeed the cornea was clearing and the pressure just hadn't been checked so we just just as all of us if if a patient is on steroids of any type. You just have to have those pressure monitored and you have to make sure because in some cases with corneal pathology it's hard to know exactly the pressures. You know just get everyone so I take a look at that nerve and make sure you're okay and both of these were tragic situations. And glaucoma sadly is a disease that once the horse is out of the barn you can't get it back. We've had a couple of these at the VA to recently, just with like compliance with post op visits to who have gotten Osirdex and then no showed their follow ups. And talking with the retina faculty there they will sometimes not even offer Osirdex if they're not going to come for those post op visits so for residents if there's any concern that they are not going to come back. But maybe talk about not doing it too. But it's double the sword to because I mean one of the points of the Osirdex is it's going to give you long term reliable treatment for whatever their underlying condition is. But then they're at high higher risk if they have glaucoma but my question was and I don't think that you can get at this at this with that particular database but does your pressure elevation with topical or periocular steroids predict elevated intracur pressure with intro vitriol treatment. I, I would doubt that people are going straight to intro vitriol without some of the other treatment options first, it would that be helpful information. And that's, that's a really good point because like looking at the, the red assert group that I highlighted that had a pretty high rate of glaucoma development. I think you're right that probably a lot of those patients had some other form of steroid treatment prior to getting a prolonged or sustained really steroid implant like that. So we did not specifically look at topical in in this scenario but I met like, it seems like some patients once they respond to some type of steroid medication we kind of label them as steroid responders so I would definitely be on higher alert if there was a patient who I knew had responded to like topical drops and then. Yeah. Sorry, this glaucoma stuff just gets me excited. Judith, I think that's an awesome idea I think we could look at that with the source database. Yeah, some people believe that there's no such thing as steroid response, or I mean that there is a steroid response but it's not a unique thing to an individual like you're a steroid responder. Some people believe that you're that you have like underlying tuberculosis work pathology. And so you're more susceptible to the steroid. And so it's not, it's not the fact that you're like a steroid responder or not it's just you have underlying tuberculosis work disease. And so that, and then it's like a dose dependent thing. So, if you give enough steroid to anyone you get a steroid response. You know, the H and minus cyclin, you know, like you have a susceptibility. Right. Oh, yes, a Q I think you could do would be because this has been done before is you could have in epic a tickler to say this person has is on oral steroids this you know it may not sort of pass into your consciousness as a patient maybe on oral steroids. Because they've got arthritis or gynecological arthritis or something like that, or they're on topical steroids. Check the pressure. And that's the thing that EMR is really good at. Yeah, it's a really good idea. We had a patient in the hospital, who was receiving very high dose steroids and they're a pediatric patient, and they complained of some vision changes. And turns out their pressure was living in the 50s in response to their high dose steroids. I wonder sometimes how many, like, ocular hypertension, or is undiagnosed patients with glaucoma were simply pediatric patients that received high dose long term steroids without any eye exams. So maybe that could be a study as well. I was just going to highlight Dr. Lara shell made a comment she said I do have a few patients though that seem to be able to get endless intraocular steroid injections and never have an IOP rise. Okay, so for now we are concluding.