TED and Graves’ disease have different
underlying mechanisms1,2

TED is distinct from Graves' disease. TED is characterized by the following2:

  • Is a serious, chronic autoimmune disease that can lead to long-term repercussions1,3-5
  • Is progressive, can worsen vision, and can potentially lead to optic neuropathy3,6,7
  • Can present with a variety of signs and symptoms3,7
  • Can reactivate or flare8
  • May lead to psychosocial difficulties9,10

IGF-1R is the root cause of TED and drives the pathophysiology
throughout the course of disease3,11

TED can progress over time, and early intervention has
been shown to reduce disease impact. Early signs and
symptoms of TED may include the following1,3,12:

Dry, gritty eyes icon

Dry eyes and grittiness1,12

Red, swollen eyes icon

Redness, swelling,
and excessive
tearing1

Pulled-back, or retracted, eyelid icon

Eyelid retraction1

Proptosis icon

Proptosis12

Eye pain or pressure icon

Pressure and/or
pain behind the eyes1,3

Diplopia icon

Diplopia12

Warning icon

Not all signs of TED may be visible, so it’s important to ask your patients if they’re experiencing new or changing symptoms.
If they are, consider a TED treatment that works at the source of the disease.3,11,13

Hear how Dr Lisa Mihora uses a team approach to treat her
patients with Thyroid Eye Disease, and learn about the importance of early diagnosis14,15

dr. mihora thumbnail
Read transcript

Hi. My name is Dr. Lisa Mihora. And I am an oculoplastics surgeon in Phoenix, Arizona. Distinguishing Thyroid Eye Disease and Graves’ disease is important. They’re often linked, but they are two different entities. And Thyroid Eye Disease can actually present before, during, or after the diagnosis of Graves’ disease.

Thyroid Eye Disease can present in patients who are euthyroid, hyperthyroid, or even hypothyroid. And because Thyroid Eye Disease is a separate and distinct disease from Graves’, treating Graves’ does not address the pathophysiology or symptomatology of Thyroid Eye Disease.

In Graves’ disease auto-antibodies target the thyrotropin receptor, which thereby triggers hyperthyroidism. Whereas in Thyroid Eye Disease, we have additional auto antigens and antibodies that are involved.

The understanding of the mechanism of Thyroid Eye Disease has changed, now that insulin-like growth factor-1 receptor, or IGF-1 receptor, has been identified.

We now know that orbital fibroblasts, which are up-regulated in Thyroid Eye Disease, are key drivers of the pathophysiology of Thyroid Eye Disease. The T-cells and fibroblasts activate, and the inflammatory response and cascade has begun.

And the pathophysiology can translate into the signs and symptoms of Thyroid Eye Disease.

Once the fibroblasts are activated, they can cause severe inflammation and over-expansion of tissues, muscle, and the fat cells that are located behind the eye.

Because this is a fixed bony orbit, this can lead to different clinical manifestations.

Inflammation can occur, as well as foreign body sensation. A patient may have excessive tearing or dry eye. There can be conjunctival or eyelid redness, as well as swelling. A patient may have orbital pain, chemosis, proptosis, or bulging eye, and diplopia, or double vision.

Because there are so many different signs and symptoms that a patient can present with, educating patients, as well as our providers, means that we can hone in on the diagnosis earlier, and potentially treat earlier.

The goal of treating Thyroid Eye Disease early, in order to help combat the symptoms a patient may have, is a team approach. A team approach between endocrinology, and ophthalmology, or oculoplastics.

Endocrinology has a very unique role, in that they specialize in treating the autoimmune disorder and the endocrine dysfunctions, such as Graves’ disease and refer early to the ophthalmologist or oculoplastic surgeon, in order to monitor the eye symptomatology.

Ophthalmologists or oculoplastic surgeons can often be the first to diagnose Thyroid Eye Disease patients. A baseline eye exam is conducted. And the patient’s Thyroid Eye Disease is evaluated.

I do co-manage patients with endocrinologists. And I find it very helpful when the endocrinologist now refers a patient early. That way, we can potentially start treatment, and start exams, and start the discussion, as early as possible.

I think that this dual approach to a patient gives a patient the best information and the best team approach, so that both aspects of the Thyroid Eye Disease can be effectively treated and managed.

Consequences of Thyroid Eye Disease (TED)

The consequences of TED can be potentially
debilitating and vision-threatening16,17

Proptosis iconProptosis icon

62% of patients

with TED experience
Proptosis2,18,19*

Diplopia iconDiplopia icon

51% of patients

with TED experience
Diplopia20†

Dysthyroid Optic Neuropathy iconDysthyroid Optic Neuropathy icon

5% to 7% of patients

with TED experience Dysthyroid
Optic Neuropathy15

(a severe manifestation of TED
that can result in vision loss)

The impact of TED on
psychological health7,9,10,17

Patient appearance iconPatient appearance icon

63% of patients

with TED experience psychosocial distress caused by a change in appearance10‡

Self-confidence icon Self-confidence icon

52% of patients

with TED experience loss of self-confidence due to TED

Emotional distress iconEmotional distress icon

45% of patients

with TED experience emotional
distress such as feeling anxious9‖

*Based on an incidence cohort of 120 patients with Graves’ orbitopathy in Olmsted County, Minnesota, who were diagnosed between 1976 and 1990.18,19

Based on a cross-sectional follow-up study carried out from 1998 to 2000 of 168 patients with Graves' orbitopathy who had started radiotherapy and/or prednisone treatment between 1982 to 1992.20

Based on a modified Graves’ Ophthalmopathy Quality of Life (GO-QOL) survey completed by 128 patients with TED.10

§Based on the responses of 250 patients with TED on a questionnaire about their quality of life, occupational disability, and use of psychotherapy.7

Based on a prospective and controlled descriptive study of 102 consecutive patients to assess the psychosocial morbidity of TED using internationally validated self-reporting questionnaires.9

Diagnosing Thyroid Eye Disease (TED)

There are a number of diagnostic protocols and tools available to aid in a TED diagnosis. The Clinical Activity Score (CAS) is one of them and may be used to identify the signs and symptoms of inflammation characteristic of TED13

Doctor using exophthalmometer to measure woman's Thyroid Eye Disease clinical activity score

CAS measurements may be required
for treatment approval

  • The score at each assessment is the number of all symptoms present.21

Clinical Activity Score

  • CAS is a 7-point composite score measuring spontaneous orbital pain, gaze-evoked orbital pain, eyelid swelling, eyelid erythema, conjunctival redness, chemosis, and inflammation of caruncle or plica. A lower score indicates fewer symptoms. The CAS is a composite score with equal weighting of a number of factors. However, the factors may not be of equal clinical weight to patients or to physicians treating these patients.21,22

Ask your patients if they are currently experiencing or have
ever
experienced the following:

  • Spontaneous orbital pain
  • Gaze-evoked orbital pain
  • Eyelid swelling
  • Eyelid erythema
  • Conjunctival redness
  • Chemosis
  • Inflammation of caruncle or plica

Symptoms may not always be noticeable during a baseline examination; at follow-up visits it is important to ask your patients if they are experiencing any new or changing symptoms.3,11,13

Hear how TEPEZZA has changed the way Dr Gary Lelli treats TED11

Dr Gary Lelli thumbnail

Dr Gary Lelli discusses the signs and symptoms of TED and the struggles his patients with TED often experience as a result.

Read transcript

My name is Gary Lelli. I’m a physician and oculoplastic surgeon specialist in New York City where I take care of patients who have eyelid, lacrimal and orbital disorders.

When patients first come to me they're feeling quite anxious. They've had a drastic change in the way that they appear and they want to know why it's happening.

It's disabling. If you're used to seeing one image and all of a sudden you begin seeing two images, you're now struggling to drive, you're worried about walking down steps and falling. It's something that's on their mind almost every minute of the day.

My most recent patient, she had told me that in addition to struggling to see, which was limiting her ability to do work, she was also routinely shutting her camera off on her Zoom calls. She became uncomfortable showing her face on camera. We're really highlighting that two things can occur here. One, she's struggling with her function. Two, now she's limiting her interaction with her colleagues because she's distraught by her appearance.

TEPEZZA really has changed the way we can think about taking care of these patients. It's our first and only FDA approved treatment for thyroid eye disease. It's been shown to be effective in decreasing proptosis, reducing diplopia for patients, improving patient's functional vision and appearance, and decreasing the inflammatory signs of the disease, namely, pain and swelling.

It's really changed the way we think about the disease, but also, it's given the patients hope that there's something they can do early in the disease process that will change the course. I'm noticing on most of these patients after two or three infusions, they have significant improvement already in multiple aspects of their disease. What that allows them to do is get back to feeling like themselves again and get back to functioning again much quicker.

A multidisciplinary team is optimal to co-manage
this complex disease13,23

  • According to the American Thyroid Association, TED is best evaluated and co-managed by an endocrinologist, ophthalmologist, and/or optometrist, and a subspecialty ophthalmologist. A subspecialty ophthalmologist is most commonly an oculoplastic surgeon or neuro-ophthalmologist, but this varies by region.13,24

INDICATION

TEPEZZA is indicated for the treatment of Thyroid Eye Disease.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Infusion Reactions: TEPEZZA may cause infusion reactions. Infusion reactions have been reported in approximately 4% of patients treated with TEPEZZA. Reported infusion reactions have usually been mild or moderate in severity. Signs and symptoms may include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache, and muscular pain. Infusion reactions may occur during an infusion or within 1.5 hours after an infusion. In patients who experience an infusion reaction, consideration should be given to premedicating with an antihistamine, antipyretic, or corticosteroid and/or administering all subsequent infusions at a slower infusion rate.

Preexisting Inflammatory Bowel Disease: TEPEZZA may cause an exacerbation of preexisting inflammatory bowel disease (IBD). Monitor patients with IBD for flare of disease. If IBD exacerbation is suspected, consider discontinuation of TEPEZZA.

Hyperglycemia: Increased blood glucose or hyperglycemia may occur in patients treated with TEPEZZA. In clinical trials, 10% of patients (two-thirds of whom had preexisting diabetes or impaired glucose tolerance) experienced hyperglycemia. Hyperglycemic events should be managed with medications for glycemic control, if necessary. Monitor patients for elevated blood glucose and symptoms of hyperglycemia while on treatment with TEPEZZA. Patients with preexisting diabetes should be under appropriate glycemic control before receiving TEPEZZA.

Adverse Reactions

The most common adverse reactions (incidence ≥5% and greater than placebo) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, dry skin, and menstrual disorders.

Please see Full Prescribing Information for more information.

INDICATION

TEPEZZA is indicated for the treatment of Thyroid Eye Disease.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Infusion Reactions: TEPEZZA may cause infusion reactions. Infusion reactions have been reported in approximately 4% of patients treated with TEPEZZA. Reported infusion reactions have usually been mild or moderate in severity. Signs and symptoms may include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache, and muscular pain. Infusion reactions may occur during an infusion or within 1.5 hours after an infusion. In patients who experience an infusion reaction, consideration should be given to premedicating with an antihistamine, antipyretic, or corticosteroid and/or administering all subsequent infusions at a slower infusion rate.

Preexisting Inflammatory Bowel Disease: TEPEZZA may cause an exacerbation of preexisting inflammatory bowel disease (IBD). Monitor patients with IBD for flare of disease. If IBD exacerbation is suspected, consider discontinuation of TEPEZZA.

Hyperglycemia: Increased blood glucose or hyperglycemia may occur in patients treated with TEPEZZA. In clinical trials, 10% of patients (two-thirds of whom had preexisting diabetes or impaired glucose tolerance) experienced hyperglycemia. Hyperglycemic events should be managed with medications for glycemic control, if necessary. Monitor patients for elevated blood glucose and symptoms of hyperglycemia while on treatment with TEPEZZA. Patients with preexisting diabetes should be under appropriate glycemic control before receiving TEPEZZA.

Adverse Reactions

The most common adverse reactions (incidence ≥5% and greater than placebo) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, dry skin, and menstrual disorders.

Please see Full Prescribing Information for more information.

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  2. Wang Y, Patel A, Douglas RS. Thyroid eye disease: how a novel therapy may change the treatment paradigm. Ther Clin Risk Manag. 2019;15:1305-1318.
  3. Patel A, Yang H, Douglas RS. A new era in the treatment of thyroid eye disease. Am J Ophthalmol. 2019;208:281-288.
  4. Rundle FF, Wilson CW. Development and course of exophthalmos and ophthalmoplegia in Graves’ disease with special reference to the effect of thyroidectomy. Clin Sci. 1945;5(3-4):177-194.
  5. Ugradar S, Kang J, Kossler AL, et al. Teprotumumab for the treatment of chronic thyroid eye disease. Eye (Lond). 2022;36(8):1553-1559.
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  7. Ponto KA, Pitz S, Pfeiffer N, Hommel G, Weber MM, Kahaly GJ. Quality of life and occupational disability in endocrine orbitopathy. Dtsch Arztebl Int. 2009;106(17):283-289.
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  10. Park JJ, Sullivan TJ, Mortimer RH, Wagenaar M, Perry-Keene DA. Assessing quality of life in Australian patients with Graves’ ophthalmopathy. Br J Ophthalmol. 2004;88(1):75-78.
  11. TEPEZZA (teprotumumab-trbw) [prescribing information] Horizon.
  12. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382(4):341-352.
  13. Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velázquez-Villoria Á, Galofré JC. Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol. 2015;2015:249125.
  14. Ozzello DJ, Dallalzadeh LO, Liu CY. Teprotumumab for chronic thyroid eye disease. Orbit. 2022;41(5):539-546.
  15. Dolman PJ. Grading severity and activity in thyroid eye disease. Ophthalmic Plast Reconstr Surg. 2018;34(4S supp 1):S34-S40.
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  20. Terwee C, Wakelkamp I, Tan S, Dekker F, Prummel MF, Wiersinga W. Long-term effects of Graves' ophthalmopathy on health-related quality of life. Eur J Endocrin. 2002;146(6):751-757.
  21. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18)(suppl):1748-1761. https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614949 /suppl_file/nejmoa1614949_appendix.pdf
  22. European Group on Graves’ Orbitopathy (EUGOGO); Wiersinga WM, Perros P, Kahaly GJ, et al. Clinical assessment of patients with Graves’ orbitopathy: the European Group on Graves’ Orbitopathy recommendations to generalists, specialists and clinical researchers. Eur J Endocrinol. 2006;155(3):387-389.
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