What is thyroid eye disease?

What is Thyroid Eye Disease?

Thyroid eye disease (TED) is an autoimmune inflammatory disorder characterized by orbital congestion, inflammation, and tissue remodeling that causes soft tissue swelling, eyelid retraction, exophthalmos (bulging eyes), restrictive extraocular muscle dysfunction, and potentially vision-threatening optic neuropathy. 1

Pathophysiology and Core Features

TED is an autoimmune condition strongly associated with Graves' disease, though the severity of eye involvement does not necessarily correlate with systemic thyroid disease severity. 2, 3 The disease process involves:

• Orbital tissue inflammation and congestion with enlargement of preseptal fat pads 1
• Extraocular muscle enlargement due to inflammatory edema initially, followed by fibrosis 1
• Autoimmune targeting of the insulin-like growth factor-1 receptor (IGF-1R) and thyroid-stimulating hormone receptor (TSHR) complex in orbital tissues 4

Clinical Presentation

Primary Manifestations

• Exophthalmos (proptosis): Bulging of the eyes, typically bilateral but often asymmetric 5, 6
• Eyelid retraction: Particularly of the upper eyelid, creating a characteristic staring appearance 5, 6
• Soft tissue congestion: Periorbital edema, conjunctival redness (chemosis), and eyelid erythema 6
• Restrictive myopathy: Affects 30-50% of patients, most commonly involving the inferior rectus muscle, followed by the medial rectus 1, 5
• Diplopia (double vision): Results from extraocular muscle dysfunction and restrictive myopathy 1, 5
• Compensatory head posture: Often a chin-up position to minimize double vision 1, 5

Vision-Threatening Complications

• Compressive optic neuropathy: Due to crowding at the orbital apex from enlarged muscles and orbital fat 1, 5, 6
• Exposure keratopathy: Corneal damage from inadequate eyelid closure due to proptosis and lid retraction 1, 5, 6
• Elevated intraocular pressure: Can occur as a complication 1, 5

Epidemiology and Risk Factors

Demographics

• Incidence: 16 per 100,000 per year in Caucasian women and 2.9 per 100,000 per year in men 1
• Female predominance: 8:1 female-to-male ratio 1, 5
• Age of onset: Most commonly in the fourth to fifth decade of life 1, 5
• Male gender paradox: Despite lower incidence, men tend to develop more severe disease 6

Modifiable Risk Factors

• Smoking: Significantly increases both risk and severity of TED 1, 5, 6
• Diseases causing reduced oxygen saturation: Such as emphysema 1, 6
• Radioactive iodine treatment: Independent risk factor for developing TED 1

Non-Modifiable Risk Factors

• High anti-thyroid antibody titers 1, 5
• Serum vitamin D deficiency 1, 5
• Low blood selenium levels 6
• Family history of thyroid eye disease or other thyroid disorders 6
• Prior orbital decompression surgery: Associated with increased risk of strabismus 1, 6
• Exposure to ionizing radiation 1, 6

Disease Classification and Activity

Severity Grading

The NO SPECS classification categorizes disease from N (no signs or symptoms) through O (only signs), S (soft tissue involvement), P (proptosis), E (extraocular muscle involvement), C (corneal involvement), to S (sight loss). 5

Activity Assessment

• Clinical Activity Score (CAS): Ranges from 0-7, with scores ≥3 indicating active inflammation 5
• Active disease: Characterized by inflammatory edema, pain, and progressive symptoms 1, 7
• Inactive disease: Characterized by fibrotic changes and stable symptoms for at least 6 months 2

Impact on Quality of Life

TED profoundly affects patients through:

• Visual dysfunction: From diplopia, reduced visual acuity, or visual field defects 1
• Disfigurement: From proptosis and eyelid changes 8
• Socioeconomic consequences: From compensatory head posture and appearance changes 1
• Chronic discomfort: From exposure symptoms and orbital pain 5

Associated Conditions

Myasthenia gravis has an increased incidence in patients with TED and should be assessed when clinical features suggest coexistence. 1, 5