Thyroid eye disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Thyroid eye disease is an autoimmune disorder affecting orbital fat, extraocular muscles and related soft tissues. It is most often associated with Graves disease, but eye symptoms can precede the thyroid diagnosis or occur during biochemical euthyroidism or hypothyroidism. The eye and thyroid manifestations share an immune background without moving in perfect synchrony. A normal thyroid result therefore does not explain away convincing orbital signs, and successful control of thyrotoxicosis does not automatically reverse established eye disease.

Patients may describe grittiness, watering, discomfort behind the eyes, altered appearance or double vision. Lid retraction produces a staring appearance and exposes more ocular surface. Enlarged or fibrotic muscles restrict movement rather than simply weakening a cranial nerve. Inferior rectus restriction can impair elevation and produce vertical diplopia. Orbital tissue expansion may push the globe forwards, but tissue crowding near the apex can compromise the optic nerve with relatively little obvious protrusion.

Assessment separates disease activity from severity. Pain, redness and inflammatory swelling suggest activity; a standardised clinical activity score helps record this consistently. Severity incorporates corneal protection, diplopia, proptosis, soft-tissue involvement, optic-nerve function and the person's daily difficulties. Neither a photographic appearance nor an activity score can substitute for testing sight. A person whose appearance causes marked distress also deserves that impact to be acknowledged, even when visual acuity is normal.

Management begins with smoking cessation support, stable thyroid control, ocular lubrication and specialist assessment according to risk. Discuss passive smoke exposure and practical help with stopping. Thyroid treatment choices need coordination with the eye team because radioiodine may exacerbate orbitopathy in susceptible patients; selected patients need prophylactic glucocorticoids, while active severe disease changes the treatment discussion. Selenium is considered for selected mild active cases, especially in selenium-deficient settings, rather than as indefinite supplementation for every patient. Compound and elemental selenium quantities are not interchangeable.

Active moderate-to-severe disease may need immunomodulatory treatment in a specialist thyroid-eye service. The EUGOGO framework includes intravenous methylprednisolone with mycophenolate, with alternative or additional therapies selected for disease features, contraindications and response. Mycophenolate use for this indication is off-label and requires explicit counselling, laboratory surveillance and pregnancy-prevention measures. Treatment aims should specify whether the main problem is inflammation, proptosis, diplopia or threatened vision; improvement in one domain does not prove that all have resolved.

Teprotumumab now has a UK licence for adults with moderate-to-severe thyroid eye disease. Licensing does not by itself establish routine NHS funding: on 7 September 2026, NICE appraisal GID-TA11995 remained in development, with expected publication on 8 October 2026. The current product information includes important hearing, glucose, infusion and reproductive precautions. Specialist selection should incorporate those risks and the actual commissioning pathway, without presenting a consultation document as final NICE guidance.

Once inflammation has settled, residual proptosis, restrictive strabismus or lid malposition may persist. Reconstructive treatment is usually staged because changing orbital volume can alter alignment, and changing alignment can affect lid position. The usual sequence is decompression, then strabismus surgery, then eyelid surgery when each is required. This planned rehabilitation is distinct from urgent decompression to rescue vision during active disease.

Key points

Thyroid eye disease can occur with normal thyroid function.
Activity describes inflammation; severity describes functional and anatomical impact.
Smoking increases risk and worsens the clinical course.
A relatively quiet eye can still have optic neuropathy.
Control thyroid dysfunction alongside the separate orbital treatment plan.
Active sight-threatening disease may require urgent surgical decompression.
Persistent inactive changes can benefit from staged reconstructive surgery.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Autoimmune thyroid association

Immune responses associated with Graves disease can also affect orbital connective tissue. Eye involvement may occur before overt thyroid disease or alongside normal or low circulating thyroid-hormone concentrations.

Smoking and susceptibility

Smoking increases susceptibility and is associated with a more adverse orbital course. Genetic and environmental influences help explain why only some people with thyroid autoimmunity develop clinically significant eye disease.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Fibroblast activation
Orbital fibroblasts participate in immune-driven tissue remodelling, with glycosaminoglycan accumulation, fluid retention and altered fat formation. These processes increase tissue volume within the fixed bony orbit.
2
Muscle restriction
Extraocular muscle inflammation and subsequent fibrosis change muscle extensibility. This produces gaze-dependent restriction and misalignment, with double vision that can persist after the most active inflammatory period has subsided.
3
Apical crowding
Enlarged orbital tissues can crowd the optic nerve near the apex. Neural dysfunction may develop without proportionate forward displacement of the globe or obvious swelling of the visible optic disc.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Lid and surface findings

Look for upper-lid retraction, lid lag, incomplete closure, conjunctival inflammation and exposure staining. Watering may represent surface irritation rather than excess effective lubrication.

Restrictive motility pattern

Ask whether double vision varies with gaze and assess ductions and alignment. Fibrotic or enlarged muscles can limit movement despite intact cranial-nerve innervation.

Optic-nerve warning signs

Compare acuity, colour perception, pupils and fields between eyes. Bilateral symmetrical disease may lack a relative afferent pupil defect, and a normal disc appearance does not exclude compression.

Disease context and trajectory

Record thyroid history, recent treatment, smoking, symptom progression and prior orbital interventions. Asymmetry can occur, but a focal mass or unusual course deserves investigation for alternatives.

Red flags requiring action

New reduction in vision, colour discrimination or visual field.
Corneal epithelial breakdown, severe exposure or inability to close the lids.
Rapidly progressive orbital symptoms or globe subluxation.
An atypical unilateral mass, marked pain or systemic illness suggesting another orbital disorder.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Structured ophthalmic baselineFirst step
Why
Measure function, exposure and anatomical change for subsequent comparison.
Interpretation and limitations
Record visual acuity, colour testing, pupils, fields, motility, corneal staining and exophthalmometry where available; deterioration in neural function carries more urgency than a stable prominence measurement.
02
Thyroid function and relevant antibodies
Why
Establish biochemical status and support the autoimmune context.
Interpretation and limitations
TSH and free thyroid hormones guide endocrine treatment; receptor-antibody testing can support diagnosis, but neither a normal hormone result nor antibody level determines visual safety.
03
Orbital CT or MRI
Why
Assess atypical disease, apical crowding or surgical anatomy.
Interpretation and limitations
Imaging can demonstrate muscle and fat enlargement and alternative lesions; the specialist selects the modality, and urgent clinical escalation is not deferred while routine imaging is requested.
04
Pretreatment systemic assessment
Why
Identify risks before systemic steroids or another immunomodulator.
Interpretation and limitations
Review infection, liver disease, cardiovascular status, blood pressure, glucose, pregnancy potential and medicine interactions; add treatment-specific blood counts, renal tests and hearing assessment where indicated.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Orbital tumour

A focal orbital lesion can cause progressive proptosis, altered globe position or optic-nerve dysfunction. A highly asymmetric course or discrete mass is less typical of diffuse autoimmune orbital involvement.

Orbital inflammation or infection

Other inflammatory disorders and orbital infection can produce pain, swelling and restricted movement. Fever, abrupt progression and associated sinus disease favour an infectious process rather than uncomplicated thyroid eye disease.

Neuromuscular diplopia

Myasthenia and ocular motor nerve disorders can cause double vision through impaired neuromuscular transmission or innervation. Their patterns differ from the mechanical restriction associated with enlarged and fibrotic orbital muscles.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Mild diseaseProtect comfort and identify progressionFirst stepSurface symptoms or mild changes without threatening visual features.

1Coordinate thyroid assessment and offer practical support to stop smoking.
2Use lubricants and address nocturnal exposure with the eye team.
3Discuss a time-limited selenium course only when clinically appropriate, checking the preparation rather than assuming elemental and compound doses match.
4Set review and provide clear instructions to seek urgent help for colour or acuity change.

02Active significant diseaseAgree a specialist treatment targetInflammation, diplopia or other changes materially affect daily function.

1Record activity, severity and patient-reported impact before selecting treatment.
2Discuss intravenous steroid-based treatment and suitable adjuncts within the specialist service.
3Screen for contraindications and arrange the monitoring required by each medicine.
4EscalationAssess response across vision, inflammation, motility and quality of life, escalating inadequate control.

03Threatened sightTreat neuropathy or corneal breakdown urgentlyNeural visual dysfunction or severe corneal exposure raises sight risk.

1Contact ophthalmology immediately and arrange assessment in an appropriately equipped service.
2Begin specialist-directed rescue treatment for optic neuropathy and intensive corneal protection where needed.
3Review visual function closely during treatment rather than relying on reduced redness.
4Arrange urgent decompression for deterioration or inadequate steroid response; do not wait through a predetermined review interval when sight worsens.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Specialist anti-inflammatory treatment, often combined with an appropriate immunomodulatory adjunct.

Intravenous methylprednisolone for active moderate-to-severe disease

A standard EUGOGO course is 500 mg intravenously weekly for six weeks, then 250 mg weekly for six weeks: 4.5 g total.

Specialist contraindication assessment includes significant psychiatric disorder, serious hepatic or cardiovascular disease, and infection or hepatitis risk. Hypertension and diabetes require control before treatment; cumulative exposure should not exceed 8 g per cycle.

Off-label specialist adjunct to intravenous methylprednisolone for active moderate-to-severe thyroid eye disease.

Mycophenolate sodium or mycophenolate mofetil

EUGOGO adjunct: enteric-coated mycophenolate sodium 360 mg orally twice daily, totalling 720 mg/day for 24 weeks. If unavailable, the equivalent mofetil regimen is 500 mg twice daily, totalling 1 g/day.

Contraindicated for this indication in pregnancy and during breastfeeding. Confirm pregnancy prevention, screen infection and monitor blood counts, liver and renal function; report fever, bruising or bleeding. Formulations must not be switched indiscriminately.

Immediate treatment for sight-threatening optic-nerve compromise while planning possible decompression.

Intravenous methylprednisolone for dysthyroid optic neuropathy

Specialist rescue uses 500–1,000 mg intravenously on three consecutive days or preferably on alternate days, with further treatment determined by urgent reassessment.

This rescue regimen differs from the weekly elective course. Poor response within one to two weeks requires urgent decompression consideration, and earlier deterioration requires earlier surgical action.

UK-licensed specialist option for adult moderate-to-severe disease, subject to the available commissioning pathway.

Teprotumumab

Give 10 mg/kg intravenously initially, then 20 mg/kg every three weeks for seven further doses, using actual body weight.

Contraindicated in pregnancy; use highly effective contraception during treatment and for six months afterwards. Assess hearing before, during and after treatment; monitor glucose, bowel disease and infusion reactions.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Dysthyroid optic neuropathy

Compression or other compromise of the optic nerve can impair acuity, colour perception and the visual field. Severe or sustained injury may leave permanent visual impairment.

Exposure keratopathy

Proptosis and lid retraction can prevent effective closure and leave the cornea poorly protected. Surface desiccation may progress to epithelial breakdown, ulceration and scarring.

Persistent functional and psychosocial effects

Residual misalignment, lid retraction and altered appearance can affect reading, driving, employment and social confidence. These consequences may continue after the active inflammatory stage has ended.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

At eye follow-up, repeat visual function and corneal assessment as well as activity, diplopia and prominence measurements; agree earlier review for a changing course.
During steroid treatment, track glucose, blood pressure, liver tests, infection and mental-state effects, and address gastrointestinal and bone protection according to individual risk and the specialist protocol.
For teprotumumab, assess glucose before infusions and during therapy, with glucose monitoring for six months afterwards. Observe during each infusion and for 90 minutes after completion.
Before mycophenolate, arrange two negative pregnancy tests, preferably eight to ten days apart. Women need reliable contraception before and during treatment and for six weeks afterwards, with two methods preferred; the male patient or female partner needs contraception during treatment and for at least 90 days afterwards.
Review driving and work safety when diplopia is present, and offer orthoptic advice, practical adaptations and psychological support when appearance or function affects wellbeing.
For Myfortic, the SmPC specifies full blood counts weekly in month one, twice monthly in months two and three, then monthly through year one. Neutrophils below 1.5 × 10^9/L or other blood disorders warrant prompt specialist review and consideration of interruption.
For a mofetil regimen, SPS recommends blood count, albumin, liver enzymes and renal function every two weeks for at least six weeks until stable, then three-monthly, with ongoing checks at least every twelve weeks; follow the specialist's individual plan.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Activity is not visual safety

An inflammatory score helps describe the disease and compare visits, but optic-nerve dysfunction can be clinically important without dramatic redness. Visual testing remains a separate part of each relevant assessment.

Appearance and anatomy differ

The amount of visible proptosis does not reliably describe the space available at the orbital apex. A less prominent eye can still have clinically significant muscle crowding around the nerve.

Supplement formulation matters

Selenium recommendations depend on the preparation and the population studied. Check the exact product and intended duration with the specialist; additional supplements can unintentionally increase total exposure.

A staged recovery

Inflammation may improve before double vision or altered lid position resolves. Explaining these separate trajectories helps patients understand why later rehabilitation may still be useful after successful medical treatment.

11Common pitfallsFrequent interpretation and management errors.

01
Attributing new reduced vision solely to dry eye without testing colour, pupils and fields.
02
Assuming normal thyroid blood tests exclude an autoimmune orbital disorder.
03
Treating a quieter external appearance as proof that optic-nerve risk has resolved.
04
Calling a licensed medicine routinely NICE-funded before a final recommendation exists.
05
Planning elective rehabilitation without checking whether disease and measurements are stable.