Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multicenter Study.

PURPOSE: To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab. DESIGN: Multicenter, retrospective, observational cohort study. PARTICIPANTS: Patients with TED of all stages and activity levels treated with at least 4 infusions of teprotumumab. METHODS: Patients were treated with teprotumumab between February 2020 and October 2022 at 6 tertiary centers. Adverse event metrics were recorded at each visit. MAIN OUTCOME MEASURES: The primary outcomes measure was AE incidence and onset. Secondary outcome measures included AE severity, AE reversibility, AE duration, proptosis response, clinical activity score (CAS) reduction, and Gorman diplopia score improvement. RESULTS: The study evaluated 131 patients. Proptosis improved by 2 mm or more in 77% of patients (101/131), with average proptosis improvement of 3.0 ± 2.1 mm and average CAS reduction of 3.2 points. Gorman diplopia score improved by at least 1 point for 50% of patients (36/72) with baseline diplopia. Adverse events occurred in 81.7% of patients (107/131). Patients experienced a median of 4 AEs. Most AEs were mild (74.0% [97/131]), 28.2% (37/131) were moderate, and 8.4% (11/131) were severe. Mean interval AE onset was 7.9 weeks after the first infusion. Mean resolved AE duration was 17.6 weeks. Forty-six percent of patients (60/131) demonstrated at least 1 persistent AE at last follow-up. Mean follow-up was 70.2 ± 38.5 weeks after the first infusion. The most common type of AEs was musculoskeletal (58.0% [76/131]), followed by gastrointestinal (38.2% [50/131]), skin (38.2% [50/131]), ear and labyrinth (30.5% [40/131]), nervous system (20.6% [27/131]), metabolic (15.3% [20/131]), and reproductive system (12.2% [16/131]). Sixteen patients (12.2%) discontinued therapy because of AEs, including hearing loss (n = 4), inflammatory bowel disease flare (n = 2), hyperglycemia (n = 1), muscle spasms (n = 1), and multiple AEs (n = 8). CONCLUSIONS: Adverse events are commonly reported while receiving teprotumumab treatment. Most are mild and reversible; however, serious AEs can occur and may warrant treatment cessation. Treating physicians should inform patients about AE risk, properly screen patients before treatment, monitor patients closely throughout therapy, and understand how to manage AEs should they develop. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

"Blue Scrub Lid Retraction": Changes in Eyelid Position on the Day of Surgery.

PURPOSE: The aim of this study is to test the hypothesis that margin-reflex distance 1 (MRD1) on the day of surgery will be higher than the MRD1 measured at the in-clinic consult visit among patients undergoing blepharoptosis repair due to an increased sympathetic drive. METHODS: Patients evaluated for involutional blepharoptosis repair were prospectively enrolled over a 12-month period in this single-center, self-controlled study. Three investigators independently determined MRD1 using cropped photos taken of patients at the in-clinic consult visit and on the day of surgery. A difference in height was tested for by using the 2-tailed Wilcoxon signed rank test. RESULTS: Evaluated in this study were 76 eyelids from 38 patients. Over 3-quarters of study participants had a higher MRD1 in the right and OSs on the day of surgery than at their in-clinic consultation visit (p < 0.001). The mean increase in MRD1 for the right eyelid and left eyelid was 1.0 mm (range: 0-3.15 mm) and 1.1 mm (range: 0-2.7 mm), respectively. CONCLUSIONS: In patients with involutional blepharoptosis, we conclude that MRD1 is higher on the day of surgery as compared with the in-clinic consult visit. This may be secondary to the stress of surgery and an associated increase in sympathetic drive. In some cases, this change in eyelid position led to resolution of apparent involutional ptosis altogether. Caution should be used when considering deferral of ptosis repair on the basis of exam findings present on the day of surgery.

A Case of the Blues-Colored Pencil Orbitopathy in an 18-Month-Old Boy.

Orbital penetrating injuries from pencils are rare. This report describes a case of penetrating orbital injury in a young child with a retained blue-colored pencil core foreign body, which led to rapid onset of orbital abscess requiring surgical drainage. Intraoperatively, orbital tissues were stained a bright-blue color. Histopathological study of specimen also highlighted bright blue aggregates of foreign material infiltrating the orbital tissues. Cultures grew Streptococcus mitis and Exophiala jeanselmei , which are rare causes of orbital abscess. Unique properties of retained colored pencil core as compared to graphite pencil core are herein discussed. Due to differences in composition, colored pencil core foreign bodies may require more timely surgical intervention compared to noncolored graphite pencil core.

Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab.

PURPOSE: In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen. METHODS: This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events. RESULTS: The study included 74 patients. Mean age was 57.8 years, and 77% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (-2.9 mm in active and -2.8 mm in minimal to no clinical activity patients, P < 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS ( P < 0.01) and reduction in ocular motility restriction ( P < 0.01) were maintained during interruption. CONCLUSIONS: Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Immunoglobulin G4 Involvement in Lacrimal Sac Squamous Cell Carcinoma.

Lacrimal sac squamous cell carcinoma is a rare but life-threatening disease that is often a delayed diagnosis secondary to difficulty in differentiating from other causes of dacrocystitis and acquired nasolacrimal duct obstruction. Chronic inflammation, including that of an underlying autoimmune disease, prior instrumentation, and poor wound healing, may be risk factors in the development to lacrimal sac squamous cell carcinoma. The authors present the first case of lacrimal sac squamous cell carcinoma associated with antineutrophil cytoplasmic antibody-associated vasculitis and immunoglobulin G4 positivity. Rather than an overlap syndrome between antineutrophil cytoplasmic antibody-associated vasculitis and immunoglobulin G4-related disease, high immunoglobulin G4 positivity may be considered an inflammatory marker of disease severity in the setting of antineutrophil cytoplasmic antibody-associated vasculitis and underlying malignancy. Inflammation-mediated tumorangiogenesis should be considered in the development of malignancy and red flags of chronic uncontrolled inflammation should warrant a lower threshold for further workup.

Delayed-Onset Inflammatory Optic Nerve Sheath Mass and Perineuritis Following Cessation of Ipilimumab and Nivolumab Therapy.

A 65-year-old male presented with headaches and painless episodes of unilateral vision loss. He had a history of renal cell carcinoma, in remission following surgery and immunotherapy with ipilimumab and nivolumab, discontinued 2 years and 3 months before presentation, respectively. MRI revealed an optic nerve sheath mass and perineuritis. After 1 month of corticosteroid therapy, there was a robust clinical and radiographic response, which relapsed dramatically following cessation. An optic nerve sheath biopsy showed chronic mild inflammation, and extensive work-up for alternative etiologies of orbital inflammation was negative. Following a prolonged taper of corticosteroids, he demonstrated complete response. In the setting of ocular immune privilege, ophthalmic immune-related adverse events (irAE) are rare, although multifarious. While on-treatment irAE are well-characterized, posttreatment irAE have become increasingly recognized across multiple organ systems. We report a case of a delayed-onset inflammatory optic nerve sheath mass and perineuritis after cessation of immunotherapy.

Predictive Modeling of New-Onset Postoperative Diplopia Following Orbital Decompression for Thyroid Eye Disease.

PURPOSE: To identify risk factors for the development of new-onset, postoperative diplopia following orbital decompression surgery based on patient demographics, clinical exam characteristics, radiographic parameters, and surgical techniques. METHODS: We conducted a multi-center retrospective chart review of patients who underwent orbital decompression for thyroid eye disease (TED). Patient demographics, including age, gender, smoking history, preoperative exophthalmometry, clinical activity score (CAS), use of peribulbar and/or systemic steroids, and type of orbital decompression were reviewed. Postoperative diplopia was determined at a minimum of 3 months postoperatively and before any further surgeries. Cross-sectional area ratios of each extraocular muscle to orbit and total fat to orbit were calculated from coronal imaging in a standard fashion. All measurements were carried out using PACS imaging software. Multivariable logistic regression modeling was performed using Stata 14.2 (StataCorp, College Station, TX). RESULTS: A total of 331 patients without preoperative diplopia were identified. At 3 months postoperatively, 249 patients had no diplopia whereas 82 patients developed diplopia. The average postoperative follow-up was 22 months (range 3-156) months. Significant preoperative clinical risk factors for postoperative diplopia included older age at surgery, proptosis, use of peribulbar or systemic steroids, elevated clinical activity score, and presence of preoperative compressive optic neuropathy. Imaging findings of enlarged cross-sectional areas of each rectus muscle to the overall orbital area also conferred a significant risk of postoperative diplopia. Regarding surgical factors, postoperative diplopia was more common among those undergoing medial wall decompression, bilateral orbital surgery, and balanced decompression, whereas endoscopic medial wall decompression was found to be relatively protective. CONCLUSIONS: This study identifies risk factors associated with the development of diplopia following orbital decompression using multivariable data. This study demonstrates that several characteristics including age, clinical activity score, the cross-sectional muscle to orbit ratios, in addition to the type of orbital decompression surgery, are predictive factors for the development of new-onset postoperative diplopia.

Development of Herpes Zoster Ophthalmicus in an Immunocompetent Pediatric Patient Following Facial Trauma.

Herpes zoster ophthalmicus (HZO) is a neuro-oculo-dermic infection caused by reactivation of latent varicella zoster virus in the dorsal root ganglia of the ophthalmic division of the trigeminal nerve. Although a rare diagnosis in an otherwise healthy, vaccinated pediatric patient, this entity may occur with increasing frequency among those with preceding trauma, particularly in the month prior to presentation. Herein, we highlight a case of HZO in a vaccinated, immunocompetent adolescent in the setting of recent facial trauma.

Intraorbital Graphite Foreign Body With a Delayed Presentation of Optic Neuropathy.

Traumatic penetrating injuries to the orbit from pencils, while uncommon, have a plethora of presentations, both acute and delayed. With the most incidents occurring in the pediatric population where obtaining a detailed history is difficult, the ability to effectively evaluate and diagnose these injuries is cumbersome, yet important. The authors report a patient who presented with optic neuropathy, blepharoptosis, and strabismus 10 months after an orbital injury with pencil graphite.

A Report of Intracranial Meningioma Recurring as Ectopic Orbital Meningioma Associated With Basal Encephalocele.

The authors describe a rare case of recurrent ectopic meningioma associated with sphenoid encephalocele in the medial anterior orbit of a 52-year-old man with a history of a resected intracranial meningioma. Typical features of ectopic meningioma are reviewed as well as potential etiologies of this very rare recurrence of intracranial meningioma in the orbit. Treatment is typically surgical excision.The authors report a rare case of recurrent orbital ectopic meningioma in the right medial canthus of a 52-year-old man.

Ultrasonic Aspiration for Debulking Infiltrative Masses of the Orbit.

PURPOSE: To demonstrate the utility of an ultrasonic aspirator (Sonopet, Stryker Corporation; Kalamazoo, MI) for debulking firm, soft tissue masses of the orbit. METHODS: Case series. The ultrasonic aspirator was used to debulk firm, soft tissue masses in 3 cases. The initial patient had a large orbitofacial mass extending to the inferior and lateral orbital apex secondary to IgG4 disease. The second patient had a lacrimal sac adenocarcinoma extending to the medial orbital apex. The third patient had a large orbital mass extending to the apex secondary to granulomatosis with polyangiitis. RESULTS: The ultrasonic aspirator facilitated debulking of infiltrative firm soft tissue masses of the orbit. The device's ability to emulsify, irrigate, and aspirate, along with its small footprint, facilitated precise sculpting and debulking to an extent which would have been difficult otherwise due to location. CONCLUSIONS: The ultrasonic aspirator allows precise sculpting of infiltrative firm soft tissue masses in the orbit and is particularly useful in cases with challenging anatomical access.

Thyroid eye disease presenting with superior rectus/levator complex enlargement.

Purpose: To describe the demographic and clinical characteristics of patients with thyroid eye disease (TED) who present with predominate superior rectus/levator complex involvement.Methods: A multi-institutional retrospective review was performed to identify patients with TED who presented with superior isolated or predominate rectus/levator involvement. Baseline and subsequent visits were reviewed to characterize the clinical course.Results: Nineteen patients were identified. All patients had imaging demonstrating an enlarged levator/superior rectus complex. At presentation, the mean clinical activity score (CAS) was 2.1 (range: 0-5). Nineteen (100%) patients had proptosis on the affected side. Lid abnormalities, including upper/lower eyelid retraction and ptosis were higher on affected side compared to the unaffected side. Eleven (58%) patients had vertical misalignment. Mean thyroid stimulating immunoglobulin (TSI) was 3.7 (range: 1-7.1). Mean follow-up time was 18 months (range: 0-60 months). At last follow-up, the mean CAS was 1.3 (range 0-5). Ten (53%) patients had proptosis. Eleven (58%) patients had vertical misalignment. Repeat imaging in eight patients showed interval enlargement of other extraocular muscles.Conclusions: The presentation of TED with superior rectus/levator complex enlargement may be under-appreciated. Orbital imaging, as well as laboratory evaluation, may help support a diagnosis of TED. In the setting of abnormal TSI and/or thyrotropin receptor antibody, presence of upper eyelid retraction, and an otherwise unremarkable laboratory and systemic evaluation, a presumptive diagnosis of TED may be made, and the patient can be followed closely, as he/she is likely to develop involvement of other extraocular muscles, consistent with a more typical presentation of TED.

Late Presentation of Enlarging Lower Eyelid Mass and Muscle Degeneration Secondary to Hyaluronic Acid Filler.

A 66-year-old female presented for evaluation of progressively worsening edema and palpable masses in both lower eyelids. While she denied prior filler to the lower eyelid or tear trough, histopathology revealed degenerating striated muscle surrounding pools of hyaluronic acid. While cases of gradually enlarging masses associated with facial filler placement have been reported, there is no literature identifying muscle degeneration adjacent to hyaluronic acid filler.

A Unique Ocular Presentation of Extragenital Lichen Sclerosus.

Lichen sclerosus is a chronic, debilitating, and recurring disease that is most commonly seen affecting the anogenital region. Extragenital locations of lichen sclerosus has been well documented, frequently seen in the shoulders, neck, trunk, breasts, and arms, however, infrequently of the face. Specifically, extragenital lichen sclerosus has been reported in several cases to be involving the infraorbital region, but to our knowledge it has never been found affecting the adnexa of the eye. To our understanding, this is the first documented report of a patient with extragenital lichen sclerosus of an eyelid.

Nodular Lymphocyte Predominant Hodgkin Lymphoma Presenting With Unilateral Orbital Involvement.

A 40-year-old white woman presented to her general ophthalmologist for swelling of the left upper eyelid that began approximately 6 months before. CT scan of the orbits with and without contrast demonstrated homogenous enhancement of the left lacrimal gland. Examination was notable for left hypoglobus and proptosis. The patient underwent left lateral orbitotomy with biopsy of the mass and frozen section analysis showed lymphoid infiltrates. Subsequent histopathologic diagnosis was consistent with nodular lymphocyte predominant Hodgkin lymphoma, a rare subtype of Hodgkin lymphoma that has only once been previously reported in the orbit. The authors review the case and the relevant literature.

The Bleph and the Brain: The Effect of Upper Eyelid Surgery on Chronic Headaches.

PURPOSE: To determine effect of upper eyelid surgery on headache symptoms. METHODS: Consecutive adults undergoing upper eyelid surgery for obscuration of superior visual field, who also reported headache symptoms for greater than 1 year completed a pre- and postoperative Headache Impact Test-6 quality of life questionnaire (study group). A cohort of patients undergoing other oculoplastic procedures with headaches also completed the questionnaire pre- and postoperatively (control group). The study was conducted over a 2-year period. Neither the patients nor the study investigators were masked. RESULTS: Twenty-eight patients met criteria for the study group, and 19 patients in the control group. Mean age was 58.7 and 60.7 years, respectively. There was no statistically significant difference in preoperative location of headaches. There was no significant difference in mean Headache Impact Test-6 scores preoperatively, 57.7 study group, 58.1 control group, p = 0.86. Mean postoperative scores were lower (improved) in the study arm, 45.3, as compared with the control arm, 58.6, p < 0.05. There was no statistically significant difference between individual preoperative survey questions between the study arm and control group, while every Headache Impact Test-6 question significantly improved in the study arm compared with the control arm. Mean Headache Impact Test-6 score improved 12.4 points in the study arm after surgery (p < 0.05), while the mean postoperative score worsened by 5 points in the control arm, but this was not significant (p = 0.48). Subjectively, 25 of 28 study patients, and 4 of 19 control patients noticed at least some improvement in headache symptoms after surgery. CONCLUSIONS: Correction of visually significant upper eyelid position may improve chronic headache symptoms.

Granulocytic Sarcoma of the Orbit Presenting as a Fulminant Orbitopathy in an Adult With Acute Myeloid Leukemia.

A 64-year-old woman with relapsed acute myelogenous leukemia (AML) undergoing salvage chemotherapy developed rapid onset of right-sided ophthalmoplegia, proptosis, optic neuropathy, and vision loss from 20/30 to hand motions over a 3-hour period on day 4 of her treatment. CT scan of her orbits revealed a superolateral orbital mass and periocular edema. She underwent immediate canthotomy and cantholysis, and lateral orbitotomy with debulking of the mass later the same day. The histopathology was consistent with aggregates of myeloid blasts. Her vision recovered to 20/20 on postoperative day 1. Orbital granulocytic sarcoma is a rare condition often concurrent with AML, typically in the pediatric population and rarely in adults. Presentation as a fulminant orbitopathy with rapidly progressive optic neuropathy and vision loss over several hours has not been previously reported.