Early: Nonspecific complaints including foreign-body sensation, redness, tearing, photophobia, and morning puffiness of the eyelids. Early symptoms are often nonspecific and may mimic allergy, blepharoconjunctivitis, chronic conjunctivitis, etc. Upper eyelid retraction tends to develop early.

Late: Additional eyelid and orbital symptoms including lateral flare, prominent eyes, persistent eyelid swelling, chemosis, double vision, “pressure” behind the eyes, and decreased vision.

Critical. Retraction of the upper eyelids with lateral flare (highly specific) and eyelid lag on downward gaze (von Graefe sign), lagophthalmos. Lower lid retraction is a very nonspecific sign and often present as a normal finding. Unilateral or bilateral axial proptosis with variable resistance to retropulsion. When extraocular muscles are involved, elevation and abduction are commonly restricted and there is resistance on forced duction testing. Although often bilateral, unilateral or asymmetric TED is also frequently seen. Thickening of the extraocular muscles (inferior, medial, superior, and lateral, in order of frequency) without involvement of the associated tendons may be noted on orbital imaging. Isolated enlargement of lateral rectus muscles is highly atypical of TED and requires further work-up and possibly biopsy. Isolated enlargement of the superior rectus can occur in TED, but should be followed carefully for alternative causes.

Other. Reduced blink rate, significantly elevated IOP (especially in upgaze), injection of the blood vessels over the insertion sites of horizontal rectus muscles, superior limbic keratoconjunctivitis, superficial punctate keratopathy, or infiltrate or ulceration from exposure keratopathy, afferent pupillary defect, dyschromatopsia, optic nerve swelling/pallor.

NOTE: Thickening of the extraocular muscles at the orbital apex can result in optic nerve compression and manifest in afferent pupillary defect, reduced color vision, visual field, and visual acuity loss. Compressive optic neuropathy occurs in a minority of patients (5%) with TED but must be ruled out in every patient at every visit. The optic neuropathy of TED almost invariably occurs in the setting of restrictive strabismus and increased resistance to retropulsion. Of note, in cases of compressive optic neuropathy from TED, axial proptosis is usually either absent or mild.

Hyperthyroidism is common (at least 80% of patients with TED). Symptoms include a rapid pulse, hot and dry skin, diffusely enlarged thyroid gland (goiter), weight loss, muscle wasting with proximal muscle weakness, hand tremor, pretibial dermopathy or myxedema, cardiac arrhythmias, change in bowel habits. Some patients are hypothyroid (5% to 10%) or euthyroid (5% to 10%). Euthyroid patients should undergo thyroid function testing every 6 to 12 months; a significant proportion will develop thyroid abnormalities within 2 years. TED does not necessarily follow the associated thyroid dysfunction and may occur months to years before or after the thyroid dysfunction. The clinical progression of TED also has only minor correlation with control of the thyroid dysfunction.

Concomitant myasthenia gravis with fluctuating double vision and ptosis may occur in a minority of patients. Always ask about bulbar symptoms (e.g., dysphagia, dysphonia, difficulty with breathing, weakness in proximal muscles, etc.) and fatigue in patients with suspected myasthenia gravis.

May be acute, recurrent, or chronic. An explosive, painful onset is the hallmark of IOIS, but is present
in only 65% of patients. Pain, prominent red eye, “boggy” pink eyelid edema, double vision, or decreased vision. Children may have concomitant constitutional symptoms (fever, headache, vomiting, abdominal pain, lethargy) and bilateral presentation, neither of which is typical in adults.

Critical. Proptosis and/or restriction of ocular motility, usually unilateral, typically of explosive onset. On imaging studies, soft tissue anatomy is involved in varying degrees. The extraocular muscles are thickened in cases of myositis; involvement of the tendon may occur, but is by no means essential or pathognomonic. The sclera (in posterior scleritis), Tenon capsule (in tenonitis), orbital fat, or lacrimal gland (in dacryoadenitis) may be involved. The paranasal sinuses are usually clear.

Other. Boggy, pink eyelid erythema and edema, conjunctival injection and chemosis, lacrimal gland enlargement or a palpable orbital mass, decreased vision, uveitis, increased IOP, hyperopic shift (typically in posterior scleritis), optic nerve swelling or atrophy (uncommon).

NOTE: Bilateral IOIS in adults can occur, but should prompt a careful evaluation to rule out a systemic cause (e.g., sarcoidosis, GPA [Wegener granulomatosis], metastases, lymphoma). Children may have bilateral disease in one-third of the cases and may have associated systemic disorders.

SEE 7.1, ORBITAL DISEASE, for general orbital work-up.

Reevaluate in 1 to 2 days. Patients who respond dramatically to corticosteroids are maintained at the initial dose for 3 to 5 days, followed by a slow taper to 40 mg/day over 2 weeks, and an even slower taper below 20 mg/day, usually over several weeks. If the patient does not respond dramatically to appropriate corticosteroid doses, biopsy should be strongly considered. Recurrences of IOIS are not uncommon, especially at lower corticosteroid doses.

NOTE: IgG4-related disease is a recently described fibroinflammatory condition typified by lymphoplasmacytic infiltration of soft tissues by IgG4+ plasma cells, often with systemic involvement. Elevated serum levels of IgG4 may be present. Clinical management follows the typical algorithm of other orbital inflammations: systemic corticosteroids followed by steroid-sparing agents in chronic or recalcitrant cases. IgG4-related orbitopathy may involve any of the orbital soft tissues, but does not usually present in the explosive fashion of classic IOIS. There is evidence from Japan that IgG4-related disease may increase the risk of eventual lymphoma.

Red eye, pain, blurred vision, double vision, eyelid and/or periorbital swelling, nasal congestion/discharge, sinus headache/pressure/congestion, tooth pain, infra- and/or supraorbital pain, or hypesthesia.

Critical. Eyelid edema, erythema, warmth, and tenderness. Conjunctival chemosis and injection, proptosis, and restricted extraocular motility with pain on attempted eye movement are usually present. Signs of optic neuropathy (e.g., afferent pupillary defect, dyschromatopsia) may be present in severe cases.

Other. Decreased vision, retinal venous congestion, optic disc edema, purulent discharge,
decreased periorbital sensation, fever. CT scan usually shows an adjacent sinusitis (typically at least an ethmoid sinusitis), possibly a subperiosteal orbital collection.

SEE 7.1, ORBITAL DISEASE.

SEE 7.1, ORBITAL DISEASE, for a nonspecific orbital work-up.