Lecture: Pigmentary and Pseudoexfoliative Glaucoma

Hey, good morning, or afternoon, or evening, wherever you all are joining from. My name is Dr. Claire Wright. I will be lecturing today. I’m just going to go ahead and share my screen here. Bear with me. So my name, again, is Dr. Claire Wright, I’m located in Memphis, Tennessee, at the Hamilton Eye Institute, assistant professor of ophthalmology, glaucoma and cataract surgeon, young in my career. I’ll be lecturing today on pigmentary and pseudoexfoliative glaucoma. Hopefully this is a good review for everyone. I have no financial disclosures. So our lecture objectives are, discuss the clinical signs and the management of pigmentary and pseudoexfoliative glaucoma. So I’m going to start with some polling questions. So question number 1, we have a 32-year-old male with a refraction of minus 6 diopters in both eyes who presents with bilateral eye pain following a heavy workout. His intraocular pressure is 32 in the right eye, 38 in the left eye. Which of the following is an associated finding? So we’ve got some clinical photos here. We’ll give you some time to answer these. And we’ll have the same questions at the end of the lecture to review to see if we learned anything. Okay. Good distribution. So I’m going to go ahead and move on to the next question. So question number 2, for the patient in the previous question, assuming he has no evidence of glaucomatous optic neuropathy, what are the chances of his developing glaucoma given his underlying condition? 5%, 15%, 30%, or 50%? Okay. Also good distribution of answers here. I’m going to go ahead and move on to the third question. So you have a 32-year-old Scandinavian female who presents for routine eye exam. You note this finding on slitlamp exam. What is another characteristic of this syndrome? Okay. All right. So we’ll move on to the fourth question. For the patient in the previous question, assuming she has no evidence of glaucomatous optic neuropathy, what are the chances of her developing glaucoma from her underlying condition? 5%, 15%, 30%, or 50%? All right. So I’m going to go ahead and kick off our lecture hour. So the first half of the presentation, I’ll be discussing pigmentary glaucoma. So first described in 1979 by David Campbell, pigmentary dispersion syndrome and pigmentary glaucoma was noted to be due to mechanical rubbing between anteriorly located zonules and the peripheral iris resulting in pigment release. Again, etiology for both pig men dispersion syndrome and, later, pigmentary glaucoma, is this rubbing of zonular fibers. This can be exacerbated by accommodation, pupillary dilation, and is also associated with posterior bowing of the iris which you can see as a little divot. This is referred as reverse pupillary block. What are our risk factors? Male sex is one. Myopia is another, with average spherical equivalent minus 3 to minus 4 diopters. A family history of pigmentary glaucoma. And also a flat cornea is associated with pigmentary glaucoma. And my literature review, that’s what I’ve seen, as well as this posterior iris insertion and this concave iris configuration as mentioned. So how do these patients present? Well, the classic presentation you may read about if you’re studying for boards and whatnot is a young myopic male, 20 to 50 years of age, sometimes exacerbated by vigorous exercise, and this can result in wide fluctuations of pressure. And important to note, 15% of patients with pigment dispersion syndrome progress to pigmentary glaucoma. So, low, but still an appreciable percentage of patients. What are clinical signs of pigmentary glaucoma? Of course you can get intermittent elevation of intraocular pressure. And essentially pigment everywhere. Krukenberg’s spindle, you can see as demonstrated in the photo, a deposition of pigment on the cornea, spindle shaped due to the aqueous currents. You can also see pigment circulating in the chamber itself. You also see classically mid-peripheral spoke-like transillumination defects of the iris, due to the exact area of the iris rubbing against the zonules. On gonioscopy, you can see what’s called a pigment reversal sign wherein the pigment deposition is denser superiorly over inferiorly. I’m not sure of the reason, if anyone knows they can comment in the comment box, my theory would be because of aqueous flow, after traumatic glaucoma. You can see pigment at or interior to Schwalbe’s line. You can have an Scheie stripe, or you may see a Zentmayer ring or optic nerve cupping. Given the association with myopia, in the peripheral retinal exam you want to look for associated signs of retinal pathology like lattice degeneration which can be seen in myopes. This photo is a gonioscopic ridge. How do we treat pigmentary glaucoma? We want to lower the pressure, if they have glaucoma, that’s obvious. You can do that pharmacologically with our standard intraocular pressure lowering drops, beta-blockers, et cetera. What about pilocarpine? You may have read this can be a classic treatment, because it can reduce that concavity, therefore mitigating that mechanical rubbing of the posterior aspect of the iris against the zonules. But it has many adverse effects, such as headaches, brow pain, and given the association of pigmentary glaucoma with myopes you really want to use this medication with caution because of the association of peripheral retinal pathology. These patients are at risk for retinal tears and detachments and if you add pilocarpine, you’ll raise that risk. Laser management, in the last decade or so, later peripheral iridotomy has been a treatment to reverse iris back bowing and reduce that iridolenticular contact in early stages of pigmentary glaucoma. If you’re reducing that contact, you’re going to release or mitigate the pigment release and lower the pressure and perhaps prevent this patient from progressing to later stages of glaucoma. That’s typically what I’m doing for early stages of pigmentary glaucoma or pigmentary dispersion syndrome. What about argon and selective laser trabeculoplasty? The bottom line is, you just need lower laser settings, due to that heavy pigmentation, to prevent intraocular pressure spike following the laser. What about surgery? Well, as with other glaucoma — glaucomatous diseases, cataract surgery plus minimally invasive glaucoma surgery is a good option depending on the staging of the glaucoma. I will say that that heavy pigmentation can be very useful for angle-based procedures because trabeculectomy mesh may be identifiable. For more severe stages where lower pressure is required, but important to keep in mind for young males, you really have to be careful and watch carefully, these patients may require more flap sutures and just closer followup to watch for that complication. So that’s pigmentary glaucoma. Now I’ll do a review of pseudoexfoliative glaucoma. So first described in 1947 as glaucoma capsulare, this was differentiated from what was previously referred to as exfoliative glaucoma. This is peeling of the anterior lens capsule seen in glass blowers, people exposed to high heat. Dr. Dvorak noted in the ’40s there was a sect etiology that looked like exfoliative glaucoma but wasn’t. This doctor remarked there were a number of cases wherein there was anterior lens capsular findings but they were more precipitous or accretions of the substance as opposed to kind of peeling or exfoliation of the lens capsule. So she proposed to call this pseudoexfoliative of the lens capsule, which I thought was interesting, so true exfoliation rather than pseudoexfoliative. I thought it would be interesting to have a slide comparing the two. Obviously we’ll focus on pseudoexfoliative, the image on the left. But you see more of this kind of material on the anterior lens capsule which then histologically classically presents as these kind of iron filings, is the classic descriptor on his toe pathology slide. It’s a substance as opposed to true exfoliation, those glass blowers. It’s probably hard to see on the screen but there’s this kind of peeling or like sloughing of the interior lens capsule which on his toe pathology has this splitting appearance. Kind of interesting how different the two are, although you can see clinically how they might be confused for each other. Let’s get into pseudoexfoliative glaucoma. This is basically an etiology, deposition infiltration of the fibrillar extracellular material in the anterior segment of the eye and systemically. This is associated with LOXL1 gene mutation, involved in elastin metabolism. These patients commonly present unilaterally or asymmetrically bilateral with regards to clinical findings. This is more common in older folks, patients over 70. And, you know, classically seen in patients of Scandinavian or Nordic ancestry, as well as Mediterranean patients. Important to note, unlike pigment dispersion syndrome and the risk of developing glaucoma, 50% of patients with pseudo exfoliation signs progress to pseudoexfoliative glaucoma, so higher risk, so these patients need to be watched closely. What are the clinical signs? Elevated intraocular pressure. In this disease you get, as opposed to mid-peripheral iris defects, you get peripapillary atrophy, often described as this moth-eaten appearance. That description has really helped me in patients where you don’t have the lens to clue you in. You look at the iris and it looks a little bit kind of eaten up around the pupillary border. That could clue you in to pseudo exfoliation. On the anterior capsule of the lens you get this bullseye pattern of this material on the anterior capsule. You can also see, you know, varying degrees of phacodonesis, iridodonesis and/or pseudo phacodonesis. This can happen independent of trauma. Gonioscopy, you can have an Sampaolesi line. If you see narrow depth, that can clue you in into pseudoexfoliative glaucoma. If you’re doing coagulation, you may see coating of zonules of this substance, it looks like snow. And you can have optic nerve cupping if there’s associated glaucoma. Some clinical photos. On the left, demonstrating IOL subluxation. In the right, you know, I guess — there is a photo here, I did find that — some coating of this — zonules with this kind of material. How do you treat it? Like other glaucomas, you want to lower the pressure. Unfortunately when these patients present, they often have higher pressure than coag patients. They respond poorly to medical therapy and more frequently need surgical intervention over more common forms of glaucoma like coag. You know of course you can use your pharmacological tools that we discussed in pigmentary glaucoma. Many times they need surgical intervention. Really important to know, for patients with these disease who need cataract surgery, you must be ready to face a complex cataract procedure due to the zonular weakness. This could manifest in various ways depending on the severity. You can have difficulty with formation, you can have shallow chamber, capsular instability, or this high risk of vitreous loss as well as late IOL subluxation, high risk of requiring second surgeries. Okay. So that’s my short presentation, hopefully that was a good review. Now I’m going to get into those poll questions I had at the beginning and see if we all were paying attention. So we have this now 32-year-old male with a refraction of minus 6 diopters presenting with bilateral eye pain following a heavy workout. I had changed it, I don’t know if you all’s countries have CrossFit, a gym where you can work out heavily. His pressure is 32 in the right eye, 38 in the left eye, which of the following is an associated finding? Okay, great. So yeah, the correct answer is C, which demonstrates — so first of all, the patient, who is a young myopic male having high pressure after a heavy workout, this is classic for pigment dispersion syndrome or pigmentary glaucoma. We’re looking for what’s a slitlamp finding of a pigmentary dispersion or pigmentary glaucoma. A is lens subluxation, that’s more common in pseudoexfoliative glaucoma. B, you’ve got in a bullseye pattern of that material deposition, again, that’s pseudoexfoliative glaucoma. C is retro illumination photo, consistent with pigmentary glaucoma, that’s the correct answer. And then D is kind of a weird photo, it looks like an eclipse or something, but it’s supposed to show another retro illumination photo of peripapillary, which is consistent with pseudoexfoliative glaucoma. So the correct answer is C, most of you got it, thank you. Question number 2, follow the patient in the previous question, assuming he has no evidence of glaucomatous optic neuropathy, what are his chances of developing glaucoma from his underlying condition? All right. So most of you got the correct answer. The correct answer is 15%. So the patient in the previous question is describing pigment dispersion syndrome. And so in pigment dispersion syndrome there’s a 15% risk of progressing to pigmentary glaucoma. 15%. All right. So now we have our 73-year-old Scandinavian female who is presenting for a routine eye exam. You note this finding on slitlamp exam. What is another characteristic of this syndrome? Okay, good. I’m going to review, most of you got the correct answer, which is LOXL1 mutation. We’ve got a Scandinavian female who on routine exam has these findings. These findings look — this looks like a moth-eaten appearance of the peripapillary order of the iris. This is consistent with pseudo exfoliation. We’re going to look for an answer choice that matches that. So choice A is mid-peripheral transillumination defects, we know that’s consistent more with pigmentary dispersion syndrome or pigmentary glaucoma, so that’s incorrect. Commonly presents in myopic males, again, more common in pigmentary glaucoma. LOXL1 mutation, that is the correct answer. And then the last answer choice, exacerbated by vigorous exercise. We know, again, that’s another association with pigmentary glaucoma or pigmentary dispersion. For the patient until the previous question, assuming she has no evidence of glaucomatous optic neuropathy, what are her chances of developing glaucoma from her, excuse me, underlying condition? I changed the question a little bit. You’ve got 5%, 15%, 30%, and 50%. Okay, great. Most of you got the correct answer, it was just 50%. In patients who have underlying pseudoexfoliation in the absence of glaucoma, the risk of developing glaucoma is much higher than that in pigment dispersion syndrome, it’s 50%. You have to watch these patients carefully. So some lecture takeaways, I apologize for the busy slide, I thought if you take anything away from this lecture, it would be this slide. So as with any glaucoma patient, you know, every patient you see, new patient, you really want to take a thorough history, as things, you know, previous surgeries, ancestry, we want to get a sense of refraction. For the exam portion, you want to look specifically for these signs of pigmentary or pseudoexfoliative glaucoma. So again, you’re going to do a refraction or auto refraction, lensometry. You’re going to look for corneal endo pigment, such as Krukenberg’s spindle, look at anterior chamber depth. You’re going to look for iris transillumination defects, mid-peripheral seen in pigmentary glaucoma, or peripapillary seen in pseudoexfoliative glaucoma. If you have a patient who dilates poorly, that is associated with pseudoexfoliative glaucoma. That’s another thing to clue you in. Moving posteriorly, you’re going to look for anterior capsular pigment or deposits, seen in both conditions. You’ll look for irido, phaco, or pseudo phacodonesis seen in pseudoexfoliative glaucoma, or pigment on gonioscopy. As I’ve mentioned several times now in this lecture, pigment dispersion syndrome, there’s a 15% risk of developing pigmentary glaucoma, so small, albeit definitely present. You need to monitor these patients. And pseudoexfoliative, in contrast, there’s a 50% risk of developing glaucoma, so you really need to watch these patients. Then of course we’ve gotten some clues about understanding key management strategies for pigmentary and pseudoexfoliative glaucoma. Of course in addition to lowering the intraocular pressure, for both conditions. And pigmentary glaucoma, you can perform a reduction of iris back bowing and posterior iris chafing. You ought to use lower laser settings, and these are pretty good angle based surgery candidates given that heavy pigmentation of the trabecular mesh work, helpful if you’re doing minimally invasive glaucoma surgeries. For pseudoexfoliative glaucoma, these patients rapidly progress, often require major incisional surgery, and you have to keep in mind that high risk of complications seen during cataract extraction. As I mentioned, due to the zonular weakness, high risk of visit riyal loss and late IOL subluxation due to that zonular loss. My references, and thank you for your attention, it was a pretty short lecture but hopefully a good review. If you have any questions, you’re welcome to type them in the Q&A, or if you’re going to watch this later, you can email me at my University of Tennessee email address seen here. So thank you very much. I’m going to stop sharing. Let’s see here. There we go. All right. So now I’m going to go ahead and go to the Q&A. So first question, is laser PI a curative treatment for pigmentary glaucoma or will most patients need to continue with medication long term? So I think it depends on, if you’re getting this early, if it’s pigment dispersion syndrome over moderate, mild, severe glaucomatous optic neuropathy, if you get this early and perform the laser, basically reversing that back bowing and, you know, stopping the pigment release. So if you get to it early, they may not need — I have a couple of patients who I treated, pigmentary dispersion patients who I treated with LPI and they don’t need any drops. It just depends on. If they do have glaucomatous optic neuropathy, depending on the staging, they may still need treatment, pharmacological treatment or surgical treatment. The bottom line is, with any glaucoma, get to it early, and you’ll be rewarded for it with fewer medications and interventions. Okay. So hopefully that answered your question. So 75-year-old male patients who have SOAG with pseudoexfoliative glaucoma, he is phakic and — basically to summarize, there is this patient, 75-year-old patient who has got pseudoexfoliation, phakic, and some cupping, on three medications. So what would be the preferred surgical option? If he’s 75 years old and he’s having a visually significant cataract, if he’s having glare, whatnot, functionally limiting, I would recommend getting to that cataract earlier rather than later because if you wait for it to get more dense, that cataract is going to be more complex to remove with a higher risk of vitreous loss. So if you’ve got cupping, I guess it depends on the staging. It sounds like this participant who is asking has performed a phakic trabeculectomy. I think that’s reasonable. We actually — kind of a sidebar that is related at the American Glaucoma Society meeting a couple of weeks ago, they had this kind of panel discussion where, you know, it was about lens removals. So they presented various cases of glaucoma. One of the cases they presented was a patient with pseudoexfoliation, asking, hey, should we do the cataract surgery now or later. It seems like across the board the panel was like, take care of it now, get that lens out, help that patient’s vision, you can do a combined trabeculectomy as you did, and you won’t have to worry as much about vitreous loss and complication. I think your treatment approach was reasonable. I know it’s kind of a roundabout way of answering your question. I think the bottom line here is, if they’ve got a cataract and they’re having some visual symptoms from it and they’ve got pseudoexfoliation, yeah, take care of that cataract and with or without concomitant trabeculectomy is reasonable. So if a pseudoexfoliative patient has signs of pseudoexfoliation, but normal visual field, how often should they be followed? Probably in my opinion this is high risk glaucoma suspect. I personally see these patients twice a year for basically alternate annual visual field, nerve scan, we use Heidelberg, I alternate that with scans. So once a year. How do you determine who is a good candidate for laser iridotomy? Specifically, it depends, in the absence of glaucomatous optic neuropathy, I always recommend LPIs in these patients to reduce that back bowing, mitigate pigmentary release, and reduce that risk of progression to glaucoma. But if they’re later in the disease course, moderate, severe stage, you know, getting close to burnt-out pigmentary glaucoma, that LPI, even if you stop the source of the pigmentary release, you’re still going to need to address the glaucoma. So it just depends, if it becomes more nuanced for more progressed stages of the disease. Plus, you know, with LPIs you run the risk of pressure spikes. It becomes a little bit more of a discussion and an individualized choice for more moderate to severe stages of disease. And you might be looking at more surgical interventions as opposed to laser for those options. So for me, definitely pigment dispersion, the absence of glaucomatous optic neuropathy, maybe mild, borderline moderate stages of pigmentary glaucoma is when I would be recommending LPI. So how do we differentiate between old maybe pig mended KPs with a Krukenberg’s spindle? KPs, which are keratic precipitates, I believe it’s called Arlt’s triangle, correct me if I’m wrong, typically in the lower aspect of the corneal endothelium, Krukenberg’s spindle is kind of about central location, in my observations of the corneal endothelium and is in a spindle shape as opposed to anteriorly on the cornual epithelium, due to the aqueous current. You kind of — if you’re having a hard time, you’re not going to hang your hat on just one finding. You’re going to look for also transillumination defects, heavily pigmented, trabecular gonioscopy. You’re not going to make a diagnosis just based on a corneal endothelial pigment, you’ll look for other findings. Looking at the kind of shape of the deposits I think will be helpful. So — all right. I’m not sure if I understand this one question. Does anterior intersection coexist with pseudoexfoliative glaucoma or pigmentary glaucoma? That’s a complex question. I think it probably depends on the patient. So certainly, you know, you can get patients with an underlying history of systemic inflammation who have, you know, underlying uveitis plus one of these two glaucomatous etiologies we discussed today. We’re trying to go for simple review here. So yeah, you may have that. But it’s kind of — that’s a little bit more nuanced. Okay. So there’s kind of a question about kind of discussing the relation between cataracts and pseudoexfoliative glaucoma. That’s just if you wait too long to take the cataract out, which I don’t recommend in pseudoexfoliative glaucoma. If you wait too long, the cataract gets too dense or unwieldy, that’s going to be a high risk for vitreous loss. I definitely wouldn’t recommend waiting until it gets to the Morgagnian cataract point before you address that. Okay. So is there a chance during laser PI that more iris pigment will be released causing aggravation of the symptoms? Sure, as with any syndrome, you’re going to run the risk of a pressure spike. So you want to counsel the patient on that, pretreat if you would like with intraocular pressure lowering medication. Typically you can do — I usually do a drop of Ramotidine. Ultimately the goal of the laser peripheral iridotomy is to reverse that back bowing. I think it’s worth the risk of pressure spike in this pigment dispersion syndrome and mild glaucoma patients. Let’s see. So yeah, with a patient, kind of older patient, 80-year-old with pseudoexfoliative glaucoma, what’s the best management strategy? She’s phakic, depends on the stage of glaucoma. And of course her health and kind of where she’s at in terms of, you know, expected life expectancy. I have a lot of patients in their 80s and 90s who are really active. So it just depends. You want to choose your, you know, surgical — choose your therapy based on the patient’s kind of, you know, other issues, like life expectancy and kind of activity level. So this patient is phakic and having some issues with the cataract, you can consider combined phacotrabeculectomy, if she’s frail you can relate to it pharmacologically. I know it’s a frustrating answer. It depends on the patient. Okay. So how do you make a choice to go for a combined phako trap as opposed to flow in pseudoexfoliative glaucoma with cataract? Well, we don’t have pressure flow in this country, I can’t wait. I would always choose phako PreserFlo, it’s a minimally invasive procedure. But we don’t have it in this show. So I can’t really answer that. Give the FDA a little more time, maybe I can come back to that. Okay. So let’s see. Can a patient have a shallow [inaudible] without pathological condition? Sure, if it’s a shorter eye, he can have a shallow chamber. You don’t necessarily need a pseudoexfoliation and kind of anterior positioning of the lens. Kind of a longer question, let me read this. 70-year-old male presenting with pressure of 36 in the right eye, 12 in the left eye, signs of pseudoexfoliation at the pupillary area in both. >>> Right tumescent white cataract with shallow angle, what is appropriate diagnosis? That’s a little tricky. Pseudoexfoliation or phakomorphic? If there’s signs of the moth-eaten appearance of the peripapillary border, if you look at the deposition of the anterior capsule and you see that, that’s probably pseudoexfoliation. In the right eye he may have combined glaucoma, for whatever reason, trauma or whatnot, that cataract has progressed more quickly. So that could be a combined mechanism glaucoma. But I would certainly with those signs of the peripapillary findings, I would be very careful during cataract surgery, watch for zonular weakness. Can we use selective laser trabeculoplasty? I remember reading somewhere that patients with pseudoexfoliative glaucoma don’t necessarily respond very well to SLT. It may depend on their staging and pressure goal. Many times these patients progress quickly, high pressure, poorly responsive to more conservative measures. And so you do oftentimes need to get to more heavier duty incisional surgery. You can try it, if there’s time, and they’re mild stage, but it may not work. So there’s a question about primary angle closure which I’m not going to answer because we didn’t discuss that today. So yes, there’s a remark about pilocarpine can cause posterior sinequia formation, that’s definitely true. I don’t use it routinely, but that is a discussed treatment for pigmentary glaucoma. Do pigmentary dispersion syndrome patients and pseudoexfoliative glaucoma patients tend to have more inflammation post cataract surgery? I don’t know. Based on my observation, I don’t think so. But, you know, that’s probably just a situation where you use individualized treatment. If you’re seeing that postoperatively, treat that as appropriate, but I haven’t seen that in my literature review. I don’t think so. Okay. How effective is SLT in pigmentary and pseudoexfoliative glaucoma? I don’t have the exact numbers, but as mentioned, SLT is just kind of anecdotally or observationally or effective in pigmentary glaucoma than pseudoexfoliative glaucoma. It’s just depending, that’s related to the clinical course. So, you know, the pseudoexfoliative glaucoma tends to rapidly progress, really high pressures, big fluctuations, typically go on to need incisional surgery. You might be just kind of wasting time either ALT or SLT for pseudoexfoliative glaucoma. Pigmentary glaucoma, you know, depending on the stage, I think that that’s a more reasonable option than in pseudoexfoliative glaucoma. So I’ve used it before in pigmentary glaucoma with good results. It makes depends on the stage. But it’s nice, you got great pigmentation of the trabecular mesh work, you just need lower laser settings because of the heavy pigmentation. Okay. So yeah, another question about followup for pseudoexfoliation in the absence of glaucoma. So yeah, I personally see these patients about twice a year for — and the one visit would be visual field RFL and six months later I do dilated photos. That’s my personal kind of followup for high risk glaucoma patients, glaucoma suspect patients. Others might see them just once a year. All right. Okay. So I’m going to go down to this question. Can you discuss again, briefly discuss again the relationship between high myopia and these conditions. So yes, in pigmentary dispersion syndrome and pigmentary glaucoma there is an association between moderate to high myopes typically in the range of minus 3 to minus 4 diopters. You want to, in addition to looking for these clinical signs of pigment dispersion syndrome, you also want to do a very detailed dilative exam to look for peripheral retinal pathology, and you really want to be mindful of this retinal pathology if you were to pry pilocarpine because of the risk of retinal tears and detachments. Also with patients wherein you’re going to be performing trabeculectomy, these patients need more sutures on the trabeculectomy flap. I don’t know of a relationship between myopia and pseudoexfoliative glaucoma. That brings us to the end of our Q&A. Thank you so much for your time and attention. I hope you enjoyed this lecture. Feel free to email me with any questions. And have a wonderful day or evening wherever you may be. Thank you so much.