MECHANISM OF DISEASE

IGF-1R activation on orbital fibroblasts is believed to control the pathophysiology of Thyroid Eye Disease (TED) throughout the course of disease1

Stimulated orbital fibroblasts causing inflammation and tissue expansion behind the eye during the pathophysiology of thyroid eye disease

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Autoantibodies initiating IGF-1R/TSHR, activating the orbital fibroblasts during the pathophysiology of Thyroid Eye Disease

Autoantibodies initiate the IGF-1R/TSHR signaling complex, and this activates orbital fibroblasts1-3

Stimulated orbital fibroblasts causing inflammation behind the eye during the pathophysiology of thyroid eye disease

Once stimulated, orbital fibroblasts cause inflammation and the expansion of muscle and fat tissue behind the eye3,4

TED DAMAGE BEGINS BEHIND THE EYE4

Before erythema or proptosis are visible, TED autoantibodies are targeting the orbital fibroblasts, specialized cells responsible for tissue and cell repair, via the IGF-1R/TSHR signaling complex.1-3 The resulting inflammatory cascade causes muscle tissue within the orbit to swell. Adipose tissue at the back of the orbit also expands. These tissue changes within the rigid, bony space of the orbit force the eye forward (proptosis) and put dangerous pressure on the optic nerve.3-5

MRI studies can provide objective confirmation of the substantial inflammatory changes in and around the orbit and show the involvement of individual muscles, including early in the course of disease.6 In one study, orbital MRI revealed extraocular muscular swelling in 70% of patients who had Graves’ disease but no visible signs of TED.7,8

The swelling of muscle and expansion of orbital fat seen on these types of imaging studies can cause ocular tenderness, pain, and pressure.  As TED progresses, the increased intraorbital volume puts pressure on the eye and optic nerve as more pronounced signs begin to appear, such as proptosis/exophthalmos, vision changes, and signs of corneal exposure.5

The consequences of TED are potentially devastating.9 Though infrequently, TED can sometimes lead to
permanent loss of vision, and more commonly, cause chronic discomfort, diplopia, and facial disfigurement.1

Early intervention is important. Prompt consultation with a TED Specialist can help improve long-term outcomes for patients with TED symptoms.10 A TED Specialist can order an MRI to look for swelling or fat around the eyes as this can be an early sign of TED.4,8

LOCATE A TED SPECIALIST NOW

IGF-1R, insulin-like growth factor-1 receptor; TSHR, thyroid-stimulating hormone receptor.

  1. 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. doi:10.2147/TCRM.S193018
  2. Krieger CC, Boutin A, Jang D, et al. Arrestin-β-1 physically scaffolds TSH and IGF1 receptors to enable crosstalk. Endocrinology. 2019;160(6):1468-1479. doi:10.1210/en.2019-00055
  3. Dik WA, Virakul S, van Steensel L. Current perspectives on the role of orbital fibroblasts in the pathogenesis of Graves’ ophthalmopathy. Exp Eye Res. 2016;142:83-91. doi:10.1016/j.exer.2015.02.007
  4. Bahn RS. Graves’ ophthalmopathy. N Engl J Med. 2010;362(8):726-738. doi:10.2147/TCRM.S193018
  5. 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. doi:10.1155/2015/249125
  6. Kilicarslan R, Alkan A, Ilhan MM, Yetis H, Aralasmak A, Tasan E. Graves’ ophthalmopathy: the role of diffusion-weighted imaging in detecting involvement of extraocular muscles in early period of disease. Br J Radiol. 2015;88(1047):20140677. doi:10.1259/bjr.20140677
  7. Villadolid MC, Yokoyama N, Isumi M, et al. Untreated Graves’ disease patients without clinical ophthalmopathy demonstrate a high frequency of extraocular muscle (EOM) enlargement by magnetic resonance. J Clin Endocrinol Metab. 1995;80(9):2830-2833. doi:10.1210/jcem.80.9.7673432
  8. Smith TJ, Hegedüs L. Graves’ disease. N Engl J Med. 2016;375(16):1552-1665. doi:10.1056/NEJMra1510030
  9. Wu CY, Niziol LM, Musch DC, Kahana A. Thyroid-related orbital decompression surgery: a multivariate analysis of risk factors and outcomes. Ophthalmic Plast Reconstr Surg. 2017;33(3):189-195.
  10. Mitchell AL, Goss L, Mathiopoulou L, et al. Diagnosis of Graves’ orbitopathy (DiaGO): results of a pilot study to assess the utility of an office tool for practicing endocrinologists. J Clin Endocrinol Metab. 2015;100(3):E458-E462. doi:10.1210/jc.2014-3146