Case Review: Signs and Symptoms of Thyroid Eye Disease

Speaker 1 (00:00): Support for this podcast comes from Bryn Mawr Communications. BMC produces a number of informative podcast series spanning a variety of topics in ophthalmology. Discover a new show at Eyetube.net/podcasts.

Dr. Uner (00:35): 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. Amina Malik. Dr. Malik is the Chief of Ophthalmic Plastic and Reconstructive Surgery at Houston Methodist Hospital in Houston, Texas, where she also serves as an Associate Professor of Ophthalmology. And I'm so excited to have her on the podcast today. Dr. Malik, thank you again for joining me.

Dr. Malik (00:59): Thank you, Dr. Uner. I'm so excited to be here today to be discussing one of my favorite topics.

Dr. Uner (01:04): Great. Let's dive right into the case. We have a 44-year-old woman who presents to your clinic with eye redness and diplopia. She reports occasional hot flashes and racing heartbeats, but thinks this might be from early menopause. She denies any chronic or recent illnesses and doesn't take any medications, but smokes a pack of cigarettes a day. Vision is 20/25 in the right eye, 20/20 in the left, normal pupils, IOP, motility, and color vision. Hertel measurements are 24 millimeters on the right and 22 on the left. External exam shows upper eyelid edema and erythema, upper lid retraction, and mild chemosis and caruncular edema in the right eye. There's mild upper lid retraction in the left eye as well. There are punctate epithelial erosions on both corneas and the remainder of the exam, including a dilated fundus exam, is unremarkable. Dr. Malik, what are your initial thoughts about this case?

Dr. Malik (01:57): Well, I think this is a really great case that showcases and highlights many of the key diagnostic features for thyroid eye disease, um, which is going to be right at the top of my differential diagnosis for this patient. Uh, you know, starting with your first comment of her having the eye redness and double vision, uh, there are many external signs and features that we should, uh, be familiar with for, uh, patients who might present with thyroid eye disease. It's a heterogeneous disease, um, with many, uh, signs and symptoms, and this includes the redness and double vision. Uh, she also has the proptosis. Uh, you, uh, reported 24 millimeters on the right and 22 on the left. Um, you know, a normal Hertel measurement for a Caucasian eye would be 21 millimeters. Um, this can vary, um, some by, uh, ethnicity. However, sometimes even more important than the actual measurement is the difference between the two eyes.

(02:52): Uh, anything two or greater could suggest, um, a pathology such as thyroid eye disease. Um, so in this situation, you know, we want to be thinking about that as it's the most common cause of unilateral or bilateral exophthalmos, um, in adults. In addition, you mentioned that her external exam showed upper eyelid edema and erythema. These are also hallmark, uh, features, um, swelling and redness, the upper lid retraction. The most common sign in patients with thyroid eye disease is actually upper lid retraction with 90% of patients having this. Um, and in particular, uh, it'll often involve the lateral upper lid, uh, classically known as the lateral flare. She also has some chemosis and caruncular edema, um, further, uh, suggesting thyroid eye disease as part of this inflammatory process. Um, the conjunctiva is also involved. On her corneal exam, there were punctate epithelial erosions, which are not uncommonly seen in thyroid eye disease, especially in cases like hers, where there is proptosis and there's lid retraction that can often be associated with lagophthalmos or poor blink leading to exposure, um, and a staining of the cornea.

(04:05): So, you know, that's definitely going to be high on her differential, um, given all of these clinical signs. And when we look at her history, uh, of these hot flashes and racing heartbeats, we are going to be concerned for, um, systemic hyperthyroidism. Um, and one of the major risk factors we know for thyroid eye disease is smoking. Uh, you know, these patients are significantly more likely to get the disease and when they have the disease, it tends to be more severe. And she's smoking a pack of cigarettes a day, so really everything pointing us towards, uh, this diagnosis. Um, now to ... There are, uh, also things we want to think about on differentials anytime we see patients. Um, orbital cellulitis can certainly present with proptosis, lid swelling, redness, conj injection, chemosis, um, and pain as well. Um, however, in, uh, orbital cellulitis, we're going to want to look for some, uh, acute onset and usually a precipitating factor, either, uh, skin penetration such as a bug bite or a trauma, um, or a history of sinus infection, um, with the ethmoid sinus being the most common source for the orbital, uh, cellulitis.

(05:17): Um, also on our differential, uh, uh, idiopathic orbital inflammation can be considered. Um, typically with these, it's also a very acute onset and pain is a hallmark feature, um, and we don't typically see lid retraction in these cases. Um, so these are all, you know, things that we want to be thinking about, um, on our differential and, uh, imaging can be very helpful too, uh, if we're not sure about the diagnosis. I think with this history, um, we, we can be pretty confident, but often imaging can be used as a diagnostic aid in cases of less certainty. And of course, what we're going to be looking for is involvement of the extraocular muscles and thyroid eye disease and it's typically sparing the tendons as opposed to idiopathic orbital inflammation or orbital myositis where you will see the tendon involved thickening of the tendons as well. So those are some important things, uh, to keep in mind when we're looking at, uh, differentiating those two entities.

Dr. Uner (06:19): Great. I think that was an excellent overview, um, of thyroid eye disease and the relevant differential diagnoses. Let's talk more about the disease. Who gets this disease and what do we know about its pathogenesis?

Dr. Malik (06:31): Yeah, so this is a disease that typically affects females more than males, although we also, um, can see it in male patients. Um, and typically these patients have a history of hyperthyroidism or Graves' disease. Uh, 90% of patients will have that. However, five to 10% of patients can be euthyroid, um, or hypothyroid. So important to keep this on our differential, you know, even in patients who, who don't have the Graves' disease. Um, and in terms of age, it has a bimodal distribution, um, affecting patients who are in the 40-year-old age group and then there's a second, secondary cohort in the older age group around 60 to 70 who can also be affected. And those, um, two, uh, age groups can have different, uh, phenotypes and presentations. Um, so really important to think about, um, in any adult patient really who's presenting with these, um, classic signs and symptoms, uh, that we discussed earlier.

(07:26): And when it comes to the pathogenesis, you know, patients are often confused, the thyroid’s in the neck, my eye is here, you know, what's going on. So we know that this is an autoimmune condition that is separate from their thyroid disorder. Now they are connected, um, however, it's important for patients to understand that they're two separate entities, um, that are each treated separately. Um, and how I sort of explain it to patients is that, uh, we know in any, uh, autoimmune thyroid condition, there are antibodies circulating in our bloodstream and, uh, our orbital fibroblasts have the insulin-like growth factor receptor and, and TSH receptor. And these receptors are upregulated in patients with Graves' disease and thyroid eye disease. And so when these antibodies are in our bloodstream and bind to these receptors, what happens? Well, it creates this downstream inflammatory reaction, uh, where we develop more fat, so there's epi- adipogenesis and there's an inflammatory, uh, response where we're getting increased release of glycosaminoglycans.

(08:30): Um, and the increased fat, the increased, um, hyaluronic acid, all of this leads to increased orbital fat as well as the extraocular muscle expansion. And when we think about our orbit, we know it's a closed bony socket, so where's the eye going to go forward, which is why we get the proptosis. Um, it's why we, uh, will often get, see, uh, double vision because of the muscle enlargement. Uh, and then also just part of that inflammatory response is why we see the lid swelling, the redness, uh, the conjunctival injection. Uh, so it's really a reaction that's occurring on the orbital cell, uh, fibroblasts, uh, where there are upregulated receptors, but we are learning more and more as time goes on about the exact pathogenesis as there's, um, still a lot we don't know about this disease.

Dr. Uner (09:17): And I think that segues, uh, really well into the clinical features. Um, you talked about a lot of the classic features, um, of thyroid eye disease when we were talking about our case. Um, but, uh, let's talk more about the other features like what are the most frequent findings you see, maybe, um, others over time, like how does the optic nerve get involved and maybe let's get into that in more detail.

Dr. Malik (09:43): You know, the most common clinical signs, again, are going to include, uh, upper lid retraction seen in 90% of patients, uh, followed by proptosis or exophthalmos. Um, often these patients will also have lid lag with down gaze. We can see that in 50% of patients. Uh, they can classically complain of pain or discomfort, uh, and that's due to, you know, the increased congestion in the orbit and sometimes it's not even a pain that they'll say, but it's almost like an awareness or a fullness or even a pressure sensation. Uh, the eye redness, uh, chemosis and caruncular edema, uh, as well as dryness on the cornea and the eyelid edema and erythema can sometimes be fluctuating too, uh, where it can be intermittent. Uh, so important to remember all of these when we talk about, uh, the, uh, signs of thyroid eye disease. And there is a close temporal relationship that exists with the development of hyperthyroidism and thyroid eye disease.

(10:39): Twenty percent of the diagnoses can be made at the same time, um, however, uh, patients can develop it at any point in their lifetime. Um, and if they don't have a formal diagnosis, they still carry a risk of developing this, uh, about 50%, uh, in five years after the eye findings. So they definitely need to be monitored and have their thyroid checked during this time. Uh, there's also the classic pretibial myxedema, which is often taught, um, but this is actually only present in about 4% of patients. I think I've seen it once, um, in my 12 years, so it's not something we see, uh, too often, but something important to think of. Um, and then one of the most important, uh, signs and symptoms, but thankfully the most rare, uh, presentation of thyroid eye disease is going to be optic neuropathy, which can lead to permanent blindness if left untreated.

(11:34): Now there are two forms of optic neuropathy, um, that can occur in these patients with thyroid eye disease. We can have compressive optic neuropathy where the increased extraocular muscles and increased orbital fat, um, can actually press on the optic nerve, um, leading to the optic neuropathy. Um, and then there's also a stretch optic neuropathy where patients are so proptotic, um, that it can actually, uh, cause pressure on the optic nerve and often on imaging we can see the globe start to take a guitar pick shape or a less round shape due to the severe degree of proptosis and I have seen both of these in my career and both of these, um, are often more, um, are more often seen in patients with a smoking history. So this is one of the most important modifiable risk factors is, uh, to advise these patients to avoid smoking primary or secondhand.

(12:27): Now, when it comes to optic neuropathy, because this is one of the conditions that patients, uh, can lose vision with, it's important to make them aware and one of the earliest, you know, signs of an optic nerve problem is going to be red desaturation. So I'll tell patients, uh, who I think, you know, want to be more closely monitored for the development of this as they can at home just cover one eye and, um, you know, check a red lipstick or a marker, the degree of red saturation and then do the other eye. And if it starts to turn, you know, orange or burnt, they really should come in for urgent imaging, um, as this is something that would be treated, um, emergently with, uh, a variety of options now, you know, we can do orbital decompression, IV steroids, um, teprotumumab, um, although that's an off label use, um, but these patients, uh, would need to be emergently treated.

Dr. Uner (13:19): That's great. I love the home idea of, uh, doing a red desaturation test. That's really clever. Um, so we talked about a variety of different factors and signs that, uh, lead to a diagnosis, but, uh, what is the formal diagnostic criteria for making the diagnosis of thyroid eye disease?

Dr. Malik (13:37): Sure. So thyroid eye disease really is a clinical diagnosis based on the, uh, myriad of signs and symptoms that we have already discussed, um, but important to also check them for any underlying thyroid dysfunction. Um, again, not just checking the thyroid levels, but importantly, also looking at the thyroid antibodies, thyroglobulin, thyroperoxidase, thyroid stimulating immunoglobulin, um, because patients might be euthyroid but could have, um, you know, these, uh, antibodies elevated. Uh, and, uh, as we discussed earlier, imaging is also important as a diagnostic aid, looking again for enlargement of the rectus muscles, um, and most commonly it's going to be the inferior rectus followed by the medial rectus and then the superior rectus and the lateral rectus. And the way I always thought about that is the inferior rectus is closest to the thyroid gland, so that's why it's most commonly, um, involved. And, uh, also important to recognize that patients’, um, antibody levels don't always correlate with the severity, um, and even their thyroid state doesn't always correlate.

(14:43): Patients can have severe thyroid eye disease and have normal thyroid levels, um, and, uh there's still just a lot we're learning about how this disease works because of the heterogeneous presentations that we see, um, both with, um, their serologic testing and their clinical courses. Um, but at the end of the day, really, it's going to be the clinical, um, signs and symptoms that help us to diagnose these patients.

Dr. Uner (15:09): I think you, um, covered the, uh, variety of different diagnostic criteria really well. Um, now, um, at this point, we'll take a short break, uh, to hear back from our sponsors. We'll be back, um, after that short break.

Speaker 1 (15:32): Support for this podcast comes from Bryn Mawr Communications. BMC produces a number of informative podcast series spanning a variety of topics in ophthalmology. Discover a new show at Eyetube.net/podcasts.

Dr. Uner (15:50): Welcome back to our episode on thyroid eye disease. We just talked about the different diagnostic criteria. Now let's talk more about the inflammatory scoring systems. Uh, Dr. Malik, you, uh, heard about the VISA system, the CAS system. How do you use these to inform your management decisions?

Dr. Malik (16:03): So these are both, um, classification systems that are, uh, used in research and in practice, uh, for the diagnosis and, uh, monitoring of patients with thyroid eye disease. Now, the VISA classification, um, is a system that assesses both the severity and the activity across four categories. So the V for vision, the I for inflammation, S for strabismus, um, and, uh, A for appearance. And it's a 10 point, uh, inflammatory scale that sort of helps determine, uh, where patients are in their disease course, uh, where they are in their activity and can help, um, clinicians decide on their treatment, uh, modalities. Um, now this is not a scale I personally use, but, you know, it has been used, um, in research, um, in specialized clinics for its ability to measure both activity and severity, unlike the more simple, um, CAS score, clinical activity score, which really focuses more, um, just on the inflammation part.

(17:03): So what is the clinical activity score? Um, so this is a, uh, seven point scoring system that, uh, looks at, uh, seven different, um, features including the orbital pain, uh, for one and then pain that worsens with eye movement, eyelid erythema, eyelid swelling, conjunctival chemosis, conjunctival erythema, and swelling of the caruncle. Um, and a score that's greater than three is considered active, um, and a score that is less than three is considered inactive or, um, quiet. Um, and then there is, um, a subsequent examination, uh, uh, clinical activity score parameters that, uh, include an increase of two millimeters in proptosis or impaired duction of at least eight degrees in any direction or a one-line decrease in Snellen vision acuity, um, and so that then becomes 10, um, on the follow-up visits. And this score, I actually also did not use until, um, the approval of teprotumumab in 2020 because that is what they used in their clinical trials.

(18:05): But, you know, it's limited because it looks at, um, overall inflammation, but, uh, it doesn't give the severity of any one of those points, you know, um, it just says if it's there or not, but doesn't give us, uh, information. So, um, it's good because, uh, we do need these objective parameters and research and to sort of help, um, guide us. But I think that we are still in need of that perfect scoring system and I think the fact that this is such a complex and heterogeneous disease, um, makes that challenging, uh, to come up with that score. Um, but, you know, that's kind of what we use at present.

Dr. Uner (18:42): I really appreciate, uh, you delving deep into this and, you know, seeing how you use these clinically versus in research, uh, and moving on to the treatment like we've been talking about, uh, from the start of the episode, what is the treatment of thyroid eye disease? Let's talk about acute management, let's talk about more chronic management.

Dr. Malik (19:01): Yeah. So, you know, I really target my treatment of patients based on their symptomology and I think it's important to realize too that these patients, uh, often can have a self-limiting disease. You know, typically in non-smokers, this can last, um, a year, um, and improve on its own, um, smokers sometimes two to three years. Um, and, you know, historically, we're also taught about the Rundle's curve, um, which there's a lot of debate now. Um, actually, uh, wrote a paper on this too about whether the Rundle's curve is, um, you know, still, still, uh, something we believe in. Um, and historically, you know, we're taught that we have this active phase of one to two years followed by a chronic or inactive phase, uh, where patients, you know, have improvement in resolution. But I think with the approval of teprotumumab, um, it's made the, it's, it's made us question, um, some of the, the simplicity of that curve.

(20:02): But that is, you know, what we're taught, um, at least what I was taught 12 years ago. I don't know about residents anymore, um, but that, that curve, um, can help us, um, guide when to treat these patients also. So if we think about what phase they're in, you know, um, and how their symptoms are, that can help us decide. So we can classify as patients as having mild, moderate, or severe disease. So when it's mild, oftentimes their complaints will just be of dryness, um, red eyes, watery eyes and these patients can be observed. Um, we often recommend lubrication, over-the-counter teardrops, sometimes prescription drops, um, to increase their tear production, um, making sure that they are establishing a youth thyroid state. So this is a condition where co-management is essential with their endocrinologists. Um, an oral selenium supplementation has also, um, been shown in some studies to be useful.

(20:58): Uh, 100 micrograms twice a day for six months, um, can be used and in, uh, the studies that were performed, they were selenium deficient populations, but, uh, those patients who took the selenium, it did slow the progression of their disease or prevent it from becoming severe in patients who had mild to moderate, um, thyroid eye disease on presentation. So this is something I do, you know, advise my patients if they don't want to take the pill. Brazil nuts are really high in selenium also and so they can just have a fist full of these. Um, now patients who have more moderate symptoms, um, we can consider additional treatment options like taping their lids when they sleep or moisture goggles. Um, sometimes I do topical, um, steroid drops, uh, if they have a lot of surface inflammation or, um, topical NSAIDs. And then other medical options can include either oral or, um, or IV steroids.

(21:51): Uh, we know that, um, in previous trials, IV steroids were found to be more, um, effective than oral steroids and, uh, better tolerated with less side effects. So typically I, um, will give the EUGOGO protocol, which is going to be 500 milligrams IV weekly for six weeks followed by 250 milligrams IV for six weeks. Um, and this is usually something I'll consider more in patients who have, um, severe disease because of some of the side effects. But something also if patients have more moderate disease and are really bothered by, um, their eyes, something, you know, to discuss. And, uh, in addition to what we're just seeing on their exam, I just want to add that it's really important to ask our patients how it's affecting their quality of life, um, because sometimes you'd be surprised where patients who have really significant proptosis are not very bothered by it whereas other patients who have milder features are on exam, you know, can't function, can't go out.

(22:50): Um, so I think it's really important to really elucidate how, um, from our patients how much it's affecting their quality of life. Um, and there are some really good questionnaires available that we can give our patients, uh, to fill out even prior to them coming into the room. When it comes to medical treatment, so we talked about the IV or steroids. Now there are also several immunomodulators, um, available. Uh, we know that teprotumumab, um, was really exciting in 2020 as the first FDA approved drug, um, for this disease and that's given as an IV medication, uh, for eight infusions and these are spaced three weeks apart. Um, and I think, you know, we've seen a lot of success with this, um, medicine, um, but we've also seen patients who've had recurrence or, you know, had side effects that are also, um, of concern. So I think patient selection, um, is really important when it comes to deciding what the best treatment is for, for your patient and tailoring it based to their individual needs.

(23:49): And there are other immunomodulators which are off label, but which have been used, um, rituximab and tocilizumab, um, and there are various papers, um, that have shown, um, success with this. Um, and then orbital radiation can also be used, um, as a modality to decrease the inflammation and orbital decompression. Of course, surgery, uh, can be done, um, in patients who, you know, are bothered by their proptosis and there are a variety of ways we can perform the orbital decompression. Um, typically, uh, I do a medial and inferior orbital bony decompressions as well as fat decompressions and for more severe proptosis, we'll add a lateral wall decompression. So we can tailor that surgery again based on how much of a proptosis reduction we're trying to achieve. So we've got, um, you know, lots of different, um, tricks in our hat for how to treat this, but I think as, uh, the future, uh, I think the future is promising because there are several new drugs also in the pipeline for the treatment of thyroid eye disease.

(24:56): So I think it's going to be great for our patients, uh, to go from having really no FDA approved treatments for this drug to, to having choices. Um, and I think we'll even learn more about the pathogenesis and this disease as some of those newer modalities, um, emerge. And I'll add that when it comes to the surgical options, um, in addition to orbital decompression surgery, uh, strabismus surgery can also be performed in patients who have double vision. Um, an eyelid retraction repair can be, uh, performed in patients who have the upper lid retraction, uh, via release of the Mueller's muscle. And for lower lid retraction, we can use a variety of different spacer grafts to help elevate the lid, um, to improve their exposure, um, and dryness. And when it comes to these three types of surgeries, the decompression, the strabismus and the eyelid surgery, we usually like to follow an order where we do the decompression surgery first because when we're decompressing the eye, that can shift the position of the eye and can sometimes affect their double vision.

(25:53): Um, and likewise, if we're doing strabismus surgery on the vertical rectus muscles, we know that they can share fascial, uh, attachments to the upper eyelid elevators. So we want to, um, do the lid retraction repair after the double vision as that can also change after surgery. So, uh, the teaching is to sort of do these in a staged process.

Dr. Uner (26:13): Yeah, that's awesome. I think that's really important and what we're taught as well. So do the orbit surgery first, then do the strabismus surgery, then the lid surgery. So, um, thank you for bringing that. Um, let's talk more about teprotumumab treatment’s, role in thyroid eye disease. Uh, you briefly mentioned it, but when do you use it and what are your thoughts on it given the side effects?

Dr. Malik (26:34): Again, this was, uh, the first FDA approved treatment for teprotumumab in 2020 and it is a fully human monoclonal antibody. Um, it's an insulin-like growth factor receptor inhibitor, um, that binds to this receptor, uh, on the orbital fibroblast surface, which we know is, um, has an overexpression of these receptors. And so by binding to these receptors, it sort of decreases that whole inflammatory cascade of the increase of glycosaminoglycans, um, and cytokines and that whole inflammatory process. Um, now in terms of the medication, you know, it's been five, no, six years, um, since it's been approved. So I've treated a variety of patients and so we have a lot of real-world data to go along with the, uh, original clinical trial data. Um, and there are, um, definitely side effects that we need to be aware of and our patients need to be educated on and patient selection is going to be key.

(27:28): Um, I'd say overall it's a very well tolerated and safe drug. Um, patients tend to complete it and do fairly well, however, important to realize that there are serious, um, potential risks, including hyperglycemia. So in patients with diabetes, it's very important to make sure that's being co-managed with endocrine to avoid, um, uh, worsening of their, um, uh, glucose levels. Hearing loss and impairment, there's been a lot of talk and research, um, going around, um, that side effect. Um, we know that it can cause hearing loss and that can be permanent. So this is something that, um, at my office we do audiograms, um, prior to initiation of treatment during treatment and after treatment, um, so that this can be closely monitored, um, because we don't want patients to end up treating one problem for a different one. Um, so I think, you know, patient selection and having that discussion before treatment is really important.

(28:22): Uh, another important side effect to be aware of is patients who have any history of inflammatory bowel disease. Uh, we want to be very careful because we know this, uh, medicine can worsen this, uh, condition. So, uh, we want to make sure that is under control, um, and diarrhea in general is also a side effect, um, for this drug. Um, some of the other milder side effects that are most commonly seen, muscle spasms or nausea, um, cramps, um, dry skin, fatigue, menstrual changes, and thinning of the nails and thinning of the hair, um, are also seen. So most, again, most of these side effects are mild and manageable, but when it comes to the more serious side effects, it's important to remember the blood sugar, um, the hearing changes, inflammatory bowel disease. Um, and these patients definitely need to be counseled that, um, they have to be using some sort of, uh, birth control during the six month treatment period as well as six months after, um, because it is teratogenic.

(29:23): Um, and another, you know, thing to be cognizant of is that it is expensive. Um, so that is something to, to keep in mind when we're selecting which patients, you know, are going to be benefiting from this, um, because that, that, uh, can be, uh, significant, um, cost burden to the health industry.

Dr. Uner (29:41): That's, that's awesome. I think it's, um, always important to be cognizant of that. So going back to our patient at the beginning, you started her on ocular lubrication, you obtained thyroid labs and the thyroid stimulating immunoglobulin assay, which confirmed hyperthyroidism from Graves' disease. Uh, when would you like to see her back and how would you counsel the patient?

Dr. Malik (30:01): Definitely I would start by, uh, sending her to an endocrinologist to get her thyroid level under control because we know that that can help, um, their eye disease. And I've seen patients who've had, you know, hyperthyroidism that comes under control and, um, their eyes can improve. Um, there are also really important lifestyle things that we can counsel her on, um, making sure that she stops smoking, um, that is going to significantly decrease her risk of disease, um, and her risk of optic neuropathy. Um, we can talk about up the selenium supplementation, uh, and we can also lubricate her eyes. She's, uh, had significant, um, staining on her cornea, so we can recommend ointment at night, taping the eyes at night, um, just to kind of decrease some of that inflammation. Um, and I would see her back probably in about three months, uh, that is my usual interval, uh, for monitoring these patients.

(30:54): Uh, again, we can counsel them on the red, uh, monitoring to make sure they're not developing worsening and I give them an educational handout and tell them if they feel like they're significantly progressing prior to their next appointment to come in sooner so we can talk about some of the alternate, um, you know, medical therapies prior, um, uh, sooner than their follow-up appointment. Um, you know, surgery, we don't usually perform until they're both clinically and radiographically stable for at least three to six months, um, because we don't want to be doing surgery if they're going to be continuing, uh, to progress. Um, and at each visit, you know, we, um carefully will measure their Hertel and, um, I'll discuss with them, you know, how their quality of life is doing and then check their, um, clinical activity score. So I think for this patient, um, hopefully with her thyroid levels improving and, um, some of that surface, um, improvement, she, she, um, sorry, the surface lubrication, we would hope to see some improvement.

(31:54): Um, I would also, uh, offer, depending on how bothered she is at her first appointment, um, this is someone I would also consider discussing, you know, IV steroids or, um, teprotumumab for because she does have the proptosis, um, and the swelling, uh, the redness, you know, her clinical activity score would be considered active. Um, so if this is something significantly interfering with her life, you know, those are, um, conversations we could have.

Dr. Uner (32:21): Yeah, definitely. I think it kind of sits in the mild to moderate category, um, of the disease where I think a lot of the treatments would be, um, as you said, uh, feasible to discuss. So great. Let's summarize what we learned from Dr. Malik. Thyroid eye disease is an autoimmune disease targeting orbital fibroblasts as we talked about. It's mostly seen in patients with, um, hyperthyroidism, but a small subset can be hypothyroid or even euthyroid, and the severity of TED doesn't parallel the serum thyroid levels. So important to, uh, keep that in mind. Uh, it's about six to seven times more common, uh, in women and more common and severe in smokers, uh, it is the most common cause of unilateral or bilateral proptosis and eyelid retraction is also the most common clinical feature. Other findings can include eyelid edema, chemosis, caruncular edema, conjunctival injection, dry eye, and strabismus.

(33:15): Treatment can be supportive, optimizing the dry eye, making sure they get selenium supplementation with or without corticosteroids and immunomodulatory therapy. Teprotumumab is an insulin-like growth factor one blocker that can be effective from moderate to severe TED. Urgent orbital decompression like we talked about is required if there's optic neuropathy or severe proptosis and decompression should be performed first followed by strabismus surgery and then followed by eyelid surgery if needed. And radiotherapy may prevent optic neuropathy as well, but its real role remains controversial with additional therapies in the pipeline for this, uh, very heterogeneous disease as Dr. Malik said. Dr. Malik, anything else you'd like to add?

Dr. Malik (33:57): No, I think you really summarized it well there. Um, it's a pretty complex disease to discuss in, you know, 20, 30 minutes, but I think that was a great summary.

Dr. Uner (34:05): Thank you. And Dr. Malik, before we end each 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?

Dr. Malik (34:17): Gosh, that is a really, uh, tough question. Um, not going to lie. Um, but if I had to go back, I mean, I've been in practice now for about, uh, 12 years. So I think, uh, it might be just to sort of learn to embrace your imperfection early. Uh, it doesn't necessarily mean you're failing, but you're actually growing. Um, you know, mistakes are our fastest teachers and, um, a lot of time we’ll grow more from reflection rather than perfection. Um, and I think compassion not just for your patients but for yourself, um, is really important as surgeons. And so, um, I'd say, you know, don't fear your mistakes that they're actually going to be some of your best teachers. Um, surgery and patients are going to challenge you, but how you respond, um, will define, uh, the surgeon and the person you become.

Dr. Uner (35:07): That's awesome. I think that was really inspirational. Uh, thank you so much for, for that. And Dr. Malik, thank you for joining us on this episode of The Pupil Pod.

Dr. Malik (35:16): Thanks so much. It was my pleasure.

Dr. Uner (35:17): And thank you to our listeners. See you next time on the Pupil Pod.