Faculty Bibliography

A 68-year-old man with a history of remote sinus surgery presented with several months of progressive diplopia, proptosis, and epiphora. He was found to have a large, cystic mass in the lateral extraconal space of the right orbit, which was removed. Pathology demonstrated an epidermoid cyst with recurrence at post-operative month 3. Follow-up resection was performed with the insertion of a modified Jones tube into the maxillary sinus to serve as a persistent outlet and prevent future recurrence. At post-operative month 18 after tube insertion, he remains without disease recurrence. The authors describe this novel technique as a method to prevent recurrence in orbital cyst management.

INTRODUCTION/BACKGROUND:Angioinvasive fungal sinusitis (AIFS) is a rapidly progressive, highly morbid infection. It can be challenging to obtain an early diagnosis, but intervention in the acute period is crucial for prognosis. Previous literature has identified numerous radiographic features with high sensitivity and specificity for AIFS, even in early disease. Bedside nasal endoscopy can substantiate the diagnosis but can also yield false negative results. Initially, these patients may present to the ophthalmologist. Thus, to avoid visual and potentially life-threatening complications, subtle clinical signs in conjunction with suspicious radiographic features must be promptly recognized by the ophthalmologist and escalated appropriately. We review, for the benefit of the ophthalmic community, the salient radiographic features of AIFS and integrate them into a decision-making algorithm for diagnostic workup and management. METHODS:A literature search was conducted using a comprehensive keyword search in the Pubmed and Embase databases. English studies from 1988 to 2022 describing the radiographic features of AIFS queried. Literature on the newly described entity, COVID-19 COVID-19-associated mucormycosis was included. The authors collected the most frequently reported indicators of AIFS. RESULTS:The authors review 4 radiographic findings that are frequently associated with AIFS, including in the early stages of disease: 1) loss of contrast enhancement in the nasal turbinate and maxilla (i.e., "black turbinate and maxillary sign"), (2) periantral involvement seen as changes in density, fat stranding or obliteration of the anterior, retromaxillary, or retroantral fat planes on CT, (3) Tissue invasion without bony erosion, (4) Hypointense T2W sinonasal secretions on MRI in the setting of acute sinusitis. The authors additionally propose an algorithm that suggests surgical exploration for patients with clinical concern for AIFS and these radiographic features, even if bedside nasal endoscopy is inconsistent with AIFS. CONCLUSION/CONCLUSIONS:The radiographic signs highlighted herein should heighten suspicion for AIFS in the appropriate clinical setting, prompting urgent surgical exploration regardless of nasal endoscopy findings.

BACKGROUND:Orbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy. AIMS/OBJECTIVE:To test the hypothesis that shared signalling pathways are activated in different forms of OID. METHODS:In this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls. RESULTS:Among the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways. CONCLUSIONS:Although OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways.

The prognostic value of mutations in G-protein genes GNAQ and GNA11 in patients with intracranial and orbital melanocytomas is unknown. The authors present a case of GNA11 mutation (GNA11Q209L) in a 32-year-old male suffering from a meningeal melanocytoma with orbital involvement and ipsilateral Nevus of Ota. The patient underwent gamma knife stereotactic radiosurgery without biopsy and later partial transcranial resection of the melanocytic tumor that was subject to immunohistochemical and molecular analysis. A 50-gene next-generation sequencing panel revealed a 626A>T mutation in the GNA11 gene. One year later, intracranial extension of the melanocytoma necessitated a ventriculoperitoneal shunt and immunotherapy. Future work is needed to determine how GNA11 mutations in melanocytomas influence prognosis and monitoring strategies.

PURPOSE/OBJECTIVE:To present a protocol for audiologic monitoring in the setting of teprotumumab treatment of thyroid eye disease, motivated by 4 cases of significant hearing loss, and review the relevant literature. METHODS:Cases of hearing loss in the setting of teprotumumab were retrospectively elicited as part of a multi-institutional focus group, including oculoplastic surgeons, a neurotologist and an endocrinologist. A literature review was performed. RESULTS:An aggregate of 4 cases of teprotumumab-associated hearing loss documented by formal audiologic testing were identified among 3 clinicians who had treated 28 patients. CONCLUSIONS:Teprotumumab may cause a spectrum of potentially irreversible hearing loss ranging from mild to severe, likely resulting from the inhibition of the insulin-like growth factor-1 and the insulin-like growth factor-1 receptor pathway. Due to the novelty of teprotumumab and the lack of a comprehensive understanding of its effect on hearing, the authors endorse prospective investigations of hearing loss in the setting of teprotumumab treatment. Until the results of such studies are available, the authors think it prudent to adopt a surveillance protocol to include an audiogram and tympanometry before, during and after infusion, and when prompted by new symptoms of hearing dysfunction.

A 10-month-old boy presented with a 3-month history of progressive left lower eyelid swelling. Examination demonstrated left lower eyelid fullness and hyperglobus with a fatty appearing inferior fornix mass. Imaging showed a mass isointense to fat in the left lower eyelid extending posteriorly, surrounding the inferior oblique with complete fatty infiltration, obscuration of the inferior rectus, and adherence to the globe. The patient underwent orbitotomy with biopsy and debulking of the tumor. Surgical pathology showed multiple fragments of adipose tissue with foci of plump and spindle-shaped cells arranged in bundles and fascicles, consistent with lipofibromatosis. This case illustrates a rare presentation of orbital lipofibromatosis in a pediatric patient.

A 79-year-old male was hospitalized for respiratory failure secondary to coronavirus disease 2019 pneumonia. Approximately 6 hours after initiating proning, left globe subluxation with darkening of the superior sclera consistent with tache noir was noted. The left globe was thought to be hypotonus secondary to ciliary body shut down after a prolonged period of high intraocular pressure. The globe was reduced in the supine position with gentle traction of the eyelids. Over the next 24 hours, the left intraocular pressure improved to 10 mm Hg, and the tache-noir de la sclérotique resolved. The authors report the first known case of globe subluxation secondary to proning.