Glaucoma associated with ocular inflammatory disease has a myriad and anatomic and physiologic causes. Understanding the underlying cause of the elevated IOP is important to controlling glaucoma progression.
Lecturer: Dr. Ramana Moorthy, Associate Clinical Professor of Ophthalmology, Indiana University School of Medicine, USA
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Good morning, everybody. Good morning from Indianapolis, Indiana. It’s probably nighttime, afternoon time, for you. Thank you so much for making the effort to join us in this lecture on uveitis. We’re specifically going to be talking about uveitis and glaucoma associated with uveitis today. I wanted to make just a couple of clarifications. I know I’m a uveitis specialist. I’m a retina specialist. So I don’t do glaucoma surgery. I used to, at the beginning of my practice, many years ago. I don’t do as much glaucoma surgery at this point. Very little. Most of my glaucoma surgery has been — is done by glaucoma specialists that are in our community. So I wanted you to be aware of that. With that in mind, though, I think we can certainly talk about glaucoma. We’ll start with our presentation here. This is a shorter presentation than the cataract presentation. Glaucoma obviously is something that dogs every uveitis patient, because there’s a fairly high predominance of it, particularly with chronic disease. Whether we’re talking about chronic infectious uveitis or chronic non-infectious uveitis, you will see patients who will develop intraocular pressure elevations that result from the structural damage to the anterior segment from the inflammatory disease, and that subsequently results in damage to the optic nerve head and the neuroretinal rim and the nerve fiber layer. As we understand it now, which then by definition means glaucoma. But it’s a multifaceted disease. It has many different mechanisms, and we’ll discuss that a little bit, and we’ll discuss a little bit about the generalities of therapy. I’m happy to discuss maybe some specifics of therapy if questions arise, but I’ll try to pull out some important procedural points also. You know, if we look at the epidemiologic studies that have been done recently, in the last couple of years, looking at the incidence of glaucoma or the prevalence of glaucoma in this community — in children, for example, the prevalence of intraocular pressure greater than 21 is pretty high. It’s happening in almost 1/6 of patients. But after one and a half years of follow-up, that increases to about 33, about a third of patients. About a 6th actually having pressures greater than 30 in children. So in children in particular, we have to be cognizant. What are the things that we need to do? And in this particular study, the SITE study suggested that, despite this, controlling inflammation is still the key to long-term success for even the management of glaucoma and other complications associated with uveitis. So inflammatory control still takes center stage in this disease process. The MUST trial, after two years of follow-up, showed that in the MUST trial — remember that they were looking at how patients who had the intravitreal Retisert implant, the fluocinolone acetonide implant that lasts for three years, was compared to systemic therapy, the traditional systemic therapy, for the treatment of chronic non-infectious uveitis. And they found that patients who had the implant were at four times greater risk for intraocular pressure elevation and greater than 10 millimeters from baseline, and are more at risk for developing glaucomatous optic neuropathy. And two thirds or more required topical glaucoma therapy in the implant group, compared to about a quarter of patients in the systemic group. But both groups got glaucoma. It just so happens that the steroid implant group, not surprisingly, had a greater risk. Other risk factors include African-American race. In this particular instance, since it’s an American study, we find glaucoma more prevalently among African-Americans in our country. And as a result, we see that. Other risk factors are the use of intraocular pressure-lowering meds at the entrance, or sometimes during the study. And the activity of the uveitis at baseline was also directly proportional to the incidence of glaucoma and elevation of intraocular pressure. So this is a very important thing to keep in mind. And the most recent study of all was done through the SITE study, and that looked specifically at a very large cohort of patients with uveitis, treated in various methods. And among these hundreds of patients that were evaluated in this retrospective analysis, we found that prior use of fluocinolone acetonide implant was the number one risk factor for ocular hypertension greater than 30 millimeters of mercury. And other things included the history of ocular hypertension in the other eye, prior use of IOP-lowering drops, or previous IOP-lowering surgery, of course. History of ocular hypertension in the other eye, current or topical corticosteroid use, more than 8 times a day, for example. So frequent topical steroid use. Periocular steroid use within three months. Previous vitrectomy surgery, which is interesting, and then current use of prednisone more than 7.5 milligrams a day maintenance, and of course, the presence of other structural damage in the anterior segment, such as the presence of peripheral anterior synechiae, indicating trabecular damage and influencing aqueous outflow. If we look specifically at the fluocinolone acetonide implant studies, we know from previous data that 40% of patients who got the implant will need surgical intervention for glaucoma at two years, and 50%, about half, will need topical medication for glaucoma at three years. The good news is, when you have this implant done and you have glaucoma surgery or even if you have cataract surgery, these patients did surgically very well. They had fairly high rates of success, in terms of having good control of inflammation, pre- and postoperatively. And that’s, again, key for surgical success in this, as it was with cataract surgery and uveitis. So we have to kind of separate again, as we do in glaucoma, ocular hypertension versus uveitic glaucoma. How do we decide when to treat somebody? If you look at patients who don’t have uveitis, how do you decide? When do you treat a patient who has elevated intraocular pressure? You’re gonna base that on the appearance of the optic nerve. You’re gonna be basing that on the presence of family history. Right? And so the same goes here. Obviously patients who get uveitis may have another risk factor, a family history of glaucoma or previous history of glaucoma. That’s going to help you. But if you see evidence of glaucomatous nerve damage, focal neuroretinal rim loss, such as inferior notching of the nerve, presence of disc hemorrhage followed by a Drance hemorrhage, if you will, along the margin of the nerve, followed by the development of focal rim loss — those are the kinds of things that will tell you: Hey, we have glaucoma going on. Even if your pressures are normal that day, remember, there’s diurnal fluctuation even hourly, and it may be very dramatic in these uveitis patients. You may measure them an hour later. They may be normal. One hour after that, they may be 35. So keep that in mind. But I think regardless of what your intraocular pressure is, if your inflammation is not controlled, you can’t abandon steroid therapy for the sake of — or antiinflammatory therapy — for the sake of controlling intraocular pressure. In fact, I would argue that those patients who have high intraocular pressures and active inflammation, controlling the inflammation is probably going to play a significant role in the control of intraocular pressure. So I would still, in the uveitis patient, put that at the top of your list of things to do, even in patients who have ocular hypertension or uveitic glaucoma. Control the inflammation. Because you can’t do anything unless you do that. If you want to do surgery on uveitis patients and they’re actively inflamed, you’re gonna have a horrible outcome, if they have bad glaucoma. You need to get the inflammation controlled. So once you control the inflammation and the inflammation is well controlled, then if you think about — hey, maybe the steroids are causing the elevation of intraocular pressure. You need to consider that. You need to consider alternative mechanisms. Is the actual inflammatory disease itself causing intraocular pressure elevation? For example, herpetic viral uveitis, like HSV, keratouveitis, or varicella zoster virus keratouveitis, or toxoplasma retinochoroiditis — all those kinds of things can actually cause and present with high intraocular pressure on initial evaluation of a patient. So those are things to keep in the differential, in the back of your mind, in evaluating these patients with elevated pressure and inflammation. And remember that uveitic glaucoma, by definition, as opposed to ocular hypertension, is when you have progressive neuroretinal rim loss, or the development of typical parametric glaucomatous visual field defects secondary to high pressures, in the setting of a history of intraocular inflammation. It doesn’t have to be active, but a history of intraocular inflammation. There are many mechanisms to the development of inflammation in a uveitis patient. The most common things that we think of are structural damage to the anterior segment. Right? The development of posterior synechiae, and then getting secondary angle closure from rotation of the ciliary body — for example, in cases where you have panophthalmitis or panuveitis, and you have the entire choroid and ciliary body thicken, causing anterior rotation of the ciliary body and the lens-iris diaphragm, causing acute secondary angle closure. Also, and you can see this in patients such as Vogt-Koyanagi-Harada disease — this is a rare presentation that can happen similarly in sympathetic ophthalmia, severe posterior scleritis, and orbital inflammatory disease — can present in this way. So patients often have pain, because of their acutely elevated IOP, and they often will have severe inflammation. They won’t typically have posterior synechiae. They’ll just have that very shallow chamber and high intraocular pressures, and a red, painful eye. So ultrasound biomicroscopy can be very helpful. If you’re lucky enough to have an anterior segment ultrasound, or someone who is skilled in doing an immersion ultrasound, that can detect anterior choroidal thickening, anterior ciliary body rotation, that’s very helpful. OCT is only marginally helpful, because it can’t look behind the iris. It can just tell you whether the chamber is shallow or what’s happening at the iris root. But it can’t really tell you a whole lot about the ciliary body. So that’s why, when we’re trying to evaluate everything posterior to the iris, but in the anterior portion of the choroid and the ciliary body, we need to look at the ultrasound biomicroscope and anterior segment ultrasound. So you treat these acute angle closure patients with lots of corticosteroids and aqueous suppressants. And do a peripheral iridotomy — you don’t do peripheral iridotomy or iridectomy, because it’s not effective. You do that in an effort to try to see — oh, is this angle closure? It’s not gonna help you, because you haven’t solved the primary problem, which is that rotation of the lens iris diaphragm, because of the severe inflammation that’s occurred in the anterior choroid and ciliary body from the inflammatory disease process. What about the more subacute or chronic angle closure patients? In these cases, the patient has pupillary block from posterior synechiae and iris bombe, and they may be subacute, but the IOP rise might be acute or very hyperacute. In other words, they might have iris bombe for a long time, and because they have chronic inflammation, their aqueous production has been suppressed. Their ciliary body is not active, not making enough aqueous, so the pressure’s low. Then you control the inflammation. Ah-ha! What happens? The ciliary body gets active again, and aqueous is being produced. So now you have an imbalance. You have aqueous being produced, but the synechiae, posterior synechiae, and perhaps even peripheral anterior synechiae, or this iris bombe have caused a secondary occlusion of the trabecular meshwork and the angle, preventing appropriate aqueous drainage, resulting in elevation of intraocular pressure. In this case, you need to consider doing a peripheral iridotomy. Multiple iridotomies may be necessary with a YAG or argon laser. Remember that when you do this — that there is a pretty high rate of spontaneous closure. That’s why you want to try to do more than one. And remember that you’ve got to use intensive topical steroids probably before and after this procedure, because you’re gonna get inflammation. These eyes are inflamed. So sometimes what I do, especially with dark irises, is that I will pretreat with argon laser, and often will give these patients peribulbar anesthesia or retrobulbar anesthesia, because it’s pretty uncomfortable. But I try to shrink the iris tissue, and then coagulate the vessels, and then go in and zap it with the YAG laser. That makes it a little bit easier. A little less bleeding in these inflamed eyes. But again, you’re gonna create inflammation. If the PIs with the laser fail, then you need to consider peripheral iridectomy surgically, and then darker irides — and when you do the peripheral iridotomy, remember, one of the things that you can do is this can help you with diagnosing uveitis. Why? You’re gonna actually get a piece of the uveal tissue that’s inflamed. And if you have a talented pathologist on your team, they can look. Hey, there’s sarcoid granulomas in the iris. Hey, there’s coccidiomycosis going on in the iris. You missed that! You know? And this may change your entire treatment paradigm from uveitis. So don’t forget that when you go in the eye to do something in these cases, whether it’s glaucoma or cataract, that you have an opportunity to potentially get at least fluid from the eye, and possibly even ocular tissue, if you’re gonna do a surgical iridectomy, or as we get later, trabeculectomy, et cetera. Chronic angle closure — that’s a more difficult thing to manage, because here we have chronic peripheral anterior synechiae. And this is very important. Let me go back to something that we didn’t cover. This talk I kind of developed as part of a large series for the residents, so I’ve already talked about some of the basics in their previous lecture. But let me cover some of the basics here for you. Obviously when you see a patient with uveitis, and they have intraocular pressure elevation, what is the first thing that you need to do in that patient, after you’ve examined the anterior segment? You need to put a drop of topical anesthetic and pull out your foremirror gonial lens or whatever — your contact gonial lens, whatever you like. I use a Zeiss foremirror. Some people use — there are many different contact lenses, et cetera, that can be used. Sussman lens, et cetera. Put it on the surface of the cornea and look at the angle. You want to know: Is this chronic? Acute? It will help you. Because if you see peripheral anterior synechiae, you know that this person has chronic uveitic problems, chronic, probably, angle closure, and that’s certainly one of the mechanisms that’s causing their pressure elevation. In these cases, chronic peripheral anterior synechiae, secondary angle closure glaucoma — you’ve got to treat with aqueous suppressants, which may be inadequate. You may be able to temporize them with carbonic anhydrase inhibitors. But these patients more likely are going to require surgical intervention at some point. And again, I caution that control of inflammation is very important in these patients beforehand. If you can get that control. Because unlike cataract surgery, I understand glaucoma is one of those situations where, if the pressure is very high, 50 or 60, you can’t wait three months to get their inflammation controlled. I get it. But try to get the inflammation as well controlled as possible prior to surgery. Because that will help you, postoperatively. Believe me. Because these patients have very, very, very sick eyes. Glaucoma eyes are sick to begin with. Uveitis eyes are sick to begin with. And you combine those two together. By sick, I mean they don’t tolerate surgery very well. So these patients with chronic angle closure will likely require goniosynechialysis, trabeculectomy, and if they’re pseudophakic, typically tube shunt placement. And with trabeculectomy, I mean of course with adjuvants such as mitomycin C. Because plain trabeculectomy generally has a very high rate of failure, according to some of the early studies in uveitic glaucoma. Now, the more common things that we see are these secondary open-angle glaucomas. Okay? So acute. Patient presenting with high intraocular pressures — we alluded to this earlier — are often associated with infectious uveitis, especially when you look at unilateral cases. Right? You see a patient who has a pressure of 41, who is presenting with a first episode of iritis, and you look and they have a dilated pupil, and they’ve got iris atrophy in a sector of the iris between 3 and 9 o’clock in the right eye, and they had a zoster rash a month earlier on that side, it’s pretty easy for you to know — hey, this is zoster iridocyclitis. That’s why they have high pressure. So you treat the inflammation, treat the infection with antivirals, such as Valtrex or acyclovir, systemically, and treat with some topical corticosteroids and cycloplegics, and their pressure will get controlled relatively rapidly. And of course, if you’re concerned that the pressure is way too high at presentation and uncomfortable, you can certainly use aqueous suppressants initially. But you may not need to, once the inflammation gets well controlled. In the chronic cases of open-angle, you did a gonioscopy, the angle is open, the pressure is high, you know, they have inflammation for ten years in their eye — this is likely caused by chronic inflammatory debris clogging the angle, causing direct damage to the trabecular meshwork and the trabecular beams that, sclerotic, and the canal — the trabecular canals have become very, very narrowed, and as a result you see the development of elevated intraocular pressure. Throw into this mix — of course, this milieu of things going on — all of the steroids that we’re pouring on. Right? Corticosteroids, we know, structurally, back from some of the histologic studies done in the 1980s, that corticosteroids cause the deposition of glycosaminoglycans in patients, and some patients who may be genetically prone are going to have very high elevation of intraocular pressure, even with low doses of corticosteroids. And the more potent the topical corticosteroids, the more likely you are to get pressure elevation. And let me digress for a moment and talk about that. So nowadays we have, in the United States and Europe, difluprednate, and some of the other places in the world — I don’t know how prevalent difluprednate availability is. We call it Durezol here in the US. But difluprednate, Durezol, is a very potent corticosteroid. It’s about 2 to 2.5 times more potent than Pred Forte. Not the generic prednisolone, but Pred Forte. And as a result, it has a tendency to cause significant pressure elevation. But, on the other hand, it’s a very, very useful drug. In fact, even in mild intermediate uveitis, I have found that topical difluprednate can be very, very helpful in avoiding more aggressive therapies such as periocular corticosteroids or even systemic corticosteroids. But difluprednate causes intraocular pressure elevation, particularly in children. You have to be very cautious. There was a report from the Northwest — from the Chicago group. Debra Goldstein and Howard Tessler reported that a significant portion, nearly 30% to 50% of children, developed intraocular pressure elevation within a couple of months of starting difluprednate therapy. So this is something you need to monitor carefully in kids in particular. And my experience has been, with difluprednate, you’re gonna see a lot more pressure problems. 25%, 30% of patients are gonna have intraocular pressure elevations with this drop. I still use it, cautiously, in these patients, when I need to. Other corticosteroid-induced ocular hypertension, of course, periocular intravitreal steroid, steroid implants. I find it a less common occurrence with oral corticosteroids. But we still need to monitor in patients who are on oral corticosteroid therapy. Corticosteroid-induced ocular hypertension and glaucoma is something that we need to consider. So let me ask: You know, if you have a patient who has been given a periocular corticosteroid injection, when do you think they’ll get the pressure elevation, most commonly? That’s right. It’s gonna be a minimum of about two to three weeks after the injection. But after that, intraocular pressure elevations can occur months later. Even after one injection, I’ve had a patient who had no family history of glaucoma, in the eye that I injected, develop IOP elevation after one periocular injection done a year and a half earlier. So these patients need to be monitored carefully, need to be told that yeah, you know, the risk is greatest early on, but it may be ongoing. In uveitis, in the most chronic uveitic glaucoma patients, we see a combination of all of these mechanisms playing a role in the development of glaucoma. So we need to use our head to try to figure out what it is that we think is, as the clinician, the most common factor that’s causing the intraocular pressure elevation, and then proceed with the treatment thereafter. So we finally got to a question. This is one of our first questions here. So a 70-year-old man with a two-week history of anterior uveitis and 3+ cells in the anterior chamber, still, an IOP of 45 after two weeks of hourly topical prednisolone, which is the following best treatment option for this patient? A, reduce the topical steroids to QID and add aqueous suppressants, because the pressure is too high? B, discontinue topical corticosteroids and add topical aqueous suppressant? C, oral corticosteroids and aqueous suppressants. And D, add oral corticosteroids and perform urgent trabeculectomy with mitomycin C. What’s the best option? Let’s see what you guys thought. It’s kind of like playing chicken. Who’s gonna blink first. What are you gonna shoot for in this patient? You gonna let the pressure scare you? All right. You ready? Let’s see what you guys got. So reduce topical — see, a lot of you guys played chicken. You guys are chicken! What’s going on? You know, you have a guy that’s got a lot of inflammation and high pressures. What did I say? You’ve got to get the inflammation controlled, right? You can’t say anything about what’s causing the pressure elevation. Is it the steroids that are doing it, only after two weeks of topicals? That’s probably unlikely, you know. It’s the inflammation. You’ve got to get the inflammation controlled. You can’t ignore the pressure. But you more importantly can’t ignore the inflammation. So the mistake, the common mistake that’s made, is cut back on the steroids and add aqueous suppressants. Then he’ll come back with 4+ cells and a pressure of 3, and synechiae all the way around, and hand-motion vision for you the next day — or the next week, I mean, or two weeks later. That’s not good. You don’t want to do that. Okay? So you can’t be afraid to control the inflammation. You can’t be afraid of the intraocular pressure. So I think one of the things that I want you to understand is that inflammatory control still is the most important — is the key. So the management is inflammation control. Okay? Then treat the trabeculitis. So what if this patient that you saw in the previous question was a viral anterior uveitis? You forgot. You looked at the iris. Oh, he’s got sector atrophy. Well, in that case, you need to start him on antivirals, and continue the steroids, and add the aqueous suppressants. Because that will control everything. But controlling the intraocular pressure with topicals or additional systemic therapy may be required to prevent glaucomatous optic nerve damage. Use gonioscopy. Important. Very much important to assess the angle, especially whenever the IOP is elevated or changes. Evaluate the optic nerve head, just like you would for a glaucoma patient. Disc photos and nerve fiber layer analysis, if you have that available. And absolutely automated visual fields, which are really difficult to do in uveitis patients, because they often have medial opacities, small pupils, other things going on. PSE cataracts, cystoid macular edema — you know, lots of other things that are going to interfere with your ability to evaluate their visual fields. But repeated visual fields, and training the patient to do visual field is very important if they have glaucoma. So that’s very important. I rely early on, of course, like most glaucoma people do, in evaluation of the nerve head. Do I see optic nerve head changes? I currently am managing a 14-year-old patient who had been very recalcitrant, bilateral chronic JIA-associated uveitis, who has been very poorly treated and managed elsewhere, and has been non-compliant. The patient’s family has been. Who is seeing me. Who is developing high pressures. Controlled inflammation. Very high pressures, despite very low levels of topical steroids. On methotrexate, combined with Humira, who is having pressures of 36 on maximum medical therapy. This patient is likely going to need a tube shunt. Is going to need some sort of a procedure done to control the intraocular pressure. But it’s much better to do it when the inflammation is controlled. But she’s already developing some optic nerve head changes. That’s what you want to try to avoid. Avoid the development of optic nerve head changes, if you can. You know, people asked about prostaglandins. A few things. A few pearls. And I’ll give these pearls again before the end of the lecture. But prostaglandin analogs don’t generally exacerbate intraocular inflammation, especially when they’re used concomitantly with immunomodulatory therapy or corticosteroids. Okay? So you can use prostaglandin analogs. I feel quite comfortable using that in chronic uveitic patients, especially when they’re on some topical low dose corticosteroid anyway. It’s not going to have the effect that you would be worried about. It is unlikely to exacerbate the inflammation. Probably unlikely to cause a worsening of cystoid macular edema, but that’s something you need to keep in the back of your mind. So I use prostaglandins. They’re not my first line therapy, but I still do. I typically use aqueous suppressants first, the alpha adrenergic alpha-2 agonists second, and then I sometimes will add the carbonic anhydrase inhibitors, of course. And then I will sometimes use — add the prostaglandins in that order. They may require surgical intervention to prevent vision loss and allow for treatment of uveitis if unable to control the pressures medically. So you can get the uveitis slightly controlled, but they’re still active when you try to taper. In these cases, yeah. You’re gonna probably need to do the glaucoma surgery, take your chances with the inflammation, be very aggressive after the glaucoma and during the glaucoma surgery, and control the inflammation. Another pearl: Typically the kinds of procedures that we do, such as ALT and SLT, are generally contraindicated in the setting of uveitis, because there’s some concern for exacerbating anterior chamber inflammation with these procedures. Occasionally steroid-induced ocular hypertension may respond to SLT. I know that some uveitis specialists are doing that. There’s some limited data on that. Glaucoma surgery is indicated when the increased intraocular pressure is unable to be controlled medically, and it’s high enough to cause progressive optic nerve head damage or already has caused that. And the need for local corticosteroid treatment is known in a known corticosteroid responder. So these are things that you kind of need to keep in mind. Who are the guys that are gonna do worst? And you have to prepare yourself that they’re probably gonna likely need some intervention, beyond just drops. There are other contraindications to glaucoma surgery. If you have somebody who has active scleritis and you have active anterior segment inflammation that is florid, this is a general contraindication. Okay? You have to review: What are the risks and benefits? If your pressure is 50, and they have 1+ cells in the anterior chamber, and they’re on Imuran, prednisone, topical Durezol, all kinds of stuff, try to see what you can do to control the inflammation as best as you can, before sending them to surgery. But likely they’re gonna need something. If they have an active surface infection, that’s a contraindication. If they have very poor visual potential, that is a relative contraindication, depending on the severity of the nerve damage, et cetera. So here’s our next question: Which of the following methods of intraocular pressure control is least appropriate for a patient with chronic anterior uveitis? Okay? Aqueous suppression with medication. Laser trabeculoplasty. Glaucoma shunt, tube shunt. Or trabeculoplasty with mitomycin C. So which of the following is least appropriate? So this is one of these negative questions that most of the board question writers don’t like. But this is just my question. So you can take it for what it’s worth. So what do you think is least appropriate? Let’s see if you guys were listening. Okay. So most of you got that right. So the least appropriate method — it’s appropriate to use aqueous suppressants. It’s appropriate to consider surgery in the most severe cases. But laser trabeculoplasty — A, it probably may not work very well. It may produce only mild reduction of intraocular pressure. But more commonly, may exacerbate inflammation. If the patient has peripheral anterior synechiae, or is at risk for that, you know that irritating the iris more from doing ALT will likely produce additional peripheral anterior synechiae. You know, even in patients who don’t have that, that is a potential complication they can develop with aggressive ALT treatment. So keep that in mind. And this goes for also these minimally invasive glaucoma surgeries. When we’re dealing with uveitic patients that have… I need to advance to the next slide. That have the… When we’re dealing with uveitic glaucoma patients, we know that the patients who have severe elevated intraocular pressures and patients who have significant glaucomatous nerve damage are the ones that are gonna need therapy. And those patients are going to require more aggressive intervention. And minimally invasive glaucoma surgery can be only marginally beneficial. Again, typically you’re messing with the anterior segment. You’re more likely to induce more anterior segment inflammation. So it is probably not going to be as effective as full thickness procedures, such as a trabeculectomy, trabeculoplasty — trabeculectomy, I mean — or potentially a tube shunt or a seton placement. So what do you need to do in the evaluation of a patient that needs glaucoma surgery in uveitis? A, you need to know the course of the pressure rise. Was it rapid? Gradual? What’s the maximum pressure? Has there been previous surgery? What are the medications that they’re on for the treatment of the pressure? The usual things. And obviously you need to look for the presence of concomitant conjunctival disease. Is there scarring of the conjunctiva from previous surgeries? With cataract significant enough that it would require concurrent extraction? Although that’s risky, in a patient with uveitis. Concurrent cataract removal and placement of tube shunt or glaucoma surgery means a lot more inflammation, a lot longer postoperative recovery for these patients. The depth of the anterior chamber. Is it shallow? Is it deep? Is it super deep? Is there a significant amount of posterior synechiae or peripheral anterior synechiae? If there’s no view of the posterior segment, a B scan may be required to rule out other things. And you need to treat the cystoid macular edema aggressively and the inflammation aggressively, prior to the surgery. I don’t have a lot of clinical photos. As I said, I’m not a glaucoma surgeon. But these are photos that I — these are probably one of your patients. I grabbed these from the Google website. So these are public domain images that I have. And these are showing tube shunt placement in patients who have chronic uveitis. These tubes were placed in the sulcus, ciliary sulcus. You can actually see them behind the iris plane, behind the intraocular lens implant, I think, in the one on the right. And on the left, it looks aphakic. But these are tube shunts that were placed in a patient who had severe uveitic glaucoma. And this has come into vogue now. Placement in the ciliary sulcus — these tube shunts can be very effective. They can be made long and avoid the corneal complications of corneal decompensation that occur with the placement of the tube shunt in the anterior chamber. That is the long-term risk for tube shunts, as you know. Which surgery do you choose? That was one of the questions that was sent to me earlier. Do you choose filtering surgery, or do you use tube shunts? I will tell you that, in general, most uveitis specialists, particularly in children, for example, in phakic children who have no cataract, if their pressure is high and they have no active inflammation, the glaucoma specialist that I work with and that I prefer — that a tube shunt be utilized. A tube shunt is very helpful. Because remember, in these patients, we’re seeing they have very, very high pressures. Not a lot of optic nerve head damage. And you need to bring the pressures to normal level. You don’t need to make the pressures ultra low. And the tubes are great for that. So a Molteno tube. Or the Ahmed valve seton can be very effective. Because especially the Ahmed valve seems to be very popular among pediatric glaucoma specialists, because it tends to kind of regulate the pressure a little bit better. You don’t get severe hypotony. And you can use a ripcord release suture on the tube, to release the tube when the aqueous production has increased. So these are important things to kind of keep in mind in these patients. So other less commonly used procedures than trabeculectomy or setons would include goniotomy. In children, sometimes that’s done if the patient has a history of congenital glaucoma. Goniotomy typically is not utilized for the treatment of uveitic glaucoma in patients. Laser cyclodestruction has to be used very much with caution. Because diode cyclophotocoagulation externally has a pretty high risk of causing a significant inflammatory response in uveitic patients, and can cause significant hypotony. Okay? And there have been reported cases of de novo development of sympathetic ophthalmia and other things from disruption of the ciliary body pigment epithelium in patients who have had very aggressive cyclodestruction procedures, either YAG cyclodestruction or transscleral cyclodestruction procedures. These are things of last resort, and should be left to a glaucoma specialist, not something that a primary ophthalmologist should be doing in uveitic glaucoma patients. Stripping of the anterior chamber angle membranes if present is probably useful. And doing goniosynechialysis during a trabeculectomy or during a tube shunt placement may be very useful in patients who have angle closure. If possible, the uveitis should be inactive for three months preoperatively. Again, this may require a lot of corticosteroid shots and elevation of intraocular pressure that you’re worried about. But if the nerve can tolerate it, get the inflammation controlled first. And then proceed with the surgery, if at all possible, keeping the inflammation quiet for three months with whatever medication necessary. And you should anticipate, with glaucoma surgery, a more vigorous inflammatory response than you would with cataract surgery alone. And if you do them combined together, you’re gonna have a lot more inflammation and really exacerbate the postoperative inflammatory response. You may have significant fibrin formation that may require the placement of — you may have to use intracameral TPA, about 25 micrograms. About a 10th of a CC, 0.05 CCs, 5/100 of a CC in the eye. That can help break up the fibrin clot, postoperatively. And lots of topical steroids and probably oral corticosteroids in these patients too. So uveitis is gonna flare up. So controlling preoperative inflammation — useful. At the time of surgery, intraoperative corticosteroid injection, perhaps intravitreal injection, or periocular injection of corticosteroids, can be very helpful. One of the good things about having a tube shunt in the eye, in a patient who has had uveitic glaucoma, is it almost gives you a free pass or a ticket to then use the steroids locally as aggressively as you want. Obviously if you’re gonna give periocular corticosteroid injections, I would not give the injection over the tube shunt plate. That’s probably not a good idea. Right? So you want to give it in other locations. I often will give an inferior retroseptal injection in those patients if they need treatment. Remember that these patients, that they have low intraocular pressures after glaucoma surgery. Hypotonous eyes are more prone to have complications when you give periocular injections. You can have a globe perforation. Because the eye is so soft, you may not be able to tell when you’re engaged the sclera. So be very, very careful in your techniques, when you’re doing periocular corticosteroid injections in hypotonous eyes, especially following previous glaucoma surgery. So treat aggressively the inflammation, once the glaucoma surgery is done, if you couldn’t do it before, because you have now a way to control the intraocular pressure mechanically. You know, there are lots of complications that can occur in glaucoma patients who have glaucoma surgery. So you can imagine that complication rate and the number of complications is greater in patients who have uveitis and glaucoma. Right? So delayed or acute endophthalmitis is certainly a possibility, especially in patients that have mitomycin C filters. Because those patients have very thin, avascular blebs. Much more prone — and these patients are on chronic local immunosuppression and systemic immunosuppression for the treatment of their uveitis. They’re more likely to develop retinal detachment and develop hypotony, which can be really devastating. Hypotony — you can’t really treat it, right? You can treat hypertension of the eye. Ocular hypertension. But you can’t treat hypotony. There’s no drug that’s very effective for hypotony. Choroidal effusions and choroidal hemorrhage are very common. Increased intraocular pressure postoperatively is very common, as is hypotony. So remember: If you’ve got a ripcord, you may want to open it a little earlier. Corneal decompensation is a chronic potential issue with tube shunts. Especially if they’re placed inappropriately in the anterior chamber. Ptosis, because of the elevated bleb, and if a large plate, a Baerveldt implant, for example, is placed, it can cause some strabismus-related issues, along with ptosis. Chronic cystoid macular edema, epiretinal membrane development, wound leaks — all these are things to consider. And development of synechiae and fibrous growth around the tube, resulting in pupil distortion and closure of the tube, can certainly happen in chronic inflammatory disease. And I’ve seen it. And this can be very, very difficult to manage. Overfiltration and low intraocular pressure is not an uncommon problem. So these patients need to be followed frequently. Steroids need to be used aggressively, and immunosuppressives as well. And topical antibiotics, with an infection. So we talked about common dilemmas. I’ll reiterate this many times during this talk. And this is basic. And forgive me if there are glaucoma specialists in the audience. As I said, I am not a glaucoma specialist. I just create glaucoma. I give my glaucoma specialists the disease to take care of. I create it and I manage it for them and get it into bad shape and then give it to them. I’m being facetious, but I don’t do glaucoma surgery anymore. But we can… SLT and MIGS have limited value in uveitis, as I mentioned. Uveal incarcerating procedures, like iridencleisis, increase inflammation. Cyclophotocoagulation causes worsening of inflammation, phthisis, and hemorrhage. Those are things to consider. Another couple of pearls: Pre- and postop inflammatory control is the key to success for surgery. And trabeculectomy is more likely to fail than seton procedure. So seton procedures are preferred, whenever the patient is aphakic or pseudophakic and preferred in phakic pediatric patients as well. And especially when the inflammation is still active, you need to consider using the seton, as opposed to using a trap. Active inflammation and IOP elevation — control the inflammation first and then the IOP. Inflammatory control is most important. No active inflammation and elevation of IOP — try to reduce the steroids and control the IOP that way. Okay? Imaging the interior segment: We talked about it earlier. And these are some of the questions that were sent to me preconference. I’m answering them in these slides. You look at — for any activity that you want to see behind the iris, you need to use an ultrasound biomicroscope. Anterior segment OCT is useful for everything from the anterior chamber to the anterior iris plane, but it’s really not helpful, unfortunately, in looking at the ciliary sulcus or to evaluate the ciliary body or anterior choroid. Uveitic eyes are sick eyes. Glaucoma eyes are sick eyes. Both together carry a cumulatively greater risk of complications after the surgery. And again, if active uveitis presents with high IOP, think of HSV, VZV, cytomegalovirus-associated uveitis. Toxoplasmosis. Think of the possibility of underlying Fuchs heterochromic iridocyclitis. You know, CMV uveitis, that I’m referring to, has been linked with Fuchs-like syndrome. It can also be linked with this so-called Posner-Schlossman syndrome, originally described. We think many of those are probably related to cytomegalovirus infection. I’m gonna go back to seeing if I can answer the questions in the chat here. There’s lots of questions. In glaucomatocyclitic crisis, usually mild anterior uveitis, rise in IOP. So first you have to treat inflammation here, or raised IOP? So the answer is of course both. You’ve got to treat a little bit of the inflammation. It’s pretty responsive to topical steroids. What I would suggest is that, in this case, do an anterior chamber tap, and send the tap for PCR, for HSV, VZV, and cytomegalovirus. Surprisingly, many of these will have viral causes, and you may be able to treat the viral cause, and by treating the viral cause, you may prevent future attacks. So that’s one of the things that we’ve learned here. So again, you treat a little bit of steroid. Pressure control. These patients usually do okay. But then the etiology is something important. Next question: What is your opinion about combined cataract and glaucoma at the same time? So as I said before, they said hit once and hit hard. Yeah. You know, that’s great if the patient is blind and can’t see because of the contract. You can’t see anything, and they’ve got bad glaucoma. You may have only one chance. I get it. But if you have the opportunity to separate these things and it’s safe to do that, I would much rather do that. I realize that prolongs the postoperative and perioperative courses of these two surgeries, but you may end up doing better in the long run for the patient, if they can get through that. When to consider the IOP elevations caused by corticosteroids? I mean after a 15-day use or a month? Well, corticosteroids can be the cause of the intraocular pressure elevation at any time after two or three weeks after initiation of therapy. So they’re in the mix. When the IOP is up, put a gonio lens on. Look at the anterior chamber angle. If the angle is open, there’s no inflammation, and you’re on QID Pred Forte, well, that’s probably playing a role in your IOP elevation. If you still have active inflammation and the angle is open and the IOP is elevated, well, there may be other mechanisms at play. Including the active inflammation. So it behooves you to control the inflammation still. Okay? So that’s very important. Even in a patient that… I think I missed the first part of the question. What is ALT? Argon laser trabeculoplasty. And that’s done for the control of inflammation — control of pressure in glaucoma patients. It’s valuable in primary open-angle glaucoma. It’s not valuable, typically, in uveitic glaucoma patients. Severe uveitis with angle closure responds well to aggressive control with steroids and iridotomy. Gives relief to patient with minimal antiglaucoma medicine. I agree. Obviously if you have acute angle closure, yes. Aggressive treatment with steroids causes an inversion of the forward rotation that’s causing the acute angle closure of the lens iris diaphragm. And that is what’s producing the — correcting the anatomic problem that has occurred, and that will control the intraocular pressure. You’re absolutely right. And I think I answered the other pre-questions. Are there any other questions? You guys have been great. I know it’s probably late in some of the places where you’re at. Are there any other general uveitis questions as well? I’m happy to answer. As I said, I’m very good at creating glaucoma, it seems, in my practice, a lot of times. I try to avoid doing that. We were talking philosophically about the patients who have chronic uveitis, especially children. How do you treat glaucoma? You know, I think one of my colleagues, Wendy Smith and Debra Goldstein, were talking about this earlier in the year. And I think — I will tell you that the key in children is to prevent complications. Treat aggressively the inflammation early on with immunosuppressive therapy. And then treat the glaucoma complications. But if you treat the inflammation, generally you can avoid a lot of the complications. Preferred procedure for aqueous tap and PCR? I do it very similarly as you would for other aqueous paracentesis. I use a topical Betadine prep. I do use a lid speculum. And you don’t have to do it at the slit lamp. Some people do just do it at the slit lamp. I just do it with the patient in the chair, and use a 30-gauge needle and TB syringe, and aspirate about a tenth of a CC. Send it immediately to your laboratory to do the analysis. You need at least a tenth of a CC in order to check for 2 or 3 viruses. Now, if you have multiplex PCR, and you have a fancy PCR lab, they’re able to do very small, tiny samples. They can do pan-pathogen PCR, in some places. They may not be readily available everywhere. How do you deal with Behcet’s disease? As these patients have a chronic course of disease, with quite a long-term follow-up? Well, Behcet is a very, very, very complex disease process. Having managed many patients with Behcet over the years, I really think that the treatment for acute flares — it’s very, very clear that those patients need anti-TNF therapies, specifically Remicade infusions, when they have explosive onset ocular disease, because those medications work even faster than corticosteroids. IV corticosteroids at high doses while hospitalized for three days, followed by gradual taper of oral corticosteroids. And then introduction of immunosuppressive therapy, specifically long-term immunosuppression, such as either azathioprine or some people use interferon in Europe. Or potentially mycophenolate. These are all agents that you can use. You can also use long-term Humira as well, for the control of Behcet vasculitis and ocular inflammatory disease in these patients. These patients are at great risk for development of glaucoma, cataract. They can develop optic atrophy from severe vasculitic problems in the retina. What is the role of topical non-steroidal drops in uveitis? Minimal. I think topical non-steroidals can be useful in the treatment of pseudophakic cystoid macular edema. They can be useful in the treatment of mild episcleritis, for example. But they’re probably not necessarily a mainstay for the treatment — topical non-steroidals, anyway — for the treatment of chronic uveitis. GDD with uveitis, glaucoma… I don’t know what GDD is, Dr. Habdeleh. GDD. I’m sorry. And it’s with… Is uveitis effect in HIV reversible by treatment? Are you talking about the immune recovery uveitis? Or anterior segment inflammation? It’s very common to see, in patients who have previous cytomegalovirus infection, once they get immune reconstitution in HIV disease, they can develop inflammation. That inflammation tends to persist and can cause cystoid macular edema. It can be very difficult to treat. But it can cause chronic problems. But generally it tends to be… Once the immune system kind of regulates itself, it tends to be self-limited. But does require treatment. Glaucoma drainage devices in uveitic glaucoma with very poor vision. So, again, poor vision may be a relative contraindication. If the patient has very advanced glaucomatous optic atrophy, and their pressures are 25, and you need them to be 10, you probably are better off using trabeculectomy if their inflammation is well controlled. If their pressures are 50 or 60, you need to use a glaucoma drainage device. Glaucoma drainage devices still work better in general, overall, in uveitic glaucoma patients, than do trabeculectomy with mitomycin C. Yeah. So NSAIDs for maintenance, drops for inflammatory control. And topical NSAIDs — oral NSAIDs probably have some role. Okay? You can use oral piroxicam, or you can use oral… And oral piroxicam has been utilized — oral NSAIDs, if you read Steve Foster’s articles, he has used them in children, and they can be very helpful in kind of mitigating the severity of mild chronic anterior segment inflammation in patients with JIA. So there’s definitely a role for those things. So they should not be pooh-poohed, the systemic stuff. The topical stuff… I don’t know that there’s a lot of role for it in the treatment of uveitis. May be useful sometimes in the treatment of CME. Use topical, then intraocular, then systemic corticosteroids in uveitis. The order I meant to sum up. Well, you know, it really depends on the nature of the disease process. There’s no cookbook method. Okay? I’m a purist. If the patient has bilateral disease and it’s severe and I can’t get it controlled with topical drops, it’s very difficult for the patients to put drops in both eyes all the time, every two hours. Those patients I’ll put on systemic therapy. Systemic steroids, followed by the initiation of immunosuppressive therapy if it’s appropriate. So yeah. Dr. Anraj was asking about JIA, juvenile idiopathic arthritis-associated uveitis. Yes, non-steroidals — systemic non-steroidals can be very useful for mild, long-term control. If you want to kind of tweak their inflammation, and inflammatory control, you can use systemic non-steroidals, with caution, in those children. Thank you so much for your attention. And I think it’s been about an hour. Oh, looks like somebody else… Dr. Adina Alexandra, 30-year-old patient, ocular hypertension after two weeks. Also systemic varicella virus. How long should I use topical aqueous suppressants? You can use topical aqueous suppressants as long as you want. But if they have systemic varicella, I hope you have them on some antiviral — systemic antiviral therapy long-term, too. Because that may be an issue in this patient. I’m not sure exactly what’s going on with that, Alexandra. But I hope that that’s helpful. But topical aqueous suppressants — you can use them as long as you need to. But make sure you have the varicella virus controlled with antivirals. Thank you very much, everybody. You’re most welcome. Take care.