 Good morning. Can you guys hear me all right? Thanks for coming to Grand Rounds today. And those of you that don't know me, I'm Craig Chai, one of the junior faculty in the Glaucoma Division. And today we're going to be talking about something that's near and dear to my heart. I went into Glaucoma for a couple of reasons. One of the main reasons was the opportunity to do international work. As I've continued to do international work, I've just seen the immense amount of just despair with Glaucoma treatment in the developing world. So today I'm going to present to you this topic. SICS is to cataract as blank is to glaucoma. And that blank is there for a reason. I don't know what the perfect analogy is to SICS to cataract as something is to glaucoma. But I'm in search of it. And that's what I've kind of committed myself to. And I think this is probably going to be a big focus of my career is to look for a cost effective solution, a surgical solution to worldwide open-angle glaucoma. So we're going to get started. I have a few disclosures to make. I am an investigator for the Hydrus Microsan, a co-investigator along with Alan Crandall. Moran is a study center for this device for the Hydrus IV study. And I also own some stock in Abbott. I don't think that's really important. So glaucoma around the world. You know, the major causes of blindness around the world have steadily changed over the last 100 years. 100 years ago, it was mainly due to corneal disease, such as dracoma. 50 years ago, much of that was due to cataracts. And presently, a lot of it's due to ARMD. This is in the developed world. Interestingly though, things really haven't changed for glaucoma. So glaucoma has been pretty steady in terms of its prevalence around the world. Anywhere between 8% to 12% in most of the studies that have been published. People are living longer. On average, about 10% of the population is at risk for developing glaucoma. And again, 50% of people are undiagnosed and untreated. So this was a paper published by Quigley back in 2006, looking at the prevalence of glaucoma around the world, based on population studies. So here in 2010, you can see that the world glaucoma prevalence was around 44 million. Much of that was in Europe and China and India and Africa in terms of the prevalence. Where most of that open angle glaucoma was found. Pushing forward into 2020, we can see that number has increased to about 58,000 or 58 million, I'm sorry. And much of it again is centered around Europe, China, India, and Africa. So glaucoma is prevalent, and it is increasing prevalence. I'm not sure who in America knows how to do that. Let's see, I'm not sure why they didn't include it. When Quigley did the study, it was based on the studies available at that time. There may have been some studies. Yeah, projections, yeah. These were based on prevalence models and using UN population, right. So just a little bit of a segue. I wanted to give you an update on the work that Moran has been doing in Haiti. Haiti is the second most populous country in the Caribbean. Catarex and glaucoma is still the major causes of visual impairment in this part of the world. And we've been focusing our work in the northern part of the country in Capatian, a city of approximately 250,000 people. We've been working together with Mike Falmyer at the University of Nebraska. And this is our third year that we've been operating in Haiti, working with our local partners. This is a picture outside of the clinic. Our host there, the name of their clinic is the Vision Plus Clinic. And it's led by Dr. Garleen Roney, Mary Carmel, and Dr. Dupuis. Our team members include some familiar faces. Many of you may remember Sonia Dar. She was a fellow here after me, now practicing in New York City. In addition, Vali, with the pun, our cornea fellow this year also joined our team. The first time that we brought a cornea specialist on our team. In addition, Joseph Chen, Michael Glaucoma fellow this year, one of Michael Glaucoma fellows also accompanied us on our trip. Lisa, he is a third year resident from Stanford who's going into retina. She'll be joining the Wilmer Department next year for her training. And she joined us along this trip as well. Judd Kahoon, one of our MD-PhD students who fresh off defending his dissertation two days later joined us on our trip and was really an instrumental part of our success. Judd did everything. He was actually the most wanted man in Capatian during this trip. Many times you could hear us calling out for Judd. In fact, there was one instance where Vali was in the midst of a corneal transplant. And Joe Chen kindly offered some help and she just said, no, I need Judd right now. Judd quickly came to the rescue and brought Vali her cornea in order to complete her transplantation. In addition, Lauren Reese is a surgical specialist with Ivantis, a company that produces the hydrous micro-stent. We were fortunate enough to take some of these micro-stents down and to implant some of the first devices in Haiti. Our team arrived in Port-au-Prince and then we took a small twin prop plane over to Capatian. We had a number of different firsts along our trip. It was the first time that we crammed three operating beds into one room. We also had the first, this was also the first time that the air conditioning broke. On the first day it was sweltering. Many of us were sweating profusely and I can remember vividly one time Vali was operating with her glasses on and her glasses started to fog up uncontrollably and she had nothing else to do except to remove her glasses and continue operating without it. Her glasses. Did you get hand cramps like with Ron James? No, no hand cramps. We were well fueled up. We had our electrolyte juice before ahead of time but a number of firsts on our trip. In addition, this was the first time that corneal transplantation had been performed in Capatian and Vali was privileged enough to be able to perform 10 corneal transplantations while we were down there. In addition, this is the first time that I was able to perform the GAP procedure that I was able to learn ahead of time and do down in Haiti. I'll go into a little bit more detail about what the GAP procedure is. In addition, this was the first time that we implanted MIG's devices in Capatian. This particular device that I'm illustrating here on the left is the Hydrus MicroStent which is the first intra-canolicular scaffold. Some of you may also recognize the picture on the bottom right here which is the ice dent produced by Glaucos. In addition, this was the first time that we were able to visit the Citadel. The Citadel is the largest fortress established in the Caribbean that was built by the local Haitians to protect them against French invasion. And now let's talk a little bit about glaucoma in this part of the world. There is no Haitian ice study that has been performed yet but there is the Barbados Ice Study. Barbados is an independent country of approximately 280,000 people in the lower Antilles. And there was a study performed called the Barbados Ice Study. Back in 1994, the results were published to give us a sense of what the prevalence of open-angle glaucoma is like in this part of the world. Around 7% of lack citizens of Barbados have open-angle glaucoma. Those of mixed background, 3.3%. In addition, what you can see from the study is that the older you are, the higher the prevalence. And also, there seems to be a disproportionate amount of men affected by open-angle glaucoma in this part of the world. So glaucoma and Haiti. What are our challenges about glaucoma and Haiti? It's extremely limited in terms of medical therapy and very expensive. Timolall is widely available and some people have proposed putting it in the water there. Next in line is Travitan. That's probably our most potent prostaglandin that we have available in Haiti but it is considerably expensive and for most of the population is unaffordable. Laser turboculoplasty is available in parts of Haiti but it's not widely available and in fact it's not available at the particular host site where we were working and it's very underutilized. There is one SLT machine in Cap-Hation that is at a local mission but unfortunately it can only be utilized when the American team comes through that help purchase that machine. So it sits there for most of the year being underutilized. So in general, glaucoma in Haiti is really a surgical problem but the question that I want to pose today is which surgery? And this could be a question posed to many parts of the world such as West Africa where the Moran has been working as well in Ghana. Is it a trap? Is terbecuolectomy really our option, our best option or surgical option for tackling glaucoma in this part of the world? Is it a glaucoma drainage device? Or is it maybe this gap procedure that we'll go into? Or maybe another mixed device that could possibly address this issue. So what are the alternatives to terbecuolectomy? This is a very, very busy slide. Terbecuolectomy for the most part has been our go-to, our gold standard for glaucoma surgery around the world. But here this is just a schematic of the different procedures that are available. This is really the sync of surgery for glaucoma surgery. We can tackle it by inflow options either using transcletal cycle photocoagulation, ECP. UC3 is basically using ultrasound technology. It stands for Ultrasound Circular Cyclocoagulation, produced and invented by Malika Hook out of Colorado. Cryotherapy really has fallen out of favor because of its collateral damage and extreme pain after treatment. Then we can come over here to the right-hand side looking at trabecular mesh work outflow procedures. And the list is long. We have the gap procedure, canaloplasty, revolutionized by Robert Stegman in South Africa. Trabecuolectomy also known as AB internal trabecuolectomy, the ice dent, second-generation devices such as the ice dent inject, which are in research trials, the hydrous micro-stent, high-frequency deep sclerectomy, eczema laser trabecuolostomy, and SLT and micro-pulse laser trabecuoleplasty. How about other bypass procedures such as glaucoma drainage devices? There's also the zen implant, which is a gel implant that diverts fluid to the subconjunctival space. And finally, another device called the infocus micro-shunt, which is also an AB external device that diverts fluid to the subconjunctival space. We also have UVO scleral outflow procedures such as the Solix gold shunt, the side-pass micro-stent as well as the ice dent supra, all diverting fluid into UVO scleral space. Lots of options, but which one is really gonna be our go-to option in the developing world? This remains to be determined. So in my opinion, I think it's an outflow procedure. I really think that in order to tackle this problem, it's gonna be an outflow procedure. And I think there's a couple of reasons. Number one, outflow procedures are physiologic, and number two, outflow procedures, I think have the greatest potential for being the lowest cost in terms of tackling this problem. So what I wanna focus on is this gap procedure. Some of you've seen a lot of press about this recently. In this year's Blue Journal, maybe three or four months ago, Ron Feldman's group out of Dallas published their preliminary results that had six months, 12 month follow-up in their population. But before we get into the gap, we need to talk a little bit about glaucoma surgery history in general. There are some major milestones that have really propelled glaucoma surgery. For a while, we've seen just stagnation glaucoma surgery, but recently in the last 10 to 15 years, there's been a real big renaissance in glaucoma surgery. Back in 1857, Von Grave presented at the first international council on ophthalmology, and he presented his technique on erodectomy to cure certain types of glaucoma. At the beginning of the 20th century, the silt lamp was invented. Shortly thereafter, Barkin was able to classify open versus closed-angle glaucoma. In the 60s, Anthony Maltino out of South Africa introduced the first glaucoma drainage device. Shortly thereafter, Watson introduced terbeclectomy, which has remained largely the gold standard for glaucoma surgery and what most trials have been compared to. In the 70s, we had some innovation in medical therapy. Beta blockers were introduced as medical therapy. In the 1990s, Carl Camus was instrumental in developing the pioneering work to propel prostaglandins as one of the major first-line drugs available for medical therapy. Now looking a little bit about terbeclectomy history, particularly in 1891, 1891, David Sintes described incision of the erodic angle. And what was interesting about this is that he described this procedure, essentially it was a goniotomy without a goniotomy lens. It was basically a blind procedure in order to incise the angle. In 1936, Barkin, with his innovation of the goniotomy lens, or gonioscopy lens, was able to introduce the goniotomy technique for congenital glaucoma. He published his results in the 40s and reported on 16 out of 17 cases that were successfully treated with goniotomy. Those cases all had primary congenital glaucoma. In the 60s, there were some advancements made in terms of angle surgery. Smith and Burien described their terbecleotomy techniques simultaneously. Smith was describing a suture technique and Burien described more of a terbecleotome type technique. Over the time, there have been some refinements in terms of the instrumentation. And here you can see the harms terbecleotome. Here's the instrument on the left, down here. And here you can see the instrument actually in action. This is an external procedure in order to be able to cleave the terbecleotomus work. So there's been a new renaissance though in the last 10 to 15 years, what I'd like to entitle terbecleotomy 2.0. And really our friends in Japan take a lot of credit for innovating and really propelling terbecleotomy as a viable technique, not only for pediatric glaucoma, but for a adult glaucoma as well. So now on to the GATT procedure. Gonioscopy assisted transluminal terbecleotomy. The technique was reported in the Blue Journal just three or four months ago by Ron Feldman's group. 85 eyes that underwent this procedure. These patients either had primary open-angle glaucoma or secondary open-angle glaucoma. It was a single-center retrospective non-comparative case series. But what was very powerful was their results. And these are preliminary results that would be looking at these results further down the line with longer-term follow-up. But with patients with primary open-angle glaucoma, their pressures were able to be decreased by 7.7 millimeters mercury at six months and 11.1 at 12 months. Even more powerful were the patients with pseudo-exfoliation and pigment dispersion glaucoma with pressure lowering at 17.2 at six months and almost 20 at 12 months follow-up. And there was no effect at all with cataract surgery as they looked at their subgroup analysis. There really was no effect with concurrent cataract surgery. Treatment failed in approximately 9% of patients. And why did treatment fail? I think Ron Feldman has really encapsulated why this may be the case. If you don't intervene early in advanced glaucoma, especially if you're gonna be operating through the canalicular system and going through the trabecular mesh work route, there is a possibility that with advanced glaucoma, the collector channels have already severely atrophied and sclerose down. So even if you bypass the trabecular mesh work, there may not be enough functioning collector channels to actually cause or lead to a reduced outflow and improve intracular pressure. So I'm gonna show you my first gap procedure done three or four weeks ago with the help of Joseph Chen. And we're just gonna go through this step by step so you can kind of visualize how this procedure works. Just a note, this is an app internal procedure. So trabeculotomy, historically, when used for pediatric cases, was done as an app external procedure. A peridomy was performed, a skeletal cut down or a skeletal flap was performed in order to identify Schlem's canal and then a catheter or a probe was used to cannulate Schlem's canal 360 degrees. So this is done through a temple approach. I've made a paracentesis and then we'll be injecting some lidocaine. The video's hanging up just a little bit. This golasic is injected into the anterior chamber to maintain that space. And that's one really important thing. Here you can see now I've placed a goniatomy lens on the surface of the eye and I'm coming in with an MVR blade to incise the angle. I need to basically create a cleft in order to bring my suture in to the canal. And you notice that there is some blood reflux. One of the beauties of this procedure is that as you decompress the eye temporarily at the beginning of the procedure, the reflux of blood comes into Schlem's canal and can identify exactly where the trabecular mesh work is and where Schlem's canal is. So after I've created the cleft, I'll come in with the viscoelastic cannula to clear the blood away. And here you can see I'll bring the cannula up into the mesh work where I've just incised it and I'm blowing some viscoelastic in order to open the lips of the trabecular mesh work. You can see that by the white behind the cannula right there. So after I've identified that, I've used in this procedure the eye track catheter which is a lighted LED catheter that allows you to be able to follow your catheter externally and know where your catheter is at all times. I'm using a micro instrument by MST in order to guide the catheter into the angle. And just a little bit, you'll see me go in with my micro force up and grab the end of the suture or grab the end of the catheter. I apologize, the video is just a little bulky and hanging up here, it was supposed to be a lot faster than this. There I've grabbed the catheter, it's distalane. And under direct Gonioscopy view, I'll be threading that into Schlem's canal. Now this technique is done with a lighted LED catheter but this procedure can be performed, can be performed just with 6O or 4O polypropylene or nylon suture. But the LED catheter definitely makes it helpful and easier to cannulate and to be able to visualize, I think for your first several cases to know exactly where you are in that space. Just push this a little bit forward. And now you can see just continuing, I'm continuing to thread the catheter into Schlem's canal. And blood is actually a good sign in this procedure. It just indicates that you have a patency of your collector channels where blood is able to reflux back into the anterior chamber. I've turned off the lights in order to be able to find out where my catheter is. And in this step here I'll be retrieving the end. The catheter has gone around 360 degrees inside Schlem's canal now. And now this is the portion where I'm actually cleaving the trabecular mesh work. I'm pulling two ends of the catheter now in order to cleave the trabecular mesh work. Ron Feldman's group has done some scanning EM of patients or I think of research animals and has found that the cleavage site for the trabecular mesh work is actually at the anterior hinge point. And so what happens is the trabecular mesh work lays down onto the surface of the iris and eventually synics there. Here I'm just clearing the microhyphaema or hyphaema out of the eye. And it's very difficult to see in this video but intraop on the table as I've pressurized the eye and increased the pressure into the anterior chamber that is pushing fluid through the trabecular mesh work through Schlem's through the collector channels and blanching the episcletal veins. And so that's basically the GATT procedure. Gonioscopy assisted transliminal trabeculotomy. Here's a picture of what it looks like Gonioscopy-wise. What's described as the trabecular shelf that's created right here. This is the iris over here. And again, it cleaves right here at the anterior portion of the trabecular mesh work. And this membrane will usually lie down on the iris. So what are the advantages of internal trabeculotomy? I think there are many but some of them just to highlight include it's easier to find Schlem's canal at internal than ab external. I've done some canaloplasty work which is done ab external. And it is a very rewarding and fun procedure to do but is technically challenging in order to be able to consistently find Schlem's canal. And I have found that with the ab internal approach the reflux of blood into the anterior chamber or into Schlem's canal really helps to identify that landmark easier. It's bleblis. I personally feel that bleblis surgery is needed in the developing world. There are difficulties with follow up and most of you know that with trabeculotomy the surgery is really not the most difficult part. It's actually the post-operative care in order to be able to modify scar tissue in order to be able to successfully maintain a bleb long term. It's conjunctival sparing. Trabeculotomy in the past had been done ab external where you did need to violate conjunctiva but here the conjunctiva is spared and this allows conjunctiva to be used later if a bypass procedure such as glaucoma drainage device or trabeculotomy needs to be performed. In addition I think it's inexpensive although you do have to invest in a gotionomy lens you do have to invest in some micro instruments. These can be reused and really the only thing that's a consumable item that you need to buy and purchase is viscoelastic and suture. It's physiologic. It really addresses the main side of resistance what we think is where the main side of resistance is in glaucoma that's trabecular mesh work and it can be performed either 180 degrees or 360 degrees depending on search and preference. And finally the post-op care is tremendously simple. Most of these patients I'm seeing as a typical cataract patient. One day, one week, one month later. And so in terms of the intensity of fallop where we're seeing patients four to six times weekly it has a major advantage of simplifying post-op care. Finally the hypotony risk is really remote and really boils down to the fact that you have episcopal venous pressure still maintaining pressure in the eye and that unless the major reason for hypotony would be just leaking wounds after the procedure. So really hypotony is a very remote risk. Here you can see a device on the bottom right. This is a new device on the market entitled the Trap 360. It is basically a trabeculotome. It's a device that can go ab internal to cannulate Schlem's canal and then a proline snare is inside of that that you roll out in order to be able to do a trabeculotome, either 180 degrees you can flip it over inside the eye and then do the other 180 degrees to complete 360 degrees total. What are the disadvantages of ab internal trabeculotome? Requires a clear cornea. So there may be times when you don't have a clear view. This can be obviated here in the States with the use of an endoscope but in the developing world where endoscopes are hard to come by this would be a major problem if you did not have a clear cornea. There is a learning curve. There is a learning curve in order to be able to do intra-op gonioscopy but it is something that is, I think with practice is easily attainable. You need micro instruments. These can be expensive but again these are reusable items. It's not titratable like a trabeculotome where you can cut sutures in order to be able to titrate the final pressure as well. Hyphaema is a common problem every patient that I've done this procedure on now has had a microhyphaema. For some patients it's been very small and for other patients it's been more significant and a lot of patients I think find this disturbing where their vision has decreased after the procedure but these usually go away within a few weeks. So in conclusion I don't know what the alternative is to SICS for glaucoma in the developing world but I'm certainly interested in finding out. I certainly think that there are challenges to glaucoma care in the developing world and I don't think bleb surgery is the way to go. I do believe that glaucoma drainage devices do have a role to play. For example if you've done a gap procedure on a patient and there really has been no response I think you can safely assume that the normal collector channel system is not working. In that case it would probably be prudent to bypass that and a glaucoma drainage device I think in the developing world would be the way to go. AuroLab has produced basically a knockoff of the bare valve which I believe is running anywhere between $20 to $30 for a glaucoma drainage device. That is a major improvement in terms of being able to supply glaucoma drainage devices to the developing world. So little by little we are making progress in terms of tackling glaucoma in the developing world. There's still a lot of progress that needs to be made. A lot of metrics that need to be measured in order to find out which is the best procedure and we can basically say that it really depends on the particular population. I think in Asia where there's a significant amount of angle closure glaucoma we've seen reduced rates of angle closure glaucoma because of FACO and because of cataract surgery. Early intervention seems to keep patients in those parts of the world from developing severe angle closure glaucoma. So with that if you have any questions be happy to answer those now. Very few. It was mainly an adult population. Yeah, where they had the biggest results were in the secondary open angle glaucomas. Pigment dispersion and pseudo-exfoliation. Yeah. And it's a tough glaucoma. Very tough. It's a malignant type of glaucoma. Those of you that have traveled down there with me it's routine for us to see patients in their 30s and 40s with pressures in 50s with cupped out nerves and already unilaterally blind in one eye. Very devastating type of glaucoma. You know, I haven't seen a lot of 2020 patients down in Haiti with glaucoma. Oftentimes they're hand motion, LP, 2080, 2060. Once in a while we're surprised that we have a patient that's 2020 but that's usually just in one eye. And you know, obviously we're in a referral center where we're seeing the worst of the worst. I'm sure there's plenty of glaucoma out there that is undetected and untreated. And I think that's an important part to talk about with tackling glaucoma in the developing world. We not only need a surgical solution but it needs to be a major public health campaign to identify patients early, to promote screening and to get people in early. Because I think with a lot of these procedures if you don't intervene early enough it doesn't really matter what happens. And then you're left with options like trabeculectomy or glaucoma drainage device. But if we're gonna try to do a physiologic type procedure either using a mixed device or a canal-based procedure like the GAP procedure I really feel like you need to do it early on while collector channels are still flowing. I said I'm taking these drops. Just a little thing about mixed devices. I think some of you are interested in expanding your repertoire and using mixed devices like the iSTEN. There's been a lot of criticism I think of using a single iSTEN with mixed results. In my own personal experience I haven't done very many of the iSTEN maybe 10 or so patients. And some of them have been home runs and some of them have been duds. And I think that really boils down to where you're placing that stent. If it's close to a functioning area, close to a collector channel that's still working I think you'll see some decent results. One of the beauties of the Hydrus MicroStEN it's really like an iSTEN as Alan likes to call it a iSTEN on steroids. You're recruiting three clock hours with the collector channels with one device. And in my limited experience using that device I've seen some very profound drops in IOP. Alan probably you too, but 40, 50% dropped in IOP just with a single Hydrus stent. And that's as in standalone procedure without cataract surgery. Case closed.