Lecture: Diagnosis and Management of Neovascular Glaucoma

>> Good morning, my name is Dr. Claire Wright, I’m Assistant Professor at University of Tennessee in Memphis. I will be lecturing on neovascular glaucoma this morning so I’m going to go ahead and enable my screenshare here and go ahead and get started here. So I have no financial disclosures. Today’s lecture objectives, we will discuss or list the most common underlying etiologies for neovascular glaucoma. We will detail key clinical features of neovascular glaucoma, we’ll discuss diagnostic workup as well as the medical and surgical management of neovascular glaucoma, or NVG. So I have three poll questions that we will review both at the beginning and at the end of the lecture, so our first question: Which of the following is not considered — and the options are. Ocular ischemic syndrome, diabetic retinopathy, central retinal artery occlusion, and central retinal vein occlusion, I’ll give you a few seconds to look at your answers here and again, we will review these at the end, as well. OK, so pretty good distribution. So again, we will review these at the end of the lecture. Our second poll question: Which of the following is not a clinical sign of neovascular glaucoma? iris rubeosis, iris atrophy, angle vessels and optic disc cupping. I’ll give you a few seconds, again, we’ll review these at the end of the lecture. OK, our third poll question: Which of the following is the optimal surgical intervention for neovascular glaucoma? For neovascular glaucoma? Cataract surgery with goniotomy, trabeculotomy with might mycin C, non-valved glaucoma non-valved glaucoma draining device. OK, NV GWAS first described in association with iris rubeosis in a writeup dated back to 1906. Neovascular glaucoma was further defined as elevated intraocular pressure in the context of new blood vessel growth and connective tissue growth. That was back in 1963. It depose by other names, or at least historically, hemorrhagic glaucoma, congestive glaucoma, thrombotic glaucoma and rubeotic glaucoma. So what’s the pathophysiology? Let’s just review the physiology and anatomy of a normal eye. So in the normal healthy eye, there’s a balance between pro-and anti-anggenic growth factors, with the pro-angiogenic growth factors being VEGF and angio poetin 2. In a normal healthy vessel, the capillaries contain nonfenestrated endothelial cells with tight intracellular junctions. And so picture here healthy blood vessel, normal amount of oxygenation or normoxia. Now, let’s contrast that with the pathophysiology of the ischemic eye. In the ischemic eye, the pro-angiogenic growth factors tip the balance in their favor and so what causes this, there’s rete ischemia, which leads to hypoxia, which then results VEGF, and leads to angiogenesis. These neovascular vessels are cruddy, this is what I tell my patients. They’re not like your healthy vessels. They’re bad, they’re kind of shoddily made. There’s little or absent muscle layer and little aventitial structures and this means they’re prone to breakage. Further, kind of flow sheets demonstrating — or demonstrating what I’ve just said, and the photo on the left is that flow sheet which demon strays how hypoxia is the stimulus for VEGF and angiopoietin two creation which then results in endothelial proliferation and angiogenesis. The photo on the right is I think an interesting image, which is a capillaroscopic image which demonstrates what I’m discussing, that results in the capillary changes in the hypoxic state. And so on the left of that image, you have what are healthy normal capillaries, and then as you proceed to the right of that image, you start to get capillary dilatation and creation of new blood vessels or angiogenesis. Capillaroscopic images are used by rheumatologists to image numerous conditions. I just thought that image was interesting. Now, what are the etiologies of neovascular glaucoma? Most common etiologies are diabetic retinopathy, central retinal vein occlusion or carotid occlusive disease, these are the most common one. There are other less common ones, including central retinal artery occlusion, but these are the three most common. Many of us are familiar with what each of these etiologies look like. These are fundus photos of each, we have central retinal vein occlusion, or CRVO, that blood and thunder fundus, with multiple regions. The central image is proliferative diabetic retinopathy characterized by microaneurysms and investigate will beading, and in this particular case you have neovascularization of the disc and probably NVE or neovascularization elsewhere. the last image on the right, ocular ischemic syndrome characterized by dot blood hemorrhages representative of retinal hypoxia. So these are just a review. We’re not going to get into each of these in detail. We’re talking about how each of these results in neovascular glaucoma. But these are the three primary etiologies, most common etiologies for neovascular glaucoma. So how do these patients present? Well, on slit lamp exam, these patients — this presentation is characterized by neovascularization of the anterior segment and that can neovascularization of the iris. I believe that’s because the thought that that part of the iris is exposed to the most VEGF and pro-angiogenic proceeding factors, because of the flow of aqueous along the pupillary edge. So you get early signs of neovascularization of the iris. These can be contrasted with healthy iris blood vessels bought of their pattern. Now, these NVI are often irregular in their appearance. These vessels can bleed resulting in hyphemia, so the way that I’ve seen this is there’s a reddish diffuse hue to kind of — or normal kind of otherwise clear structure, so nonpigmented trabecular meshwork, etc., sometimes you can even see the angles branching — excuse me, the vessels branching within the angle, but more often than not the way I way it is mostly nonpigmented trabecular meshwork and this can lead to eventual synechial closure. Now, these patients can often, but not always, present with elevated intraocular pressure. The reason for that, it can either be because of an open-angle mechanism or a closed-angle mechanism. in the open-angle mechanism, this is because of the mechanical blockage of the trabecular meshwork because of those vessels, but you can also get congestion of red blood cells if there’s a hyphemia, so numerous etiologies for patients with high intraocular pressure in neovascular glaucoma with an open angle. Many times these patients progress to synechial angle, so these images, open angle with NVA, and then the beginnings of synechial closure. So what ought to be your diagnostic workup? There’s numerous important things here. You have to know why the patient has neovascularization. Do they have a history of diabetes? If yes, how is their blood pressure/blood sugar control. Standard patients who are not aggressively treated, whose blood sugar was not aggressively treated were at three times the risk of developing neovascularization of the disc over nine years. Now, this is NVD, as opposed to neovascular glaucoma, but perhaps you could be generous in your extrapolation that then there may be a parallel with the incidence of neovascular glaucoma development. So how A1C, poorly controlled blood sugar on a daily basis, more likely to progress in neovascular glaucoma. However, I’ve seen patients who have gotten their blood sugar under control with healthy A1Cs, who still — there almost gets a point where the eye is just going off on its own somewhat independently of kind of systemic blood sugar control. But usually in those situations, there is a history of poor blood sugar control at some point, which then started that angiogenic stimulus. Now, if they don’t have diabetes, do they perhaps have a history of a central retinal vein occlusion? If so, when was it? When was it diagnosed? If it wasn’t owe pigsly diagnosed, when did the (officially diagnosed) If they’re going to develop neovascular glaucoma, typically it’s in the 90-day period. So it’s called 90-day glaucoma. It takes about that time frame on average for that angiogenic stimulus to start to take its effect with angle changes and elevated pressure. Now, if they don’t have a known history of diabetes, and that’s been ruled out, with blood sugar checks, A1C checks and there’s no evidence of a central retinal vein occlusion, particularly if it’s a unilateral presentation, well, you better rule out ocular ischemia, so you need to obtain a carotid ultrasounds to rule out carotid stenosis, and in many times they may need to get a carotid endarterectomy. Check the glucose, A1C and the blood pressure. Equally important is finding the why of the neovascularization? I’m a glaucoma specialist so I’m going to get a visual field, I’ll rule out any underlying edema, and whether you’re doing this yourself or working with a retina specialist, it’s prudent to obtain a fluorescein angiography to look for regions of hyperperfusion or neovascular which may be occult and may be picked up on IVFA. So these are some IVFA images of central retinal vein occlusion, proliferative diabetic retinopathy and ocular ischemic syndrome. What is our management? This isn’t rocket science, you just need to lower the pressure and you can do that with medications or surgery. I’m a glaucoma specialist so I’m going to focus on the first bullet point, but also you need to reduce that angiogenic stimulus, and so many times that consists of pan-retinal photocoagulation to treat those regions of hypoperfusion so that that eye doesn’t continue to create VEGF and then if they have macular edema, can you treat that with anti-anti-VEGF injections, in patients with florid ang genesis, I will often recommend that they see my retina colleague for an anti-VEGF injection to help regenerate those vessels. That helps minimize the risk of intraoperative hemorrhage and can improve the overall IOP-lowering effect from surgery. So we’ll talk more about management in the further slides. So let’s talk first about medication management. So now aqueous suppressants are thought to be more theoretically useful, but really the reality, at least in my practice is I often am putting these patients on maximum tolerated topicals, regardless of whether or not they’re aqueous suppressants as a temporizing measure before surgery, so many of these patients end up requiring surgery. Now, in the interim, some patients require systemic anhydrase inhibitors, typically those medicines are acet zolemide. You need to make sure they don’t have a sulfa allergy or renal dysfunction. Many of my patients here in Memphis are very poorly controlled diabetics with end-stage renal disease and so if that’s the case, I can still use a systemic carbonic — CAIDiamox, essentially, but I’m doing it at the lowest tolerated dose. And I counsel them, hey, you’re getting dialyzed but I’m not going to go too hard on this. Other considerations, if you’re seeing these patients acutely in the ER setting, pressure is really high, well, if it’s safe to, you can do an AC paracentesis for immediate lowering, but it can be a little bit tenuous in these patients, especially if they have florid Rubiosis, you don’t want to accidentally nick one of those blood vessels, because it may do more harm than good, but if you can safely get a AC tap in. As I’ve mentioned before, severe cases are often refractory to medical therapy and require surgery. So we’ll talk about surgical management. Just across the board, in literature and in my experience and patients do better with a glaucoma drainage device over trabeculectomy. That is because of the risk of trabeculectomy-flap scarring from neovascularization of vessels, and also, just think about there’s that pro angiogenic stimulus with VEGF, angiopoietin 2, circulating around, going through that flap, so these flaps will just scar much more easily than nonneovascular glaucoma patients, so my preferred glaucoma drainage device, well, if you don’t have access to glaucoma immigrants plants, you’ve got to go what you gotta do. More use of 5 fluoro uracil insections in the postoperative period to control scarring. Now, let’s talk more about glaucoma drainage devices, there are valve and non-valve and I apologize if this is very basic for some of you, but in these patients with neovascular glaucoma, my preference is valved GDDs over a non-valved GDD, like an Ahmed valve which is the clear one. You’re not messing around with like a ligating suture that’s going to break down after 6 weeks, and these patients are just have already failed many times maximum medical therapy, so — and some of these patients aren’t good at following up, really, so you don’t want to muck around with seeing them on a regular basis, starting medications like one at a time, waiting for that ligating suture to break down. Just put a valved GDD and you’ll get immediate pressure lowering. And there’s less risk of hypotony. These patients — I don’t have this backed up today here with what’s in the literature, but these patients, like, don’t do great. You know, you put the tube in, you get the pressure down, you start the drops one at a time. My observation is that that hypertensive phase, which many of us see following Ahmed glaucoma-draining devices, it tends to be more acute. Many times these patients you put the tube in and they end up on all of the drops anyways, so it’s challenging this is a very challenging form of neovascular glaucoma. What I emphasize to my patients is hey, it’s my job to get your pressure down and you’ve got to continue to see your retinal colleague for serial anti-VEGF if needed, to decrease that hypoxic stimulus, got to keep on getting your blood sugar under control. These patients require a lot more counseling and ophthalmic intervention because of that provide poxic stimulus and those pro-angiogenic growth factors. The other thing I’ve observed is that in these valved glaucoma-draining devices, you’re getting immediate aqueous drainage and what’s in that aqueous than VEGF and angiopoietin 2 and so many of these patients end up with those pro-angiogenic factors outside of, you know, around the plate and it’s going to cause maybe more scarring than in a patient without underlying NVG, so that exposure to that plate and that kind of capsule to those pro angiogenic growth factors might, you know, just ultimately limit how much of a sustained pressure-lowering we get. So it’s very challenging. Now, you can also do cyclophotocoagulation in refractory cases. I typically reserve CPC for patients who have already had Ahmed valve already. Micropulse laser is also an option and it has less chance of hypotony than a CPC but typically I’m reserving lasers for patients who are already status post Ahmed valve. Patients are more at risk of — so that’s another consideration to proceed with caution particularly with CPC in patients with neovascular glaucoma. So that’s what I have. I know it’s kind of a quick and dirty review, but you know, that’s neovascular glaucoma is just the most common glaucoma that I’m facing here in Memphis, most likely related to higher incidence of diabetes in my pop population here, and, so thank you for listening. What we’re going to do now is review those questions that I had at the beginning of the lecture. So the first question is: Which of the following is not considered a common cause of neovascular glaucoma, ocular ischemic syndrome, diabetic retinopathy, central retinal artery, central retinal artery occlusion, or central retinal vein occlusion. Three of these are the most common causes. One is not. All right, good. So, yeah, central retinal artery occlusion, which most of you got, it’s not considered a common cause, underlying etiology for neovascular glaucoma. Great. So we’ll go ahead and answer our next question: Which of the following is not a clinical sign of neovascular glaucoma? iris rubeosis, iris atrophy, iris atrophy, angle vessels and optic disc cupping? I’ll give you guys a few second and enter this review. OK, good. So the answer here I was getting at which of the following is not a clinical sign of neovascular glaucoma is iris atrophy. We’ve reviewed in this lecture, iris rubeosis, angle vessels and if the patient has glaucoma, most likely they have optic disc cupping, so iris atrophy is the answer I was looking for here. Last question: Which of the following is the optimal surgical intervention neovascular glaucoma, if you have everything available to you? Cataract surgery with goniotomy, trabeculectomy with might mice yip C, non-valved glaucoma drainage device or valved glaucoma drainage device such as an Ahmed? All right, so the answer I was looking for here, which most of you go got, is a valved glaucoma drainage device. Now, of course if you’re in a part of the world that doesn’t have access implants, then you gotta do what you gotta do, but you’re going to have to closely watch these patients because they’re going to be more prone to neovascularization of the flap. So the takeaways of this lecture here: The most common etiologies for neovascular glaucoma are diabetic retinopathy, central retinal vein occlusion and ocular ischemic syndrome. Key clinical features can include neovascularization of iris and angle. Management includes determining etiology for neovascular glaucoma and control intraocular pressure with medications but know that many of these are refractory and require surgery, and what I recommend are valved drainage devices, Ahmeds. If you have any questions or anything you want to correct about what I’ve discuss, areas of future discussions or lecture, happy to take feedback. So thank you so much. What we’re going to do now is I’m going to stop sharing, so I’m going to stop sheer and I’m going to review questions that may have came up in the Q & A. So thank you so much so much. Yeah, I I believe this question is asking what is the preferred treatment, well, that depends — we use Avastin here or Bevuzisumab mostly. There’s a patient with pseudoexfollative glaucoma, high pressure in presentation, CRVO, 360 synechial closure. Would you proceed with Ahmed valve? Yes, I would start with Ahmed valve. I really don’t do much CPC unless they’ve already had an Ahmed valve. So I would do an Ahmed valve. All right, I would not do a peripheral iriedotomy in a Rubyotic pupil because of risk of bleeding, and if you need to do a PI to rule out pupillary block or whatever, just get the patient to a retina specialist to regress that NVI with laser or anti-VEGF. What do you think is better in terms of neovascular glaucoma management? Well, I typically my retina colleagues are do intravitrial anti-VEGF and so I don’t have tons of experience with intracamera, but typically we’d get good results with intravitrial. I would not recommend laser in these patients. Selective laser trabeculectomy in these patients. I mean what’s going to happen if you do the laser in the angle when there’s neovascularization of the angle, could cause bleeding, neovascular glaucoma is not an indication for SLT. I’m skipping questions on things not related to neovascular glaucoma. What are the challenges while performing trabeculectomy. In neovascular glaucoma? Well, I’m not doing that mostly but in eyes in which I’m doing Ahmeds in with neovascular glaucoma, there’s just abnormal blood vessels everywhere, including the sclera and episclera, so I use judicious cautery for my tube patients, but you just imagine, well, if I had to make a trab flap in these patients, they’re going to need a lot of cautery, you’re trying to control blood vessels, but you know, so the challenges are intraoperative bleeding, and just postoperatively risk of bleeding and scarring, so it’s just hard to manage these patients with a trabeculectomy. I think. How does visual acuity affect — now, if they have any vision at all, I’m going to put a tube in their eye. So it doesn’t — if they’re NLP and it’s a blind, painful eye I’m recommending enucleation with my plastics colleagues. OK, why not non-valved GDD? We discussed that, risk of hypotony, poor performance in my patients, you’re mucking around with things like a ligating suture, and you know, you don’t get as immediate lower pressuring, which is ultimately safer for the eye, and there’s a higher risk of hypotony in those patients and so I’m doing a valve glaucoma-drainage device such as an Ahmed to not have to worry about them not showing up, to manage their inevitably high pressure until that ligating suture breaks down. That’s a little bit outside of my pursue as I’m a glaucoma specialist and not a retina specialist, but you’re doing PRP, you could do PRP fill-in, you might need to do some anti-VEGF. What is first, PRP or valve surgery? You’re going to get a different answer if you’re talking to me or any retinal colleagues, but the pressure is really high, you gotta get the pressure down. So my preference is put a tube in the eye, but they might need anti-VEGF beforehand. Does atropine have a role? No, What would be an ideal treatment. OK, so that’s a great question. For patients you’re diagnosing a CRBO in, they need to be monitored I would say ever, every four to six weeks with serial fundus exams, to watch for the development of neovascularization of the angle. So it’s called 90-day glaucoma because you typically get presentation of neovascular glaucoma so you really need to watch these patients closely. You’re welcome. Do you keep a patient with NVG with topical steroids long-term despite no pain? No, no, I really only use — in patients — what I use long-term low-dose steroids and [unclear] for are patients who have a blind, painful eye. So we try that first and if it’s still painful, I recommend enucleation. I’ve included my email in the PowerPoint and so you’re welcome to review that you’d like to reach out to me. Which anti-VEGF is best? Whatever you have available. We typically use bevusizumab because that’s what we have in our institution. OK, does age factor in terms of which method to use to correct neovascular glaucoma? I don’t think so. I think this applies. You just have to take, you know, management of high pressure in children and depending on the age, like babies less than 12 months or whatever, they require closer management postoperatively, that’s a whole other conversation in terms of surgery and post-operative care in infants. But I typically recommend — you know, these are recommendations that I think apply to all age groups. How many doses of anti-VEGF is optimum? That’s a good question for my retina colleagues, I’m not sure, I think in this country we really can’t do more than one injection, whatever the standard dose is, more often than every four weeks. is there any is there any special situation of NVA which contradicts anti-VEGF? Not sure what that means, but I can’t think of any. How many times can valves be repeated? Well, I’ve seen patients who’ve had three tubes in the eye. You only have four quadrants to work with, so I guess four times. Will emergency Ahmed valve control IOP without adequate anti-VEGF treatment, yes, you need to reduce that hypoxic stimulus with PRP or anti-VEGF treatments. ) reading) So now, if you don’t have an Ahmed valve available or if it’s very expensive, if you’re looking for IOP control, I would start trabeculectomy. If it’s just refractory to treatment, patient — I wouldn’t recommend evisceration or enucleation until the patient doesn’t see, so those are the patients that I’m referring for evisceration or enucleation, patients with blind, painful eyes. I personally do not perform psycho photo in blind, painful eyes, for me, I’m a little bit nervous about theoretical risk, so I just refer these patients for oculo plastics management. Typically I’m putting these patients on drops to temporize them for surgery and many times these patients need to be put back on drops after surgery, so yeah, if I’m setting them up for surgery I’m starting them on drops to get the pressure down, because I want to make sure they can tolerate the drops and aren’t allergic to them, because they’ll need them long term. I don’t have — FDA likes to limit things here when they’re doing their job but I’ve heard about Paul’s valve instead of Ahmed valve but I don’t have any experience with it. NLPI as I mentioned, I don’t personally do laser, I know of people who who do, I think that’s kind of an individual decision, but certainly if the patient really felt strongly about not having enucleation and wanted to have a laser, I would consider a laser, but typically blind, painful eyes, I refer to plastics. (Reading) So make sure they’re doing their drops, if the surgery fails, typically and if they only have one tube in their eye, I would consider, I would do — it just depends on the situation but I would do micropulse laser, because that can get the pressure down, especially in the presence of a tube, I don’t have data to back this up, but my observation at this institute is patients who are status post Ahmed valve have pretty good pressure-lowering effect after micropulse. I think it’s almost like it kind of improves fluid, you know, aqueous egress, I’m not sure, I need to look at the data there, but patients who are status post micro-valve, I’m recommending micropulse. Yeah, what is the role of anti-VEGF agents, we’ve discussed that. How much time should we wait to do drainage device after anti-VEGF? That’s a great question. I was just reading that you kind of get this golden window of a couple weeks, like one to three to four, where in that anti-VEGF is kind of kicking itself into gear, helping regress those vessels and at my institute with my patients here, I would like to do an Ahmed valve within one to two weeks of anti-VEGF injection, to try to get that tube in the eye while vessels are regressed. Let’s see here. We talked about how vision affects my decisionmaking, any vision at all, I’m going to put a tube in the eye. What is PRP valve surgery? That just depends on who you’re talking to, but really get the pressure down lower, because you can get flashings any vision loss in glaucoma is irreversible, so we want to get that pressure down lower. That’s a priority. Is it OK to do intravitreal anti-VEGF? Yes, if the pressure is high, you can do a tap, anti-VEGF injection, repeat tap. That’s what we do at our institution here. Neovascular glaucoma it is so hard to get the pressure down. It is. I hate NVG. If you only are have access to a cryo laser, yes, you just have to be careful because I believe that the risk of hypotony is higher in these patients with NVG as opposed to patients with other kinds of glaucoma. I (reading) Yeah, I think so, you have to consider that taken the good withed bad, you need to reduce those vessels, you’ve got to reduce that stimulus and you’re most likely going to put a tube in the eye anyways. Let’s see. What are the symptoms, actually? Good question. So in patients with — who are have acute NVG, they’re going to present with oftentimes — well, many times they have decreased vision regardless if there’s an underlying, you know, thing like diabetic retinopathy, central retinal vein occlusion, etc., a lot of times they’ve had blurry vision already, but it can get blurrier because of decreased vision, so pain, red eye, headache, things like that, symptoms basically from high pressure. So that would be the symptoms that I would expect with patients. You do bleb-er-vision, just lift up that flap, try it again. What is the mechanism of diabetic retinopathy leading to blindness? We did not get into diabetic retinopathy today. After the Ahmed valves be on steroids for about 6 weeks, if if they’re having a steroid response, I kind of taper to that or switch to a lower-potency steroid like Loprednol. What is the management of NVG without visualization of the fundus? We see that a lot. So well, got to get the pressure down, drops, surgery, and then once you temporize that pressure, why is the vision blurry? Is it vitreous hemorrhage? Is it a cataract? But really, priority is getting the pressure down. Why not non-valve GDD as effective as valve GDD? We kind of explained this. Now, it’s not a matter of effective, it’s just that you need to get immediate pressure-lowering response and so you get that with valved GDDs, because you’re getting immediate egress of aqueous through that valve as opposed to non-valved. The reason why the non-valved is you can’t have immediate — you need to do a ligating suture to basically — you need time for that plate to develop a capsule around it, OK? Because if you have immediate outflow through the non-valved tubes, you’re going to get hypotony. So non-valved you need to have a ligating stitch to allow around 6 weeks to allow a capsule to form around that straight. During that time, think about it, these patients really need regular follow-up, they need to typically be put on max drops afterwards, you may need to ligate — basically laser that ligating suture early, but like really the reality is, at least in my patients with neovascular glaucoma, you need immediate pressure lowering now, you can’t muck around with making sure they’re reliable, getting to see you, you just need to put a tube in that eye, get the pressure lowered. It’s not that the non-valves aren’t effective. They’re great; you get lower pressures with them. But you need immediate pressure lowering in these patients and so you’re just not messing around with that, put an Ahmed in these patients. So can NVG happen with — oh, without. Yeah, those are the most common. You can get different etiologies which I just didn’t cover here and so the answer is yes. What is your opinion needling drainage implant and pressure — I haven’t really done that, I don’t really know if there’s a role for that here. Typically that’s for other reasons, not related to NVG. How do prevent NVG? Great question. This goes back to counseling the patient: Controlling blood sugar, making sure their underlying risk factors are being addressed in those ways and basically serial and regular eye exams for vision, pressure checks, gonioscopies and dilated fundus exams, and so that would be it. I think I’m going to call it there. Thank you so much for participating. I hope you got a lot out of this, and feel free to reach out to me with questions and have a wonderful day or evening wherever you are.