Inflammatory orbital disease is benign space-occupying inflammation involving orbital tissues.
Inflammatory orbital disease is inflammation that can affect any or all structures within the orbit. The inflammatory response can be nonspecific, granulomatous, vasculitic, or due to reactive lymphoid hyperplasia. The inflammation can be part of an underlying medical disorder (eg, IgG4-related disease, 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.
In this image, axial and coronal CT scans show findings in thyroid eye disease. Bottom: The axial CT scan shows tendon-sparing enlargement of the medial rectus muscle, bilaterally. Top: The coronal CT scan shows enlargement of the inferior, superior, and medial rectus muscles more on the right than left.
Images courtesy of Richard C. Allen, MD, PhD.
Symptoms and Signs of Inflammatory Orbital Disease
Symptoms and signs of inflammatory orbital disease typically include pain along with swelling and erythema of the eyelids. Proptosis (exophthalmos), 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 that occur in almost all orbital inflammation (ie, proptosis, diplopia, periorbital edema, retrobulbar pain). Severity of TED ranges from mild (no diplopia, mild lid retraction, mild proptosis) to moderate-to-severe (one of the following: diplopia, lid retraction > 2 mm, proptosis > 3 mm, moderate to severe soft tissue involvement) (2). Vision-threatening complications are rare but can be caused by compressive optic neuropathy or severe exposure keratopathy (1).
Symptoms and signs references
1. Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc. 1994;92:477-588.
2. Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velázquez-Villoria Á, Galofré JC. Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. J Ophthalmol. 2015;2015:249125. doi:10.1155/2015/249125
Diagnosis of Inflammatory Orbital Disease
CT or MRI
Similar symptoms and physical findings occur with inflammatory orbital disease and orbital infection, but there is no history of trauma or adjacent focus of infection (eg, sinusitis) with noninfectious orbital inflammation. Neuroimaging with CT or MRI is required. The presence of adjacent sinus involvement seen on imaging in orbital infection can distinguish infection from noninfectious inflammation. In thyroid eye disease, tendon-sparing enlargement of the inferior rectus and medial rectus muscles is common. For chronic or recurrent disease, biopsy may be useful to find evidence of an underlying medical condition.
Treatment of Inflammatory Orbital Disease
Glucocorticoids, radiation therapy, and/or immunomodulating medications
Some surgery
Treatment of inflammatory orbital disease depends on the type of inflammatory response and may include oral glucocorticoids, radiation therapy, and one of several immunomodulating medications. In difficult cases of inflammatory orbital disease, particularly those with granulomatous inflammation and vasculitis, some initial success has occurred with monoclonal antibodies against tumor necrosis factor (TNF)-alpha or with lymphocyte depletion using rituximab (Treatment of inflammatory orbital disease depends on the type of inflammatory response and may include oral glucocorticoids, radiation therapy, and one of several immunomodulating medications. In difficult cases of inflammatory orbital disease, particularly those with granulomatous inflammation and vasculitis, some initial success has occurred with monoclonal antibodies against tumor necrosis factor (TNF)-alpha or with lymphocyte depletion using rituximab (1, 2).
Treatment of ophthalmopathy in patients with Graves disease may require selenium, glucocorticoids, orbital radiation, and sometimes surgery (Treatment of ophthalmopathy in patients with Graves disease may require selenium, glucocorticoids, orbital radiation, and sometimes surgery (3, 4). Teprotumumab, an ). Teprotumumab, aninsulin-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 of eye disease, as determined by clinical signs and symptoms(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 al. Treatment of orbital inflammation with rituximab in Wegener's granulomatosis. Clin Exp Rheumatol. 2012;30(1 Suppl 70):S7-10.
2. Garrity JA, Coleman AW, Matteson EL, et al. Treatment of recalcitrant idiopathic orbital inflammation (chronic orbital myositis) with infliximab. Am J Ophthalmol. 2004;138(6):925-930. 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. 2022;51(2):287-304. 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. 2021;185(4):G43-G67. doi: 10.1530/EJE-21-0479
5. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748-1761. 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. 1998;338(2):73-78. 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. 2015;133(3):290-296. doi: 10.1001/jamaophthalmol.2014.5103
Key Points
Consider inflammatory orbital disease if patients have 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 glucocorticoids, radiation therapy, immunomodulating medications, or other measures.
