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 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. Rehan Hussain. Dr. Hussain is a board-certified ophthalmologist and vitreoretinal surgeon at Midwest Retina Consultants in Illinois, and I'm so excited to have him on the podcast today. Dr. Hussain, thank you again for joining me.
Rehan M. Hussain (01:05):
It's been an honor. I really appreciate the invitation.
Ogul Uner (01:08):
Thank you. So, let's delve right into our case. We have a 36-year-old male who's coming to your clinic with a five-day history of blurred central vision and distortion in his right eye. There's no associated pain, redness, or photophobia. He reports going through a divorce recently and uses intranasal fluticasone for allergic rhinitis. Best corrected visual acuity is 20/40 in that right affected eye, 20/20 in the left. IOP and anterior segment exams are normal. You do a DFE. The right eye shows this well circumscribed area of serous retinal elevation involving the macula, no hemorrhage or exudation, left eye is normal. You do an OCT through the area. It shows a dome-shaped serous retinal detachment with clear subretinal fluid and some RPE irregularity in the far superior macula of that same eye. Dr. Hussain, what are your initial thoughts about this case?
Rehan M. Hussain (01:56):
Yeah, so just from my pattern recognition and seeing it so often, you've described a textbook case of central serious retinopathy. So, talking about the history, you mentioned the divorce, you talked about the fluticasone. So, he's got two major risk factors already. We know he's stressed out, he's taking steroids, so that already kind of pushes you strongly towards considering that diagnosis. We had already mentioned that he had basically a lack of inflammation, lack of photophobia, redness, pain, so you're kind of ruling out the inflammatory spectrum of diseases that can cause a serous retinal detachment. So, you told me what the exam findings are, of course, probably in the real-world OCT would already be obtained. I would probably be looking to get an FA based on that. I'm sure it would confirm there's subretinal fluid, maybe looking for other things like a PED, maybe examining the thickness of the choroid, which I probably wouldn't measure it, but I'd eyeball it and just say, "Does this look thick?" You mentioned too that this is a young person, so that kind of eliminates the likelihood of it being wet macular degeneration.
(03:01):
And so yeah, I mean it's just classic central serious retinopathy. So, I would do the FA. Well, I don't actually always get the FA on the first visit. It kind of depends how the flow of the day is going, but I would consider that or maybe just say, "You know what? I'm very confident that this is CSR and I might get an FA on a subsequent visit if things aren't improving and take it from there."
Ogul Uner (03:20):
That's perfect. And so, our topic is CSR, as you said, central serous chorioretinopathy. Tell us more about what this disease is. And you mentioned other etiologies in your differential diagnosis. Kind of talk about your algorithm when you see someone who looks like they have CSR, what are other things you're thinking of?
Rehan M. Hussain (03:41):
Yeah. So, CSR, it can be acute or it can be chronic. It's a condition characterized by thickened choroid, dilated outer choroidal vessels. There's a spectrum of diseases of which CSR kind of falls in the middle of that spectrum and it's characterized by a serous retinal detachment. We're going to get into these other diseases I guess later on, so I'm not going to get into that yet. But when I'm thinking about the differential diagnosis, other things that I didn't mention, I probably won't repeat. The wet AMD, of course, something about age, presence of drusen, presence of hemorrhage, family history, but then there's things like even a choroidal tumor, like a nevus can leak fluid or a vascular choroidal tumor can leak fluid. So, you would think about that. But a lot of times you would just see that on the exam. Even a melanotic nevus, you would still kind of be able to tell that it's on there, but it does help to get imaging like fundus photos, fundus autofluorescence.
(04:38):
Sometimes it can make it more obvious than your exam. So, I would do those types of tests. I would also perhaps ask about some systemic issues, sleep apnea is a risk factor, certain medications, and maybe even beyond steroids, you would have maybe a milder association, but you would ask about those things. And then Cushing’s syndrome or things like that nature, you would want to inquire about that because that can have an association.
Ogul Uner (05:04):
I think you hit it right on the head. You talked about how it's a disease of leakage at the level of the RPE. We have these dilated choriocapillaris vessels. You talked about the different spectrum. I think VKH is definitely something that this can be confused with. So, you mentioned the importance of ruling out inflammation and then looking to see sometimes not in the acute stage, but in the chronic stage, you mentioned that there could only be pigment changes. So sometimes these can look like pattern dystrophy or other inherited retinal dystrophies. So, you mentioned the importance of multimodal imaging as well. You also talked about some risk factors. So, you said that you would check for systemic associations like endogenous hypercortisolism or Cushing’s syndrome. You talked about sleep apnea; you talked about steroids. What other risk factors do we see in patients with CSR? What's a classic CSR patient who walks through your door?
Rehan M. Hussain (06:00):
Yeah. You ask them their profession and there's the stereotypes like engineer, lawyer, high achieving person, type A personality, that's kind of classic. I guess I've heard caffeine might be a loose association. I don't know if I ask people. I don't know if it really changes much, but I do ask them about that. But in the real world, there are people who don't check any of the boxes. Some people are so chilled. They're like, "Oh, I'm not stressed. I don' take any steroids." It just happens anyway. So, I think it's good to know what the classic findings are but then be open-minded that there are a lot of people who just get it who don't even have an obvious risk factor.
Ogul Uner (06:37):
Yeah, definitely. And then as we talked about, corticosteroids could be very varied as well. If someone's getting intramuscular corticosteroids, inhalation, epidural, even other routes can be associated with CSC. So, as you said, the fluticasone use, even though it's far from the eye, can definitely be implicated in it. And interestingly, use of certain intraocular steroids, like topical steroids are not as implicated as systemic ones, which I've always found really interesting.
Rehan M. Hussain (07:08):
That is very interesting. But going back to what you said, a lot of people don't even realize they're on steroids. I asked about creams because a lot of dermatologic conditions, they're taking a steroid or inhalers. So, a lot of people don't even know until you ask them or then you're like, "Oh, I get an injection in my spine or my hip." And you're like, "Okay, that's definitely high risk." So, you have to really push people because they won't know half the time.
Ogul Uner (07:30):
Definitely, definitely. Some organ transplant recipients may not know that they are on low dose prednisone either. It's very common for those patients to be on certain immunosuppressive agents, so they'll know that, but in most cases, they have a very low dose, sometimes 5 mg of oral prednisone or 2 mg of oral prednisone with it and they may not completely realize that. So, I think you hit it right on the head that it's important to ask for that. Moving on to the clinical features, you mentioned that CSR could be acute or chronic. Let's discuss how acute CSR presents and how you distinguish that from chronic CSR.
Rehan M. Hussain (08:06):
Yeah. So acute CSR, they just show up with the symptoms. They have a scotoma or metamorphopsia. It'll be their first time. They're usually anxious about it. There'll probably be a more exaggerated presentation. Well, it doesn't always, but sometimes you'll see a lot of fluid, and you won't see usually those long-term pigmentary changes yet. That's something that develops later on down the line. But if you're looking for a chronic CSR, there may or may not be fluid. You could catch them at a moment where the fluid's gone, but you just see this sort of weird pigment granularity. The fundus autofluorescence looks salt and pepper. You might even see previous guttering, pigmentary changes on the autofluorescence. So, you can't rule out CSR even if there's not fluid because you could say, oh, okay, maybe you had it and it’s hard to prove it, but it's definitely in the back of your mind when you see somebody without fluid but have those changes.
(08:57):
And as you had alluded to earlier, you definitely also consider things like a pattern dystrophy or kind of like less common diagnoses that we probably in the day-to-day forget about sometimes to even consider. And in CSR, it can be bilateral, it can be unilateral. So, it's definitely in consideration regardless of if it's either bilateral or unilateral.
Ogul Uner (09:17):
Yeah. I think you summarized really well that depending on the time period, it can change as well. If you've had fluid for three months or four months, generally the acute stage is how this is characterized. I think you hit it really well that these patients tend to come in really anxious because they tend to have this hyperopic shift from the elevation of the retina. Most of the time you can have this dome shape or the subretinal fluid with this serofibrinous exudate and you're going to have different patterns of exudation. You talked about the presence of a PED that can be seen in about 60% of eyes. So, in addition to subretinal fluid, sub-RPE fluid is something to look out for. And then in chronic CSR, you mentioned the bilaterality. I think I read that about 40% of these can be bilateral, so it's really important to image the fellow eye.
(10:08):
Even if you don't see anything, I think the FAF features are very important, and we'll talk about those more. And I think the treatment kind of differs based on those as well. But before we talk about imaging and further treatment, let's take a quick break to hear more from our sponsors.
Speaker 1 (10:33):
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 (10:59):
Welcome back. Let's talk more about CSR imaging and treatment. So, Dr. Hussain, what is your imaging of choice in these patients? If you had to pick one modality of anything that we use in clinic, what would it be? Do you find that ancillary imaging modalities help you in your management and what does multimodal imaging classically show?
Rehan M. Hussain (11:21):
Yeah, I think for me, the non-negotiable is always OCT. It's easiest to get, it's quick, it's not invasive. It mostly confirms the diagnosis if you have good pattern recognition of everything else. So that's kind of essential and it's the best to monitor response too because you're going to get that pretty much every visit to see how it's going. I think FA is nice for sure to prove it, to see if you're going to do a targeted approach of some sort, where to focus that at, where the leakage is happening. There's ICG, which I'll honestly say I'd never do that. I'm sure at academic centers maybe that happens, but in the real-world private practice, not so much. And then the fundus autofluorescence is nice too because you can show those chronic changes at the pigmentary RPE level with that, but not essential, but nice to have, good for educating the patient and all that.
Ogul Uner (12:11):
Yeah. And do you use OCT angiography in any of these patients?
Rehan M. Hussain (12:17):
I've had a few jobs, and not all places have the OCT angiography, so I wouldn't say it's an essential thing. One of my jobs I would probably do it because I'm just so curious to see it and it's nice because sometimes, they can develop a CNVM and it's good to have a photo of that. But no, that's not really a part of my typical workup.
Ogul Uner (12:34):
Yeah. I think you highlighted really well that different imaging modalities show different things. In the BCSC, they'll classically talk about the different FA findings, which can really differentiate it from a CNV. So, the so-called ink blot appearance where you'll see this hyper fluorescence and it'll continue to enlarge. It's seen in about 30% of patients. Another classic smokestack pattern can be seen in about 12% and then this minimally enlarging spot in about 7%. And as you said, the leaking areas can correlate to the hyperreflective areas on infrared as well. So, looking at the infrared image with your OCT, if you don't have access to fundus imaging, or FAF can also be helpful. You talked about ICG. Again, it's largely been supplemented by OCT even for detecting those possible areas of CNV or those hotspots, the vascular hyperpermeable areas, but it can be a helpful adjunct. So, I think you've summarized that really well.
(13:38):
You mentioned that CSR sits in the middle of a spectrum of diseases. Could you talk more about what that spectrum represents and how does CSR fit into that spectrum?
Rehan M. Hussain (13:49):
Yeah, so there are four that we're going to cover here. And so, at the most mild form, there's PPE, pachychoroid, pigment epitheliopathy, sorry. And for that one, the patients are probably underdiagnosed a ton because they don't have symptoms, there's no fluid. It's really just an exam finding or imaging finding of this thickened choroid with dilated outer choroidal vessels, maybe some mild RPE changes. But since they're not symptomatic, they're probably not complaining or getting it checked out, probably way underdiagnosed. I probably am not, even if I'm seeing it, thinking about it, it could easily be just kind of missed or glossed over because it's not something that is really drawing a lot of attention. Then you have CSR, which is the big name that everyone knows, which we spend most of our time discussing. And basically, they're symptomatic now and there's fluid. I'm not going to repeat everything we just said.
Rehan M. Hussain (14:42):
Then you have pachychoroid neovasculopathy, and that is basically a type 1 CNVM that forms, really kind of have a lot of overlapping features with wet AMD, except I guess the demographic is different. It'd be more like in a younger patient, there'd be absence of drusen, probably be unlikely to get hemorrhage, but I'm sure there could be a secondary CNVM in some rare cases. But you would treat that with an anti-VEGF agent if there was fluid and they can have a good prognosis. And then the more severe spectrum would be polypoidal choroidal vasculopathy, which is kind of like a variant of wet AMD, but it has some unique features. One, demographically, it's less likely to be Caucasian, more likely to be African American or Asian. They can get a lot of exudation and hemorrhage. Interestingly, there have been studies that said anti-VEGF alone isn't as good as anti-VEGF plus PDT, but those studies were done when we had LUCENTIS.
(15:40):
So, I'd be curious now that we have VABYSMO or EYLEA HD, maybe people don't use PDT as much. I know PDT is not even that readily available in a lot of places in the community. So, while the data supports that, maybe it doesn't actually happen in the real world as much as you would think. But those are basically the different flavors of pachychoroid spectrum of disease.
Ogul Uner (16:02):
I think you summarized that really well with varying degrees of severity. I think there have been some more recent studies looking at second generation anti-VEGF agents in PCV and that they work pretty well. And as you said, PDT may not be as available. So, I think that segues really well into our treatment question. So how do we treat CSR? How do we treat acute CSR? Is there treatment for chronic CSR? And how do you discuss these options with your patients?
Rehan M. Hussain (16:34):
Because we know it has a self-resolving course in many instances, it is reasonable to just watch it first. You want to tease out why it's happening and see if there's something you can reverse. So, if they're on a steroid, that's the easiest. If you can convince their doctor who's giving it to them that it's safe to kind of wean off the steroid, then you have that discussion. Stress is hard to fix because the divorce of this patient is not going to go anytime soon. A lot of things in life are stressful. These people maybe have a personality predisposition to be stressed out because they're type A. So, I mean, you just say, oh, try to find some way to do yoga or something. And I don't know if it really works, but you just have to mention that. But yeah, I mean, first I would observe, but I actually have a pretty low threshold to offer a mineralocorticoid agonist.
(17:26):
Even though I know the data's not great, I think the patients just kind of like that I'm taking it seriously and starting something. And people are generally open to trying a pill and I'm like, "Hey, listen, this may or may not work. If it feels like it's working, it could be just that the disease got better on its own. But if you're really kind of eager to get this on the right track and you don't want to wait three or four months to start it, we can probably try it now." And I've never gotten burned on that. I know you have to think about sure they urinate more often because it's a water pill, their potassium levels could get elevated. And I would probably just do a little bit of a probe into their medical history, like do you have some sort of cardiac issue or hyperkalemia could be a problem or some sort of renal problem.
(18:07):
But if they don't have that, and they usually don't because they're younger patients, then I try it and I say it's true, it does look better, but I tell them, "Hey, I don't know if it's better because of this or because it would've gotten better." But then I'll usually keep them on that. I do eplerenone and I'll keep them on that. I'll start at 50 and then if it's good for a while, I'll drop them to 25 and then I'll taper off. It's not a steroid, but I kind of treat it like a steroid. And that makes it, I don't know. It just feels like I'm not blowing them off, but if it doesn't work out well, then you start to think about the other options. We know PDT is probably the most effective, but it's not really easy to do that. I think at my office, we have one, but no one really uses it and you have to get a nurse to come and do an infusion.
(18:53):
So, it's just kind of like not really something I've had an option at most of my jobs. So, I might refer somebody out if they need it. And so, I know another option is focal laser and maybe that's got minimal benefit, but I'll sometimes try it. If there is just a really focal leakage point, I might do like a light laser, nothing crazy, nothing too hot, see what happens. And it has worked on some occasions, but I tell them there's no great treatment for this. So, if it doesn't, then I say, "Oh, maybe we'll just refer you to some other place like an academic center where you can get PDT and see what happens with that." But PDT has risk too. There can be vision loss related to that. So yeah, always just weighing the pros and cons.
Ogul Uner (19:35):
Yeah, I think that was a great overview. You talked about the acute and chronic states. Acute CSR, I think it's important to emphasize that it mostly resolves in two to three months. In most cases when I see an acute CSR patient, I'll generally see them in two to three months again to see. And then most of them will attain excellent visual results with resolution. But yes, you talked about mineralocorticoid receptors, I believe antagonists. Okay. Yeah. Antagonists. So, they have shown some benefit and anecdotal reports as you mentioned. And then other treatments like PDT, argon laser, you talked about using anti-VEGF if they have secondary CNV or systemic medical treatment like you talked about. It's interesting that with PDT, you can either use half- or full-fluence, and half dose apparently is as good as full, which is great. And then you talked about laser photocoagulation as well.
(20:34):
So, it's interesting. I think the problem here is really at the level of the RPE and the choriocapillaris. So, targeting those sites I think makes sense. So, I think that's how PDT makes sense too. And you mentioned that FA and ICG can be helpful in identifying those hotspots. So that was great. And so, going back to our patient who's having an acute CSR episode, how would you treat and counsel them?
Rehan M. Hussain (21:01):
So yeah, in this scenario, it's a brand-new consult. It has been not that long. So, I would run through the whole spectrum of options and it's kind of a discussion. I kind of feel out the situation. Some of them might really want quick resolution because they're like, "Oh, I'm a driver. I'm a pilot, something like that. I can't really afford to have this." So then okay, that's the first one. I'm like, "Okay, let's just try the eplerenone, see what happens." There are really not a lot of downsides, at least from my experience. So, I would see if they're willing to wait and if they're anxious, then I'd probably start with that. And I would just go through the algorithm, like I said, that I just described earlier, consider the focal laser because it's just the most accessible for me. And then if not, then the PDT would be the third option.
Ogul Uner (21:48):
And have you seen a lot of recurrence in these patients? How do you think about talking about the relapse risk and watching these patients? How often would you follow them?
Rehan M. Hussain (22:00):
Yeah, recurrence definitely does happen. Thankfully, I mean, it's usually not as bad for some reason on subsequent ones, but it varies. I usually see them every few months, something like two to three months, depending on how severe it is, how worried they are. If they really don't want to get treatment, then it's not really as much urgency to see them sooner because it's not going to change a whole lot. So, factor that in.
Ogul Uner (22:26):
And you mentioned that older age, male sex, and insomnia severity index score were found to be independently associated with persistent or recurrent CSR. So, you talked about the importance of minimizing stress, stopping steroids, discussing with PCP, and then I think sleep apnea screening. Even though we don't have formal guidelines on or monitoring for hypertension, I think it's a good idea to discuss the evaluation with the PCP and make a decision as to whether those conditions should be evaluated for.
Rehan M. Hussain (23:01):
Definitely. Yeah. You can really save a person's life kind of, because we know sleep apnea is associated with a lot of problems at a cardiovascular level. So yeah, definitely good to communicate with the PCP and get that looked into.
Ogul Uner (23:17):
I think you summarized it really well. And so, let's summarize together what we learned from Dr. Hussain. So central serous chorioretinopathy is an idiopathic disease characterized by choroidal hyperpermeability, which leads to RPE dysfunction and the subretinal fluid accumulation. We talked about it being one of the pachychoroid diseases that kind of sits in the middle of the spectrum. The spectrum consists of PPE or pachychoroid pigment epitheliopathy, then CSR, then pachychoroid neovasculopathy and polypoidal choroidal vasculopathy. CSR presents in mostly young to middle-aged males, type A personality, high stress, steroid use can be seen, and steroid exposure can be with any route. So definitely ask about oral, topical, inhaled, and even dermatologic forms to identify risk. They can also be on hormonal therapy, so testosterone is something to ask for as well. Patients can present with metamorphopsias and vision loss with exams showing subretinal fluid and RPE changes.
(24:19):
If they have an Amsler grid, they may notice some changes on the Amsler. OCT will classically show a serious neurosensory detachment with or without a PED or pigment epithelial detachment. The autofluorescence can be very helpful. It can show these gravitational tracts in chronic disease and FA will classically show either the ink blot, the smokestack, or this expansile dot pattern. And the ICG will show these hotspots of choroidal hyperpermeability. The disease can be categorized as acute, which will self-resolve in about two to three months. It has a great visual prognosis or chronic that will lead to RPE atrophy and can even result in permanent vision loss if the fovea is affected. And we talked about treatment being observation in most cases in the acute form. Cessation of steroids can be very helpful and systemic medications like the mineral corticoid receptor blockers can be used even though they've not shown to be consistently effective in studies.
(25:16):
And PDT can be very helpful in chronic cases as it directly targets those abnormal blood vessels leading to that exudative pattern. And anti-VEGF can be useful in secondary macular neovascularization. So always ask about stress, steroid use, sleep apnea, and think of pulmonary and systemic hypertension as well in patients and work with their PCP to reduce their risk of recurrence of this potentially blinding condition. I remember in residency, we had a patient who had bilateral central serous chorioretinopathy from undiagnosed pulmonary arterial hypertension, and they had an undiagnosed cystic fibrosis variant that was leading to it. So that was a big learning point for me. And obviously this is a very common disease. Not everyone will have this, but especially in bilateral cases or very severe cases, it's important to think of the systemic factors. Dr. Hussain, anything else you'd like to add?
Rehan M. Hussain (26:16):
You summarized it so well. I mean, I don't think there is anything to add at this point. Very good job.
Ogul Uner (26:20):
Great. Thank you. And Dr. Hussain, before we end the episode, I ask all of my guests a question. And 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?
Rehan M. Hussain (26:32):
I think when you're in that stage when you're a med student or a resident and you're kind of planning your career, the most important thing to do is just get on the scene, put yourself out there. Don't be afraid to seek out mentorship because those connections are just so crucial towards you kind of discovering yourself even more because people will kind of, I think– Well, you can find somebody that you want to role model yourself after, but then they can take you under their wing, introduce other people. It helps you, I think, learn so much, not just about the science behind our field, but just the social aspect, which is so important to advance your career. So, I think it's just important to get out there, go to as many meetings, present as many papers, go on the podium as much as you can, and don't be shy to seek out mentorship.
Ogul Uner (27:19):
I think that's great. We all are here thanks to our mentors and the great relationships that we've developed. So, I think that was a great answer and thank you so much for that. And Dr. Hussain, thank you for joining us on this episode of the Pupil Pod.
Rehan M. Hussain (27:32):
Thank you so much for the invitation. Very good discussion.
Ogul Uner (27:36):
And thank you to our listeners. See you next time on the Pupil Pod.
