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Key Features

  • A syndrome of clinical and orbital imaging abnormalities caused by deposition of mucopolysaccharides and infiltration with chronic inflammatory cells of the orbital tissues, particularly the extraocular muscles

  • The early inflammatory stage typically lasts 18–36 months, during which there is active lymphocytic infiltration into retrobulbar tissues

  • The active inflammatory stage then tends to evolve to a chronic, fibrotic, "burned out" stage in which treatment of the exophthalmos is medically resistant to glucocorticoid treatment

  • Radioiodine therapy, possibly indirectly due to induction of hypothyroidism, and cigarette smoking increase its severity

  • Ethanol injection of thyroid nodules has been reported to be followed by severe disease

Clinical Findings

  • Primary clinical features

    • Upper eyelid retraction (Dalrymple sign)

    • Lid lag with downward gaze (von Graefe sign)

    • Staring appearance (Kocher sign)

  • The following can also be seen:

    • Proptosis

    • Lid retraction and lid lag

    • Conjunctival chemosis and episcleral inflammation

    • Extraocular muscle dysfunction

  • Corneal drying may occur with inadequate lid closure

  • Eye changes may sometimes be asymmetric or unilateral

  • Resulting symptoms

    • Cosmetic abnormalities

    • Surface irritation, which usually responds to artificial tears

  • Patients with severe exophthalmos can experience

    • Diplopia from extraocular muscle entrapment

    • Optic nerve compression, causing

      • Progressive loss of color vision

      • Visual acuity

      • Visual fields (inferior especially)

  • Symptoms of active retrobulbar inflammation include

    • Retrobulbar aching

    • Orbital inflammation and edema worse after recumbent sleep

    • Edematous or erythematous eyelids

    • Conjunctival redness or chemosis (edema)

    • Recent progression in exophthalmos

    • Recent diplopia or strabismus

    • Recent loss of visual acuity

  • Differential diagnosis

    • Congenital proptosis

    • Asymmetry in orbital protrusion

    • Dural carotid-cavernous sinus fistula

    • Ocular myasthenia


  • Exophthalmometry should be performed on all patients with Graves disease to

    • Document the degree of exophthalmos

    • Detect progression of orbitopathy

  • The protrusion of the eye beyond the orbital rim is measured with a prism instrument (Hertel exophthalmometer)

  • Maximum normal eye protrusion varies between kindreds and races

    • About 24 mm for Blacks

    • About 20 mm for Whites

    • About 18 mm for Asians


  • General eye protective measures include wearing glasses to protect the protruding eye and taping the lids shut during sleep if corneal drying is a problem

  • Methylcellulose drops and gels ("artificial tears") may also help

  • Mild disease: Oral selenium (100 mcg twice daily) may slow progression

  • The Mourits clinical activity score

    • Helps grade the severity of thyroid eye disease

    • Therapy in addition to selenium is warranted for active thyroid eye disease with a clinical activity point score ≥ 3

    • One point is given for each of the following manifestations:

      • Pain or pressure in the periorbital area

      • Pain with eye movement

      • Swelling of the eyelids

      • Erythema of the eyelids

      • Conjunctival injection

      • Chemosis

      • Caruncle inflammation

      • Increase in proptosis of ≥ 2 mm within 3 months

      • Decrease in eye movement within 3 months

      • Decrease in visual activity within 3 months

  • Intravenous pulse methylprednisolone


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