Thyroid eye disease

Overview

•TRAbs bind TSH receptors on orbital fibroblasts → glycosaminoglycan deposition + adipogenesis → extraocular muscle swelling + orbital fat expansion → raised intraorbital pressure → proptosis, lid retraction, optic nerve compression
•Occurs predominantly in Graves' disease; affects ~30% clinically

Risk Factors

Smoking - most important modifiable risk factor (4-8x increased risk)
Radioiodine therapy - precipitates/worsens TED in up to 15% of Graves' patients
High TRAb titre
Poor thyroid hormone control
Female sex
Older age
⚠️
Radioiodine is contraindicated in active or severe TED. If used in mild TED, co-prescribe prophylactic oral corticosteroids. Antithyroid drugs (carbimazole, propylthiouracil, methimazole) and thyroidectomy do not worsen TED.

Presentation

•Proptosis (exophthalmos) - anterior globe displacement
•Lid retraction - upper lid above limbus, 'staring' appearance; hallmark sign
•Lid lag - upper lid fails to follow globe on downgaze (von Graefe's sign)
•Diplopia - commonly vertical; inferior rectus most often affected
•Gritty/dry eyes, eye pain - corneal exposure and lacrimal involvement
•Reduced colour vision (red desaturation) - earliest and most sensitive sign of compressive optic neuropathy
•Reduced visual acuity - late feature of optic nerve compromise
🚨
Any patient with Graves' disease who reports colour vision loss (especially red desaturation) requires urgent same-day referral to eye casualty - this is an early warning of compressive optic neuropathy which can progress to irreversible sight loss.

Investigations

🏆 Gold standard

•TSH receptor antibodies (TRAbs) - >90% sensitivity and specificity for Graves' disease

🥇 First-line

•TSH + free T4/T3; Clinical Activity Score (CAS); formal visual acuity, colour vision (Ishihara plates), visual fields; Hertel exophthalmometry

🥈 Second-line

•MRI/CT orbits - enlarged extraocular muscles (fusiform belly swelling), increased orbital fat, optic nerve compression at orbital apex

Management

•Foundation (all patients): achieve euthyroidism; smoking cessation; avoid radioiodine if active TED
•Conservative: artificial tears/lubricating ointment (corneal protection); selenium 100 micrograms twice daily for 6 months (mild active TED); prism spectacles for stable diplopia
•Active moderate-severe TED (CAS ≥3) - first-line: IV methylprednisolone (pulsed weekly/fortnightly over 12 weeks) - more effective and better tolerated than oral prednisolone
•Active moderate-severe TED - second-line: orbital radiotherapy; mycophenolate mofetil if steroids fail/contraindicated
•Sight-threatening TED: emergency surgical orbital decompression if no response to IV steroids within 2 weeks, or immediately if vision critically threatened
•Rehabilitative surgery (inactive disease ≥6 months): orbital decompression first → squint surgery → eyelid surgery last

Complications

Key complications of thyroid eye disease
ComplicationKey featuresFrequency
Exposure keratopathyCorneal damage from incomplete lid closure due to proptosis and lid retraction; pain, redness, photophobia, tearing; can progress to ulcerationMost common complication
Compressive optic neuropathyEnlarged muscles compress optic nerve at orbital apex; red desaturation (earliest), RAPD, visual field defects, reduced VA, disc oedema/atrophySight-threatening; less common
DiplopiaFibrosis of inferior rectus most commonly; restricts upgazeCommon
Globe subluxationGlobe displaced forward beyond eyelids; ophthalmological emergencyRare
Acute glaucomaSecondary to raised intraocular pressure; presents with acute red eye, fixed dilated pupil, halosUncommon