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Thyroid eye disease: The masquerading eye disorder— a guide to accurate diagnosis and collaborative care

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Podcast

In this episode, four expert faculty talk about the importance of early diagnosis and treatment of thyroid eye disease. They discuss the differential diagnosis, screening tests, and the need for multidisciplinary management for these patients.

In this episode, four expert faculty talk about the importance of early diagnosis and treatment of thyroid eye disease. They discuss the differential diagnosis, screening tests, and the need for multidisciplinary management for these patients.

To start us off, what's the current theory about the pathogenesis of thyroid eye disease?

Dr. Douglas:

Currently, our consideration for the pathogenesis revolves around two receptors that the body recognizes as an autoimmune antigen or as non-self. The idea is that the TSH receptor and the IGF-1 receptor both are targets of the immune system and the body attacks both of these. The TSH receptor is largely on the thyroid gland, and that's why people have thyroid problems such as hyperthyroidism and also autoantibodies generated to that molecule.

The IGF-1 receptor is primarily on the orbital tissue. These two receptors are very closely linked such that the orbital tissue is attacked and the IGF-1 receptor is attacked and continuously stimulated. What happens is, the tissue around the eye expands and it gets inflamed. That also helps us to understand the basis of future treatments and understanding how those two receptors are the target of the immune system.

Thank you. Dr. Douglas. Dr. McGee, what are the most common risk factors for thyroid eye disease that you see in your practice?

Dr. McGee:

I think the biggest risk factor that I see is someone that has been diagnosed with Graves disease and they're a smoker, so they're two to eight times more likely to have thyroid eye disease based on that, so smoking cessation is certainly a big piece to that. The other thing is looking at patients and giving them the knowledge of what this could look like when they have Graves, even if they're euthyroid or hypothyroid, they can actually still get thyroid eye disease.

About 10% of patients can actually have thyroid eye disease alongside euthyroid and hypothyroid, letting them know symptoms and some signs that they might even see and that this could be a potential. Because what we do know is patients typically with thyroid eye disease go undiagnosed for a long time, and so the earlier that we can diagnose a patient, the earlier they can get treatment. Things to watch out for our patients that have dry eye disease.

That have allergic conjunctivitis without any allergic symptoms as far as the itching they will have, but they won't have the pillar that you generally see with allergic conjunctivitis. Then also double vision if they have any changes in their LID structure. Because over half of patients wind up with diplopia, about 90% of patients will have lid retraction at some point. Those are all things to be on the lookout for. In a patient, that could be something subtle that they notice that maybe we don't notice.

I always educate to go back, especially with a dry eye patient that seems to be recalcitrant. It's really difficult to diagnose thyroid eye disease early, but if you have a dry eye patient and patient has dry eye symptoms, itching, watering, burning, a deep ocular pain, dry eye typically has a sharp shooting pain like an ice pick, but with thyroid eye disease, it's a deep orbital pain. Anything new and different or you're treating a dry eye patient and they're just not getting any better, that's a moment to pause and ask yourself, what did I miss?

Ask some of those questions, dig a little bit deeper and make sure that we don't have thyroid eye disease happening versus dry eye disease. That's how it's presented in my clinic where patients came in thinking they had dry eye or thinking they had allergic conjunctivitis and in the absence of other signs, we went down the path with blood work and found out they had thyroid eye disease. Those are some things that can help us in the primary eye care setting.

Dr. Leibowitz, what are the early symptoms of thyroid eye disease?

Dr. Leibowitz:

First of all, thyroid eye disease has more abnormal presentations than there are normal presentations, so you always have to suspect thyroid eye disease in any case. But the most common symptoms that you should look at are dry eye, first of all, because lots of people come in with a dry eye. They have conjunctival and corneal problems where they'll have conjunctival chemosis, conjunctival injection or redness, exposure keratopathy dry eye and grittiness, excessive tearing.

Now, the tearing is really very interesting because people think that if they have tearing, they can't possibly have a dry eye, but they do all the time. There's only two reasons why people have tearing. One is that the nasal lacrimal system is blocked, and two is that it's dry. You have to explain and look at their cornea with stain, and you'll see that they have a dry eye. With the dry eye they'll have photophobia and blurry vision.

Now, that's for the conjunctival and cornea problems. You'll also see eyelid retraction, which is to me the most common thing that you see in thyroid eye disease. 91% of people that have thyroid eye disease have eyelid retraction. There's very few things that cause eyelid retraction besides thyroid eye disease. There's eyelid edema, there's lag ophthalm, and then there's redness and swelling of the eyelid. Also, obviously, if they have proptosis, that's a dead giveaway, but you'll measure it with the hertel.

62% of people that have thyroid eye disease have proptosis disfigurement and they complain of pressure behind the eye, that's pretty common. Then the last part is they will have extraocular muscle problems with diplopia. 51% of thyroid eye disease patients have diplopia. They'll have strabismus with double vision, and also they'll complain about pressure and pain behind their eyes. These are the main issues. But as I said, there's so many other issues with thyroid eye disease because it's a systemic disease.

I've seen patients that came in that looked like they had a contact dermatitis and swelling of the lower lids, and when I had them tested, they were all hyperthyroid. Be suspicious about thyroid eye disease for no matter what strange presentations that they have. But if they have dry eye, lid retraction, proptosis and extraocular muscle problems, then you'll know pretty much that it's thyroid eye disease.

Thank you. Dr. McGee, how does thyroid eye disease impact the quality of life for patients and their families?

Dr. McGee:

It greatly affects their quality of life. When you look at the average journey for a patient being six years through their prognosis, diagnosis of thyroid eye disease, you absolutely have to manage the patient and the expectations from the family members too. They're not going to understand that this can be that long of a disease progression. Also, the quality of life is greatly affected just based on how many doctor's appointments they have.

There was a survey that was done and looking at on average with a mild thyroid eye disease patient. These patients will visit a doctor almost 22 times a year, and if they have severe thyroid eye disease that can double. Imagine your quality of life and what that would look like when you have that many doctor's appointments. When you look in the mirror and you don't look like yourself because you have proptosis. Or you can't drive because you have double vision and you have to rely on a family member to take you places or do anything, you lose your independence.

There's all of those pieces that have to be discussed and is really important for the patient and for their family members to fully understand what this journey can look like and that we have resources and we have a team in place to help them through that. But I think the longevity of the disease is certainly a big piece of this. Now that we have different ways to treat thyroid eye disease, the earlier we get to it, the better and we can help with quality of life when we intervene earlier. I think those are all really big pieces to know. Just to make sure that we are supporting that person not only with their physical changes, but also what happens with their quality of life and making sure they don't fall into depression and manage their anxiety as well.

Thank you. Given all of this, how should clinicians approach the evaluation of a patient with symptoms consistent with TED, Dr. Leibowitz?

Dr. Leibowitz:

The thyroid eye disease evaluation consists of a few problems. First of all, there's the clinical assessment and we go by what the CAS score or the clinical activity score. There are seven problems that you check off whether the patient has those issues on the CAS score, and there's also severity measurements. You also want to measure with a hertel exophthalmometer, whether they have proptosis or not. You want to record whether they have diplopia and you want to check their ocular motility, have them look up down left and right.

Then you want to look at the cornea with the slit lamp, see whether there's corneal involvement with the dry eye, and also you want to test to see whether there's optic nerve involvement. I test every patient for color vision, which is more sensitive for optic nerve involvement. But you want to see obviously, when you take their vision, whether their vision is decreased, whether they have a afferent pupillary defect and so on. That's the clinical assessment.

But then you go onto the laboratory testing. I test quite a few laboratory tests. I test TSH and free T-3 and free T-4 on everyone. I also like to get a TSI, which shows the level of inflammation. Then I test the antibodies, the TPO and what they call T-Rab or TR antibody. The last part as I also get a imaging, which you can either do an orbital CT without contrast or an orbital MRI with fast saturation with and without contrast.

I prefer getting an orbital CT because it's so much quicker. Because I've had both tests and getting an orbital CT without contrast, you don't have to order a creatinine to test their kidneys for whether they can have the die or not. Also, it's just so much quicker. Orbital MRI, which is better for soft tissue will also, you need contrast and it just takes like 20 minutes instead of two minutes. I always prefer getting orbital CT. I get these on every patient as a baseline. Then I'll check to see them again the next time and try to record to see if there's any difference in the clinical activity.

Thank you, Dr. Leibowitz. Dr. Douglas, in approaching the evaluation, what are some of the other conditions that can present in similar ways?

Dr. Douglas:

Whenever we think about thyroid eye disease, we also have to think about other conditions that can present both with eye bulging or inflammation around the eyes. Some of the common characteristics of thyroid eye disease are eye bulging of one or both eyes. It's the most common cause of both and inflammation around the eyes. A lot of times or many times you'll notice that there's an inflammation around the eyes, meaning the eyelids are inflamed and swollen.

Almost looking like an allergy, or either an allergy to a topical cream or even seasonal allergies because they'll cause the eyes to be red also. That has to be eliminated. But those usually don't last that long. Other conditions that cause bulging of the eyes often are diagnosed with a CT scan or an MRI scan so that we can see behind the eyes. In those conditions, what we're looking for, is we're looking for masses that may be pushing the eye forward. Those can be benign. You may be born with those and they expand over time, or they can be actually more serious and require either surgical removal or further treatment. But it's good to both investigate the inflammation around the eye and why the eye is bulging with either further testing or a deep in-depth history.

Dr. Smith, what are some signs and symptoms that should make a provider more suspicious of thyroid eye disease?

Dr. Smith:

Many of my patients complain of persistent eye dryness, grittiness and superficial eye pain, swelling and sensitivity to wind and sun. They complain of looking more wide-eyed with increased eye prominence. Progression of these features suggests clinically active TED and the need for increased surveillance, more frequent follow-up and referral to my oculoplastic colleagues.

Thank you. Dr. Douglas, now that we've heard about the signs and symptoms, what's the most effective way to work up a patient when you suspect thyroid eye disease?

Dr. Douglas:

One of the things that we often think about in thyroid eye disease is A. Making the diagnosis and then B. categorizing how severe the disease is. First, in making the diagnosis, almost all, about 95% of patients with thyroid eye disease also have Graves disease or some form of thyroid autoimmunity. One of the first things we do is our thyroid testing, and that's often at baseline a TSH, just measuring the hormone. But it can also be a little bit more in depth, measuring both the T-3, T-4 and then finally may even measuring the antibodies that are directed against the thyroid.

Finally, once that is established, we can then also think about the eye disease and a diagnosis of thyroid eye disease can also be done with a CT or an MRI scan of the orbits. Because what we see there is an expansion of the muscles that move the eye that are often implicated in this disease process and are very evident on these types of scans.

Thank you. Dr. Smith, what's the role of the endocrinologist in managing patients with thyroid eye disease?

Dr. Smith:

By virtue of their training in systemic disease, endocrinologists are well poised for monitoring and treating a multisystemic process like Graves' disease and thyroid eye disease. Because of the close association existing between TED and thyroid autoimmunity and the frequent thyroid dysfunction occurring in TED patients, endocrinologists can co-manage this disease syndrome by making early diagnosis, prescribing medications specifically for treating TED and ensuring the patients are maintained in a euthyroid state. The importance of which in optimizing TED outcomes cannot be overstated.

Dr. Leibowitz, what's the role of the oculoplastic surgeon in managing a patient with thyroid eye disease and how have newer therapies changed this role?

Dr. Leibowitz:

Oculoplastic surgery are really, in my opinion, the main person taking care of thyroid eye disease. But they want to do this in conjunction with the endocrinologists. Before Tepezza and other newer medications were on the market, what we used to do is, in the acute phase of thyroid eye disease, we would just do supportive measures with treating the dry eye and so on and waiting until they went into what we called the plateau phase.

In that phase we would do surgery. In the acute phase, they could either have treatment with steroids, IV steroids, as well as radiation, which I was never big on. Then in the chronic phase, we would do surgery and the surgeries would consist of three types of surgeries. We would do them in this order. The patient may or may not need any or all of them. The first surgery we would do is orbital decompression to get the eyeball back in the socket.

After orbital decompression if they had double vision, I would send them to strabismologists or the muscle doctor. Usually pediatric ophthalmologists do that kind of surgery. I don't do strabismus surgery. Then the third set of surgeries would be lid surgery for treating their lid retraction either upper or lower lids. The reason we do it in that order is because each one of those surgeries can cause problems with the next set of surgeries.

It's kind of like you put in the plumbing in the wall before you put the drywall up, otherwise you have to repeat it. That's how we would treat them from a surgical standpoint. Well, since Tepezza has come out, it's changed everything. Tepezza was tested in the acute phase, but it was approved for all phases of thyroid eye disease. As clinicians, we tried it on chronic patients also, and it seemed to work just as well as it did in the acute phase.

Now the most recent studies have come out and showed for the chronic phases of thyroid eye disease that it works very well also. My paradigm has changed completely. I try to have the patients get Tepezza first, and then I see what surgery they need after that Tepezza treatment. Because usually the Tepezza treats the exophthalmos and the diplopia very well. They either may or may not need decompression or they may need some decompression afterwards, but it really has been a game changer.

As far as the diplopia, I haven't really had to refer anybody off for strabismus surgery after Tepezza. Tepezza doesn't really work on the lid retraction, so quite a few people have still had to have lid retraction surgery after Tepezza. Tepezza also really hasn't really been shown to work on the dry eye, so we still have continued treatment for the dry eye.

Dr. Douglas, what strategies characterize optimal multidisciplinary care for patients with TED?

Dr. Douglas:

Multidisciplinary care is actually critical for thyroid eye disease. You can imagine that you have a thyroid component. Having an internist endocrinologist weigh in upon the appropriate endocrinologic control of the thyroid, treatment of the thyroid, which can be done very well, is critical. It does have some, even though small, bearing upon the eye disease. Then in addition, those patients are often referred to an ophthalmologist.

Often an ophthalmologist makes sure that there are no visual compromise that can occur with thyroid eye disease and often makes even a tertiary referral to an oculoplastic surgeon who can then diagnose thyroid eye disease and create a treatment plan, whether that be medical or surgical for that matter. But you can also imagine that each of these components has to rely upon each other and communicate with each other. It's critical not only from the diagnosis and treatment of the thyroid components and how someone feels, to also treatment of the thyroid eye disease by the subspecialist oculoplastic surgeon. Could these all be coordinated? You probably should see each of these specialists at some point throughout a diagnosis of thyroid eye disease for optimal care.

Thank you. Dr. Smith, how does an integrated healthcare approach in therapeutic management impact patient outcomes?

Dr. Smith:

Co-managed TED offers the best chance for the best possible outcomes by involving healthcare providers with specialized clinical tools to a complex disease such as TED. The important and addressable components that impact clinical outcomes can be achieved.

Lastly, Dr. McGee, can you comment on how healthcare providers can manage patients' expectations during the diagnostic journey?

Dr. McGee:

I think it's really important to give patients what to expect and also to give them comfort that they're going to have a team of professionals that's going to help them through this journey. When you look at the statistics on how patients feel through this journey and then what they considered themselves healthy and well, and what physicians consider themselves healthy and well is very different. The typical journey for a patient through thyroid eye disease lasts almost six years, and it's a variety of individuals.

It's an endocrinologist. It's going to be their team in an optometrist, an oculoplastic specialist. Sometimes there's even a neuro-ophthalmologist involved as well. But bottom line is, there's a team that's going to help this patient through their journey. I think it's really important that they understand and know that they have a team behind them that's going to help them through this. I think it's really important for doctors that are watching to make sure that you have a team in place.

I'm in private practice. I don't work in a tertiary setting, but I certainly have a team of individuals who we work with that can manage a patient through a journey of thyroid eye disease. I went out and solicited that and put this group together in my own community. I think that's really important for the patient to fully understand that they're not alone in this, and we're going to be able to help them throughout their prognosis with thyroid eye disease.

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