What is the appropriate work‑up and management for a patient presenting with bilateral proptosis, eyelid retraction, diplopia, and restrictive strabismus, who has a history of thyroid dysfunction or autoimmune disease and may also have myasthenia gravis?

Thyroid Eye Disease: Work-up and Management

Initial Diagnostic Work-up

A patient presenting with bilateral proptosis, eyelid retraction, diplopia, and restrictive strabismus requires a comprehensive ophthalmologic examination, orbital imaging, thyroid function testing, and assessment for concurrent myasthenia gravis. 1

Essential Clinical Examination Elements

• Measure proptosis using exophthalmometry to establish baseline and track disease progression 1
• Perform complete sensorimotor examination with forced duction testing to confirm mechanical restriction; look for fixation duress (brow elevation and augmented eyelid retraction on attempted upgaze) as a pathognomonic sign of restrictive strabismus 1
• Document the pattern of strabismus: hypotropia with esotropia is most common due to inferior and medial rectus involvement, though global extraocular muscle involvement frequently occurs 1
• Map binocular visual fields to define the region of single binocular vision and measure duction deficits using uniocular fields of fixation 1
• Screen aggressively for compressive optic neuropathy by checking visual acuity, color vision, visual fields, pupillary responses, and fundus examination for disc edema or atrophy 1
• Obtain OCT and Humphrey visual fields as ancillary screening tools for optic neuropathy 1
• Assess for myasthenia gravis if clinical examination suggests coexistence, as the incidence of myasthenia is increased in thyroid eye disease patients 1, 2

Medical History Priorities

• Ask specifically about weight changes, tachycardia, and unexplained fatigue to assess thyroid dysfunction 1
• Document smoking history and counsel immediate cessation, as smoking is the strongest modifiable risk factor that dramatically worsens disease severity and treatment response 1, 2, 3
• Inquire about compensatory head posture (often chin-up position) used to minimize diplopia 1

Required Imaging and Laboratory Studies

• Order orbital CT or MRI to confirm diagnosis and evaluate extraocular muscle size and orbital fat volume; look for tendon-sparing enlargement of muscles (most commonly inferior rectus, then medial rectus) and bilateral but often asymmetric proptosis 1, 2
• Coordinate thyroid function tests and thyroid antibody studies with endocrinology, though patients may be hyperthyroid, hypothyroid, or euthyroid at presentation 1
• Check thyroid-stimulating immunoglobulin (TSI) levels, as they are detectable in >95% of patients and correlate with disease activity and severity 4
• Measure vitamin D levels, as deficiency is an independent risk factor for developing thyroid eye disease 1

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Management Strategy

Treatment must be sequenced based on disease activity and severity, prioritizing vision-threatening complications first, followed by rehabilitative surgery only after the inflammatory phase has resolved and alignment has been stable for at least 6 months. 1, 2

Immediate Vision-Threatening Conditions (Require Urgent Treatment)

• Compressive optic neuropathy demands urgent orbital decompression, high-dose intravenous corticosteroids, or orbital radiation 1, 2
• Severe exposure keratopathy with corneal ulceration requires aggressive lubrication and may necessitate urgent surgical intervention 1, 2
• Markedly elevated intraocular pressure must be monitored and treated to prevent vision loss 1

Conservative Management for All Patients

• Prescribe ocular lubricants (artificial tears and ointments) liberally to combat exposure from eyelid retraction and proptosis 1, 2, 5
• Consider punctal plugs to improve tear retention and reduce corneal exposure risk 1, 2
• Mandate smoking cessation counseling at every visit, as continued smoking dramatically worsens prognosis 1, 2, 3
• Supplement selenium in patients with documented selenium deficiency, as it reduces inflammatory symptoms in mild disease through antioxidant effects 1, 2

Medical Therapy for Active Moderate-to-Severe Disease

• Teprotumumab (IGF-1R inhibitor) significantly reduces proptosis and Clinical Activity Score in patients with active disease 1, 2, 4

  • Critical caveat: Assess for pre-existing hearing loss before treatment and counsel about hearing risk, as 30% of patients experience hearing impairment 2, 4
  • Additional side effects include hyperglycemia; contraindicated in pregnancy 2
  • High relapse rate and cost are significant limitations 4

• Intravenous methylprednisolone remains the treatment of choice in many settings for active inflammation, particularly outside the United States 3, 4

• Tocilizumab (IL-6 receptor blocker) is effective for steroid-resistant cases 4

• Orbital radiation may be added for patients with residual inflammation to facilitate steroid weaning 5, 3

Observation Strategy

• Observe patients without diplopia in primary gaze or reading position and those whose strabismus angle is not yet stable 1, 2
• Continue observation if orbital decompression is planned, as this procedure significantly changes ocular alignment 1

Temporary Diplopia Management

• Prescribe Fresnel or ground-in prisms for temporary relief while awaiting definitive treatment or for modest residual deviations 1, 2
• Consider chemodenervation during the active phase to provide temporary diplopia relief and possibly reduce final misalignment 2

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Surgical Rehabilitation (Only After Disease Stabilization)

Surgery must be delayed until the inflammatory stage has subsided and the angle of deviation has been stable for at least 6 months. 2, 3

Mandatory Surgical Sequence

The surgical sequence must follow this strict order to avoid complications: 2

1. Orbital decompression first (if needed for proptosis or optic neuropathy) 1, 2, 3
2. Strabismus surgery second to address diplopia, as decompression can worsen or create new strabismus 1, 2, 3
3. Eyelid surgery last to correct retraction, as earlier surgeries affect lid position 2, 3

Strabismus Surgery Principles

• Recession of restricted muscles is the mainstay; resection is generally avoided in restrictive disease 2
• Vertical deviations are more challenging than horizontal (66% vs 84% success after primary surgery) because the inferior rectus is most commonly affected 2
• Perform systematic preoperative and intraoperative assessment of forced ductions and ocular torsion to minimize undesired outcomes 1, 2
• Use absorbable sutures (6-0 polyglactin) for muscle isolation and reattachment; consider non-absorbable sutures for large inferior rectus recessions to reduce postoperative drift 1, 2
• Adjustable suture technique remains controversial: some surgeons report better success while others avoid it due to overcorrection and muscle slippage concerns 1, 2

Critical Surgical Pitfalls to Avoid

• Do not perform strabismus surgery during active inflammation, as the deviation will continue to change 2
• Do not perform eyelid surgery before strabismus repair, as muscle surgery affects lid position 2
• Counsel patients preoperatively that recession of fibrotic muscles predictably worsens proptosis; consider orbital decompression consultation before strabismus surgery in patients with concurrent significant proptosis 1, 2
• Recession of inferior rectus carries specific risks: lower lid retraction, consecutive hypertropia, and A-pattern exotropia in downgaze 1, 2
• Thyroid eye disease is the most common risk factor for pulled-in-two syndrome (spontaneous horizontal muscle transection during surgery), requiring careful surgical technique 2

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Multidisciplinary Coordination

Management requires collaboration between ophthalmology (preferably an experienced strabismus surgeon), endocrinology, oculoplastics, and neuro-ophthalmology. 1, 2

• Inform all providers about the diagnosis and work collaboratively on the treatment plan 1
• Coordinate thyroid function optimization with endocrinology, as achieving a euthyroid state minimizes exacerbation risk 5, 3
• Refer to neuro-ophthalmology or oculoplastics for screening and management of optic neuropathy 1
• Ensure the ophthalmologist has experience with complex strabismus and severe restrictive disease; orthoptists can assist with examination and nonsurgical management under supervision 1, 2