Ocular and orbital tumors in childhood.

Pediatric tumors of the eye and orbit can be benign or malignant as well as congenital or acquired and are usually distinctively different than those seen in adults. Although most of these neoplasms are benign (eg, dermoid cyst, chalazion, molluscum), their location near and within a vital organ can result in serious dermatologic and ophthalmologic sequelae. Lesions discussed include vascular lesions, retinoblastomas (the most common primary pediatric intraocular malignancy), rhabdomyosarcoma (the most common primary pediatric orbital malignancy), Langerhans cell histiocytosis, and metastatic lesions to the orbit (neuroblastoma, Ewing sarcoma). Although cysts and ocular melanoma can occur within the pediatric population, these conditions are covered in other contributions in this issue of Clinics in Dermatology.

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.

Intralesional or intraorbital rituximab injection for the management of biopsy-proven idiopathic orbital inflammation involving the lacrimal gland.

OBJECTIVE: To evaluate the efficacy of intralesional rituximab injection for the management of idiopathic orbital inflammation (IOI) involving the lacrimal gland, which is the most common subtype. METHOD: Eighteen consecutive patients with biopsy-proven IOI involving the lacrimal gland were included. Rituximab (50 mg/5 mL) was injected intralesionally at monthly intervals. RESULTS: Clinically, all patients presented with upper eyelid swelling and ptosis. Most patients (56%) had periocular pain and a palpable superotemporal mass. Biopsies showed chronic inflammation without fibrosis in 14 patients (78%) and chronic inflammation and fibrosis in 4 patients (22%). Intralesional rituximab was injected once in 1 patient (6%) because of complete response after the first injection, twice in 11 patients (61%), and 3 times in 6 patients (33%) because of partial response after 2 injections. After a mean follow-up of 33 months (median, 33 months; range, 11-59 months), 16 patients (89%) showed a clinical response, including 14 patients (78%) a complete response (i.e., disappearance of all lesions) and 2 patients (11%) with a partial response (i.e., ≤30% decrease in lesion diameter). Two patients (11%) did not respond after 3 injections and were placed on systemic corticosteroid and methotrexate therapies. Two patients (11%) with a complete response developed subsequent recurrence 12 and 49 months after their last injections. Both were treated with 2 additional rituximab injections, 1 month apart, and showed complete response when examined 27 and 11 months after treatment, respectively. CONCLUSION: Intralesional rituximab injection may be an effective treatment for IOI involving the lacrimal gland, achieving a 78% complete response rate in this series. Local treatment with rituximab has the potential to avoid the ocular and systemic side effects of corticosteroid and systemic immunosuppressive treatment.

Do Not Fall for This; Diagnostic Challenges in Orbital Floor Fractures With Extraocular Muscle Entrapment.

Extraocular muscles that are entrapped in orbital fracture sites require emergent surgical treatment. Muscle entrapment can present with subtle findings or mimic other conditions, contributing to delays in diagnosis. Here, we present two cases of extraocular muscle entrapment that were not immediately identified. By discussing the diagnostic challenge in these cases, we aim to increase the comfort of all physicians in identifying muscle entrapment in the emergency department.

Progression of Subperiosteal Orbital Abscess after Clinical Resolution on Intravenous Antibiotics and Steroids.

We present a case of a 7-year-old boy who was presented with a small medial subperiosteal orbital abscess (SPOA) and trace superior phlegmon and who was initially treated with intravenous (IV) antibiotics, corticosteroids, and observation. After clinical resolution and discharge, the patient returned with superior migration of his abscess requiring surgical drainage. Potential factors leading to readmission are discussed, including the anti-inflammatory and immunosuppressant effects of steroids, and presence of early surgical indictors such as bony dehiscence and proptosis. This case highlights the need for careful consideration of initial imaging and presence of a non-medial phlegmon prior to initiation of steroids.

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.

Comparison of Postoperative Infection Rates After Office-based Oculoplastic Procedures Using Sterile and Clean Gloves.

PURPOSE: To compare postoperative infection (PI) rates using sterile and clean-boxed gloves in office-based oculoplastic procedures. METHODS: Prospective, comparative study of patients undergoing oculoplastic procedures by a single surgeon (RS) in an office-based procedure room between October 2018 and September 2020. Participants included were 18 years or older. Excluded were patients on oral antibiotics within 2 weeks before the procedure, had a follow-up period of less than 1 week, had a contaminated wound, had complex reconstructions, or had multiple simultaneous procedures performed. Oculoplastic procedures were performed using either sterile or clean-boxed gloves. The main outcome measure was the frequency of postoperative infection. RESULTS: Three thousand one hundred twenty-nine patients, 1,815 (58%) of whom were women, with a mean age of 60 (18-102) years were included. One thousand five hundred seventy procedures were performed with sterile gloves, while 1,559 were performed with clean-boxed gloves. The patients in the 2 groups were similar in age, gender, and number of high-risk individuals. One patient in the sterile glove group who underwent upper blepharoplasty (0.064%) and one patient (0.064%) in the clean-boxed glove group who had an external levator advancement blepharoptosis repair developed PI. Neither patient had risk factors for infection, and both infections resolved after 1 week of oral amoxicillin-clavulanate 875/125 mg twice daily. CONCLUSIONS: In minimally complex in-office oculoplastic procedures, using sterile versus clean-boxed gloves resulted in similar low infection rates in this large cohort. The healthcare benefits may not outweigh the costs of using sterile gloves universally for office-based oculoplastic procedures.

Intravascular Large B-cell Lymphoma Diagnosed by Nasal Biopsy in a Patient Presenting with Bilateral Ptosis and Ophthalmoplegia.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of lymphoma, involving the lumen of predominantly small blood vessels, especially capillaries. The orbit is an uncommon site of involvement for IVLBCL, and diagnosis before autopsy is even more rare as most cases are established post-mortem. Herein, the authors describe a 73-year-old male who presented with 3 weeks of progressive bilateral ptosis and ophthalmoplegia. Computed tomography (CT) and subsequent magnetic resonance imaging (MRI) revealed diffuse abnormal thickening and enhancement of bilateral orbital apices, superior orbital fissures, and cavernous sinus, along with persistent focal opacification of the left frontal and ethmoid sinuses. Infectious and inflammatory workup of serum and cerebrospinal fluid was negative. Ethmoidal sinus and middle turbinate biopsy confirmed intravascular large B-cell lymphoma and the patient was started on R-CHOP chemotherapy regimen.

Tarsal Ectropion Repair With Modified Bick Eyelid Tightening and Inverting Sutures.

PURPOSE: The authors report on a 10-year experience of correcting tarsal ectropion using a combined method of modified Bick eyelid tightening (MBLT) and inverting sutures. METHODS: Retrospective, interventional case series of consecutive patients with tarsal ectropion who underwent MBLT and inverting sutures by a single surgeon (RS) between July 2010 and July 2020. Thirty-four patients, 24 of whom were female, with a mean age of 81.6 years (range 59-92) were included. Eight patients had bilateral disease. All procedures were performed under local anesthesia in an office setting. Treatment success was defined by eyelid position, symptoms, and need for reoperation. RESULTS: Thirty-one patients (91%) had a successful outcome. Three patients (9%) had satisfactory results with improved symptoms and mild residual ectropion, for which further surgery was not required. No patients had poor results. The mean follow-up time was 4.5 months (range 3-11 months). The inverting sutures were well tolerated in all cases and none had to be removed due to ocular surface discomfort. There were no visible scars from the inverting sutures in any patient at postoperative month 3. CONCLUSIONS: A combination of eyelid tightening using MBLT and inverting sutures is a simple and effective treatment for lower eyelid tarsal ectropion with minimal tissue dissection.

Cemiplimab for Orbital Squamous Cell Carcinoma in 11 Cases.

PURPOSE: To review the demographics, clinical features, and response of orbital squamous cell carcinoma treated with cemiplimab. METHODS: This is a retrospective multi-institutional series. Patient characteristics, drug dosing, duration, and response to treatment were evaluated. RESULTS: The study cohort consisted of 11 patients from 5 institutions. All patients received a regimen of 350 mg q 3 weeks and an average of 11.2 cycles (SD 5.8). No patient experienced significant side effects requiring treatment or cessation of cemiplimab. Complete response was achieved in 9 patients (82%) treated with cemiplimab. CONCLUSIONS: Immune checkpoint inhibitors, such as cemiplimab provide a globe-sparing option for the treatment of orbital squamous cell carcinoma. It is important to consider these agents especially when orbital exenteration is the alternative.

Simultaneous Orbital and Intracranial Abscesses in 17 Cases.

PURPOSE: To describe the demographics, clinical presentation, treatment, and outcomes of a rare cohort with simultaneous orbital and intracranial abscesses. METHODS: A historical cohort study of 17 patients with simultaneous orbital and intracranial abscesses between 2010 and 2018 was performed. The demographics, location of abscesses, treatment, and outcomes of these patients were analyzed. RESULTS: The mean age was 26.9 years (range 5-83 years). Fourteen patients (82%) were male. In this cohort, the most common orbital abscess location was the superior orbit, involved in 14 patients (82%). The most common site of intracranial abscess was the frontal lobe, involved in 16 patients (94%). Concurrent sinus disease was present in 16 patients (94%). Surgical evacuation was the standard of treatment, with 94% of patients undergoing at least one surgical procedure. Streptococcus species were the most common, isolated from 6 sinus cultures (43%), 3 orbitotomy cultures (21%), and 4 craniectomy cultures (36%). Staphylococcus species were also common. Most patients (94%) had stable or improved mental status and visual function at the conclusion of their treatment. CONCLUSIONS: Simultaneous orbital and intracranial abscesses are rare. Local invasion from the orbit into the intracranial space may occur from direct spread, thus superior orbital abscesses pose the greatest risk for intracranial spread. Additional factors such as infection with Streptococcus and Staphylococcus species as well as male sex appear to be risk factors for intracranial spread. For those who develop intracranial abscesses, young age and absence of seizures or altered mental status at presentation may be associated with favorable outcomes.

Carcinoid Tumors of the Orbit and Ocular Adnexa.

PURPOSE: Well-differentiated neuroendocrine or carcinoid tumors are found most commonly in the gastrointestinal tract. When metastatic to the orbit, they tend to have a propensity for the extraocular muscles. The purpose of this study was to better understand the diversity in presentation of orbital carcinoid disease and to determine predictors for survival. METHODS: In this observational cross-sectional cohort study, data from 8 tertiary orbital practices were compiled. Demographic, clinical, pathologic, American Joint Committee on Cancer stage and grade, imaging, and management data were extracted for all the patients. Descriptive statistics were calculated. Subgroups were compared utilizing analysis of variance analyses and Kaplan-Meier curves. Time to progression and disease-specific and overall mortality were calculated. Comparisons were performed for the following a priori pairs: unknown versus known primary tumor, single versus multiple extraocular muscle involvement, unilateral versus bilateral orbital disease, extraocular muscle versus other orbital involvement, and excisional versus incisional surgery. RESULTS: A total of 28 patients with carcinoid tumors of the orbit were identified. Of these, 57.1% of patients were female, the mean age at diagnosis of the primary tumor was 58.8 years and the mean age at diagnosis of orbital disease was 62.6 years. At primary presentation, all patients were American Joint Committee on Cancer stage III or IV and 21.4% demonstrated carcinoid syndrome. Muscle involvement was noted in 78.6% of patients, and of these, 72% were noted to have single muscle disease. Eight patients had no primary tumor identified; 3 of these 8 demonstrated disseminated disease at the time of diagnosis. The overall 5-year survival rate was 81.8% from diagnosis of primary tumor and 50% from diagnosis of orbital disease. Subgroup analysis revealed that patients with unilateral orbital disease when compared with bilateral orbital disease had a longer progression-free survival and time to death from all causes (p = 0.025). Patients with disease localized to the orbit at presentation had longer time to death than those with disseminated disease. Treatment with surgery, radiation, or octreotide did not appear to affect survival. Patients managed with systemic chemotherapy had a shorter time of survival than the rest of the group. All other subgroup comparisons were not found to be statistically significant. CONCLUSIONS: Neuroendocrine tumors of the orbit represent a wide spectrum of disease, with some cases being part of disseminated disease, while others being localized presentations. This heterogeneity may be responsible for the slightly higher overall survival in these patients than others with metastatic carcinoid tumors in other locations.