 Adam Jorgensen is one of our senior residents. He's headed for a career in glaucoma. And keeping that in mind, Adam's topic is risk factors for trabeculectomy failure. That is still your topic, correct? Oh, good. There we go. Great. All right, thanks. So I'm talking today about risk factors for trabeculectomy failure. And I have no financial conflicts of interest. I'm glad that I'm following Zach's talk on quality improvement because this is kind of the issue that I'm talking about. I like this quote. I came across this years ago when I was reading one of Dr. Gawande's books. But I guess research in general has always seemed very daunting to me. And when I read this, it made it seem like something that I could definitely do for the rest of my life, where it comes down to counting something, tracking outcomes, writing it down, and sharing it with other people, and seeing how you can use those to get better. And so that's essentially the project that I'm going to talk about what we decided to do. So how this came about over the course of about a year at the VA, our glaucoma surgeries, it seemed like there were a lot of patients that were getting re-operated on, specifically after trabeculectomies. It seems like their bleb was scarring down quickly, their pressure was rising, and a lot of these patients were needing more surgery or just failing. And so just talking among the residents, we felt this to be kind of uniformly the case. And so we weren't sure if there were preventable risk factors that could be avoided that were contributing to this problem. Fortunately, Eileen Wong had the foresight to kind of construct this QI project about this and recruited myself and Ashley Bernheisel. And so we've kind of been exploring this issue and our questions have been, what is actually the rate of our trabeculectomy success in VA cases over the course of a year? How does this compare with other reported outcomes? And if our success rate is lower, what preventable risk factors could be addressed or could at least be thought about to try to get our outcomes better. And so what we did is reviewed all the cases done in a one year period. We kind of timed this over an academic year and wanted to make sure that we had some decent followup for the most recent patients that we looked at as well. We looked at demographics as well as pre and postoperative visual acuity pressure and medications. And we defined success as a pressure reduction of at least 20% and a final intraocular pressure of at least 18 or lower. And the reason we chose that is that there are several other bigger trabeculectomy outcome studies that use that same criteria. So it makes it easier to compare. We reviewed a total of 13 cases. So we didn't have a large sample size to draw conclusions from. Salt Lake City VA population, these were white males. They all had primary open angle glaucoma. 62% of them had combined surgery with fake almost vacation. And 92% were resident performed. One other case was fellow performed surgery. So we got a 16% overall reduction of intraocular pressure. In medications we got down 40%. Visual acuity got a little worse, 22% worse after surgery. And this was at a mean duration of 46 weeks of follow up. So our overall success rate based on our criteria was 54% and 15% were a success without ever having need for medications or for any blood needling after surgery. So comparing this with other reported outcomes, at one year based on Kaplan-Meier analysis on a lot of, I'll say three or four larger trabeculectomy studies, they're in the range of about 70, in the 70s percent. So this was indeed lower than we would expect for our trabeculectomy outcomes. Looking at the time course of post-operative intraocular pressure right after surgery, a week after it went up a little to 18 and then a month after surgery, it was pretty much where it was gonna stay right around 13 and a half or so. 77% of our patients underwent laser sutralysis and the mean number of laser sutralysis procedures on patients that had it done was two. On average, the first procedure was done at almost two weeks and these were done up to eight weeks after surgery for patients that had multiple laser sutralizes. So I was gonna talk some about, there was some risk factors that are commonly reported for trabeculectomy failure listed here. And essentially all of these, I don't think we had enough numbers to really assess diabetes, but essentially all of these can be excluded in our VA patient population based on the demographics. And so I wanted to look at some other potential risk factors for failure in our population. And so we kind of brainstormed and talked about this, could it be our actual VA population that is more at risk for failure? Could it be that it's resident performed surgery or could it have to do with surgery, factors regarding the surgery itself, the mitomycin C concentration at a livery time or method or the timing of argon laser sutralysis? At the end of my discussion, I'll open this up and if anyone has any other ideas for potential things that could be looked at, we'd be all ears. So looking at the VA patient population, I found one study that showed they looked specifically at VA patients undergoing trabeculectomy and they were actually performed by residents or fellows. And they overall had good outcomes. This was in Houston, so the demographics don't exactly match ours in Salt Lake City. But overall, they reported 87% success at 12 months. Their criteria was a little looser than ours. And so they demonstrate pretty well that it's not necessarily just the VA patients that puts them at greater risk. So next question, does this have to do with resident or fellow performed surgery? I actually mentioned this last year at this talk, but I had looked at multiple studies, looked at resident or fellow, sorry, just resident performed trabeculectomy versus attending. And four of these didn't really show a difference. One was from the UK, so Dr. Patel, we can put less weight on that one. He's not in here. And then a groundbreaking study here from Moran that I'm still in the process of publishing showed that fellow performed surgery is also successful and safe compared to attending performed. So that's that issue. And then things start to get muddier, looking at mitomycin concentration. So there've been a lot of studies that try to identify a very specific time and concentration of mitomycin to give in a trabeculectomy to have the best outcome. And so there's been these, some papers talk about a one size fits all where there's one concentration and duration that's best for everybody. And some people advocate a custom tailored approach based on patient's risk factors for failure. So again, they're looking at a one size fits all versus a custom tailored approach. Everyone's still awake, okay. And then, so there was a recent study and this was not at all the first of these studies that was looking at whether or not titrating mitomycin C concentration and duration based on preoperative risk factors led to better outcomes. So they looked at 155 eyes. They're looking at things like degree of inflammation, neovascularization, patient age, and almost everything that I listed as known preoperative risk factors. They varied their concentration and duration. And their conclusion was that there was really no correlation between success and titration of mitomycin C based on any patient variables. And then there's this other group that came out just this year with a study showing that we can't even necessarily know the concentration of mitomycin C that we're getting. This group looked at 60 samples of mitomycin C that they had acquired from various pharmacies and that had been kind of preserved and prepared different ways. And they used high performance liquid chromatography and showed that overall concentration was 12.5% lower than what was expected and there was a wide range going down almost half of the percent, half of the concentration that they had ordered. Looking here at the chart, they kind of, this box plot shows different methods of preparation. And you can see that there's a couple of these like the frozen samples and maybe the dry powder that really tend to be below standard of what you'd expect for mitomycin concentration. So in addition to concentration and duration of exposure, there's different methods of delivering the mitomycin C. So one method is to inject it in the subtenon space at the beginning of surgery. Then after taking down the congenitiva, you still rinse it out. Or the more traditional method is after creating a pyritomy and dissecting down to bear sclera, you put mitomycin soaked sponges into that space and leave them for a certain duration of time then remove them and irrigate it. And I found one paper that looked at these two methods of mitomycin C delivery. So again, it's hard to draw a lot of conclusions from one paper, but this group presented in 2013, they injected in 125 and placed a sponge in 57. They had similar ILP reduction, but they felt that the sponge group was more likely to need more intervention after surgery, have 5FU injections or develop vascularized blood. These complications were similar between the two groups. And so their conclusion was that the injection technique appeared safer compared to the other. Looking at argon laser sutralisis timing, the general thought on this is that the earlier is better for laser sutralisis timing. There's been a couple studies that show that really 14 days out from a trabeculectomy, if you have pressure about eight, then that's ideal. But that's gonna ensure that you have enough flow through the scleroflap that you're not promoting collagen crosslinking and scarring, but also you're kind of balancing that with the risk of hypotony. And so there have been a few authors that feel that eight is really the goal for 14 days after surgery. And there's been this and a couple other studies that show better outcomes in patients who have early laser sutralisis compared to late, talking about within the first 10 days compared to later. But of course, there has to be contradictions in the glaucoma literature. And a more recent study showed that this group looked at late laser sutralisis compared to early in 75 eyes. And 64% had procedure done within seven days and had a good decrease in intraocular pressure. But 36% had laser sutralisis late, you know, the third quartile was 69 days. So we're talking several, several weeks down the road. And still overall had an intraocular pressure that decreased from 21.7 to 14.7, indicating that maybe it doesn't have to be early. You can still get a good effect from later. This is from that same study. And this is when they did multiple laser sutralisis procedures. And what they're showing is that the amount of intraocular pressure lowering with the first, which had been done at a median time of three and a half days, the second at a median time of seven days, and the third at a median time of 240 days, all showed pretty good intraocular pressure lowering. And their conclusion was that there was no correlation between the degree of pressure lowering and the time of laser sutralisis when they considered all the procedures. So looking at these conflicting reports, and this reflects multiple other reports that are out there, I think the ideal timing probably depends on actual surgeon factors, scleroflap thickness and suture tightness, degree of post-op inflammation and vascularity, and probably other things. And kind of the conclusion that I drew is it probably depends on, you know, it's probably something that each surgeon needs to determine the best plan for themselves because there's not gonna be a best fit for everybody. My conclusions looking at all this is that there are a lot of risk factors for trabeculectomy failure. I'm sure that I haven't covered nearly all of them here. And that there are a lot of parts of the surgery that are either based on theory largely or are surgeon specific and the data is very mixed. And so, you know, I think in glaucoma surgery it's very difficult to draw conclusions from the literature and, you know, expect the same consistent results among surgeries. The data's very mixed. I think in our case further investigation, the first thing could be to look at more patients. 13 is not really enough to really have good numbers to make strong analysis. And so this is kind of just a preliminary glance. But I think we could also look at mitomycin preparation techniques and concentrations of mitomycin obtained at the VA versus at other pharmacies such as here at Moran. And again, I'm very open to any other ideas that anyone may have. These are my references and I appreciate, again, Dr. Wong and Dr. Bern Heisel as well as Dr. Chia for their help in putting this together. Yeah, Dr. Mamos, please. You know, Adam, whenever you're looking at outcomes and trabeculectomy, especially at the VA, there's another factor and I don't know how to put this delicately, but it's follow-up and compliance. So first of all, if the patients aren't as compliant and maybe you don't show up for the follow-ups as often, maybe you don't use the drops, but what comes as a field works very important that the surgeon does follow-up and watches the patient carefully and does everything. And probably the VA system is sometimes the person who does the surgery maybe doesn't do all the post-ops and maybe somebody else does the post-ops and they're not familiar. Somewhere in there, things can kind of fall through the cracks, either the patients don't come or the follow-up's not done. And I'm wondering if that has any impact in that success rate and I don't know how to study that, but that may be another factor that's involved in the success rate overall. That's a great point, I totally agree. Dr. Roscoe? So Craig and I have had analysis as well and it does seem to be that these trials are failing a higher rate at the VA and there is so much variability. And on to the next point, even when there are complications, I would give you one suture tighter and one suture looser. So then I would know which ones would cut post-op. So again, that follow-up is a missing VA that could be clinical at all. I think looking at them, I'd advise them in preparation there is definitely key. I would be very interested in what you found. And just from a post-op analysis for one other contributing factor, not to say that it's higher in this population, you mentioned age of patients, but also preoperative medications. So if patients who are on more medications preoperatively for a longer time period have been very good studies to show that that also causes inflammatory cytokine changes that could potentially put them in a high risk for trap failure. So that could be another thing you can add to this. I did kind of pass that. Yeah, thanks for pointing it out. And thank you also for your help following up these patients, post-ops and the VA. Dr. Frederick. I'm not saying that you shouldn't try and figure out what's going on, but do you think that just putting tubes in these people would be more successful in the long run and just get the same result pressure-wise? Well, I don't know if it's that simple. I don't know if just putting tubes in, we don't know what those outcomes would be either. So it's something to consider. Maybe we should just try doing a higher proportion of tubes and see if our outcomes end up better. Adam, I have a question. I appreciate your taking a look at this. I think that's the only way we can really learn is to examine our results and try to figure out what we're doing right, what we're looking at. I was curious though, you can specify whether or not you, all the residents use the same concentration, did they use the same technique? Was that all standardized or was it variable? It was, yeah. Thanks for pointing that out. The concentration of mitomycin was always the same, 0.2 milligrams per ml. And the surgical technique is the same every time as well. And I could have gone through the exact technique, but it is standardized between two weeks. And what is the time of mitomycin so that it's standardized? That, I'm trying to recall. Re-injected everybody? Oh, that's right. We all inject them with sub-conjunction, so it wasn't done with sponges. So that's one thing that we did have as a constant throughout this year. Is that all these patients received on marriage either 0.2 ml or 0.1 ml, between 0.1 and 0.2 ml. So we're talking about 10 to 20 micrograms. So that's the part that we couldn't control. So there's no, there's no sponges involved with this, so we didn't have any time duration to do so. We were all given a second to then just allow us to sit there and examine it. Thanks Dr. Chance. Yeah. A couple of comments and a question. So these type of studies are incredibly important for a couple of reasons. Take cataract surgery for instance of one of the trainees. We don't actually have any clue across the country what the benchmark is. Everyone probably assumes they're doing pretty well, but we don't actually know how to work on that. And the other reason in this type of study, particularly the VA is important as well, is it would be not a stretch of the imagination at all to have complaints about patient care in high departments and then have Congress several degrees away from that, say, why are we having breast and breast spate veterans care if they can deliver adequate or similar care? So these other two studies that you mentioned, I think were really important because again, both of them found aside from the visual outcomes in California, but both of them found success rates that were quite high, specifically mentioned comparable to the attendance. So to define a little bit, at RVA it's interesting, Jason Bolton, whether the chief of the VA, blood coma surgeon, very conservative, so when Dr. Chia came in, there was a huge part of patients that potentially could have had surgery much sooner, and so I don't know if you think that might have a difference in our early failure rate because so many of these folks were really advanced. I think it's something that Laura alluded to was just an exposure to pre-operative medications. I feel like that's a real thing and patients have been paid for VA care for years. The tissues are much more friable and much more likely to discard whether it be a tumor or a drug. So I think that's something that we should look at. It's hard to know if we don't get great mysteries all the time. Patients are on multiple medications, it's cross-clinidism, but I would say for the most part, we don't have a lot of patients on preserving free drugs at the VA because we're formulae. Yeah. So it's gonna be true. I'd be good to watch that. Last quick question, one of the patients that had visual acuity loss, were they due to, do you guys have a visual acuity progression or was it a cataract progression if you would just turn the track? I didn't look closely at each visual acuity course to be able to answer that, sorry. Because if it's due to visual field or glaucoma progression, then that gets back to Ray and Jefferson in terms of these patients who have a visual acuity drop. I believe they were the patients that had the major visual acuity drops were pseudo-faking. Have a good time. All right, thanks.