Orbital Inflammatory Syndrome (OIS): Diagnosis, Treatment, and Referral Guidelines


As part of a thorough history, it’s important to ask about the use of medications associated with OIS, such as bisphosphonates taken for the treatment of osteoporosis.

A comprehensive ophthalmic evaluation is performed. Pain can be an important symptom of OIS, particularly in myositis and dacryoadenitis. It’s important to rule out infectious orbital cellulitis, which in the vast majority of cases originates from paranasal sinusitis. 

Most often an orbital CT scan with contrast will clearly image the orbit and paranasal sinuses and aid in the diagnosis. A CT scan is typically preferred as the initial imaging modality of choice as it is quickly obtained, has high spatial resolution, and shows bony anatomy in detail that is important in cases of infection or malignancy. MRI can subsequently be obtained if needed to augment the workup. 

An orbital biopsy helps to confirm the diagnosis of OIS in cases in which other etiologies are not found with laboratory testing or other less invasive testing. The histopathology may demonstrate specific signs, such as granulomatous inflammation (as in either sarcoidosis or granulomatosis with polyangiitis) or a high number of IgG4 plasma cells (as in IgG4-related disease).

To rule out infection or systemic disease, clinicians might order these additional tests:

  • A complete blood count and basic metabolic panel
  • Thyroid studies: free T4, T3, thyroid peroxidase antibody (TPO), thyroid-stimulating hormone (TSH), thyroid-stimulating immunoglobulin (TSI), and thyrotrophin-binding inhibitor immunoglobulin (TBII)
  • Tests for antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin converting enzyme, rapid plasma reagent, rheumatoid factor, and quantiferon gold (T-spot) to rule out tuberculosis. 


In very mild cases, observation may often be the first choice. Oral NSAIDs are commonly used as first-line therapy in mild cases. 

Systemic corticosteroid therapy (oral prednisone) is used in many cases of typical dacryoadenitis or myositis. A taper is typically performed over six to eight weeks, and is tailored to the patient’s improvement in signs and symptoms.

Second-line immunosuppressive therapies (cyclosporine, cyclophosphamide, tacrolimus, methotrexate, rituximab, and others) are often used for OIS linked to systemic conditions as well as for sclerosing OIS. 

Other options include orbital radiation therapy and, very rarely, surgical debulking.

Referral Guidelines

Any patient with orbital inflammation should be referred to an orbit specialist. Treatment can be complex, encompassing therapies for systemic disease, as well as corticosteroids, surgery, and radiation. The orbit specialist typically coordinates care with other specialties, such as rheumatology, to meet all of the patient’s needs. 

Suzanne Freitag headshotSuzanne Freitag, MD

Associate Professor of Ophthalmology, Harvard Medical School

Director, Ophthalmic Plastic Surgery Service, and Co-Director, Center for Thyroid Eye Disease and Orbital Surgery at Mass. Eye and Ear