 So if we just get, we see, you'd like to see just standard. All right. So I'm going to switch gears a little bit. So I'm going to talk about inter-cameral antibiotics for prophylaxis and an ophthalmitis. It's a practice that has a good head of steam in Europe and we're a little bit slow in the United States. We'll kind of talk about the evidence for and against the prophylaxis and ophthalmitis. We'll talk about the options of prophylaxis that we have and then really should you adopt inter-cameral antibiotics into your practice for prophylaxis. So unlike Dr. Mamelis, my travel slides are more local. I don't go to Singapore or Europe very often, but this was my family and I recently went to Zion National Park and so I'll have to show you some pictures of us there. It's tough to get six people to look at the camera at once, but it was a lot of fun. So we'll talk about a case that presented while I was on retina and then talk about the epidemiology of an ophthalmitis, some of the organisms that we see, the different types of antibiotic prophylaxis, talk about the different drugs that are used. There's a little bit of literature on the cost analysis and there's quite a bit on safety. And then we'll look at some of the bigger studies and then come to some conclusions. So we had a 56-year-old who presented with pain in the eye and blurred vision just five days after cataract surgery woke up. Everything had gone fine in the surgery and just had this new blurry vision and pain. She'd had her right eye done two weeks before her left eye. Looking back at her chart, she had received moxifoxis in just after this surgery for every two hours for the first day and then she was on it four times a day along with Pretforte and Catorilac. Her acuity at the time of presentation was 20-50, her pressure was okay at 20. But this is post-op day number one, sorry, in Tracelle and Flair. No intracamilar pre-op antibiotics were used at that time and then received one drop of Gatifoxis at the end of the case. So pretty unremarkable surgery. She looked good on post-op day one, doing well, healing well. If you look at her course, she said at 7 a.m. she just woke up and vision was bad and lots of stuff floating around in her vision. So she called and came in. Her pressure was 13 with a vision of 2,100 in her left eye. She had four-plus cell, a little hypopion. She had vitreous cell. Couldn't see the fund that's because of the amount of haze that was present. So the question is, does this end ophthalmitis? Is this TAS? Is there a retained lens fragment? Is this a uveotic syndrome? Those are the types of things that you think about. Her presentation is a little bit late for TAS. When we look at the differences between TAS and end ophthalmitis, TAS is this toxic anterior segment syndrome. It's acute. It's sterile. It's usually within 24 to 48 hours. Really the timing is everything. It's not an infectious process. This is just an exuberant inflammatory response to something surrounding the surgery. They usually have marked blurred vision and the rule is really no pain, although there are some patients who present with pain. And limbis to limbis corneal edema can kind of help you with TAS versus end ophthalmitis. You can have iris damage and glaucoma, but it's really marked anterior segment inflammation, which is difficult to differentiate from end ophthalmitis. But TAS usually does not have a lot of inflammation in the vitreous, so a B scan can help if you can't see the fundus. These are some pictures from a book chapter that Dr. Mamelis had published recently. The top picture, you could say that's end ophthalmitis or TAS. It's hard to know, but the bottom picture with limbis to limbis corneal edema is not always typical in end ophthalmitis, more so in TAS. So in our patient, we felt like this was acute post-operative end ophthalmitis. Her vision was better than light perception, so according to the EVS, we did an in-office tap and inject. We use a vitrector now to get a good vitreous sample in the retina clinics and then send it for Gramstein and in cultures. Standard injections is vancomycin, septazodium, and then dexamethasone here at our institution. And then we kept her on her moxifloxan topical and then Pred-4-10-Catorlac, kept those going just four times a day and added atropine and oral moxifloxacin. So 1995 is when EVS came out. It's been a long time ago, we're almost 20 years, but it was a very important study that helped really change end ophthalmitis from a surgery, automatic surgery to an in-office procedure if the patient has LP vision or better. If their vision is LP or worse, then there's a three-time-better chance. You see that 33% of patients achieve 20-40% versus 11% if you do a tap and inject. So there still is a role for vitrectomy in patients who have really poor vision, who present with end ophthalmitis. Majority of cases are gram-positive according to the EVS study, but the actual level is true today. So what's the epidemiology of end ophthalmitis? There's a huge range in the literature, all the way down to, in some cases, even 0% in some cohorts, up to 0.345%. Some have even reported up to 1%, 1 in 100 cases in some areas. So there's an interesting review of over 3 million patients with an overall rate of 0.128%. You can see the different changes of the decades, but it's low in the 90s, and then it's kind of spiked up again in 2002-2003. A Canada study, their rates were about 0.14 to 0.15. Complications definitely increase the risk. If you have an unplanned anterior vitrectomy, your risk goes up by 10 times. And despite what you may hope or think, residents just don't increase the risk according to a couple of studies. You can't just blame it on the resident. But again, these are rare events, and it's very difficult to understand the differences in varying practices. But we'll kind of explore a lot of that today. We've had a couple of published studies here from the Moran Eye Center. So 1997-2003, our rate was about 0.19%, and that dropped to 0.05%, really around the use of topical fluoroquinolones for prophylaxis. So last seven years, I'm not 100% sure if anybody knows what our rate's been, but that's the published data. Okay. And again, when you have that level at law, it's one or two. They look all the time. Okay, so pretty similar to that. In Erevin, they did, they published a study that was 42,000 consecutive cases. Their rate was 0.09% over two years, and they have a practice where they have reusable gowns and gloves and tubing and solutions, and they steam sterilize. Significant cost savings is not a lot of increased risk in their study. So what are the possible sources of infection? So you have anything that has direct access to really the surgical wounds. So you have your ocular tear film, your eyelids, the adnexa around the eye. Your irrigating solutions, anything that you put into the eye, anything from tri-pan blue to the BSS bottle to your cannulas that you're inserting, all the topical medications that are put in before, after, during the surgery. Your surgical instruments, even IOLs, anything that goes into the eye. The surgeon's respiratory flora, the assistant's flora. You know, you get a break and a glove. You get access to skin flora. Even the operating room air. I mean, there's just so many different ways to get bacteria in and around the eye during the surgery. So the EVS showed they did an interesting portion of their study. They showed the IOLids of patients with an ophthalmitis and 68% had indistinguishable flora on their IOLids compared to what was growing in their eye. So we know the IOLids are a big source of infections. So what organisms are involved in the acute cases? It's really these gram positives that are the most common. It's coag negative staff and staph aureus and strep. You get some gram negatives that are rare but have poor outcomes. And then chronic cases. We had a case that when I was on retina of coag negative staff that had been going on for a few months. That was finally diagnosed by a tap. And then you have blood associated. So lots of different types have endophthalmitis and different bacteria associated with the different types. Another interesting study they did, they just did congenitival swabs of 200 cases after cataract surgery. This is right after cataract surgery. 80% of them had positive bacterial growth. Half of them were propionobacterium. So we're not always effective at getting rid of all the bacteria even after iodine and all that we do around the surgery. One of the biggest concerns is that MRSA is on the rise. There was a series that was published where they looked back at all their cases. They had looked at their staph aureus and ophthalmitis. And there were zero cases of MRSA up to 1992. And then almost half of their cases of staph aureus infections were MRSA between 1995 and 2008. The biggest problem with this bug is it's resistant to a lot of fluoroquinolones. And so you end up vancomycin is the best thing to kill them. But kind of a scary rise in statistics, not just in eyes, but really in all of healthcare, these resistant organisms. So our patient grew out gram positive bacteria. It was coag-negative staph. It was pan-sensitive. The day after she presented with an ophthalmitis we injected another dose of vancomycin directed at those gram-positive organisms to kind of help her heal. So what do we know about coag-negative staph? There's 32 known species. There's 15 that are known to be in humans. And it's about 10% of all nosocomial infections. If you look at the number of cases of bacteremia, there's a lot of cases of this just from coag-negative staph. There's catheter-related things with central lines. UTIs are really commonly caused by it. Shunts in the CNS, endocarditis, any surgical site has the risk of dysbacteria causing an infection. So the majority of times when you're testing for infections, this is thought to be a contaminant, but it can be an organism that actually causes real infections. These are the common bacteria that fall into coag-negative staph. So staph saprophyticus is a really common urinary tract infection, and then staph epidermidis is really the main one that we see. Staph lubedumensis, something like that. It's one of the resistant ones, so they always test specifically for that when they're looking at these endothelitis cases. The scary thing is that these, they're normal skin form, and look at the number of colony forming units that are just a centimeter squared of skin. I mean, there's tens to hundreds of thousands of these bacteria. So do you know if you took the entire bacterial lobe for an average human body? How much it would weigh? I don't. It's kind of gross to think about it. In terms of the entire bacterial lobe between our gut, skin, and the world we have, and it's not really crazy to talk about, if you do a biopsy in front of them, you never spill on them. If I don't, you spill on them. So we just got to understand the bacteria. Right. The critical growth of that now, the big thing they're doing is the fecal implant. Yeah, we're learning more and more. So if we look at co-agnetive staff, the antibiotics that are good against it, penicillin is by and large the main antibiotic for co-agnetive staff. But because of resistance, you know, you have forquinolones and vancomycin that are used as well in cases where there's resistance to penicillins. Cephalosporins are good. There's a lot of resistance to the macrolides, clinomycin, urethromycin, all those other different antibiotics. No, better than cipro. Not Bessie, sorry. It's just better than ciprofloxin. So there's different generations of the quinolones, and the newest one is Bessifloxin, but ciprofloxin was one of the first or second generations. It's not as good as moxie. Another slide. I just forgot the name of this. Weeping rock. It's like a straight-up trail, just a half mile, it's beautiful. There's no water running off the mountain, but it's still just porous rocks just kind of leak water all year round. So what do we do to reduce the risk of inoptimitis? So we use sterile techniques. One of the most important things that we know is keeping the lashes out of the way. Drape the lashes, get the lead speculum, keep them out of the field. We use a lot of single-use instruments. If not, we have thorough cleaning of instruments. Negative pressure ORs to try to help with that air. Then cleaning solutions, whether it's the patient's scrub or the surgeon's hand scrubs. Iodine is by far and away the most accepted, but chlorhexidine is also a close second. 99.99% killing rate, say with iodine. Then we use prophylactic antibiotics, and there's some patient instructions that we use as well to try to reduce the risk. So wounds have been shown to be important. There's a lot of conflicting evidence as I reviewed the literature on this. Infrotemporal wounds in right eyes thought to be closer to the lid had a higher risk in a Baskin Palmer study. Definitely a wound leak post-op day one. 44 times the increased risk of inoptimitis. There's some studies that showed clear corneal incisions had an increased risk. Other studies that showed that it didn't. The thought is you get some egressive fluid with post-op manipulation, you get hypotony. Those wounds can open up a little bit easier, maybe than scleral wounds that are covered by conjunctiva. In Sweden, they showed that there really wasn't a lot of difference between clear corneal and sclera. I think the jury's still out on smaller incisions. There's not a lot of published data. They do. They are using all intracameral. Smaller and smaller incisions out there, but the advocations for that is less end up the minus, but there's not a lot of good published data on that. I think everyone understands that you should put a suture in if you don't have a watertight wound at the end of the case. That's the biggest deal, is making sure that your wounds are watertight. What do we tell patients? People are different on this. Some people put patches. Some people put shields. Others don't. There was a study that showed there wasn't a lot of difference between patching or shielding patients. No swimming or showering up to a week, heavy lifting. Everyone has different ways or different preferences on what they say. I tried to tell a patient not to lift anything heavy at their job for a few days, and Dr. Taven rebuked me. He just doesn't believe in it. People just have different practice patterns on how they do this. Patient instructions is a big area where we don't know for sure, but for sure dirty hands rubbing your eyes is probably not a good thing. So, prophylaxis. There was a study in 2002 where they looked at all the different types of prophylaxis, and the only one that was shown to have moderately important outcomes clinically was iodine. None of the other ones showed any importance. So they looked at all these different ones, and the only recommendation was a recommendation of B on this iodine, but lash trimming, irrigating the surface, antibiotics, irrigating solutions with antibiotics, heparin. Lots of different things just didn't seem to help. So what are the different types of prophylaxis? By and large, the most commonly used is just topical antibiotics. There's differences in practice whether you use them before surgery or around surgery and after surgery. Most people use them after surgery, but that's not universal. Not everybody uses antibiotics the same day of surgery as I looked at the literature, and there isn't a lot of people who use them before in the literature, but again, it's just, there's a broad range of different practice patterns. Intracameral, again, this is off-label, completely off-label, so it's important to understand the risks of that, but we'll talk about the evidence behind that. These are the different antibiotics that are used in that. Subconjunctival, in some areas of the world, that's just what they do. They just inject antibiotics under the congeal at the end of the case. There's some places that use oral and even IV moxifoxicin around the time of the surgery, and then there's some that are putting antibiotics into irrigating solutions. Those are the different ways that we can use antibiotics prophylactically. So let's look at some of these antibiotics. The fourth generation fluoroquinolones are probably the most broadly used here in the United States. Gattifoxicin and moxifoxicin are the most common. Levofoxicin is what they used in the ESCRS study, not used a lot in the U.S., and Bezifoxicin is a newer one. I don't see it used very often. The way it works is it blocks DNA gyrase and topoisomerase from forming, which are important in DNA replication. It really covers gram negatives and gram positives. Pretty much everything on the spectrum that causes endophthalmitis, the only risk are the resistant bacteria for fluoroquinolones. Side effects, none of these are really side effects with local use. These are more systemic use, QT prolongation, tendon rupture, hepatotoxic. Alcon specifically labels moxifoxicin not for intracular use. It's important to know if you're going to use this one. There was a rabbit study that checked anterior chamber and vitreous samples after injection of moxifoxicin, and it showed that you had a good MIC of really all the pathogens for up to two and a half hours after injection. They checked corneas and they didn't find any toxicity in the corneas of these rabbits. There was another study that showed intracam... There aren't a lot of studies on moxifoxicin, but these are small studies, 2600 eyes, you only have 1,000 and 1,300 eyes. No intracameral moxifoxin, one endophthalmitis event, zero in the group with intracameral, but again these numbers are too small. There's none in the literature that have enough to really tell if moxifoxin is good. There are some studies that showed that it's safe up to 150 micrograms per ml in concentrations within the eye and all you need is up to two and a half micrograms per ml to get above the concentrations and to kill most bacteria within the eye. This is the scary article that I found is the resistance patterns with coag negative staff in ophthalmitis to all the fluoroquinolones. You're getting up to almost half a half of bacteria that are causing an ophthalmitis that are resistant to fluoroquinolones and that's definitely gotten worse over the last decade or so, two decades. So what about cephalosporins? This is the most common one used in Europe, cepheuroxium and cephasilin. So these are against cell walls of their beta-lactamase antibiotics. They work against gram positive and gram negative. The one gap of coverage is interococcus, which can be a really bad infectious organism for in ophthalmitis. There is the penicillin cross-reactivity. Historically it was thought to be 10%, but in allergies it's really felt to be more like 1% of patients who are allergic to penicillin will have this. There are some cases of anaphylaxis in the literature after intracameral cepheuroxium injections. About vancomycin. So there's a few studies on vancomycin that are out there. The way that it works is it blocks cell wall synthesis as well. This is the key to it. It only works against gram positive. There's no gram negative coverage. But by and large it kills any MRSA bacteria. There's a little bit of resistance, but not much out there at all. This is the key to it for me is the CDC has put out an advisory saying we do not recommend using vancomycin for endophthalmitis prophylaxis. And their fear is that resistance pattern that's occurred with fluoroquinolones is really our strongest antibiotic against MRSA. Another study with serial taps using vancomycin it showed that it stayed at a good concentration for more than a day against all the bacteria that can cause infections as far as gram positives. Some of the studies that are out there, 0% no endophthalmitis in 19,000 cases using intracameral vancomycin. Another study in Asia where the rate is .01% using vancomycin. So it appears to be very effective. But again the advisory by the CDC is something to keep in mind. So what do we know about the use of antibiotics in Europe? Here in the United States only about a quarter of people were using them in 2007. Most said that they would use them if there were some available commercially. They didn't want to worry about the compounding effects or problems. In the UK about half of people were using it. In Europe it went from 60% in 2010 up to 75% in 2014. Most are using sephiroxine there. Looking back at our patient she's two months now after presenting with endophthalmitis. She has a visual acuity of 2080. Her eyes are pretty quiet. She just has a lot of vitreous debris and has plans to have attracted me to get that cleared out to help her with her visual recovery. This was a tough hike. The lower middle and upper emerald pools we planned to go to the lower because it was a paved trail and then we thought, heck, let's go. So we picked up our kids and went up to the upper ones. It was a lot of fun. It's scary hiking with kids in Zion but you can do it even with four. We had two in backpacks and then the two younger ones hiked. So this is probably the biggest study out there that's the best data at least. It's a prospective randomized study of 16,000 patients where they had intracameral sephiroxine and they compared that with just topical prophylaxis but they used levofloxacin which is one of the big downsides to their study. So they found that the rate in intracameral sephiroxine was .07% and then topical levofloxacin was .3% which is a pretty high baseline rate to be comparing it to and so they showed this 5.8 fold reduction which was, you know, big news but again I think this baseline is way too high to have a good comparison. They didn't use the fourth generation fluoroquinolones like we use now. In Spain, good study out of Spain with sephiroxine, 19,000 patients. They had a total of 44 cases of inoptimitis with an overall rate of .2, again a pretty high rate. Most were these gram positives. They found that the number needed to treat to prevent an inoptimitis infection with intracameral sephiroxine was 182 patients. That's how many you had to treat to prevent it. This is one of the biggest issues is these negative culture ones that make it kind of difficult. They kind of skew the numbers pretty bad but most of them are coag negative staff on the culture positive. This is their graph from before introduction of intracameral sephiroxine to after. You can see a huge drop in the rate in their cohorts. It showed just the relative risk is .06 if you use intracameral sephiroxine versus not. So a pretty big risk reduction, .93. They looked a little bit at the cost analysis there in Spain. It only cost them one euro to use sephiroxine. The cost of inoptimitis for them is about $1,300. And so you'd save $1,178 or euros for every 182 patients you treat. In the U.S. the cost is about $1,400 for every case of inoptimitis. So they compared the cost of fluoroquinolones, just topical fluoroquinolones versus sephiroxine. Fluoroquinolones would have to be 19 times as effective as sephiroxine to balance out the cost differential just because of the expensive of fluoroquinolones. This is a good study out of Canada. So they looked at their practice over eight years and they tried to identify different things that were more risky for inoptimitis. So they had 75,000 cases. So all their rates very low. It's .03%. They didn't find any effect with intracameral subconge antibiotics. They definitely saw that using fourth generation fluoroquinolones topically lowered the odds. And then if you put in a drop of timolol at the end of the case, increase your odds of inoptimitis. So these are the different things that they do in their practice. Half of patients or half of the doctors use pre-op antibiotics. Most use same day. Not very many of them are using intracameral and if they do it's vancomycin. Some are using subconge sephylsporins. Some are using steroids. Most of them actually. And then these glaucoma drops. The timolol inoptimitis rate for them was .2% compared to their overall rate of .03. So a pretty significant increase risk with using topical timolol at the end of the case. No difference. So they found that a temporal incision was more riskier than a superior incision. And then their wound types didn't have any difference in their population studies. There were when I started the literature search on this, there were well over 100 articles on it. Is there a difference? Yeah. There were some articles on it. It was a big review. So the different types of antibiotics that they use after the case, if you see polymix and B just was not very good for them. That was the only one that had significance. Having a higher rate if that was used for prophylaxis compared to the others. Tanzania threw out a little letter in JSCRS that showed they initiated intracameral sephiroxime in a month. They're having one a month. They're having a pretty high rate. Their surgical volume is about 7,000 cases a year. Mosha Farr and Vitaly published a paper from here. They looked at nine centers in seven states. More than 20,000 patients, the rate using topical fluoroquinolones was about 0.07%. Moxifloxin was a little bit worse compared to Gattifloxin, but not statistically different. So what about the Swedes? They seem to have the lowest rate of endophthalmitis reported out there. Over almost 500,000 cases, their rate is 0.029%. It's felt to be unethical in Sweden to not use intracameral sephiroxime. So it's pretty widespread there and they do not use any topical antibiotics. They only use the intracameral. I was going to go through all these different things, but I'm going to skip this. This just goes over all the different rates. Just to point it out, the endophthalmitis rate without intracameral antibiotics was about 0.3 in all of these studies combined and with intracameral was about 0.05. So they showed kind of a big difference between the two. So if you're going to use the intracameral antibiotics, these are different doses that use. Moxifloxin does not need to be compounded. You can just use the bottle. It's self-preserved and most people are injecting about 0.5 up to 1 ml. Or sorry, 0.5 ml. That is the bottle that Alcon says not to use. That's really the only way that it's available. Vancomycin and sephiroxime it's a milligram per 0.1 ml and then sephazolin is 2.5 per 0.1 ml. So you can compound any of those into that dose. So what are the problems? We had the big Avastin outbreak of strep in Florida in 2012. There's concentration issues you had. There's a couple of reports. You know, you had 50 to 100 times the recommended dose and 40 to 50 milligrams of sephiroxime. This study actually had pretty bad outcomes. Half the eyes had pretty poor vision afterwards. Yeah, definitely. These cases actually turned out okay. In these six cases they had pretty good visual outcomes. And you know, this hit the news a couple years ago with the big meningitis outbreak with epidural steroids. So it's a big problem with just the stigma that's out there on compounding pharmacies and you're definitely at a huge risk by using compounding pharmacies based on some of the outcomes of these studies. TAS is a huge deal. If you want to avoid TAS you've got to have the preservative-free, you have to have proper concentration, you have to have the pH. All of the different things have to be in good balance in order for that to be prevented. Looking forward at some of the different ways we're thinking about prophylaxis. Japan is looking at antibiotic delivery using IOLs and they basically put antibiotic on the IOL on the surface of it to have that kind of always in there for a longer period of time. In Brazil they're looking at time-release subconge, ciprofloxan tramsin alone rather than just putting that depot in right after the case. They're trying to have a time release over about a month. And then modifying IOLs to reduce any adherence of bacteria as well as there are different ways that they're doing this. So what's commercially available if you wanted to get one of these products? There actually is now a commercially available Cepiroxin single unit dose that's not preserved, it's preservative-free that can be used for this rather than using a compounding pharmacy. Not here. Yep, can't get any of it here. Moxifloxan again you can just use the bottle. Alcon has that label on it. And then you have to compound these three antibiotics. So I think there's some good evidence that intracameral antibiotics do decrease the incidence and then ophthalmitis. I think one of the biggest problems with most of the studies that I saw is that their baseline rates were quite high. And what they were able to get to wasn't a whole lot different from just using topical flu or equivalents from a lot of the studies that are out there from the United States. You have to watch out for compounding issues and this puts you at big legal risk. You're using an off-label medication. There's not a lot of protection for you without good informed consent with your patients. The CDC again, they advise against the use of vancomycin. So that's another arrow in the opposite defendants quiver. And maybe it's the combination of prophylaxis which is sort of what we use now. We use iodine and we use topical flu or equivalents. Maybe throwing in that intracameral sephiroxine to help with some of those gram negatives and gram positives is the best way to go. But I think the jury is still out. So the question is what will you do? Does this change your practice? I like this number .029%. I like some of the numbers that have 0%, but .01% in vancomycin. But using sephiroxine seems like a pretty good, safe way to do it. Getting your rates down to .02%. I'm not ready to use vancomycin given the CDC recommendations and different things. Jim? So in the studies in Sweden the cases of culture proven and ophthalmitis I think 12 out of 13 in their big study were resistant to sephiroxine. They didn't have any cases that were susceptible to sephiroxine that caused endophthalmitis. Beyond that there weren't a lot of great ones for intracameral use. Absolutely, you saw the pattern with fluoroquinolones. Yeah, Dr. Mamos? I think it's a really nice review. The data that you put in for the law is pretty compelling to come on out. The ESCRS study that we did has a lot of differences with the control group. They weren't getting out by autopilot in the day. It's still bristle on there. Their rate of development was amazing. Now there's really good jump in the data that shows what's coming from here. And so you're not going to see it happen. I don't even get to feel like every have my eye closed off is popular. There's no study. There's a complicated three-step process where you can take the bottle and think about but you have one outbreak where pharmacists say, hey, you can save money by using my station. Yeah, you get one outbreak of tasks and it just ruins your entire hope of preventing vision loss. So the latest academy practice guideline there are, I don't know, we're probably close to 1,000. Yeah, there's the good ones. Most of it is junk. Maybe because there's not the power to detect. And you got to keep remembering that if you've got an incidence of 1 in 2,000 and you have, you know, and something in the 800 vision study and small numbers even on the Navy's statistics you have to know that all it takes is one crazy outbreak. But as we reviewed it if you look at the overall information there are some conclusions. So I think that's absolutely correct. I don't think anyone can doubt the problem the United States has mentioned is it's tasks. Nick and I were involved in a court case where they used the DSS plus additive. A lot of people don't know the DSCRS study. They had a bad outbreak of death. You were there. I finally got a few very unheard of and I said, well, they said it wasn't too bad and the guys knew about it. What they did there is they had some people who mixed it with sterile water. So, you know, rather than using even sterile saline instead of sterile water. Big issue, big issue. We can go on about that bilateral. I just, those of you who saw the AGO just had an article again they keep talking about the simultaneous and the simultaneous cataracts here they only have the risk of like individual either individual then you can't have a similar risk in both sides. Well, the tasks 100 percent over and over again. Sometimes where you can totally re-grade the patient and the rest of the people are going out of the bottle. The range of what they have to do as part of particulates and the way of other things is totally different. If somebody gets in trouble with that it's going to be something you can't do better. But that's the big concern that's going to happen. I think that all of those work they work so much differently. That is getting enough antibiotic that it's likely to be greater tougher with the MRSA. The topical of the day of surgery the life is getting in the eye. Cypher flax system showed that Cypher was not penetrating yet. Sub-conjuctival there's some good work done actually out of New Zealand and Australia and they've shown that also. It's pretty simple understanding. The idea is you're contaminating the Andrew Chamber. If you culture carefully at least 30% of the time you're going to find there's some bacteria left that haven't done studies with Nick and Louie Ann. I can tell you that the Andrew Chamber if you have something higher than the MIC inside the eye on the first day you're likely to be protected. That was our overall recommendation. I think defense wise we're doing a lot of defense work right after surgery it's not likely to get it. You're not going to get any concentrations. And Nick's right you cannot put a study together one that we really they just did a cost analysis they came up with 200 you talked about the clear corneal the one thing absolutely everybody has shown when we move from going square with the corneal Medicare data showed there was a clear three times increase in the incidence that ended off the widest in that early period. That seems to have largely disappeared I think it was because there was a lot of the people who had been left and that 44 figures was the study that came out of RAM it was a 44 whole increased risk to end off the widest and we showed if we had a broken capsule of corneal it was a 14 fold and so right now I think as long as you're getting a 4th generation you're getting frequently the data of surgery you're getting something subconscientiable which most of us don't like to do that or it's going to hold better there's lots of fascinating stuff in this area well just this 19,000 patients that you just point out that's a good friend, Steve Larson who has become over to say that's an eye on this issue that's associated with bilateral simultaneous surgery that's self-recorded by large groups and we already know many of those people who know those who have it who've seen cases of them so there's zero in 19 there's leave them out sending a letter out how many cases you've done I don't know I've done 5,000 I don't think I've had out much zero so that study is not a study the reason why such a big risk with our big surgery it was not uncommon to see always flowing from the enter chamber out to study quite a while ago which is a whole host of different viral infection there's a better way to think of it the bacteria that got out of the cases of them that was a B- and then you need to use antibiotics preoperative antibiotics has really no good studies showing the degree of bacterial load a little but it's also been now in particular the studies done using antibiotics in association with film we started going along we did a study it should have been published in a good journal for some reason we actually looked at conjugal type of culture the opposite kind of data to see what the new looks like across the country and I was PI of that study our MRSA rate all of it largely related to our old brand a number of years ago you were recommending that the patients wear their patch for maybe 4 hours and then take them off and use the antibiotics frequently