Cellular pattern and orbital fat involvement are possible risk factors for the failure of corticosteroids in patients with pure idiopathic orbital inflammation syndrome: lessons from the French prospective SIOI cohort study (part II).

PURPOSE: To better characterise the effects of corticosteroids on the course of pure idiopathic orbital inflammation syndrome (pIOIS). METHODS: This was a national, multicentre, prospective, non-interventional cohort study (SIOI). Among the 35 patients with histologically proven orbital inflammation who had previously been studied for their IgG4 immunostaining status, we selected those with a negative IgG4 status (ie, pIOIS) who received corticosteroids as single first-line treatment. Clinical, morphological and pathological findings at diagnosis and during follow-up from treatment initiation to study completion were analysed. Patients were assessed for their response to prednisone after the 24-month prospective phase in terms of remission (≤10 mg/d) or failure (>10 mg/d). Daily standard doses of prednisone (DSDP) were calculated at different time-points and compared between response groups. RESULTS: Of the 17 patients with pIOIS included in the final analysis, two-thirds received corticosteroids only. DSDP (mg/kg-day) were significantly higher at the time of failure in eight patients (47%) than in nine (53%) remitting at M24 (0.16 vs 0.045; p: 0.03). Notably, patients with pIOIS with a cellular pattern or orbital fat involvement tended to receive higher daily corticosteroid doses in the event of failure than remission (0.16 vs 0.045 and 0.12 vs 0.042, respectively). During treatment, maximal DSDP was 0.52 in failed patients. CONCLUSION: The highest corticosteroid doses were insufficient to prevent failure in patients with pIOIS, particularly in those with a cellular pattern or orbital fat involvement. Large-scale interventional studies are now necessary to clarify prognostic factors and optimise corticosteroid management in patients with pIOIS.

An Evidence-Based Approach to Diagnosing Patients Presenting With Orbital Inflammatory Syndromes (An American Ophthalmological Society Thesis).

PURPOSE: The initial management of patients presenting with orbital inflammatory syndromes varies-with some pursuing a diagnostic workup while others treat without any testing. The evidence behind this rationale is limited. A review of patients with orbital inflammation is performed with an analysis of diagnostic testing to develop a workflow for such patients. DESIGN: A retrospective review of patients presenting with acute orbital inflammation at a single institution from 2011 to 2020 was conducted. METHODS: Orbital imaging was required for inclusion. Patients with high suspicion of neoplasm, bacterial infection, vascular malformation, or thyroid eye disease were excluded. A review of presenting clinical findings, laboratory workup, orbital imaging, and biopsy were performed. Statistical analysis was performed identifying statistically significant diagnostic and treatment maneuvers. RESULTS: In total, 172 patients met inclusion criteria (66% female, mean age 46 years). The primary clinical presentation was myositis, dacryoadenitis, and infiltrative in 67, 73, and 32 patients (39.0%, 43.0%, 18.6%, respectively). Laboratory studies were conducted in 145 (84%) while biopsy was performed in 55 (32%). Specific orbital inflammation (SOI) was diagnosed in 29 (16.9%) with the most frequent diagnoses being sarcoidosis, IgG4-related disease, inflammatory bowel disease, and systemic lupus erythematosus. The majority (147, 85.5%) was initially treated with steroids, but steroid-sparing agent use was statistically higher in patients with SOI. CONCLUSIONS: In patients presenting with orbital inflammatory syndromes, distinguishing myositis, dacryoadenitis, and infiltrative disease has workup and differential diagnosis impacts. Because SOI is relatively common, sequelae of SOI, and potential steroid-sparing therapy needs, diagnosis via an evidence-based systemic approach is critical. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Orbital Mass Identified With Point-of-Care Ultrasound in a Child Presenting With Eyelid Swelling.

ABSTRACT: Point-of-care ultrasound was used in a child presenting to the emergency department with progressively worsening left eyelid swelling. The early use of ultrasound was helpful in detecting a soft tissue mass that is exhibiting pressure effect on the eyeball. Point-of-care ultrasound helped expedite advanced imaging and consultation with the specialist. The patient eventually had a biopsy and was diagnosed with idiopathic orbital inflammation.

Lateral micro-orbitotomy as the technique of choice for orbital pseudotumor in IgG4-RD. Case report and review of the literature.

Immunoglobulin G4-related disease (IgG4-RD) is characterized by a systemic fibroinflammatory infiltrate that often involves the orbit in addition to other tissues. Thus it has to be considered in the differential diagnosis of orbital tumors. We report the clinical case of a 64-year-old woman who presented with right mydriasis, progressive proptosis and paralysis of the third cranial nerve of 1 year of evolution. Cranial MRI identified an intraconal lesion of the right orbit, located between the external and inferior rectus muscles and the optic nerve, and she was scheduled for surgery by transcranial approach with lateral micro-orbitomy. A satisfactory macroscopic excision was achieved with no remarkable complications and a definitive deferred histological result of pseudotumor by IgG4-RD. Follow-up for 24 months showed no tumor recurrence, and the patient clinically improved from ophthalmoplegia. This case highlights the efficacy of lateral orbitotomy in the etiologic diagnosis and successful therapeutic outcome of complex orbital lesions associated with IgG4-RD pseudotumor.

Nonspecific Orbital Inflammation (NSOI): Unraveling the Molecular Pathogenesis, Diagnostic Modalities, and Therapeutic Interventions.

Nonspecific orbital inflammation (NSOI), colloquially known as orbital pseudotumor, sometimes presents a diagnostic and therapeutic challenge in ophthalmology. This review aims to dissect NSOI through a molecular lens, offering a comprehensive overview of its pathogenesis, clinical presentation, diagnostic methods, and management strategies. The article delves into the underpinnings of NSOI, examining immunological and environmental factors alongside intricate molecular mechanisms involving signaling pathways, cytokines, and mediators. Special emphasis is placed on emerging molecular discoveries and approaches, highlighting the significance of understanding molecular mechanisms in NSOI for the development of novel diagnostic and therapeutic tools. Various diagnostic modalities are scrutinized for their utility and limitations. Therapeutic interventions encompass medical treatments with corticosteroids and immunomodulatory agents, all discussed in light of current molecular understanding. More importantly, this review offers a novel molecular perspective on NSOI, dissecting its pathogenesis and management with an emphasis on the latest molecular discoveries. It introduces an integrated approach combining advanced molecular diagnostics with current clinical assessments and explores emerging targeted therapies. By synthesizing these facets, the review aims to inform clinicians and researchers alike, paving the way for molecularly informed, precision-based strategies for managing NSOI.

A Case of Idiopathic Orbital Inflammation With Elevated Anti-Mumps Immunoglobulin M Antibody.

A 21-year-old female presented with periocular swelling, diplopia, and painful ophthalmoplegia in the OS. Orbital magnetic resonance imaging revealed an enhanced soft tissue mass involving the left medial rectus muscle. Laboratory test results revealed leukocytosis, elevated reactive C-reactive protein, and positive serum levels of anti-mumps immunoglobulin M (IgM) antibody without systemic manifestations of mumps infection. The clinical course was refractory, and the patient showed a poor response to high-dose steroids. An incisional biopsy revealed stromal fibrosis with focal lymphoid aggregates, indicating sclerosing inflammation. Myopathy of the medial rectus progressed to superior, inferior, and lateral recti involvement of the left orbit. Immunosuppressive agents, including steroids, were administered for 22 months after disease onset. The mumps IgM antibody level was positive for over 5 months and became negative upon testing performed 1 year after the first visit.

ANCA-associated kidney disease preceded by orbital pseudotumor.

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are distinct immune disorders with overlapping clinical and laboratory features. While ANCA positivity excludes IgG4-RD in the 2019 ACR/EULAR classification, this criterion is not uniformly applied, and AAV can form inflammatory masses in various organs and show increase in IgG4 + plasma cells, similar to IgG4-RD. CASE DIAGNOSIS/TREATMENT: A 5-year-old female with history of orbital mass diagnosed as IgG4-RD presents with acute kidney injury. She has a myeloperoxidase ANCA, and kidney biopsy shows pauci-immune crescentic glomerulonephritis and acute tubulointerstitial nephritis with increased IgG4 + plasma cells and tubular basement membrane (TBM) deposits. CONCLUSION: In isolation, TBM deposits and increased IgG4 + plasma cells are suggestive of IgG4-RD. In the context of a positive ANCA and pauci-immune crescentic glomerulonephritis, however, increased IgG4 + plasma cells due to AAV are favored. In cases with features of IgG4-RD, ANCA positivity suggests an alternate diagnosis of AAV to be more likely.

Orbital inflammatory pseudotumor: new advances in diagnosis, pathogenesis, and treatment.

Orbital inflammatory pseudotumor (OIP) is a benign, non-specific inflammatory disorder that commonly occurs in middle-aged adults and is usually unilateral but can occur bilaterally. Its clinical manifestations have tremendous clinical heterogeneity and vary according to the site of infiltration and the degree of lesions, including orbital pain, swelling, diplopia, proptosis, restricted eye movement, and decreased visual acuity. Clinical features, Image characteristics and pathological examinations often need to be evaluated to confirm the diagnosis. Currently, there is no systematic research on the pathogenesis of OIP, which may be related to immunity or infection. The first-line treatment is glucocorticoids. Radiotherapy, immunosuppressants, and biologics can be considered for treatment-resistant, hormone-dependent, or intolerant patients. In this review, we aim to summarize and focus on new insights into OIP, including new diagnostic criteria, pathogenesis, and discoveries in new drugs and treatment strategies. In particular, we highlight the literature and find that T cell-mediated immune responses are closely related to the pathogenesis of OIP. Further exploration of the mechanism and signaling pathway of T cells in the immune process will help to identify their therapeutic targets and carry out targeted therapy to treat refractory OIP and reduce the side effects of traditional treatments.

[Role of imaging classification in the diagnosis and management of orbital inflammatory pseudotumor].

Orbital inflammatory pseudotumor (OIP) is a kind of orbital idiopathic benign space-occupying lesion with no clear etiology and mainly characterized by inflammatory response. The clinical diagnosis of OIP should be based on exclusion of other diseases or surgical biopsy. Medication and surgical excision are both diagnostic and therapeutic methods. The choice of which is a problem that baffles clinicians. This article discusses a new strategy basing on the imaging features and classifications of OIP. It is expected to be further discussed and promoted in clinical practice to improve the diagnosis and treatment of OIP.

Orbital inflammatory pseudotumor revealing multi-organ immunoglobulin G4-related disease.

Relatively recently, the concept that immunoglobulin G4 (IgG4)-related disease is a distinct chronic inflammatory disorder rather than a subset of Sjögren's syndrome has been accepted. IgG4-related disease (IgG4-RD) is a fibro-inflammatory systemic immune-mediated condition that can affect the pancreas, salivary glands, and lymph nodes. Almost every organ may be impacted synchronously or metachronously by this illness, which causes the development of sclerotic masses of varying sizes. Numerous other rheumatic diseases can present with characteristics of IgG4-RD, making it difficult to distinguish between them. However, cases of IgG4-RD involving the bilateral orbits, and pancreas with biological abnormalities are rare. We present a case of an 18-year-old female with vitiligo since the age of 3 years who presented with acute pancreatitis and acalculous cholecystitis, bilateral orbital masses, palpebral edema, and eosinophilia. The patient was diagnosed with IgG4-RD in keeping with clinical presentation and the elevated serum IgG4 level and after elimination of other differential diagnoses. The patient's symptoms gradually relieved after glucocorticoid therapy. This case presents an uncommon combination of clinical features infrequently reported in the literature. Multi-organ IgG4-RD is a multisystemic mass, commonly creating diagnostic challenges for clinicians. Furthermore, and more importantly, it highlights the need to keep a differential of IgG4-RD in mind, to aid in the early and correct treatment of the disease.

Orbital Inflammatory Pseudotumor following mRNA COVID-19 Vaccination.

The authors present a case of orbital pseudotumor after mRNA COVID-19 vaccination. A 40-year-old otherwise healthy woman was referred to our oculoplastics unit because of left blepharoptosis of 2 months duration starting 1 week after she received her first Pfizer-BioNTech mRNA vaccination. On presentation, her best-corrected visual acuity was 20/20 in each eye. The external examination revealed left blepharoptosis and mild upper eyelid swelling. Orbital magnetic resonance imaging revealed left lacrimal gland enlargement with homogeneous contrast enhancement and diffuse mild enlargement of the left lateral and superior rectus muscles. The results of the extended workup for autoimmune and infectious etiologies and the systemic examination findings were normal. Systemic corticosteroids were started for the orbital pseudotumor. The presented case of orbital pseudotumor development after the mRNA vaccine may be considered to be an immunological process targeting the orbital tissue following immunization, although the cause-effect relationship remains uncertain.

Recurrence of Idiopathic Orbital Inflammation: An 11-year Retrospective Study.

PURPOSE: The high recurrence rate of idiopathic orbital inflammation (IOI) has been reported. This study aims to determine existing predictive factors for the recurrence of IOI. METHODS: This was an 11-year retrospective study with at least a 12-month follow-up. Fifty patients with biopsy-proven IOI admitted between 2006 and 2017 at our tertiary hospital were observed. We compared the clinical characteristics, histopathological profile, and biomarker expressions (mast cell, immunoglobulin G4, tumor necrosis factor-alpha, and transforming growth factor-beta) of 16 patients with recurrence (Group I) and 34 patients with no recurrence (Group II). Statistical comparison and multivariate analysis were performed to establish the predictive factors. RESULTS: We discovered five recurrence predictive factors: presentation of proptosis (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.36-18.03), visual impairment (OR 15, 95% CI 1.58-142.72), extraocular muscle (EOM) restriction (OR 3.86, 95% CI 1.07-13.94), nonanterior involvement (OR 7.94, 95% CI 1.88-33.5), and corticosteroid (CS) alone treatment (OR 7.20, 95% CI 1.87-27.8). On multivariate analysis, nonanterior involvement and CS alone treatment were validated as predictive factors (area under the curve = 0.807 [95% CI 0.69-0.92]). Histopathological profile and biomarker expressions were not associated with recurrence. However, there was a 22-fold higher recurrence risk for granulomatous-type patients given CS alone treatment. CONCLUSION: Unlike the five clinical characteristics mentioned, both histopathology and biomarker variables were not associated with recurrence. CS alone treatment for patients with nonanterior involvement or granulomatous type is proven to increase the risk of recurrence. Therefore, we suggest not giving CS without any combination treatment with other modalities for this group of patients.

Clinical heterogeneity between two subgroups of patients with idiopathic orbital inflammation.

OBJECTIVE: Idiopathic orbital inflammation (IOI) is a group of orbital inflammatory diseases of unknown etiopathogenesis. We investigated whether patients with IOI have clinical heterogeneity based on the presence (typical group) or absence (atypical group) of a unique onset that periocular inflammatory symptoms emerge suddenly but progress slowly. METHODS AND ANALYSIS: This retrospective cohort study included 195 patients diagnosed with IOI. We analysed the clinical data of patients, including the outcomes of corticosteroid treatment, in two subgroups stratified on the basis of the presence (130 patients) or absence (65 patients) of the unique onset. RESULTS: Patients in the typical group were significantly younger at disease onset than those in the atypical group (median age; 52 vs 65 years, p=0.002); had more ocular adnexa-specific lesions, namely, dacryoadenitis, myositis, scleritis and optic perineuritis (78% vs 45%, p=0.00001); and had significantly fewer associations with immune-mediated inflammatory diseases (4% vs 15%, p=0.004). Among 30/119 patients (25%) who were steroid refractory in the typical group, a long period of time from symptom onset to initiation of treatment was a significant steroid-refractory risk factor (OR: 16.7), whereas, among the 18/40 patients (45%) who were steroid refractory in the atypical group, intraconal diffuse lesions were a significant steroid-refractory risk factor (OR: 8.8). CONCLUSION: This cohort study suggests clinical heterogeneity between the two subgroups of patients with IOI.