 Good morning, everyone. We have two talks today. There they are. We have two of our pgy to presenting. Lydia sour will go first is our resident expert in all things. I'm going to start with Dr. Petty. I'm going to talk about her pigment and macular pathology and she will be presenting on the benefit of fluorescence lifetime imaging in macular tn-dictator type 2. So we'll get started with her and then Dr. Petty, I'll get that update in between. How does that sound? Perfect. Can you see my slides? Yep. Video is good. Audio is good. Great. So thank you very much for having me today to present at Grand Rounds and I would like to talk about the benefit of fluorescence lifetime imaging of termoscopy flio in understanding macular tn-dictator type 2. And I do not have any financial disclosures, but the flio device was provided to the University of Utah by Heidelberg Engineering at no cost, and it's not yet FDA approved and only used for research purposes. And I would also like to thank the LMI, the Lowry Family and the ARCS Foundation. To start off with, I would like to talk a little bit about patient experiences, patients that have MacTel. How is it when they are getting the diagnosis and are they getting diagnosed correctly or incorrectly? So this is from one patient, you can find it online. It says the retina specialist diagnosed me with MacTel on my first visit. I had a follow up appointment a few weeks later for OCT exam. He told me that there was no no known cause for MacTel and no treatment. He said I should have an eye exam every six months to track changes in my vision. He did not paint a picture of gloom and doom, but also did not offer much information. He told me that he had only seen about 10 patients with MacTel during his entire career. Another patient describes, I was misdiagnosed with cone dystrophy for the first couple of years. The question I asked in my first, I was asked in my first diagnostic appointment was, have you ever been a San Gaser? I had no idea what that was, and had to look it up online when I got home. I received the correct diagnosis for MacTel only when I thought a second opinion at a research hospital. Another patient, Deborah, her path to receiving the diagnosis of MacTel was also not straightforward. She went to retinal specialist because her vision was getting blurry, and she was seeing squiggly lines. That is where stride lines did not appear straight. She was initially told that she had macular degeneration with a retinal bleed and began to receive an heritual injections. After being treated for about two years, she switched retinal doctors as she moved across the country and then was diagnosed correctly with MacTel later on. And she said, I had all sorts of people looking at my eye. At the time they said there's no cure. They don't know what causes it, and they don't know how fast it will progress. They said it will only affect my central vision, and it will probably take years. And that's where things stood for a while. So with those impressions, I would like to start and just highlight the importance of diagnosing diseases correctly and understanding the differences between different macular diseases in the human eye. These quotes came from the Lowy Medical Research Institute who provides a very excellent resource for patients and physicians, and it's a privately funded organization that really pushes the research in the MacTel group, and I'm very honored to be part of this research and share what we have found in the last couple of years. So MacTel, it's a rare bilateral disease that leads to gradual loss of central vision. The prevalence was said to be between one in a thousand to one in 20,000. But due to it being misdiagnosed very frequently, we believe that the prevalence is much higher. The age of onset is typically between 40 and 60 years, and it's likely an autosomal dominant disease with vertical transmission. Sometimes it's mistaken for AMD because macular degeneration has a similar pattern of neurovascularization, and retina alterations usually begin in the temporal paracental area. And that area temporal to the phobia is really believed to be the epicenter of the disease. Later on, the disease may encompass the entire area of six degrees horizontally to five degrees vertically centered at the phobia and we call that the MacTel zone. And there are multiple promising clinical trials ongoing at the moment. So diagnosing MacTel with retinal imaging, we have a lot of different imaging modalities available, including fluorescein angiography that commonly shows vascular changes and leakage, but it does not show all the changes that can occur in MacTel. OCT on the other hand is a noninvasive technique that shows asymmetry of the phobia and hypo reflective cavities in the neurosensory retina. And it is used for the inclusion in clinical trials. And there are a lot of other imaging modalities such as cold focal reflectance imaging or known as blue light reflectance imaging macular pigment density where instead of a central peak we have a ring surrounding the MacTel region and confocal adaptive optics of thermal scopes. It usually take a long time and are not as feasible in the clinical arm. And then we have fluorescence lifetime imaging of thermoscopy, which is a new technique that I would like to talk a little bit about today. This was a photograph that I took a couple, a couple months ago. This was comet neo ice back in 2020. And when we look at the black and white picture we see what's going on. But when we look at a picture in color, it just has a lot more detail, and we can appreciate the beauty of this comet a lot better. Anyway, we look at the human eye and we are very used to looking at these black and white images. But when we take it to a colorful image, we may notice differences that areas that appear dark may not appear the same and in the color image. When we look at an eye with Druzen and macular degeneration. When we look at the colorful flio image here it shows us a complete different pattern. Or in this eye, a patient that was diagnosed with MacTel that looks nearly normal when we just look at the outer fluorescence image, but with flio we can appreciate a ring of prolonged lifetimes as a sign of the disease. And this is briefly what is flio flio is a non invasive imaging technique. It's produced by Heidelberg engineering, and it takes approximately two minutes to take a picture of the eye of patients. It was developed in Germany, and this is the first publication that was ever published in 2002, and the images look completely different. At that time, the acquisition time was about 20 to 25 minutes. A few years later, the images started to look more similar to what we're used to today. There have been a lot of different publications in the recent years, and it has gained a lot of interest to investigate flio in the scientific community. When we think of flio, I always think of it a little bit like OCT. When we look at the very first images of OCT, it looked completely different. And until we're getting to the high resolution OCT, that is kind of the next step of OCT imaging. Currently, these images look completely different from the beginning. I'm wondering if flio may be similar in that, and it's very exciting to be part of this research. And I don't think we know yet where it's going, but we know that it's very helpful. So what is flio? It is fluorescence-based. So fluorescence, when there's energy that goes on to a molecule, the molecules are elevated to a higher vibrational level. And as they fall back to the lower vibrational level, they sign out photons. And those photons is what we call fluorescence. Essentially, there are three dimensions that we can look at from these photons that come back. We can look at the spectrum of those photons, so the wavelengths. We can look at the brightness, which is what we do in auto fluorescence imaging. And then we can look at the lifetime, which is the time it takes for those photons to come back. What we do with flio is we look at that lifetime. We have a 256 by 256 pixel image, and in each of these pixels, we count the photons that come back over time. So we receive a statistic of photons that in the beginning we would have the impulse, and then we just take the time and collect the photons that come back. So these blue dots would be the amount of photons over time. And we can then approximate that decay and get a certain time. And when we look at different spots in the retina, we see that in the phobia, the curve is much more steep than at the optic nerve. And that is the difference in the different lifetimes that we measure. We also look at two spectrowave length channels, but I'm not going to touch on that very much today. But what we see in the healthy image is always a very similar pattern of long lifetimes at the optic nerve and short lifetimes in the phobia. The short lifetimes I believe to be macular pigment, the kind of intermediate lifetimes, I believe to come from the retinal pigment epithelium and the lipofusin, and then long lifetimes stem from collagen and elastin. So from this image from the healthy eye to all the retinal diseases, it is very striking that we see a lot of different patterns in the different retinal diseases. And today, as I mentioned, I will highlight the findings that we've had in macular telangiectasia type 2. So when we first looked at patients with MacTel, what we saw is that there's always a temporal crescent of prolonged flea lifetimes that we can see in our images. And I would like to show the very first slide that I ever showed to Dr. Bernstein. These are the first four patients at the Moran that received MacTel. And I kind of showed him, oh, it looks like there's this prolongation of lifetimes, this blue crescent that we can see in all of these images. And when we clinically look at patients that have advanced MacTel, such as this individual who is a male that is only 24 years old. But when I would look in his eye as a PTY2, I would likely realize that there is hopefully realize that there's a bull's eye maculopathy. And when we look at other imaging in OCT, we see hypo reflective cysts and outer fluorescence imaging, we see that there are abnormalities. We see that in blue light reflectance, there's a bull's eye. There's a lot of leakage in fluorescent angiography. And when we look at the FLIO image, we clearly can see that that area shows abnormalities, so that instead of just a center of short red lifetimes, there is a prolongation of lifetimes in a green light pattern. But when we look at this eye, frankly, if I would see this patient in clinic, I'm not sure if I would be advanced enough to pick up that how altered the phobia is. And also looking at clinical imaging in this patient, it's a 56 year old with 2020 vision. This could be just a regular eye exam. I think in the OCT, we would, our attention would be drawn to this hypo reflective cyst. But if the cyst would be absent, which can also happen, I think it would be very difficult to really understand what's going on. There's a little bit of leakage in fluorescent angiography. But FLIO very, very clearly shows the temporal crescent and leaves no doubt that this patient has MacTel. In addition, FLIO may be able to pick up asymptomatic family members. So this is another family where both parents had a healthy clinical exam, but the daughter has MacTel. And if we look and compare the images from the parents, we can see that the mother is likely the carrier of the disease. And in the past two years, we've done in the past couple of years, we've done a big analysis looking at family members. So first degree family members of patients with MacTel. And we think that there are differences. There are some patients, family members that are that have a signature of MacTel, and others that do not. So we are hoping to see those patients again and see if the signature indeed is an early sign of MacTel. What we do know is that there is one gene that has been found in the Syrian metabolism that can cause MacTel. And we have a family at the Moran Eye Center. This is the 24 year old pro band who has MacTel, and he has two sisters, one of which is carrying the gene mutation and the other one is not. Both sisters age 26 and 28 had a normal healthy clinical exam. But when we look at flu imaging, we could see that there are changes in the exam of the sister that has the gene mutation. And that is despite, as I mentioned, pretty, pretty normal clinical exam, including OCT imaging and fluorescein angiography. In addition to looking at, and that is very helpful because if we know that a person has the disease and with clinical trials approaching, it would be very helpful for those patients to be diagnosed correctly and early on in the disease. We also looked at changes over time and had 66 patients with MacTel, 66 eyes with MacTel that we investigated longitudinally. And we saw that the FLIO lifetimes in the MacTel zone prolonged and they prolonged by about nine picoseconds and eight picoseconds in the two respective spectral wavelength channels. We also found that this is independent of macular pigment, because in a lot of discussions, it was us, it's just the macular pigment that is going down over time. But we could show that there's no correlation of the changes in FLIO lifetimes with changes in macular pigment. So it really is something that is changing in the retina that cannot be associated with macular pigment. Oh, it's not caused by macular pigment I should phrase it that way. We also looked at OCT over time and found that in the first spectral channel where we see all the MacTel changes with best contrast. These changes correlated to changes in the ellipsoid zone, which was indicated to be correlated with progression of MacTel. The changes of the ellipsoid loss correlated with the FLIO lifetimes and also with different differences in the ellipsoid zone correlated with differences in the FLIO lifetimes. And what I would like to highlight is that we can see the changes in FLIO, even before there are changes in OCT before there's ellipsoid zone loss and before there are cystic cavities. The disease progresses, the OCT progresses, but FLIO lifetimes prolong as well as this highlighted in this slide. So what we know at this point is that in MacTel, we see that these prolonged FLIO lifetimes in a temporal crescent or a ring within the MacTel zone, and the FLIO lifetimes show this pattern very early in the disease, possibly even in the second generation of patients that have not even been diagnosed yet. And this change is visible prior to structural changes and structural damages. The FLIO lifetimes prolong over time and the temporal crescent turns into a ring and progression of disease can therefore be monitored with FLIO. And that prolongation of lifetimes is independent of macular pigment, but maybe related to structural changes in the ellipsoid zone. What we really do not know is what is causing this prolongation of FLIO lifetimes and other factors such as diabetes that could influence this pattern. So in the last year, we looked at patients with diabetes. We have 89 eyes from 89 patients that have MacTel and have, excuse me, 45 of those were not diabetic and 18% were pre-diabetic and 37% were diabetic. We had an independent grader that graded the diabetic retinopathy in these eyes and we included all confounders such as cataracts or AMD or other retinal diseases. And we looked at the areas of interest, so the MacTel zone and kind of the central areas in a standardized grid. And what we found that was really surprising because a lot of patients with MacTel have diabetes is that the pattern is visible in patients with and without diabetic retinopathy. And but it is completely independent of diabetes. So the FLIO lifetimes were completely, there was no significant difference between diabetic, pre-diabetic and not diabetic patients that had MacTel in the FLIO lifetimes. And in addition, FLIO lifetimes also did not correlate with the A1C and with the BMI. And we were very surprised that there was no correlation to the diabetes. So, although MacTel has that high prevalence of diabetes, FLIO lifetimes and longitudinal changes associated or found in FLIO associated with MacTel seem to be unrelated to diabetes. And the last study that we just submitted to Aval in addition to looking at diabetes right now is that we look at the sensitivity and specificity of FLIO. And we have had 161 patients that were referred for FLIO imaging at the Moran Eye Center between 2018 and 2022. Out of those patients, 119 had MacTel and showed the FLIO pattern. Five patients clinically had MacTel, but the FLIO was inconclusive due to cataract and image quality in three and two cases respectively. And then 37 patients were referred for FLIO imaging that clinically did not have MacTel but were diagnosed later on with other retinal diseases such as cornwadgistrophy, tamoxifen retinopathy, hydroxychloroquine toxicity, AMD and others. And the FLIO imaging was negative in all of these cases. So, the ability of FLIO to detect the disease related changes in patients with MacTel has proven to be very helpful in the clinical practice at the Moran Eye Center. And in our cohort of the 161 patients that were just referred with the question is it MacTel or not. And the high sensitivity of 96% and the specificity of 100% when determining if a patient has MacTel or not. And here are a few patients where FLIO is helpful in research and in clinical practice. If you look at AMD versus MacTel, I didn't talk about the AMD pattern a lot, but all eyes with AMD have this ring of blue that we cannot see in eyes with AMD with MacTel, whereas MacTel has in the first spectral channel, the temporal crescent of blue of long lifetimes that we can see even if a patient has both AMD and MacTel. Here's an example of comparing MacTel to hydroxychloroquine toxicity, where we can see that, although in on first glance, these two diseases may look similar. But when we look at the first and the second channel that I highlighted here, hydroxychloroquine toxicity looks very different. And we can distinguish it with using FLIO, just because the lifetime distribution between the two channels is differs between the two diseases. And then this is a patient who was initially believed to have MacTel, because they have the cystic lesions and OCT imaging, they had a bold zymaculopathy. The macular pigment had a ring, but it was not the typical ring outside the MacTel zone that would be kind of around 6 to 7 to 8 degrees. But instead it was a ring that was much more narrow to the phobia. And when we looked at this patient later on, we realized that this was temoxifen retinopathy and not MacTel. So just looking at next steps, what are our next projects with MacTel and FLIO. We have a collaboration with San Diego, where there's a group that looks at metabolomics data, and we would like to correlate our findings to the metabolomics data from our patients. We also are hopefully very soon going to receive a high-resolution OCT that we can compare to FLIO imaging. And then we're also collaborating with the neurology department to see if neuropathy, which is also common in patients with MacTel, can be compared with FLIO by looking at punch biopsies. We also have a collaboration with Dr. Aaron Lee, looking at artificial intelligence, and there will be a poster at AVO from their group this year as well. Kind of looking at if artificial intelligence can pick up the different signatures in FLIO much easier than we may be able to in clinic when we just don't get the pictures. So to conclude my talk, FLIO shows very early changes in MacTel even before structural damages are visible. FLIO is helpful in the diagnosis of MacTel, and the FLIO lifetime changes correlate with the ellipsoid zone loss, which has shown to indicate progression of MacTel. And there are a lot of other factors that do not correlate with FLIO lifetime changes. What I think is kind of the point where we're at right now is that if we find out what is causing the progression, so the further prolongation of our lifetimes, we may be able to determine what the actual cause of the progression of MacTel is, which would be exciting to find out. And with that, I would like to thank all of our collaborators, especially Dr. Bernstein, who has been an amazing mentor, as well as everyone else at the Moran Eye Center that has been involved in this, and again the LMI and the Loei family. And thank you all for your attention. Thanks Lydia. We can open up for questions we have about four or five minutes for questions if anyone has any. Lydia, I have a question, you know, with how genetically complex this disease is, and then with its, you know, clinical presentation being variable, so many kind of subclinical findings with that specificity and sensitivity. Could this or do you anticipate this becoming perhaps a gold standard for diagnosis of subclinical at least. I think the limitation, mostly is that we do not have flio available at many centers, and I think for the gold standard we would need more, more flio devices in the first place, but the MacTel foundation and the LMI they're very very interested in this. I think, and we think as well that flio is a could possibly be the gold standard, if there would be more devices available I think that's really the limiting factor that it's such an early, early in the stage of the technology that we think that it is helpful and that we see the signature very easy, and better than in other modalities. But yeah, as I mentioned there just some limitations. Perfect Monica I've gone ahead and asked you to unmute so you should be able to unmute yourself. Go ahead and yes. Can you hear me okay. Perfect, Lydia thank you so much for this impressive talk. Can you give us a short insight in the current status of therapeutical trials in MacTel. Yeah, so. I know that there are a couple of ongoing trials. I don't know if the latest data has been published on the CNTF trial but it seemed like there was initially a very, a very positive like a difference when there's there's an implant that just as a neuro protective factor that gets implanted in the device and the more nice and as part of this study. The initial report showed that there's a difference, and then we're still following these patients over time, but it seems to be promising. Dr. Bernstein knows a little bit more about the current state because I'm not as familiar with the very recent data because all the MacTel meetings are just coming up early this year when we'll get an update. So, I think that is something to stay tuned. Great. This is Dr. Bernstein just to give you the update. The phase two for the CNTF trial was positive. And they've gone to the phase three. And that is, and we're part of that but the data has it's still not quite closed so we have not released the data on that yet so I don't know, and no one knows yet but it should be announced within the next year. And we're also looking at some nutritional interventions with syring but those are still in the early stages. Awesome. Well thank you so much Lydia. Thank you. As far as the update for the PG Y3 class I've talked with my classmates here. I have to be a little bit cryptic maybe but I'll give a hint at where we're headed. I can say that alley likes the front of the eye, or is drawn to the front of the eye I am drawn to the back of the eye coal. The inflow and outflow of the eye and Abigail, the things around the eye. So between the four of us, we have a pretty comprehensive set of interests. But there's like a new multi specialty practice. Exactly. Exactly. Speaking of multi specialty. Tyler Etheridge, going to be giving our, our next presentation he's a resident where as many hats among them. Ultra endurance athlete and stuntman. And he is going to be talking about the use of intracameral tissue plasminogen activator in uveatic cataract surgery. Go ahead. Thank you, Sean. I don't know if getting hit by a car counts as me being a stuntman but I was referring to a different stuff but that. All right. Here, let me share my screen. We can say the screen audio is great. Perfect. Hello. Thank you Sean for that introduction. I'll be presenting a research project that I was fortunate enough to be a part of as an intern during my elective year experience. I have no conflicts of interest. Gyitis is a group of eye diseases, which are characterized by ocular inflammation due to autoimmune infectious or malignant etiologies. The presence of intraocular inflammation as well as its first line treatment steroid therapy, both accelerate cataract formation. Furthermore, cataract surgery itself can exacerbate intraocular inflammation, which can lead to progression of eye disease and vision loss. Therefore, the ability to control intraocular inflammation perioperatively is critical for patients with uveitis. An inactivator or TPA has been used as an adjunct postoperative therapy to control intraocular inflammation after adult and pediatric cataract surgery, as well as for fibrinolysis after retina surgery. However, there are limited reports on its use at the time of cataract surgery or in patients with uveitis. Therefore, we report the largest case series of intra-cameral TPA used at the time of cataract surgery. Specifically, we selected four patients with uveitis who are at higher risk for postoperative inflammation, including patients requiring posterior synecialysis and assess postoperative vision, intraocular pressure, postoperative signs of inflammation, and intraoperative and postoperative complications. The retrospective chart review is conducted to identify patients with uveitis who received intra-cameral TPA at the time of cataract surgery. All patients received care at the Moran Eye Center, and the surgeries were performed by four different anterior segment surgeons between January 2015 and January 2021. The patients were included if they had a history of prior or current uveitis, and if the surgery was a primary cataract extraction. In total, 36 consecutive eyes from 31 patients met inclusion criteria. 26 of the 36 eyes completed 12 months of follow-up. Six patients were lost to follow-up after post-op month one, and one was lost to follow-up after post-op month six. An additional patient died from unrelated systemic disease after six month follow-up, and six patients are still awaiting their 12 month follow-up visits. Here we present the preoperative data. The mean age of our patient population was 36, with the youngest patient being five years old. The anterior uveitis was the most common subtype, and idiopathic was the most common diagnosis, followed by HLA B27 associated anterior uveitis, and then sarcoidosis. Eyes were without active inflammation for a mean of 5.8 months prior to cataract extraction. Over 90% of eyes had at least one coexisting ocular disease or structural complication, with cystoid macular edema, glaucoma, and epiretinal membrane being the most common. Preoperative central macular thickness was obtained from 24 eyes with a mean of 340 microns. 24 eyes were on at least one steroid sparing immunomodulatory therapy at the time of cataract surgery. 23 of the 24 patients on immunomodulatory therapy were on an anti-metabolite, with 18 of those patients on additional immunomodulatory therapy. And then one patient was on rotuximab monotherapy. Periodically beginning one week prior to surgery, patients were treated aggressively with systemic and local, as well as topical steroids and NSAIDs to prevent any uveitis flare. Pre-prednisolone eyes received perioperative oral steroids with a mean prednisolone equivalent dose of 45 milligrams per day, leading up to surgery. Three eyes received perioperative intravitrile dexamethasone injection prior to surgery. Mean topical prednisolone equivalent dose was 3.5 drops per day, and mean catarlac equivalent dose was 2.7 drops per day. Here we present the intraoperative data. Every cataract surgery was performed using fecal emulsification. The most common type of lens implanted was a one piece acrylic. The remainder were three piece lenses. The vast majority of lenses were placed in the capsular bag. Cinequialysis of posterior and or peripheral anterior Cinequiae was performed in 61, sorry, 94% of cases. Tri-pan staining was used in 61% of cases and 83% of cases required an iris expansion device, either an iris hook or meliugin ring. The capsular tension ring was placed in three cases due to diffuse zonular weakness, and there were no cases of vocal zonular loss. Over half of these cataract surgeries were combined with a ParsePlanet attractomy. In one case, an unplanned ParsePlanet attractomy and retinal detachment repair was performed due to intraoperative discovery of a tractional macula off retinal detachment. We had a history of retinal detachment with silicone oil in the eye, and the view of the posterior segment prior to surgery was poor. A one-time intraoperative IV methylprednisolone dose was administered in two cases, while intraoperative local steroid injections were used in 11 cases. Three cases did not receive any perioperative or intraoperative systemic or local steroids. In most all cases received intracameral antibiotics at the end of surgery. At the completion of surgery, TPA was injected intracameraly. The two doses injected were 12.5 micrograms and 25 micrograms. The dose given was at the discretion of the surgeon. 34 cases were uncomplicated. Two surgeries experienced complications, including one anterior capsular tear and one posterior capsular tear. The anterior capsular tear occurred in a patient with a dense, fibrotic anterior capsule that required micro scissors to create the entire capsulotomy. Here we present the postoperative data. Preoperatively, mean log-mar best corrected visual acuity was one or a SNELIN equivalent of 2200. The patients had a best corrected visual acuity of greater than or equal to 1.3 log-mar or SNELIN equivalent 2400 or worse. And only four patients had a best corrected visual acuity of 0.3 log-mar or a best corrected visual acuity of SNELIN 2040. Postoperatively, mean log-mar best corrected visual acuity was 0.7 or a SNELIN equivalent of 2100. Half of patients were able to achieve a postoperative best corrected visual acuity of 0.3 log-mar or better at 12 month follow-up. And only five remained at a best corrected visual acuity of greater than or equal to 1.3 log-mar. The improvement in visual acuity was statistically as significant across all time points using a mixed effects ANOVA model. Multiple comparisons test showed statistically significant improvement in visual acuity from baseline to postoperative month one, month six and month 12. Mean preoperative IOP was 15. The baseline IOP lowering medication use was uncommon. Ocular hypertension was reported in 10 patients at postoperative month one, which dropped to two patients by post-op month six. Postoperative mean IOP remains stable at all time points using a mixed effects ANOVA model. As expected, there was an increase in the number of IOP lowering medications used at postoperative week one corresponding to ocular hypertension or steroid response. However, this returned the baseline by postoperative month one. The most used IOP lowering medications were carbonic and hydrogen inhibitors, beta blockers and alpha adreneric agonists. Prior to surgery, almost all eyes had minimal to no anterior chamber inflammation with an AC cell grade of 0.5 or less in 32 patients. By postoperative month one, most eyes 28 achieved an AC cell grade of 0.5 or less, which remains stable through postoperative month 12. Preoperatively, approximately half of eyes had a vitreous haze grade of 0.5 or less, though vitreous haze grade was unreported in 13 patients. At postoperative month 12, 22 eyes achieved a vitreous haze grade of 0.5 or less, with only three eyes having an unknown vitreous haze grade. Preoperatively, mean post-tier Cineca was 8.2 clock hours, which improved to 0.1 clock hours by post-op month 12. Additional postoperative inflammation was noted in 45%, 48%, 45% and 32% of eyes at post-op week one, month one, month six and month 12. Corneal edema was the most common at postoperative week one, and cystoid macular edema was the most common at all of the time points. Of eyes with cystoid macular edema, mean central macular thickness was 644, 481, 517 and 503 microns respectively. New postoperative ocular diseases occurred in a low percentage of patients. Six eyes experienced hythema at post-op week one. This was not unexpected as 94% of patients required Cinecolysis and iris manipulation during their cataract surgery. Five cases resolved spontaneously without further intervention. One eye was found to have iris lens chafing from a haptic in the sulcus before persistent hythema and was taken back to surgery for IOL repositioning, after which the hythema resolved. One eye was noted to have a hythema at post-op month six, but had also undergone parched plan of atrectomy three weeks prior. Four eyes underwent repeated parched plan of atrectomy. One required torque IOL repositioning due to a rotation of their IOL, which was complicated by posterior capsular tear and result in sulcus placed IOL. Finally, mean oral prednisolone equivalent, topical prednisolone equivalent, and catorlac equivalent. They decreased over time as expected. A few patients required escalation of their IMT during their 12 months following cataract surgery with more requiring adjunctive local or topical steroids. However, most eyes did not require escalation of IMT or steroid therapy. In discussion, the dose of TPA injected at the end of the case was at the discretion of the surgeon. Either a 25 microgram or 12.5 microgram dose were administered based on patient age with children tending to receive the lower dose. There was improvement in best corrected visual acuity postoperatively with only 13 eyes having a best corrected visual acuity of 2400 or worse. And only five eyes saw 2040 or better preoperatively compared to almost half of eyes achieving a postoperative best corrected visual acuity of 2040 by the 12 months follow up, and only five eyes remaining at 2400 or worse. However, if you look at the mean change in visual acuity, these eyes only gained one line of vision, and this is likely due to the complexity of their underlying disease, as well as multiple co morbid ocular diseases, which may limit their visual potential. We did see a significant improvement and post here synika postoperatively going from a mean of 8.1 clock hours to 0.1 clock hours. Six eyes did experience postoperative high FEMA at week one, five of which resolved without further intervention. We did select for patients with uveitis who are at higher risk for postoperative inflammation and complications and most of whom who received post here synika lysis and iris manipulation at the time of surgery. This review of the literature on the topic shows that doton at all performed a prospective cohort study investigating TPA in refractor in refractory toxic anterior chamber segment syndrome after cataract surgery. 40 eyes were enrolled and treatment was performed 20 days after surgery results showed that one day after treatment, there was complete clearance of vibrant reaction in 80% of eyes and partial and 20%. With evaluation the fiber and reaction had completely resolved in 95% of patients mean visual acuity was not statistically significantly different. And there, however, there were no cases of high FEMA or increase in Dracula pressure or other complications. The authors concluded that intracameral TPA at a dose of 25 micrograms is safe and effective for the treatment of refractory fiber and reaction after cataract surgery. President Adams investigated the use of TPA retrospectively in the treatment of postoperative fibrinous membrane formation following pediatric cataract surgery. Of the 37 patients studied for underwent intracameral TPA injection. With the meantime to injection after surgery of seven days results showed that there was complete resolution of a fibrinous membrane in all cases, and without any complications of three month follow up visit. The authors concluded that TPA may be used safely and effectively at a dose of 25 micrograms for severe fibrinous membranes following pediatric cataract extractions. Satiri at all performed the only double blind randomized control trial to evaluate the efficacy of intracameral TPA and the prevention of a fibrinous effusion after Lensectomy, anterior vitrectomy and cataract surgery in children. 34 eyes were included and results showed the incidence of an intraocular fiber membrane formation was statistically significantly lower in the case compared to the control group at two weeks of postoperative follow up. However, there's no statistically significant difference at the one and three month follow up visits. And the frequency of pigmented IOL precipitates was however significantly different between the two groups. The authors concluded that prophylactic pro phylactic intracameral TPA is effective in the prevention of a fibrinous effusion at the first two weeks after cataract surgery in the pediatric age group and decreases the incidence of pigmented IOL precipitates. And finally, we ended at all evaluated the effect of low dose three microgram intracameral TPA as an adjunct to lysine extensive recent onset posterior synechiae associated with uveitis in the setting of impending pupillary seclusion in a retrospective case series of three patients. Two of which had acute uveitis with rapid and complete synechialysis and one had an acute reactivation of their recurrent uveitis with subtotal synechialysis due to incomplete lysis of chronic synechiae. With resolution of inflammation all patients regain their pre uveitis flair visual acuity without any complications from the injections. The authors concluded that intracameral TPA as an adjunct to maximum anti inflammatory therapy in eyes with extensive recent onset posterior synechiae associated with uveitis leads to rapid lysis of synechiae reducing the risk of pupillary seclusion and its associated glaucoma. Limitations of our study included was a retrospective case series with its inherent limitations and lack of control group. We also have yet to gather 12 month follow up data from the remaining six patients. In conclusion, we report the largest case series of intracameral TPA use at the time of cataract surgery in patients with uveitis TPA has been shown to be effective for controlling post operative inflammation in uveatic cataract surgery. However, given the rates of post operative high FEMA further research to assess its safety is needed. Future directions for this project include a multicenter randomized control trial to further evaluate the safety and efficacy of TPA in uveatic cataract surgery. Here are my references. I'd like to thank doctors for Rochelle and went and who for their ongoing support and allowing me to be a part of this project, as well as the research group, including Elizabeth and Deborah for their continued support and putting up with me on a near daily basis. I think I have some time for questions. We've got plenty of time we've got about 10 minutes. Welcome back to Dr who and welcome back Tyler great great study I mean a lot of great data collection. You know, I would assume certainly that these patients had the highest risk of post operative inflammation, and that that's why they were, you know, given intracameral TPA. Would it be reasonable, or why would it not be reasonable to go back and look at other, you know, uveatic patients who have undergone cataract surgery with uveitis for the same time period to try at least and at least have some sort of comparison group, or is that are the patient groupings just that different that it wouldn't be helpful. Yeah, I think that's a great thought and something that we considered the difficulty is I feel like each uveitis patients is in some way so different. So, for example, having a cataract and fibrin and being well controlled for their uveitis, and then having done or go cataract surgery. I just don't know the patient population as far as the numbers that we've that we have. However, maybe that first law Rochelle and we can talk to that looks like that law Rochelle has her hand up. Go ahead. Hi, that was a great presentation Tyler thank you a lot of data there. Hi Jeff, I was looking at this, we did include patients with with four surgeons and because Dr Chia had done some of these cases before I started doing most of the combined uveated cataract surgeries. And so at least in my practice. So what I decided to use TPA on was when they I was doing basically more than just one clock hour of posterior synecialysis. And you can see in that data that out of all these patients, the synecialysis was performed in 94% of the cases so we were really targeting patients with anterior uveitis that had posterior synecial formation. And I think that's for two reasons. One of them is, I think that the actual manipulation of the iris tissue to lice the synecii is part of what causes the Can you hear us still Marissa we Marissa we just lost about 15 seconds sorry about that. The last thing you heard me say. That's a good question, rewind about 20 seconds it was, it was just when you were talking about that, you know, these patients did require synecialysis. Right, so we, I, at least in my practice I only do TPA when I'm lysing more than like one clock hour of sneaky I, and that's for, for two reasons first I think that the manipulation of the iris tissue lysis of the synecii is part of what causes this exuberant fibrinous reaction and the high FEMA. And then also the presence of posterior synecii itself is probably an indication of those patients with anterior uveitis that these really robust anterior segment inflammation in the first place and so I don't typically do this in patients that just have intermediate uveitis or that have had maybe one or two cases of anterior uveitis in the past without any synecii formation so I do think we're we're choosing the patients to use TPA and that have indications of a robust anterior segment inflammation in the past. I'm not saying this is anecdotal but in the beginning, more early on in my career I wasn't doing it as consistently, and I have I remember one patient, and it was an adolescent we did combined cataract surgery and I think truthfully I probably just forgot to use the TPA it wasn't in the forefront of my mind. And of course she developed this hugely fibrinous reaction, despite pre treating with prednisone and everything. And we did have to go back to the operating room to do an AC wash out and I used TPA at the time of the AC wash out and then the next day she was just perfect and that case, like really cemented it for me that anytime we do posterior synecialysis that that I do think TPA offers a benefit. So, at least in in my patients I don't have a control anymore of patients that I've done cataract surgery on and have not used TPA. We'd have to look at sort of the broader brand surgeons that are still doing uveated cataract surgery and not using TPA in order to get the data for more of a control set, but that is a great idea. Tyler loves mining data but I would I would anticipate over that same same time frame that just, you know, looking back for synecialysis cataract patients would surprise me if you could find a similar number that again could could strengthen that. And of course, you know we ran into the difficulties of how do you do the chart review for these patients. Are surgeons listing posterior synecialysis as a as a procedure code and I think that's inconsistent so it can be difficult to identify these patients I really try to list it as a separate procedure code when I'm when I'm doing surgery and so it also helps for data mining in the future. So, just want to other aspect to consider. And who I feel like we just need to hear from you since you're here. Any pearls of wisdom. Oh, I'm here to support Tyler. I need all the sport I can get. And Judith Warner did just note if it is included in the operative report report it can be found so that that is a possibility that even if it wasn't listed as a an actual procedure code that that could be identified. So Judith, does it have to be listed as a like diagnosis or procedure performed or if it's just listed in the text of the surgery can it also be like searched that way. Well we have to check with the data folks but from what I understand it can actually be thought, especially in the epic age, it can actually be sought with like a word search. It's, it's moderately time consuming to set that search up, but are the data people can actually find an actual word in the operative report itself, not just in the diagnosis codes. The diagnosis codes are way easier, but you know you can you can also make a wide net and search for, you know, cataract surgery and somebody with uveitis and then you know that's ever been diagnosed with uveitis. Then you can narrow it down from there but that's, that's the kind of painful process that everybody would prefer to avoid. And then Tyler can just spend the next 10 years his life reading through all those operative reports. Great time. Sounds like a job for a medical student. No I've used that text finding feature through the EDI group and it does work and you can find words you can specify words on either side of your chosen phrase or word, you can you can get pretty creative with it.