ABOUT TED

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 TED

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 TED7§

Emotional side of Thyroid Eye Disease iconEmotional side of Thyroid Eye Disease 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 TED

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

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

TEPEZZA mechanism of action iconTEPEZZA mechanism of action icon

See how TEPEZZA works to treat Thyroid Eye Disease

Find a Thyroid Eye Disease specialist iconFind a Thyroid Eye Disease specialist icon

Find a TED Specialist

INDICATION

TEPEZZA is indicated for the treatment of Thyroid Eye Disease regardless of Thyroid Eye Disease activity or duration.

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 controlled with medications for glycemic control, if necessary. Assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to monitor while on treatment with TEPEZZA. Ensure patients with hyperglycemia or preexisting diabetes are under appropriate glycemic control before and while 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, weight decreased, nail disorders, and menstrual disorders.

Please see Full Prescribing Information or visit TEPEZZAhcp.com for more information.

P-TEP-US-01064 04/23

INDICATION

TEPEZZA is indicated for the treatment of Thyroid Eye Disease regardless of Thyroid Eye Disease activity or duration.

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 controlled with medications for glycemic control, if necessary. Assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to monitor while on treatment with TEPEZZA. Ensure patients with hyperglycemia or preexisting diabetes are under appropriate glycemic control before and while 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, weight decreased, nail disorders, and menstrual disorders.

Please see Full Prescribing Information or visit TEPEZZAhcp.com for more information.

P-TEP-US-01064 04/23

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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.
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  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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  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.
  16. Shan SJ, Douglas RS. The pathophysiology of thyroid eye disease. J Neuroophthalmol. 2014;34(2):177-185.
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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
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