Search

Teprotumumab, a monoclonal antibody targeted against the insulin-like growth factor 1 (IGF-1) receptor, was recently approved by the United States Food and Drug Administration for the treatment of thyroid eye disease (TED). Phase 1 studies of teprotumumab for the treatment of malignancies demonstrated an acceptable safety profile but limited effectiveness. Basic research implicating the IGF-1 receptor on the CD-34+ orbital fibrocyte in the pathogenesis of TED renewed interest in the drug. Two multicenter, randomized, double-masked, clinical trials (phase 2 and 3) evaluated the efficacy of 8 infusions of teprotumumab every 3 weeks versus placebo in 170 patients with recent-onset active TED, as defined by a clinical activity score (CAS) of at least 4. Teprotumumab was superior to placebo for the primary efficacy end points in both studies: overall responder rate as defined by a reduction of 2 or more CAS points and a reduction of 2 mm or more in proptosis (69% vs. 20%; P < 0.001; phase 2 study) and proptosis responder rate as defined by a reduction of 2 mm or more in proptosis (83% vs. 10%; P < 0.001; phase 3 study). In both studies, treatment with teprotumumab compared with placebo achieved a significant mean reduction of proptosis (-3.0 mm vs. -0.3 mm, phase 2 study; -3.32 mm vs. -0.53 mm, phase 3 study) and CAS (-4.0 vs. -2.5, phase 2 study; -3.7 vs. -2.0, phase 3 study). Teprotumumab also resulted in a greater proportion of patients with a final CAS of 0 or 1, higher diplopia responder rate, and a larger improvement in the Graves' Ophthalmopathy Quality of Life overall score. More than half of patients (62%, phase 2 trial; 56%, phase 3 trial) who were primary end point responders maintained this response at 51 weeks after the last dose of therapy. The most common adverse events reported with teprotumumab included muscle spasms (25%), nausea (17%), alopecia (13%), diarrhea (13%), fatigue (10%), hearing impairment (10%), and hyperglycemia (8%). Teprotumumab is contraindicated for those with inflammatory bowel disease and who are pregnant. Although the current dosing regimen has proven effective for TED, dose-ranging studies including variable concentrations, infusion frequencies, and durations of teprotumumab therapy in the setting of TED have not been performed.

This study evaluates a web-based tool designed to augment telemedicine post-operative visits after periocular surgery.Adult, English-speaking patients undergoing periocular surgery with telemedicine follow-up were studied prospectively in this interventional case series. Participants submitted visual acuity measurements and photographs via a web-based tool prior to routine telemedicine post-operative visits. An after-visit survey assessed patient perceptions. Surgeons rated photographs and live video for quality and blurriness; external raters also evaluated photographs. Images were analyzed for facial centration, resolution, and algorithmically detected blur. Complications were recorded and graded for severity and relation to telemedicine.Seventy-nine patients were recruited. Surgeons requested an in-person assessment for six patients (7.6%) due to inadequate evaluation by telemedicine. Surgeons rated patient-provided photographs to be of higher quality than live video at the time of the post-operative visit (p 0.001). Image blur and resolution had moderate and weak correlation with photograph quality, respectively. A photograph blur detection algorithm demonstrated sensitivity of 85.5% and specificity of 75.1%. One patient experienced a wound dehiscence with a possible relationship to inadequate evaluation during telemedicine follow-up. Patients rated the telemedicine experience and their comfort with the structure of the visit highly.Augmented telemedicine follow-up after oculofacial plastic surgery is associated with high patient satisfaction, rare conversion to clinic evaluation, and few related post-operative complications. Automated detection of image resolution and blur may play a role in screening photographs for subsequent iterations of the web-based tool.

A patient with thyroid-associated ophthalmopathy was treated with teprotumumab and developed symptoms concerning for inflammatory bowel disease after her sixth infusion. Colonoscopy was performed, and mucosal biopsies identified evidence of active colitis consistent with a diagnosis of ulcerative colitis. Despite treatment with budesonide and mesalamine, the patient continued to be symptomatic one and a half months after cessation of teprotumumab and required infliximab to achieve good control of her inflammatory bowel disease. This case represents the first report of new-onset inflammatory bowel disease arising during treatment with teprotumumab.

OBJECTIVEHyperostosing sphenoid wing meningiomas cause bony hyperostosis that may extend into the orbit, resulting in proptosis, restriction of extraocular movements, and/or compressive optic neuropathy. The extent of bony removal necessary and the optimal reconstruction strategy to prevent enophthalmos is debated. Herein, the authors present their surgical outcomes and reconstruction results.METHODSThis is a retrospective review of 54 consecutive patients undergoing resection of sphenoid wing meningiomas associated with bony hyperostosis. The majority of cases were operated on by the senior author. Extent of tumor resection, volumetric bone resection, radiographic exophthalmos index, complications, and recurrence were analyzed.RESULTSThe median age of the cohort was 52.1 years, with women comprising 83% of patients. Proptosis was a presenting symptom in 74%, and 52% had decreased visual acuity. The WHO grade was I (85%) or II (15%). The median follow-up was 2.6 years. On volumetric analysis, a median 86% of hyperostotic bone was resected. Gross-total resection of the intracranial tumor was achieved in 43% and the orbital tumor in 27%, and of all intracranial and orbital components in 20%. Orbital reconstruction was performed in 96% of patients. Postoperative vision was stable or improved in 98% of patients and diplopia improved in 89%. Postoperative complications occurred in 44% of patients, and 26% of patients underwent additional surgery for complication management. The most frequent complications were medical complications and extraocular movement deficits. The median preoperative exophthalmos index was 1.26, which improved to 1.12 immediately postoperatively and to 1.09 at the 6-month follow-up (p < 0.001). Postoperatively, 18 patients (33%) underwent adjuvant radiotherapy after subtotal resection. Tumors recurred/progressed in 12 patients (22%).CONCLUSIONSResection of hyperostosing sphenoid wing meningiomas, particularly achieving gross-total resection of hyperostotic bone with a good aesthetic result, is challenging and associated with notable medical and ocular morbidity. Recurrence rates in this series are higher than previously reported. Nevertheless, the authors were able to attain improvement in proptosis and visual symptoms in the majority of patients by using a multidisciplinary approach.

BACKGROUND: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. METHODS: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5?*?5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete. FINDINGS: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). INTERPRETATION: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. FUNDING: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

Purpose The usefulness of topical antibiotic prophylaxis for routine oculofacial plastic surgery is not well established. Given concerns such as contact dermatitis, antibiotic resistance, and healthcare costs in conjunction with a low baseline rate of surgical site infections, the investigators sought to determine the frequency of infection with and without the use of topical antibiotic prophylaxis. Design Randomized, controlled, unmasked clinical trial. Participants Adult patients undergoing routine periocular surgery without prior history of periocular surgical site infection, need for perioperative oral or parenteral antibiotics, or allergy to all study medications. Methods Participants were randomized before surgery to receive either antibiotic or placebo (mineral oil and petrolatum-based) ointment after surgery. Outcomes were measured at the first postoperative visit. The 2-tailed Fisher exact test was used to compare outcomes between groups. Main Outcome Measures The primary outcome was the incidence of surgical site infections. The secondary outcomes included stratification of infections by patient risk characteristics, incidence of allergic contact dermatitis, and incidence of wound complications. Results Four hundred one participants were enrolled and randomized, and 13 participants did not proceed with surgery or were lost to follow-up. High-risk features for infection were identified in 24% of the placebo group and 21% of the antibiotic group. Surgical site infections were more common in the placebo group (2.7% vs. 0.0%; P = 0.025). The rate of contact dermatitis was similar (0.5% vs. 0.5%; P = 1.00), as was the rate of wound dehiscence (2.7% vs. 3.5%; P = 0.77). Among the placebo group, the incidence of infections in the low- and high-risk participants was 2.9% and 2.2%, respectively. Infections were treated with oral or topical antibiotics and resolved without complication, except in 1 patient who required 2 subsequent surgeries to address the sequelae. Conclusions After routine oculofacial plastic surgery, patients treated with a topical antibiotic ointment showed a lower risk of surgical site infection compared with patients treated with a nonantibiotic ointment.

To identify initial, preintervention magnetic resonance imaging (MRI) findings that are predictive of visual and mortality outcomes in acute invasive fungal rhinosinusitis (AIFRS).Retrospective cohort study.Patients with histopathologically or microbiologically confirmed AIFRS cared for at a single, tertiary academic institution between January 2000 and February 2020.A retrospective review of MRI scans and clinical records of patients with confirmed diagnosis of AIFRS was performed. For each radiologic characteristic, a modified Poisson regression with robust standard errors was used to estimate the risk ratio for blindness. A multivariate Cox proportional hazards model was used to study AIFRS-specific risk factors associated with mortality.Identification of initial, preintervention MRI findings associated with visual and mortality outcomes.The study comprised 78 patients (93 orbits, 63 with unilateral disease and 15 with bilateral disease) with AIFRS. The leading causes of immunosuppression were hematologic malignancy (38%) and diabetes mellitus (36%). Mucormycota constituted 56% of infections, and Ascomycota constituted 37%. The overall death rate resulting from infection was 38%. Risk factors for poor visual acuity outcomes on initial MRI included involvement of the orbital apex (relative risk [RR], 2.0; 95% confidence interval [CI], 1.1-3.8; P = 0.026) and cerebral arteries (RR, 1.8; 95% CI, 1.3-2.5; Plt; 0.001). Increased mortality was associated with involvement of the facial soft tissues (hazard ratio [HR], 4.9; 95% CI, 1.3-18.2; P = 0.017), nasolacrimal drainage apparatus (HR, 5.0; 95% CI, 1.5-16.1; P = 0.008), and intracranial space (HR, 3.5; 95% CI, 1.4-8.6; P = 0.006). Orbital soft tissue involvement was associated with decreased mortality (HR, 0.3; 95% CI, 0.1-0.6; P = 0.001).Extrasinonasal involvement in AIFRS typically signals advanced infection with the facial soft tissues most commonly affected. The initial, preintervention MRI is prognostic for a poor visual acuity outcome when orbital apex or cerebral arterial involvement, or both, are present. Facial soft tissues, nasolacrimal drainage apparatus, intracranial involvement, or a combination thereof is associated with increased mortality risk, whereas orbital soft tissue involvement is correlated with a reduced risk of mortality.

Primary ductal adenocarcinoma (PDA) is a rare epithelial tumor of the lacrimal gland. Herein we report 5 cases and reviewed 29 published cases of PDA of the lacrimal gland. Among these 5 cases, the most common clinical presentation was painless swelling and/or proptosis of their eye. The size of the lesions ranged from 1.6 to 2.5 cm. Histopathologic examination revealed proliferations of ductal or gland-like cells with vesiculated pleomorphic nuclei and prominent nucleoli. Tumor cells stained positive for epithelial and apocrine differentiation markers. Immunohistochemistry for human epidermal growth factor 2 (HER- 2/neu) were positive in 2 of the 4 cases. Four of the five patients were alive at last follow-up. One died with bone metastases, which were diagnosed 25 months post exenteration, and then survived an additional 51 months. On reviewing of twenty-nine previously published cases of PDA, the mean age of diagnosis was 58 years, with a male predominance (75%). Fifteen patients (54%) had distant metastases, 1 (4%) had local recurrence, and 10 (37%) suffered from a PDA-related death. PDA is a high-grade aggressive epithelial tumor of the lacrimal gland. Though rare, awareness and recognition of this malignancy is important in order to help determine prognosis and treatment options.

Background: We have previously reported that the safety and efficacy of ipilimumab in real-world patients with metastatic melanoma were comparable to clinical trials. Few studies have explored health-related quality of life (HRQL) in real-world populations receiving checkpoint inhibitors. This study reports HRQL in real-world patients receiving ipilimumab and assesses the prognostic value of patient-reported outcome measures. Patients and methods: Ipi4 (NCT02068196) was a prospective, multicentre, interventional phase IV trial. Real-world patients (N = 151) with metastatic melanoma were treated with ipilimumab 3 mg/kg intravenously as labelled. HRQL was assessed by the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire at baseline and after 10-12 weeks. Results: The European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire was completed by 93% (141/151 patients) at baseline, and by 82% at 10-12 weeks. Poor performance status and elevated C-reactive protein (CRP) were associated with worse baseline HRQL. Clinically relevant and statistically significant deteriorations in HRQL from baseline to weeks 10-12 were reported (P

We describe a 4-year-old boy who presented with progressive right periorbital edema and proptosis, with no systemic symptoms, who was found to have B-lymphoblastic leukemia (B-ALL). Magnetic resonance imaging (MRI) showed an enhancing mass centered in the right superolateral extraconal orbit. Orbital biopsy was consistent with B-ALL (CD99, TdT, LCA cocktail, CD34, CD79, CD10, PAX5, MIB1 positive; CD3, CD20 negative). A subsequent bone marrow aspirate confirmed a diagnosis of B-ALL with 80% blasts by flow cytometry and haploid cytogenetic findings. The patient improved clinically after chemotherapy. There are seven cases previously reported in the literature with hematogenous orbital masses at initial presentation of childhood ALL, but all with systemic symptoms or an abnormal complete blood count (CBC) at presentation. Our case is the first report in which an orbital mass preceded detectable systemic or laboratory evidence of ALL. This patient highlights the importance of differentiating benign causes of eyelid swelling from malignant ones.

ObjectivesTo evaluate whether use of an antibiotic improves the efficacy of care for a chalazion or hordeolum.MethodsA cross-sectional retrospective review was performed. All patients treated for a newly diagnosed chalazion or hordeolum at the University of California, San Francisco from 2012 to 2018 were identified. Patients were excluded when clinical notes were inaccessible or there was inadequate documentation of treatment modality or outcome. Patient demographics, setting of initial presentation, treatment modalities, antibiotic use, and outcomes were analyzed.ResultsA total of 2,712 patients met inclusion criteria. Management with an antibiotic was observed in 36.5% of patients. An antibiotic was 1.53 times (95% confidence interval [CI], 1.06-2.22, P=0.025) more likely to be prescribed in emergency or acute care setting for a chalazion. Older age was associated with a higher risk of receiving an antibiotic for a hordeolum (adjusted RR 1.07 per decade, 95% CI, 1.05-1.11, P

Background: Understanding how periocular nonmelanoma skin cancer (NMSC) impacts quality of life (QoL) provides insight into the patient experience. Objective: To prospectively measure QoL of indivi...

Primary ductal adenocarcinoma of the lacrimal gland is an aggressive neoplasm and can be seen either as a de novo malignancy or in the setting of a carcinoma ex pleomorphic adenoma. Carcinoma ex pleomorphic adenoma carries an overall unfavorable outcome; however, prognosis depends on the type and grade of the malignant component, presence of retained myoepithelial component, and extend of invasion beyond the capsule. Herein, the authors describe a 78-year-old man diagnosed with an incidental, intracapsular, high-grade ductal adenocarcinoma in situ ex pleomorphic adenoma, who is free of disease at 9 months subsequent to complete resection. It is important to recognize the morphologic features of intraductal and intracapsular neoplasms to prevent unnecessary morbidities due to extensive surgical interventions or radiotherapy.Morphologic features of intracapsular ductal carcinoma in situ ex pleomorphic adenoma, which shows better clinical outcomes with complete excision than its invasive counterpart.

PURPOSE Invasive fungal sinusitis is a rare but potentially lethal disease that primarily affects immunocompromised patients. The purpose of this study was to review an academic medical center's experience in the presentation, diagnosis, and treatment of invasive fungal sinusitis. METHODS A retrospective chart review was performed at a single institution over a 17-year period. Medical records, radiographic imaging, and operative reports were analyzed. Bivariate and multivariable analyses were performed to determine factors that affected visual acuity outcomes and mortality. RESULTS Fifty-five patients with histopathologically confirmed invasive fungal sinusitis were included. The average duration of follow up was 1.8 ± 2.6 years (range: 1 week to 10 years). The most common causes of immunosuppression were hematologic malignancy (45%), diabetes (31%), and organ transplantation (9%). At presentation, 35% of individuals were neutropenic (absolute neutrophil count < 500/μl). All patients received systemic antifungal treatment. A surgical intervention was performed on 50 patients (91%), and all but one had functional endoscopic sinus surgery. Nine (16%) patients underwent orbital exenteration. Multivariable analysis of visual acuity outcomes demonstrated that individuals infected with Zygomycota had 6-7 lines worse vision than those infected with Ascomycota (mean difference in logMAR 0.66, 95% confidence interval 0.27 to 1.06, p = 0.001). Patients who had functional endoscopic sinus surgery had 7-8 lines better visual acuity than those without functional endoscopic sinus surgery (mean difference in logMAR -0.76, 95% confidence interval -1.13 to -0.38, p < 0.001). The overall death rate due to infection was 24%. Bivariate models demonstrated no difference in mortality in patients receiving exenteration versus those who did not (p = 0.14). Multivariable analysis of mortality demonstrated that neutropenia increased mortality (adjusted odds ratio 10.05, 95% confidence interval 1.49 to 67.67, p = 0.02). Having a greater number of surgeries was associated with an increased rate of survival (adjusted odds ratio 0.39, 95% confidence interval 0.15 to 0.96, p = 0.04). CONCLUSIONS Invasive fungal sinusitis is an aggressive disease with significant mortality. Patients with neutropenia had a lower rate of survival, and infection with Zygomycota was associated with worse visual acuity outcomes. Those having functional endoscopic sinus surgery had better final visual acuity, and an increased number of surgeries was associated with a decreased chance of death. Exenteration yielded no observed survival benefit.Endoscopic sinus debridement portends better visual acuity outcomes in patients with invasive fungal sinusitis, whereas exenteration yields no difference in survival benefit.

Purpose: To review and summarize the epidemiology, clinical presentations, histopathologic characteristics and management of dacryops.Methods: A comprehensive PubMed, Embase and Google Scholar search of all articles written in English and non-English language articles with abstract translated to English on dacryops were reviewed. Data reviewed included epidemiology, etiology, pathogenesis, clinical presentations, histopathologic characteristics and management of dacryops.Results: Lacrimal ductal cysts or dacryops are classified based on locations: palpebral lobe cysts (simple dacryops); orbital lobe cysts; cysts of the accessory lacrimal glands of Krause and Wolfring; and cysts of ectopic (choristomatous) lacrimal glands. The exact etiology of dacryops remains unknown. Dacryops is usually asymptomatic but can present with varied symptoms depending on the type and associated complications. While complete excision of dacryops is generally recommended, marsupialization is also a safe and effective method for the treatment of dacryops in the palpebral lobe of lacrimal gland. Complete surgical excision via orbitotomy is required for deep orbital lesions.Conclusion: Dacryops is an uncommon benign cystic lacrimal gland tissue neoplasm. Dacryops can be classified into four types based on locations. Lesions could be either superficial that can be seen through the fornix or deep into the orbit. Observation is also an option for small or asymptomatic lesions. Surgery remains the mainstay of treatment for symptomatic cases, but approaches are different depending on the location of the lesions.

Ductal carcinoma of the lacrimal gland is a very rare and aggressive neoplasm, with clinical and histopathologic similarities to salivary ductal carcinoma. Of the 25 previously reported cases, 2 patients had metastases to local lymph nodes confirmed on pathologic examination. The authors now report the clinical presentation, histopathologic and immunohistochemical features, and the treatment of a third patient with lacrimal gland ductal carcinoma with spread to local lymph nodes. In contrast to ductal carcinoma, lymph node involvement has not been reported in the largest series of adenoid cystic carcinoma, a much more common lacrimal gland malignancy. This case highlights the need for possible lymph node surveillance in patients with lacrimal gland ductal carcinoma.

The authors conducted a retrospective case series of patients undergoing a lateral tarsal strip procedure with "en glove" placement of an acellular porcine dermal collagen matrix for correction of mild to moderate lower eyelid retraction. A detailed description of this minimally invasive technique with retrospective analysis of outcomes is provided. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, IV.

PURPOSE Pain relief for a blind painful eye often follows an escalating paradigm of interventions. This study compares the efficacy of common interventions. METHODS A retrospective chart review of blind painful eye cases was conducted at a single tertiary institution from April 2012 to December 2016. Demographics, etiology, treatment, and pain level were assessed. RESULTS Among 99 blind painful eyes, 96 eyes initially received medical therapy (topical steroids, cycloplegics, and/or hypotensives), with pain relief in 39% of eyes. Minimally invasive interventions (laser cyclophotocoagulation, retrobulbar injection, or corneal electrocautery) were performed 41 times in 36 eyes, 34 of which had failed medical therapy, and led to pain relief in 75% of eyes. Evisceration or enucleation was performed in 28 eyes, and long-term pain relief was achieved in 100% of eyes. Surgery allowed discontinuation of oral analgesics in 100% of cases versus 20% for minimally invasive therapy (p = 0.005) and 14% for medical therapy (p = 0.0001). Compared with medical therapy, minimally invasive therapy was 2.5 times more likely to achieve lasting pain relief (p = 0.003) and surgical therapy 35.6 times more likely to achieve lasting pain relief (p = 0.011). High initial pain score was associated with nonsurgical treatment failure. CONCLUSIONS Medical therapy provides pain relief in a moderate number of patients with a blind painful eye. When medical therapy fails, minimally invasive therapy and surgical interventions are successively more effective in relieving ocular pain. High initial pain score is a risk factor for nonsurgical therapy failure and may merit an earlier discussion of surgical intervention.

Purpose: To report a diagnostically challenging case of cranial neuropathy due to perineural invasion by a basal cell carcinoma presenting 7.5 years after treatment of the primary tumor with Mohs micrographic surgery. Observations: A 62-year-old male with a history of Mohs micrographic surgery for basal cell carcinoma (BCC) of the left brow presented with insidious onset of diplopia and paresthesia localizing to the ipsilateral cranial nerves V1, V2, and VI. He had no evidence of recurrent cutaneous BCC. Magnetic resonance imaging of the orbits and skull base identified equivocal, subtle abnormalities in the ipsilateral superior orbital fissure and cavernous sinus, with normal appearance of the clinically involved nerve branches. A radiographically normal branch of cranial nerve V was biopsied and histopathology identified perineural invasion by recurrent basal cell carcinoma. Conclusions and importance: The diagnosis of perineural invasion by BCC can pose several challenges, including subtle to absent imaging findings of clinically involved nerves and a lengthy latent period following primary tumor treatment. This case represents, to our knowledge, the longest reported interval between primary treatment and biopsy-proven recurrence with perineural invasion by BCC. Keywords: Basal cell carcinoma, Perineural invasion, Cranial neuropathy, BCC, Perineural spread

Purpose : To assess whether a modified treatment ladder algorithm incorporating transcutaneous retrobulbar amphotericin B (TRAMB) for invasive fungal rhino-orbital sinusitis (IFROS) can reduce the risk of exenteration without compromising survival. Design : Retrospective, comparative clinical study with historical controls. Methods : Fifty consecutive patients with biopsy-proven invasive fungal sinusitis and radiographic evidence of orbital involvement were evaluated at a single tertiary institution from 1999-2020. TRAMB was incorporated as part of the treatment algorithm in 2015. Demographics, underlying immune derangement, infective organism, ophthalmic examination, surgical care, and survival were compared in a quasi-experimental pre-post format, dividing patients into a pre-2015 group and a post-2015 group. Risk of exenteration and mortality were the primary outcomes. Results : Baseline characteristics did not differ significantly between the two groups. Nearly all patients underwent a surgical intervention, which most commonly was functional endoscopic sinus surgery with debridement. TRAMB was administered to 72.7% of the post-2015 group. Exenteration was more common in the pre-2015 group (36.4% vs. 9.1%; 95% CI [5.2, 48.8]; p = 0.014), while mortality was similar (40.0% vs. 36.7%; 95% CI [-22.1, 29.3]; p = 0.816). After adjusting for potential confounders, patients treated after 2015 were found to have lower risk of exenteration (RR 0.28; 95% CI [0.08, 0.99]; p = 0.049) and similar risk of mortality (RR 1.04; 95% CI [0.50, 2.16]; p = 0.919). Conclusion : In comparison to historical controls, patients with IFROS who were treated with a modified treatment ladder algorithm incorporating TRAMB had a lower risk of disfiguring exenteration without an apparent increase in the risk of mortality.

A patient with thyroid-associated ophthalmopathy was treated with teprotumumab and developed symptoms concerning for inflammatory bowel disease after her sixth infusion. Colonoscopy was performed, and mucosal biopsies identified evidence of active colitis consistent with a diagnosis of ulcerative colitis. Despite treatment with budesonide and mesalamine, the patient continued to be symptomatic one and a half months after cessation of teprotumumab and required infliximab to achieve good control of her inflammatory bowel disease. This case represents the first report of new-onset inflammatory bowel disease arising during treatment with teprotumumab.

Acute invasive fungal rhinosinusitis is a rare, although highly morbid, infection primarily affecting immunosuppressed individuals. The same population is at particularly high risk of complications and mortality in the setting of SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome. The authors present a case of acute invasive fungal rhino-orbital mucormycosis in a patient with COVID-19 and discuss the prevalence, diagnosis, and treatment of fungal coinfections in COVID-19. Prompt recognition, initiation of therapy, and consideration of the challenges of rapidly evolving COVID-19 therapy guidelines are important for improving patient survival., The authors report a case of acute invasive rhino-orbital mucormycosis in the setting of concurrent COVID-19-associated acute respiratory distress syndrome and the dilemma posed of treating both entities concurrently.

Teprotumumab, a monoclonal antibody targeted against the insulin-like growth factor 1 (IGF-1) receptor, was recently approved by the United States Food and Drug Administration for the treatment of thyroid eye disease (TED). Phase 1 studies of teprotumumab for the treatment of malignancies demonstrated an acceptable safety profile but limited effectiveness. Basic research implicating the IGF-1 receptor on the CD-34+ orbital fibrocyte in the pathogenesis of TED renewed interest in the drug. Two multicenter, randomized, double-masked, clinical trials (phase 2 and 3) evaluated the efficacy of 8 infusions of teprotumumab every 3 weeks versus placebo in 170 patients with recent-onset active TED, as defined by a clinical activity score (CAS) of at least 4. Teprotumumab was superior to placebo for the primary efficacy end points in both studies: overall responder rate as defined by a reduction of 2 or more CAS points and a reduction of 2 mm or more in proptosis (69% vs. 20%; P0.001; phase 2 study) and proptosis responder rate as defined by a reduction of 2 mm or more in proptosis (83% vs. 10%; P0.001; phase 3 study). In both studies, treatment with teprotumumab compared with placebo achieved a significant mean reduction of proptosis (-3.0 mm vs. -0.3 mm, phase 2 study; -3.32 mm vs. -0.53 mm, phase 3 study) and CAS (-4.0 vs. -2.5, phase 2 study; -3.7 vs. -2.0, phase 3 study). Teprotumumab also resulted in a greater proportion of patients with a final CAS of 0 or 1, higher diplopia responder rate, and a larger improvement in the Graves' Ophthalmopathy Quality of Life overall score. More than half of patients (62%, phase 2 trial; 56%, phase 3 trial) who were primary end point responders maintained this response at 51 weeks after the last dose of therapy. The most common adverse events reported with teprotumumab included muscle spasms (25%), nausea (17%), alopecia (13%), diarrhea (13%), fatigue (10%), hearing impairment (10%), and hyperglycemia (8%). Teprotumumab is contraindicated for those with inflammatory bowel disease and who are pregnant. Although the current dosing regimen has proven effective for TED, dose-ranging studies including variable concentrations, infusion frequencies, and durations of teprotumumab therapy in the setting of TED have not been performed.

Purpose A significant percentage of colorectal cancer patients proceeds to metastatic disease. We hypothesised that mitochondrial DNA (mtDNA) polymorphisms, generated by the high mtDNA mutation rate of energy-demanding clonal immune cell expansions and assessable in peripheral blood, reflect how efficiently systemic immunity impedes metastasis. Patients and methods We studied 44 rectal cancer patients from a population-based prospective biomarker study, given curative-intent neoadjuvant radiation and radical surgery for high-risk tumour stage and followed for metastatic failure. Blood specimens were sampled at the time of diagnosis and analysed for the full-length mtDNA sequence, composition of immune cell subpopulations and damaged serum mtDNA. Results Whole blood total mtDNA variant number above the median value for the study cohort, coexisting with an mtDNA non-H haplogroup, was representative for the mtDNA of circulating immune cells and associated with low risk of a metastatic event. Abundant mtDNA variants correlated with proliferating helper T cells and cytotoxic effector T cells in the circulation. Patients without metastatic progression had high relative levels of circulating tumour-targeting effector T cells and, of note, the naïve (LAG-3+) helper T-cell population, with the proportion of LAG-3+ cells inversely correlating with cell-free damaged mtDNA in serum known to cause antagonising inflammation. Conclusion Numerous mtDNA polymorphisms in peripheral blood reflected clonal expansion of circulating helper and cytotoxic T-cell populations in patients without metastatic failure. The statistical associations suggested that patient’s constitutional mtDNA manifests the helper T-cell capacity to mount immunity that controls metastatic susceptibility. Trial registration ClinicalTrials.gov NCT01816607; registration date: 22 March 2013.

PURPOSE: Intravenous antibiotic prophylaxis is used for many clean-contaminated surgeries or clean surgeries with an implant, but its value for clean orbital surgery has not been determined. This study investigated infection risks and adverse effects related to antibiotics in patients undergoing orbital surgery. METHODS: A prospective, nonrandomized comparative case series of all patients undergoing orbital surgery with participating surgeons between October 1, 2013, and March 1, 2015. Types of surgery, antibiotic regimens, corticosteroid use, antibiotic side effects, and surgical site infections (SSIs) were entered into an electronic database and subsequently analyzed. Cases in which patients received postoperative oral antibiotics were analyzed separately. RESULTS: Of 1,250 consecutive orbital surgeries, 1,225 met inclusion criteria. A total of 1208 patients were included in the primary analysis: 603 received no antibiotic prophylaxis (group A), and 605 received a single dose of intravenous antibiotic (group B). Five patients (0.42%) developed an SSI, 3 in group A and 2 in group B. The difference in SSI rates was not statistically significant between the 2 groups (p = 0.66). Antibiotic prophylaxis, alloplastic implants, paranasal sinus entry, and corticosteroid use were not associated with differences in SSI rates. All SSIs resolved on a single course of oral antibiotics; an implant was removed in 1 case. There were no complications associated with a single dose of intravenous prophylaxis. However, 12% of 17 patients (group C) who received 1 week of oral postoperative prophylactic antibiotics developed antibiotic-related complications (diarrhea, renal injury), yielding a number needed to harm of 8.5. CONCLUSIONS: In this large series, antibiotic prophylaxis does not appear to have reduced the already low incidence of SSI following orbital surgery. Given the detriments of systemic antibiotics, the rarity of infections related to orbital surgery, and the efficacy of treating such infections should they occur, patients undergoing orbital surgery should be educated to the early symptoms of postoperative infection and followed closely, but do not routinely require perioperative antibiotics.

PURPOSE Advances in surgical approaches have improved access for total or near-total resection of spheno-orbital meningiomas (SOM). Herein, the outcomes of multidisciplinary resection and reconstruction of SOM via frontotemporal orbitozygomatic craniotomy at a single institution are evaluated. METHODS A retrospective chart review was performed of all patients with SOM who underwent joint neurosurgical and oculofacial plastic resection via frontotemporal orbitozygomatic craniotomy between January 1999 and December 2018. Demographic data, clinical presentation, risk factors for meningioma, radiographic imaging, pathology results, postoperative outcomes, and surgical complications were reviewed. The outcome measures assessed included visual acuity, pupillary function, color vision, ocular motility, visual fields, and proptosis. RESULTS A total of 48 patients were identified having had multidisciplinary frontotemporal orbitozygomatic craniotomy for SOM of which 43 met inclusion criteria. A mean follow-up period of 23.9 ± 20.4 months (range 1-60) was observed. There were 35 patients who underwent primary resection and 8 patients who had prior surgical resection. The main presenting complaints were proptosis (88%), headache (44%), and reduced vision (12%). Gross total resection was achieved in 15 patients (35%) while near-total or subtotal resection was achieved in the remainder. Histologic analysis revealed World Health Organization grade I meningioma in 72% of tumors, grade II in 23%, and grade III in 5%. Mean visual acuity (Logarithm of the Minimum Angle of Resolution) improved from 0.24 ± 0.46 preoperatively to 0.09 ± 0.13 postoperatively (p = 0.03). Surgery improved proptosis, with a reduction in mean Hertel exophthalmometry from 22.37 ± 3.78 mm to 17.91 ± 3.84 mm (p < 0.001), of which 80% had no residual proptosis or developed subsequent recurrence. Exophthalmic index calculated by radiologic evaluation also improved from a mean preoperative value of 1.32 ± 0.19 to 1.12 ± 0.13 at the 6-month interval after surgery (p < 0.001). Before surgery, 19 (45%) patients had a relative afferent pupillary reaction with improvement in 9 (24%) after surgery. Of the 14 (33%) patients with preoperative ocular motility deficit, 7 (16%) had resolution of ocular motility deficit postoperatively. The most common surgical complications were temporalis muscle atrophy with temporal hollowing (14%), wound infection (7%), neurogenic strabismus secondary to trochlear nerve palsy (5%), restrictive strabismus (5%), and aponeurotic blepharoptosis (5%). CONCLUSIONS Multidisciplinary frontotemporal orbitozygomatic for resection of SOM is a safe and effective means of tumor removal. It can provide improved visual acuity and proptosis metrics, as well as relief of optic neuropathy and ocular motility deficits.

Purpose: This article reviews cases of nasolacrimal obstruction (NLO) secondary to maxillofacial hardware placement. Methods: A retrospective review was performed at a single institution from 2012 to 2017 of patients with NLO following maxillofacial reconstruction. The study was approved by the Institutional Review Board of the University of California, San Francisco, adhered to the tenets of the Declaration of Helsinki, and was Health Insurance Portability and Accountability Act compliant. Patients were included if external dacryocystorhinostomy (DCR) confirmed previously placed maxillofacial hardware as the primary contributor to lacrimal outflow obstruction and had at least 3 months of follow-up. Results: Of 420 patients who underwent external DCR, 6 cases of implant-related NLO were identified. The mean age was 47.3 ± 9.6 years and 66.7% of patients were male. All patients presented with epiphora and 50% also had chronic dacryocystitis. Patients had prior maxillofacial hardware placement for paranasal sinus tumors (66.7%) or facial fractures (33.3%). In addition to external DCR, all patients had revision or removal of implants that were impeding lacrimal outflow by 2 mechanisms: (1) an orbital implant impinging the lacrimal sac or nasolacrimal duct (NLD) and/or (2) maxillofacial screws placed into the bony NLD or nasolacrimal fossa. Five of the 6 patients (83.3%) had complete resolution of symptoms and patency of the nasolacrimal system at their last follow-up visit (range 3-30 months). Conclusion: NLO secondary to hardware placement, though infrequent, is underreported. Two mechanisms of hardware-induced NLO were encountered in this case series. Specific attention to nasolacrimal anatomy at the time of maxillofacial reconstruction may help minimize implant-induced NLO.

A 14-year-old female with juvenile idiopathic arthritis presented with left-sided recurrent painful periorbital swelling of 5 months duration. MRI revealed enlargement of the left lacrimal gland with extensive inflammatory change involving the orbital and periorbital soft tissues. Lacrimal gland biopsy showed evidence of chronic inflammation, and she had intralesional steroid injection at the time of biopsy. She remained asymptomatic at 6-month follow-up visit. Although juvenile idiopathic arthritis is usually related to intraocular inflammation, it may rarely be associated with dacryoadenitis.

Silent sinus syndrome (SSS) is a rare disease characterized by spontaneous enophthalmos and hypoglobus secondary to collapse of the orbital floor in patients with asymptomatic maxillary sinusitis. Radiographic findings include ipsilateral maxillary sinus opacification, lateralization of the uncinate and middle turbinate, and infundibular occlusion. We present a case series of three patients with clinical and radiographic evidence of SSS but without maxillary sinus opacification. Although uncommon, an aerated maxillary sinus in patients with unexplained enophthalmos, hypoglobus, and maxillary atelectasis should not exclude the diagnosis of SSS. Laryngoscope, 128:2004-2007, 2018.

A 68-year-old man with known history of IgG4-related disease presented with a 1-year history of mucoid discharge OD and progressive proptosis OS. MRI showed diffuse enlargement of the left lacrimal gland along with prolonged infiltrative changes involving the left extraocular muscles, supraorbital nerve, and infraorbital nerve. No identifiable masses were noted in either nasolacrimal drainage system on MRI. Due to clinical evidence of nasolacrimal duct obstruction, a right external dacryocystorhinostomy was performed along with biopsies of the right lacrimal sac and left lacrimal gland. Immunohistochemical stains identified IgG4-positive plasma cells in the biopsy of the right lacrimal sac indicative of secondary acquired nasolacrimal duct obstruction despite the absence of mass forming lesions on exam and nasolacrimal imaging. This report is the first to describe nasolacrimal drainage system IgG4-related ophthalmic disease involvement in an otherwise clinically and radiographically normal appearing tear drainage system.

Intravenous tocilizumab has been demonstrated to be an effective disease modifying agent in the treatment of moderate to severe active thyroid eye disease. The authors describe 2 patients treated with tocilizumab using home subcutaneous administration over an accelerated, biweekly course. Both patients exhibited improvement in thyroid eye disease clinical activity and proptosis.

A 68-year-old immunocompromised man with rhino-orbital-cerebral mucormycosis was treated with retrobulbar injections of amphotericin B deoxycholate in conjunction with intravenous antifungals and endoscopic sinus debridement. Transient episodes of orbital inflammation were noted after retrobulbar injections, but progression of orbital infection was halted and visual acuity restored with eventual hospital discharge. To the authors' knowledge, clearance of orbital mucormycosis with retrobulbar amphotericin B injections has not been previously reported. This intervention may be a viable therapeutic option in cases of orbital mucormycosis where aggressive orbital debridement is not favored and/or the burden of orbital disease is not substantial. However, physicians should be aware of the risk of transient orbital inflammation secondary to retrobulbar amphotericin B deoxycholate.

The authors describe, for the first time to their knowledge, a case of a congenital macrocystic lymphatic malformation of the orbit with associated venous stasis retinopathy that acutely normalized after drainage and sclerotherapy of the lesion. Prenatal ultrasound revealed prominence of the left orbital soft tissue, and at birth, the patient was noted to have unilateral proptosis, tortuous retinal vessels, and intraretinal hemorrhages in all 4 quadrants in the left eye. MRI demonstrated a primarily intraconal, multiloculated, T2-hyperintense mass consistent with a lymphatic malformation. Ultrasound-guided cyst aspiration and sclerotherapy was performed, with subsequent improvement of the proptosis and resolution of the vessel tortuosity and intraretinal hemorrhages. Although venous stasis retinopathy is usually related to central retinal vein occlusion or carotid artery occlusive disease, any entity that increases orbital venous resistance can generate retinal venous dilation and intraretinal hemorrhages, including an orbital lymphatic malformation.

To summarize the ocular and systemic associations of floppy eyelid syndrome (FES) as well as provide an up-to-date review on the pathogenesis and treatment strategies.Virtually all patients with FES have obstructive sleep apnea (OSA). However, a significantly lower proportion of patients with OSA have FES. Although some studies demonstrate no association between OSA and FES, almost all show at least an association with increased eyelid laxity, which may be a less severe form of FES. FES has also been associated with keratoconus (KCN) and glaucoma. Decreased corneal hysteresis has been found in FES, KCN, glaucoma, and OSA and may be related to matrix metalloproteinase (MMP) upregulation. Hypoxia-reperfusion injury, leptin resistance, and mechanical forces all may lead to increased MMP activity, contributing to elastin breakdown in the tarsus and other tissues throughout the body. Management of FES begins with investigation for OSA. Treating OSA with continuous positive airway pressure (CPAP) or surgical uvulopalatoplasty may improve FES. Surgical treatments for FES should reduce horizontal eyelid laxity while maximizing the stability of the tarsus. Collagen crosslinking may prove a helpful modality for stabilizing the tarsus in the future.FES is associated with OSA, glaucoma, and KCN. MMP upregulation and lower corneal hysteresis have been found in these conditions, pointing toward a potential common pathogenesis.