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.

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.

Clinical Outcomes of IgG4-Related Ophthalmic Disease and Idiopathic Sclerosing Orbital Inflammation.

PURPOSE: To compare the clinical features, treatment outcomes, and prognoses of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and idiopathic sclerosing orbital inflammation (ISOI). METHODS: This retrospective case series included 40 and 22 biopsy-proven cases of IgG4-ROD and ISOI, respectively. The authors reviewed medical charts and images to determine the clinical presentation, involvement pattern, and treatment outcomes. The main outcome measures were differences in disease manifestation, treatment modalities and efficacy, medication-free remission rate, and predictive factors for remission. RESULTS: The median ages were 51 (range 31-72) and 39 (range 9-73) years in the IgG4-ROD and ISOI groups, respectively. The most frequently involved sites were the lacrimal gland (39 cases, 98%) in IgG4-ROD patients and the extraconal region (15 cases, 68%) in ISOI patients. No significant difference was observed in the initial treatment response between the groups. Medication-free remission was achieved in 22 (55%) IgG4-ROD patients and 10 (45%) ISOI patients; none of the IgG4-ROD patients showed permanent ocular dysfunction, while half of the ISOI patients had permanent visual loss or limited ocular motilities. Multivariate analysis indicated that extraocular muscle enlargement (odds ratio, 0.11; 95% confidence interval, 0.01-0.98) and IgG4:IgG ratio on histopathology (odds ratio, 0.08; 95% confidence interval, 0.01-0.86) were negatively associated with medication-free remission in IgG4-ROD patients. CONCLUSIONS: Although IgG4-ROD and ISOI share common histological findings of mass-forming sclerosis, IgG4-ROD frequently has a more indolent clinical course, whereas ISOI often demonstrates a more aggressive clinical course, resulting in ocular dysfunction even after remission. Different pathogeneses may account for the different disease characteristics.

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.

Long-term follow up of systemic rituximab therapy as first-line and salvage therapy for idiopathic orbital inflammation and review of the literature.

PURPOSE: To report long-term outcomes of systemic rituximab therapy for idiopathic orbital inflammation (IOI) as both primary and salvage therapy and to review the English literature. METHODS: A retrospective review of four consecutive biopsy-proven IOI cases managed with systemic rituximab including demographics, management, and outcomes, and review of English literature, were performed. Primary outcome measures included resolution of symptoms, recurrence, and length of follow up. RESULTS: Of four cases, systemic rituximab was the first-line therapy in two cases and salvage therapy in two cases. The mean age of the patients was 62 years (range, 50-68 years). The orbit was involved in three cases and extraocular muscle in one case. Systemic rituximab (1 g weekly for 4 weeks) was given for one session in three patients and for 12 sessions in 1 patient. All four patients responded with the resolution of all symptoms without recurrence after at least 5 years of follow up. Review of the literature showed systemic rituximab had provided clinical improvement at shorter follow up in 14 of 15 cases when used as a salvage therapy. CONCLUSIONS: Systemic rituximab therapy seems to be an effective therapy for IOI as salvage or first-line therapy with long-term clinical durability.

The potential of tear proteomics for diagnosis and management of orbital inflammatory disorders including Graves' ophthalmopathy.

BACKGROUND: Orbital compartments harbor a variety of tissues that can be independently targeted in a plethora of disorders resulting in sight-threatening risks. Orbital inflammatory disorders (OID) including Graves' ophthalmopathy, sarcoidosis, IgG4 disease, granulomatosis with polyangiitis, and nonspecific orbital inflammation constitute an important cause of pain, diplopia and vision loss. Physical examination, laboratory tests, imaging, and even biopsy are not always adequate to classify orbital inflammation which is frequently deemed "nonspecific". Tear sampling and testing provide a potential "window" to the orbital disease process through a non-invasive technique that allows longitudinal sampling as the disease evolves. Using PubMed/Medline, we identified potentially relevant articles on tear proteomics published in the English language between 1988 and 2021. Of 303 citations obtained, 225 contained empirical data on tear proteins, including 33 publications on inflammatory conditions, 15 in glaucoma, 15 in thyroid eye disease, 1 in sarcoidosis (75) and 2 in uveitis (77,78). Review articles were used to identify an additional 56 relevant articles through citation search. In this review, we provide a short introduction to the potential use of tears as a diagnostic fluid and tool to investigate the mechanism of ocular diseases. A general review of previous tear proteomics studies is also provided, with a focus on Graves' ophthalmopathy (GO), and a discussion of unmet needs in the diagnosis and treatment of orbital inflammatory disease (OID). The review concludes by pointing out current limitations of mass spectrometric analysis of tear proteins and summarizes future needs in the field.

IgG4-related disease in patients with idiopathic orbital inflammation.

BACKGROUND: To identify the prevalence of positive IgG4 immunostaining in orbital tissue among patients previously diagnosed with nongranulomatous idiopathic orbital inflammation (IOI) and to compare the clinical characteristics of patients with and without IgG4-positive cells. METHODS: A retrospective review of all patients with a histopathologic diagnosis of IOI was performed. Immunohistochemical staining was performed to identify IgG-positive cells and IgG4-positive cells. Multivariate analysis was performed using likelihood ratio-test logistic regression on the differences between IgG4-related disease (IgG4-RD) and non-IgG4-RD. RESULTS: Of the 45 patients included, 21 patients (46.7%) had IgG4-positive cells, with 52.4% being male and a mean age of 55.9 ± 13.4 years. Bilateral ocular adnexal involvement (adjusted odds ratio [aOR] = 9.45; P = 0.016) and infraorbital nerve enlargement (aOR = 12.11; P = 0.008) were frequently found in IgG4-RD patients. Complete remission occurred in 23.8% of IgG4-RD patients and 41.7% of non-IgG4-RD patients. IgG4-RD patients had more frequent recurrent disease than non-IgG4-RD patients. CONCLUSIONS: Nearly 50% of IgG4-RD patients were previously diagnosed with biopsy-proven IOI. IgG4-RD was more frequent in patients with bilateral disease and infraorbital nerve enlargement, showing the importance of tissue biopsy in these patients. Immunohistochemistry studies of all histopathology slides showing nongranulomatous IOI are highly recommended to evaluate for IgG4-RD.

Case Report: Idiopathic Sclerosing Orbital Inflammation.

SIGNIFICANCE: Idiopathic sclerosing orbital inflammation (ISOI) is characterized by insidious, chronic, progressive inflammation and fibrosis that damage ocular structures and produce a mass effect. This case highlights the challenges in diagnosis and management of ISOI, as well as the associated ocular morbidities, including potential vision loss. PURPOSE: The purpose of this study was to provide education regarding a rare condition that exhibits variable presentation and has an unpredictable success rate with regard to treatment paradigm. Improved therapeutic options are promising. Ultimately, early detection and management are key and may allow for better visual outcome. CASE REPORT: A 46-year-old woman presented with complaints of chronic right-sided facial headaches and eye pain and gradual right globe prominence over the previous 6 months. Worsening vision and decreased right peripheral visual field were also noted. Upon examination, an afferent pupillary defect and florid disc edema were evident. Imaging studies revealed an orbital and extraorbital infiltrative mass involving the right orbital apex, inferior orbital fissure, pterygopalatine fossa, and cavernous sinus. Right anterior orbitotomy with biopsy revealed fragments of fibroconnective and adipose tissue with sclerosis and chronic focal inflammation, consistent with ISOI. Treatment included intravenous methylprednisone, followed by oral prednisone, beginning at 60 mg/d with a slow taper thereafter. Signs and symptoms improved dramatically and eventually resolved. Vision significantly improved, and the afferent pupillary defect resolved. The patient remained asymptomatic at 3-month follow-up. CONCLUSIONS: Idiopathic sclerosing orbital inflammation is difficult to diagnose and manage. No large studies exist because of the rare nature of the disease. Slowly progressive, nonspecific signs and symptoms may delay recognition and treatment. Orbital imaging and histopathologic analysis are critical for definitive diagnosis. Conventional treatment with corticosteroids is not uniformly successful, but newer combined therapy options can improve outcomes. Early identification and treatment are key to management and ultimate preservation of function and vision.

Rituximab Therapy for Recalcitrant Idiopathic Sclerosing Orbital Inflammation.

Three patients (3 female patients; aged 7, 35, and 61 years) who had recalcitrant idiopathic sclerosing orbital inflammation were treated with rituximab. The disease was bilateral in 1 patient (4 orbits in total): diffuse in 2 and localized in 2 orbits. It caused optic neuropathy in 1 orbit of each patient. Conventional immunotherapy and tumor debulking surgery were unsuccessful in controlling the disease. After rituximab infusions (375 mg/m2/week for 4 weeks), all patients improved symptomatically. Radiologically, the local lesions resolved completely and diffuse lesions partially. Two patients with recurrent inflammation during follow up (78, 58, and 51 months) responded well to immediate, short-term steroid treatments. Short-term rituximab therapy can induce effective remissions in patients with refractory idiopathic sclerosing orbital inflammation. Early and local lesions may respond better to treatment than diffuse lesions. Nevertheless, inflammatory exacerbations can occur during late follow up.

Bilateral idiopathic orbital pseudotumour in a child: a case report.

BACKGROUND: Idiopathic orbital pseudotumour is rare in children. We report a case of bilateral paediatric idiopathic orbital pseudotumour and review the characteristics of this case. CASE PRESENTATION: A 14-year-old female patient presented at our Department of Pulmonary and Critical Care Medicine (PCCM) with complaints of recurrent severe cold and cough for 3 weeks, which had been treated with an intravenous antibiotic. Meanwhile, the patient developed swelling of both eyelids during the period of cold and cough, but her symptoms did not improve after the ocular administration of tobramycin dexamethasone eye drops. The patient was referred from the respiratory medicine ward to our department because of gradually worsening ocular pain, visual deterioration, increased intraocular pressure and serious nausea/vomiting within 24 h of hospitalization. The diagnosis of bilateral idiopathic orbital pseudotumour was made ultimately because of the course of the disease, exclusion of diagnoses such as bacterial ocular infection or malignant tumours and subsequent evidence from orbital magnetic resonance imaging (MRI). Favourable progress in the ocular tension and eyelid swelling was achieved through treatment with intravenous dexamethasone. The binocular intraocular pressure gradually declined to approximately 15 mmHg, and there was favourable progression in the patient's vision to 20/40 in both eyes on the ninth day of hospitalization. CONCLUSIONS: Our patient developed rapidly progressive acute orbital signs and symptoms and anterior inflammation, such as pain, proptosis, limited ductions, periorbital oedema, chemosis, vision loss and high intraocular pressure. This case highlights that idiopathic orbital pseudotumour is an uncommon but important cause of acute orbital syndrome in children.

[Painful orbital swelling in a 61-year-old female patient]. / Schmerzhafte Schwellung der Orbita bei einer 61-jährigen Patientin.

Adenocarcinoma of the esophagus is the oncologic entity with the most progressive incidence in western countries over the last 30 years. This is caused by, among other factors, a growing rate of obesity and the associated gastroesophageal reflux disease. Typical sites of metastasis include the liver, lymph nodes and peritoneum. Adrenal glands and thoraco-abdominal skeleton can also be affected. Cerebral metastasis is infrequent and there are only a handful cases described in the literature. The case presented here relates to a 61-year-old woman with osteolytic metastasis that was infiltrating the orbital cavity and was initially diagnosed as a dacryoadenitis.

Neuro-ophthalmic complications of IgG4-related disease.

PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is increasingly recognized as a fibroinflammatory disease with a plethora of organ-specific manifestations but a particular predilection for head and neck tissues, including the nervous system. This review discusses general features and organ-specific presentations of IgG4-RD as well as treatment considerations, particularly emphasizing features of neuro-ophthalmic interest. RECENT FINDINGS: IgG4-RD is emerging as a common cause of several fibroinflammatory disorders in the head and neck that were previously considered idiopathic, such as sclerosing orbital pseudotumor, orbital myositis, hypophysitis, and hypertrophic pachymeningitis. New and unusual presentations continue to be described, including a number of vascular manifestations. Substantial progress has been made in elucidating the cell types involved in IgG4-RD, and new pathogenic models are being proposed. Although clinicopathologic correlation remains the cornerstone of diagnosis, ancillary tests such as flow cytometry for circulating plasmablasts and PET-computed tomography have high sensitivity, and certain radiologic features are recognized to be particularly suggestive, such as infraorbital nerve enlargement in IgG4-RD orbitopathy. IgG4-RD often responds to steroids but incomplete responses and relapses are common. Rituximab is emerging as a promising new therapy. SUMMARY: The current review summarizes manifestations of IgG4RD that are of particular relevance to neuro-ophthalmic practice.

Bilateral Orbital Pseudotumor in a 3-Year-Old Child: A Case Report.

Orbital pseudotumor is a rare, idiopathic, inflammatory process within the orbit. Early diagnosis is essential to prevent corneal, retinal and extraocular muscle damage. This article describes the presentation and clinical course of a 3-year-old male with bilateral orbital pseudotumor.

Intralesional corticosteroid injections as treatment for non-infectious orbital inflammation.

A retrospective single-center chart review identified 19 patients treated with intralesional corticosteroid injection between 2007 and 2015 for orbital inflammatory disease. Patients were treated in the office, or intraoperatively at the time of orbital exploration and biopsy, with 5-40 mg of triamcinolone acetonide. Average follow up time was 2.44 years. Information recorded included visual acuity and eyelid position measurements, pre-injection treatment, post-injection treatment, complications, and exam findings. Nine of the identified patients received intraoperative injections, 9 in the office setting, and one received an injection in each. Eight patients (42.1%) were on oral corticosteroids prior to the injection. All patients showed initial clinical improvement after 1-2 injections and no more than a 1-2 line difference in visual acuity. Overall, six patients (31.6%) required repeat injections due to recurrence of inflammation, and seven (36.8%) required additional oral corticosteroids beyond the initial taper. Patients pre-treated with oral corticosteroids were more likely to need repeat injections (83.3% vs 16.7% respectively, p = 0.04). Compared to injections performed in the office setting, intraoperative injections were associated with fewer repeat injections (0% vs. 60.0% respectively, p = 0.01) and less need for post-injection oral steroids (0% vs. 58.3% respectively, p < 0.01). There were no systemic or permanent side effects observed from the injections. Two patients (10.5%) had transient post-injection intraocular pressure elevation, which resolved. Intralesional orbital corticosteroid injection is an effective first-line and adjunctive treatment for localized and diffuse non-infectious orbital inflammation.

A rare case of orbital granulomatous inflammation from explosive hydraulic oil masquerading as orbital cellulitis.

The differential diagnosis for acute orbital inflammation is broad. We report a case of granulomatous orbital inflammation due to high-pressure oil injury to the orbit presenting as an atypical orbital cellulitis. Here we review the presentation and treatment of orbital inflammation from oil.

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.

IgG4-related disease in the eye and ocular adnexa.

PURPOSE OF REVIEW: IgG4-related disease is a multi-organ fibro-inflammatory disease with characteristic histopathology showing lymphoplasmacytic infiltration, increased IgG4+ plasma cells and elevated IgG4/IgG ratios (>40%). The lacrimal gland is the most common ocular site of involvement. Scleritis and intraocular involvement in IgG4-related ophthalmic disease (IgG4-ROD) have recently been reported. The purpose of this review is to describe orbital and intraocular IgG4-ROD with a focus on publications since 2016. RECENT FINDINGS: Case reports of scleritis and uveitis in IgG4-ROD have been described since 2012. Systemic prednisone is recommended as the first-line treatment, but immunosuppressive therapy may be required for steroid-sparing or in steroid-resistant cases. High rates of systemic IgG4-RD involvement exist in patients with bilateral IgG4-ROD or if the lacrimal gland is involved. Rituximab is the most specific immune targeted therapy available with high rates of remission. SUMMARY: IgG4-ROD is an emerging cause of scleritis and uveitis and should be considered in any patient with multisystem inflammatory disease. New targeted immune therapies may improve outcomes and lead to clinical remission.

Idiopathic Orbital Inflammation Associated With Relapsing Polychondritis.

The authors describe a patient with recurrent idiopathic orbital inflammatory disease as an unusual presentation of relapsing polychondritis. There are very few reported cases in the literature of relapsing polychondritis associated with idiopathic orbital inflammation. Clinicians should be aware of the orbital and ophthalmic presentations of relapsing polychondritis.