IgG4-related Orbital Disease Presenting as an Orbital Apex Lesion.

IgG4-related disease is an uncommon multisystem inflammatory disease characterized by tissue infiltration by IgG4 plasma cells, extensive fibrosis, and sclerosing inflammation. Diffuse orbital involvement extending to the orbital apex and cavernous sinus has been reported, but a solitary well-circumscribed lesion at the apex has not been previously reported. Herein, we report a unique case of IgG4-related orbital disease presenting as a solitary well-circumscribed orbital apex lesion causing subacute visual decline in a 45-year-old male. MRI demonstrated bilateral lacrimal gland and infraorbital nerve enlargement and an 18 × 7 mm left orbital apex lesion demonstrating homogeneous contrast enhancement and isointense signal on T2. He was initially treated with tapering systemic corticosteroid therapy with improvement in his vision; however, he experienced visual deterioration 3 months later with recurrent inflammation. He subsequently commenced high-dose systemic corticosteroid therapy and rituximab infusions with improvement of left visual acuity to 6/7.5 + 2.

Magnetic Resonance Imaging of Idiopathic Orbital Myositis.

PURPOSE: To characterize the qualitative and quantitative features of idiopathic orbital myositis (IOM) on MRI. METHODS: This was a multicenter retrospective study of patients with active IOM with MRI. Patients with incomplete clinical records, poor-quality or interval scans without active myositis, and specific orbital myositis (i.e., orbital myositis secondary to an identified condition) were excluded. An enlargement ratio was calculated by dividing the diameters of the affected extraocular muscle (EOM) by the contralateral unaffected EOM. RESULTS: Twenty-four patients (mean age: 44.4 ± 17.8 years-old, male: 11) between 2011 and 2022 were included. One case (4.2%) was pediatric (17 years old), and 6 cases presented with recurrence. Active IOM was characterized by fusiform EOM enlargement, high T2 signal, and contrast enhancement. Average maximal EOM diameters ranged from 4.6 to 7.7 mm (enlargement ratio: 1.4-2.2). Eighteen (75%) patients had single EOM involvement, most commonly the medial rectus. Other ipsilateral structures affected included focal orbital fat (16/24, 66.7%) and lacrimal gland (8/24, 33.3%). Contralateral changes in the EOM and/or lacrimal gland were observed in 7 patients (29.2%). Patients presenting with recurrence were likely to develop ongoing recurrent episodes (p = 0.003). CONCLUSIONS: Various radiological patterns of involvement described including EOM enlargement, contrast enhancement, abnormal signal, and involvement of other orbital structures are indicative of active IOM. IOM remains a heterogeneous spectrum of acute and chronic clinico-radiological presentations. Inflammation may involve other ipsilateral or contralateral orbital structures or may be bilateral despite presenting clinically as unilateral disease. Quantitative measurements may have utility in differentiating IOM from other causes of orbital myositis.

Ameloblastic Carcinoma With Orbital Invasion.

Ameloblastic carcinomas are malignant tumors arising from the odontogenic epithelium and defined as having features of ameloblastic differentiation in addition to cytological features of malignancy. Orbital involvement is rare and generally involves invasion of the orbital floor, apex, or soft tissue. This report describes an advanced presentation of ameloblastic carcinoma with orbital invasion and provides a review of the literature. A 58-year-old male presented with a 2-year history of a mid-facial mass, causing intracranial invasion and distortion of most skull foramina, nasopharynx, nasal cavity, and both orbits. Notably, there was an en-plaque pattern of circumferential tracking of the tumor along both orbital walls without invasion beyond the extraconal space, causing compression of the orbital apex and proptosis. Histology demonstrated nests of ameloblastic carcinoma and the advanced tumor was deemed nonresectable, with treatment being palliative.

Sinonasal Chondrosarcoma With Unusual Orbital Invasion.

A case is presented of a 43-year-old male with a chronic history of progressive nasal obstruction and epiphora. MRI confirmed a heterogeneous mass involving the middle and superior turbinates with T2 hyperintense and calcified components, with extension into the inferomedial orbit. Tissue biopsy revealed a grade 2 chondrosarcoma of the conventional subtype. Endonasal wide local resection of the lesion was performed with clear margins. The patient had no functional sequelae and will undergo routine surveillance.

Transorbital Endoscopic Approach to the Foramen Rotundum for Infraorbital Nerve Stripping.

PURPOSE: To develop and evaluate a transorbital endoscopic approach to the foramen rotundum to excise the maxillary nerve and infraorbital nerve branch. METHODS: Cadaveric dissection study of 10 cadaver heads (20 orbits). This technique is predicated upon 1) an inferior orbital fissure release to facilitate access to the orbital apex and 2) the removal of the posterior maxillary wall to enter the pterygopalatine fossa (PPF). Angulations along the infraorbital nerve were quantified as follows: the first angulation was measured between the orbitomaxillary segment within the orbital floor and the pterygopalatine segment suspended within the PPF, while the second angulation was taken between the pterygopalatine segment and maxillary nerve as it exited the foramen rotundum. With refinement of the technique, the minimum amount of posterior maxillary wall removal was quantified in the final 5 cadaver heads (10 orbits). RESULTS: The mean distance from the inferior orbital rim to the foramen rotundum was 45.55 ± 3.24 mm. The first angulation of the infraorbital nerve was 133.10 ± 16.28 degrees, and the second angulation was 124.95 ± 18.01 degrees. The minimum posterior maxillary wall removal to reach the PPF was 11.10 ± 2.56 mm (vertical) and 11.10 ± 2.08 mm (horizontal). CONCLUSIONS: The transorbital endoscopic approach to an en bloc resection of the infraorbital nerve branch up to its maxillary nerve origin provides a pathway to the PPF. This is relevant for nerve stripping in the context of perineural spread. Other applications include access to the superior portion of the PPF in selective biopsy cases or in concurrent orbital pathology.

Corneal Neurotization for Neurotrophic Keratopathy: A Multicentre Experience.

PURPOSE: Corneal neurotization is an emerging technique that offers potential for visual rehabilitation in neurotrophic keratopathy. This study reports on a multicenter experience and outcomes for both direct and indirect methods of corneal neurotization. METHODS: Retrospective case series. Sixteen patients with neurotrophic keratopathy who underwent corneal neurotization across 5 centers in Australia and Israel were identified for inclusion. Corneal neurotization was performed via direct neurotization from the ipsilateral or contralateral supraorbital/supratrochlear nerve or by the use of an interpositional sural nerve graft. Change in corneal sensitivity (measured in millimeters by the Cochet-Bonnet aesthesiometer), visual acuity, and corneal health. RESULTS: Over a mean follow-up period of 31.3 months (range: 3 months-8 years), mean corneal sensitivity improved from 3.6 mm (range: 0-25 mm) to 25.3 mm (range: 0-57 mm). Visual acuity improved on average from 20/380 to 20/260. Twelve of 16 patients (75.0%) improved in at least 2 out of the 3 main outcome measures. Nine patients (56.3%) showed an improvement in visual acuity; 13 (81.3%) showed an improvement in average corneal sensitivity; and 11 (68.8%) showed an improvement in corneal health. There were no intraoperative or postoperative complications. CONCLUSIONS: Corneal neurotization is an emerging surgical treatment option for the management of neurotrophic keratopathy. With appropriate case selection, outcomes are favorable and complication rates are low, for a condition that is otherwise challenging to manage. Patients with severe neurotrophic keratopathy should be considered for this surgical treatment option.

Extraocular muscle enlargement and proptosis in carotid cavernous fistulas.

PURPOSE: To evaluate the prevalence and pattern of extraocular muscle enlargement and proptosis in patients with carotid cavernous fistulas (CCF). METHODS: We conducted a retrospective study on patients with digital subtraction angiography (DSA) confirmed CCFs with neuroimaging (computed tomography or magnetic resonance imaging) performed prior to the DSA. The maximum extraocular muscle diameters were recorded. Extraocular muscles were considered enlarged if they were greater than two standard deviations above the normal muscle diameters. Proptosis was defined as the distance between the interzygomatic line to the anterior globe of ≥2 mm compared to the contralateral orbit or ≥21 mm. RESULTS: Forty orbits from 20 patients were included. The mean age of participants was 65 ± 15 years and 13 (65%) were female. Thirteen (65%) fistulas were indirect and seven (35%) were direct. There was enlargement of at least one muscle in 11 (27.5%) orbits, and this was not correlated with the type of fistula (direct/indirect). The inferior rectus was most commonly enlarged in seven orbits (17.5%), followed by the medial rectus in five orbits (12.5%). Proptosis was found in 17 (43%) orbits and was more common ipsilateral to the fistula (58% ipsilateral group vs 19% contralateral group, p < .01). CONCLUSION: Extraocular muscle enlargement was observed in over one-fourth of CCFs. When enlarged, the inferior and medial rectus muscles are most commonly involved. These findings may help clinicians and radiologists when evaluating the CT or MRI scans of patients with suspected CCFs.

Microbiology of acute bacterial dacryocystitis: a tertiary institutional experience in South Australia.

PURPOSE: To provide a comprehensive microbiological profile of bacterial dacryocystitis in South Australia. By identifying the specific microorganism and antibiotic susceptibility, this study intends to aid ophthalmologists in choosing appropriate empirical antibiotic therapies and development of evidence-based clinical guidelines. METHOD: A retrospective study was conducted at the Royal Adelaide Hospital (RAH) over five years (2018-2023) of patients with acute dacryocystitis. The study included 43 patients, and data encompassed demographic information, clinical presentation, microbiological analysis, management, and outcomes. Patients with chronic dacryocystitis were excluded. RESULTS: Among the 43 patients included in the study (female 28 (65%), mean age: 64 years old), the most common clinical features were pain (74%) and swelling (70%). Organisms were identified in 49% of patients, with the predominant bacteria being Staphylococcus aureus (42%), Streptococcus species (19%), and Escherichia coli (8%). Aggregatibacter species (8%), Morganella morganii (4%), Enterobacter cloaceae (4%), Hafnia alvei (4%), mixed anaerobes (4%), E coliforms (4%) and Pseudomonas aeruginosa (4%) were also identified. The most frequently prescribed empirical antibiotics were amoxicillin-clavulanic acid (50%), flucloxacillin (33%) and cefalexin (18%). CONCLUSION: The microbiological trends of acute dacryocystitis have largely remained consistent, with a predominance of Gram positive organisms. This is the most recent profile analysis of acute dacryocystitis in South Australia and will help form evidence-based clinical guidelines.

Aneurysmal Bone Cyst of the Orbit With USP6 Gene Rearrangement.

PURPOSE: Aneurysmal bone cyst (ABC) of the orbit is a very rare tumor, occurring mostly in the pediatric population, and can result in sight threatening complications and disfigurement. This review discusses previously reported cases with a focus on evolving treatment options and molecular genetics. METHODS: We report the youngest case of an orbital ABC with a confirmed gene fusion: a 17-month-old girl, with confirmed FGFR-UPS6 (Fibroblast Growth Factor Receptor 1-ubiquitin specific peptidase 6/tre-2). A literature search for relevant publications on the topic was performed via Medline and PubMed, with the appropriate data extracted. RESULTS: Thirty-two cases of orbital aneurysmal bone cyst were identified in the literature. Presentations are varied and can include pain, proptosis, decreased vision, and extraocular motility disturbance. Typical imaging and histopathology findings are discussed, in particular the usefulness of identifying USP6 gene arrangements. Treatment modalities are reviewed including surgery, embolization, and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors. Recurrences can occur, usually within 2 years. CONCLUSIONS: Orbital ABC is a neoplasm that presents unique diagnostic and treatment challenges. Gene rearrangements can confirm primary ABC and rule out other underlying pathology. Disfigurement and sight threatening complications can occur due to both the disease process and with treatment. Outcomes may be improved with the use of systemic therapy.

Recurrence Following Globe Sparing Excision for Basal Cell Carcinoma with Anterior Orbital Invasion.

PURPOSE: Globe-sparing excision for periocular basal cell carcinoma (BCC) with orbital invasion has evident benefits, but the ensuing morbidity and characteristics of recurrence are not well elucidated. This study aims to describe the extent of visual morbidity following globe-sparing excision, and the clinicoradiological characteristics of tumor recurrence. METHODS: Multicentre retrospective case series. RESULTS: Eight patients were identified for inclusion in this series. Time to recurrence following globe-sparing excision ranged from 3 to 12 years. Seven patients (87.5%) presented with recurrent disease originating from the medial canthus. Clinical features at presentation included contracture ( n =4, 50.0%), upper lid ptosis ( n =3, 37.5%), a palpable mass ( n =2, 25.0%), and hypoesthesia ( n =2, 25.0%). Radiologically, tumor recurrence was predominantly characterized by isointense signals on T1 and T2-weighted sequences ( n =5, 62.5%) with moderate contrast enhancement. The most common histologic subtype in recurrent tumors was a mixed nodular and infiltrative growth pattern ( n =5, 62.5%). Perineural invasion was a feature in four (50%) cases. Salvage therapy in the form of exenteration was performed in seven cases. Vismodegib and adjuvant radiotherapy were provided for one case with surgically unresectable tumor recurrence. CONCLUSIONS: Globe-sparing excision for invasive periocular BCC can be complicated by late recurrence that develops rapidly despite silent neuroimaging for years. Early clinical signs are subtle. High-risk features predictive of recurrence include medial canthus location, mixed histological subtypes, and perineural invasion. Patients with such characteristics require lifelong clinical and imaging surveillance following globe-sparing excision.

Varicella zoster virus meningoencephalitis presenting as orbital myositis - a case report.

The authors present a case of meningoencephalitis caused by Varicella zoster virus (VZV) infection, which initially manifested as orbital myositis followed by rapid progression to orbital apex syndrome, meningoencephalitis and death. There was no development of a cutaneous rash. An orbital biopsy demonstrated VZV infection, which was confirmed on a lumbar puncture. In this case, VZV meningoencephalitis was not responsive to steroid or antiviral therapy. This case highlights an atypical presentation of VZV with orbital myositis preceding intracranial involvement.

Disseminated thrombosis of the internal jugular vein, superior ophthalmic vein and cavernous sinus as the primary manifestation of occult malignancy: a case report.

Internal jugular vein (IJV) thrombosis is a life-threatening condition most often associated with local risk factors such as head or neck infection or central venous catheterisation. Underlying malignancy is a rare but important aetiology to consider in patients presenting with spontaneous IJV thrombosis. We describe a case of necrotic cervical lymphadenopathy with thrombosis of the IJVs, cavernous sinuses and superior ophthalmic veins in a patient with metastatic squamous cell carcinoma, which was further complicated by an orbital compartment syndrome. The differential diagnosis of IJV thrombosis includes a range of infective, metastatic and thrombophilic pathologies. This case illustrates that, in the absence of an underlying precipitating factor, spontaneous IJV thrombosis should prompt further systemic investigations. Furthermore, patients with thrombotic events affecting the orbital venous drainage system should be monitored closely for signs of an acute orbital compartment syndrome.

Orbital apex syndrome in herpes zoster ophthalmicus clinical features, treatment and outcomes: a case series and literature review.

Orbital Apex Syndrome (OAS) complicating Herpes Zoster Ophthalmicus (HZO) is associated with significant visual impairment. We present four patients with HZO OAS, to highlight clinical features and outcomes in order to promote earlier recognition and management of this potentially sight-threatening complication. CT and MRI imaging findings included expansion and enhancement of extraocular muscles and intraconal fat and involvement of the orbital apex and cavernous sinus. All patients received systemic steroid and antiviral therapy, but a standardised dosage and duration of treatment remains to be defined. Final visual acuity and extraocular motility outcomes were variable.

Optic nerve infiltration in systemic non Hodgkin lymphoma.

Optic nerve infiltration secondary to systemic non-Hodgkin lymphoma (NHL) is a rare phenomenon. We present a 55-year-old man with low-grade systemic NHL who initially presented with an isolated optic neuropathy and non-specific neurological symptoms. We further present a literature review of systemic NHL with radiological evidence of optic nerve infiltration. On magnetic resonance imaging, the characteristic features include optic nerve enhancement and enlargement, while leptomeningeal enhancement is uncommon. Cerebrospinal fluid analysis and optic nerve sheath biopsy can return false negative results, and when such investigations are inconclusive, biopsy of the optic nerve substance has a high diagnostic yield. Although rare, lymphomatous optic nerve infiltration must be considered in the differential diagnosis of a pale swollen optic disc.

Cutaneous squamous cell carcinoma radiographically mimicking infiltration into the lacrimal gland.

Cutaneous squamous cell carcinoma (SCC) is a common malignancy of the skin, with the potential for local invasion and metastasis. Here, we present a case series of two patients with SCCs, suggesting radiological infiltration of the lacrimal gland on magnetic resonance imaging. However, histopathological examination revealed lymphoplasmacytic infiltration of the lacrimal gland consistent with dacryoadenitis, with no evidence of SCC infiltration. Our cases highlight the potential for peritumoural inflammation to cause dacryoadenitis and radiologically mimic tumour infiltration into the lacrimal gland.

Multi-resistant Enterobacter cloacae dacryocystitis and preseptal cellulitis: case and review of literature.

A 61-year-old man with no significant past medical history presented to a quaternary ophthalmic referral center with acute right-sided medial canthal pain, periorbital edema, and erythema despite oral antibiotic therapy. CT imaging confirmed the presence of right preseptal cellulitis and lacrimal sac aspiration identified Enterobacter cloacae. A diagnosis of acute right-sided dacryocystitis with preseptal cellulitis was made. He was successfully treated with broadening of antibiotic therapy to intravenous meropenem. Symptomatic resolution was noted on follow-up without evidence of disease recurrence. This unusual case of Enterobacter cloacae dacryocystitis and preseptal cellulitis highlights the increasing prevalence and challenges of treating these uncommon organisms.

Microbiology of bacterial orbital cellulitis-tertiary institutional experiences in South Australia: a multi-centre retrospective study.

PURPOSE: This study describes the microbiology of bacterial orbital cellulitis (OC) over an 11-year period and its clinical associations at three tertiary institutions in Adelaide, South Australia. METHODS: Multi-centre retrospective study of the microbiology of bacterial OC between January 2012 and August 2022. Pre-septal cellulitis was excluded. Differences in means were determined by the Independent Samples t-test, and categorical data was analysed via Pearson's Chi square. A P-value < 0.05 was statistically significant. RESULTS: 99 patients (male: 69, mean age: 22.0 ± 23.8 years old), of which 70.7% were aged ≤ 18 years. Sinus and orbital abscess cultures had the greatest positive yield (73.7%). Frequency of organisms: Streptococcus species (34.3%), Staphylococcus aureus (28.3%), Haemophilus species (5.1%), mixed anaerobes (3.0%), Enterobacter cloacae (2.0%), Moraxella catarrhalis (1.0%), Pseudomonas aeruginosa (1.0%), Corynebacterium species (1.0%), Klebsiella pneumoniae (1.0%), Proteus mirabilis (1.0%), Citrobacter koseri (1.0%), and Enterococcus species (1.0%). Streptococcus species predominated in the paediatric population, with a statistically significant difference in mean age between Streptococcus species and Staphylococcus aureus (14.1 ± 16.5 vs 27.6 ± 24.6 years old, respectively) (P = 0.028). No organism was cultured in 32.3% of cases. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 28.6% of all Staphylococcus aureus isolates, with 50% occurring between 2021 and 2022. CONCLUSION: Yearly microbiological trends have remained largely constant in South Australia. The causative organism was not identified in 32.3% of cases, further emphasising appropriate empirical antibiotics, and obtaining microbiology from various sources. MRSA OC remains of increased clinical and public health concern and may be associated with a more aggressive disease course.

Orbital inflammation following COVID-19 vaccination: A case series and literature review.

PURPOSE: The purpose of the study was to report three cases of orbital inflammation following administration of the COVID-19 vaccination, manifesting as Tolosa-Hunt syndrome (THS) and orbital myositis. METHOD: A retrospective case series and literature review of patients who developed orbital inflammation following a COVID-19 vaccination. RESULTS: One patient presented with Tolosa-Hunt syndrome (THS) 14 days following her third (booster) COVID-19 vaccination, one patient developed orbital myositis 10 days following his first COVID-19 vaccination and one patient developed recurrent orbital myositis 1 and 7 days following her second and fourth COVID-19 vaccination. All patients received the Comirnaty vaccine (Pfizer-BioNTech). A thorough systemic autoimmune disease workup in both patients was unremarkable. Two patients had a prior history of orbital inflammation, with previous involvement of other different orbital structures. Characteristic MRI features for each pathology were observed, supporting the clinical presentation of THS and orbital myositis. There was complete resolution of THS following corticosteroids, with no recurrence at 2 months. Meanwhile, one case of orbital myositis self-resolved at 2 months without use of systemic corticosteroids, while the other patient with orbital myositis required treatment with intra-orbital steroid injections and oral corticosteroids. CONCLUSION: Orbital inflammation has been recognised as a rare adverse effect following COVID-19 vaccination. We present a case series of THS and orbital myositis as varied presentations of this entity.

Methicillin-resistant Staphylococcus aureus-associated orbital cellulitis: a case series.

PURPOSE: In recent years, methicillin-resistant Staphylococcus aureus (MRSA) orbital cellulitis (OC) has drawn increasing clinical and public health concern. We present a case series of MRSA OC encountered at four Australian tertiary institutions. METHODS: A multi-centre retrospective case series investigating MRSA OC in Australia from 2013 to 2022. Patients of all ages were included. RESULTS: Nine cases of culture-positive non-multi-resistant MRSA (nmMRSA) OC were identified at four tertiary institutions across Australia (7 male, 2 female). Mean age was 17.1 ± 16.7 years (range 13-days to 53-years), of which one was 13 days old, and all were immunocompetent. Eight (88.9%) patients had paranasal sinus disease, and seven (77.8%) had a subperiosteal abscess. Four (44.4%) had intracranial extension, including one (11.1%) case which was also complicated by superior sagittal sinus thrombosis. Empirical antibiotics, such as intravenous (IV) cefotaxime alone or IV ceftriaxone and flucloxacillin, were commenced. Following identification of nmMRSA, targeted therapy consisting of vancomycin and/or clindamycin was added. Nine (100%) patients underwent surgical intervention. Average hospital admission was 13.7 ± 6.9 days (range 3-25 days), with two patients requiring intensive care unit (ICU) admission due to complications related to their orbital infection. All patients had favourable prognosis, with preserved visual acuity and extraocular movements, following an average follow-up period of 4.6 months (range 2-9 months). CONCLUSION: NMMRSA OC can follow an aggressive clinical course causing severe orbital and intracranial complications across a wide demographic. However, early recognition, initiation of targeted antibiotics and surgical intervention when required can effectively manage these complications and achieve favourable visual outcomes.

Rational design of chimeric antigen receptor T cells against glypican 3 decouples toxicity from therapeutic efficacy.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has yielded impressive clinical results in hematological malignancies and is a promising approach for solid tumor treatment. However, toxicity, including cytokine-release syndrome (CRS) and neurotoxicity, is a concern hampering its broader use. METHODS: In selecting a lead CAR-T candidate against the oncofetal antigen glypican 3 (GPC3), we compared CARs bearing a low- and high-affinity single-chain variable fragment (scFv) binding to a similar epitope and cross-reactive with murine GPC3. RESULTS: Where the high-affinity CAR-T cells were toxic in vivo, the low-affinity CAR maintained cytotoxic function against antigen-positive tumor cells but did not show toxicity against normal tissues. High-affinity CAR-induced toxicity was caused by on-target, off-tumor binding, based on the observation that higher doses of the high-affinity CAR-T caused toxicity in non-tumor-bearing mice and accumulated in organs with low expression of GPC3. To explore another layer of controlling CAR-T toxicity, we developed a means to target and eliminate CAR-T cells using anti-TNF-α antibody therapy after CAR-T infusion. The antibody was shown to function by eliminating early antigen-activated, but not all, CAR-T cells, allowing a margin where the toxic response could be effectively decoupled from antitumor efficacy with only a minor loss in tumor control. By exploring additional traits of the CAR-T cells after activation, we identified a mechanism whereby we could use approved therapeutics and apply them as an exogenous kill switch that eliminated early activated CAR-T following antigen engagement in vivo. CONCLUSIONS: By combining the reduced-affinity CAR with this exogenous control mechanism, we provide evidence that we can modulate and control CAR-mediated toxicity.