Assigned status Up to Date by Nagham Al-Zubidi, MD on February 09, 2019.
- ICD 242.90- 242.91
Thyroid eye disease (TED) also known as Thyroid associated ophthmopathy(TAO), Grave’s orbitopathy ,Graves’ Ophthalmopathy, or Graves’ eye disease. TED is an autoimmune is an autoimmune disease caused by antibodies directed against receptors present in the thyroid cells and extraocuar muscles and soft tissue of the orbit. The disorder characterized by enlargement of the extraocular muscles, fatty and connective tissue volume.
TED generally associated with Hyperthyroidism in about 90% of the cases, However about 10% of patients with TED have either a normal-functioning (Euthyroid) or under-functioning thyroid (Hypothyroidism e.g. Hashimoto's thyroiditis) . While restrict control of thyroid function is crucial in patients with TED, the course and severity of ocular manifestation does not always correlate with thyroid hormone levels.. Thus, treatment of thyroid dysfunction does not necessarily affect course of Grave’s ophthalmopathy.
Include genetic, environmental, and immune factors. Among the environmental factors, cigar smoking considers the most consistently linked risk factor to the development or worsening of the disease. Patients treated with I131 are at increased risk of developing TAO
TED has a higher prevalence in women than men. Both men and women demonstrate a bimodal pattern of age of diagnosis. The median age is 43 years for all patients, with a range from 8 to 88- year. Patients diagnosed over 50 -year have worse prognosis overall.
Although the underlying mechanisms of action of these processes are not completely understood however the presumed mechanism is: activation of orbital fibroblasts by Graves' disease-related autoantibodies, which lead to the release of T cell chemoattractants, initiating an interaction in ultimately result in fibroblasts expressing extracellular matrix molecules, biologic materials proliferating and differentiating into myofibroblasts or lipofibroblasts and deposition of glycosaminoglycans which bind water that lead to swelling, congestion in addition to connective tissue remodeling results in extraocular muscle enlargement and orbital fat expansion.
The patient complains of gritty sensations, photophobia, lacrimation, discomfort, and forward protrusion of the eye. In more advanced cases, patient may complain of double vision and or blurred vision.
- Lid retraction i.e. Dalrymple’s sign occurs in 37-92% patients.
- Lid lag of the upper eyelid on downward gaze i.e. Von graffe’s sign and lid oedema.
- TAO is the most common cause for both unilateral and bilateral axial proptosis ( exophthalmos). There is increased resistance to retropulsion. Hertel’s exophthalmometer is used for the measurement of proptosis.
- Bulbar conjunctiva can have deep injection i.e. goldzeiher’s sign. Exposure keratopathy ocular emergency can occur further due to lagophthalmos, which is a major cause for decrease visual acuity and blurred vision in TAO apart from compressive optic neuropathy.
- Extraocular muscles frequently involved in TAO. The most commonly affected muscle Mnemonic “I'M SLOw” Inferior rectus followed by medial, superior, levator, lateral rectus and oblique. Extraocular muscles affected results in ocular misalignment, diplopia. Inability to look up when the eye is adducted i.e. double elevator palsy.
- Compressive optic neuropathy ocular emergency, occurs in <5% of patients with typical TED resulting in slowly progressive fulminant visual loss. It occurs due to compression from the oversized recti and orbital fat causing compartment syndrome at the apex of orbit. It is characterized by decrease in vision, color vision, contrast sensitivity and relative afferent papillary defect. The characteristic visual fields commonly show central, cecocentral, paracentral, and nerve fiber layer bundle defects. Optic nerve head examination can be normal, optic disc edema, or pallor.
- Clinical course: TED typically has a progressive inflammatory phase followed by a stable post-inflammatory phase.
- The pattern of the disease follow the Rundle’s curve which describe the plot of orbital disease severity against time
- Initial phase- inflammatory phase duration may last from 6 – 18 months with orbital and periorbital signs i.e. proptosis and retraction.
- Static phase- decrease in the inflammatory phase and minimal improvement.
- Quiescent phase- gradual improvement with improved motility and retraction of the muscles
The diagnosis can be done clinically with the characteristic clinical picture, restrictive nature of the disease and associated systemic thyroid disease. Though not diagnostic, thyroid hormone levels, thyroid-stimulating immunoglobulins, anti thyroid antibodies can be suggestive of diagnosis.
Ultrasonography Both A-scan and B-scan transocular echograms can be used to visualize the orbital structures and determining recti muscles are enlargement. Advantage is its low cost, lack of ionizing radiation and relatively short examination time Computed tomography scan Can distinguish normal structures from abnormal structures of different tissue density. It demonstrates enlargement of the bellies and sparing of the tendons. It helps in assessing the relationship between the optic nerve and muscles at the apex, which helps in planning for the surgical intervention if needed.
Magnetic resonance imaging It again demonstrates fusiform rectus enlargement and orbital fat expansion. It assesses water content in the muscles, which correlates with the active inflammation.
- Orbital pseudotumour
- Caroticocavernous fistula
- Inflammatory orbitopathy e.g, granulomatosis with polyangitis
- Orbital myositis (OM)
- Orbital tumors
- IgG4 disease
Conservative Both smoking cessation and euthyroid status help preventing further exacerbation and decrease the duration of active disease. For corneal exposure, lubricants, taping and protective shields can be tried and if necessary tarsorrhapphy can be done. For diplopia, Fresnel prisms or occlusion therapy should be considered. Others are lifestyle modifications e.g. sodium restriction to reduce water retention and tissue edema. Sleeping with the head of the bed elevated to decrease orbital edema. Oral NSAIDs can be used for periocular pain. In addition Selenium has shown significant benefit in European patients with mild, non‐inflammatory orbitopathy.
Systemic steroids To decrease orbital inflammation oral prednisone in a dose of 1- 1.5-mg/ kg can be given for a suggested maximum period of 2 months. Intravenous (IV) corticosteroids pulse methyl prednisolone can be considered as an alternative.
Orbital Radiation Can be used alone or in conjunction with corticosteroids The radiation therapy works on the similar mechanism of decreasing inflammation. Typical dose of 2000 cGy for each orbit 200 cGy / day given over a period 10 days. It generally improves vertical motility. Radiation retinopathy can occur as a side effect. Orbital decompression It enlarges the existing space by partial removal of bony walls and periosteum. The most commonly done decompression involves the posteromedial wall followed by floor and lateral wall.
- Azathioprine is a chemotherapeutic agent that inhibits DNA synthesis.
- Rituximab is a monoclonal antibodies targets CD‐20 on B‐cells
- Teprotumumab is a human monoclonal antibody (against the IGF‐1‐R) (phase II clinical trial) in patients with active, moderate to severe TED.
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