This autoimmune disorder is the most common orbital disease

Thyroid Eye Disease (TED) is a multisystem inflammatory disease that occurs when the immune system attacks the eyes, orbit, and, in some cases, surrounding tissues. In North America and Europe, TED is the most common orbital disease.¹ TED is often, but not always, associated with the systemic condition Graves’ disease, which accounts for 90% of patients with TED.² Graves’ disease, an autoimmune disorder, is caused by antibodies directed against receptors present in the thyroid cells and also on the surface of the cells behind the eyes.

This column, the first in a series on TED, will describe the condition to lay the groundwork for additional articles.

CAUSES AND PROGRESSION

What initially triggers TED still remains a mystery. However, we do know that autoantibodies target the orbital tissues, especially the extraocular muscles and orbital fat. When these autoantibodies bind to the orbital tissues, they activate an inflammatory response, leading to tissue expansion, swelling, and fibrosis. Orbital inflammation occurs earlier in the disease, followed by fibrosis caused by orbital fibroblasts.

The disease process follows a curve called Rundle’s curve where there is an active and inactive phase. This curve helps demonstrate the importance of early treatment during the active phase to minimize long-term effects.³

To monitor the amount of in-flammation and disease progression, the main antibody, thyroid-stimulating immunoglobulin (TSI), can be measured within the bloodstream. Elevated levels of insulin-like growth factor (IGF-IR) have been found in patients who have TED, and it is thought that IGF-IR activates and stimulates orbital fibroblasts.⁴ Pro Tip: Have the patient screened for these biomarkers when TED is suspected, as it can occur when other thyroid measures, such as TSI and the hormones triiodothyronine and thyroxine, are normal.

POPULATIONS AT RISK

The majority of patients who have TED are females between the ages of 40 to 44 and 60 to 65, and men between the ages of 45 to 49 and 65 to 69.⁴ Females are affected more often, with 0.016% of women to 0.003% of men. Ethnicity can also play a role, as there is a higher incidence of TED among Pacific Island/Asian and Black individuals.

Other risk factors for TED are family history of thyroid disorders or TED, smoking or cigarette exposure, presence of thyroid-stimulating hormone receptor antibodies (TSHR) or TSI, and radioactive iodine therapy.

Those who have Graves’ disease and smoke increase their risk of developing TED seven times compared to nonsmokers.

PREVENTION

Avoiding or decreasing exposure to the risk factor of smoking may help limit disease severity and progression. Also, avoiding stress and maintaining adequate Vitamin D and selenium levels have been found to possibly help prevent the worsening of TED.^2,5 OM

The next TED column will appear in the May 2022 issue of OM and address how to diagnose TED. The column will include a discussion of signs, symptoms, and diagnostic tools.

References

1. Liaboe CA, Simmons BA, Clark TJ, et al. EyeRounds. Thyroid eye disease. webeye.ophth.uiowa.edu/eyeforum/patients/thyroid-eye-disease.htm . September 1, 2016. Accessed December 28, 2021.
2. Bartley, G B. “The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota.” Transactions of the American Ophthalmological Society vol. 92 (1994): 477-588.
3. Sabini, Elena et al. “Does Graves’ Orbitopathy Ever Disappear? Answers to an Old Question.” European thyroid journal vol. 6,5 (2017): 263-270. doi:10.1159/000477803
4. Tramontano D, Cushing GW, Moses AC, et al. Insulin-like growth factor-I stimulates the growth of rat thyroid cells in culture and synergizes the stimulation of DNA synthesis induced by TSH and Graves’-IgG. Endocrinology. 1986;119(2):940-2.
5. Bahn RS. Graves’ ophthalmopathy. N Engl J Med. 2010 Feb 25;362(8):726-38. doi: 10.1056/NEJMra0905750. PMID: 20181974; PMCID: PMC3902010.

Dr. Huegel graduated from the Southern College of Optometry and is currently completing her residency in ocular disease and anterior segment at Associated Eye Care in Stillwater, Minn.