The Rate of Re-treatment in Patients Treated with Teprotumumab: A Multicenter Study of 119 Patients with 1 Year of Follow-up.

PURPOSE: To determine the rate of re-treatment in patients who receive a full course of teprotumumab therapy for thyroid eye disease (TED) and drivers of re-treatment. DESIGN: Multicenter retrospective study. PARTICIPANTS: All patients who received a full course of treatment and had available data at 1 year after initial treatment were included. METHODS: Charts were reviewed for the following information: age, sex, months since diagnosis of TED, smoking status, and prior treatments. Further, the clinical activity score (CAS), proptosis, and the Gorman diplopia score were reviewed at baseline, at the end of the first course, and at baseline for the second course in those who received it. A logistic regression model was created to review the drivers of re-treatment. MAIN OUTCOME MEASURES: Rate of re-treatment and the drivers of re-treatment. RESULTS: One hundred nineteen patients were included from 3 centers across the United States. The overall re-treatment rate was 24% (29/119). No difference was found among the 3 sites (P = 0.6). In univariable analyses, at baseline, no difference was found in proptosis (P = 0.07), diplopia score (P = 0.4), or duration of TED (P = 0.4) between patients who were re-treated and those not re-treated. From the re-treated group, 82% showed a significant proptosis response (≥ 2-mm reduction from baseline) after the initial course, whereas 68% of patients who were not re-treated showed a clinically significant proptosis response (P = 0.16). The mean ± standard deviation difference between the end of the first treatment and at baseline before the second treatment (in those who received it) was 2 ± 2 for CAS, 2 ± 4 mm for proptosis, and 1 ± 1 for diplopia score. Age was the only significant driver of re-treatment (P < 0.05). Re-treated patients were 7 years older than patients who were not re-treated (60 years vs. 53 years; P < 0.05). CONCLUSIONS: In patients receiving a full course of teprotumumab therapy, the rate of re-treatment was 24%. Age was the only driver of re-treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Novel Association Between Human Papillomavirus and Thyroid Eye Disease.

Context: Thyroid eye disease (TED) is an autoimmune disease characterized by orbital inflammation and tissue remodeling. TED pathogenesis is poorly understood but is linked to autoantibodies to thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R). Objective: To explore the potential involvement of viral infections in TED pathogenesis. Methods: Using NCBI BLAST, we compared human TSHR and IGF-1R proteins to various viral proteomes, including Papillomaviridae , Paramyxoviridae , Herpesviridae , Enterovirus , Polyomaviridae , and Rhabdoviridae . Enzyme-linked immunoassays (ELISAs) were performed on orbital adipose tissue samples from 22 TED patients and controls to quantify antiviral antibody titers. Demographics and clinical data were reviewed. Results: Homology analysis revealed conserved motifs between TSHR and IGF-1R with several viral proteins, particularly the human papillomavirus 18 (HPV18) L1 capsid protein. Basic demographic and clinical information between the cohorts were comparable. ELISAs showed statistically significant differences in the average HPV18 L1 IgG normalized optical density levels among tissues of control ( M = 0.9387, SD = 0.3548), chronic TED ( M = 2.305, SD = 1.064), and active acute TED ( M = 4.087, SD = 2.034) patients. These elevated HPV18 L1 IgG titers did not statistically correlate with TSH, T4, or TSI levels, and were elevated in TED patients irrespective of treatment with teprotumumab, indicating a direct immunological response to HPV. Conclusions: This study presents the first molecular evidence linking HPV and TED, highlighting molecular mimicry between HPV capsid protein and key autoimmunity targets in TED. This suggests an immunological link contributing to TED's pathogenesis, opening new avenues for understanding and managing the disease.

Erdheim-Chester Disease With Eyelid and Orbital Involvement: A Review of Treatment Modalities at One Institution From 2014 to 2022.

PURPOSE: To review all cases of Erdheim-Chester disease (ECD) with orbital involvement treated at Bascom Palmer Eye Institute in Miami, Florida from 2014 to 2022 and compare presentations, treatment modalities, and outcomes. METHODS: A retrospective chart review of all patients diagnosed with ECD who presented to Bascom Palmer Eye Institute from 2014 to 2022 was performed. Data collected included demographics, pretreatment history and ophthalmic examination, pathology report, treatment, subsequent examination, and relevant laboratory results. Histopathology, treatments, and outcomes were reviewed and compared between patients. RESULTS: Four cases were included. Primary treatments included vemurafenib (n = 2), cobimetinib (n = 1), and prednisone (n = 1). All patients demonstrated improvement of ophthalmic symptoms. Vemurafenib was the only medical treatment that was tolerated well and resulted in significant improvement in proptosis despite some reported dry eye; all other medications were discontinued due to intolerable side effects. CONCLUSIONS: BRAF inhibitors such as vemurafenib have been used as novel therapy in the treatment of ECD. Vemurafenib demonstrated its utility in reducing proptosis in ECD patients at one ophthalmic institution. Vemurafenib may be a favorable treatment option for BRAF -positive ECD patients presenting with orbital disease.

Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.

PURPOSE: Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. METHODS: This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. RESULTS: Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. CONCLUSIONS: Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

Superior Visual Field Testing Using Virtual Reality With and Without Eye Tracking for Functional Upper Eyelid Surgery Evaluation: A Pilot Study.

PURPOSE: To assess the sensitivity and specificity of superior visual field tests administered in virtual reality (VR) with eye tracking (VR-ET) and without eye tracking (VR 0 ) for the fulfillment of insurance coverage criteria for functional upper eyelid surgery as compared with standard automated perimetry (SAP). METHODS: This prospective cross-sectional study included 78 eyes from 41 patients with ptosis, brow ptosis, and dermatochalasis undergoing functional upper eyelid surgery evaluation. Participants underwent serial superior visual field tests using SAP and VR 0 or VR-ET in randomized order. Fulfillment of insurance coverage criteria for blepharoplasty was defined as a 30% increase in the grid seen from the untaped to the taped state. The main outcome measure was the sensitivity and specificity of VR 0 , VR-ET, and overall VR in meeting insurance coverage criteria as compared with SAP. RESULTS: VR had a sensitivity of 84.1% and specificity of 67.6%, with no significant difference between VR 0 and VR-ET. SAP agreed on insurance coverage criteria fulfillment with VR 0 in 28 (71.8%) eyes and with VR-ET in 32 (82.1%) eyes. Insurance coverage criteria fulfillment rates varied significantly by diagnosis on SAP ( p = 0.012) but not VR ( p = 0.059). CONCLUSIONS: VR may be an alternative to SAP for functional upper eyelid surgery evaluation. Future studies are needed to determine differences in patient satisfaction, testing and waiting time, and test-retest reliability between VR and SAP.

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.

Update on thyroid eye disease: Regional variations in prevalence, diagnosis, and management.

Thyroid eye disease (TED) is a rare disease that can lead to decreased quality of life, permanent disfigurement, and vision loss. Clinically, TED presents with exophthalmos, periorbital edema, extraocular muscle dysfunction, and eyelid retraction, and can lead to vision-threatening complications such as exposure to keratopathy and dysthyroid optic neuropathy (DON). Over the last several years, significant advancements have been made in the understanding of its pathophysiology as well as optimal management. Ethnic variations in the prevalence, clinical presentation, and risk of vision-threatening complications of TED are summarized, and risk factors associated with TED are discussed. Additionally, significant advances have been made in the management of TED. The management of TED traditionally included anti-inflammatory medications, orbital radiation therapy, orbital surgical decompression, and biologic therapies. Most recently, targeted therapies such as teprotumumab, an insulin-like growth factor-1 receptor antagonist, have been studied in the context of TED, with promising initial data. In this review, updates in the understanding and management of TED are presented with a focus on the international variations in presentation and management.

Lateral Tarsal Strip Complications With and Without Conjunctiva Stripping.

PURPOSE: The lateral tarsal strip (LTS) procedure is commonly used to correct eyelid malposition. When performing LTS, some surgeons elect to remove conjunctiva from the tarsal strip, while others do not. It has been hypothesized that without conjunctival stripping, the buried conjunctival tissue can cause complications such as inclusion cysts and granulomas. However, there is limited data comparing LTS cases with and without conjunctiva removal. The authors sought to evaluate whether conjunctival stripping had any impact on complication rates with LTS. METHODS: LTS operations for ectropion correction were retrospectively reviewed and were separated into 2 cohorts, Con (conjunctiva not removed) or Coff (conjunctival removed). Charts were reviewed for outcomes and complications including inclusion cyst formation, granuloma formation, wound dehiscence, infection, and focal rim tenderness. RESULTS: The complication rate was 10% versus 8% for Con versus Coff respectively ( p = 0.54). The common complications of LTS surgery were granuloma (4%), wound dehiscence (3%), focal rim tenderness (3%), and infection requiring antibiotics (<1%). There was no significant difference in these complications between the Con and Coff cohorts. CONCLUSIONS: Complications in both groups were minimal, similar to prior studies, and there was no difference between the 2 cohorts. While it has been suggested that buried conjunctiva may result in increased complication rates, the author's findings suggest that removing the tarsal conjunctiva is a superfluous step in the LTS surgery and does not affect complication rates.

Advances in magnetic resonance imaging of orbital disease.

Magnetic resonance imaging (MRI) is increasingly used by the orbital surgeon to aid in the diagnosis, surgical planning, and monitoring of orbital disease. MRI provides superior soft tissue detail compared with computed tomography or ultrasound, and advancing techniques enhance its ability to highlight abnormal orbital pathology. Diffusion-weighted imaging is a specialized technique that uses water molecule diffusion patterns in tissue to generate contrast signals and can help distinguish malignant from benign lesions. Steady-state free precession sequences such as Constructive Interference in Steady-State (CISS) and Fast Imaging Employing Steady-state Acquisition (FIESTA) generate highly detailed, 3-dimensional reconstructed images and are particularly useful in distinguishing structures adjacent to cerebral spinal fluid. Magnetic resonance angiography can be used to characterize vascular lesions within the orbit. New developments in magnetic field strength as well as the use of orbital surface coils achieve increasingly improved imaging resolution.

Updates on the understanding and management of thyroid eye disease.

Thyroid eye disease (TED) is a complex disease associated with myriad clinical presentations, including facial disfigurement, vision loss, and decreased quality of life. Traditionally, steroid therapy and/or radiation therapy were commonly used in the treatment of active TED. While these therapies can help reduce inflammation, they often do not have a sustainable, significant long-term effect on disease outcomes, including proptosis and diplopia. Recent advances in our understanding of the pathophysiology of TED have shifted the focus of treatment toward targeted biologic therapies. Biologics have the advantage of precise immune modulation, which can have better safety profiles and greater efficacy compared to traditional approaches. For instance, the insulin-like growth factor-1 receptor (IGF-1R) has been found to be upregulated in TED patients and to colocalize with the thyroid-stimulating hormone receptor (TSHR), forming a signaling complex. Teprotumumab is an antibody targeted against IGF-1R. By inhibiting the IGF-1R/TSHR signaling pathway, teprotumumab may reduce the production of proinflammatory cytokines, hyaluronan secretion, and orbital fibroblast activation in patients with TED. Due to promising phase II and III clinical trial results, teprotumumab has become the first biologic US Food and Drug Administration (FDA)-approved for the treatment of TED. In addition, there are currently ongoing studies looking at the use of antibodies targeting the neonatal Fc receptor (FcRn) in various autoimmune diseases, including TED. FcRn functions to transport immunoglobulin G (IgG) and prevent their lysosomal degradation. By blocking the recycling of IgG, this approach may dampen the body's immune response, in particular the pathogenic IgG implicated in some autoimmune diseases. Advances in our understanding of the pathophysiology of TED, therefore, are leading to more targeted therapeutic options, and we are entering an exciting new phase in the management of TED. This review will cover recent insights into the understanding of TED pathophysiology and novel treatment options as well as ongoing studies of new potential treatment options for TED.

Thyroid eye disease with choroidal folds.

Purpose: To determine the clinical course of patients with chorioretinal folds (CRF) in thyroid eye disease (TED).Methods: A multi-center retrospective case series of patients with TED who developed CRF.Results: Ten patients (17 eyes) with CRF related to TED were identified. The mean age of presentation was 59.3 ± 8.3 years old. The majority of patients were male (70%), hyperthyroid (70%), hyperopic (53%), had a history of radioactive iodine (60%), and currently on methimazole treatment (30%). Three patients (3 eyes) had unilateral involvement of CRF with bilateral TED. The average clinical activity score was 3.6 ± 2.1 at the time of presentation. The most commonly enlarged extraocular muscles were medial (76%), inferior (64%), superior (64%) and lateral rectus (35%). Compressive optic neuropathy was seen in 47% of eyes. Treatment included oral prednisone (70%), orbital decompression (59%), thyroidectomy (20%) and tocilizumab (10%). The CRF did not resolve over a follow up period of 24.7 ± 23.7 months in 70% of eyes. There was no significant difference in average axial length (25.7 ± 4.9 mm) and optic nerve to optic strut distance (37.8 ± 3.9 mm) between patients with CRF and the eight age-and sex-matched TED control patients without CRF (p = 0.81 and 0.65 respectively). A univariable and multivariable analysis found an enlarged inferior rectus as a factor in TED patients with persistent CRF.Conclusions: CRF are often an indicator of visually threatening situations and often do not resolve despite treatment of TED.

Pathological Features and Clinical Course in Patients With Recurrent or Malignant Orbital Solitary Fibrous Tumor/Hemangiopericytoma.

PURPOSE: A risk assessment score for metastasis based on age, tumor size, and mitotic figures has been suggested for nonorbital solitary fibrous tumor (SFT)/hemangiopericytoma. The authors herein examine the clinicopathological features of recurrent and metastatic orbital SFT and evaluate the existing risk assessment score for orbital SFT. METHODS: The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried for patients with recurrent or malignant orbital hemangiopericytoma/SFT. The medical records were reviewed for clinical and pathologic findings, treatments, and outcomes. RESULTS: Eight patients from 3 institutions were identified with recurrent orbital hemangiopericytoma/SFT. Median age at diagnosis was 59 years, and 4 patients were women. The mean size of tumor was 2.1 ± 1.1 cm. All patients were initially treated with surgery and experienced local recurrence after a median of 4 (range 0.5-10) years. Five patients were treated with orbital radiation. Two patients also developed distant metastases and eventually died of their disease. Median Ki-67 was 5% (range 1-65%) and 5 mitotic figures/10 high-power fields (range 2-30). The previously described risk stratification model for nonorbital SFT did not correlate with the propensity to develop metastases in this cohort; however, both patients with distant metastasis had > 4 mitotic figures /10 high-power fields. CONCLUSIONS: In this cohort of recurrent orbital hemangiopericytoma/SFT, median time to recurrence was 4 years underscoring the importance of careful continued follow-up. The current risk stratification models have limited use for orbital lesions, mostly due to the fact that orbital SFTs are smaller than even the smallest size criteria in this risk assessment model.

Zygomatic dental implant induced orbital fracture and inferior oblique trauma.

A 51-year-old female underwent four upper zygomatic dental implants (ZI) and one upper and four lower conventional implants. Immediately postoperatively, the patient had pain and diplopia upon manual elevation of the edematous eyelid. Panoramic x-ray showed a malpositioned right upper ZI, requiring removal of the right upper ZI the following day. The patient had delayed referral to ophthalmology one month later for persistent diplopia. Computed tomography scan and magnetic resonance imaging demonstrated a right inferolateral fracture with fibrosis surrounding the inferior oblique muscle. Clinical exam showed right lower eyelid retraction, right hypotropia, and inability to elevate in adduction, consistent with a right inferior oblique paresis. Surgical exploration revealed incarceration of lid and orbital tissue into the fracture. After repositioning of the prolapsed tissue, a high-density porous polyethylene implant was placed for fracture repair. The inferior fornix was reconstructed with amniotic membrane and 5-fluorouracil was injected into the scar tissue. Six months later, the patient underwent strabismus surgery with resolution of symptoms.

The Effect of Prostaglandin Analogue Bimatoprost on Thyroid-Associated Orbitopathy.

Purpose: We characterize the effect of bimatoprost on orbital adipose tissue in thyroid-associated orbitopathy (TAO) with clinicopathologic correlation. Methods: Orbital adipose-derived stem cells (OASCs) from types 1 and 2 TAO and control patients with and without exposure to 1 µm bimatoprost were examined via immunohistochemistry, RT-PCR, and Western blot for cell viability, migration capacity, lipid content, adipocyte morphology, mitochondrial content, and levels of adipogenic markers. A retrospective chart review was performed for clinicopathologic correlation. In mice, optical coherence tomography and pattern electroretinography were performed at baseline and at 1 month following a retrobulbar injection of bimatoprost, followed by orbital exenteration for histopathologic examination. Results: Types 1 and 2 TAO-derived cells had a significantly higher migration capacity and lipid content than those of healthy controls. With the addition of bimatoprost, types 1 and 2 TAO and control adipocytes exhibited a significant decrease in lipid content with morphologic transformation into smaller and multilocular lipid droplets, and an increase in mitochondrial load and UCP-1 expression consistent with an increase in brown adipose tissue turnover. Retrobulbar injection of bimatoprost in mice did not alter the gross morphology, retinal thickness, or ganglion cell function in vivo. Conclusions: Bimatoprost inhibits adipogenesis in OASCs and upregulates pathways involved in the browning of adipocytes. Furthermore, retrobulbar injection of bimatoprost is tolerated without immediate adverse effects in mice. Our results suggest a potential future application of prostaglandin analogues in the treatment of TAO.

Orbital Fractures.

Anatomic, rather than volumetric, reconstruction leads to improved outcomes in orbital reconstruction. Endoscopic visualization improves lighting and magnification of the surgical site and allows the entire operative team to understand and participate in the procedure. Mirror-image overlay display with navigation-guided surgery allows in situ fine adjustment of the implant contours to match the contralateral uninjured orbit. Precise exophthalmometry is important before, during, and after surgery to provide optimal surgical results.

RNA-Sequencing Gene Expression Profiling of Orbital Adipose-Derived Stem Cell Population Implicate HOX Genes and WNT Signaling Dysregulation in the Pathogenesis of Thyroid-Associated Orbitopathy.

Purpose: The purpose of this study was to characterize the intrinsic cellular properties of orbital adipose-derived stem cells (OASC) from patients with thyroid-associated orbitopathy (TAO) and healthy controls. Methods: Orbital adipose tissue was collected from a total of nine patients: four controls and five patients with TAO. Isolated OASC were characterized with mesenchymal stem cell-specific markers. Orbital adipose-derived stem cells were differentiated into three lineages: chondrocytes, osteocytes, and adipocytes. Reverse transcription PCR of genes involved in the adipogenesis, chondrogenesis, and osteogenesis pathways were selected to assay the differentiation capacities. RNA sequencing analysis (RNA-seq) was performed and results were compared to assess for differences in gene expression between TAO and controls. Selected top-ranked results were confirmed by RT-PCR. Results: Orbital adipose-derived stem cells isolated from orbital fat expressed high levels of mesenchymal stem cell markers, but low levels of the pluripotent stem cell markers. Orbital adipose-derived stem cells isolated from TAO patients exhibited an increase in adipogenesis, and a decrease in chondrogenesis and osteogenesis. RNA-seq disclosed 54 differentially expressed genes. In TAO OASC, expression of early neural crest progenitor marker (WNT signaling, ZIC genes and MSX2) was lost. Meanwhile, ectopic expression of HOXB2 and HOXB3 was found in the OASC from TAO. Conclusion: Our results suggest that there are intrinsic genetic and cellular differences in the OASC populations derived from TAO patients. The upregulation in adipogenesis in OASC of TAO may be is consistent with the clinical phenotype. Downregulation of early neural crest markers and ectopic expression of HOXB2 and HOXB3 in TAO OASC demonstrate dysregulation of developmental and tissue patterning pathways.

Primary Cribriform Carcinoma of the Eyelid With Neuroendocrine Features: A Case Report.

A variety of tumors may involve the eyelid, most of which are primary, but rarely can be metastatic. Previously reported eyelid primary carcinomas with neuroendocrine features include Merkel cell carcinoma, apocrine and eccrine gland carcinoma, sebaceous gland carcinoma, and one report of primary "well-differentiated neuroendocrine tumor." Herein we report the first case of primary cribriform carcinoma of the eyelid with neuroendocrine features. The patient is a 75-year-old black man who presented to the clinic with a 5-year history of a slowly growing, non-painful, non-exudative lesion of his left lower eyelid. Examination disclosed a non-tender 8 mm by 9 mm ovoid, firm, euchromic subdermal non-adherent nodule involving the left lower eyelid with no madarosis or loss of lid margin architecture, but with overlying induration. An incisional biopsy demonstrated nodules and aggregates of tumor composed of cuboidal hyperchromatic basoloid cells with occasional mitotic figures within sheets in a mostly cribriform and occasionally papillary pattern. The tumor was diffusely positive for cytokeratin, Epithelial Membrane Antigen, and p40 and focally positive for synaptophysin. The tumor was negative with antibodies for Cytokeratin 20 (CK20), p63, CD10, Thyroid Transcription Factor-1, Cytokeratin 7, Prostate Specific Antigen, and Epithelial Specific Antigen. Oncologic evaluation was negative for metastases. The patient underwent a complete excision of his eyelid tumor with 5 mm margins using Mohs surgery, with subsequent reconstruction using a Hughes tarsoconjunctival flap, myocutaneous advancement flap, and lateral canthal tendon plication.

J Drugs Dermatol. 2017;16(2):173-174.

Idiopathic Unilateral Enlargement of the Extraocular Muscles in an Infant.

A 6-month-old boy presented with a unilateral motility deficit of the right eye in all fields of gaze. Neuroimaging revealed unilateral enlargement of the medial, lateral, and inferior rectus muscles with sparing of the tendons. An evaluation for thyroid eye disease, idiopathic orbital inflammation, myositis, inflammatory and neoplastic infiltration of the muscle, vascular anomalies, and metastatic neuroblastoma was unrevealing. Biopsy of the muscle revealed normal architecture with an absence of inflammation, infiltration, or fibrosis. A review of the literature reveals the exceptionally rare nature of this finding. While the authors cannot rule out an atypical case of congenital euthyroid eye disease, this constellation of findings is not consistent with thyroid eye disease and may represent previously described cases of idiopathic enlargement of the extraocular muscles.