Orbital inflammation presents clinicians with the challenge of diagnosis by exclusion, as etiologies ranging from idiopathic to neoplastic have overlapping presentations.
We limit the definition of orbital inflammatory syndromes in this article to non-infectious disorders, including autoimmune, neoplastic and idiopathic. We further divide this definition into primary orbital inflammation and inflammation secondary to a separately definable orbital process.
Of the patients referred to an orbital specialist, orbital inflammation accounts for up to 60% of cases. The majority of cases are thyroid-related orbitopathy, followed by lymphoproliferative disorders and idiopathic orbital inflammation (IOI), with a small percentage of specific primary orbital inflammatory syndromes.1-3 The differential diagnosis for orbital inflammation necessitates a comprehensive work up to guide the clinician toward an effective treatment strategy and/or the need for outside specialty referral.
The purposes of this discussion are to briefly offer our clinical perspective in working up primary and secondary orbital inflammatory disorders and to detail the diagnostic considerations for IOI.
ORBITAL INFLAMMATORY DISORDERS
The shared clinical presentations for the various orbital inflammatory disorders make this a diagnostic challenge. In thyroid-related orbitopathy, the most common cause of orbital inflammation, patients typically have a characteristic presentation with retraction of the eyelids, lid lag and unilateral or, more commonly, bilateral proptosis. Furthermore, this condition can typically be identified serologically.2 Other common primary causes include granulomatosis with polyangiitis (formerly Wegener’s granulomatosis), sarcoidosis and IgG4-related disease, which can also be distinguished using clinical findings and serology (Table 1).2
|Primary Orbital Inflammation|
|TYPE||COMMON CLINICAL FINDINGS||LABS AND TESTING|
|Thyroid-related orbitopathy||Bilateral: variable onset, eyelid retraction, proptosis, eyelid lag, optic neuropathy, ocular motility restriction||Thyroid Function Tests: T3/T4, TSH. TSH-stimulating autoantibodies|
|Sarcoidosis||Unilateral or bilateral: acute or subacute onset, mass, swelling, ocular motility restriction||ACE, chest imaging, pulmonary function test|
|Granulomatosis with polyangiitis (Wegener’s)||Unilateral or bilateral: acute or subacute onset, dacryoadenitis, sinusitis||c-ANCA, pulmonary function test, CBC and BMP|
|IgG4-related disease||Unilateral or bilateral: minimal pain, periorbital or eyelid swelling, erythema, proptosis||IgG4 serology and renal function tests|
|Secondary Orbital Inflammation|
|TYPE||COMMON CLINICAL FINDINGS||LABS AND TESTING|
||Unilateral: variable to insidious onset, solitary mass, swelling, ocular motility restriction||CBC and BMP, CT or MRI imaging of orbits and brain.|
|Orbital cellulitis or trauma||Unilateral: acute onset, erythema, chemosis, sinusitis||CBC, CT imaging of orbits and sinuses, trial of antibiotics|
The second most common cause of orbital inflammation, lymphoproliferative disorder, is classified as a secondary orbital inflammation. Other secondary causes often have obvious clues for their clinical presentation, such as infection or trauma, which can rule out primary inflammation (Table 1). These are beyond this article’s scope.
IDIOPATHIC ORBITAL INFLAMMATION
If there is a negative work up of primary and secondary orbital inflammations, the diagnostic consideration should be given to IOI, a diagnosis of exclusion that accounts for about 6% of orbital disorders.2 This definition of IOI (also called non-specific orbital inflammation, orbital inflammatory syndrome and orbital pseudotumor) is clinical and consists of subtypes with individual anatomical patterns within the orbit.4 Their locations are typically, but not exclusively, unilateral and can be myositic, lacrimal, anterior, diffuse, apical or a combination.2,3 Clinical examination and CT or MRI imaging, obtained during the rule-out of other causes, aid in isolating the particular subtype(s) (Table 2, page 52).
|IOI ANATOMICAL SUBTYPE||CLINICAL FEATURES||CT AND MRI|
|Myositic (extraocular muscles)||Orbital pain (with or without movement), periorbital edema, decreased EOM, diplopia, injection and proptosis||Irregularly enlarged muscles with tendon involvement and extension into orbital fat; swelling of sclera and Tenon’s capsule|
|Lacrimal||Localized pain, temporal eyelid swelling, palpable lacrimal gland and an S-shaped deformity of lid||Enlargement of lacrimal gland and adjacent tissues in superotemporal orbit|
|Anterior (globe and adjacent orbit)||Orbital pain, uveitis, lid injection and swelling, proptosis, decreased vision, retinal detachment||Thickening of sclera and choroid with possible extension along optic nerve|
|Diffuse||Shared features of myositic and anterior subtypes, with possible involvement of neurosensory structures||Entire orbit may be obscured due to diffuse enhancing|
|Apical||Disproportionate orbital pain, decreased vision and EOM, proptosis and chemosis||Apical infiltration with possible extension along muscles and optic nerve|
In most cases of IOI, biopsy is not required for determining treatment.5 Often, the clinical and radiologic presentation for IOI overlaps with infectious orbital cellulitis, making it a diagnostic dilemma.
Since empiric treatment with corticosteroids has the potential for exacerbating an orbital infection, an equivocal patient is often first empirically treated with broad spectrum IV antibiotics.
If the patient’s condition is refractory to antibiotics and fungal etiologies have been ruled out, the patient is then treated empirically with corticosteroids in what has been termed a “corticosteroid trial.” The “corticosteroid response is defined as a dramatic improvement of signs and symptoms within 48 hours after administration of systemic prednisolone, 1 mg/kg/d.”6 The myositic subtype of IOI is distinctly characterized by this response.
However, in patients with other forms of IOI, “the diagnostic corticosteroid trial has poor specificity and low positive predictive value.”6 The power of using such a trial is further questioned by studies that have reported variable responsiveness of the different subtypes.4 Thus, the response to a corticosteroid trial should be considered a “useful diagnostic indicator that is not [in itself] diagnostic.”7
When to consider biopsy
If corticosteroids do not provide a quick response or if there are atypical findings, biopsy should be performed. Biopsy is considered a low morbidity procedure and is a “critical diagnostic option ... that ... should be tailored to individual risks.”4,6 The benefits of a biopsy procedure often far outweigh the risks, particularly in ruling out other causes of primary and secondary inflammation that correlate with increased systemic morbidity (Figure 1). In cases where orbital tissue is easily accessible for biopsy (e.g., anterior and lacrimal subtypes), a biopsy is sometimes considered before a steroid trial.2
The morbidity of biopsy increases with sampling for the myositic and apical subtypes that may present a risk of injury to the muscle or optic nerve.3,7 In addition, myositic subtypes are typically not biopsied due to their dramatic response to steroids.
For biopsies of orbital tissues, a minimally invasive approach under local anesthesia is often the preferred technique.8 Fine-needle aspiration is indicated in patients with a history of systemic lymphoma or metastasis.4
With this review, we have aimed to provide a practical approach for the clinician to navigate the diagnostic challenges of primary and secondary orbital inflammation. We gave our clinical perspective on IOI, which is becoming a less frequent diagnosis as we continue to investigate and understand the underlying pathogenesis and clinical findings of the specific subtypes.3 OM
- Weber AL, Romo LV, Sabates NR. Pseudotumor of the orbit. Clinical, pathologic, and radiologic evaluation. Radiol Clin North Am. 1999;37:151-168.
- Yuen SJA, Rubin PA. Idiopathic orbital inflammation: Distribution, clinical features, and treatment outcome. Arch Ophthalmol. 2003;121:491-499.
- Rootman J. Diseases of the Orbit: A Multidisciplinary Approach. Philadelphia, PA: Lippincott Williams & Wilkins; 2002.
- Mombaerts I, Rose GE, Garrity JA. Orbital inflammation: Biopsy first. Surv Ophthalmol. 2016;61:664-669.
- Gordon LK. Orbital inflammatory disease: a diagnostic and therapeutic challenge. Eye. 2006;20:1196-1206.
- Mombaerts I, Bilyk JR, Rose GE, et al. Consensus on diagnostic criteria of idiopathic orbital inflammation using a modified delphi approach. JAMA Ophthalmol. 2017;135:769-776.
- Swamy BN, McCluskey P, Nemet A, et al. Idiopathic orbital inflammatory syndrome: clinical features and treatment outcomes. Br J Ophthalmol. 2007;91:1667-1670.
- Goldberg RA, Rootman DB, Nassiri N, Samimi DB, Shadpour JM. Orbital tumors excision without bony marginotomy under local and general anesthesia. J Ophthalmol. 2014;2014:424852.
- Takahira M, Ozawa Y, Kawano M, et al. Clinical aspects of IgG4-related orbital inflammation in a case series of ocular adnexal lymphoproliferative disorders. Int J Rheumatol. 2012;2012:635473.
- Nonspecific orbital inflammation (idiopathic orbital inflammation, orbital inflammatory syndrome, orbital pseudotumor). EyeWiki. http://eyewiki.aao.org/Nonspecific_Orbital_Inflammation_(Idiopathic_orbital_inflammation,_Orbital_inflammatory_syndrome,_Orbital_pseudotumor ). Published October 21, 2017. Accessed March 24, 2018.
- Ding ZX, Lip G, Chong V. Idiopathic orbital pseudotumour. Clin Radiol. 2011;66:886-892.