Minimally-invasive glaucoma surgery (MIGS) is the term used to describe the rapidly evolving group of alternatives to conventional glaucoma surgery. During this webinar we will discuss the current status of MIGS including the Who & When (patient selection), the What (MIGS definitions), the Where (MIGS-related anatomy and physiology) and the Why (review of the peer-reviewed MIGS literature). We’ll also review basic techniques and steps that surgeons considering getting started with MIGS can try out and practice in their operating theatre.

Lecturers: James D. Brandt, M.D. & Michele C. Lim, M.D., Tschannen Eye Institute, University of California, Davis, Sacramento California USA

Transcript

DR BRANDT: Hi, everybody. My name is James Brandt. Sitting next to me is Dr. Michele Lim. And just so you know who we are, we’re both at the University of California, Davis, at the Tschannen Eye Institute. We’re both glaucoma specialists, and we are both also volunteer faculty with Orbis International, which is our connection in part to the Cybersight program, and we’re happy to talk with you today about MIGS and perhaps how you might want to get started doing some of the MIGS procedures in your own practices. These are our financial disclosures. I’m involved with several of the companies, including those that have MIGS products or MIGS products in the pipeline. And Dr. Lim works with some of these companies as well. And I was taught as a young person when presenting a story — this is nothing less than a story — to always teach or organize my talks around the five Ws, of the who, what, when, where, and why, to tell a story. So we’re gonna do that today. Not necessarily in that order. And we’ll cover the why of MIGS, the what and where of MIGS, and then the who and when. And you can read faster than I can talk, in terms of what we’re gonna cover in those overviews. So let’s start off with why. We have a treatment paradox in glaucoma. Specifically, we have great medical treatments for the disease that are highly effective, and yet our patients don’t take their drops. And we know that many of our patients — at least half — don’t take their drops, and much of the progression of disease that we deal with is related to this. So why don’t we do surgery? It is in many cases a surgical disease. And yet we don’t do surgery as the primary treatment in part because of these sorts of things. We have infections, late term infections, from trabeculectomies, and with hardware we sometimes see erosions of the various drainage devices that we use, and so there are obviously problems with the surgery. And we have a large group of patients in this group, including, as you can see here, the patients that are targeted with various MIGS approaches. Those patients with low severity glaucoma, and even up to moderate severity glaucoma comprise the — at least half if not the majority of the patients who have glaucoma that need treatment. So MIGS hits that sweet spot of the patients with low to moderate severity glaucoma that need something surgical, especially if they’re non-adherent with their topical treatments. So what are MIGS? As you know, MIGS stands for minimally invasive glaucoma surgery, and this comprises this group of procedures that avoid the complications and relative unpredictability of conventional glaucoma surgery. They’re designed to preserve as much of the conjunctiva as possible, and the purpose of preserving the conjunctiva obviously is to preserve options for later on. The MIGS can be designed to use an implant that stays in the eye or a surgical device that incises or excises or ablates tissue, and at least in the United States, most of these procedures were designed or regulated to be done at the time of cataract surgery or in pseudophakic eyes. And we classify the MIGS based on the anatomy and the approach and whether or not there is an implant. The classification also is based on the anatomy. So the anatomy, meaning where the device or the procedure is located, either in the canal, the suprachoroidal space, or fistulizing surgery. So let’s start with canal-based surgery. And specifically incisional canal-based surgery. One could argue that the goniotomy, which was designed and developed in the 1940s, believe it or not, is the original MIGS, and is still, I would argue, quite relevant today. In part because it is the least expensive of all the MIGS. You only need an operative gonioprism, which starts cost-wise $200 to $300, and can be resterilized and reused many times. A little bit of viscoelastic, and a disposable needle. It is effective in juvenile glaucoma, steroid induced glaucoma, and some forms of uveitic glaucoma, and I would argue that you need the skills to do a goniotomy which are foundational for the other canal-based MIGS. Later failures of goniotomy are believed to be due to closure and scarring of the trabecular meshwork leaflets, and so we also think about excising rather than incising tissue in some of these procedures. GATT is another procedure that incises the trabecular meshwork. And this is a procedure that was developed several years ago, by the group in Texas headed by Davinder Grover, and I would be happy to send people copies of the original reports of this procedure, but it basically involves cannulating the canal of Schlemm to 360 degrees using an ab interno approach, and I’ll show you a quick video of this procedure. We use the iScience canaloplasty catheter, which makes the procedure expensive, but with some experience, you can do this procedure with a simple nylon or prolene suture. Here is a quick video — I’ll speed it up here, in the interests of time. But you can see that we can incise the canal of Schlemm, feed this catheter into the anterior chamber, and much of this procedure, as you’ll see in all of these MIGS procedures, is learning the ergonomics of the procedure. How to hold your hand. Where to approach, and so on. Here I’m using an MVR blade to incise the trabecular meshwork. And you’ll see in a second we approach the meshwork at the anterior edge of the meshwork, and peel the trabecular meshwork down. Again, I’ll speed things up here. And the catheter is advanced into the canal of Schlemm. And with the blinking light, you can see it advance all the way around the canal, until it comes around, and here you can see it reappearing as it has traveled 360 degrees. The device is grasped and pulled out of the eye, and here you’ll see… Speed this up here again. The device is used to pull and essentially create a 360-degree trabeculotomy. And you can see what is left behind is an open canal and some bleeding in the anterior chamber angle. We also do these procedures in babies, and here you can see some results that show the open canal. And the results are quite promising and quite good in young children. Another approach is to use the Trab360 device, which is a device specifically designed for doing two 180-degree trabeculotomies to open the canal, and these are particularly useful in children. Here you can see a case done on the Flying Eye Hospital with Orbis a few years ago, and again, in the interests of time, I’ll speed this up a little bit. Making two side ports, filling the eye with viscoelastic, and then inserting this device and with the Gonioprism… Advancing this device, which inserts a small suture into the canal of Schlemm, the thumb wheel on the handle of this device advances the blue-dyed nylon into the canal of Schlemm, and in a second, you’ll see it advance into the canal. This is also a very useful device for treating juvenile glaucoma, steroid-induced glaucoma, and in this case pediatric glaucoma. And in a moment, you’ll see how one can — once this device is in place — the device can be used to tear open the canal, and with some practice, this can be done 180 degrees. You then flip the device open and recannulate the canal in the opposite direction. So these are among the more invasive of the MIGS, but they still qualify as MIGS in my opinion, because they are ab interno, they avoid violating the conjunctiva, and with skill, they can be — with some experience — they can take just a few minutes, and open up the canal very nicely. So we don’t know why these incisional angle surgeries fail when they do. Do they fail due to scarring or closure of the trabecular meshwork? And we don’t know whether the mechanisms of failure are different in younger patients, compared to adults. But we don’t know also whether or not removing or ablating the tissue is preferable to simple incisions. And there are several ablative canal-based procedures. They include the trabectome, which is an ablative procedure that uses a special instrument that cauterizes the tissue as it goes through the canal of Schlemm. The results in the early 2000s looked very promising, but the device is not as popular as it once was, because it is indeed quite expensive. There are excisional canal-based surgeries, including the Kahook Dual Blade device, which scrapes along the canal, and is designed to scoop out the trabecular meshwork. This device has been very promising, and there are some good results that have… I’ll turn off the sound from this video that is on the website for the device. But here you can see it scrapes along here, and excises a very nice piece of trabecular meshwork. The preliminary results for this device are very promising, as I said. And here are some publications. One of the few that has been published looking at the intermediate-term results, just out to six months. There are no head to head comparative studies, either retrospective or prospective. And as I pointed out earlier, the mechanism of action and in fact the mechanism of failure for these various procedures is probably different among the different types of glaucoma. And important to our global audience here today, the cost spread for these different devices is very significant. All of them require an operative gonioprism, which can be disposable or reusable, and a goniotomy is the cheapest of all, where the only disposable part of the procedure is a 25-gauge disposable needle, and then the rest of the procedures ramp up, as seen here, with Trabectome having a reasonable per-case cost, but you need to buy a $30,000 or $40,000 machine to drive the thing. So implant-based MIGS will — I’m gonna ask Dr. Lim to take over at this point. And discuss the various implant-based MIGS from now.DR LIM: All right. Thank you very much, Dr. Brandt. That was an excellent review of those different devices. So as Dr. Brandt mentioned, I am gonna talk about implant-based MIGS, meaning devices that you actually can implant, either ab interno or ab externo. So I wanted to just give you an outline of what I’m gonna be talking about, and to set the scene, in the United States we have these tough federal regulations from our government that have to be satisfied before we can bring a new device into clinical practice. And so there was a paper published in 2015 that talked about a suggested study design to try to get more standardization in the preparation of getting these devices onto the market. And so I’ll be talking a little bit about that, and then I’ll go through some of the ab interno procedures and some of the bleb-based MIGS that require antimetabolites. This was a paper published in 2015, with guidance for both industry and also FDA staff. What their recommendations were: To include patients that must have glaucoma, and that might sound a little bit funny. Why wouldn’t you study people with glaucoma? But a lot of the early studies, with earlier MIGS that have come out in past years, included people, for instance, with ocular hypertension, and perhaps even glaucoma suspects. So their definition of glaucoma is pretty standard. They use both visual field parameters and also optic nerve findings that I’ve written a few details here to guide people as to who should be in a study. So that recommendation that you should include somebody who doesn’t have an MD or a mean deviation worse than -12 is a good one, because you don’t want to use a device whose outcome you’re not sure of in people who have really severe glaucoma. These are suggested effectiveness endpoints, and by effectiveness endpoints, that means: What do you really need to see in a procedure to know that it has a beneficial effect for your patient? So one, the patients should be followed a minimum of 12 months, and more if possible. Medications should be washed out at baseline. And the primary endpoint that was suggested was the percentage of subjects whose pressures were reduced by at least 20% or more. In a mean diurnal pressure reading. The secondary endpoint is to have a mean diurnal pressure change from baseline, and I’ll be going through some literature to show you how that’s published in the data. The original iStent — maybe some of you have had some experience with. So I was going to just bring that up, and show you the difference between the original iStent, and what’s out now, which is the iStent Inject. So the original iStent is just one stent that’s implantable. In the United States, at least, we are only allowed to implant these as part of cataract surgery. And this is just an example of what the device looks like once it’s implanted. You see just this little metal snorkel that sits in the angle, right at the area of the trabecular meshwork and Schlemm’s canal. So the iStent Inject is a newer technology that is evolving in the United States. It consists of two stents. They actually look like little earrings, and are actually supposedly easier to place in the angle. This is the data, and I apologize — this probably looks very small on your screen. But this table is meant to point out that there are different studies comparing one iStent versus multiple iStents, versus the injectable stents. And so the different categories are here. What you can see is that, with more implantation, with the implantation of more devices, the percent lowering of pressure is more profound. I wanted to concentrate on a couple of studies. So this one is iStent Inject. These are prospective studies. And these are iStent Inject, combined with cataract surgery. There are two studies. One had a washout of medication at baseline. The other did not. They both published results on what percent of patients reached 20% or more reduction of pressure from baseline. And not surprisingly, the first paper that had washout of medication had a higher percentage of participants that reached that 20% reduction. What I also wanted to point out is the final pressures that were reported at 3 and 4 years after surgery. And you can see they’re in the mid-teens. These are two other studies that I wanted to show you. These are iStent Inject, implanted by themselves. So there was no cataract surgery involved in these patients. First of all, who are the patients included in these studies? They were patients with open-angle glaucoma, and in one study, they had to be on at least one medication, and in the other study, on two medications. They both had washout of medications at baseline. So in the first study, by Fea et al., it was actually a prospective randomized study. Patients were randomized to either receive the iStent Inject, which, again, to remind you, are two implants, versus patients who were randomized to receive two glaucoma medications. And in the second study, by Voskanyan, this was a comparative study, so the patients just received the iStent Inject. And these are the outcomes. So the percentage of people who reached a 20% or greater lowering of pressure was quite high, both in the iStent group and in the patients that were randomized to medications. And so what the authors concluded in the study was that the efficacy of iStent was at least as good as putting a patient on two medications, and as Dr. Brandt pointed out earlier in his talk, for the purpose of keeping patients adherent with their medication, it might be more beneficial to implant the stents and not worry about whether your patients are taking the medications or not. So in the second study, 81% of patients reached that 20% reduction, and that was with or without medications. And finally, at the 12-month postop time point, the mean intraocular pressure was actually quite low in the first study for both groups, and fairly low in the second group. Perhaps there was an advantage to the iStent Inject versus implanting just one iStent. There were adverse events reported in iStent papers. As a generalization, I would say that there are not a lot of adverse events that are reported. But of the ones that were reported, these three were probably the most prominent. One, that the iStent was injected, but not visible. That there was an obstruction over the stent, and that the patients had elevated pressure after implantation. Next I want to talk about bleb-forming MIGS. And these are really exciting technologies that represent the newest of the devices that are coming out here. These are the characteristics of these MIGS. One is that there is external bypass of the aqueous humor flow. So we’re not talking about implanting something in the trabecular meshwork, but bypassing that area altogether. There is bleb formation, and these procedures do require the use of mitomycin to suppress fibrosis. So when you look at those three things, you’re probably scratching your heads and wondering… Well, why are these MIGS? They sound just like a trabeculectomy or a glaucoma drainage device. I’m gonna show you why. Because there is minimal disruption of the conjunctiva and sclera in these procedures, and I’ll demonstrate those for you, or talk about them. The first technology is called the XEN Gel Stent. This is a product put out by Allergan. It’s a gelatin material derived from porcine dermis. The device that’s being marketed in the United States at this time has a 45-micrometer lumen, and this is the size determined to prevent hypotony. It is designed for an ab interno approach. Very challenging. So here are the Gel Stent studies. And these are several that have been published. I just wanted to point out to you that the first couple of studies used the stent with the larger lumen, and the latter studies used the 45-micrometer lumen. What you see is that the pressure reduction is quite remarkable here. I wanted to concentrate, however, on one particular study, because I think this study was well designed, and it was also the pivotal clinical trial used for our FDA approval in the United States. This paper was by Davinder Grover from Texas, and colleagues. It was a prospective multicenter nonrandomized trial. What is unique about this paper is that it was a standalone procedure performed in patients with refractory glaucoma, meaning glaucomas that were very difficult to control. And when you look at the history of MIGS, the iStents and over things like that, most of the patients enrolled in those studies were patients that had very, very early forms of glaucoma. So these are tough patients that we see in our glaucoma clinics. The inclusion criteria really demonstrates how tough these patients were. They were patients that had prior filtering or cilioablative procedures, meaning cyclophotocoagulation, or they could be uncontrolled on maximum medications. 84% of these patients had prior glaucoma surgery in this study. Here’s the study protocol. There was in this protocol a small conjunctival incision made, and the reason why that had to be done was to apply mitomycin with sponges. So in the United States, the only FDA-approved method of applying mitomycin is through this type of sponge procedure, which is considered standard and traditional. Although now a lot of people apply mitomycin as an injectable, and that’s an off-label use. So the implant is still inserted ab interno in this study. And this just shows you how much of the stent was visible both inside the eye and outside of the eye. Here are the primary and secondary endpoints. So again, they adhered to the 12-month minimum follow-up. And you can see that 75% of patients achieved a pressure lowering of greater than 20%. The secondary endpoint is changing pressure from baseline at 12 months, and again we see a marked decrease in pressure. This is the mean pressure reported in the study, and again, you’ll see at the 12-month time point that the mean pressure is almost 16 millimeters of mercury, so mid-teens still. To put that in perspective, I want to compare it to what you get from trabeculectomy. You can see that the pressures achieved with trabeculectomy and mitomycin C are still quite a bit lower than what was reported in the Gel Stent study. The safety profile seems pretty reasonable, based on complication rates. A couple of note, however. There was a significant needling rate. And when you hear surgeons talk about their XEN Gel Stent experience at meetings, they will definitely mention that needling rate is pretty high. So now actually there’s a lot of chatter going on in the United States and internationally about inserting the Gel Stent from outside of the eye, which was not the original intent, but there might be an advantage here, in that you can leave part of the stent outside of the eye above the Tenon’s layer, and it’s been identified that Tenon’s obstructing the Gel Stent might be why there is so much needling needed when injecting ab interno. Other adverse events that have been reported are pressure rise, low pressures, and wound leak. Although I would say in this study, because they had to open the conjunctiva, this may be the reason for the wound leak. And you might not see that in the traditional implantation of the Gel Stent. So one shortcoming, I think, of this paper, is that there was no information on bleb appearance. Why that’s important to me is that some of the advantages of these new devices is that the bleb phenotype or the appearance of the bleb may be different than what we see in trabeculectomy, and because of those differences, we may be able to avoid some of the trabeculectomy complications. I did find this paper evaluating specifically bleb morphology after the Gel Stent. And they did grading of the bleb, they also used confocal microscopy to look at the wall of the bleb, as well as anterior segment OCT. So what these investigators found is that the bleb had a focal appearance. It was low in height. That low profile is good. And vascularization was minimal. Also that the borders were diffuse. So with confocal microscopy, they found that the stromal density of the bleb wall was lower in the success group, and with anterior segment OCT, a higher bleb wall reflectivity was seen in the failure group. I next want to move on to the InnFocus MicroShunt. This is not yet approved in the United States, but is being implanted in Europe and other countries. This is what the implant looks like. It’s made out of a material called SIBS, which is a plastic-like material. It does require the use of mitomycin, because you’re shunting fluid out into the subconjunctival space. And so in initial studies, mitomycin was delivered by sponge. This is my crude drawing of where the implant sits in the eye. Because I wanted to point out that the outflow portion of the implant, which is posterior right here, pushes fluid out kind of in the area of the superior rectus muscle. And we’ll talk about why that might be important later. So this is a video kindly provided by Dr. Brandt, and what we see is that we incise the conjunctiva, to be able to get into that subconjunctival space and apply mitomycin with sponge. There’s a special 3-millimeter ruler that comes with the InnFocus, and also a special needle and blade device that makes the tunnel into the anterior chamber. And you can see it’s a long tunnel through the sclera, which is nice, because it’s going to protect the implant from erosion years down the road. You can see the surgeon carefully inserting the knife to achieve a position in the mid-anterior chamber. You don’t want it too close to the endothelium nor too close to the iris. Next, here’s the implant. It’s plastic and it looks like a little spaghetti noodle here. Next the surgeon is implanting the device very carefully here, and the device has this kind of arrow-like flange that helps seat it in the tunnel that you made here, and prevents it from either migrating forward into the anterior chamber or migrating out of the anterior chamber. And as I pointed out before, the posterior part of the implant device puts fluid out right around the superior rectus muscle. Here you can see that there’s aqueous already emanating from the implant itself, and you can see it trickle out onto the Weck-Cel here. So the next step would be to carefully tuck the posterior part of the implant underneath the Tenon’s and conjunctiva, and then do a watertight closure, as you would do with a fornix-based trabeculectomy. That was a nice case, Dr. Brandt. Here you can see how the tube sits in the anterior chamber. It does have sort of a long passageway into the eye. My preference would be that it would be shorter, but because the flow characteristics are dependent on the length of the tube, the tube has to be a certain length here. So you can see it right there. As I said before, this is not approved in the United States yet, but there is a randomized, multicenter study that’s ongoing. UC Davis is one of the clinical sites. And the patients are randomized to either receive the InnFocus MicroShunt or trabeculectomy. So this is a true head to head competition with a device that is competing with trabeculectomy for those very low pressures. There is a study out there in the literature that you can find, published by Juan Batlle from Puerto Rico and colleagues. I’ll show you what the findings were. It was a retrospective study. It was a little bit of a mixed bag of study eyes, because some of the patients had combined cataract surgery, and others had just the implant. It was a study in which there was a small number of patients enrolled, and it was single site, with one surgeon performing the surgery. These are very, very impressive results, very exciting, but couched with the fact that the sample size was small. So there are few patients in this study. And also that you’re looking at both cataract and standalone procedure. But you can see the pressures are very low. And we’ll see what the FDA clinical trials show us. So at three years, 82% of patients had pressures less than 14 without medication, and 95% with or without, which again, is quite impressive. As far as complications go, tube touch to the iris was noted in 13%. Some patients did suffer from hypotony. So you can see shallow or flat anterior chambers were noticed in some of these patients, and also transient hypotony, but those resolved. This paper was good, in that it did provide bleb grading characteristics. So they used the Indiana bleb appearance grading scale. The grading was done with photographs, not live at the slit lamp. And at three years, what the study published is that the blebs were low profile, small in area, and minimally vascular, which are all characteristics that are very advantageous for your bleb, to avoid erosion and leakage. So here are photographs published in the study, and again, what I wanted to point out is that the bleb formation is more posterior to what you would see in a trabeculectomy. The trabeculectomy blebs, of course, hug the limbal line a little bit more, and why is this advantageous? Because there’s more protection from the eyelid, when the bleb is posterior, just like in a glaucoma drainage device. And I think the incidence of erosion and leakage may be less in a bleb like this. You can also see that it’s not avascular. That there’s a minimal amount of vascularity, which will also prevent it from leaking in the future. And again, I wanted to point out: You may be seeing these more posterior blebs because of where the aqueous humor is put out, at the end of this tube device here. So again, the questions that I would ask myself about both the InnFocus MicroShunt and the XEN Gel Stent are: Are the bleb characteristics different from trabeculectomy? Rating of bleb position in relation to the limbus would be helpful, and how would injecting mitomycin change things in these studies? So if we have time, Dr. Brandt, I would like to end my portion of the talk with the CyPass story. I guess you could also call it… MIGS gone awry. So I don’t know if people have heard of what’s happened with CyPass. That it has been recalled from the market. Just to remind you of what CyPass is, this is a suprachoroidal shunt. So it’s placed to purposely create a cleft from the suprachoroidal space, to promote outflow and low pressures. And this is the design and how it looks in the eye. It kind of sticks out a little bit there in the angle. The device recall was voluntary by Alcon. It occurred in August of last year. And it was followed up by an FDA warning and recommendations in September and October in the United States. So the initial study for CyPass was called the COMPASS study, and the COMPASS study lasted for 24 months, and it showed very good results with a very low complication rate. But the company to their credit decided to carry out the COMPASS study further. They called it the COMPASS XT study. You can see the number of patients enrolled in that was less than the original COMPASS study. There was patient dropoff at that point. And the visits were carried out to 60 months. What we see in these two graphs is that there’s a problem with the endothelial cell count in the corneas of these patients. You don’t see them in the first 24 months of the study, but as we get out to months 48 and 60, we begin to see a significant difference between patients receiving CyPass, which is the blue bars, versus patients that were control, which is the yellow bar. Those were patients receiving cataract surgery alone. In the first graph, you see that the endothelial cell loss is much greater in the CyPass group, versus the cataract surgery-only group, and in the second set of data here, you see that the proportion of patients with greater than 30% loss of endothelial cells was greater in the CyPass group again. And what is that magic number of 30%? It’s actually the threshold at which it’s considered a meaningful loss of cell population. So what the company does point out in their data is that if you look at the subjects with endothelial cell loss greater than 30%, there was really no impact on the clarity of the cornea. With the exception of one patient, who had corneal edema at month 51. This was assessed by the investigator. The implant was trimmed. And the edema resolved, fortunately for this patient. They did a risk analysis study, and what they found is that the number of rings visible in CyPass correlated to the endothelial cell loss, and so the greater number of rings visible, the greater the cell loss, which makes sense. Because that means the implant is sticking out further, and probably touching the cornea. This is a really nice table put out by George Durr and IK Ahmed in Glaucoma Today. You can find this on the internet. And it does a comparison of not just CyPass, but other MIGS devices out there, specifically looking at endothelial cell loss. And so you can see with the iStent Inject and the Hydrus, there is no significant difference between control and treatment groups. CyPass, we know there is a significant difference. And there are many devices for which we don’t know the results yet. So how does MIGS endothelial cell loss compare to traditional glaucoma surgeries? Because I think this would be a fair comparison, to look at CyPass versus trabeculectomy and glaucoma drainage device. These results were published, again, in George Durr and IK Ahmed’s paper, and they do show that the rate of loss in CyPass is similar to — definitely the glaucoma drainage devices, in which you have a tube in the eye, and perhaps a little bit more than standard trabeculectomy, in which there’s no device. So once this recall came out, a lot of surgeons were taken by surprise, because this is the first device recall in the history of glaucoma surgeries. And surgeons were asking themselves… Well, what do we do now? And these are questions you should be asking yourself, if you plan on embarking on a MIGS device. So the recommendation is that the device should be evaluated with gonioscopy. And what their findings were — were that 15 subjects were noted to have actually a change in the number of CyPass rings visible. So these were patients that were followed from visit to visit, and there’s a question about whether the CyPass can migrate. So 7 patients had more rings that were visible with each successive visit, but also 7 patients had fewer rings visible, and one had one that had variable ratings. So their recommendations are to do gonioscopy in your patients that have received CyPass, to note the position of the rings in relation to the cornea, and also to consider if you have at your disposable these devices, corneal pachymetry, and also more important specular microscopy, to do endothelial cell counts. There are recommendations of when to intervene. So these are important. They say that in eyes with 0 to 1 ring visible, unless there’s corneal decompensation, you should not intervene or try to do anything with that implant. In eyes with 2 to 3 rings visible, even with those, unless corneal decompensation is present, they still recommend no intervention, but perhaps following these patients more closely. What happens if you do have to revise the CyPass? What do you do then? With greater than 1 ring visible, they say consider repositioning, removal, or trimming the end. For repositioning, the recommendation is to try to push it in deeper, within 7 to 10 days of the surgery. However, if you are further than 7 to 10 days out, fibrosis can form around the implant, or even through the fenestrations, making it very difficult to remove. So in that case, the consensus was to not try to move the device, but to try to trim it, if you do have corneal edema. So I’m gonna turn over this next section to Dr. Brandt on who and when, for patient selection.

DR BRANDT: Thanks, Dr. Lim. So to continue with the theme of who, what, when, where, and why, I would like to go briefly over patient selection for MIGS. Again, emphasizing that most of these devices are designed for the low severity to moderate severity glaucoma. However, the fistulizing procedures or the bleb-forming procedures that Dr. Lim reviewed are more likely to be used for the more severe forms of glaucoma, patients who need much lower intraocular pressures. So to summarize patient selection, all of the canal-based and suprachoroidal MIGS devices are approved at least in the United States for adult patients who have mild to moderate disease, and they also need to have open anterior chamber angles. And again, in the United States, these were regulated primarily and approved to be implanted at the time of cataract surgery. That’s not necessarily the case outside the United States, where many of our audience today are watching from. The canal-based incisional surgeries that I started off with can be used in a variety of other glaucoma diagnoses, and they are my go-to procedures for juvenile open-angle glaucoma, steroid-induced glaucoma, and others where the assumption is that the primary blockage or cause of the elevated pressure is in the trabecular meshwork. And finally, the bleb-creating MIGS are those that can be used in more advanced disease, but again, we have very limited long-term data, and we do not have head to head comparisons to trabeculectomy. At least, until the regulatory trial for the InnFocus MicroShunt is released hopefully in the next couple of years. So when Cybersight asked us to give this talk, they emphasized to me that many of the people in the audience are people that are thinking about getting started with MIGS. So we do have some suggestions. On how to get started with MIGS. And first of all, you’re already starting by attending this lecture and other lectures. And many of the companies that design these devices and market them will provide hands-on wet and dry lab courses, at a variety of meetings around the world. Also to get started: Do gonioscopy regularly on your patients, if you’re going to be doing them at the time of cataract surgery, and I would also visit gonioscopy.org. It’s wonderful and full of hints on brushing up your gonioscopy skills. Many surgeons have not done it since residency, and it’s really important to recognize the wide variability in the anatomy and pigmentation of the anterior chamber. It’s also worthwhile, if you’re thinking about starting MIGS, to purchase a gonioscopy prism, and start practicing with it in the operating room. I would say when you start doing MIGS procedures, specifically canal-based surgery, it is the ergonomics — how you hold your hand, how you tilt your microscope and the patient’s head — that is often the hardest part of learning how to do this. These MIGS procedures are not outside the realm of an experienced surgeon, but getting the ergonomics right, the hand positioning, and so on, takes a little bit of time to learn. After performing temporal clear cornea phaco, go ahead and have a patient turn their head away from you and rotate the microscope 30 or 40 degrees towards the patient. Practice holding your gonioprism with your non-dominant hand, and the key is to have the gonioprism sort of float on the surface of the cornea, with a generous blob of viscoelastic, so that you don’t distort your view by pressing on the cornea. That takes a little practice to get good at doing that. And then once you feel comfortable with establishing a good view of the anterior chamber, try inserting a Sinskey hook or something similar across the anterior chamber, so that you get that three-dimensional ergonomics. And this will help you learn how to coordinate your two hands without distorting your view. Your first patient should be somebody with a wide open-angle. Somebody who is a moderate myope is probably the best. And I would also suggest considering retrobulbar or peribulbar block for your first few cases, because you just want to have as controlled a situation as possible. And explain to your patient that they’re gonna need to turn their head, so you don’t want to find out in the operating room that they have neck mobility issues. You want to verify this. And I would also recommend doing a dry run with your surgical team. The future of MIGS is very interesting. We’re just at the beginning of what is an exciting surgical revolution in glaucoma. I would argue that many of the MIGS approaches that are being marketed today and promoted probably won’t be in wide use ten years from now. This is a rapidly developing field. And other approaches that we aren’t discussing here are in early stage or regulatory trial development. But what I can confidently say is that we are missing long-term data, and especially prospective randomized head to head comparisons of the different devices, and comparison to each other and to conventional glaucoma surgery. And the InnFocus MicroShunt trial is probably going to be the first head to head comparison of a new device to standard trabeculectomy. So with that, we can close our talk, and start answering any online questions. I think we have about 10 minutes or so to answer questions. And I will wait for us to be able to see.

DR BRANDT: So if you think you need to lower the intraocular pressure, why don’t you do a trabeculectomy or prefer the use of a MIGS? Well, perhaps we’ve answered some of that question during the talk. Ultimately, we want to lower the pressure, and generally lower is better, but not always. The lower and more aggressive you are in lowering intraocular pressure, you then start dealing with complications and problems related to having the pressure too low. Or long-term problems with infection or bleb leaks, and so on. So it is a balancing of risk versus benefit. And the hope is that some of these MIGS procedures will have some improvements on the complication side of glaucoma surgery, compared to trabeculectomy. Do you have anything to add?

DR LIM: No, I think the safety profile is really what you’re after. Because trabeculectomy, while it works very, very well — we all know, as trabeculectomy surgeons, that as time passes, you can start to see more and more complications, such as the bleb leaks and the endophthalmitis. I think also that the recovery of patients from MIGS procedure also tends to be a lot more comfortable and more rapid.

DR BRANDT: And return as part of that recovery — is return of baseline vision is much faster. The patients who have trabeculectomies often are pretty miserable with induced astigmatism, shallow chambers, and all the optical problems that happen with trabeculectomy are eliminated for the most part with the various MIGS procedures. Suitability of MIGS procedures on pediatric patients. I definitely do… I wouldn’t say MIGS procedures — certainly not implant-based MIGS procedures — on the primary congenital glaucoma. But I definitely do incisional glaucoma — incisional angle surgery on the primary congenital glaucomas and the JOAG patients. My go-to procedure is generally a GATT procedure, procedure if I can see into the anterior chamber adequately to do angle surgery. The youngest patient I’ve done a GATT procedure on is about 6 weeks of age, and it really depends on both the view and the size of the eye, to be able to cannulate the canal. The reason that I prefer these ab interno types of circumferential angle surgeries are that it is a definitive procedure for opening up the anterior chamber angle, and let’s face it — as glaucoma surgeons, we are like chess players. We’re always thinking about what’s the next step if this procedure fails, because none of our procedures work forever, with rare exceptions. And in many of these children, we need to be thinking about whether or not we’re gonna need to do a trabeculectomy or need to put a glaucoma drainage device in, and sparing the conjunctiva is advantageous in these patients. So my general approach is to do — try to do an ab interno angle surgery on the primary congenital patients. In terms of juvenile open-angle glaucoma procedures, if they are presenting in their teens or 20s, those patients usually have primarily a trabecular meshwork dysfunction, and doing an angle procedure specifically ab interno, and sparing the conjunctiva, often works and may buy us 5 or 10 years before we need to do anything else, and sparing the conjunctiva is clearly advantageous for subsequent filtering surgery. So what our experience with CyPass… We started doing the CyPass about six months or so before the device was pulled from the market. So I have about a dozen patients with the CyPass in place. The majority of them did very well. We have not seen any problems with endothelial breakdown or loss in our group, but we’re monitoring them every six months with endothelial cell counts and pachymetry. Stay tuned. We have not seen any problems. We have not put in the XEN Gel Stent, because we’re part of the clinical trial group for the InnFocus MicroShunt. And we’re excited about that, but we’re masked as to the results of that trial. Do you have any more comments about that?

DR LIM: Just that there is some exciting news coming out with people who are implanting the XEN Gel Stent externally just really using the needle and not opening up the conjunctiva. And I think some of these are gonna be presented at the American Glaucoma Society that’s coming up in a month in San Francisco. So we’ll have to see how that works out.

DR BRANDT: That’s true, and I think that is a good example of how these devices, when they get approved by the FDA, the FDA regulates the trials, but once they’re out on the open market, surgeons tend to modify how these devices are done. A good example of that is the Express Shunt, which was originally approved as a device to do essentially a full thickness procedure, and that was quickly abandoned, because there were far too many people with hypotony, and it was modified after the FDA approved it for marketing to be placed under a scleral flap, which was clearly not the original intent of the device. But it worked better. And I think you’re gonna see something similar with the XEN Gel Stent and the InnFocus MicroShunt. Within a few years of either of them being approved, you’re gonna see them used very differently than the regulatory trials required. And part of that is because the FDA wanted to do head to head comparisons to trabeculectomy. And they required the manipulation of the conjunctiva to be standardized in both arms of the clinical trials. But that’s not how these devices will end up being used. Are there any other questions? Well, thank you very much for your attention today, and I wish you a good weekend, to everyone from around the world who joined us.

DR LIM: Thank you.

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February 15, 2019

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