Inflammatory orbital disease is benign space-occupying inflammation involving orbital tissues.
Inflammatory orbital disease, also called orbital pseudotumor, is inflammation that can affect any or all structures within the orbit. The inflammatory response can be nonspecific, granulomatous, or vasculitic or due to reactive lymphoid hyperplasia. The inflammation can be part of an underlying medical disorder (eg, IgG4-related disease or granulomatosis with polyangiitis) or can exist in isolation. Patients of all ages can be affected. The process can be acute or chronic and can recur.
The most common etiology of noninfectious inflammatory orbital disease is thyroid eye disease (TED), also known as Graves ophthalmopathy. The pathogenesis of TED is poorly understood but may result from immunoglobulins directed against the thyroid-stimulating hormone (TSH) receptors on orbital fibroblasts and fat, resulting in release of pro-inflammatory cytokines, inflammation, and accumulation of glycosaminoglycans.
Inflammation of orbital tissues can be caused by infections.
Other causes of noninfectious, noninflammatory orbital disease include tumor, vascular malformations, and trauma.
Images courtesy of Richard C. Allen, MD, PhD.
Symptoms and Signs of Inflammatory Orbital Disease
Symptoms and signs of inflammatory orbital pseudotumor typically include a sudden onset of pain along with swelling and erythema of the eyelids. Proptosis, diplopia, and vision loss are also possible. In cases of reactive lymphoid hyperplasia or IgG4-related disease, there are typically few symptoms other than proptosis or swelling.
Ophthalmopathy in TED may occur before the onset of hyperthyroidism or as late as 20 years afterward, and frequently worsens or abates independently of the clinical course of hyperthyroidism. Of patients with TED, up to 5% may have hypothyroidism or show typical ophthalmopathy in the presence of normal thyroid function ("euthyroid Graves disease") (1). Symptoms and signs of TED include those that are specific to the condition (ie, eyelid retraction) as well as the nonspecific symptoms seen in almost all orbital inflammation (ie, proptosis [exophthalmos], diplopia, periorbital edema, retrobulbar pain). Vision-threatening complications are rare but can be caused by compressive optic neuropathy or severe exposure keratopathy (1).
Symptoms and signs reference
1. Bartley GB: The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc 92:477-588, 1994. PMID: 7886878
Diagnosis of Inflammatory Orbital Disease
CT or MRI
Similar symptoms and physical findings occur with inflammatory orbital pseudotumor and orbital infection, but there is no history of trauma or adjacent focus of infection (eg, sinusitis) with inflammatory orbital pseudotumor. Neuroimaging with CT or MRI is required. A useful imaging feature in distinguishing an infection from noninfectious inflammation is the presence of adjacent sinus involvement in orbital infection. For chronic or recurrent disease, biopsy may be used to find evidence of an underlying medical condition. In thyroid eye disease, tendon-sparing enlargement of the inferior rectus and medial rectus muscles is common.
Treatment of Inflammatory Orbital Disease
Corticosteroids, radiation therapy, and/or immunomodulating medications
Some surgery
1, 2), if the inflammation is primarily vasculitis.
3, 4insulin-like growth factor 1 (IGF-1) receptor inhibitor, is effective therapy for moderate-to-severe ophthalmopathy (5). Treatment of concomitant hyperthyroidism includes thionamides, radioiodine, or surgery. However, radioiodine therapy may accelerate progression of ophthalmopathy (6) and is therefore contraindicated in the active phase, which is typically determined by clinical signs and symptoms as indicated by the clinical activity score (6). Surgical decompression for severe thyroid eye disease may be needed. Surgical thyroidectomy may help resolve or prevent progression of ophthalmopathy (7).
Treatment references
1. Baslund B, Wiencke AK, Rasmussen N, et alClin Exp Rheumatol 30(1 Suppl 70):S7-10, 2012. PMID: 22272561
2. Garrity JA, Coleman AW, Matteson EL, et alAm J Ophthalmol 138(6):925-930, 2004. doi: 10.1016/j.ajo.2004.06.077
3. Hoang TD, Stocker DJ, Chou EL, et al: 2022 Update on clinical management of Graves disease and thyroid eye disease. Endocrinol Metab Clin North Am 51(2):287-304, 2022. doi: 10.1016/j.ecl.2021.12.004
4. Bartalena L, Kahaly GJ, Baldeschi L, et al; EUGOGO†: The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol 185(4):G43-G67, 2021. doi: 10.1530/EJE-21-0479
5. Smith TJ, Kahaly GJ, Ezra DG, et alN Engl J Med 376:1748-1761, 2017. doi: 10.1056/NEJMoa1614949
6. Bartalena L, Marcocci C, Bogazzi F, et al: Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. N Engl J Med 338(2):73-78, 1998. doi: 10.1056/NEJM199801083380201
7. Stein JD, Childers D, Gupta S, et al: Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease. JAMA Ophthalmol 133(3):290-296, 2015. doi: 10.1001/jamaophthalmol.2014.5103
Key Points
Consider inflammatory orbital disease if patients have sudden onset of pain and eyelid swelling and erythema.
Consider thyroid eye disease if inflammatory orbital disease has no apparent cause.
Obtain MRI or CT.
Treatment may include corticosteroids, radiation therapy, immunomodulating medications, or other measures.
