Thyroid Eye Disease

Cross-reference the endocrinology-diabetes Graves’ disease pages for the thyroid-function side of management.

Thyroid eye disease (TED, also known as Graves’ orbitopathy) is a potentially sight-threatening autoimmune condition affecting 25–50% of patients with Graves’ hyperthyroidism; up to 10% of TED occurs in euthyroid or hypothyroid patients. Onset is typically within 2 years of the Graves’ disease diagnosis.

Pathophysiology (brief)

Thyrotropin receptor autoantibodies (TRAbs) cross-react with TSH receptor and IGF1R on orbital fibroblasts, driving T-cell activation, glycosaminoglycan (hyaluronan) accumulation in extraocular muscles, and orbital fibroblast-to-adipocyte differentiation — producing periorbital oedema, proptosis and restricted eye movement. The inferior rectus is most commonly involved (61.8%), followed by medial, superior and lateral rectus.

Clinical presentation

TED has an active inflammatory phase followed by an inactive phase (usually after 12–18 months) — proptosis and extraocular muscle dysfunction can persist in up to 50% of patients even once inflammation settles.

• Active phase: watery/gritty eyes, photophobia, redness, eye pain, blurred vision (mimics dry eye) — eyelid oedema is often worse in the morning and can be mistaken for hayfever/allergic conjunctivitis
• Eyelid retraction and proptosis give a characteristic staring appearance
• Extraocular muscle involvement → diplopia, reduced motility (especially upgaze/abduction)
• In 3–5% of cases: dysthyroid optic neuropathy (DON) — progressive vision loss, reduced colour vision, RAPD, visual field defects — a sight-threatening emergency

Exclude other differentials, especially with unilateral presentations or euthyroid status: orbital myositis, idiopathic orbital inflammation, sarcoidosis, orbital tumour, lymphoproliferative disease, vascular malformation (see penetrating-eye-injury.md’s orbital-swelling differential and the orbital-varix case discussion below), carotid-cavernous fistula, myasthenia gravis. Investigate with baseline bloods + CT or MRI orbit/brain.

Risk factors

• Smoking is the most significant modifiable risk factor for TED development and progression
• More common in females, but males tend to have more severe eye disease
• High thyrotropin receptor autoantibody (TRAb) titres increase relative risk
• Risk factors for progression to DON specifically: diabetes, obstructive sleep apnoea, higher clinical activity score (CAS) at presentation, TRAb ≥5.0 IU/L, older age at diagnosis, smoking

Screening and grading

All Graves’ disease patients should be screened for TED at every visit (~3-monthly). Screen for: new upper-lid swelling/lower-lid “bags”, eye redness, a more wide-open appearance, spontaneous or movement-related retrobulbar pain, blurred/double vision.

Clinical Activity Score (CAS) — the standard tool for active vs inactive disease (≥3/7 initial, or ≥4/10 subsequent = active):

#	Item	Score
1	Retro-orbital pain	1
2	Pain on eye movement	1
3	Eyelid erythema	1
4	Conjunctival hyperaemia	1
5	Eyelid oedema	1
6	Conjunctival chemosis	1
7	Swelling of caruncle/plica	1
8 (at 1–3mo)	Increased proptosis ≥2mm	1
9 (at 1–3mo)	Reduced motility ≥8° any direction	1
10 (at 1–3mo)	Decreased VA ≥1 Snellen line	1

EUGOGO severity grading:

Severity	Definition
Mild	Minor impact on daily life; ≥1 of: lid retraction <2mm, mild soft tissue involvement, proptosis <3mm above normal, no/intermittent diplopia, lubricant-responsive corneal exposure
Moderate-to-severe	Sufficient impact to warrant immunosuppression/surgery; ≥2 of: lid retraction ≥2mm, moderate-severe soft tissue involvement, proptosis ≥3mm above normal, diplopia (inconstant/constant)
Sight-threatening	Dysthyroid optic neuropathy and/or corneal breakdown

Approximately 20–30% of patients develop moderate-to-severe disease; 3–5% develop DON or permanent vision loss.

Thyroid-stimulating immunoglobulin (TSI) vs thyroid hormone levels

Thyroid hormone levels do not reliably correlate with TED activity or severity — even once euthyroid, continue screening for TED throughout the disease course. TSI assay has been shown to correlate better with disease severity.

General measures (all patients)

• Smoking cessation
• Restore euthyroid status (co-manage with endocrinology)
• Lubricating eye drops (ointment at night)
• Dark sunglasses for photophobia
• Head elevation when sleeping (reduces oedema)
• Patching one eye for diplopia
• Selenium 100 mcg BD for 6 months in active disease
• Correct vitamin D deficiency if present
• Statin if concurrent hypercholesterolaemia

When to refer

Routine referral: diagnostic uncertainty; any ocular symptoms in a Graves’ disease patient; unilateral/atypical presentation (may need orbital biopsy to exclude other orbital pathology); CAS ≥3; significant impact on daily/visual function; stable-phase disease needing surgical correction.

Urgent referral: suspected DON, corneal breakdown from exposure, rapidly progressive proptosis or globe subluxation.

Ophthalmologist-led treatment (for context, not GP-initiated)

• IV methylprednisolone — first-line in Australia (EUGOGO protocol: 500mg weekly ×6 weeks, then 250mg weekly ×6 weeks); improves activity/quality of life with fewer side effects than oral steroids, but doesn’t reliably improve proptosis/motility. Avoid with uncontrolled diabetes, severe hypertension, hepatitis, heart failure.
• Teprotumumab — a human monoclonal antibody against IGF1R, FDA-approved 2020 and TGA-approved March 2025; indicated for active moderate-to-severe TED. 8 doses over 6 months; reduces CAS to 0 in 62% of trial patients and proptosis by ≥2mm in 75%; cut orbital decompression rates to 4.1% vs 25% with steroids/radiation alone. Requires hearing monitoring; specialist-administered only.
• Rituximab (anti-CD20) and tocilizumab (IL-6 receptor antagonist) — second-line steroid-sparing options for poor responders/recurrence; tocilizumab contraindicated in diverticular disease (GI perforation risk)
• Orbital radiotherapy — often combined with IV steroids, especially for myopathic subtype; 92% DON response with combination therapy vs 65% with steroids alone; avoid in diabetic retinopathy and age <35 (head/neck malignancy risk from radiation)
• Surgery (stable phase, or urgently for sight-threatening disease) — orbital decompression first (for DON/severe exposure keratopathy urgently, or proptosis correction electively), then strabismus surgery once swelling settles, then eyelid surgery for cosmetic/functional correction

Driving

Drivers with TED-related diplopia must notify their driver licensing authority. Diplopia generally makes a driver unfit unless corrected with lenses or an occluder (after a 3-month adaptation period). See vision-and-fitness-to-drive.md for the full visual-standards framework, including state-based mandatory reporting obligations.