Thyroid Eye Disease Characteristics and Management

Common Symptoms and Clinical Findings

• Thyroid eye disease is characterized by soft tissue congestion, eyelid retraction, exophthalmos, restrictive extraocular myopathy, and optic neuropathy, according to the American Academy of Ophthalmology 1, 2
• Soft tissue congestion with enlargement of the preseptal fat pads is a common symptom 3, 4
• Eyelid retraction, particularly of the upper eyelid, is a frequent finding 3
• Exophthalmos or proptosis is a key feature of thyroid eye disease 1, 5
• Diplopia or double vision due to restrictive extraocular muscle myopathy is a significant symptom 3, 4
• Compensatory head posture, often in a chin-up position, is used to minimize double vision 4
• Vision loss can occur due to corneal exposure or compressive optic neuropathy 1, 3, 5
• Elevated intraocular pressure is a potential complication 1, 2

Risk Factors and Disease Associations

• There is a female predominance in thyroid eye disease, with a female to male ratio of 8:1, as noted by the American Thyroid Association 1, 2
• The typical onset of thyroid eye disease is in the fourth to fifth decade of life 1, 2
• Smoking significantly increases the risk and severity of thyroid eye disease, according to the American Academy of Ophthalmology 4, 5
• Diseases causing reduced oxygen saturation, such as emphysema, and exposure to ionizing radiation are risk factors 1, 2, 4, 5
• High anti-thyroid antibody titers and serum vitamin D deficiency are associated with an increased risk of thyroid eye disease 1, 2

Treatment Approach and Management

• Restrictive myopathy affects 30-50% of thyroid eye disease patients, most commonly the inferior rectus muscle, followed by the medial rectus, as reported by the American Academy of Ophthalmology 4, 2
• Strabismus surgery can restore binocular vision in primary gaze and reading position, according to the American Association for Pediatric Ophthalmology and Strabismus 4, 2
• Disease presentation is typically bilateral but often asymmetric, as noted by the American Academy of Ophthalmology 5
• A small percentage of thyroid eye disease patients have co-existent myasthenia gravis, according to the American Academy of Neurology 2

Clasificación y Manejo de la Oftalmopatía Tiroidea

Criterios de Clasificación

• La enfermedad muy severa se caracteriza por neuropatía óptica compresiva o queratopatía por exposición severa que amenazan la visión, requiriendo descompresión orbital urgente 6, 7
• La clasificación NO SPECS incluye categorías como N (no signos o síntomas), O (solo signos), S (involucramiento de tejidos blandos), E (involucramiento de músculos extraoculares), C (involucramiento corneal), y S (pérdida de visión) 7

Consideraciones Clínicas

• Entre 30-50% de pacientes con oftalmopatía tiroidea desarrollan miopatía restrictiva que causa diplopía y postura compensatoria de la cabeza 6
• La descompresión orbital previa aumenta el riesgo de estrabismo, especialmente con la edad 6

Medical Necessity Determination for Second Course of Tepezza

Disease Severity and Treatment Eligibility

• The American Academy of Ophthalmology guidelines recognize teprotumumab reduces proptosis and Clinical Activity Score (CAS) in patients with active Thyroid Eye Disease (TED), with a CAS of 5 meeting the threshold for moderate-to-severe active disease 8, 9, 10
• The Clinical Activity Score ranges from 0-7, with scores ≥3 indicating active inflammation, and a CAS of 5, combined with documented symptoms, demonstrates active moderate-to-severe disease that satisfies medical necessity criteria 8, 9, 10

Safety and Efficacy of Retreatment

• The American Academy of Ophthalmology guidelines note teprotumumab should be considered with caution in patients with pre-existing hearing loss, and critical caveat: Assess for pre-existing hearing loss before retreatment and counsel patient about hearing risk 8, 9, 10
• Teprotumumab reduces extraocular muscle size and orbital fat volume, preventing mechanical complications, with the American Academy of Ophthalmology guidelines supporting its use in patients with active TED 8, 9, 10

Specialist Recommendation and Treatment Response

• The ophthalmologist's impression explicitly recommends a second course of teprotumumab if thyroid function tests are controlled, with the patient's prior positive response in 2021 suggesting a high likelihood of quality of life benefit with retreatment 10
• The American Academy of Ophthalmology guidelines support the use of teprotumumab in patients with active TED, with the patient's CAS of 5 and documented symptoms indicating active disease that satisfies medical necessity criteria 8, 9, 10

Retreatment with Tepezza for Thyroid Eye Disease

Patient Evaluation and Monitoring

• Measure and document current proptosis by exophthalmometry to establish baseline and track response, and screen for optic neuropathy with visual acuity, color vision, visual fields, pupillary exam, and fundus examination, as recommended by the American Academy of Ophthalmology 11
• Assess diplopia using standardized grading to quantify baseline severity, and consider orbital imaging to evaluate extraocular muscle size and orbital fat volume 11
• Document current Clinical Activity Score (CAS) to establish baseline for treatment response monitoring, with a CAS ≥3 indicating active inflammation, and CAS ≥5 with documented symptoms demonstrating active moderate-to-severe disease 11

Treatment Considerations

• The American Academy of Ophthalmology guidelines note that teprotumumab should be considered with caution in patients with pre-existing hearing loss, and patients should be counseled about hearing risk before retreatment 11
• Establish baseline audiometry and monitor throughout treatment to assess hearing changes, which may be permanent in rare cases 11
• Consider alternative treatments, such as orbital decompression, high-dose steroids, or radiation treatment, if inadequate response to retreatment occurs, and strabismus surgery may be needed for persistent diplopia 11

Treatment of Thyroid Orbitopathy

Initial Assessment and Treatment Approach

• A multidisciplinary approach combining endocrinology, oculoplastics, and neuro-ophthalmology is recommended for thyroid eye disease management, with treatment sequenced based on disease activity and severity, as recommended by the American Academy of Ophthalmology 12, 13

Surgical Rehabilitation Sequence

• Surgery should be delayed until the inflammatory stage has subsided and the angle of deviation has been stable for at least 6 months, though earlier surgery in select patients can have satisfactory outcomes, according to the American Academy of Ophthalmology 14
• The surgical sequence must follow this order:

Strabismus Surgery Considerations

• Recession of restricted muscles is the mainstay of surgical correction; resection is generally avoided in restrictive disease, as per the American Academy of Ophthalmology 14
• Vertical deviations are more challenging than horizontal deviations (66% vs 84% success after primary surgery) because the inferior rectus muscle is most commonly affected, according to the American Academy of Ophthalmology 14
• Systematic preoperative and intraoperative assessment of forced ductions and ocular torsion minimizes undesired outcomes, as recommended by the American Academy of Ophthalmology 12, 14
• Recession of inferior rectus muscle carries specific risks: lower lid retraction, consecutive hypertropia, and A-pattern exotropia in downgaze, as noted by the American Academy of Ophthalmology 12, 14
• Consider orbital decompression consultation before strabismus surgery in patients with concurrent significant proptosis, as muscle recession predictably worsens proptosis, according to the American Academy of Ophthalmology 12, 13

Technical Surgical Details

• Absorbable sutures (6-0 polyglactin) are generally preferred for muscle isolation and reattachment, as recommended by the American Academy of Ophthalmology 12, 14
• Non-absorbable sutures may reduce postoperative drift in large inferior rectus recessions, according to the American Academy of Ophthalmology 12, 14
• Adjustable suture technique remains controversial: some surgeons report better success while others avoid it due to overcorrection and muscle slippage concerns, as noted by the American Academy of Ophthalmology 12, 14
• Thyroid eye disease is the most common risk factor for pulled-in-two syndrome (spontaneous horizontal muscle transection during surgery), requiring careful surgical technique, as per the American Academy of Ophthalmology 14

Nonsurgical Diplopia Management

• Fresnel or ground-in prisms provide temporary relief while awaiting definitive treatment or for small residual deviations, as recommended by the American Academy of Ophthalmology 14
• Chemodenervation during active phase may provide temporary diplopia relief and possibly reduce final misalignment, according to the American Academy of Ophthalmology 14

Provider Requirements

• Management requires an experienced ophthalmologist comfortable with complex strabismus and severe restrictive disease, with orthoptists providing valuable assistance under supervision, as recommended by the American Academy of Ophthalmology 12, 13, 15

Common Pitfalls to Avoid

• Do not perform strabismus surgery during active inflammation as the deviation will continue to change, as noted by the American Academy of Ophthalmology 14
• Do not perform eyelid surgery before strabismus repair as muscle surgery affects lid position, according to the American Academy of Ophthalmology 14
• Do not underestimate the complexity of vertical deviations in thyroid eye disease, particularly inferior rectus involvement, as recommended by the American Academy of Ophthalmology 14
• Do not forget preoperative counseling about potential worsening of proptosis with muscle recession surgery, as per the American Academy of Ophthalmology 12, 13

Management of Mild Graves‑Related Exophthalmos

Conservative Management

• Initial approach for mild exophthalmos without diplopia, optic‑nerve compression, or severe soft‑tissue involvement is conservative care focused on ocular surface protection, smoking cessation, and close observation. 16, 17
• Artificial tears and lubricating ointments should be applied regularly to prevent exposure keratopathy caused by eyelid retraction and mild proptosis. 16
• Punctal plugs may be used to improve tear retention and further reduce the risk of corneal exposure. 16
• Patients must be counseled to stop smoking immediately; smoking markedly increases the risk and severity of thyroid‑eye disease. 16
• In individuals with documented selenium deficiency, selenium supplementation can lessen inflammatory symptoms of mild disease through antioxidant effects. 16

Observation Strategy

• Mild exophthalmos may be observed when there is no diplopia in primary gaze or reading position. 16, 17
• Observation should continue as long as the clinical picture remains stable—no new diplopia, optic‑nerve involvement, or worsening corneal exposure.

Criteria for Escalating Therapy

• Development of diplopia in primary gaze or reading position signals restrictive myopathy and warrants therapeutic escalation. 16, 17
• Evidence of compressive optic neuropathy (decreased visual acuity, color‑vision loss, relative afferent pupillary defect) mandates escalation. 16, 17
• Severe corneal exposure with ulceration despite maximal lubrication is an indication to move beyond conservative measures. 16

Advanced Therapeutic Options

• Teprotumumab effectively reduces proptosis and Clinical Activity Score in patients with active disease, but carries risks such as hearing impairment, hyperglycemia, and is contraindicated in pregnancy. 17
• Orbital decompression surgery is reserved for cases of severe proptosis or compressive optic neuropathy that do not respond to medical therapy. 16, 17

Clinical Pearls / Pitfalls

• Prompt smoking‑cessation counseling is essential; continued smoking dramatically worsens prognosis. 16
• Immunosuppressive agents (steroids, teprotumumab) should not be started for truly mild disease without evidence of progression, given the benign natural history and potential adverse effects. 17

Differentiating Ocular Myositis from Thyroid Eye Disease

Clinical Presentation Overlap

Epidemiology and Laterality

Imaging Findings

Management of Thyroid Eye Disease

Diagnostic Pitfalls

Management of Active Thyroid Eye Disease with Positive TSH‑Receptor Antibodies – Evidence‑Based Recommendations

Initial Assessment and Imaging

• Document baseline proptosis with exophthalmometry, evaluate diplopia in primary and reading gaze, and screen for compressive optic neuropathy using visual acuity, color vision, visual fields, pupillary response, and fundus examination. 21
• Obtain orbital CT or MRI to verify tendon‑sparing enlargement of extra‑ocular muscles—most frequently the inferior and medial rectus—and to quantify the degree of proptosis. 21

Conservative Management of Mild Disease (CAS < 3)

• Prescribe regular artificial tears and lubricating ointments to prevent exposure keratopathy caused by lid retraction and mild proptosis. 21
• Offer punctal plugs to enhance tear retention when lubrication alone is insufficient. 21
• Require immediate smoking cessation, as tobacco use markedly worsens disease severity and prognosis. 21
• Supplement selenium in patients with documented selenium deficiency to mitigate inflammatory symptoms through antioxidant effects. 21

Management of Sight‑Threatening Disease (Compressive Optic Neuropathy or Severe Exposure Keratopathy)

• Initiate urgent orbital decompression, high‑dose corticosteroids, or orbital radiation without delay for compressive optic neuropathy or corneal ulceration despite maximal lubrication. 21
• Do not postpone decompression surgery while attempting medical therapy when there is vision loss, an afferent pupillary defect, or abnormal color vision. 21

Surgical Sequencing for Rehabilitation

• Perform strabismus surgery as the second operative step (after any needed decompression) to address diplopia, because orbital decompression commonly worsens or creates new strabismus. 21
• Counsel patients pre‑operatively that recession of restricted muscles—especially the inferior rectus—will typically increase proptosis, so a concurrent evaluation for decompression is required when significant proptosis is present. 21