Tooley, Andrea A.

Background: Corticosteroid therapy is often employed in thyroid eye disease (TED), but its efficacy is variable. Teprotumumab and tocilizumab have been considered as effective alternatives. This study aims to evaluate their clinical outcomes and safety in patients with steroid-resistant TED. Methods: A retrospective case–control study was conducted between 2018 and 2022 within a national multicenter health system. Thirty-seven patients with moderate to severe steroid-resistant TED treated with teprotumumab or tocilizumab (cases) were compared with steroid-naïve patients treated with similar therapy (controls). Due to lack of steroid-naïve patients treated with tocilizumab, a control subgroup for tocilizumab was not included in the analysis. Demographic and clinical characteristics were described. Proptosis, diplopia, clinical activity score (CAS), and disease severity (European Group on Graves' orbitopathy classification) were evaluated at weeks 0, 12, 24, and 52 after therapy initiation. Results: Thirty-one patients received teprotumumab (13 cases and 18 controls) and 6 received tocilizumab (cases). The mean age was 57 years (standard deviation ±14.3), median duration of TED was 11.5 months (interquartile range [IQR]: 7.2–17.7), and median excess proptosis was 4 mm (IQR: 2–8) above the upper limit of normal for sex and race. At week 24, in the teprotumumab cases, 81% had proptosis response (reduction of ≥2 mm), 45.5% resolution of diplopia, 85.7% disease inactivation (CAS <3), and 58.3% reverted to mild disease severity. There were comparable results in teprotumumab controls, with no significant differences between subgroups. In the tocilizumab cases, 50% had a proptosis response, 16.7% resolution of diplopia, 100% disease inactivation, and 75% returned to mild disease. In the teprotumumab cases, there was a trend toward worsening proptosis and diplopia between weeks 24 and 52. In the same time frame, the tocilizumab cases had a trend toward worsening diplopia, disease activity, and severity. In the teprotumumab subgroup, 46.2% experienced otic changes and 23.1% hyperglycemia. In the tocilizumab subgroup, there were no reported adverse events. Conclusions: Teprotumumab and tocilizumab improved inflammation in patients with moderate to severe TED who had failed previous steroid therapy. Additionally, the teprotumumab cases demonstrated similar improvement in proptosis and diplopia to the teprotumumab controls. Further evaluation, particularly regarding the long-term response and side effect profile, of these medications in steroid-resistant TED is needed.

We present clinical and imaging predictors of ocular injuries that required medical management versus surgical intervention in cases of orbital fractures. From 2014 to 2020, a retrospective review of patients with orbital fractures who received ophthalmologic consultation and computed scan (CT) analysis at a level I trauma center was performed. Inclusion criteria were patients with confirmed orbital fracture on CT and ophthalmology consultation. Patient demographics, associated injuries, comorbidities, management, and outcomes were collected. Two hundred and one patients and 224 eyes (11.4% bilateral orbital fractures) were included. Overall, 21.9% of orbital fractures presented with a significant concomitant ocular injury. Associated facial fractures were present in 68.8% of eyes. Management included surgical treatment in 33.5% of eyes and ophthalmology-directed medical treatment in 17.4%. On multivariate analysis, clinical predictors of surgical intervention were retinal hemorrhage (OR=4.7 (1.0–21.0), P=0.0437), motor vehicle accident injury (OR=2.7 (1.4–5.1), P=0.0030) and diplopia (OR=2.8 (1.5–5.3), P=0.0011). Imaging predictors of surgical intervention were herniation of orbital contents (OR=2.1 (1.1–4.0), P=0.0281) and multiple wall fractures (OR=1.9 (1.01–3.6), P=0.0450). Predictors of medical management were corneal abrasion (OR=7.7 (1.9–31.4), P=0.0041), periorbital laceration (OR=5.7 (2.1–15.6), P=0.0006), and traumatic iritis (OR=4.7 (1.1–20.3), P=0.0444). We demonstrated a 22% incidence of concomitant ocular trauma in orbital fracture patients at our level I trauma center. Predictors of the surgical intervention included multiple wall fractures, herniation of orbital contents, retinal hemorrhage, diplopia, and motor vehicle accident injury. These findings emphasize the importance of a multidisciplinary team in managing ocular and facial trauma.

Purpose: To determine treatment outcomes, recurrence rates, and predictors of recurrence, to inform future therapeutic approaches for spheno-orbital meningiomas (SOM). Methods: A retrospective single-center study of SOM treated from 1990 to 2021 was conducted with comprehensive neuro-ophthalmologic follow-up at Columbia University Medical Center (CUMC). Recurrence requiring reintervention was defined clinically as worsening of visual acuity, visual field defect, or ocular motility after an initial period of stabilization or 6 months of improvement following treatment, or radiologically as either a regrowth with an increase in tumor size by 20% at the site of previous growth or a new region of tumor growth. Results: In total 46 patients met the inclusion criteria. The mean follow-up was 106 months (range 1–303). Dictated by the phenotype of the disease, patients underwent either gross- (50%), near- (17%), or subtotal resection (26%). Removal of the anterior clinoid process (ACP) was performed in 52% of patients. Nine patients (20%) required an enucleation or exenteration. Radiotherapy was employed at some point of treatment in 50% of cases. Inherited cases (24%) were referred to CUMC for treatment following 1 or more recurrences. The total recurrence rate, including inherited cases, was 54%, occurring at a mean interval of 43 months. The recurrence rate of patients treated solely at CUMC was 40%, occurring at a mean interval of 41 months. A subset of patients (32%) had 2 or more recurrences. Histopathology at the first surgery was WHO grade I (87%) and II (13%) and at the final surgery was WHO grade I (74%), II (21%), and III (4%). A subset of grade I tumors that received radiotherapy (35%) evolved to a higher grade or developed multiple recurrences without a change in histologic grade I. Grade II tumors and treatment with radiotherapy increased the odds of recurrence. Removal of the ACP and gross total resection decreased the odds of recurrence. Conclusion: Due to the routinely long interval to tumor recurrence, lifelong surveillance of patients with SOM is prudent. ACP resection and gross total resection, where possible, reduce tumor recurrence and the need for further treatment. Radiotherapy should be reserved for higher-grade meningiomas and select grade I tumors.

Purpose: To present 5 cases of alemtuzumab-induced thyroid eye disease (AI-TED) and review the literature to highlight the natural history, severity, and outcomes as compared with conventional thyroid eye disease (TED). Methods: A multi-institutional retrospective case series of patients with AI-TED was compiled. Chart review evaluated for clinical characteristics, imaging findings, and treatment for AI-TED. Additionally, a comprehensive review of the literature identified all previously published cases of AI-TED. Results: Five new patients with AI-TED were included in this series. The average clinical activity score on presentation was 2.8 (range 1–4) and reached an average peak of 5.0 during the active phase of the disease (4–7). Patients were treated medically with selenium (40%) or monoclonal antibodies including teprotumumab or tocilizumab (40%). Surgical treatment with orbital decompression for compressive optic neuropathy was performed on 2 (40%) patients. Combined with 11 previously reported cases, these 16 patients with AI-TED had an average clinical activity score on presentation of 3.3. The average length of the AI-TED phase was 14.0 months, and all patients were treated with medical and/or surgical interventions for their disease. Conclusions: Clinical and imaging findings in AI-TED mirror that of conventional TED, however, AI-TED may present with greater severity. AI-TED may develop many months after Graves’ disease; therefore, providers should be aware of this association and monitor patients for the development of severe TED.

Purpose: To review clinical presentations of periocular sebaceous carcinoma (SC) and introduce standardized nomenclature for multicentric and multifocal disease presentation. Methods: A comprehensive PubMed/Medline search was conducted to identify all articles reporting periocular multicentric or multifocal SC presentations. The authors also highlight an additional case of SC presenting with 2 clinically distinct tumor foci and complete secondary invasion of the lacrimal gland. Results: This review summarizes clinical presentations of periocular SC exhibiting discrete foci of microinvasion reported in the literature. Discrete microinvasion was associated with high rates of misdiagnosis (80%), simultaneous involvement of both upper and lower eyelids (80%), pagetoid spread (80%), multinodular growth (33%), local tumor spread (60%), previous eyelid manipulation (40%), and local recurrence (40%). Eyelid multifocality with clinically discrete nodules (42%) was associated with more advanced disease including orbital extension and regional invasion (80%). Conclusions: Despite previous reported associations with poorer outcomes, there is no consensus in the definition or nomenclature for discrete microinvasive or clinical disease presentations in periocular SC. The authors recommend defining multicentric disease as discrete foci of microinvasive tumor with basement membrane disruption and multifocal disease as discrete clinically evident nodules involving both the upper and lower eyelids. Differentiating between discrete microinvasive (multicentric) and clinically nodular (multifocal) disease may improve risk stratification to most accurately identify patients who require more aggressive management and surveillance.

Purpose: The purpose of this study was to characterize intradiploic dermoid and epidermoid orbital cysts to determine any differences in clinical, radiographic, or surgical features. Methods: A retrospective review was performed of patients presenting with intradiplopic dermoid or epidermoid cysts. Additionally, a complete review of the literature was performed to identify cases of intradiplopic orbital dermoid and epidermoid cysts. Data collected included age, sex, presenting symptoms, location of intradiplopic cyst, ophthalmic findings, treatment, and follow-up. Clinical features of dermoid versus epidermoid cyst were compared. Additionally, machine-learning algorithms were developed to predict histopathology based on clinical features. Results: There were 55 cases of orbital intradiploic cysts, 49 from literature review and six from our cohort. Approximately 31% had dermoid and 69% had epidermoid histopathology. Average age of patients with dermoid cysts was significantly lesser than that of patients with epidermoid cysts (23 vs. 35 years, respectively; P = 0.048). There was no difference between sex predilection, presenting symptoms, radiographic findings, or surgical treatment of dermoids and epidermoids. The majority of patients (64%) underwent craniotomy for surgical removal. Machine-learning algorithms KStar and Neural Network were able to distinguish dermoid from epidermoid with accuracies of 76.3% and 69%, respectively. Conclusion: Orbital intradiploic cysts are more commonly epidermoid in origin. Dermoid cysts presented in younger patients; however, there were no other significant differences in features including ophthalmic or radiographic findings. Despite similar features, machine learning was able to identify dermoid versus epidermoid with good accuracy. Future studies may examine the role of machine learning for clinical guidance as well as new surgical options for intervention.

Purpose: To morphologically describe and mathematically quantify a novel clinical feature of thyroid eye disease (TED). Methods: A retrospective study was conducted of TED patients and age-sex-matched normal controls. The arched Rainbow Brow appearance in TED patients was determined by unanimous agreement of 3 oculoplastic surgeons. Eyebrow curvature was assessed by plotting 15 points along the eyebrow in ImageJ. The fourth-degree polynomial (y = ax4 + bx3 + cx2 + dx + e) was fitted to each eyebrow. Results: Two hundred seventy-one eyes were analyzed (200 TED and 71 age-sex-matched normal controls). A Rainbow Brow was identified in 42% of TED patients. A unilateral Rainbow Brow was seen in 15% of patients. The fourth-degree polynomial coefficients yielded significant differences between Rainbow Brow patients and age-sex-matched normal controls for the coefficients a, b, c, and d. Similar analysis of TED patients with and without a Rainbow Brow showed differences in coefficients a and b. Age >50 years (p = 0.009) and the presence of brow fat expansion (p < 0.001) were associated with the presence of a Rainbow Brow. Proptosis >24 mm showed a trend toward association with the presence of a Rainbow Brow (p = 0.057). When considering the contribution of these features in a multivariable analysis, only brow fat expansion was a significant contributing factor (p = 0.009). Conclusions: The Rainbow Brow is a distinct entity in TED and is likely consequent to brow fat pad expansion. Patients with a Rainbow Brow have different eyebrow curvature as compared to both normal age-sex-matched controls and TED patients without a Rainbow Brow.