Nonspecific Orbital Inflammation
Diagnosis of nonspecific orbital inflammation (NSOI, also known as idiopathic orbital inflammation) remains a diagnosis of exclusion, made only after all specific causes of inflammation have been eliminated. The condition is characterized by a polymorphous lymphoid infiltrate with varying degrees of fibrosis, without a known local or systemic cause.
Although controversial, the pathogenesis of NSOI appears to be immune-mediated due to its association with systemic immunologic disorders, including Crohn disease, systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus, myasthenia gravis, and ankylosing spondylitis. In addition, NSOI typically responds rapidly to treatment with corticosteroids and other immunosuppressive agents, indicating a cell-mediated component.
The symptoms and clinical findings in NSOI vary, depending on the degree and anatomical location of the inflammation. In order of frequency, NSOI tends to occur in the 5 following orbital locations or patterns:
extraocular muscles (myositis)
lacrimal gland (dacryoadenitis)
anterior orbit (eg, scleritis)
throughout the orbit (as diffuse inflammation)
Although it is usually limited to the orbit, NSOI may also extend into the adjacent sinuses or intracranial space. Deep, boring pain occurs in many cases; pain associated with ocular movement suggests myositis. Symptoms of vision impairment may occur with involvement of the optic nerve or posterior sclera. Signs include extraocular muscle restriction, proptosis, conjunctival inflammation, chemosis, and erythema and edema of the eyelid (Fig 4-17).
Imaging studies such as CT, MRI, and ultrasonography reveal enlargement of affected tissues and may show other characteristic findings. Up to 50% of cases show thickening of the extraocular muscle tendon insertions (Fig 4-18), in contrast with TED, which typically spares the muscle insertions. Involvement of the retrobulbar fat pad may produce fat stranding, and tendonitis may produce contrast enhancement of the sclera. B-scan ultrasonography often shows an acoustically hollow area that corresponds to an edematous Tenon capsule (T-sign).
Figure 4-17Nonspecific orbital inflammation (NSOI). A, Photograph of a patient presenting with acute onset of inflammation of the left eyelid, proptosis, pain, and left lateral rectus paresis. B, Axial CT scan shows left-eye proptosis and hazy inflammatory swelling of lateral rectus and lacrimal gland, suggestive of a diagnosis of NSOI. C, Coronal CT scan shows inflammatory process adjacent to the lateral rectus. D, Photograph shows marked improvement of inflammatory changes in the patient after a 48-hour course of oral prednisone.
(Parts A and D courtesy of Keith D. Carter, MD; parts B and C courtesy of Robert C. Kersten, MD.)
Figure 4-18 Axial CT scan shows myositis of the left medial rectus muscle with involvement of the tendon (arrow).
(Courtesy of Bobby S. Korn, MD, PhD.)
A prompt initial response to high-dose (1 mg/kg oral prednisone or equivalent) systemic corticosteroids supports the diagnosis; this response is observed in most myositic cases and in about 80% of nonmyositic cases. However, inflammation associated with other orbital processes (eg, metastases, lymphoma, ruptured dermoid cysts, infections) may also improve with systemic corticosteroid administration. In 1 study, 50% of biopsied inflammatory lacrimal gland lesions were associated with systemic disease, including GPA, sclerosing inflammation, Sjögren syndrome, sarcoidal reactions, and autoimmune disease.
Given the low morbidity associated with biopsy, the possibility of other orbital processes responding to treatment with corticosteroids, and the high incidence of systemic disease involving the lacrimal gland, many experts recommend diagnostic biopsy of all nonmyositic lesions not attached to the optic nerve. Surgical debulking of idiopathic dacryoadenitis during the biopsy procedure may carry a therapeutic as well as a diagnostic benefit.
In cases of myositis, lesions attached to the optic nerve and lesions involving the orbital apex may produce characteristic clinical and radiographic findings to strongly support the presumed diagnosis, and the risk associated with biopsy may outweigh the risk of a missed diagnosis.
Not all patients with NSOI present with the classic signs and symptoms; some patients present with atypical pain, limited inflammatory signs, or a fibrotic variant called sclerosing NSOI. Simultaneous bilateral orbital inflammation in adults suggests the possibility of systemic vasculitis. Any diagnostic uncertainty mandates a thorough systemic evaluation. In children with NSOI, approximately one-third of cases present bilaterally and approximately one-half present with systemic signs, such as headache, fever, vomiting, abdominal pain, and lethargy. Uveitis, elevated ESR levels, and eosinophilia are also more common in children with NSOI. Pediatric NSOI is not generally associated with systemic disorders.
On histologic examination, NSOI is characterized by a pleomorphic cellular infiltrate consisting of lymphocytes, plasma cells, and eosinophils with variable degrees of reactive fibrosis. The sclerosing subtype of NSOI demonstrates a predominance of fibrosis with sparse cellular inflammation. Hypercellular lymphoid proliferations represent clinical and histologic entities that are different from NSOI.
Mombaerts I, Bilyk JR, Rose GE, et al; Expert Panel of the Orbital Society. Consensus on diagnostic criteria of idiopathic orbital inflammation using a modified Delphi approach. JAMA Ophthalmol. 2017;135(7):769–776.
As previously mentioned, initial therapy for NSOI consists of systemic corticosteroids, with a typical initial daily adult dosage of 1 mg/kg prednisone. Acute cases generally respond rapidly, with abrupt resolution of pain. Steroid taper begins after maximal clinical response; it should proceed more slowly below about 40 mg/day and even slower below 20 mg/day, based on the clinical response. Rapid reduction of systemic steroids may allow for recurrence. Some investigators believe that pulse-dosed IV dexamethasone followed by oral prednisone may produce clinical improvement when oral prednisone alone fails to control the inflammation. Sclerosing NSOI responds poorly to steroids and to low-dose fractionated radiotherapy; it typically requires more aggressive immunosuppression with agents such as cyclosporine, methotrexate, or cyclophosphamide.
Mombaerts I, Rose GE, Garrity JA. Orbital inflammation: biopsy first. Surv Ophthalmol. 2016;61(5):664–669.
Rootman J. Orbital Disease: Present Status and Future Challenges. Boca Raton, FL: CRC Press; 2005:1–13.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.