Thyroid Eye Disease: Overview, Diagnosis, and Current and Emerging Treatment Options

Thyroid eye disease (TED) is a chronic endocrine, autoimmune disease characterized by immune-mediated orbital inflammation that greatly impacts a person’s vision.

The condition often occurs in people with hyperthyroidism or Graves’ disease (GD), but also can occur in association with hypothyroidism, euthyroidism, and Hashimoto’s thyroiditis. GD affects approximately 1% to 2% of the adult population, with an estimated 40% of GD patients subsequently developing TED over the course of their lifetime. The onset of TED typically occurs between 30 and 50 years of age, with the disease course more severe after age 50.

Etiology

The complete etiology of TED is unknown. However, it is understood that it involves an autoimmune inflammatory response within the orbit. Orbital fibroblasts are central to disease development due to their higher expression of thyroid-stimulating hormone (TSH) receptors. Different fibroblast subpopulations contribute to distinct disease patterns, leading to either orbital fat expansion or fibrotic enlargement of the extraocular muscles.

Epidemiology

The prevalence of TED is about 50% among patients with Grave’s disease. The annual incidence is 16 per 100,000 women and 2.9 per 100,000 men in the United States.

Individuals who are Black, ages 40 to 69, women, and who have preexisting autoimmune conditions experience a higher incidence of TED. Smoking is also strongly associated with severity of TED. There is also evidence of genetic and environmental factors that can affect disease prevalence and severity.

Pathophysiology

Due to the absence of orbital lymphoid tissue, active inflammation in TED eventually settles, leading to a stabilization of disease.

TED progression is commonly sorted into 3 phases:

1. Active or inflammatory phase: A steep rise in disease severity, lasting 6 months to 5 years.
2. Static or plateau phase: Disease activity persists but does not progress.
3. Inactive or burnout phase: TED usually improves after 18 months of disease activity. However, this disease rarely resolves completely and residual fibrotic changes persist in the orbit.

Symptoms

Common symptoms can include:

• Ocular discomfort
• Upper eyelid retraction
• Dry eyes
• Tearing
• Inflammation
• Erythema
• Light sensitivity
• Sensation of a foreign body present in the eye

Diagnosis

TED is evaluated based on disease activity and severity. The most well known classification system is the NO SPECS classification, which grades clinical severity based on no signs or symptoms, only (mild) signs, soft tissue involvement (eyelids and conjunctiva), proptosis, extraocular muscle involvement, corneal involvement, and sight loss (optic nerve injury).

Patients may present to various care settings and require thorough evaluation for ocular and orbital manifestations, thyroid status, and cardiovascular risk, with prompt initiation of thyroid hormonal treatment.

Treatment/Management

Management requires an interdisciplinary team that includes an ophthalmologist, an oculofacial plastic surgeon, an endocrinologist, an optometrist, a primary care clinician, and pharmacists. 

About 80% of TED cases require management with topical lubricant eye drops, 5% require systemic corticosteroids or immunomodulatory therapy, and about 15% of patients undergo surgical intervention.

Long-term follow-up and close monitoring for disease complications is necessary.

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