IgG4-related disease in patients with idiopathic orbital inflammation syndrome: data from the French SIOI prospective cohort.

PURPOSE: To better characterize IgG4-related disease (RD) in the setting of idiopathic orbital inflammation syndrome (IOIS). METHODS: National, multicentre, prospective, observational cohort study. Among the patients consecutively included in the French multicentre SIOI cohort, we selected those who underwent orbital and/or adnexal biopsy. Clinical, morphological and pathological findings at diagnosis were blindly analysed. Serum IgG4 levels at inclusion were measured and all available biopsy specimens were immunostained for IgG4 and IgG. Biopsy samples with more than 10 IgG4-positive plasma cells per high-power field and a IgG4+/IgG+ plasma cell ratio above 40% were scored as positive. IgG4-positive patients were then screened for comprehensive diagnostic criteria for IgG4-RD. RESULTS: Of the 87 patients included, 35 had histologically documented IOIS. Thirteen patients (37%) with a mean age at onset of 27 years (range 21-78) had IgG4-positive biopsies, among which 10 patients (77%) and 3 (23%, with IgG4 serum levels >1.35 g/L) were considered as having probable and definite IgG4-RD, respectively. The latter 13 patients more frequently fulfilled histological criteria for IgG4-RD (including plasmacytic infiltrate (p = 0.006), fibrosis (p = 0.0025) and periphlebitis (p = 0.075)) than IgG4-negative patients. Storiform fibrosis was exclusively found in orbital tissues from IgG4-positive patients (n = 3, 23%). Eosinophilia associated with recurrent sinusitis or asthma was a prominent feature in patients with definite IgG4-RD. CONCLUSIONS: More than one-third of patients with biopsy-proven IOIS satisfied criteria for IgG4-RD, but only a few had a definite type.

Radiotherapy for Orbital Pseudotumor: The University of Florida Experience.

BACKGROUND: To evaluate outcomes after definitive radiotherapy for orbital pseudotumor. METHODS: We reviewed adult patients treated between 1971 and 2012. RESULTS: 20 patients with 8.0-year median follow-up were analyzed. Symptoms improved in 75% of patients: 40% showed a complete response, 35% partial response, and 20% had stable disease. The disease progressed in 1 and recurred in 8 patients. Local control rates were 63% and 53% at 5 and 10 years, respectively. The most common toxicities were cataracts (10%) and dry eye (10%). CONCLUSIONS: Radiotherapy for orbital pseudotumor is well-tolerated and results in long-term control in most patients, with local control in over half.

[Idiopathic orbital inflammatory syndrome: Report of 24 cases]. / Syndrome d'inflammation orbitaire idiopathique : à propos de 24 cas.

BACKGROUND: Idiopathic orbital inflammatory syndrome (IOIS) is an inflammatory condition of unknown etiology. The inflammation may affect all the structures within the orbit (anterior, diffuse, apical, myositic, dacryoadenitis) and corresponds to uniquely orbital inflammation without an identifiable local cause or systemic disease. The goal of this study is to describe the clinical and radiographic characteristics of IOIS and discuss the role of orbital biopsy in this condition. PATIENTS AND METHODS: This is a retrospective review of the charts of 24 patients diagnosed with IOIS at Fattouma Bourguiba hospital, Monastir, Tunisia, from January 2007 to December 2015. This study included all patients with IOIS and a minimum follow-up of six months. All patients had a complete ophthalmological examination and orbital and head CT scan and/or MRI. A work-up was performed in all cases to rule out local causes and systemic disease. Only 11 patients underwent biopsy. The diagnosis of the clinical entity IOIS was made according to the Rootman criteria. Oral steroids were the first line therapy. A bolus of intravenous methylprednisolone was administered first in vision-threatening cases. Response to treatment was defined as disappearance of signs and symptoms of IOIS. RESULTS: Orbital pain was the most common symptom (62.5%), followed by proptosis and decreased vision (37.5% each). Best-corrected visual acuity (BCVA) was greater than 5/10 in 70.7% of patients. Lacrimal gland enlargement was observed in 3 patients. Oculomotor disorders were present in 70% of cases and 20.8% of patients had compressive optic neuropathy. Orbital imaging showed, in most cases, oculomotor muscle inflammation (87.5%) involving particularly the superior rectus muscle (54.2%) and inflammation of orbital fat (66.7%). Fifty percent had myositic inflammation. Biopsy was performed in 11 patients, showing nonspecific inflammation (n=10) and the sclerosing form (n=1). A total of 83.3% of patients received oral corticosteroids for a mean duration of 5.5 months. CONCLUSION: IOIS is a diagnosis of exclusion, based on history, clinical course, response to steroid therapy, laboratory tests, or even biopsy in selected cases. Orbital imaging provides valuable clues for diagnosis of IOIS and for identification of affected structures. Prolonged steroid therapy is necessary as IOIS classically responds to steroids; nevertheless, partial recovery or relapses often occur.

Factors associated with multiple recurrences of nonspecific orbital inflammation aka orbital pseudotumor.

OBJECTIVE: To assess clinical characteristics of patients at risk for recurrent nonspecific orbital inflammation (NSOI). METHODS: This was a retrospective comparison study with a 24-month follow-up, in a clinic-based population in rural India. The medical records at two eye care centers were searched from March 2001-2014. A total of 153 patients with recurrent NSOI, 107 of whom had a single recurrence (Group 1) and 46 of whom had multiple recurrences (Group 2). Clinical and demographic data were compared between both groups. Comparisons of mean values were done with multiple 2-tailed independent T tests, and differences in proportions were compared using Chi-squared tests. A multivariate logistic regression model was used to determine which factors were predictive of patients having multiple recurrences. RESULTS: Several factors were independently related to multiple recurrences (P < 0.05 for all): age ≤16 years (2.5 OR, 95% CI 1.3-3.6), bilateral disease (3.2 OR 95% CI 1.4-5.1), presence of optic disc edema or T-sign on B-scan ultrasonography (3.9 OR 95% CI 1.8-6.2), sclerosing variant (8.5 OR 95% CI 5.4-11.3), corticosteroid taper <4 weeks long (2.8 OR 95% CI 1.1-4.2), autoimmune disease among 1st degree relatives (2.2 OR 95% CI 1.2-3.3). In patients with recurrent disease, the interval between the initial episode and the first recurrence was predictive of further recurrences: ≤3 months (3.2 OR, 95% CI 2.0-4.5) and ≥12 months (0.21 OR, 95% CI 0.01-0.39). CONCLUSION: Younger patients and those with bilateral disease are more apt to have recurrences of NSOI. Other factors that increase the risk of multiple recurrences include a T-sign, optic disc edema, poor initial response to steroids, a sclerosing variant, a recurrence within 3 months, and those who underwent a rapid steroid taper.

The impact of IgG-4-ROD on the diagnosis of orbital tumors: A retrospective analysis.

This study was to determine the prevalence of immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD) among patients who have previously undergone biopsy and were diagnosed to have idiopathic orbital inflammatory disease (IOID) or orbital lymphoproliferative disease (OLD), namely, lymphoma and benign reactive lymphoid hyperplasia (BRLH). This is a retrospective cross-sectional study. The charts and slides of all patients who underwent biopsies and were histopathologically diagnosed to have either IOID or OLD were reviewed. Demographics, clinical features, initial histopathological diagnoses, treatment received, and final outcome were noted. Using the diagnostic criteria for diagnosis for IgG4 disease, those cases that would classify as "possible IgG4-related disease (IgG4-RD)" were reviewed, reclassified, and reassigned a diagnosis of IgG4-ROD. We reviewed 105 patients' clinical charts. Of these 105 patients, upon reviewing the histopathology, 18 (17.15%) patients were found to fit the diagnostic criteria for possible IgG4-ROD. Of these 18 patients who were now reassigned the diagnosis of IgG4-ROD, the most common previous histopathological diagnosis was found to be IOID, for eight patients (44%), then BRLH, which was noted in five patients (27.8%), followed by lymphoma, which was noted in two patients (11.1%). Previously diagnosed cases of IOID and OLD were found to fulfill the criteria for IgG4-ROD. Given the advent of recent diagnostic and histopathological techniques, all cases of suspected IOID and OLD should be screened for IgG4-ROD and all previously diagnosed cases must be closely followed up, given the systemic implication of IgG4-RD. Histopathological reassessment of previously diagnosed cases may be considered.

Clinical Features and Treatment Outcomes of Orbital Inflammatory Disease in Singapore: A 10-Year Clinicopathologic Review.

PURPOSE: 1) To assess the clinical profile and treatment outcomes of orbital inflammatory disease in the local population, and 2) classify patients using current histopathological criteria. METHODS: Ten-year retrospective clinicopathologic review of patients diagnosed with orbital inflammatory disease who underwent tissue biopsy from January 2001 to December 2011 at a tertiary referral centre in Singapore. Data collection included patient demographics, clinical presentation, investigations, systemic disease, histopathology review, clinical classification, medical and surgical management, response to treatment and recurrence rates. RESULTS: The study comprised 70 patients. Thirty-seven (52.9%) had nonspecific inflammation distributed as follows: lacrimal (n = 23), diffuse (n = 5), anterior (n = 5), myositic (n = 4). Thirty-three (47.1%) had specific inflammation of the following subtypes: idiopathic sclerosing inflammation (n = 9), granulomatous disorders (n = 8), transitional lesions (n = 5), vasculitis (n = 4), and others (n = 7). A total of 76.8% of patients received oral prednisolone, with a median duration of three months. Response to treatment was good in 71.9% of patients. Recurrence occurred in 22 (32.8%) patients at a mean interval of 20 months after completion of treatment, and was higher in myositic and vasculitic subtypes. There was no significant correlation between duration of treatment and recurrence. CONCLUSIONS: This study has re-emphasized the importance and utility of orbital biopsy and histopathologic typing for optimal management of orbital inflammatory disease. It has also improved the knowledge of the rate and response to treatment of its various subtypes.

A prevalence study of IgG4-related ophthalmic disease in Japan.

PURPOSE: Immunoglobulin (Ig)G4-related ophthalmic disease belongs to a category of ocular adnexal lymphoproliferative disorders, the most frequent group of orbital tumors and simulating lesions. The aim of this study was to elucidate the number of IgG4-related diseases of orbital lymphoproliferative disorders and correlate ages and sex of such patients from 18 centers in Japan. METHODS: One thousand and fourteen patients with orbital lymphoproliferative disorders were enrolled in this study. All had pathologically diagnosed lymphoproliferative disorders with surgical samples of ocular adnexal tissue. Patients with conjunctival lesions and intraocular lymphoma were excluded. RESULTS: Of the 1,014 cases of orbital lymphoproliferative disorders 404 (39.8 %) had extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, 156 (15.4 %) had other malignant lymphomas, 191 (18.8 %) had non-IgG4 orbital inflammation, 219 (21.6 %) had IgG4-related orbital inflammation, and 44 (4.3 %) had IgG4-positive MALT lymphoma. Median age of the IgG4-related orbital inflammation group was 62 years, which is significantly lower than that of the MALT lymphoma group (median 66 years) and higher than the non-IgG4 orbital inflammation group (median 57 years). The male/female ratio was 105/114 in the IgG4-related orbital inflammation group. CONCLUSIONS: Nearly a quarter of orbital lymphoproliferative disorders in Japan are related to IgG4.

Idiopathic orbital inflammatory pseudotumor in Chinese children.

PURPOSE: To study the clinical features of idiopathic orbital inflammatory pseudotumor (IOIP) in Chinese children. METHODS: Pediatric patients with IOIP seen between Jan. 1, 1978 and Dec. 31, 1999 in the Eye Hospital, Zhongshan Ophthalmic Center, Sun Yat-sen University were evaluated retrospectively. Their clinical features were compared with those of adult cases of IOIP. RESULTS: Of the 209 cases, 24 (11.5%) were equal to or less than 20 years old; 14 were female and 10 were male. There were 11 in the right eye, 9 in the left eye and 4 in both eyes. Palpable mass (58%), ocular motility restriction (46%), swollen eyelid (42%), proptosis (42%) and high orbital pressure (42%) were the five most common presenting signs in children with IOIP. Ptosis occurred more often in pediatric IOIP cases (38%) than in adult IOIP cases (9%) (P < 0.0003). However, compared with adult IOIP cases, pediatric patients showed less proptosis (69% vs. 42%, P = 0.0074). According to radiological and surgical findings, a local mass within the orbit was the most frequent subtype (50%), followed by dacryoadenitis (29%), myositis (8%), perineuritis (4%), eyelid pseudotumor (4%), and diffuse orbital inflammation (4%). The frequency of clinical subtypes in children was similar to that in adults. After systemic corticosteroids, surgical management and local radiotherapy the full recovery response rate was 29% and the total effective rate was 92%. CONCLUSIONS: Pediatric IOIP accounted for 11.5% of all IOIP patients. Pediatric cases had more sign of ptosis and less sign of proptosis than in adult IOIP. The full recovery response rate was low in children with IOIP.

Survey of 1264 patients with orbital tumors and simulating lesions: The 2002 Montgomery Lecture, part 1.

OBJECTIVE: To determine the incidence of specific orbital tumors based on patients referred to an ocular oncology center. DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 1264 consecutive patients referred to an ocular oncology service because of space-occupying orbital lesions. METHODS: A retrospective chart review was carried out for 1264 consecutive patients referred for a suspected orbital mass over a 30-year period. The lesions were grouped into general categories, as shown in "Results." The specific diagnosis in each case was based on clinical findings, computed tomography scan results, magnetic resonance imaging results, and histopathologic analysis results, when available. The number and percentage of benign and malignant tumors per age group also was determined. MAIN OUTCOME MEASURES: The incidence of orbital tumors and pseudotumors. RESULTS: Among 1264 consecutive patients, the number and percentage of lesions in each general category were as follows: cystic, 70 cases (6%); vasculogenic, 213 cases (17%); peripheral nerve lesions, 23 (2%); optic nerve and meningeal tumors, 105 (8%); fibrocytic lesions, 13 (1%); osseous and fibro-osseous tumors, 21 (2%); cartilaginous lesions, 1 (<1%); lipocytic and myxoid lesions, 64 (5%); myogenic tumors, 36 (3%); lacrimal gland lesions, 114 (9%); primary melanocytic lesions, 11 (<1%); metastatic tumors, 91 (7%); lymphoma and leukemia lesions, 130 (10%); secondary orbital tumors, 142 (11%); histiocytic lesions, 17 (1%); thyroid-related orbitopathy, 67 cases (5%); other inflammatory lesions, 133 cases (11%); and miscellaneous other lesions, 13 (1%). The most common diagnoses were: lymphoid tumor (139 cases;11%), idiopathic orbital inflammation (135 cases; 11%), cavernous hemangioma (77 cases; 6%), lymphangioma (54 cases; 4%), meningioma (53 cases; 4%), optic nerve glioma (48 cases; 4%), metastatic breast cancer (44 cases;4%), orbital extension of uveal melanoma (41 cases; 3%), capillary hemangioma (36 cases;3%), rhabdomyosarcoma (35 cases; 3%), dermolipoma (31 cases; 3%), herniated orbital fat (30 cases; 2%), dermoid cyst (26 cases; 2%), varix (26 cases; 2%), dacryops (19 cases; 2%), and other less common lesions. Of the 1264 lesions, 810 (64%) were benign and 454 (36%) were malignant. The percentage of malignant lesions was 20% in children (age range, 0-18 years), 27% in young adults and middle-aged patients (age range, 19-59 years), and 58% in older patents (age range, 60-92 years). Rhabdomyosarcoma was the most common malignancy in children, representing 3% of all orbital masses, and lymphoma was the most common malignancy in older patients, representing 10% of cases. CONCLUSIONS: A variety of tumors and pseudotumors can involve the orbit. In this series of 1264 lesions, 64% were benign and 36% were malignant. The percentage of malignant tumors increased with age, with malignancies being common in older patients because of the higher incidence of lymphoma and metastasis in the elderly.

Orbital tumors in the older adult population.

PURPOSE: To determine the types and frequency of orbital tumors in the older adult population. DESIGN: Retrospective consecutive case series. PARTICIPANTS: Two hundred consecutive patients aged 60 years or older with an orbital tumor managed at a tertiary referral center. MAIN OUTCOME MEASURES: The relative incidence and management of orbital tumors in patients aged 60 years or older. RESULTS: Of approximately 950 consecutive patients with orbital space-occupying lesions managed over a 25-year period on the Oncology Service, 200 patients (21%) were 60 years or older at the time of diagnosis. The orbital tumor was unilateral in 183 patients (92%) and bilateral in 17 patients (8%). The most common clinical features at presentation included mass in 51 patients (26%), proptosis in 36 (18%), and pain in 30 (15%). The mean duration of symptoms was 11 months before referral. The orbital tumor was malignant in 125 patients (63%) and benign in 75 (27%). The most common diagnoses were malignant lymphoma in 47 patients (24%), idiopathic orbital inflammation in 19 (10%), and cavernous hemangioma in 15 (8%). The diagnosis was made with clinical findings and imaging studies in 58 patients (29%) and additional histopathologic examination in 142 patients (71%). Of 217 tumors, the main tumor location was in the superior half of the orbit in 106 lesions (49%), in the anterior orbit in 100 (46%), and in the extraconal space in 135 (62%). Imaging studies showed a mass with well-defined margins in 90 tumors (41%) and ill-defined margins in 127 (59%). The tumors were solid in 203 cases (94%), cystic in 6 (3%), and mixed in 8 (3%). Over a mean of 31 months follow-up, 50 (25%) patients had orbital tumor-related systemic involvement (metastasis or lymphoma), and 150 (75%) remained free of systemic involvement. CONCLUSIONS: Orbital tumors in the senior adult population are malignant in 63% of cases. Malignant lymphoma is the most common tumor in this age group, accounting for 24% of cases. Overall, 25% of patients have systemic problems related to the orbital process develop, so systemic evaluation is warranted.

Idiopathic orbital pseudotumours in adults.

We treated 24 cases of orbital pseudotumour from January 1981 through January 1993. The clinical characteristics and treatment outcomes were analyzed retrospectively by reviewing the medical records, radiological studies, and histological examination. All patients presented with symptoms related to the eye (proptosis, lid swelling, limited ocular motion and/or pain, chemosis, and visual disturbance), while only five patients had symptoms pertaining to the ear, nose, and throat besides the ophthalmological symptoms. Plain X-ray findings were not contributory to the diagnosis. Computed tomograms (CT) showed non-specific findings such as hypertrophy of the extra-ocular muscles and well-defined or poorly defined mass. Pathological findings were non-specific, only to reveal benign lymphoid hyperplasia and inflammatory cell infiltration with necrotizing vasculitis. Twenty-four patients were treated with high-dose steroid therapy which resulted in a significant improvement in 10 patients (42%).

[Pseudotumor orbitae--a chameleon in diagnosis and therapy?]. / Der Pseudotumor orbitae--ein Chamäleon in Diagnostik und Therapie?

Between 1972 and 1988, 25 patients were diagnosed and treated for "pseudotumor orbitae" in the Departments of Radiotherapy and Ophthalmology of Münster University Clinics. All cases had been initially confirmed by histology. Later in seven cases (28%) the histology showed a definitive alteration, and eventually turned to malignancy in five patients. Criteria indicating such a shift are seen in higher age, subacute onset of the disease, low pain, minor signs of inflammation, low echoes in ultrasound diagnostics, and the absence of "Dutcher bodies" in histiocytes, if these are evident in histology. These patients at increased risk of malignant transformation should be considered for radiotherapy at an earlier stage than prescribed by the current routine.