Speaker 1 (00:00):
Tarsus Pharmaceuticals Incorporated applies proven science and new technology to revolutionize treatment for patients across several therapeutic categories, starting with eye care. Their lead product, XDEMVY Lotilaner Ophthalmic Solution 0.25% is FDA approved in the United States for the treatment of Demodex blepharitis. Learn more at tarsusrx.com.
Ogul Uner (00:45):
Welcome to the Pupil Pod where we use clinical cases to guide discussions on board review topics. I'm your host, Ogul Uner, and my guest today is Dr. Arsham Sheybani. Dr. Sheybani is a board-certified glaucoma specialist, professor of ophthalmology and residency program director at Washington University in St. Louis. And I'm very excited to have him on the podcast today. Dr. Sheybani, thank you for joining me.
Arsham Sheybani (01:08):
You are pretty phenomenal with the pronunciation of my name. It's like you're almost speaking legit Iranian. That’s amazing.
Ogul Uner (01:16):
Thank you. I appreciate that. With that, let's dive directly into our case. We have an 82-year-old woman who presents with five days of worsening left eye pain, redness, and blurry vision. She reports poor vision in this eye for several years, and she was told she had a dense cataract, but denies any history of ocular surgery, trauma, or known uveitis. Visual acuity is hand motion in that left eye, and the intraocular pressure is 48 mmHg. Examination reveals conjunctival injection, mild corneal edema, a deep anterior chamber, but there's 3+ cell in these tiny white particles in the AC and a dense hypermature cataract. You try to perform a gonioscopy, it's hazy, but it shows an open angle. And upon closer inspection, you see an intact lens capsule. Dr. Sheybani, what are your thoughts about the case and what additional questions would you like to ask this patient?
Arsham Sheybani (02:13):
Yeah, you look at a patient and one of the most important things before I even jump into any of this is what does the other eye look like? And is it pseudophakic? Is it phakic? What's the anatomic angle structure? You're trying to get a sense of, and you might say, oh, the angle looks open here, but you're going to get a sense of, what is their true physiology on the side that's not impacted? Because if you do see that maybe you have grade one angles on the contralateral eye and they're still phakic and it's not as hypermature, then you might lean toward a different route where you think the angle's closed because the lens is just so thick. Or if you're like, man, the other side is really open, they're phakic, but there's no chance this would be a primary angle closure mechanism, then you start going down the routes of, and without surgery or trauma, maybe phacoantigenic isn't a thing, but phacolytic could be.
Arsham Sheybani (03:05):
And one of the exam findings you might look for are, well, what does that hypermaturity look like? When they get really, really hypermature, enough for these higher molecular weight lens proteins to leak out, well, sometimes you'll actually see a little nugget of a very dense core, nuclear core that's kind of floating or swimming in this white sea of essentially just breakdown of protein and lens material, some of that does seep through an intact capsule. So I think contralateral eye is important. Also, what does that cataract look like? And then what are your KP findings? Because we have to be really mindful of this. Primary angle closure is going to be way more common of an issue and you can still get cell and flare with an acute primary angle closure attack. And I think sometimes what happens is we'll get referrals for what's truly primary acute angle closure glaucoma and the cell because of the attack and the ischemia that the IOP caused causing cell release inflammation, people are like, "Oh, it's probably a primary uveitic process." No, the uveitis is coming secondary from just the pressure going really high suddenly.
Ogul Uner (04:14):
Yeah, I think those were excellent points. I really liked how you mentioned that the angle closure mechanisms are just more common. And in this case, when you look at the contralateral eye, exactly like you said, that other eye is deep and quiet and still is phakic. So how does that help you in your decision pathway?
Arsham Sheybani (04:39):
Yeah, that's super helpful. So then the other side's open and you start going, well, again, let's just try to cover all bases. Was this a patient that had a prematurity? And I mean, 82, stuff like this isn't going to come up, but sometimes you could have eyes that are smaller on one side if they're more impacted than the other. And so that's kind of put them more into an angle closure. But I feel more comfortable this is more of an open angle mechanism. And the primary uveitic processes are still in play here, but if you start seeing, you're like, there's kind of chunkier white stuff. I mean, I think TB, syphilis, sarcoid are really going to be in your differential, but with a super hypermature cataract, you're like, ah, I might be leaning more toward this is protein seeping out from the lens capsule that's intact.
Ogul Uner (05:27):
You mentioned that there are several different lens-induced glaucomas. We talked about it maybe being a secondary angle closure mechanism and then an open angle glaucoma like we talked about. Could you maybe take us through your schematic? Where does phacolytic fit in this schema? You mentioned phacoantigenic. Talk us through how you think about whether an angle's open or closed and how you get through that decision tree.
Arsham Sheybani (05:53):
Yeah, absolutely. And the maturity of the cataract sometimes doesn't matter. If you look at patients that are microspherophakic, they'll have normal axial lengths, but really myopic refractions. And so if you do an ultrasound and you actually see this very, like a UBM especially, a very rounded spherical lens, well, that could just be a lens dislocation. So, a zonule problem that's causing the secondary angle closure. They might've had trauma that they don't even remember. And again, the zonules are bad and that's what's moving everything forward causing angle closure. So that's one set of it. The other side is the lens could just be so big, and you measure it with a biometer and it's like 6.5 millimeters. Well, in some people that could be enough to where it's going to take up space in an eye that might not have had as much space to give.
Arsham Sheybani (06:44):
And now you're going to get a secondary mechanism from just the lens being big. It's not even that it's dislocated. But then you start kind of thinking, well, say now we're going on the open spectrum. Uveitis aside, it's hard usually to get a lens that's hypermature without inflammation necessarily that's causing an open angle mechanism. Certainly, you remove the cataract, you're going to drop pressure, but that's not going to be why your pressure's like 50, 60. So now you kind of start thinking, am I just dealing with an opening angle glaucoma? That's very separate from this though. You have inflammation in the eye and you have a hypermature cataract. And so if you had a history of prior trauma or surgery, we actually, probably several times a year, two to three times a year, we'll get aborted cataract surgeries.
Arsham Sheybani (07:32):
And so, they've started the procedure, the zonules are really bad, and because the surgeon's really smart, they're like, look, we could potentially salvage this, keep an in-bag type of lens. They'll stop. And it's remarkable with steroids how well those eyes can really quiet down before we go in, sometimes two to three weeks afterwards. But if you don't go in and you don't do steroids, because that capsule's open, you're going to have this reaction, this hypersensitivity reaction to the lens proteins because again, they're exposed to the lens and you're not supposed to have that exposure. So that's more phacoantigenic glaucoma. And then when you look at someone who has a hypermature cataract and no lens capsule violation, but you start to see these whitish proteins floating around with a pretty significant reaction, you're going to have some chemosis, hyperemia. Well, now you start going, this might be a phacolytic component. And I think without taking an AC sample and 100% verifying it, it's still going to be a clinical diagnosis.
Ogul Uner (08:30):
Moving on to more of the phacolytic glaucoma diagnosis, since that's what we're considering in this patient, what are some clinical findings that you would see and what other etiologies are in your differential diagnosis?
Arsham Sheybani (08:44):
It does match with this case presentation where you will get a hyperemic reaction. It'll probably smolder for a few days. It's not going to be like they can tell you, oh, 100% it just started at this time point. So kind of more of a semi-acute type of presentation, which is what you're dealing with here. And the vision's probably going to be bad for some time. You're not generally going to find someone, because sometimes you'll get in a diabetic cataract like a flash white cataract. That's not going to lead to phacolytic. This requires a cataract that has been mature, mature for a while, hard to say exactly how long. And then over time that hypermaturity actually liquefies a bit. And when you get that liquefication inside the capsule, some of these larger molecular weight proteins can leak out. You might see a hypopyon or what we call a pseudo-hypopyon where you see this layering of even either the inflammatory reaction or the lens material layering at the bottom of the eye.
Arsham Sheybani (09:41):
Again, syphilis, sarcoidosis, TB, those are the big ones to kind of think about like Behçet's, another one that'll cause a pseudo-hypopyon. You could certainly have an endogenous endophthalmitis. This is something that you do have to be aware of. Say they've had bacterial seeding from a UTI and now it's an inflammatory reaction from an actual endophthalmitis in the eye. So those are critical things to rule out. But in this case, you're seeing the inflammation, super mature cataract, you kind of start leaning toward that side. And I think you've mentioned this before too, the lack of KP generally for that, it's not going to be this big mutton fat looking thing on the endothelium, but for the amount of inflammation, it's a little surprising you might not have as many KP as what you might expect, like large KP.
Ogul Uner (10:29):
I think that's a very big point that people really like harping on tests or when they look at these lens induced glaucomas, really there shouldn't be any KPs in phacolytic glaucoma. If you see KPs, you really should be leaning towards phacoantigenic. I really liked how you included endophthalmitis. I think that's something that people may not think about as much, but especially in these older patients who are more prone to getting infections, I think it's very, very important to keep in mind. And so let's say we take someone who's had phacolytic glaucoma for whatever reason, maybe they got enucleated or maybe they're postmortem and we're now taking a look at their eye. What would the pathology show in these patients when we look under the microscope?
Arsham Sheybani (11:15):
Yeah, you should have some lens protein material. People haven't really, as far as I know, found a true opening or anything in the capsule. This stuff is still going through the lens capsule on histopathology. And then you'll probably get recruitment of white blood cells that are coming in there. And generally the cataract itself, I think that's what I was alluding to clinically. It's not like you're going to get this 4+ NS or a black cataract that's going to cause this. There is some liquefication of the cataract, so it might have a little bit of whiteness to it with a core of an extremely dense lens in the very late stages. So, I think that's kind of what you're looking for on pathology. I don't know if you had any other ideas.
Ogul Uner (12:01):
I think you talked about it very consistently. There are these leakages of lens proteins that are thought to really clog the trabecular meshwork. It's really not direct lens fragments, like you said. The capsule's otherwise intact, the angle appears open. And something that was taught to me when I was a resident was that anything that has the name “lytic” in it has macrophages involved in the pathology. So “phacolytic” is macrophages engorging the leak lens proteins. For example, hemolytic glaucoma happens because of the hemosiderin-laden macrophages and phacolytic occurs because of lens-laden macrophages. So it's something to think about, not really clinically relevant, but I think really talks about the close relationship with inflammation and how these processes take place. And you mentioned the treatment for a little bit, but talk to us more about how you treat these patients acutely. When do you take this lens out and what are your thoughts on that?
Arsham Sheybani (13:10):
Yeah, first you do need to cool off the process that's going on. It's not like it's like an emergency situation to rush into it. So certainly hitting with steroids and treating the pressure topically is going to be what you want to do. You don't want to jump in and be like, I'm just going to do surgery in this case with a pressure really high. Now you're exposing yourself for things like suprachoroidal hemorrhage intraoperatively. But if you get things under control, generally your cornea will improve. I will even advocate using Muro if you have just corneal edema, definitely hit hard with steroids and then cycloplegia. And the reason is if the process goes on for too long while you're trying to kind of medically manage sometimes, there is a chance you're going to get synechial formation on the capsule. And sometimes that can make the case it's already difficult, a little bit more difficult.
Arsham Sheybani (13:53):
But yeah, topical drops generally, you might have to switch to orals if the pressure stays high, but the goal ultimately is you got to get the lens out. And so once things have settled down, your view is clear, then it's time to do it. And usually within a week or two, you should be able to gain control there enough to take them to the OR. You do have to be mindful though, if the cornea is trashed, sometimes you'll have to scrape the epithelium just to get a better view. There are techniques that are called tangential lighting where we'll go in and we'll put a light, almost like a sclerotic scatter type of situation, very high intensity light right at the limbus and allow that to actually illuminate internally. But the probably critical component that'll get your view clear—say the inflammation is under control, but those lens material, those particles are not going to go away—is make paracenteses, irrigate that out, and then you'll immediately have a little bit of a clear view until you start your cataract.
Arsham Sheybani (14:45):
And things like trypan are going to be important to stain the capsule. Be very cognizant of actually having an Argentinian flag sign because it could be intumescent as well. So needle decompression techniques to prevent that capsule runout are also going to be critical.
Ogul Uner (15:00):
I liked how you walked through a lot of the surgical steps as well. Before we switch gears, let's hear from our sponsors. We'll take a short break.
Speaker 1 (15:14):
Tarsus Pharmaceuticals Incorporated applies proven science and new technology to revolutionize treatment for patients across several therapeutic categories, starting with eye care. Their lead product, XDEMVY Lotilaner Ophthalmic Solution 0.25% is FDA approved in the United States for the treatment of Demodex blepharitis. Learn more at tarsusrx.com.
Ogul Uner (15:39):
Welcome back. We were talking about phacolytic glaucoma. Now we're going to switch gears to one of the angle closure variants that you mentioned, which we call phacomorphic glaucoma. Let's discuss the classic presentation in these patients and how do we differentiate this from a primary angle closure mechanism?
Arsham Sheybani (15:58):
Perfect. So, let's just rule out the zonule issue because that'll be one thing. And certainly on these cases, I'm getting UBMs if my view's not great when they're very hypermature, but the other eye is going to matter here. So, if the other eye itself is grade zero angles with a normal-ish looking cataract, but maybe 2+ and this size maybe 3+ to 4+, I would still favor primary angle closure as the mechanism. But if the other side looks pretty open and this one side's really hypermature, your biometry is going to help you. It should show a difference, maybe like 0.8 millimeters or one millimeter difference between the lens thickness between the eyes. And the reason why you get angle closure from a mature cataract is as that lens swells or thickens, it doesn't necessarily swell, but it'll thicken over time in the anterior posterior pathway, you're going to end up where you're going to push the iris forward.
Arsham Sheybani (16:53):
So you could have a purely pushing mechanism with a large lens that obstructs the angle. Now, the second thing that can happen is as the lens gets thicker, it'll actually induce a pupil block mechanism. Similar to primary angle closure glaucoma, you've just now compressed that lens against the iris, against the pupil border, and what we call the iridolenticular channel. So the channel between where the lens and the iris sits that moves the fluid from the ciliary body into the anterior chamber, that thickening of the lens could actually cause more compression of the iris against the lens, and now you'll get a pupil block mechanism. So that on UBM, and sometimes anterior segment OCT, you can see as a very curved, rounded iris, kind of like a bombé but more subtle. A PI there could actually help. If it's really phacomorphic from size pushing forward and you don't have a lot of pupil block, PI might relieve things.
Arsham Sheybani (17:52):
You have to be mindful, check for PAS, because if they have a lot of peripheral anterior synechiae and it's almost 360, if you PI that, you could tip them over if the pressure's not bad yet because there's not much TM left and the pigment will shed in that area. But usually you're going to want to get the lens out here. And it's the same type of thing as far as medical management. But yeah, you always have to, in the back of your mind, also be mindful of zonule issues.
Ogul Uner (18:16):
I think that was really comprehensive. You talked about when you would do an LPI. I think the UBM findings are really important. Do you do indentation gonioscopy? I know some people use different gonioscopy tools that may not allow them. Do you find that helpful? Tell us more about that.
Arsham Sheybani (18:35):
Yeah. So indentations where you're taking pressure with the gonioscopy mirror and you're pushing against the anterior chamber or the cornea to try to deepen the anterior chamber, always do dynamic gonioscopy is what I call it, which is you're varying the pressure just to see what you can do to induce an opening of the angle, check for PAS or see if there's plateau, and then take a light hand and you kind of back off. So you're almost like your gonio is going from periods where you're hardly touching the eye, the meniscus comes and leaves versus pressure. But to do proper indentation gonioscopy to try to break an angle closure attack, unlikely you're going to do it in phacomorphic. But in a primary angle closure glaucoma and they come in with acute angle closure, you can potentially do that by two mechanisms. You have to have the gonioscopy mirrors, and I won't even be specific with these, but just look for where the lens sits.
Arsham Sheybani (19:28):
If the lens rests on the sclera, you're not going to be able to do it. If the lens only rests on the cornea, then you'll be able to do indentation to potentially break an acute angle closure attack in someone who has primary angle closure. And you also have to remember if the pressure's high, say the pressure's coming in at 50, you're going to have to push with 60 to 70 mmHg. And the mechanism that's occurring here is one, you might burp some of that fluid that's caught behind the iris causing that pupil block through that area. And two, maybe you deepen things just with the compression, pushing things back and pushing the iris back so that you can allow for the fluid to flow through the TM. The reason why it doesn't work all that well all that often is a couple of things.
Arsham Sheybani (20:16):
One, you might not be pushing enough. Two, if the pressure's really high, your Schlemm’s might be collapsed. And so then it doesn't really matter what you do, you're probably not going to open things up. In primary angle closure, actually glaucomas, even though the AC's shallow, I still prefer an AC tap for a couple of reasons. One, it'll immediately open up that canal. So you want to get down to a pressure of maybe sequentially you start from 50 to 30 to 20, but down to 10s because you want episcleral venous pressure to give you a little bit of back pressure and push that canal back open. And then two, it reduces the ischemic effect that you have on the iris and the tissues that are absorbing your glaucoma medications because they're not going to work or be as responsive to anti-glaucoma drops in a high pressure situation where you could have ischemia.
Arsham Sheybani (21:05):
But you have to be mindful though, if you're not comfortable, the AC is too shallow, you might not be able to do an AC tap. And then don't forget to use oral agents. Someone who's naive to oral acetazolamide, they could have 40% to 60% of their aqueous humor production reduced just with that pill.
Ogul Uner (21:21):
I really liked how you talked about how it works in certain variants and not others and the role of the AC paracentesis in this scenario as well. You talked about how cataract surgery, again, is the definitive measure. Do you tend to go sooner in patients who have phacomorphic glaucoma compared to if they have a phacolytic mechanism because maybe there's not a lot of inflammation in the eye, or do you kind of favor again, medically treating the pressure and then whenever the pressure's normal, going in and doing it?
Arsham Sheybani (21:52):
I do think you want to do what you can to keep the pressure normal, but don't sit there and wait forever and kick the can down the road in these cases. If you've hit them with kitchen sink type of treatment with drops and orals, going to the OR is going to be critical, but counseling is probably the most important. One, you don't even know what their optic nerve function's going to be like. Two, you don't know what the zonules are going to be like. Three, the pupil might remain dilated because it's already caused sphincter ischemia. They might have a mid-dilated pupil the entire time. And then the other one, if you have to go in, because you have to, if you're trying to save the vision, in a high pressure situation, they're higher risk for suprachoroidal hemorrhages even when you make their paracentesis. Say some OVD burps out of the eye on accident, that'll shallow the AC, drop the pressure immediately, and now you can have a suprachoroidal hemorrhage. Because these eyes are also generally, if it's true, primary angle closure, there'll be a little shorter axial length, thicker sclera.
Arsham Sheybani (22:44):
And if it's phacomorphic, maybe less of a risk of that. But again, generally these are going to be slightly older patients, with more friable vessels, so the decompression is very real. That could cause problems. So, the counseling's critical, but I think go in as early as you possibly can without rushing in, but you got to give yourself a shot to cool things off of meds.
Ogul Uner (23:03):
I like how you really prioritize the medical management and that really decreases the surgical risk that our role plays as well. So, great.
Ogul Uner (23:15):
Let's summarize what we learned from Dr. Sheybani. We talked about lens-induced glaucomas, which comprise a heterogeneous group of glaucomas that are characterized by abnormalities in the angle or aqueous outflow that results directly either from the position, the size, the integrity, or the protein content of the crystalline lens. We talked about the hypermature cataract with a little bit of liquefication that is important for the phacolytic mechanism. It can be grouped as open angle or closed angle. Open angle ones are phacolytic glaucoma, lens particle glaucoma, or phacoantigenic glaucoma. And phacolytic glaucoma involves the leakage of these lens proteins through the capsule of a mature or hypermature cataract. You can see cells or white particles in the AC, an open angle on gonioscopy, and those lens-laden macrophages if you do pathology. Remember that “lytic” indicates the process involves macrophages. There'll be no KPs unlike phacoantigenic glaucoma, and the primary treatment is IOP reduction and inflammation control with medical treatment followed by prompt cataract surgery.
Ogul Uner (24:19):
We talked about phacomorphic glaucoma, which is a secondary angle closure glaucoma that occurs because the angle's narrowing from that mature cataract leading to pushing the iris forward or acutely precipitated by an intumescent cataract leading to a pupillary block. Though the symptoms can be similar, the angle will be closed on gonioscopy. We talked about how the fellow eye is really important to look at, especially in this scenario, but in any case where the fellow eye may have a normal AC depth or be pseudophakic, which may distinguish that from primary angle closure. We talked about how UBM can be very important in looking at zonule structures and other findings that we may not see on exam. And the primary treatment like phacolytic is IOP reduction, consideration of an LPI if there is an adequate view and we think there is a pupillary block mechanism, maybe you're seeing a little bit of that iris bombé, followed by prompt cataract surgery.
Ogul Uner (25:16):
Dr. Sheybani, anything else you'd like to add?
Arsham Sheybani (25:19):
No, I think you got it covered beautifully.
Ogul Uner (25:21):
Well, thank you. And Dr. Sheybani, before we end the episode, I ask all my guests a question. My question for you is, if you could go back in time and give your younger self one piece of advice, what would it be?
Arsham Sheybani (25:33):
It's probably something that I tell our trainees now, and especially when you start, and let's keep it more kind of related to medical and surgical fields, but I think a lot of times we get into really tough clinical or surgical situations and you worry about what's going to come down the line and you just want to get out of that situation. You don't want to be sitting there forever with phaco complications, but typically that's the wrong way to go. So I would say don't rush through adversity, think through it. And that's probably the best advice that I could give anyone as they're going through training and for the rest of their career.
Ogul Uner (26:13):
I really like that. It's very insightful thinking about what happened, how we can get better is ultimately what makes us humans, but better surgeons and better doctors. So thank you for that insightful comment. And Dr. Sheybani, thank you for joining us on this episode of The Pupil Pod.
Arsham Sheybani (26:34):
Thanks for having me. A lot of fun. Good pearls here. Thank you.
Ogul Uner (26:38):
And thank you to our listeners. See you next time on the Pupil Pod.
