Wendy Smith, M.D., is an ophthalmologist at Mayo Clinic in Minnesota. Dr. Smith, who specializes in ocular inflammation and immunology and medical retina, joins our podcast to share her expertise in the evaluation and treatment of patients with uveitis. Dr. Smith breaks down her work-up and treatment algorithms, concerns for chronic immunosuppression, and when to refer.
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Welcome to the Mayo Clinic Ophthalmology podcast brought to you by Mayo Clinic. I'm your host, Doctor Andrea Tooley and I'm Doctor Eric Botham. We're here to bring you the latest and greatest in ophthalmology medicine and more in today's episode, we are joined by Doctor Wendy Smith. She is a UBI Itis expert here at the Mayo Clinic. She is gonna take us through sort of run of the mill cases in uveitis and what every ophthalmologist is needs to know and some of the really tough ones with advances in therapeutics that you'll wanna understand. Dr Wendy Smith is a uveitis and medical retina specialist here at Mayo Clinic in Rochester, Minnesota. Doctor Smith did her clinical fellowship in uveitis and medical retina at the National Eye Institute Neinih. She is the current chair for the Basic and Clinical Science course on uveitis and ocular inflammation section for the A AO and directs the Medical Retina Fellowship here at Mayo. Welcome Dr Smith. Thank you. It's great to have you part of our podcast. We've been excited to have you on in particular because of your expertise with some of the toughest patients. You get the hardest ones in the department. I can speak of one. Even today. I saw that I was like, thank you for seeing Wendy yesterday. Um, certainly you do manage some of the conditions that make us all nervous. And yet you also manage uveitis conditions that are sort of run of the mill or simple share with us a little bit about the types of patients you see and um the workups you do and what you think about when patients hit your door. Uh We'll talk about some of the zebras, but just what's your practice like on a day to day basis? Yeah. Well, I'm my waiting room is really mixed. I, I definitely have um Children um maybe about 10% of my patients with Ivies are, are pediatric and then um I have younger working age patients and I have um older patients as well. So Ivies can affect anyone. Um common. Uh I mean, we are a tertiary care center, so we do get a lot of fifth opinion patients, but we provide primary care here too for our region. So we get a lot of um newer diagnoses of uveitis. So um common is definitely anterior uveitis. Um and some of the, the relatively simple cases may never need to come and see me, um which is fine, but I would say um certainly a common cause of anterior uveitis um can be HLAB 27 which is AAA genetic Association. Um and there's sort of some, there are some characteristic ways that, that, that uveitis may present. And I think the great thing about our training program is that most of the residents have a chance to see an HLAB 27 uveitis patient present because it can be quite dramatic with high grade inflammation and um needing a lot of uh treatment and follow up initially. And um so I think getting a handle on that is great for our residents because we want them to be wonderful comprehensive ophthalmologists when they finish and they are, which is great. We, we do get a lot of different, you know, varieties from the really basic to the really complex U Vitti. And I'm so glad that you mentioned HLAB 27 and anterior U Vitis or Iris, talk to us about when a comprehensive is, is OK to manage basic iritis anterior Vitis and then when to refer and what your kind of algorithm for treatment is there. Because I think that's always the question, you know, how long can you keep this patient? And then when do you need to send them off to a U VA specialist? Yeah. So certainly um usually the first line of treatment for anti U Vitis um after you've uh established that it's not infectious um would be uh steroid drops and encyclopedic um initially but not usually chronically. Um And so if you're able to quiet the uveitis with a tapering course of topical um prednisoLONE for example, um they're able to get off drops after about six weeks and remain off drops for at least three months. Then this is something that could potentially continue to be managed with steroid drops as needed. But if they um recur very soon after tapering off, um within a week, within a month, even three months, if they have complications from the steroids, um uh cataract progressing elevated eye pressure, they can't be controlled, Um or the uh topical steroids are definitely not sufficient. So they have macular edema, um other complications, then that's something where it would may be appropriate to seek further evaluation. That's a really good overview. I'd be curious too about kind of the general work up for, you know, straightforward without complication, an inter U Vitis, ho how much testing blood tests and work up do you do? And then how much do you just kind of say idiopathic? Um Yeah, I mean, I think what we try to teach the residents is that the, the first work up um should be your history. Um So, uh you know, I I don't very often get to see acute new cases of anterior Vitis because those often will, will go through the resident clinic or they will see their local eye doctor, um optometrist or ophthalmologist first. However, um when I see them to recreate that, you know, what happened at the beginning, I, I want to know how the symptoms started. Um If they had any infections in the month before, if they had any recent vaccinations or medication changes, um What are their other medical conditions to try to get a sense of, of what risk factors there might be out there? And then it really depends on um what you see. Um if a patient presented with elevated intraocular pressure, that's not typical for iritis. Um So that might make you start thinking about herpetic cause. Um Otherwise, really, um there's not a lot of work up that you would do if they don't have any other symptoms outside their eyes. So, um pretty much always for any new case of uveitis should still rule out syphilis. It can occasionally present just as anterior uveitis. Um Now, if the patient is four years old, ok, probably we don't need to do the test then. Um but otherwise, uh the, the common, the most common type of anti uveitis is idiopathic undifferentiated. So, without any other clues, you don't have to do a very extensive work up. So just straight up anti uveitis, it's a very acute presentation. I'm going to check HLAB 27 and syphilis. Um if uh it's a little more indolent or chronic, then I may also do ace and lysozyme and a chest X ray looking for Avens soar coos. Um And after that, a lot of the other labs that are kind of done as, as what people think might be a standard uvs work up aren't really appropriate A N A for example, almost never is relevant without any other symptoms outside the eyes. Um And uh rheumatoid factor, same thing. Uh uveitis is actually very rarely associated with rheumatoid arthritis. So, without any other symptoms, no other joint pain or no history of something that sounds like inflammatory arthritis, you, you wouldn't need to do that, that lab either. So helpful and it's just so, so helpful. Thank you. And then the last thing I'll say that that seems to go commonly into a uti work up. But I don't, most uveitis specialists don't think is appropriate is Lyme testing. So we are in a Lyme endemic area, but actually uveitis is only very rarely associated with Lyme disease. So I need other history that would make me think the patient could have Lyme. So you pulled a tick off of yourself. You show me your bull's eye rash, you have migratory arthritis. Um You, you have, you have been camping and rolling around, you know, in ticks, then. Yes, but otherwise not just you have anterior Vitis. I'm going to check line. That's, that's not part of the work up for that kind of presentation. Ok. So a comprehensive ophthalmologist, you may be listening and I think typically greatly appreciate the opportunity of sending a patient your way to say, please help me fix this situation. But there's also and so often becomes a chronicity to them. What's your ideal model? Especially someone that is a patient from 34 hours away or more. Do you find that your average U Vitis patient is best co managed or is best kind of staying home to the more advanced care site? Um I know there's a timidness for referring doctors to know if they're doing enough for their uveitis patients. So just share, what do you recommend for relations when relationships with colleagues? And when is it OK to co manage and when is it not? Yeah, that's, that's a great question. So, um there's a couple of reasons why patients come to mayo in general. Um and sometimes a big part of it is um education and, and the, the chance for the patient to ask questions about their condition. So, um for some of these patients who may have had chronic anti e Vitis for, for five, even 10 years, um you know, I'll, I'll do an overview of their, of their exam and their history and see if they have any complications from the U Vitis or the treatment thus far. I'll explain everything to them, what I'm seeing and what I'm thinking and if there, it seems like there's any holes in the work up, um then we might recommend additional testing and then depending on what's going on, if they clearly have uncontrolled uveitis or they're coming up on needing um cataract surgery, for example, and they don't have control, then I'll, I'll sort of make an outline of suggestions um for management locally. Um And then it depends on the patient, some patients, um I'm not going to be able to make those recommendations right away. I need to see them a couple of times um to see how, how things change, if we're going to change treatment a little bit. Um So I may ask if the patient is able to come back so I can follow along for a little while and then trans transition care back. Sometimes they definitely come from way too far away. It's just not going to be convenient. So then again, I'll put some guidelines in my summary saying if this happens, then try that. And then um you know, at the end of it all, I say welcome to come back for re evaluation if, if there are additional questions or something changes. Um We, we, you know, as, as we all know, we have patients that come from far away and it's, it's a major burden potentially to come here. So, yeah, I really um really do like to try to co manage if at all possible um for the health systems. Uh There are um several of our optometrists and um some of the general ophthalmologists that sometimes I will um electronic consult through the chart. So they'll send me an update and tell me what happened and then I'll um try to in a timely fashion, not always as timely as I wish, um advise them on, on what they could do to save the patient a trip back to Rochester. And I imagine because so often you're co managing he with other colleagues here at Mayo. I mean, uveitis can spill over into other ocular disease, consistent with glaucoma or retinal disease. And also systemically share with us just in your average um recommendation that they see someone else in our department or else here at Mayo, which specialists are you reaching out to the most? And which should a referring doctor think about? Well, maybe I need more than one with this visit to be consulted. Yeah, so sometimes um I I far and away outside of ophthalmology work with rheumatology the most, we have an amazing rheumatology department here. We are spoiled with a number of rheumatologists that we have. Um And so um I also uh require that we have ophthalmic records before we schedule a new patient with me. And um either I review them or my technician reviews them because we like to pres schedule as much as possible. So if it looks like they are going to also need to see oculoplastics, then we'll already reach out to try to set that up so that we can coordinate within a day or so of the, the visit with me. Um And similarly, sometimes, sometimes um it's not clear if they want to see rheumatology here. So then we'll, we'll ask the scheduler to talk to the patient and say, you know, did you want to see rheumatology here or the referring doctor? Was that your intent? Occasionally? Um the referral gets triaged to rheumatology and if the patient seems to only have Vitti rheumatology may recommend that they only see me or I'll review it and say no, I I we need both of us at the same time. So it varies. But as as much information ahead of time really helps us pres schedule. Um because people are, people are really accommodating at mayo, but sometimes there's just things we're not going to be able to get within the same week um of a patient's visit. Yeah, along with that, the rheumatology, uh vein and, and coordinate with room, a lot of the care for some of these complex U vs are um biologic medications and immunosuppressive. And I know there's a lot of new exciting therapeutics kind of on the horizon we briefly talked about that. Could you give us a little crash course in um some of the therapeutics for U Vitis? What common ones you use? And then what are exciting new developments? Yeah. So, um so when you move on to systemic medication, um the the for acute inflammation, it's still corticosteroids, um whether it's drops or injections or oral or IV um and those often, you know, we I will manage on my own unless it's a pediatric patient. And then I want to involve rheumatology or pediatrics. Um after that, um you break it down in indeed into a mechanism of drug. And so the conventional immunosuppressives, which are, for the most part, oral um are still pretty much the first line of treatment. And um again, spoiled here with so many rheumatologists, but many ophthalmologists um will be comfortable prescribing and managing um oral immunosuppressives on their own. Um after that, um for sure, the, the, the major game changer in the past um just about 15 years um are the biologics. And so the, the only systemic medication that is FDA approved to treat non infectious U Vitis is the TNF inhibitor, Adalimumab. Um And uh this medication is um increasingly used for all types of ocular inflammation. Um some of that would be off label like sclerosed, for example. Um and that um that particular biologic Adalimumab increasingly is the first choice for some patients. There are fewer side effects potentially. Um and patients tend to tolerate a little better. It works a little faster than conventional immunosuppressive. So that's been a medication that we increasingly use. Um something that will change how we use it is that there will now be um a biosimilar which is the equivalent of a generic of Adalimumab. Um biosimilars, just like other generic type drugs are not entirely exactly the same as the original drug. Um And I think most of us um anticipate that insurance companies will require us to use biosimilars. Um So whether there will be any concerns that it's not um, doesn't work the same, uh for certain disease entities like UVII, I don't think we know yet. Um, but I, I know we'll be using them. I, I have two kind of questions along those lines. One is, are you starting with conventional immunosuppressives? You know, you're starting with oral predniSONE and then doing something like methotrexate before, then you move on to biologics and, and we can use brand names here. I think we're talking about Humira, um or riTUXimab or, or whatever. Are you, are you kind of going along that line or are you jumping right to Humira? Uh And then I'm a follow up question but answer that first. That's a good one. Yeah. So we, we do tend to um acute inflammation, use steroids. Um Still most, for most patients would go to a conventional one like methotrexate. Um And then if you um have you can't get off steroids or you still have active inflammation, you might add Humira. Um But for some uh for some types of uveitis, um for example, birdshot uveitis, which we have a lot of um here in the upper midwest, uh I often want the combination of the conventional immunosuppressive and the TNF inhibitor most commonly Humira right away because it, it's often a later diagnosis. It's a more um chronic uh and can be very destructive to the retinal function. So you want to be more aggressive um sooner. Um I think for Birdshot and then for some other entities. Um You, you may want to go also first to Humira again, it's the side effect profile. Um that, that will tend to push people that way a little bit. Um Plus the um the uh severity of uveitis might make one think about using a biologic like Humira first, the other biologics, um the other TNF inhibitors um uh riTUXimab you mentioned, which is a CD 20 biologic CD 20 targeting. Uh those are not, again, not FDA proved. And so if you don't have any other systemic diagnosis, it will be more difficult to get those approved by insurance. And so often we, we also start with conventional immunosuppressives to say, hey, we use these other medications and now we, we need to do the next step. Yeah, you said exactly what my next question was, which was on the insurance line. How often are you having to do this fail first or proving that they failed either conventional or predniSONE before they let you go to the Yeah, I think, I mean, I again, we still tend to, we won't even unless it's very severe uveitis. We're not going to try to go often to a biologic first um for, for many types of uveitis. But I think the, the um the bar is being moved higher and higher by insurance companies and more and more um approvals and appeals and letters and denials um seem to be happening. And so I I anticipate, it will only get harder. It's so frustrating when you know what a patient needs and you can't get it directly to them. Question about the side effect profile. You mentioned risks with any of these drugs. And I remember at the start of COVID, everyone that was all my patients that were on immunosuppression was, were quite worried about what this new infection was gonna bring to their lives. What is your, when you discuss most people are comfortable with methotrexate and predniSONE. It's, they've been around so long. But in terms of the biologics, what are the um, side effects that you see the most commonly generating a change in care or generating symptoms that the patient isn't quite even aware of? But what are the ones that you think of the most or do we need to keep in mind as ophthalmologist? Yeah. Um, so I'll, I'll before I answer that question and if I forget it, remind me, um, there is good data in the uveitis literature looking at the risks of immunosuppression because that's definitely something that patients are worried about. And, um, parents of Children with uveitis worry about when we talk about using systemic immunosuppression. Um And if you think about the worst side effects that can happen with medications, the likelihood of a really severe, um, you know, something that will impact your life for a long time happening is the highest with chronic use of predniSONE. So that's actually one of the, the relatively more dangerous things we can use if we use it the wrong way and too long for the, for the non predniSONE immunosuppressives. Um There was a big study that looked at patients with uveitis on systemic immunosuppression compared to patients with uveitis who were not on systemic immunosuppression. And compared to patients in the general population who didn't, don't have uveitis at all. And the two questions they ask are if you're on immunosuppression and you have uveitis, so you're more likely to die sooner and are you more likely to die from cancer? And the answer is no, which should be reassuring. But of course, the that the answer is still, the question is still, but what about you could still get cancer even if it doesn't kill you. And obviously, none of us would, would willingly want to put that increase that risk too much for any patients. So for pretty much all of the classes of medications, except for the very old class, the alkylating agents, which is cyclophosphamide and chlor Amil, there does not seem to be a significantly increased risk of cancer um beyond some of the risk that you can also see in general from having a systemic inflammatory disease. Um The, the, the original version of that study had um kind of incomplete data on the TF inhibitors Humira. And so there was a, a thought that perhaps there was a signal there that suggested some additional risks for patients, but now with another seven plus years of data, um, that signal has not borne out. Um So in terms of what you think about for patients and risks, um, actually with the TNF inhibitors, you don't need as much lab monitoring compared to methotrexate or Mycophenolate. So you don't tend to see the effects on, um, blood counts as, as much as you might with those other medications. Um, as I said, many patients don't have much in the way of day to day symptoms. Um, uh, but, uh, there can be, um, some patients may describe kind of an overall fatigue. I've had a few patients, um, who seem to have headaches that correlate with being specifically on Humira. There can be some weight, weight gain issues, um, with the t of inhibitors including Humira. Um, and sometimes they very rarely, there can be some sort of, um, not well defined, uh, effects on, on mood and, and uh, and psychiatric issues. I've had a few patients who, who just wouldn't tolerate the medication for that reason, but it's, it's pretty rare. Um, most commonly we, we stopped, we stop using Humira because it's not working for uveitis. I would say above and beyond, uh for the immunosuppression that you're um, concerned with COVID. Um, yeah, we were, we were all scared, um, very scared and I delayed many people for a while, delayed, um, putting patients on immunosuppression for the first time as we tried to figure out what, what the risk would be. Um, we learned that the risk is a little bit different, depending the risk of infection is different, depending on the mechanism of the mechanism of the drug. And, um, that your response to the vaccination is affected, depending on the immunosuppression that you're on. So, um, that has, has influenced the recommendations that have been made um, over the past few years in terms of uh vaccination and um prophylaxis if you're exposed to COVID. And of course, as COVID has changed, so have the recommendations. Yeah, I've had quite a few patients on riTUXimab who just cannot develop a nano response to the COVID vaccine no matter what their B cells are just so deplete that it's not gonna happen. So then when the prophylaxis was available, the shed worked, that was an option. And then um those are the patients that would still be treated with, with Palo. But I think right now until that changes, I think you're comment about the psychiatric conditions, the psychologic responses of disease. I, you know, is, is something that I, I don't think we give enough attention to at least in my pete's population. I think there's a component of a stress, a un communicated stress response. Um even if it's not communicated the fear of the parents over the child, losing vision, how that can play can play out in the child's life is quite a interesting journey to have empathy for, to communicate through, to address. And they, it just, I think one to be for these chronic conditions to continue to revisit and talk through. I don't know too many of my young uh patients with uveitis that are on methotrexate that like the color yellow because methotrexate is yellow and they'll see something yellow, even a school bus or, and they get this sort of visceral reaction in their gut that just, they don't like the color yellow. And it's interesting how, how often our medical diseases are having influence on their, on their overall behavior. Um, and so it's just important, it's nice that you brought that up and I think it's important for our, our listeners to just appreciate and not just UV patients but all of our patients, but it certainly in these ones with chronic diseases. Yeah. Wow. Yeah, I think for the, for some of the pediatric patients, sometimes there's a, also a fear that it's something that they've done wrong or, you know, when the U Vitis flares up that, you know, they, they feel like it's their fault and now there is an adherence to medication component. Um, but otherwise, you know, we don't know why people get uveitis for the most part. Um, we don't know why people flare up. Um, and so sometimes, yeah, I, I try to try to feel out how, you know, how a patient is feeling about things. Um, it is a lot of stress, both adult and adult and child's Children, um, with uveitis, uh, because you, you know, you really want, they really want their disease to be controlled. They don't want to be on medication. Everybody, of course, hopes for the Magic Wand treatment that makes it all go away. Um, and for the most part with IIS, um, as a chronic condition, um, it's an ongoing, um, fight. I think our residents are quite in tune with encouraging patients with diabetes or high blood pressure to keep those things under control because their eye health, long term, we gonna be impacted in ways that we've richly studied. It's hard with uveitis. I think we've grown to realize very few of them, especially some of the childhood ones for me. But, you know, others that just they're not expected to burn out, they're going to be chronically with them. And there's overlying curiosity, fear dark cloud on the horizon is certainly something that uh affects them. And just the importance of, as you're saying, compliance. Um, uh, you know, there's a certain transition whether in youth or adults but in youth, going from the parents doing this to me to, I need to manage this myself. And those are all important windows to have supportive care and appreciate the teamwork. You've been to our, our side, any advice on others in terms of managing these meds, I assume your average comprehensive ophthalmologist working with a patient with uveitis, you know, knows their resources in their area. But other plugs for the medication side, is it just know your rheumatologist? Well, yeah, I think, you know, that certainly many U Vitis specialists are, are going to be comfortable, uh, managing medications. The big hurdle can be, um, administrative help. So, if you need to get prior authorizations of medication, um, the TNF inhibitors, uh, Humira, for example, has to be sent by a specialty pharmacy. So, you know how you need to know how to send the prescription properly to the specialty pharmacy. So that takes a lot of administrative support for, for, for even for a UVI a specialist. So some people will um have a nurse that, that works with their practice, for example, or, or another administrative type person. Um Otherwise indeed, you know, the the average ophthalmologist, we, we wouldn't expect somebody to have the experience to do that. So, partnering with a rheumatologist um in the community is important. And unfortunately, um you know, some, not all, every rheumatologist may be comfortable um treating a patient with uveitis because they can't evaluate the, the inflammation at all. So there what's really important um from the ophthalmologist is really good communication. Um and it can't be in our hieroglyphics or our abbreviations. It needs to be dear doctor. So and so um the U VS is well controlled. Um can we please continue this regimen if it's medically safe? And if it's not being really clear about that because I, I've, you know, sometimes I have patients referred to me by rheumatologists outside of mayo saying, you know, what, what's the situation? We don't know what to do because we can't tell if you know what's going on with the uveitis. So we, we all need to be really good about communication with each other. Yeah, this is such a high yield, really fantastic overview. Thank you so much for breaking it down. I think it's super helpful to anyone out there seeing patients with Uu Vitis so much to recognize and appreciate and caring for these patients. So, thank you so much for your expertise. It was wonderful to chat with you. You can find all episodes of the Mayo clinic ophthalmology podcast on our website. Thank you for listening and we definitely look forward to sharing more.
