Thyroid Ophthalmopathy

Description

Thyroid ophthalmopathy, also known as thyroid eye disease or Graves’ ophthalmopathy, is an autoimmune condition characterised by inflammation and swelling of the extraocular muscles, orbital fat, and connective tissues within the orbit. It is the most common cause of unilateral or bilateral proptosis in adults.

Pathogenesis

Thyroid ophthalmopathy is caused by autoimmune-mediated activation of orbital fibroblasts by autoantibodies targeting the thyrotropin receptor (TSHR)¹. These fibroblasts differentiate into adipocytes and myofibroblasts, leading to increased adipogenesis and glycosaminoglycan production. The accumulation of glycosaminoglycans and expansion of adipose tissue cause tissue swelling and orbital congestion. Cytokines released by activated T-cells further exacerbate inflammation and fibroblast proliferation. The resultant tissue remodelling and fibrosis can lead to proptosis, extraocular muscle dysfunction, and optic neuropathy. Genetic predisposition, such as polymorphisms in immune-regulatory genes, and environmental factors like smoking, amplify the autoimmune response, aggravating disease severity² .

Epidemiology, Risk Factors & Associations

• Most common in patients with Graves’ disease.
• Females are more commonly affected than males.
• Smoking significantly increases the risk.

Clinical Features

• Eyelid retraction, proptosis (bulging eyes), and swelling.
• Symptoms include dry eyes, blurred vision, double vision, and discomfort in the eyes.
• In severe cases, it may cause sight-threatening corneal ulceration or compressive optic neuropathy.

Complications

• Compressive optic neuropathy, which can lead to vision loss.
• Exposure keratitis due to inability to close the eyes completely.
• Cosmetic disfigurement and psychosocial distress.

Pathological Features

Histopathology

• Macroscopic: Enlargement and congestion of extraocular muscles.
• Microscopic: Infiltration of inflammatory cells, fibrosis, and swelling in orbital tissues.

Serology

• Elevated thyroid-stimulating hormone (TSH) receptor antibodies.

Biochemistry

• Abnormal thyroid function tests (raised free T4 and T3, suppressed TSH).

Radiological Features

General Features

• Characteristically demonstrates bilateral, symmetric, enlargement of the extraocular muscles with an order of predilection that follows the mnemonic I’M SLow
  • Inferior rectus (most common)
  • Medial rectus
  • Superior rectus
  • Lateral rectus
• Coca-Cola bottle sign – describes the spindle-shaped extraocular muscle belly enlargement with sparing of the musculotendinous junction forming an appearance of a traditional Coca-Cola bottle
• Increased volume and density of orbital fat.
• Exopthalmos – defined as >21 mm (or approximately two-thirds of the globe) anterior to the interzygomatic line (a line drawn between the lateral ribs of the zygomatic bones)
• The optic nerve may be straightened or appear stretched
• Lacrimal gland enlargement may also be seen.
• Superior ophthalmic vein dilatation due to compromised orbital venous drainage at the orbial apex.

CT

• Non-contrast: Shows enlarged extraocular muscles with sparing of the tendon, increased orbital fat, and apical crowding.
• Contrast-enhanced: Muscles may show enhancement.

MRI

• T1: Enlarged extraocular muscles appear isointense to othe facial muscles.
• T2: Hyperintense signal in the involved muscles due to oedema.
• T1 C+: Enhancement of the involved muscles and orbital fat.

Ultrasonography

• Thickening of the extraocular muscles can also be seen on ultrasound.

Grading and Staging

Clinical Activity Score (CAS) and NOSPECS are two systems used for grading and staging.

Diagnosis

Diagnosis is based on clinical symptoms, ophthalmologic examination, thyroid function tests, and imaging.

Differential Diagnosis

Imaging-based

• Orbital pseudotumour – Presents with rapid onset, pain, and is usually unilateral. 2nd most common cause of exophthalmos. Imaging demonstrates tendon involvement which is key to differentiating it with thyroid ophthalmopathy. Higher values on ADC support diagnosis over lymphoma/malignant disease. Any muscle is affected although superior and medial rectus muscles are most frequent.
• Orbital cellulitis: Usually associated with recent sinusitis or systemic infection. Would demonstrate fat stranding on imaging and be associated with fever.
• Orbital lymphoma: Would typically show a diffusion-restricting (low ADC values) discrete mass rather than diffusely enlarged muscles.

Management

Management is usually multi-disciplinary involving endocrinologists, ophthalmologists, and radiologists. First-line management involves addressing modifiable risk factors such as smoking cessation and control of thyroid function. Further management may involve steroids, radiotherapy or surgical decompression. Surgery or radioablative ¹³¹iodine to treat underlying thyroid disease.

References

1. Bahn, R.S. (2010). Graves’ Ophthalmopathy. New England Journal of Medicine, 362(8), 726-738. ↩︎
2. Smith, T.J., & Hegedüs, L. (2016). Graves’ Disease. New England Journal of Medicine, 375(16), 1552-1565. ↩︎