Lecture: Evaluating Medical vs. Surgical/Laser Treatment of Glaucoma

>> DR. LOUIS CANTOR: Good day, everyone. Welcome to this morning’s discussion regarding the entire spectrum of glaucoma therapy. This is a very broad topic, so we’ll have a lot to cover and a lot to get through. I’m Lou Cantor, professor emeritus at Indiana University. For those of you who don’t know where Indiana or Indianapolis is, we’re about three hours south of Chicago. I look forward to answering your questions at the end, during the question and answer session. We’re going to talk about how to approach glaucoma therapy. Any of these subtopics, laser therapy, incisional, could probably fill the entire hour. Again, we’re going to try to put some perspectives on things, hit some highlights, and talk about how we approach our patients with different therapeutic approaches and based what’s available in your particular area or region. Here is my disclosures to start with, none of which I believe are especially relevant to the discussion. So let’s talk about glaucoma just very briefly for some background. So glaucoma is a group of diseases that share this common pathway of optic nerve damage and associated visual field loss for which elevated pressure is just a risk factor. We know there are other factors that are going on behind the scenes that are independent of pressure. But currently, elevated intraocular pressure is the only therapeutic approach we have to modify the course of the disease. We know that about 4% of persons, depending upon the studies, that have pressures over 21 develop new glaucoma damage, that a lot of ocular hypertensives per year develop glaucoma. But we also know about one-third of glaucoma patients do not have consistently elevated pressure above 21. So we have to be on the lookout for those patients as we can be fooled. Even patients with high pressures, a third of the time, their pressures may be normal, depending upon when you check them. How is the pressure generated? Again, just some very brief background here. What happens and how is the intraocular pressure modulated. This ties into our therapeutic approaches. Aqueous production is one end of the equation, the amount of fluid being put into the eye. This is produced in the ciliary body, as shown in the image here, in what’s called the nonpigmented ciliary epithelium. There are several methods that do this, secretion being the primary process for producing aqueous inside the high. Aqueous production happens at a certain rate, about two to three microliters per minute. Therefore, given the average eye, the entire aqueous in the chamber will turn over in about a hundred minutes, since the volume of the eye is two to three milliliters. It varies during the day and night. Those patterns are complex in some patients. But it does go down at night. The reason that’s important is, do we want to give an aqueous suppressant at night as a medication when normally the aqueous production goes down by nearly 50% at night anyway, and overall the amount of aqueous produced decreases with age as well. So aqueous suppressants may be less effective when the aqueous production is less. Aqueous outflow, we have the two sides of the equation, it’s primarily the trabecular outflow that determines the intraocular pressure. It’s a pressure-dependent. We’ll look at the medications and how they affect the trabecular outflow. And we’ll also look at the medications that affect the unconventional or what’s called the uveal scleral outflow which accounts for a small percentage of the total outflow of the eye, although it varies in patients. Trabecular outflow increases as the pressure increases. This is a look at our meshwork and the complex channels that fluid has to go through and between before reaching the canal and ultimately exiting the eye in this complex connection with the epi scleral venous system. And all that is involved with aqueous outflow. There’s a lot of areas for resistance, but the primary areas, again, are at the trabecular meshwork and at the canal which can actually collapse, I’ll show a picture of that. And the episcleral venous pressure provides a somewhat lower limit to how low pressure can go without some sort of surgical intervention. And this is, again, the uveoscleral outflow, it goes through the supraciliary and suprachoroidal space. All of this combined leads to the intraocular pressure. In the majority of glaucoma patients, the problem is at the trabecular meshwork in the canal. That’s where the majority of resistance is. There isn’t glaucoma where you make too much aqueous, for example. It’s really an outflow problem. Therefore a lot of our therapies are directed at that. When we start thinking about treating glaucoma, it’s important to think about what’s our goal, what kind of glaucoma are we dealing with. There are various standards recommended through the American Academy of Ophthalmology, preferred practice patterns, and others globally, the American Glaucoma Society, the European Glaucoma Society and so forth. In general, if you have an ocular hypertensive, we’re usually not too aggressive with treatment. We may just observe. If we decide to treat, we probably just want to get the pressure into the low 20s. If it’s above that, 20 or 25% below, whatever their baseline pressure was, that would be a not unusual goal. Most of these patients, quite honestly, I will watch and observe, unless they have a lot of risk factors that suggest to me they’re at high risk of developing glaucoma. In a patient with mild glaucoma damage, which is defined as optic nerve damage but no visible or discernible visual field loss, getting the pressure under 21 with a 30% reduction below baseline is usually considered a reasonable target. For moderate and severe glaucoma, we get progressively more aggressive. And I think it’s important here to also bring up the point that in glaucoma, we have a real tendency to overtreat glaucoma suspects and ocular hypertensives but to undertreat real glaucoma with damage. We need to be aggressive and probably more aggressive than we are, many times, in our patients with moderate to severe disease. Now, there’s some things that may modify what we might think of for the target pressure. If a patient has had a history of a disc hemorrhage, as shown in the image here, a thinner central cornea, we may be fooled by the pressure a little bit. If they have severe glaucoma in the fellow eye, they have a strong family history of blindness due to glaucoma, they’re younger, we may want to set our targets lower, and maybe that patient with mild or moderate disease, we want to treat them as if they have advanced disease and be more aggressive because of factors like this. Sometimes we can be a little looser with our standards as well. If a patient has short life expectancy, poor medical history and status, if their disease is shown to be very slowly progressive or stable, and if they have a thick central cornea, those may be reasons to be a little bit less aggressive with the target for what we want to achieve with the pressure lowering. So how do we lower pressure? How do we start to address it? I’m going to start with the medical treatment approach and run through the classes of medicines. There’s obviously, on a global level, there’s going to be a lot of variability in what’s available, if any medicine are available, or certain medicines. But I’ll give a broad overview that’s certainly representative of what we have here in the U.S. and many parts of the world, but not everywhere. Most commonly, our most common class of medications that are used today, especially as initial therapy, are the prostaglandins, we’ll talk about those. We have adrenergic agents we use in glaucoma. They’re sort of contradictory. We use beta-blockers, particularly nonselective beta-blockers, and also adrenergic agonists. So we have blockers and agonists that are effective. Parasympathomimetic agents. And we have others. We have the newest class, the Rho-kinase class of drugs. We have combination agents. I won’t say much about hyperosmotic agents but they are available for short term emergency treatment or presurgical. So while this is the standard accepted sort of paradigm for how to treat glaucoma, this is under a lot of discussion. Traditionally it’s medical therapy, trying to stick with as few medicines as possible, starting with the prostaglandin. As we’ll talk later, laser has moved up in this paradigm and is being considered more and more as an initial therapy for some patients or at least earlier in the course of therapy, not after you’re on already maximum controlled medical therapy. Surgery, however, for the most part, is still not your first choice, though it may be very effective. We’ll talk about surgery. But it’s where surgery is applied and balancing that with the potential risks of surgery versus the long term benefits. So we’ll talk about this whole scheme as we go forward. So back to medical therapy. As I mentioned, our beta adrenergic antagonists, the beta-blockers, there’s a variety of those that are nonselective. The number one and the oldest in the group is timolol. Betaxolol is for patients that have predispositions for asthma. Adrenergic agents, particularly alpha 2, presented by brimonidine. Carbonic anhydrase inhibitors, we have the oral agents as listed here but most commonly we’re using the topical forms which took many decades to develop. Prostaglandins, again, usually our first line therapy for starting medical therapy. Latanoprost was the first innovator in this class and has changed how we treat glaucoma. Our newest is the Rho-kinase class represented by netarsudil, and again, the parasympathomimetics, represented by pilocarpine primarily. We have a lot of fixed combinations. In the U.S., we have timolol and brimonidine. Latanoprost and netarsudil. And there’s others throughout the world, triple combinations in some parts of the world, although not the U.S. Some patients bring me bottles that have a quadruple combination. I worry about when you start putting too many medications in one bottle. These medications don’t always mix together well. And I think it would be very difficult to get the full effect, if you’re combining too many medications together. And that’s even an issue with some of our fixed combinations of two medicines. There’s evidence that one of our older fixed combinations, timolol and dorzolamide, isn’t as effective as when used separately. Then there’s the hyperosmotic agents for urgent use. I always like to tie the agents back to the mechanism of action, how these drugs work. Cholinergic agents increase outflow. Prostaglandins increase uveoscleral outflow and/or trabecular outflow to varying amounts. The Rho-kinase is a trabecular outflow drug. Then our selective alpha 2 agonists increase uveoscleral outflow. If we begin to think about mechanism, we begin to think, how do I want to use these drugs, how do I want to combine them. I think it makes most sense, and I try to many times, when I’m starting therapy, and particularly when I’m advancing therapy, to think about combining different mechanisms. For example, I’ll try not to add an outflow drug if I’m already on an outflow drug. I’ll try to combine an outflow drug with an inflow drug. I think that in general, many times, we’ll give a better result, depending upon, again, what’s available in your area. It’s just one way to think about our medications, not just haphazardly and randomly, by chance, but to think about the mechanism and to apply that to how we might treat a patient to get the best pressure-lowering effect. The other thing about medications that I want to — and I’m not going to go through these slides in great detail. Lee Alward did a magnificent review of the side effects many years ago. But all our drugs have side effects. We have to keep in mind not only the pressure-lowering effects, but what are we subjecting the patient to. With timolol, the primary ones are cardiovascular, slowing the heart rate, lowering the blood pressure, and pulmonary. There are others as well. If you ask patients, these are — some of these other side effects that I won’t read through all of them, are much more common than you might initially assume, because we don’t ask about them, and patients don’t voluntarily relate these symptoms sometimes. With alpha 2 agonists, decrease in blood pressure, dry mouth, dry nose, drowsiness and fatigue are very common. With the anhydrase inhibitors, we get a fair amount of red eye and we can get a contact dermatitis, hypersensitivity reaction. Systemically, metallic taste is a very common thing that I hear, even when — especially with the drops. But systemically, some patience talk about paresthesia, even with the drops, not just oral medicines. Stevens-Johnson remains questionably associated. But we have to be thoughtful to see if a patient develops severe reactions. Prostaglandins, most of the symptoms are local, ocular, redness of the eye. You get periorbitopathy, darkening of the skin. Iris pigmentation can be seen as well. Artificially in those patients who have light tan high risk to start with. Patients with very blue iris or dark iris typically don’t show this. Systemically it has been associated with some systemic inflammatory systems. These are relatively infrequent. And our old friend pilocarpine has a long list of side effects as well, especially if a patient overuses it. Trouble with vision, some pain around the eye from ciliary spasm, redness of the eye, stinging, conjunctivitis and so forth. So just a reminder that these drugs do have side effects. The Rho-kinase class seems to be very safe systemically but does cause some unique ocular side effects. Hyperemia is not uncommon. Subconjunctival hemorrhage. How do we minimize side effects from our medications? This picture shows two things, I love this picture, because when I show it to people, they say, well, she’s doing nasal lacrymal occlusion, preventing eyedrops from absorbing systemically and increasing the amount of time the drug stays on the eye and penetrates better. The only problem is that’s not what she’s doing. She’s trying to do that, but if you look where she’s pinching, she’s really just pinching the side of her nose. I try to teach patients to do good lacrymal occlusion. You have to push way back deep with a lot of pressure. Most patients just push on the side of their nose like what she’s doing. But what she’s doing, that is as effective as nasal lacrymal duct occlusion. She’s closing her eyes. Simple eyelid closure decreases by 50% the amount of drug that gets into your system, number one, and number two, it allows for the drug to stay on the eye longer and get better absorbed. So just simple eyelid closure. I stopped trying to train patients and teach them how to do nasal lacrymal occlusion because nobody can do it right consistently. But everybody can close their eyes. So we talked about establishing this target, this goal, which is where we want the pressure to be, where glaucoma damage is no longer likely to progress and is halted. Now, let’s move on to laser. And we’ll speak to it for a few minutes. There’s been a lot of changes in how we apply laser. I’m going to stick to open angle glaucoma. There just isn’t time to go through all the angle closure laser surgical options and studies right now. So we’re going to stick to open angle glaucoma. The primary laser that was first introduced for this, now 40 years ago, was argon laser trabeculoplasty, where a small 50-micron spot of argon laser in the range of about seven to — I rarely went over a thousand but you could go up to 1200 milliwatts depending on the pigmentation in the eye. I would usually do 100 spots over 360 degrees and do an entire treatment. I did not like dividing the treatment, because I just wanted to get it done. And you’re supposed to treat the very anterior half of the pigmented meshwork, so you’re sort of half in the pigmented and nonpigmented meshwork, and you get a bubble formation. That would sort of be our endpoint because the laser energy would be absorbed and cause a tissue reaction that I’ll show you in a minute, and that would ultimately lead to the effect that we would see about a month later, as it has time to take effect. This is what the gonioscopic picture of the laser spot looks like. That’s not great focus, but oftentimes it’s hard to get that really well-focused and to get it right in the right spot on the meshwork. More recently, we’ve had the SLT laser, it’s called Q switched laser. It’s actually a 532 laser that is frequency doubled to give it 1064, which is infrared. It’s got a 400 micron spot. And again, I usually apply 100 spots over 360 when I do this treatment. This is comparison of the size of the ALT, the argon laser trabeculoplasty with the white dots, versus the SLT, which is 400 microns. Most people have been astonished when they think of this. With the ALT, placement of the spot was very important and is very important, if you’re using that laser, because you don’t get it in the right place, it won’t do anything. With the SLT laser, the spot is so big, it’s almost impossible to miss the meshwork. And you’re just trying to get the laser energy in there, and it works by a different mechanism. So the SLT laser is more forgiving and allows you to have greater assurance that if you’re looking at the meshwork and you’ve got your spot reasonably well centered, you’re going to hit the meshwork, you just can’t miss it. This is what the ALT laser does on scanning electron microscopy. It creates a thermal burn, as shown in figure A there. There’s a higher magnification view of some other parts of it. But look at figure A there on your left. That’s what the argon laser trabeculoplasty does, it creates this coagulate burn, versus SLT, where the laser energy is absorbed within the trabecular meshwork cells, and it initiates a sort of a biologic cytokine response that brings in various factors to help clear up the meshwork and open it up without the thermal energy burn of the meshwork. So for this reason, one of the primary advantages of SLT is that you can repeat it. SLT and ALT work the same as an initial treatment. There’s no studies that show any different effect as primary laser treatment. However, SLT is a bit more effective and safer for repeat treatment. And we’ll talk about that a little bit more in a second. Here’s one of the early studies looking at SLT laser. And this is looking at SLT laser as well as patients who had a repeat, who had a prior ALT laser and got an SLT as a secondary procedure. You can see it works the same. So it works very well as a repeat laser for most patients. Most recently, just in the last couple of years, we’ve had the LiGHT trial which looks at primary SLT versus eyedrops for treatment of glaucoma. This was a large study, over 700 eyes, standard randomization, you know, moderate to severe glaucoma, some ocular hypertensives who elected for treatment as well, and the pressure ranges are given. The majority of the patients throughout the study had just one laser. Medication burden was reduced. They got good pressure-lowering. And disease progression seemed to be improved or better, lower, in the SLT group. And it seemed that the patients who started with eyedrops were more likely to need surgery. This is looking at repeat laser from that study via — the red line represents repeat, so you can get good success. This shows as the SLT laser, primary laser, begins to stop working, which they can do over time, over a year or two, the average is about 50% of the time the pressure is creeping back up after two years. You can repeat the laser and regain a good response for repeat laser. So the take-home points from that study were that patients may be offered laser trabeculoplasty as a primary therapy, and this represents a big change. Still today, though, a majority of patients will opt for, and certainly the patients I treat opt for at least trying a drop or two first, but laser is certainly reasonable to consider earlier or as primary. Patients with severe disease did worse regardless of medicine or laser. You can repeat it. It seemed to be pretty cost effective compared to drops. Again, depending upon what the situation is with the availability, cost, generics for medication in your region. It’s typical after these — in this side note, to check these patients after a month. That may not be necessary, but I still do that. Now, what about beyond laser? Let’s talk about surgery. Incisional surgery. The biggest change in glaucoma has occurred here with the evolution and introduction over the past decade or so of the microinvasive glaucoma surgical approaches, the MIGS procedures. So what is a MIGS procedure? These microinvasive glaucoma surgeries. They’re designed to be clear corneal with minimal tissue manipulation, safe, rapid visual recovery, and of course to lower pressure and be efficacious. There’s a whole classification of the use of these different devices now. Steve Vold did a nice summary a few years ago. This just keeps getting more and more layers added to it, but it certainly has increased in use, MIGS, especially in earlier stages of glaucoma, before going to our more invasive procedures of tube shunts and trabeculectomy that we’ll discuss in a minute. Again, going back to our mechanism, the problem in glaucoma is that the meshwork and the canal stop functioning. And therefore the resistance to outflow goes up and up. And so most of the procedures today are focused on the canal of Schlemm and the trabecular meshwork. This is a procedure that is not a MIGS procedure, but I think it’s very instructive, what’s trying to be accomplished here. This was a procedure called canaloplasty. I used to do this procedure very commonly. This is an external approach, conjunctival incision. These are some intraoperative photos I took. A deep sclerectomy. This is a nonpenetrating approach. There’s a superficial flap and you remove a deep scleral flap and amputate it and you unroof Schlemm’s canal. There’s still the inner wall of the canal there, and Descemet’s. You put a catheter in it. You can thread that catheter around for a 360 degrees, and retrieve it as it comes out the other end and tie a suture to it. In this case it’s a 9-0 Prolene. Then you back that catheter back all the way around, 360 degrees in the eye, while injecting viscoelastic and dragging the suture behind it. Once you have the tube out, you cut the suture from the tube, and then tie it. And now this is a gonioscopic picture that shows the suture in place that’s in the canal with some tension on it after viscodilating the canal and going for 360. These are some pictures, ultrasound photographs, that show what that looks like. On your left is a preoperative photo of typically what the outflow system looks like. You don’t see the canal. The meshwork isn’t visible on the ultrasound. But the canal is completely collapsed. On the right is what happens after canaloplasty. The arrow is actually pointing to the suture, it’s hard to see. There’s a little white dot at the end of the arrow. That’s actually the suture. You see how it’s pulling the canal open. And by viscodilating the canal, you create microruptures so fluid can get into the canal. That’s essentially in many ways what we’re trying to accomplish with these MIGS procedures, to get fluid through the trabecular meshwork and into the canal and keep the canal dilated and open and functioning so that fluid can then go downstream where it’s supposed to go. So these are some of the goals of the treatment. Your quality of life is a big thing with the MIGS procedures. And patients have high expectations. We have a lot of different MIGS options. I would like to break them up into what I consider mini-MIGS, a small area of the meshwork and canal. I put phaco, just straight cataract surgery, in this, because cataract surgery is a pretty decent glaucoma surgery in many patients. But the phaco combined with the stent, these affect a small area, usually under three clock hours of the meshwork is bypassed by the stent. Then we have more Max-MIGS which involve 180 to 360 degrees of the canal. Then we have less invasive glaucoma surgeries. These are bleb forming surgeries with tube shunts. The XEN is what we have available, there’s also PresrFlo in other areas of the world. There’s been a lot of interest in the super choroidal space, but currently there’s no devices for that available in the U.S. And trabs and tube shunts. I like to emphasize patient selection when it comes to MIGS procedures. There’s a lot we could talk about here, but I think the most important thing is, would you want to do a MIGS procedure in someone who has advanced field loss such as on the right that is beginning to threaten fixation? Or is the patient on the left the more likely candidate and a more favorable candidate? And while there are reports of using MIGS procedures successfully in patients with advanced disease, I’m not fully on board with that yet. So I prefer to keep the MIGS procedures for the more mild to moderate disease for most patients. There’s exceptions to everything, but think about stage of disease when you’re choosing how to proceed. Here is a list of the various canal-based procedures from iStent to Hydrus. These all increase trabecular outflow by bypassing the trabecular meshwork in some way and getting fluid into the canal. And there’s a lot of options. It depends on what’s available in your area. A simple goniotomy, taking a needle, you can take a 25 gauge needle and just bend the tip of it and use that as a goniotomy blade. It works very well and costs nearly nothing. These are standard needles. So you can do this with devices or you can get creative on your own as well. As I said, the suprachoroidal procedures, none are presently marketed in the U.S. The CyPass was withdrawn due to concerns about loss of endothelial cell. There’s these translimbal devices, the XEN being the one we have available in the U.S., a trans-limbal tube to bypass — basically a safer, less invasive trabeculectomy. It doesn’t always work as well as a trabeculectomy, certainly. But it is a less involved approach and for some patients may be a reasonable approach. And this is kind of what they look like. They’re fairly small, and the PreserFlo is there by the penny on the left, and that’s the XEN implant on the right. These are fairly small devices, and seem to be tolerated very well. This was a study done several years ago, I’ve always liked the way that they present it, and I don’t think anything is substantially fundamentally changed since they did this study out of Italy. Looking at a systematic review and meta-analysis of studies looking at MIGS procedures. And they had a set of criteria, and they had reasonable criteria to include, like reasonable followup, and usually sorts of quality standards. They looked at all the procedures that they could. They ended up looking at over 3,000 studies. And what’s critical here is that they identified over 3,000 studies that related to the procedures that they had available and found that only 33 of them that met the criteria to be included in their analysis. 1%, essentially. So it does limit the data. That’s still true today. The majority of studies on these are nonrandomized case series, case reports and things that don’t provide us generalizable information that you can really apply to patients. So they had only 33 decent quality studies to look at. And these are those studies. And the individual studies aren’t important here. What’s important is to look at that line down the middle. And the dot with the bar, that’s the mean with the standard deviation of the amount of pressure reduction obtained versus the control in those studies. And if you’re to the left, that means you lowered pressure, minus two, minus four elements, compared to control. On the right means that the MIGS procedure actually did worse, that the pressure was higher. And if you look at this and just look up and down the graph, you see that in general, the MIGS procedures are effective, have some wide range of variability, depending upon the device. But the pressure-lowering on average is fairly modest, maybe around four millimeters or so, or less. So these are often not the paradigm shift for a patient procedure. They may get them off a medicine or two. They may lower their pressure a little bit. But if you really need a lot of pressure-lowering, there are other procedures to consider. And here that brings us to our standard and what I consider our gold standard procedures of trabeculectomy, this guarded partial thickness filtering procedure we’ll talk about, and tube shunt. Trabeculectomy indications, it’s generally when the pressure can’t be maintained by nonsurgical therapies and you need to move ahead, because there’s damage. You’ve either exceeded maximum tolerable medical therapy, tried laser, and the optic nerve is still failing or likely to fail and visual loss is progressing. Those are standard indications for trabeculectomy. The technique, trabeculectomy is a bit of an art. There’s a lot of different ways to do it. It’s not as standardized with a device. Some of the MIGS procedures, what’s nice about them is they’re very standardized, you go in, you put this device. It’s not as surgeon-dependent. Trabeculectomy is still very surgeon-dependent, how you apply antifibrotic agent, how you make it. I’ll run through the steps here pretty quickly just to give you some of my thoughts. One of the first debates you hear is, should you do a limbus or fornix-based conjunctival flap. Here’s the pros and cons. I do a limbus-based conjunctival flap with a fornix incision. I get the best results. I’ve done these procedures now for over 40 years. But occasionally I’ll do a fornix-based flap with a limbal incision because of certain things about that patient. I can do both, but I get better results myself because of how do I it. But you can’t isolate any one step in the surgical success. It depends on a lot of other parts. This whole thing has to work together like a symphony. It’s not that one step is going to make or break the procedure. Most of the time we’re going to use mitomycin. Several years ago they did a hand raise, how many people are using mitomycin in glaucoma surgery, this was at an American Glaucoma Society meeting, 100% of people raised their hands. The problem is we’re using them very differently. The concentration, the time, how we apply it, do we inject it, do we use a sponge. Most of the time people are soaking a sponge or cutting a piece of a Wexel. Sponges are not designed as drug delivery devices, they’re designed to absorb stuff, not release it. So I think we get a lot of variability in how people may press on the drug or how much they saturate and how much actually gets to the tissue. It’s not as controlled as we would like it. But it is effective. It is effective. But in a lot of different ways that individual surgeons have taken advantage of to try to improve their outcomes and they get good results. The scleral flap that you make for trabeculectomy, what does matter is the relationship of the flap to the underlying sclerostomy, the hole, and it would be about half to two-thirds scleral thickness. You don’t want it too thin or too thick. What doesn’t matter is the size or shape of the flap, whether it’s triangular, trapezoidal, four millimeters, two millimeters. What matters is will it leak at the end. So you can do a lot of different flap shapes, sizes, as long as the relationship to the sclerotomy allows it to leak. You can create the underlying sclerotomy with a punch or a blade. There’s certain ways to do that. There’s an express shunt which I’ve used for some time which standardizes this approach. But there’s a lot of different ways to create the hole so that this can leak and form the fistula we want. I still like to do an iridectomy. I find if I don’t do an iridectomy, there’s a higher risk of the iris getting into the sclerotomy. But you do have to be careful when you do an iridectomy not to get into the ciliary processes or the zonules or the anterior hyaloid. How you close the scleral flap differs amongst surgeons. I usually just put if two sutures and leave them fairly loose. Some people put in multiple sutures and they want it pretty tight at the end because they plan on releasing sutures or cutting sutures or doing suture lysis. Then the conjunctival closure. A lot of people do this differently. You close it separately or in a single layer. There’s lots of different ways to close a fornix-based incision with a limbal incision. This is one of my cases where I’m closing the conjunctival tenons in a two-layer fashion. I’m as far back in the fornix as I can be. If you’re doing a limbal incision, you can do wing suture, one on each end, and pull the flap down. Or there’s an approach where you run a mattress suture along the limbus as well to close that kind of incision. Lots of different ways to do it. What you want to achieve is something that’s watertight. I find that in general, if you have a limbal incision, it’s more likely to leak, and it’s harder to get it watertight, but you certainly can. And then post-op, my mantra is always the success of surgery for trabeculectomy, 50% of it is what happens in the operating room. The other 50% is what happens postoperatively in how we manage that patient, and constant monitoring and followup, releasing sutures, how you taper the steroids, doing massage, all sort of things to try to assess or to improve the outcome of the surgery. Suture lysis is something that can be performed to release sutures, in a planned or unplanned fashion. I usually don’t plan on lysing sutures. If the bleb isn’t as high as I want or it’s not leaking as much as I want I’ll use a laser and cut one or both of my sutures. We created a grading scale many years ago to look at the height, extent, vascularity and so forth of blebs. You have to be comfortable dealing with blebs, monitoring them, and scheduling patients for followup as appropriate depending on their bleb. There’s a lot of different things that can happen with complications from glaucoma surgery that we need to be aware of. As I said, with postoperative care, there’s a lot of different options to look at. If the pressure is low, with a low bleb, you may have leakage, choroidal effusion. If you have low bleb but high pressure, you may be looking at aqueous misdirection or pupillary block. If you have high bleb but low pressure, you may be looking at overfiltration or high bleb with high pressure, you may be looking at a suprachoroidal hemorrhage. You need to be able to work through these options and know how to recognize the complications of surgery and manage them. Certainly infection is a concern over time. Usually infections start with a bleb leak then progress to infection because the blood leak was allowed to persist or maybe wasn’t identified. Lots of risk factors for infection. Mostly antimetabolites and avascular blebs. There’s a lot of different reasons for tube shunts. Even primary tube shunts have been looked at as primary surgery. But usually it’s after other things have failed. We’ve had nonvalved tube shunts, the Molteno, Baerveldt, we have valved, primarily presented by Ahmed today, that restrict some of the outflow. These devices do vary in size and it does appear from studies that have been done, that the maximum amount of effect you can get from a single quadrant device is probably around 250 square millimeters. So I use, when I use, for example, the Baerveldt, I’ll use the 250 over the 350, except for on individual cases. Trabeculectomy and tube shunt in general, trabeculectomy works better than tube shunts in many studies. But there are higher complication rates with trabeculectomy reported, particularly wound leaks and bleb associated problems, encapsulated blebs and other things also occur. There was a study, another study looking at trabeculectomy versus tube shunt after five years of followup. Very similar pressure reduction, if you look at the larger graph. Just more meds were required in the tube shunt group. There’s the primary tube versus trabeculectomy. So the previous study was done after trabeculectomy had failed. This is looking at primary tube versus trabeculectomy. Large number of eyes, randomized. And the primary TBT study showed similar results you. Get the early hypertensive phase. That’s why the tube shunt has that pressure spike, that’s the hypertensive phase. Long term, the results are similar. A little bit better with the trabeculectomy. More meds in the tube shunt group. Similar results here, trabeculectomy survival curve was better. So the take-home points is that tube shunt surgeries as primary before trabeculectomy have greater risk of failures, more need for medicines, but they have a lower postoperative failure rate. I think trabeculectomy still remains the gold standard for glaucoma surgery. It’s been shown to decrease the rates of localized and global visual field loss as well. And I’ll end with this slide. This is something, a slide I’ve used for years. You can put medications in your head on the graph where the ALT/SLT lines are, and it sort of shows you where everything starts to line up in terms of how these different procedures work and how they’re reported over time. Phaco can work. Laser trabeculoplasty can work. That’s about 20% decrease, 25% decrease in pressure. Medicines, 25 to 30%. Then you get the various iStent, canaloplasty. With that I will end my formal presentation and we’ll turn to the Q&A. So the first question here in the Q&A is how is the efficacy of nonselective I assume beta-blocker differ from selective beta-blockers. They’re similarly effective. In studies head to head, the nonselective probably works a little better and is a little bit more effective. The only time that I really use nonselective beta-blocker is in patients with a known history of pulmonary disease. Next question is what are some — it just moved on me. Sorry, it jumped to the bottom. I’ll reorient the questions here. What are some cases where we cannot combine outflow pathway with inflow pathway drugs? There really aren’t any, unless patients have intolerance to the drug. So that’s always a limiting factor, because of ocular, systemic side effects. You can really always look to do that, and you just have to see what patients tolerate. Is the outcome of mixed procedures hampered if performed after a repeated SLT? Great question. In the Black population can [indiscernible] be combined with MIGS procedures in advanced disease. To answer the first part of that question, it’s been unclear what the effect of SLT has on MIGS, but it’s thought to be minimal effect, if at all. So many patients that have MIGS procedures have had previous laser. In the Black population specifically, I don’t know that we have studies that will address that for us. So I can’t really answer that. I really wouldn’t see a circumstance where you would combine a MIGS and a trab unless you’re doing a trabeculectomy after a MIGS procedure has proven to be insufficient. There’s lots of patients who have had phaco with a, say, MIGS procedure performed, their disease is uncontrolled a couple of years later, you’ve already done 360 degrees of MIGS procedure, and then your next step is a trab or a tube shunt depending upon your preference. I think we’ve talked about some of the surgical interventions. Again, the main scenario seems to me that selects patients is how advanced is the disease. Earlier disease, with the more limited MIGS, what I call the mini-MIGS, more moderate disease I go to the more 360 MIGS, and if their disease is more advanced than that, then I’m probably looking at a more invasive procedure such as a trabeculectomy. Yeah, I’m sorry I don’t speak Spanish. If someone could translate for me. In early glaucoma diagnosis, OCT or canpemetry — I lost the — if I understand the question, in terms of diagnosing glaucoma, I never try to rely on one thing. Pressure, optic nerve, digital feel. That classic triad, I think you have to look at everything and it has to all fit together and make sense. There are times when the field looks worse but the patient’s pressure is fine and the OCT looks stable. You’re not going to necessarily make a change, unless you see all those factors starting to line up. So I would — it’s not a question of which is better. It’s a question of all of the diagnostic testing in glaucoma should work together. There’s different lenses for the use of ALT. Generally I use a three mirror gonial lens. It’s the little thumbnail looking round one. It just depends on which lens, which type of contact lens you have available to you, as long as you can get a good view of the meshwork. But most standard multimirror ones, three or four mirror lens, will have different lenses for looking at different angles into the eye. And you want the mirror that gives you the best view of the meshwork. How many times can SLT be repeated? Great question. I have one patient where I’ve done it eight times. And it still works. It’s not working as well now as it used to, perhaps. But this is a patient who is very resistant to any surgery. He had surgery in the other eye elsewhere some time ago and it didn’t go so great. So he’s really big on laser and it’s still working. The answer is you can keep repeating it as long as it’s still working. But there probably is a limit. And I think that that person, that patient is an exception. So you just have to evaluate the treatment and the options, see how it worked last time. In general, the laser is never going to work better when you repeat it than it did the time before. So if it didn’t work great, and we’re off three months, there’s probably little reason to repeat it, because you’re not going to do any better. So that’s my rule of thumb, that if they got a good response the last time and it lasted a while, you know, probably at least a year, and their pressure is creeping back up, then I’m inclined to at least offer it as an option, to repeat it. If it didn’t work well, I’m not expecting anything more than that if I were to repeat it. There’s an ophthalmology resident here. Glaucoma medications can cause a wide range of effects. How do you manage switching from one medication, what are your main considerations when deciding to make a substitution? Great, great question. So when adding medications, you have to think about what the medicine you’re on is doing first. All of our drugs have a certain failure rate. For example, a beta-blocker, 25% of the time, if a patient’s been on timolol or similar beta-blocker for two years, it’s going to be ineffective. They will have tachyphylaxis to the drug and it’s not working. So your ideal thing is to recognize that and not to add another drug to a drug that’s not working, but to stop the first drug. Now, sometimes it’s hard to tell. So if a patient’s pressure is creeping up, and I don’t know if it’s their glaucoma getting worse or the drug just getting less effective, I’ll sometimes just stop the drug briefly, have them back in a month, and see what the pressure did. If it didn’t change, then that tells me that drug wasn’t working. So then it’s important to stop that drug and start something else. If the pressure goes up, then you know the drug was effective. It’s just now the pressure’s gotten higher. So then you have to add something to it or advance the treatment or do something else. So I think that’s the main caveat, is we tend to add too many drugs on top of drugs that just aren’t working. And we need to — we need to be vigilant and take the extra steps to sort of weed that out. If a patient achieved the target but is experiencing significant side effects, what do you do? Well, if you’re asking patients to continue doing something that’s causing bad side effects, you’re ultimately going to fail. Whether it’s tolerability issues or systemic issues doesn’t matter. Our point with treatment is to maintain quality of life. And if you’re causing someone severe side effects, that’s impaired. So I think it’s ultimately a losing battle if you’re trying to work around side effects and ask a patient to continue to do that. It’s not a reasonable thing to do. I wouldn’t do it. I wouldn’t want to be on something long term that’s causing these side effects. So their compliance is going to go down. So you should stop what’s causing side effects and advance therapy. Our goal is to prevent blindness and maintain quality of life. And sometimes that just involves changing course. So the priority is to preserve quality of life and prevent blindness. So switch course if you have to. Don’t ask patients to do things that you wouldn’t do yourself long term. Retinal attachment. Is there any treatment in future — yeah, I’m not sure I quite follow the whole question, but retinal attachment, obviously if there’s been a macula off RD or chronic RD, visual prognosis is very poor. The key to retinal attachments, and I’m not a retinal specialist, is to diagnose them early, get them fixed hopefully before the detachment has progressed through the macula where there’s going to be likely long term compromised vision. What is my opinion on trabeculectomy performed with an amniotic membrane graft and what are the advantages? That’s a good question. Some of my associates have done this. I haven’t done the amniotic membrane for trabeculectomy. I’ve used it a few times to help repair blebs, leaks and things where we needed some tissue. So I think, you know, the jury is out on what it does, if it can augment trabeculectomy, I would look forward to those studies. I just don’t know that we have evidence to date that amniotic membrane improves the outcomes. But it’s an interesting question for sure. My regimen for topical steroids post-trabeculectomy, it’s important to look at the eye and not say, you’re going to do it four times a day for four weeks or you’re going to do it less frequently and so forth. I think what you really have to do is look at the eye. So I will usually start on — I typically use four times a day steroid unless the patient has a particular inflammatory component or it looks very inflamed, sometimes we’ll bump it up to six times a day. I’ll generally maintain that regimen for at least three to four weeks and then start a slow taper. But I’m looking at the eye. If the eye looks particularly inflamed or the conjunctiva looks particularly inflamed, I’ll slow down my taper. If it looks quiet or there’s hypotony, I’ll back off. It depends on how inflamed the eye looks. In general, four times a day for three to four weeks, then a gradual taper until we’re off the steroid by two months. The recovery period for MIGS is much quicker than trabeculectomy or tube shunt, no question. A phaco MIGS procedure can look every bit just like a cataract surgery on day one. They can have 20/20, 20/25 vision in a quiet eye and you can’t tell you they had a MIGS procedure done just by looking at them from across the room. That’s not a case for trabeculectomy or tube shunt, you can tell when those patients have had that surgery. So MIGS are much quicker visual recovery. And that’s one of the good selling points of a MIGS procedure, is that fast visual recovery. But the trabeculectomy and the tube shunt, you’re looking for more the long term control of glaucoma in patients who need it. Can ALT be performed after inefficient repeated SLT? Good question, but I’ve not seen data looking at ALT after failed SLT. But I wouldn’t have any reason to expect that it would work. So I don’t know of a study to reference on that. But some patients just don’t respond to laser for whatever reason. And you just have to move on to something else, whether it’s ALT or SLT. If you’ve tried SLT and it didn’t work, I don’t see a reason to go to ALT. And likewise, if you performed ALT and it didn’t work, there’s no reason to go to SLT, because as a primary treatment, they work the same. There’s no difference in the studies. Our prostaglandin analogs contraindicated after surgery? There’s always that risk. When we talk about cataract surgery and uveitis, most of the time you can get by with a prostaglandin if you need it, but it’s one more risk factor. It’s like, for cataract surgery, what are the risk factors for getting postoperative macular edema? It’s diabetes, maybe they’ve got vascular disease, and now prostaglandin. It’s one more risk factor for that patient to get macular edema, likewise uveitis, it’s one more factor that could increase the inflammation. Not that it does all the time. But it could. And then next question is do I have experience with MLT. I don’t, actually. I’ve read the articles on it. Again, if you look through the history of laser, there’s been lasers used in glaucoma for decades and decades, even before ALT, people are firing different things into the eye. And they all worked and they all worked about the same. So anything that gets laser energy into the meshwork can stimulate it. And I think it’s more of a biologic response that happens, whether there’s thermal damage or not, you get this biologic response with cytokines and upregulation of proteinases and recruitment of macrophages that cleans out the meshwork and sort of rejuvenates it a bit. But I don’t have direct experience with the MLT. What are the major complications of trabeculectomy? I think I went through the major list. And the most worrisome of those is of course bleb-associated infections, because that can cause you to go blind. You can also get hemorrhages and other things that can be very devastating postoperatively. But in the long term, bleb-associated infections are the thing that we need to — we need to look at blebs more, we need to Seidel test them with fluorescin. It’s often the source of where the bacteria come from that cause the infection. So we have to be treating dry eye. We’ve got to be treating blepharitis. We’ve got to be monitoring the blebs to prevent it. Why do we have to wait for the vision to fail before doing trabeculectomy? We don’t. In fact we shouldn’t. We should be doing surgery and doing whatever intervention it takes to prevent vision loss. And I think that relates back to my point, that if in real glaucoma, moderate to severe glaucoma that’s progressing, we need to advance therapy and get to whatever it’s going to take to stop it. So we shouldn’t wait. We should be doing some of these things earlier and not waiting, and really hone in on what is it going to take in that patient to preserve their vision and their quality of life. So I would not wait. Oftentimes, unfortunately, patients present when they’re pretty far advanced. And in those patients, you know, I think we have to be aggressive. There’s a question, how do you decide on which step to use. Interesting and great question. We get asked that sort of thing. There’s so many options right now. That’s why I sort of had those — so there’s the mini-MIGS like I listed. It’s whatever you’re comfortable with. They all seem to work fairly much the same in terms of outcome. I think you need to get familiar with one of them and get good at it. If it’s more the maxi-MIGS where you’re going 360, there are several devices and approaches, they all work approximately the same. You need to get good at one of those. There’s little nuances to the technique for each one. So I think it’s choosing within that class what’s available in your area, what makes sense, and then getting good at it yourself. How much reduction by ALT/SLT? It’s generally around 25%. There’s a range of course to the effectiveness. You’re not going to typically get the 35, 40% reduction in pressure, you can get, say, with a prostaglandin analog. You may in some patients. The average is around that 20 to 25% pressure reduction, which is about similar to a beta-blocker in terms of medications. What are my thoughts about combining different MIGS with phaco? Many of the MIGS procedures are approved, at least in the U.S., only to be used in combination with phaco, because that’s how the studies were performed. They were added on to phaco because they are more effective in that situation, and that’s how they were studied, because phaco, you know, lowers the pressure to start with, so you add something to it, it makes sense to maybe get patients off meds. So — but there are also some of the MIGS procedures that can — the more canaloplasty devices that can be used stand alone as well. The majority are not only effective when combined with cataract surgery in the U.S., at least, their approval is to be used in combination, not as a standalone procedure. From those three options of management, which one is the most commonly used? I think still the most commonly used approach to dealing with glaucoma is still medications. I think the majority, every market study shows globally that medication use far, far outweighs laser or surgical options. But I think we’re also slowly seeing a migration of laser and surgery higher up in the hierarchy, and that we’re moving more towards other interventions after maybe a couple of meds have failed, instead of going to three or four, which gets very complicated for patients. So — but I think still today, medications clearly are the most commonly used approach for glaucoma, and will remain so for a while. That doesn’t necessarily mean forever. What is the best treatment for pseudo exfoliation glaucomas or other secondary glaucomas? Secondary glaucomas is a broad topic, but just with pseudo exfoliation, I think you treat it just like primary open angle glaucoma but more so. Pseudo exfoliation tends to respond less well to medicines and even laser, so you do end up in surgery earlier. And it can be more aggressive and just doesn’t respond well. I think the steps are the same. You start with medicines or laser and then you advance and try to control it. Most patients with pseudo exfoliation can be controlled, you know, can be controlled without having to go to surgery. You know, but if you have to go to surgery and medicines and laser, my usually first choice would be a trabeculectomy before a tube shunt. Others would differ. But that’s what I would do. What is the best option in advanced glaucoma, IOP control with drops, worsening visual field? So while we use the pressure to gauge our treatment and set our goals, if the glaucoma is getting worse, it doesn’t matter what the pressure is. It needs to be lower. So if the visual field is truly worsening, and the pressure is ten, that means something, that the disease is progressing. So you have to treat the disease, which means you have to advance the therapy. Now, with drops, a pressure of ten that you’re obtaining in the office, you know, most of the time what that means is that the pressure is ten for three seconds, when the patient comes in to be checked every three or four months or six months or whatever it is. So that doesn’t mean the pressure is ten at fault. So a pressure of ten on drops can be highly variable. A pressure of ten on no medicines after a trabeculectomy is essentially a flat line. That pressure doesn’t vary. So the assumption is, if someone’s getting worse with a pressure of ten, probably the pressure isn’t always ten. There’s some variability going on, either just from peak/trough effects from the medicines, compliance, whatever it is. But you need to advance. You’re not treating the pressure, you’re treating the disease. The pressure is only a surrogate for what’s going on with the disease. And the disease is nerve damage and field loss. And if they’re getting worse, you need to be doing more. Is the outcome of MIGS affected by the level of pigment in the trabecular meshwork? There’s some thought that areas within the meshwork, often the pigmentation is not regular, there’s hyperpigmented and hypopigmented areas. It’s not that the collector channels may be more associated with the pigmented areas and therefore if you place your stents, if you’re doing those near that, that it may work better. But in general, you’re bypassing the trabecular meshwork when you do these procedures. So I think the level of pigmentation is of less importance than it might seem. There aren’t studies that show that it really matters. Can you perform SLT in neo-vascular glaucoma controlled with anti-VEGF and laser with persistent ocular hypertension? You could try it. My guess is that the results are probably not going to be well or be good. When you have neo-vascular glaucoma, what causes the pressure elevation is that a fibrovascular membrane grows over the trabecular meshwork, and even if you treat them and it regresses, there’s still this fibrous membrane that’s blocking the meshwork itself. And that’s what’s causing the elevated pressure. So I would not be optimistic about SLT laser in a neo-vascular eye, even when it’s been successfully treated, because the mechanism for the pressure elevation is different. It’s not what goes on in primary open angle glaucoma. When do you remove releasable sutures or do suture lysis? You know, it depends on how you do the surgery. Some people do their trabeculectomies and they don’t want — they want to do everything to avoid hypotony and low pressure early on, so they will tie the sutures tight, planning that at one week I’m going to release these two sutures, and in four weeks I’m going to release these two or whatever. They have a plan. Then they modify that plan depending upon what the patient looks like. Other times, such as in my case, on the opposite end of the spectrum, I like to leave the eye fairly leaky at the end. I leave the anterior chamber really filled with viscoelastic at the end of surgery. And I count on that to hold the chamber for a while until the eye starts to heal. And I never plan on suture lysis unless the pressure starts to creep up, where they’re not draining as much as I like, then I would release a suture. For me, that’s probably — I’ll do suture lysis, one in every 15 to 20 trabeculectomies. So, you know, 5% of the time, maybe, I’m doing suture lysis. I’ve used releasable sutures in the past. The primary situation where I’ve used releasable sutures is in patients who I consider to be at very high risk, particularly of suprachoroidal hemorrhage, maybe they’re aphakic or high myope, and I want to control it without doing super lysis. The problem with suture lysis with a laser, if you have subconjunctival hemorrhage, you can’t see the suture to lyse it, you can’t see it. With a releasable, at least if it’s exposed on the cornea, you can always release it whenever you want. So in some of these really high risk eyes, I have done releasable sutures where I put a suture through the sides of the flap and loop it out underneath the limbus and tie it on the cornea, and then at whatever point I want I can just cut that suture and pull it out. But those are relatively small number of cases. Do you perform trabeculectomy with mitomycin or without? I do mitomycin in every case. What I do do is vary the concentration a bit in higher risk eyes. I use .4 milligrams per CC concentration of mitomycin. So someone who’s failed a previous surgery maybe has some conjunctival scarring, an African American patient who I see, someone who’s at higher risk for failure, I’ll use .4 mitomycin. For the standard trabeculectomy, in someone who I don’t consider has a lot of risk factors for failure, I’ll use .2 milligrams per CC, and I’ll use it for two minutes in all patients and rinse the eye off very thoroughly afterwards. But I use mitomycin 100% of the time currently. Do you think 180 degrees KDB performed through two incisions — I mean, if you can get to 180 degrees, I think that’s hard even with two incisions. If you’re good enough with interoperative gonioscopy and can get more of the angle, you can get it up to five or six clock hours, yeah, you might improve the outcome. I don’t know if studies have said how much angle, but it would make sense, the more you can do, the likely more effect you might get. Trabeculoplasty recovery period. After laser trabeculoplasty, I assume this means when do you know what you’ve got. Generally you don’t know the pressure response right away. It takes at least a month, maybe six weeks. So I still always see these patients back four to six weeks after the laser. And then assess what the outcome is. And in the meantime, I try not to change anything else. I don’t change their medicines, keep everything else the same so I can isolate what’s been the effect of the laser. How about patients with preexisting corneal dystrophies? A lot of the topical glaucoma medications can exacerbate particularly dry eye. When you’re talking about the corneal dystrophy such as epithelial dystrophies, if you have a marginal cornea that’s on the edge of developing frank edema or corneal edema, you may tip them over with a CI. So you have to be careful with those medicines. Preservatives are another issue in patients with corneal disease. A lot of patients, the BAK and the formulation can be rough on cornea if there’s already preexisting corneal problems. So you may need to consider nonpreserved options for the medications if available. Getting towards the end of the questions, but also the end of our time. I’ve seen a small [indiscernible] which resolves spontaneously in two to three months, is this common? No, it’s not common. I don’t know how that could have been associated with the laser. Anything is possible, I suppose. But I suspect it may have been just a coincidence. I do not use steroid drops post-SLT of any sort, pre- or post-. I did with ALT. But SLT, really depends on that biologic response, and you don’t want to suppress that. It’s more theoretical than evidence to show this in my — in full disclosure. But — so I don’t use any steroid or nonsteroidal drops or anything pre- or post-SLT laser. I just do the laser. Is there a role for OCT angiography in the diagnosis of glaucoma earlier? Great question, great area of research to look at what’s going on from a vascular standpoint. At current, our current understanding of OCT angiography and what’s going to around the optic nerve in glaucoma is incomplete in how well this may be — or how helpful it may be. At some point I wouldn’t be surprised if we do more vascular analysis in patients with glaucoma to give us some clue as to what’s going on with their disease, because I think there are some vascular — at least vascular auto regulatory anomalies. Can I please enumerate again on Rho-kinase. The main things I said about Rho-kinase inhibitors is that they improve trabecular outflow, and they also do lower empty scleral venous pressure, the only class of drug that does that. Very safe drug systemically. From an ocular standpoint, you get subconjunctival hemorrhages, these little small ones that are not unusual, sometimes they’re bigger. You get corneal deposition of the drug in this whorl-like pattern. But a very effective drug, a new class of drugs for us. It’s another tool. It causes a lot of red eye and a lot of patients don’t tolerate it but it could still be very useful. A bleb infection after trabeculectomy. It depends on the status of the infection. I break it down into three categories, bleb infections. Number one is an infection that’s isolated to the bleb. So it’s just a blebitis, if you will. There’s no anterior chamber infection or anything else. That’s stage 1. Stage 2, you’re now getting some spillover inflammation into the anterior chamber with some flare in cell, maybe a little hypopyon. And grade 3 is full-blown endophthalmitis with vitreal involvement. The last one is easily, phaco to my retinal colleagues, they do full bother tap and inject, vitrectomy if needed and so forth. They get the full retinal treatment for endophthalmitis. The grade 1 where there’s just some isolated infection of the bleb, I will treat aggressively with topical antibiotics and fortified antibiotics off and on, hourly, every other hour basis. But just topically. Maybe add an oral fluoroquinolone, I would use moxifloxacin or one of the four quinolones. Stage 2 is where it gets a little tougher, where there’s some spillover inflammation. I will often treat them with, you know, aggressive topical, again, just like a bleb infection. I will definitely add oral antibiotics, you can get pretty good penetration with oral antibiotics with those eyes as well. And that will often be sufficient. But I will follow those patients every day. And if they show any signs that they’re progressing to an endophthalmitis, I’ll get them to my retina colleagues and let them take over from there. Oh, on the chart, what is ELT? That’s excimer trabeculoplasty. That’s an approach that Mike Berlin and others have worked on, where with an excimer laser, a blade, a small area of the trabecular meshwork and create an opening so the fluid can go through. And I think that’s our last question. So with that, I want to thank everyone for their attendance for the great questions. Hopefully this was useful. And I look forward to seeing you on a future Cybersight adventure and discussion. Thank you very much. >> Thank you, Dr. Cantor.