Idiopathic orbital inflammation (IOI) was first described in

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1 Original Investigation Pediatric Idiopathic Orbital Inflammation: Clinical Features of 30 Cases Jordan Spindle, M.D.*, Sunny X. Tang, M.D.*, Brett Davies, M.D., Edward J. Wladis, M.D., Elena Piozzi, M.D, Marco Pellegrini, M.D., Sara E. Lally, M.D., Carol Shields, M.D., and Roman Shinder, M.D.* *Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, New York; Department of Ophthalmology, The University of Colorado, Denver, Colorado; Lions Eye Institute, Albany Medical College, Albany, New York; A.O. Ospedale Niguarda Ca Granda, Milan, Italy; Eye Clinic, Department of Biomedical and Clinical Science, Luigi Sacco Hospital, University of Milan, Milan, Italy; and Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, U.S.A. Purpose: Pediatric idiopathic orbital inflammation (IOI) is a rare entity with little known about the clinical presentation and natural history. The authors report the demographics, clinical presentations, radiographic and histopathologic characteristics, and treatment outcome of 30 children with IOI. Methods: Retrospective chart review of 30 patients 18 years and younger diagnosed with IOI and statistical analysis using analysis of variance and Fisher s exact test. This study was reviewed and approved by the Institutional Review Board of SUNY Downstate Medical Center. Results: There were 9 males (30%) and 21 females (70%) with pediatric IOI who presented at a median age of 11 years (range 2 18 years). Primary IOI was found in 19 patients (63%) and recurrent IOI in 11 patients (37%). Overall, 26 patients (87%) had unilateral IOI while 4 patients (13%) had bilateral disease at presentation. There were 12 patients (40%) with systemic constitutional signs. The most common ophthalmic findings included periorbital edema (n = 20, 67%) and blepharoptosis (n = 17, 57%). All patients had orbital radiography with common findings of dacryoadenitis (n = 12, 40%), orbital mass (n = 12, 40%), or myositis (n=10, 33%). The presence of a radiographic orbital mass was significantly related to the clinical presence of blepharoptosis (p = 0.03). The most common treatment was oral glucocorticoids in 24 patients (80%). Over mean follow up of 19 months (range 6 64 months), females were more likely to display recurrent disease (p = 0.01). Conclusions: Idiopathic orbital inflammation is an uncommon but important cause of acute orbital syndrome in children, manifesting as a bilateral condition in 13% and with constitutional symptoms in 40%. Posttreatment recurrence is found in 37% of cases. (Ophthal Plast Reconstr Surg 2015;XX:00 00) Accepted for publication March 31, Supported by the Research to Prevent Blindness, New York, NY, who had no role in the design or conduct of this research. Oral presentation at the American Society of Ophthalmic Plastic and Reconstructive Surgery, November 2012 in Chicago, IL. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Roman Shinder, M.D., Department of Ophthalmology, SUNY Downstate Medical Center, 541 Clarkson Ave, E bldg, 8th Fl, Suite C, Brooklyn, NY shinder. roman@gmail.com DOI: /IOP Idiopathic orbital inflammation (IOI) was first described in 1905 by Birch-Hirchfield who termed the condition orbital pseudotumor. 1 This term was used to describe orbital disease with an idiopathic cause, spontaneous resolution, and nongranulomatous changes on histopathology. 1 Idiopathic orbital inflammation is currently understood to be a benign, noninfectious, space-occupying lesion typically presenting in the third to sixth decade of life. It accounts for 6% to 16% of all orbital lesions and is a common entity requiring orbital biopsy. 2 5 Idiopathic orbital inflammation is the third most common cause of unilateral proptosis in adults after thyroid eye disease and lymphoproliferative disease. 6,7 It typically presents with acute orbital signs and symptoms, such as pain, proptosis, ocular injection, limited ductions with diplopia, periorbital edema, chemosis, and less commonly vision loss. 2,8,9 Idiopathic orbital inflammation has historically shown no sex or racial predilection. However, recent studies have shown a middle aged female predominance. 8 While IOI is well described among adults, it has a very low incidence in the pediatric population with approximately 70 reported prior cases, 1 and therefore little is known about the clinical presentation and spectrum of disease. It is reported to differ from IOI in adults in that affected children more often have bilateral disease, as well as constitutional signs and symptoms, such as headache, fever, malaise, emesis, anorexia, lethargy, abdominal pain, and weight loss. 2,6,10 The most frequent ophthalmic clinical findings are palpable mass, decreased ocular motility, eyelid swelling, pain, proptosis, and increased intraocular pressure. 2 Reportedly, pediatric cases are more commonly associated with iritis, eosinophilia, and optic disk edema. 10,11 The authors herein review pediatric IOI through the collaborative experience in 30 consecutive patients. METHODS The authors report the demographics, clinical presentation, radiographic and histopathologic characteristics, and treatment outcome of patients 18 years or younger diagnosed with IOI. Records of 30 patients were reviewed from January 2005 to July 2013 from 6 institutions in the United States and Italy. Diagnosis of IOI was made based on the following clinical criteria: acute, benign, noninfectious, inflammatory disorder of the orbit without local or systemic cause. Data were collected regarding patient age, race, sex, primary versus recurrent disease, past medical history, laterality. The data regarding eye findings included visual acuity, intraocular pressure, pupil size and reactivity, extraocular muscle movements, external examination, slit lamp examination, and fundus examination. Ophthal Plast Reconstr Surg, Vol. XX, No. XX,

2 J. Spindle et al. Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015 All patients received a rheumatologic evaluation and an extensive serologic workup that included a complete blood count, comprehensive metabolic panel, angiotensin converting enzyme, lysozyme, antinuclear antibody, rheumatoid factor, thyroid function testing and thyroid-stimulating hormone receptor antibodies, antineutrophil cytoplasmic antibody, Sjogren s syndrome antibodies, and rapid plasma reagin. Immunoglobulin G-4 was checked in all patients who presented subsequent to Orbital radiography was obtained on all patients, and biopsy was offered in each case to parents except those children who presented with a primary isolated myositis or optic perineuritis. This study was reviewed and approved by the Institutional Review Board of SUNY Downstate Medical Center. The research adhered to the tenets of the Declaration of Helsinki, and the Health Insurance Portability and Accountability Act. Statistical analyses were conducted using Stata v Comparisons among categorical variables (sex, race, clinical variables) were analyzed using the Fisher s exact test. Age was compared across other categories using analysis of variance. RESULTS Demographic and Clinical Characteristics Patient demographics and constitutional clinical findings are summarized in Table 1. There were no significant age by sex, age by race, or sex by race interactions. There was no effect of age (p = 0.81) or sex (p = 0.29) on bilateral versus unilateral disease. There was a significant interaction between race and laterality as all patients with bilateral disease were African American (p < 0.02). Constitutional symptoms were present in 12 patients (40%) and there was no relationship of age (p = 0.10), sex (p = 0.70), or race (p = 0.43) with constitutional symptoms. There were 19 patients (63%) with primary IOI, and 11 patients (37%) with recurrent IOI, with median age of initial diagnosis at 11.1 years (range 5 17 years). Age and race did not significantly differ between primary (mean age 10.1 years) and recurrent (mean age 12.9 years) disease (p = 0.08). Recurrence manifested on average 1.7 years (range years) after initial presentation. Females (11 of 21, 52%) were significantly more likely to develop recurrent disease than males (0 of 9, 0%; p = 0.01). Recurrence was more likely to be associated with bilateral disease (100% recurrent) compared with unilateral disease (27%; p = 0.01). Three of 4 patients with bilateral disease presented with bilateral symptoms on first episode, 1 patient presented with right medial rectus myositis followed 1 year later with left lateral rectus myositis. TABLE 1. Demographics and constitutional signs Features n (%) Mean age (years) (n = 30 patients; 11 (12, 2 18) median, range) Sex Female 21 (70) Male 9 (30) Ethnicity Caucasian 14 (47) African American 11 (37) Hispanic 5 (17) Laterality Unilateral 26 (87) Bilateral 4 (13) Constitutional signs 12 (40) Headache 6 (20) Fever 3 (10) Malaise 2 (7) Nausea/Emesis 1 (3) Ophthalmic findings are listed in Table 2 and included periorbital edema (67%), blepharoptosis (57%), pain (40%), and decreased extraocular movements (37%) most commonly. Pain was more common in older children (mean age 13 years) compared with those without pain (mean age 10 years; p = 0.05). The correct diagnosis of IOI by first health care provider occurred in 10 (33%) of the patients, with 20 (67%) misdiagnoses including orbital or preseptal cellulitis (n = 10, 50%), conjunctivitis (n = 4, 20%), malignancy (n = 3, 15%), chalazion (n = 1, 5%), allergic reaction (n = 1, 5%), and migraine headache (n = 1, 5%). Initial health care providers ranged from pediatricians, emergency room physicians, optometrists, nurse practitioners, and general ophthalmologists. Imaging and Biopsy Radiographic findings are shown in Table 3. All patients had orbital radiography with 10 patients (33%) having computed tomography, 14 patients (47%) having magnetic resonance imaging, and 6 patients (20%) having both modalities. Age, sex, and race did not differ when considering the radiographic findings. The presence of an orbital mass was significantly related to the clinical presence of blepharoptosis (p = 0.03). There was no relation between the presence of an orbital mass and either the presence of proptosis or limitation of extraocular movements. Biopsy was performed in 16 patients (53%), which were all consistent with the classic histopathologic features of IOI including mixed inflammatory infiltrates of lymphocytes, plasma cells, eosinophils, and the presence of fibrosis without neoplastic cells, granulomatous disease, or vasculitis. Immunohistochemistry ruled out orbital IgG4 in each case. Ten children (33%), who presented with either primary myositis of 1 rectus muscle or optic perineuritis were not biopsied. In addition, the parents of 4 (13%) children deferred biopsy when suggested. Treatment and Response Treatment algorithms were based on patient age, severity and extent of clinical and radiographic findings, initial versus recurrent disease, past treatments and responses, recurrence during tapering or completion of primary therapy, rheumatologist and pediatrician suggestions, and parent preferences. Treatments included oral corticosteroids (n = 24, 80%), steroid sparing immunosuppressive therapy (n = 2, 7%), oral corticosteroids followed by chemoradiation (n = 1, 3%), intravenous corticosteroids followed by oral corticosteroids, rituximab and intravenous immunoglobulin (IVIG, n = 1, 3%), and observation (n = 3, 10%). When oral steroids were given the tapering dose began at 1 mg/kg/day. Mean follow-up time was 14.1 months (range 3 54 months) with clinical improvement noted in all patients when compared with presentation. At last follow up, 25 patients (83%) had complete resolution, 2 patients TABLE 2. Ophthalmic signs on presentation n (%) Total 30 (100) Periorbital edema 20 (67) Blepharoptosis 17 (57) Periorbital pain 12 (40) Decreased extraocular movements 11 (37) Proptosis 7 (23) Conjunctival injection 6 (20) Abaxial globe dystopia 4 (13) Chemosis 3 (10) Periorbital erythema 3 (10) Vision loss 3 (10) Lacrimal gland enlargement 2 (7) Optic disk edema 2 (7) Palpable mass 1 (3) Iritis 1 (3) Choroidal folds 1 (3) The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.

3 Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015 Pediatric IOI TABLE 3. Radiographic findings (7%) had residual mechanical blepharoptosis from periorbital edema, 2 patients (7%) had residual proptosis, and 1 patient (3%) was being treated for uveitis. Four patients in this study were initially treated with steroids (oral prednisone or prednisolone 1 mg/kg), and later switched to a steroid sparing therapy. One patient, a 9-year-old African American female suffered multiple bilateral recurrences as well as weight gain and glucose intolerance on oral corticosteroid therapy. She was given IV corticosteroids, IVIG, and rituximab as an inpatient and then discharged on methotrexate with full resolution on last follow up of 24 months. An 18-year-old Caucasian male had a recurrence of orbital signs while on an oral corticosteroid taper and was switched to methotrexate with clinical improvement noted at last follow up of 15 months. A 15-yearold African American female originally diagnosed at age 10 years and treated with oral corticosteroids was treated with chemoradiation on recurrence with full resolution on last follow up of 27 months. Another 11-year-old Hispanic female originally diagnosed at age 10 years was switched to a steroid sparing agent on recurrence due to concerns of growth suppression. She obtained full resolution without recurrence at last follow up of 24 months. Representative Cases n (%) Dacryoadenitis 12 (40) Orbital mass 12 (40) Myositis 10 (33) Diffuse orbital inflammation 4 (13) Bone remodeling 3 (10) Scleral enhancement 3 (10) Optic nerve sheath enhancement 1 (3) Case 1 A 10-year-old female with no past medical or ocular history presented with 1 week of painful right superior periorbital edema and complete mechanical blepharoptosis (Fig. 1A). Constitutional symptoms included malaise and headache. She was diagnosed with preseptal cellulitis by an outside physician and started on an oral antibiotic. On ophthalmic examination the patient was afebrile, and the periorbital edema and ptosis were noted. Visual acuity, pupil response to light, confrontational visual field, globe position, and fundoscopic exam were within normal limits. There was tenderness to palpation of the right superior orbital soft tissues, and there was limited supraduction, adduction, and abduction with binocular diplopia in extremes of gaze. The patient underwent orbital magnetic resonance imaging with contrast that displayed an enhancing right superior and lateral orbital extraconal mass involving the lacrimal gland, lateral rectus, and superior muscle complex (Fig. 1B). An extensive serologic workup was negative including normal white blood cell count. An incisional biopsy was consistent with IOI. Oral corticosteroid therapy was begun at a dose of 1 mg/ kg/day. A brisk clinical improvement was noted within 48 hours with the child denying pain or tenderness, regaining full ocular movements with resolved diplopia, with improved residual right upper eyelid edema and blepharoptosis (Fig. 1C). The child was tapered off corticosteroids over 6 weeks and showed complete clinical resolution without recurrence at last follow up 17 months following presentation. Case 2 A 12-year-old male with no past medical or ocular history presented to the emergency room with a 4-day history of a painless left red eye. On ophthalmic examination, there was tender edema centered in the left lacrimal fossa, inferonasal globe dystopia, limited left abduction with binocular horizontal diplopia in left gaze, injection of the temporal bulbar conjunctiva and palpebral lobe of the lacrimal gland (Fig. 2A, B). The child was afebrile, and visual acuity, pupil response to light, confrontational visual field, and fundus exam were normal. Extensive serologic workup was negative, and orbital computed tomography disclosed an enlarged left lacrimal gland with involvement of the lateral rectus muscle (Fig. 2C). Incisional biopsy of the lacrimal gland was consistent with IOI. The patient was started on oral corticosteroids at 1 mg/kg/day. There was rapid clinical resolution within 3 days, and the steroids were tapered over 6 weeks. At last follow up 15 months after presentation the child remained asymptomatic without recurrence. DISCUSSION Idiopathic orbital inflammation is uncommon in the pediatric age group. 1 Many of the same clinical and radiographical findings seen in adults with IOI are also noted in children afflicted with this disease. Idiopathic orbital inflammation can involve any of the orbital soft tissues with the rectus muscles (myositis) and the lacrimal gland (dacryoadenitis) being the most commonly involved sites. 12 Clinical improvement can occur spontaneously over time; however, corticosteroids have been shown to hasten resolution and decrease risk of flare ups or recurrence when tapered gradually over several weeks to months. 6,13 15 Mottow et al. 11 studied 29 cases of pediatric IOI, which they defined as disease in a patient 20 years of age. The most common ophthalmic findings in their series were periorbital edema (93%), pain (69%), and blepharoptosis (42%). The cohort displayed less periorbital edema (67%) and pain (40%), with similar rate of blepharoptosis (57%). The smaller proportion of patients with periorbital edema and pain in this study should be noted as to not exclude IOI from the differential diagnosis in children with orbital syndromes lacking these findings. Mottow et al. also found that children who underwent biopsies (55%) for diagnostic confirmation were more likely to suffer residua from their disease, which was not found in this study. In 6 cases, they FIG. 1. A, Clinical photograph at presentation showing right upper eyelid edema and mechanical blepharoptosis. B, Coronal T1-weighted orbital MRI with gadolinium showing an enhancing right superotemporal extraconal orbital mass. C, Clinical photograph 2 days following the initiation of oral corticosteroids showing improved right upper eyelid edema and mechanical blepharoptosis. MRI, magnetic resonance imaging The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. 3

4 J. Spindle et al. Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015 FIG. 2. A, Clinical photograph in left gaze at presentation showing limited left abduction, left superotemporal periorbital edema, and temporal bulbar conjunctival injection. B, Clinical photograph in down gaze with digital retraction of the left upper eyelid showing erythema of the temporal bulbar conjunctiva and palpebral lobe of the lacrimal gland. C, Coronal orbital CT showing enlargement of the left lacrimal gland with adjacent involvement of the lateral rectus muscle. CT, computed tomography. noted permanent reduction in visual acuity, persistent proptosis, and/or extraocular muscle limitation. 11 Of note, most of these biopsies were performed before the availability of computed tomography to help in diagnostic evaluation and disease localization. Besides this potential iatrogenic explanation, another possibility is a selection bias if the authors performed biopsies on the more advanced cases that may have suffered persistent ophthalmic signs and symptoms regardless of biopsy. There were 16 patients (53%) in this study, who underwent biopsy, 8 of which were patients with recurrent disease. Biopsy was universally recommended to parents except in cases of isolated primary myositis or perineuritis. There was no increased risk of recurrence or other ophthalmic sequela noted in the patients that underwent biopsy in this study. It is the belief that biopsy should be offered to all patients excluding those with primary myositis or optic nerve perineuritis to rule out malignancy or other infectious or inflammatory disorders. Yan et al. 2 compared IOI among 185 adults and 24 children (defined as 20 years of age). They found blepharoptosis to be more prevalent and proptosis to be less prevalent in children than adults. 2 The most frequent presenting signs in children they studied were palpable mass (58%), motility limitation (46%), and swollen eyelid (42%). 2 Periorbital pain was only seen in 17% of studied children, as opposed to previous studies of adults with IOI that report pain in up to 75%. 5,15 This was consistent with the cohort where less than half of children presented with pain. Additional studies have found the medial and lateral rectus muscles to be the most commonly affected extraocular muscles in IOI with no difference noted between adult and pediatric cases. 8,16,17 In this study, most of the patients were found to have multiple tissues involved at presentation including lacrimal gland, extraocular muscle, and orbital fat. Isolated involvement of tissues, such as pure myositis or dacryoadenitis represented the minority of cases. Constitutional signs, such as headache, emesis, anorexia, malaise, abdominal pain, and weight loss have also been reported in approximately 50% of pediatric cases, 2,6 which is consistent with the study population in whom these signs were noted in 40% of children. Approximately, one third of pediatric cases are reported to present with bilateral disease; 11 however, this study showed only 13% of cases to be bilateral. Bilateral involvement is reported to be more predominant in children but 1 report showed that 3 of the children with presumed bilateral IOI were ultimately diagnosed with a systemic cause of disease. 6 Bilateral involvement is much more common in thyroid eye disease, sarcoidosis, and granulomatosis with polyangitis which should be ruled out in any patient presenting with suspected bilateral IOI. 8 This has led to the suggestion that workup with a pediatric rheumatologist may be helpful in these cases. In this study, there was a significant interaction between race and laterality as all patients with bilateral disease were African American (p = 0.02). Recurrence rates in the pediatric population are reported as high as 76%. 11 Historically, the patients most likely to recur are those with bilateral disease at presentation or iritis. 11 Eleven patients (37%) in this study had recurrences with all 4 bilateral cases being recurrent. One patient in this study that had recurrent unilateral disease also had iritis on initial presentation. In recent series, most of the patients with IOI were female; however, the sex of the patients with bilateral and/or recurrent disease is not described. Of note, all patients with recurrent disease in this study were female, as were all bilateral cases. This may point toward a potential autoimmune etiology for IOI, as females are known to have a higher prevalence of autoimmune diseases. Additional studies are needed to elucidate this finding. The etiology of IOI remains unknown, although several theories have been described including autoimmune disorders, upper respiratory infections, viral illnesses, and aberrant wound healing. 8,9,12,16,18 20 Idiopathic orbital inflammation is a diagnosis of exclusion and it is therefore paramount to approach the evaluation with a thorough differential diagnosis. In the pediatric population, this should include orbital cellulitis, rhabdomyosarcoma, neuroblastoma, leukemia, thyroid eye disease, Langerhans cell histiocytosis, paranasal sinus mucocele, lymphangioma, ruptured dermoid cyst, infectious dacryoadenitis, among others. A thorough evaluation for a systemic cause, such as sarcoidosis, thyroid eye disease, granulomatosis with polyangitis, and Langerhans cell histiocytosis should be performed especially in patients with bilateral disease. 6,21 24 The diagnostic workup should also include a computed tomography and/or magnetic resonance imaging which may show a focal or diffuse process that usually enhances with iodinated contrast or gadolinium. 5,23 25 Despite being a benign entity, IOI may cause vision loss, oculomotor dysfunction, and other ocular sequela. 6,15 Steroid therapy has been the mainstay of treatment; however, in the pediatric population adverse effects may limit long-term use of this modality especially in the setting of multiple recurrences. Localized steroid injections and intravenous rituximab have been used in adults with success. Additional studies are needed to help elucidate their usefulness in children. Immunosuppressive therapy, chemotherapy, radiation, and intravenous immunoglobulin have been reported treatment modalities 8,9,23,26 28 and may be beneficial in this population to prevent long-term consequences. Although this study is limited by its retrospective design, referral bias to academic and tertiary care centers, and limited number of patients, it nevertheless represents the largest series of pediatric IOI cases to date. The authors also acknowledge that when evaluating pediatric patients with orbital inflammation, workup and treatment algorithms often differ among physicians. Each patient in this study underwent exhaustive clinical, serological, radiographic, and in some cases histopathologic workup to rule out systemic causes. Although biopsy was suggested in all cases excluding isolated primary myositis and perineuritis, it The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.

5 Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2015 Pediatric IOI was deferred by parents in 4 (13%) of the cohort. The authors did not choose to exclude these patients as the authors thought they added important data to the study, and presented and responded to treatment as would be expected with IOI. Past published series on this topic also included patients without a histologic confirmation, and underscores the reality that some parents are unwilling to consent to orbital incisional biopsy for their children and the inherent risks thereof. It is imperative to include a multidisciplinary team of physicians including ophthalmologists, pediatricians, rheumatologists, endocrinologists, and radiologists to diagnose and treat these patients in a timely and effective manner. REFERENCES 1. Kitei D, DiMario FJ, Jr. Childhood orbital pseudotumor: case report and literature review. J Child Neurol 2008;23: Yan J, Qiu H, Wu Z, et al. Idiopathic orbital inflammatory pseudotumor in Chinese children. Orbit 2006;25: Swamy BN, McCluskey P, Nemet A, et al. Idiopathic orbital inflammatory syndrome: clinical features and treatment outcomes. Br J Ophthalmol 2007;91: Shields JA, Shields CL, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions: the 2002 Montgomery Lecture, part 1. Ophthalmology 2004;111: Mendenhall WM, Lessner AM. Orbital pseudotumor. Am J Clin Oncol 2010;33: Belanger C, Zhang KS, Reddy AK, et al. Inflammatory disorders of the orbit in childhood: a case series. Am J Ophthalmol 2010;150: Weber AL, Romo LV, Sabates NR. Pseudotumor of the orbit. Clinical, pathologic, and radiologic evaluation. Radiol Clin North Am 1999;37:151 68, xi. 8. Yuen SJ, Rubin PA. Idiopathic orbital inflammation: ocular mechanisms and clinicopathology. Ophthalmol Clin North Am 2002;15: Espinoza GM. Orbital inflammatory pseudotumors: etiology, differential diagnosis, and management. Curr Rheumatol Rep 2010;12: Berger JW, Rubin PA, Jakobiec FA. Pediatric orbital pseudotumor: case report and review of the literature. Int Ophthalmol Clin 1996;36: Mottow L, Jakobiec F, Smith M. Idiopathic inflammatory orbital pseudotumor in childhood I. Arch Ophthalmol. 1978;96: Mombaerts I, Goldschmeding R, Schlingemann RO, et al. What is orbital pseudotumor? Surv Ophthalmol 1996;41: Slavin ML, Glaser JS. Idiopathic orbital myositis: report of six cases. Arch Ophthalmol 1982;100: Mombaerts I, Schlingemann RO, Goldschmeding R, et al. Are systemic corticosteroids useful in the management of orbital pseudotumors? Ophthalmology 1996;103: Yuen SJ, Rubin PA. Idiopathic orbital inflammation: distribution, clinical features, and treatment outcome. Arch Ophthalmol 2003;121: Mombaerts I, Koornneef L. Current status in the treatment of orbital myositis. Ophthalmology 1997;104: Siatkowski RM, Capó H, Byrne SF, et al. Clinical and echographic findings in idiopathic orbital myositis. Am J Ophthalmol 1994;118: Alshaikh M, Kakakios AM, Kemp AS. Orbital myositis following streptococcal pharyngitis. J Paediatr Child Health 2008;44: Casteels I, De Bleecker C, Demaerel P, et al. Orbital myositis following an upper respiratory tract infection: contribution of high resolution CT and MRI. J Belge Radiol 1991;74: Purcell JJ, Jr, Taulbee WA. Orbital myositis after upper respiratory tract infection. Arch Ophthalmol 1981;99: Harris GJ. Idiopathic orbital inflammation: a pathogenetic construct and treatment strategy. Ophthal Plast Reconstr Surg. 2006;22(2): Ho VH, Chevez-Barrios P, Jorgensen JL, et al. Receptor expression in orbital inflammatory syndromes and implications for targeted therapy. Tissue Antigens 2007;70: Gordon LK. Orbital inflammatory disease: a diagnostic and therapeutic challenge. Eye (Lond) 2006;20: Jacobs D, Galetta S. Diagnosis and management of orbital pseudotumor. Curr Opin Ophthalmol 2002;13: McNicholas MM, Power WJ, Griffin JF. Idiopathic inflammatory pseudotumour of the orbit: CT features correlated with clinical outcome. Clin Radiol 1991;44: Paris GL, Waltuch GF, Egbert PR. Treatment of refractory orbital pseudotumors with pulsed chemotherapy. Ophthal Plast Reconstr Surg 1990;6: Shah SS, Lowder CY, Schmitt MA, et al. Low-dose methotrexate therapy for ocular inflammatory disease. Ophthalmology 1992;99: Diaz-Llopis M, Menezo JL. Idiopathic inflammatory orbital pseudotumor and low-dose cyclosporine. Am J Ophthalmol 1989;107: The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. 5