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.

Effectiveness of An Intraoperative Lagophthalmos Formula for Levator Resection in Patients With Congenital Ptosis.

PURPOSE: To evaluate the effectiveness of an intraoperative lagophthalmos formula (IOLF) for levator resection in congenital ptosis and investigate the optimal preoperative conditions for IOLF application. METHODS: This retrospective interventional cohort study evaluated 30 eyelids of 22 patients with congenital ptosis who underwent levator resection using the IOLF to calculate the extent of surgical correction under general anesthesia. Surgical success was defined as margin reflex distance-1 (MRD1)≥3 mm in each eye and a difference of MRD1 1 mm between the eyes at 6 months postoperatively. Logistic regression was performed to investigate the preoperative conditions associated with surgical success. RESULTS: Among 30 eyelids, 19 had good-to-fair levator function (LF) (≥5 mm) and 11 had poor LF ( 4 mm). The overall success rate was 90.0% (n=27/30), whereas the under-correction rate was 10.0% (n=3/30). The surgical success rate was 100% (n=19/19) in eyelids with LF ≥5 mm and 72.7% (n=8/11) in eyelids with LF 4 mm. Patients with preoperative MRD1≥0 mm (versus MRD1<0 mm, odds ratio=34.5, P =0.0098) or a combination of preoperative MRD1≥0 mm and LF≥5 mm (versus MRD1<0 mm and LF 4 mm, odds ratio=48.0, P =0.0124) more likely had successful surgical outcomes. CONCLUSIONS: Levator resection using the IOLF can provide satisfactory results for congenital ptosis regardless of LF. Preoperative MRD1≥0 mm may be suitable for IOLF application, and the combination of preoperative MRD≥0 mm and LF≥5 mm may be the optimal preoperative condition for IOLF application.

Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma of the Orbit: Three Cases and Review of the Literature.

The authors present 3 patients from this retrospective case series to review the clinical findings, imaging, pathology, and treatment of orbital atypical lipomatous tumor/well-differentiated liposarcoma. Pathology of biopsy specimens ranged from spindle cell proliferations mimicking neurofibroma to proliferations of well-differentiated adipocytes. Immunohistochemical stains were positive for murine double minute 2 in 1 case, and fluorescent in situ hybridization showed amplification of murine double minute 2 in 2 cases. Treatments ranged from serial debulking, proton beam irradiation, and exenteration. None of the patients developed metastases. A literature review supported the low-grade nature of this lesion. Orbital atypical lipomatous tumor/well-differentiated liposarcoma is a low-grade, indolent liposarcoma that may be locally invasive. The histologic diagnosis is enhanced with immunohistochemical staining for murine double minute 2 and fluorescent in situ hybridization analysis for amplification of murine double minute 2. Although treatment may vary according to the individual, conservative therapies may be attempted prior to radical surgery.

Necrotic uveal melanoma presenting as orbital cellulitis with intraocular hemorrhage: A case report.

PURPOSE: To report a case of necrotic uveal melanoma presenting as orbital cellulitis with an intraocular hemorrhage. OBSERVATIONS: A 61 year-old non-verbal male presented with a two-week history of right eyelid swelling and erythema unresponsive to antibiotics. In addition to these signs of orbital cellulitis, he presented with an opaque media precluding fundus visualization. He was later found to have a collar-button shaped mass consistent with uveal melanoma on B scan ultrasonography during an exam under anesthesia. The patient underwent enucleation with histopathology confirming a necrotic uveal melanoma. CONCLUSION AND IMPORTANCE: This case demonstrates how necrotic uveal melanoma can present as orbital cellulitis and the importance of keeping the diagnosis on the differential.

Assessing the Effectiveness of Arnica montana and Rhododendron tomentosum (Ledum palustre) in the Reduction of Ecchymosis and Edema After Oculofacial Surgery: Preliminary Results.

PURPOSE: The purpose of this study was to provide preliminary data on the potential effectiveness of the combination of topical Arnica montana and Rhododendron tomentosum (Ledum palustre) in reducing postoperative ecchymosis and edema in a select population of healthy volunteers after oculofacial surgery. METHODS: This retrospective review examined the postoperative course of healthy volunteers using topical Arnica and Ledum after undergoing common oculofacial procedures, including blepharoplasty, browpexy, and rhinoplasty, in the hands of 4 surgeons at tertiary referral centers from July 1, 2012 to December 31, 2012 using medical records review. Each patient included had used topical hydrogel pads (OcuMend, Cearna Inc., Chicago, IL) containing Arnica 50 M (10) 50% and Ledum 50 M (10). The pads were applied bilaterally after surgery through postoperative day 6. At each postoperative visit, the patients were evaluated by their respective surgeons and assigned a subjective physician-patient rating score comparing each patient's observed healing compared with expected healing if not using Arnica/Ledum. Photographs of patients undergoing equivalent procedures, but not using Arnica/Ledum were used as controls for comparison. Physician-patient rating scores were categorical: markedly accelerated healing defined as approximately 7 days ahead of expected, accelerated healing, defined as <7 days ahead of expected, and no appreciable difference from expected. The proportion of patients with each physician-patient rating score was calculated for postoperative days 1 to 2, 3 to 5, 6 to 8, and overall. Difference of proportions was calculated with 95% confidence intervals using Newcombe unpaired difference comparison of proportions. Photographs documenting the clinical progression of selected patients are provided. RESULTS: A total of 27 patients (16 females, 11 males) were included in the study. Age range was 18 to 70 years. The majority of patients were white (52.9%), and underwent blepharoplasty (78.9%). The median duration of follow-up was 7 days, range 1 to 14 days. The proportions of patients with markedly accelerated healing were 38.5% (5 of 13), 85.7% (6 of 7), 60.0% (12 of 20), and 51.9% (14 of 27) at POD 1 to 2, 3 to 5, 6 to 8, and overall, respectively. The proportions of patients with accelerated healing at the same time points were 15.4% (2 of 13), 14.3% (1 of 7), 30.0% (6 of 20), and 37.0% (10 of 27), respectively. The proportions of patients with no appreciable difference at the same time points were 46.2% (6 of 13), 0% (0 of 7), 10.0% (2 of 20), and 11.1% (3 of 27) of patients, respectively. The proportion of patients using Arnica/Ledum with markedly accelerated healing was significantly more than the proportion of those demonstrating no appreciable difference from expected at POD 3 to 5 (85.7% vs. 0%, p = 0.05), POD 6 to 8 (60.0% vs. 10.0%), and overall (51.9% vs. 11.1%, p = 0.05). No adverse effects were reported. CONCLUSIONS: The preliminary results from this study demonstrate that the combination of topical Arnica montana and Rhododendron tomentosum (Ledum palustre) may be effective in reducing postoperative ecchymosis and edema after oculofacial surgery.