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 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.

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.

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.

Canine idiopathic orbital inflammation: A case series of four affected dogs (five orbits).

PURPOSE: In humans, idiopathic orbital inflammation (IOI) is a diagnosis attributed to benign, inflammatory orbital conditions without identifiable local or systemic cause. We describe the clinical signs, imaging and histopathological findings, management and outcome of four dogs diagnosed with IOI. METHODS: Multicentric retrospective study. RESULTS: A total of four dogs (five orbits) of three different breeds (three cases were English Springer Spaniels [ESS] or ESS-cross) and ages ranging from 3 to 12 years were included. Initial presenting signs were unilateral and included exophthalmos, enophthalmos, globe deviation, thickening and protrusion of the third eyelid and conjunctival hyperemia. Computed tomography and magnetic resonance imaging identified heterogeneous space-occupying, contrast-enhancing orbital lesions in all cases. Sparing of the retrobulbar space was detected in four of five orbits. Histopathology revealed mixed inflammatory infiltrates of lymphocytes, plasma cells, and histiocytes. Immunohistochemistry was performed in two cases highlighting the presence of histiocytes and lymphocytes, predominantly T cells. Resolution of clinical signs was achieved in two cases managed with oral immunosuppressant medication (corticosteroids alone or combined with cyclosporine or azathioprine), one went into spontaneous remission, one resolved with topical corticosteroids, and one underwent exenteration. Recurrence occurred in two cases within 15 months of initial diagnosis and required further immunosuppressant medication. One case developed signs in the contralateral orbit within 8 months of presentation. CONCLUSIONS: IOI is an uncommon condition in dogs. Its diagnosis relies on the combination of advanced imaging and histology. As in humans, it appears that spontaneous remission and recurrence may occur requiring long-term immunosuppressant medication.

Features of ophthalmic, magnetic resonance imaging, and histopathology of a feline case of idiopathic sclerosing orbital pseudotumor.

In the present report, we describe a case of sclerosing orbital pseudotumor in an 11-year-old castrated male American Shorthair cat. Ophthalmic exam showed lagophthalmos, retracted right upper eyelid, and resistant to retropulsion in his right eye. Under magnetic resonance imaging (MRI) scans, increased volume of the extraocular muscles (EOMs) of the right eye was prominent. Immunosuppressive dosage of prednisolone partially ameliorated the clinical signs, but some clinical signs were still gradually progressive or persistent. In the second MRI scan, decreased diameter of the thickened right extraocular muscles was found. After the third MRI scan, enucleation of the right eye was performed due to substantial adverse effects of systemic steroid therapy. Histopathological examination revealed no evidence of neoplastic transformation nor infection. Feline restrictive orbital myofibroblastic sarcoma (FROMS) was therefore excluded, suggesting unknown causes of extensive fibrotic changes in the right orbit of the affected cat.