Menstrual Irregularities and Amenorrhea in Thyroid Eye Disease Patients Treated With Teprotumumab.

PURPOSE: To evaluate the rates of amenorrhea and menstrual irregularities in patients with active thyroid eye disease treated with teprotumumab. METHODS: A retrospective review was conducted of patients with active thyroid eye disease treated between 2020 and 2022 at a single institution. Female thyroid eye disease patients with regular menstruation at baseline who completed 8 infusions of teprotumumab were assessed. Patient-reported irregularities in menstruation or amenorrhea were recorded during routine clinic visits. Two sample t tests were used to assess differences between patients endorsing and denying menstrual irregularities. RESULTS: Twelve patients met the inclusion criteria. The mean age was 38.33 ± 9.6 years (range 25-53 years). The average follow-up after treatment completion was 11.43 months. Nine patients (75%) reported changes from their baseline menstruation. Four patients (33.3%) reported irregularities during treatment only. Three patients (25%) had persistence of irregularities after treatment; these patients regained normal cycles at an average of 3 months following teprotumumab completion. Two patients (16.7%) did not regain their normal cycles at the time of their last follow-up. One 53-year-old patient-reported persistent amenorrhea after treatment completion. One patient-reported menorrhagia at a 4-month follow-up. No significant age difference was found between patients with or without reported menstrual changes ( p = 0.43). CONCLUSION: Abnormalities of menstruation, including amenorrhea, were reported by 75% of patients treated with teprotumumab. These changes reverted to baseline after treatment in most affected patients.

Pathologic Features, Treatment, and Clinical Outcomes of Lacrimal Gland Cancer.

OBJECTIVES: Lacrimal gland cancer is a rare malignancy with little data known about its pathologic characteristics or optimal management. We performed a large database analysis using the National Cancer Database (NCDB) to elucidate this unusual condition. METHODS: Patients with lacrimal gland cancer diagnosed between 2004 and 2018 were included in the analysis. Using available clinical data, we excluded all patients with histologies likely reflective of lacrimal sac or duct cancer, which are coded similarly to lacrimal gland cancer in the NCDB. Kaplan-Meier analysis was used to estimate overall survival (OS), and Cox proportional hazards models were used to indicate covariates associated with survival. RESULTS: A total of 440 cases of lacrimal gland cancer were included in the analysis, with a median follow-up of 52.9 months. The five-year OS for the entire cohort was 65.0%. Adenoid cystic carcinoma was the predominant histology (47.3%). Cox models showed that improved OS was associated with surgical resection (UVA: p < 0.001; MVA: p = 0.035). A detriment in OS was associated with increasing age, Charlson-Deyo score of 1, T4 stage, and positive margins and on UVA for adenocarcinoma and malignant mixed tumor histology. CONCLUSION: Adenoid cystic carcinoma comprises the plurality of lacrimal gland cancers. About half of patients with lacrimal gland carcinoma will live beyond 10 years, underscoring the importance of reduced morbidity of treatment. Surgical management is associated with improved prognosis. Further study will elucidate the role of surgical excision and radiotherapy in lacrimal gland cancer.

Prospective Assessment of Otologic Adverse Events due to Teprotumumab: Preliminary Results.

OBJECTIVE: To assess a series of patients receiving teprotumumab therapy and objectively quantify the rates of otologic adverse events. STUDY DESIGN: A prospective cohort study of adult patients receiving teprotumumab between May 2020 and January 2022. SETTING: Tertiary referral center. METHODS: Prior to treatment initiation, an ototoxicity-specific audiometric battery was completed, which included conventional audiometry (frequencies 250-8000 Hz), ultrahigh-frequency audiometry (9000-20,000 Hz), tympanometry, speech discrimination scores, and distortion product otoacoustic emissions (DPOAEs). Testing was then repeated after treatment completion. RESULTS: In total, 35 patients were recruited, with a median (range) age of 48.5 years (21-74), and 8 (22.8%) were male. The most common subjective symptom reported was a hearing decline (25.7%), followed by aural fullness (17.1%) and tinnitus (14.3%). Fourteen patients had both pre- and posttreatment audiometric data. Among them, 3 patients (21.4%) were found to have changes in standard frequency audiometry, and 10 (71.4%) had changes in high-frequency audiometry, with 2 patients having changes in both. Less than half (n = 5) of the 11 patients with changes in standard or high-frequency pure tone hearing noted subjective hearing decline. Changes in DPOAE were noted in 4 patients out of 13 (30.7%). Two patients discontinued treatment due to hearing decline. Finally, 3 patients (8.6%) were diagnosed with patulous eustachian tube (PET) by an otolaryngologist, and another 3 patients are suspected to have PET based on symptom description during ophthalmologic follow-up. CONCLUSION: In our cohort, a high incidence of otologic symptoms was found to be associated with teprotumumab usage. Subjective hearing decline, changes in ultrahigh-frequency hearing as well as eustachian tube dysfunction may be encountered and suggest the potential ototoxicity of teprotumumab.

Pigmented Inflamed Seborrheic Keratosis of the Bulbar Conjunctiva.

A 57-year-old Black man presented with the recent onset of a pigmented temporal epibulbar lesion. As pigmentation of conjunctival epithelial lesions is correlated with complexion pigmentation, the lesion was presumed to represent a pigmented ocular surface squamous neoplasia (OSSN). Excisional biopsy, however, revealed a pigmented conjunctival seborrheic keratosis, a rare occurrence. The lesion lacked cytologic atypia. Intralesional processes of dendritic melanocytes were demonstrated by hematoxylin-eosin and Melan-A stains. Melanophages also contributed to clinical pigmentation. Subepithelial lymphocytic infiltration, elevated Ki67 proliferative rate, prominent mitotic activity, and subtle spongiosis afforded evidence of inflammation rather than malignancy in a lesion devoid of cytologic atypia.

Globe Compression by Bone Fragments in Orbital Blow-in Fractures: A Case Series and Systematic Review.

PURPOSE: The purpose of this study was to describe the clinical characteristics, management, and outcomes of orbital blow-in fractures involving compression of the globe by bone fragments. METHODS: A retrospective case series and systematic literature review were performed. RESULTS: Three male patients (mean age 29 years) with orbital blow-in fractures causing globe indentation presented with extraocular movement restriction, choroidal folds, and B-scan ultrasonography demonstrating deformation of the globe contour by a hyperechoic bone fragment. All underwent surgical repair within 1 day of presentation resulting in improved visual outcomes. An additional 10 cases were identified in the literature review. The majority of patients were male (80%) with a mean age of 29 years. Fractures originated primarily from the lateral orbital wall (50%) or the orbital roof (40%). Globe compression was evident on CT of the orbit (100%) and ultrasonography (30%). Common presenting signs included decreased visual acuity (70%), restriction of supraduction (40%) or abduction (40%), choroidal folds (30%), brow laceration (40%), periorbital edema (40%), and hypoglobus (40%). Most patients underwent surgical intervention (80%) involving fracture reduction (50%) or fragment removal (38%). Reported postsurgical outcomes were excellent with resolution of diplopia, motility, and visual acuity. CONCLUSION: Globe indentation from blow-in fractures are rare. Clinicians should be suspicious in cases of high-velocity trauma to the superolateral orbit with hypoglobus, motility limitation, and indentation of the globe upon dilated exam. Prompt diagnosis and early surgical removal of the compressive orbital bone fragments in a multidisciplinary fashion can lead to good visual, functional, and cosmetic outcomes.

Targeted Neoadjuvant Intra-arterial Chemotherapy in Lacrimal Gland Adenoid Cystic Carcinoma: A Histological Correlation Using Apoptotic Tumor Markers.

Neoadjuvant intra-arterial cytoreductive chemotherapy is used for the treatment of lacrimal gland adenoid cystic carcinomas (ACC) to improve outcomes in this condition with an otherwise dismal prognosis. We share our experience in the management of an advanced case of ACC using a novel, highly targeted intra-arterial cytoreductive chemotherapy delivery technique involving both the internal and external carotid circulation, with an attempt to correlate the effect histologically. Refinement of the chemotherapy delivery using the tumor's vascular anatomy and appropriate blood vessel selection may lead to future globe sparing procedures without compromising survival.

Congenital Eyelid Imbrication and Floppy Eyelid Syndrome in a Patient With Cat Eye Syndrome.

A newborn male with cat eye syndrome presented with progressively worsening bilateral upper eyelid imbrication, floppy eyelids, and ptosis. Despite conservative management, he remained unable to open his eyelids. Surgical correction was planned to prevent bilateral sensory deprivation amblyopia and was delayed until 5 months of age due to systemic health concerns. Bilateral full-thickness wedge excision and frontalis suspension with silicone rods in a double rhomboid fashion was performed. Postoperatively, the patient demonstrated spontaneous eyelid opening, resolution of spastic eversion of the upper eyelids, and adequate eyelid closure. The authors present the first case of concurrent floppy eyelid syndrome and upper eyelid imbrication reported in a cat eye syndrome patient.

Teprotumumab and Hearing Loss: Case Series and Proposal for Audiologic Monitoring.

PURPOSE: 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.

Central Retinal Artery Visualization with Cone-Beam CT Angiography.

Background There are multiple tools available to visualize the retinal and choroidal vasculature of the posterior globe. However, there are currently no reliable in vivo imaging techniques that can visualize the entire retrobulbar course of the retinal and ciliary vessels. Purpose To identify and characterize the central retinal artery (CRA) using cone-beam CT (CBCT) images obtained as part of diagnostic cerebral angiography. Materials and Methods In this retrospective study, patients with catheter DSA performed between October 2019 and October 2020 were included if CBCT angiography included the orbit in the field of view. The CBCT angiography data sets were postprocessed with a small field-of-view volume centered in the posterior globe to a maximum resolution of 0.2 mm. The following were evaluated: CRA origin, CRA course, CRA point of penetration into the optic nerve sheath, bifurcation of the CRA at the papilla, visualization of anatomic variants, and visualization of the central retinal vein. Descriptive statistical analysis was performed. Results Twenty-one patients with 24 visualized orbits were included in the analysis (mean age, 55 years ± 15; 14 women). Indications for angiography were as follows: diagnostic angiography (n = 8), aneurysm treatment (n = 6), or other (n = 7). The CRA was identified in all orbits; the origin, course, point of penetration of the CRA into the optic nerve sheath, and termination in the papilla were visualized in all orbits. The average length of the intraneural segment was 10.6 mm (range, 7-18 mm). The central retinal vein was identified in six of 24 orbits. Conclusion Cone-beam CT, performed during diagnostic angiography, consistently demonstrated the in vivo central retinal artery, demonstrating excellent potential for multiple diagnostic and therapeutic applications. © RSNA, 2021 Online supplemental material is available for this article.

Eosinophilic mucin chronic rhinosinusitis with orbital involvement: management strategies based on clinical presentation.

Allergic fungal sinusitis (AFS) and eosinophilic mucin chronic rhinosinusitis (EMCRS) are subtypes of a chronic rhinosinusitis with eosinophilia that have different diagnostic criteria but are phenotypically similar. Ophthalmic complications may be the presenting symptoms. Treatment of ophthalmic complications is typically directed at reducing the inflammatory burden in the sinuses and rarely requires direct surgical intervention. However, atypical cases with associated subperiosteal abscess may necessitate orbital surgery. The authors present 2 cases of EMCRS with orbital involvement - one that responded to the traditional treatment of oral corticosteroids and functional endoscopic sinus surgery (FESS), and the other requiring surgical drainage of a subperiosteal abscess in order to describe the management strategies based on clinical presentation.

Ophthalmic artery occlusion due to orbital compartment syndrome after a frontotemporal craniotomy.

A 32-year-old female with a right frontal lobe glioma underwent an elective frontotemporal craniotomy. One hour postoperatively, the patient developed a right orbital compartment syndrome (OCS) with unilateral acute vision loss, proptosis, afferent pupillary defect, and complete ophthalmoplegia. The patient underwent emergent lateral canthotomy and inferior cantholysis. Neuroimaging revealed extensive vascular congestion along the extraocular muscles at the orbital apex. Retinal imaging demonstrated an ophthalmic artery occlusion. OCS following a frontal or frontotemporal craniotomy relates to increased orbital venous congestion from direct compression of the myocutaneous flap and subsequent intraorbital pressure elevation, vascular compromise, and ocular ischemia.

Conjunctival Exophytic Schneiderian-type Papillomas: A Rare Occurrence.

Conjunctival papillomas are common tumors that exhibit an exophytic growth pattern, comprised of multiple filiform fronds of squamous epithelium that contain fibrovascular cores. The inverted (endophytic) variety of papilloma, often termed "Schneiderian," rarely occurs on the conjunctiva, with only 15 cases reported to date. Endophytic and exophytic papillomas are well described arising in the sinonasal Schneiderian epithelium where a low rate of malignant transformation may occur in the endophytic type; malignant transformation in exophytic sinonasal papillomas is exceedingly rare. The authors describe 2 cases of exophytic conjunctival papillomas with the morphology of a sinonasal or Schneiderian-type papilloma. Both were pink, sessile acquired growths in women in the sixth decade of life involving the inferior conjunctival fornix or nasal limbus. Nonkeratinizing squamous epithelium along with numerous goblet cells, intraepithelial mucinous cysts, and microabscesses were present. Immunohistochemistry showed reactivity for cytokeratin 7 and wild-type staining for p16 and p53, paralleling the findings in common conjunctival papillomas; both were also driven by low-risk human papillomavirus.

Double Frost Suture Technique for Simultaneous Skin Grafting of the Upper and Lower Eyelids.

The double Frost suture is a useful supplement to the reconstruction of ipsilateral upper and lower eyelid defects with full-thickness skin grafts. This technique involves silk traction sutures that overlap the upper and lower eyelids to place them on maximal stretch after placement of 2 full-thickness skin grafts. It has the added benefit of protecting the cornea and compressing both grafts under 1 bolster. The authors illustrate this technique in 2 pediatric cases-a congenital melanocytic kissing eyelid nevus and a periocular burn. Each case resulted in large upper and lower anterior lamellar defects, which were reconstructed with supraclavicular and retroauricular free skin grafts. The double Frost sutures counter vertical cicatricial forces during graft healing, obviating the need for staged procedures. Both described cases resulted in excellent graft survival with minimal contracture.

Partial Vision Loss After Orbital Decompression in a Patient With Thyroid Eye Disease, Chorioretinal Folds, and Disc Edema.

ABSTRACT: Concomitant chorioretinal folds with disc edema can be seen in cases of thyroid eye disease presenting with compressive optic neuropathy and may portend optic nerve ischemia. We describe an unusual case of a 64-year-old man who developed partial vision loss after orbital decompression.

Orbital and Eyelid Inflammation With "Muciphages" and Extravasated Mucin From an Ethmoido-orbital Mucocele.

A 22-year-old woman presented with an acute compressive optic neuropathy due to a ruptured ethmoido-orbital mucocele. She underwent urgent orbital decompression and drainage of the mucocele via an endoscopic approach. Postoperatively, her course was complicated by an orbital compartment syndrome supervened, exhibiting severe eyelid edema caused by infiltration with mucin and mucin-containing macrophages ("muciphages"). Biopsy of the eyelid showed infiltration with "muciphages," macrophages laden with extravasated mucinous material. This is the first report that documents the clinical and histopathologic course of orbital inflammation following mucocele extravasation into the orbit and eyelids.

Multicameral Steatocystoma Simplex of the Caruncle.

A yellow cyst of the caruncle in a 68-year-old man displayed the characteristic sebaceous glands and sebocytes of steatocystoma within the cyst wall, with a unique configuration of multiple branching compartments. The cyst lining was of trichilemmal character, lacking a keratohyalin granular layer, and replicated the immunohistochemical characteristics of a previously reported caruncular steatocystoma with the exception of a positive trichilemmal marker, calretinin, in the present case. Four previous cases of caruncular steatocystoma have been described, only one of which incorporated immunohistochemical analysis. Steatocystoma develops from a sebaceous gland duct, which displayed in this case multiple chambers subdividing what is usually a single round lumen.