Teprotumumab for the Treatment of Active Thyroid Eye Disease.

BACKGROUND: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). RESULTS: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. CONCLUSIONS: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).

Necrobiotic Xanthogranuloma With Associated Monoclonal Gammopathy Presenting as an Eyelid Nodule.

Necrobiotic xanthogranuloma (NXG) is a progressive non-Langerhans cell histiocytosis with a predilection for the periorbital area. NXG is most commonly associated with monoclonal gammopathy and ophthalmic complications. The authors present a 69-year-old man who was evaluated for a left upper eyelid nodule and plaques on the lower extremities, trunk, abdomen, and right upper extremity. Biopsy of the eyelid was supportive for NXG. Serum protein electrophoresis was positive for a monoclonal gammopathy, IgG light chain kappa. MRI showed preseptal involvement. The periocular nodules cleared with a high dose of prednisone; however, the other skin lesions persisted. Bone marrow biopsy showed kappa-restricted 6% plasma cells and he was treated with intravenous immunoglobulin. This case illustrates the importance of clinicopathologic correlations to render an NXG diagnosis.

Inflammation and Fibrosis in Orbital Inflammatory Disease: A Histopathologic Analysis.

PURPOSE: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens. METHODS: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 countries. Seventy-four specimens were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 24 with NSOI, and 12 healthy controls. RESULTS: The mean inflammation and fibrosis scores for healthy controls were 0.0 and 1.1, respectively. Orbital inflammatory disease groups' inflammation (I) and fibrosis (F) scores, formatted [I, F] with respective p -values when compared to controls, were: TAO [0.2, 1.4] ( p = 1, 1), GPA [1.9, 2.6] ( p = 0.003, 0.009), sarcoidosis [2.4, 1.9] ( p = 0.001, 0.023), and NSOI [1.3, 1.8] ( p ≤ 0.001, 0.018). Sarcoidosis had the highest mean inflammation score. The pairwise analysis demonstrated that sarcoidosis had a significantly higher mean inflammation score than NSOI ( p = 0.036) and TAO ( p < 0.0001), but no difference when compared to GPA. GPA had the highest mean fibrosis score, with pairwise analysis demonstrating a significantly higher mean fibrosis score than TAO ( p = 0.048). CONCLUSIONS: Mean inflammation and fibrosis scores in TAO orbital adipose tissue samples did not differ from healthy controls. In contrast, the more "intense" inflammatory diseases such as GPA, sarcoidosis, and NSOI did demonstrate higher histopathologic inflammation and fibrosis. This has implications in prognosis, therapeutic selection, and response monitoring in orbital inflammatory disease.

Orbital MALT lymphoma with amyloid deposition.

MALT lymphoma is a commonly encountered orbital tumor, and primary amyloidosis is frequently found to be an independent orbital lesion. Orbital MALT lymphoma with associated amyloid deposition is considered rare, with only 12 cases previously published. We describe a 33-year-old man, the youngest patient reported to-date, with a mass in the superonasal quadrant of the right anterior orbit. Pathology demonstrated extranodal marginal zone lymphoma in mucosa-associated lymphoid tissue with associated amyloid deposition. Systemic work-up revealed no other site of either lymphoma or amyloidosis. The patient underwent local irradiation and subsequent surgical resection of the residual mass. Persistent lymphoma was found and treated with rituximab.

Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment: OPTIC-X Study.

PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. PARTICIPANTS: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. METHODS: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. MAIN OUTCOME MEASURES: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. RESULTS: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. CONCLUSIONS: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.

Management of periocular cutaneous squamous cell carcinoma with perineural invasion: a case series and literature review.

PURPOSE: To review and elucidate the complex, multimodal management of periocular cutaneous squamous cell carcinoma (SCC) with perineural invasion (PNI), and offer practical, evidence-based patient care recommendations. METHODS: Three exemplary cases of high-risk periocular cutaneous SCC with PNI were selected from a single surgeon's experience. The clinical courses, management, and clinical outcomes, with follow-up intervals of 19, 19, and 24 months after presentation, were reviewed. The English-language literature on PNI, with attention to the management of cutaneous SCC of the head and neck (SCCHN), was reviewed. RESULTS: PNI of cutaneous SCCHN portends aggressive tumor behavior and a worsened prognosis. Treatment is multimodal, with varied combinations of surgical excision, radiotherapy (RT), and systemic chemotherapy. Retrospective reports from multiple institutions involve heterogenous patient populations, treatment strategies, and confounding variables that preclude formulation of a standardized treatment paradigm. Newer, comparative studies of advanced RT techniques (e.g., hyper-fractionation), novel systemic chemotherapeutic agents (e.g., cetuximab, cemiplimab), and varied integrative regimens are providing additional insights. Prompt initiation of adjuvant therapies (within 6-8 weeks of surgery), and careful evaluation of lymphatic basins can increase oncologic control. Utilizing deep-tissue fixation of advancement flaps and eyelid stabilization can enhance functional and aesthetic results. CONCLUSIONS: Management of cutaneous SCC with PNI remains complex and in most cases requires combined-modality therapy directed by a multidisciplinary tumor board. With novel therapies and new treatment patterns, optimal combinations and intensities of individual modalities require further elucidation. The oculofacial plastic surgeon plays a pivotal role - in diagnosis, coordination of interdisciplinary management, thoughtful surgical reconstruction, and postoperative surveillance.

Case Report: Idiopathic Sclerosing Orbital Inflammation.

SIGNIFICANCE: Idiopathic sclerosing orbital inflammation (ISOI) is characterized by insidious, chronic, progressive inflammation and fibrosis that damage ocular structures and produce a mass effect. This case highlights the challenges in diagnosis and management of ISOI, as well as the associated ocular morbidities, including potential vision loss. PURPOSE: The purpose of this study was to provide education regarding a rare condition that exhibits variable presentation and has an unpredictable success rate with regard to treatment paradigm. Improved therapeutic options are promising. Ultimately, early detection and management are key and may allow for better visual outcome. CASE REPORT: A 46-year-old woman presented with complaints of chronic right-sided facial headaches and eye pain and gradual right globe prominence over the previous 6 months. Worsening vision and decreased right peripheral visual field were also noted. Upon examination, an afferent pupillary defect and florid disc edema were evident. Imaging studies revealed an orbital and extraorbital infiltrative mass involving the right orbital apex, inferior orbital fissure, pterygopalatine fossa, and cavernous sinus. Right anterior orbitotomy with biopsy revealed fragments of fibroconnective and adipose tissue with sclerosis and chronic focal inflammation, consistent with ISOI. Treatment included intravenous methylprednisone, followed by oral prednisone, beginning at 60 mg/d with a slow taper thereafter. Signs and symptoms improved dramatically and eventually resolved. Vision significantly improved, and the afferent pupillary defect resolved. The patient remained asymptomatic at 3-month follow-up. CONCLUSIONS: Idiopathic sclerosing orbital inflammation is difficult to diagnose and manage. No large studies exist because of the rare nature of the disease. Slowly progressive, nonspecific signs and symptoms may delay recognition and treatment. Orbital imaging and histopathologic analysis are critical for definitive diagnosis. Conventional treatment with corticosteroids is not uniformly successful, but newer combined therapy options can improve outcomes. Early identification and treatment are key to management and ultimate preservation of function and vision.

Teprotumumab in Clinical Practice: Recommendations and Considerations From the OPTIC Trial Investigators.

BACKGROUND: Thyroid eye disease (TED) is a vision-threatening and debilitating condition that until very recently had no Food and Drug Administration (FDA)-approved medical therapies. Teprotumumab has recently been approved to treat TED. We aim to provide guidance for its use, based on the input of the US investigators who participated in Phase 2 and Phase 3 clinical trials. METHODS: An expert panel was convened on October 11th and November 16th of 2019. All panel members had extensive experience as investigators in the Phase 2 and/or Phase 3 clinical trials of teprotumumab. Consensus among those investigators was reached to determine patient characteristics most appropriate for teprotumumab treatment. Safety guidelines were also reviewed and agreed on. RESULTS: The authors recommend that teprotumumab be considered first-line therapy for patients with clinically significant ophthalmopathy, including those with disease duration exceeding 9 months. The clinical activity score (CAS) may be useful for longitudinal monitoring but should not be used to determine treatment eligibility. Criteria will likely be expanded after more experience with the drug. Using teprotumumab for patients with TED with substantial signs, symptoms, or morbidity without a CAS score of >4 (e.g., progressive proptosis, diplopia, and early compressive optic neuropathy) or more, could be considered. Diabetes mellitus and inflammatory bowel disease comorbidities should not be exclusionary, but stringent monitoring in these patients is recommended. Drug dosing, administration interval, and duration should adhere to the study protocol: 8 infusions, separated by 3 weeks. Patients with more severe disease may benefit from additional doses. Corticosteroids can be used before or during teprotumumab therapy. Clinical and laboratory monitoring should be consistent with good clinical practice for patients receiving teprotumumab. CONCLUSIONS: Confirming the efficacy of teprotumumab usage outside the narrow parameters of the completed clinical trials will require rigorous scientific validation. As a step in that direction, we believe its on-label usage is appropriately applied to all patients with TED with substantial symptoms or morbidity, as judged by their physician.

Fate and Management of Incompletely Excised Solitary Fibrous Tumor of the Orbit: A Case Series and Literature Review.

PURPOSE: There is an imperfect correlation between the histology and behavior of solitary fibrous tumor (SFT). In addition, recurrence is common, and dedifferentiation may occur over time. Preferred primary treatment is intact excision, but friable pseudocapsules and tenacious attachments can thwart this goal in the crowded, visually sensitive orbit. This study addresses the fate and appropriate management of incompletely excised orbital SFT. METHODS: Among a single surgeon's 7-case experience with orbital SFT, 3 cases involved incomplete primary excision, either before (2 cases) or after (1 case) referral. We reviewed the clinicopathologic data in these 3 cases, with follow-up intervals of 18, 21, and 52 years after initial presentation. We reviewed the English-language literature on SFT, with special attention to evolving nomenclature, orbital involvement, recurrence, malignant transformation, and management options. RESULTS: Benign versus malignant designations of SFT vary with histological and behavioral criteria. Approximately 150 orbital cases have been reported. Published rates of primary malignancy and recurrence across all histologic categories are 6% to 12% and 30% to 37%, respectively. We identified 43 well-documented recurrences (range, 6 months-33 years; median, 3 years) and 10 cases of histological dedifferentiation (range, 14 months-33 years). Because of SFT's rarity and needed follow-up intervals, the value of adjuvant therapy is not yet proven. In follow up of 18, 21, and 52 years after initial presentation, our 3 cases with incomplete excision showed either no recurrence (Case 1) or no morphological dedifferentiation (Cases 2, 3). CONCLUSION: A treatment algorithm is predicated on the completeness of surgical excision and histological features. However, we recommend case-by-case multidisciplinary decisions in a tumor-board setting.

Teprotumumab for Thyroid-Associated Ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).

The spectrum of orbital dermoid cysts and their surgical management.

PURPOSE: The purpose of this study is to describe a spectrum of surgical approaches to orbital dermoid cysts, influenced by the anatomic location of the expanded cyst wall and other factors. METHODS: In this retrospective case series, we reviewed cases of dermoid cysts surgically excised during a 39-year period (1977-2016). Cysts were categorized according to the location of the expanded cyst wall and other considerations. The impact of these factors on surgical management was determined. RESULTS: We identified six dermoid cyst growth patterns based on the anatomic location of the expanded cyst wall that influence the surgical approach: anterior to the frontozygomatic suture (FZS), superior to the FZS, medial to the FZS and other lateral wall sutures, traversing the FZS and other lateral wall sutures, nasoglabellar, and sinus tract from the orbit to the skin. Two additional factors influencing surgical methodology included satellite inflammatory pseudocysts and recurrence after surgical resection. CONCLUSION: Orbital dermoid cysts are not monolithic lesions. Functional and aesthetic outcomes can benefit from considering the anatomic pattern of cyst wall expansion and other factors in their surgical management.

Surgical Management of a Recurrent Odontogenic Keratocyst With Orbital and Temporal Fossa Invasion.

Odontogenic keratocyst is a benign locally aggressive odontogenic cyst with a high recurrence rate. This report presents an unusual case of a recurrent odontogenic keratocyst with zygomatic bone involvement and orbital and temporal extension resulting in globe compression. Odontogenic keratocyst is reviewed, and surgical management of the cyst is discussed.The authors present a case of a recurrent odontogenic keratocyst involving the zygoma with orbital and temporal invasion; aggressive surgical resection and reconstruction was required.

Surgical Timing for Congenital Ptosis Should Not Be Determined Solely by the Presence of Anisometropia.

PURPOSE: Timing of surgery in children with congenital ptosis is a critical component of care, and anisometropia is frequently cited as an indication for early intervention. The purpose of this study is to evaluate the change in refractive error following surgery for congenital ptosis to better inform decisions regarding the timing of surgery. METHODS: A retrospective review of clinical records was performed on patients who underwent surgical correction of congenital ptosis in an academic oculoplastic surgery practice from 2002 to 2017. Patients with complete preoperative and postoperative refractive data were included in the study. Changes in refractive error following surgery were analyzed. RESULTS: Among 184 pediatric patients who underwent ptosis surgery during the study period, 56 patients (71 eyes) met inclusion criteria. The mean age at surgery was 5.1 years. Mean refractive error change in all the operated eyes was a 0.82 D decrease in spherical equivalent (p = 0.1920) and a 0.40 D increase in cylinder (p = 0.0255). There were no statistically significant changes in spherical equivalent or cylinder in the control eyes. CONCLUSIONS: The authors data did not show movement toward normalization of refractive error following ptosis surgery. In fact, it showed a statistically significant worsening of astigmatism following surgery. Because refractive error does not improve following surgery, anisometropia should not be the sole indication for early surgery in congenital ptosis.

Herpes Zoster Ophthalmicus With Orbital Findings Preceding Skin Rash.

The authors describe 2 patients who presented with orbital findings and later developed vesicular lesions that were positive for varicella zoster virus and consistent with Herpes Zoster ophthalmicus. One case is the first to involve dacryoadenitis and orbital myositis preceding disseminated Herpes Zoster. In the other case, a patient developed zoster orbital syndrome leading to elevated intraocular pressure, loss of vision, and afferent pupillary defect. Canthotomy and cantholysis were required to restore vision. In both cases, the orbital syndrome developed prior to the vesicular rash. These cases highlight the need to consider Herpes Zoster ophthalmicus in patients with orbital syndrome not responding to conventional treatment.

Oncocytic Adenocarcinoma of the Orbit.

Oncocytic adenocarcinoma of the orbit is a rare tumor, with 1 case of nonlacrimal sac, nonlacrimal gland origin, and a poor outcome previously reported. An 85-year-old man with a 2-month history of left-sided epiphora, enlarging eyelid nodules, and diplopia in left gaze was found on imaging to have a poorly circumscribed, nodular mass of uniform radiodensity in the inferomedial orbit. Incisional biopsy revealed morphologic and immunohistochemical features of oncocytic adenocarcinoma with origin in the caruncle suspected, and CT of the neck, chest, abdomen, and pelvis showed no metastases or remote primary tumor source. Based on multidisciplinary consensus, orbital exenteration with adjuvant radiation therapy was performed, and there was no evidence of residual or recurrent tumor 2 years after treatment.

Langerhans Cell Histiocytosis of the Orbit: Spectrum of Disease and Risk of Central Nervous System Sequelae in Unifocal Cases.

PURPOSE: To describe the spectrum of disease extent and clinical response in Langerhans cell histiocytosis (LCH) presenting with orbital involvement and to determine if unifocal orbital disease increases the risk for central nervous system sequelae (CNS-LCH). METHODS: Retrospective chart review of patients with orbital LCH representing a range of severity treated at the Children's Hospital of Wisconsin from 2003 to 2011; analysis of current international treatment protocols; literature review. RESULTS: Six patients presenting with orbital LCH are described: 1 with unifocal orbital disease completely responsive to local measures; 1 with multifocal bone disease completely responsive to local intervention; 1 with unifocal orbital disease incompletely responsive to surgical intervention, and requiring systemic chemotherapy; and 3 with multisystem disease at presentation. Literature review identified 806 cases of CNS-LCH. Orbital involvement could be determined in 11 cases. Of these, 6 had multisystem disease and 3 had multifocal bone disease; 1 presented with unifocal orbital disease but progressed to multifocal bone involvement; 1 had insufficient clinical information to distinguish unifocal from multisite presentation. No cases of CNS-LCH directly resulted from isolated unifocal orbital disease. CONCLUSIONS: Initial treatment of orbital LCH should depend on disease extent at diagnosis. Unifocal cases that completely respond to biopsy, curettage, and/or corticosteroid instillation may be managed with initial oncologic staging and careful long-term observation, with default to chemotherapy for local recurrence or multisite progression. There is currently little evidence that unifocal orbital disease increases the risk for CNS-LCH and therefore warrants prophylactic systemic chemotherapy in all patients.

Subperiosteal abscess of the orbit: evolving pathogens and the therapeutic protocol.

PURPOSE: Because of widespread antibiotic use, immunization against selective species, and the emergence of hypervirulent organisms, we sought to determine changes over time in the bacteriology of sinusitis-related subperiosteal abscess (SPA) of the orbit and their impact on patient outcomes under a uniform management protocol. DESIGN: Comparative case series. SUBJECTS: Patients≤18 years of age with sinusitis-related SPA treated from 2002 to 2012; comparable cohorts from earlier time frames. METHODS: We analyzed culture results and outcomes in surgical cases, compared overall and age-specific results with those in a 1977 through 1992 patient series, and compared the proportion of patients<9 years old requiring surgery among 1988 through 1998, 1999 through 2008, and current cohorts. MAIN OUTCOME MEASURES: Patients requiring surgery; prevalence of pathogens; criteria prompting surgery; visual and systemic outcomes. RESULTS: Ninety-four patients met inclusion criteria: 53 (56%) recovered with medical therapy alone and 41 (44%) underwent surgical drainage. Compared with the 1977 through 1992 cohort, there was increased representation of Streptococcus anginosus group, S aureus, and group A ß-streptococci. Methicillin-resistant S aureus (MRSA) accounted for 4 of 7 S aureus isolates. Of 94 patients, 74 (79%) were <9 years of age: 53 (72%) recovered without surgery and 21 (28%) underwent drainage. Comparable figures were 67.5% versus 32.5% and 85% versus 15% in 1988 through 1998 and 1999 through 2008 cohorts, respectively. Whereas patients≥9 years old in the 1977 through 1992 cohort had a higher proportion of positive cultures and more varied pathogens than younger patients, in the current series both groups had similar culture yields and aerobic constituencies. Anaerobes were isolated from only patients≥9 years old in both series. In cases positive for MRSA and other aggressive aerobes, initial findings prompted early drainage; outcomes were not compromised by adherence to the treatment protocol. CONCLUSIONS: The proportion of children<9 years requiring surgery for sinusitis-related SPA has remained a minority (15%-32.5%), without a clear upward trend over 25 years. Anaerobes continue not to factor in the younger subgroup, but more aggressive aerobic pathogens, including MRSA, have emerged. In such cases, surgical criteria that supersede age are triggered under the current treatment algorithm, and modification is not recommended.

Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling.

Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA. Formalin-fixed, paraffin-embedded orbital biopsies were obtained from controls (n=20) and patients with GPA (n=6), NSOI (n=25), sarcoidosis (n=7), or thyroid eye disease (TED) (n=20) and were divided into discovery and validation sets. Transcripts in the tissues were quantified using Affymetrix U133 Plus 2.0 microarrays. Distinct gene expression profiles for controls and subjects with GPA, TED, or sarcoidosis were evident by principal coordinate analyses. Compared with healthy controls, 285 probe sets had elevated signals in subjects with GPA and 1472 were decreased (>1.5-fold difference, false discovery rate adjusted p<0.05). The immunoglobulin family of genes had the most dramatic increase in expression. Although gene expression in GPA could be readily distinguished from gene expression in TED, sarcoidosis, or controls, a comparison of gene expression in GPA versus NSOI found no statistically significant differences. Thus, forms of orbital inflammation can be distinguished based on gene expression. NSOI/pseudotumor is heterogeneous but often may be an unrecognized, localized form of GPA.

Surgical timing and postoperative ocular motility in type B orbital blowout fractures.

PURPOSE: To determine whether patients with Type B orbital blowout fractures (soft-tissue distortion disproportionate to bone-fragment displacement) repaired within 7 days of injury have statistically greater postoperative vertical binocular fusion than similar patients who undergo later surgery. METHODS: Prospective and retrospective surgical case series. Inclusion criteria were orbital floor (with or without medial wall) blowout fracture repair, preoperative coronal orbital CT scans, and patient age of at least 12 years at time of postoperative binocular visual field. RESULTS: Twenty-five patients met inclusion criteria. Ten patients (group 1) had surgery within 7 days of injury, and 15 patients (group 2) had surgery more than 7 days after injury. The total cohort had a median postoperative vertical binocular fusion of 90°. Group 1 had postoperative vertical binocular fusion averaging 100°. Nine of 10 patients (90%) were above and 1 of 10 (10%) were below the median for the entire cohort. Group 2 had postoperative vertical binocular fusion averaging 70°. Three of 15 patients (20%) were above and 12 of 15 patients (80%) were below the median for the entire cohort. The difference between the average postoperative vertical binocular fusion of the 2 groups was statistically significant by two-tailed unpaired t test with p value 0.0022. CONCLUSIONS: Patients with Type B orbital blowout fractures (soft-tissue distortion disproportionate to bone-fragment displacement) have statistically greater average postoperative vertical binocular fusion if repaired within 7 days of injury than similar patients who undergo later surgery.

Intraepithelial sebaceous carcinoma: a case report of an unusual occurrence.

Sebaceous carcinoma is a malignant neoplasm that occurs most commonly in the periorbital area, usually the eyelid. Its periocular location predisposes to smaller biopsies, thus complicating diagnosis. The neoplasm tends to exhibit aggressive local behavior, metastasizing to regional lymph nodes, and distant organs. Disease limited to the epithelium is rare, with less than 10 cases reported in the literature. We present the case of a 73-year-old woman who presented with left upper eyelid entropion and conjunctival erythema. Multiple punch biopsies showed an intraepithelial proliferation of atypical basaloid cells with enlarged and hyperchromatic nuclei intermingled with vacuolated cells containing bubbly cytoplasms and scalloped nuclei, consistent with a diagnosis of intraepithelial sebaceous carcinoma. After subsequent orbital exenteration and histological examination, a wide intraepithelial sebaceous component was identified; however, there was no invasive growth. This case highlights the rarity and the potential diagnostic pitfalls of intraepithelial sebaceous carcinoma.