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.

Auditory precision hypothesis-L2: Dimension-specific relationships between auditory processing and second language segmental learning.

Growing evidence suggests a broad relationship between individual differences in auditory processing ability and the rate and ultimate attainment of language acquisition throughout the lifespan, including post-pubertal second language (L2) speech learning. However, little is known about how the precision of processing of specific auditory dimensions relates to the acquisition of specific L2 segmental contrasts. In the context of 100 late Japanese-English bilinguals with diverse profiles of classroom and immersion experience, the current study set out to investigate the link between the perception of several auditory dimensions (F3 frequency, F2 frequency, and duration) in non-verbal sounds and English [r]-[l] perception and production proficiency. Whereas participants' biographical factors (the presence/absence of immersion) accounted for a large amount of variance in the success of learning this contrast, the outcomes were also tied to their acuity to the most reliable, new auditory cues (F3 variation) and the less reliable but already-familiar cues (F2 variation). This finding suggests that individuals can vary in terms of how they perceive, utilize, and make the most of information conveyed by specific acoustic dimensions. When perceiving more naturalistic spoken input, where speech contrasts can be distinguished via a combination of numerous cues, some can attain a high-level of L2 speech proficiency by using nativelike and/or non-nativelike strategies in a complementary fashion.

Subcutaneous tocilizumab for active thyroid eye disease refractory to orbital radiation and systemic steroids in tobacco smokers.

PURPOSE: Tocilizumab (TCZ) through intravenous infusion has been shown to effectively treat active thyroid eye disease (TED) refractory to systemic steroids. TCZ is also available as a self-administered subcutaneous injection, but data demonstrating the efficacy of this formulation are limited. This study investigated the efficacy and safety of subcutaneous TCZ (SC-TCZ) for the treatment of active, moderate-to-severe TED in smokers. MATERIALS AND METHODS: This retrospective clinical case series evaluated the clinical outcomes and adverse effects of SC-TCZ when taken for a minimum of 4 months by patients with moderate-to-severe TED and a current or recent history of cigarette smoking. RESULTS: Three patients received SC-TCZ every 1-2 weeks (4.6-11.2 mg/kg/month). The average pre-to-posttreatment clinical activity score reduction was 5.4, and proptosis was reduced by an average of 2.0 mm. No serious adverse effects were reported. CONCLUSION: SC-TCZ may be a useful and effective therapy for treating challenging cases of inflammatory TED and offers a safe alternative to office or hospital-based infusions. Further studies are needed to better understand optimal dosing regimens and relative efficacy compared to monthly TCZ infusions and other immunotherapies.

Efficacy of lateral orbital rim decompression in patients with prior rim-sparing, three-wall orbital decompression.

PURPOSE: The purpose was to study the effects of removal of the lateral orbital rim in patients with prior three-wall decompression for thyroid eye disease (TED). MATERIALS AND METHODS: This was a single-institution retrospective case series of patients presenting with symptoms and signs of residual symptomatic proptosis that had previously undergone three-wall decompression for TED. Data collected included patient age, gender, presenting symptoms, ocular history, proptosis reduction, and complications. RESULTS: Eleven orbits were identified. The mean preoperative exophthalmometry for the operative eye was 24.0 mm with 2.7 mm of relative proptosis. Removal of the lateral orbital rim resulted in a mean reduction in proptosis of 2.5 mm (range: 0.5-5.0 mm, P < 0.001). There was no significant change in diplopia, lagophthalmos, margin reflex distance (MRD) 1, MRD2, or exposure keratopathy. No canthal deformities were noted. All subjects reported satisfaction with functional and cosmetic outcomes of lateral orbital rim removal, and none reported problems with external contour irregularities of the lateral canthal region. CONCLUSION: Removal of the lateral orbital rim as part of a maximal orbital bony decompression adds to the decompressive effect of proptosis reduction with minimal side effects.

Stereotactic navigation in orbital decompression surgery - Does it shorten operative time and improve outcomes?

PURPOSE: Stereotactic navigation is being increasingly used for orbital decompression (OD). Recent studies have cited clinical benefits of navigation including greater proptosis reduction but have differed regarding effects on operative time. This study aimed to evaluate navigated vs. non-navigated OD with respect to operative time and proptosis reduction. MATERIALS AND METHODS: Retrospective nonrandomized comparative trial of navigated vs. nonnavigated OD. Operative time and proptosis reduction were recorded and analyzed for all patients. RESULTS: A total of 30 orbital decompressions were included; 14 were performed with stereotactic navigation (SN), and 16 were performed without SN. On average, the SN group took 19 minutes longer for 3-wall decompressions (p = 0.185), 25 minutes shorter for balanced decompressions (p = 0.025), and 18 minutes longer (p = 0.067) for lateral wall decompressions. Mean proptosis reduction (PR) in 3-wall decompressions was greater in the SN group (p = 0.02). Among balanced wall decompressions, mean PR was 4.25 mm and 3.67 mm for the SN and non-SN groups (p = 0.30), respectively. For lateral wall decompressions, mean PR was 2.63 mm with SN and 2.50 mm without SN (p = 0.45). CONCLUSIONS: This study showed no difference in operative times between navigated and non-navigated OD, although empirical experience showed variable times required for registration and intraoperative troubleshooting of the navigation system. This study also found that navigation increased proptosis reduction for all types of OD. Further randomized controlled trials are needed to better understand the impact of navigation technology on operative times and surgical outcomes.

Lateral Tarsal Strip Complications With and Without Conjunctiva Stripping.

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

Outcomes of corneal neurotisation using processed nerve allografts: a multicentre case series.

BACKGROUND: Corneal neurotisation is a rapidly evolving procedure treating neurotrophic keratopathy. The variety of surgical techniques used and corresponding outcomes after corneal neurotisation are not well understood. This study describes the techniques and outcomes in the largest case series of corneal neurotisation using processed nerve allografts to date. METHODS: This is a retrospective case series of patients who underwent corneal neurotisation with human cadaveric processed nerve allografts. All patients had preoperative and postoperative description of best corrected visual acuity and measurement of corneal sensation. Comparative studies after stratification of techniques were performed. RESULTS: A total of 17 patients were identified. The cause of corneal anaesthesia was prior infection in eight cases, trigeminal nerve palsy in eight cases and ocular trauma in one case. There were no intraoperative or postoperative complications. Following neurotisation surgery, the time to first gain of corneal sensation and maximal gain of sensation occurred at a mean of 3.7 months (range 1-8 months) and 6.6 months (range 3-15 months), respectively. The mean preoperative and postoperative corneal sensation as measured by Cochet-Bonnet aesthesiometry was 0.36 cm (range 0-3.2 cm) and 4.42 cm (range 0-6 cm), respectively (p<0.01). Visual acuity was unchanged after neurotisation. There were no statistical differences in outcomes based on end-to-end versus end-to-side coaptations, donor nerve selection or laterality of donor nerve. CONCLUSION: Corneal neurotisation with processed nerve allografts is a safe and effective procedure. This study provides further evidence for the use of processed nerve allografts for corneal neurotisation.

Identification of Non-Fatal Opioid Overdose Cases Using 9-1-1 Computer Assisted Dispatch and Prehospital Patient Clinical Record Variables.

Background: The current epidemic of opioid overdoses in the United States necessitates a robust public health and clinical response. We described patterns of non-fatal opioid overdoses (NFOODs) in a small western region using data from the 9-1-1 Computer Assisted Dispatch (CAD) record and electronic Patient Clinical Records (ePCR) completed by EMS responders. We determined whether CAD and ePCR variables could identify NFOOD cases in 9-1-1 data for intervention and surveillance efforts. Methods: We conducted a retrospective analysis of 1 year of 9-1-1 emergency medical CAD and ePCR (including naloxone administration) data from the sole EMS provider in the response area. Cases were identified based on clinician review of the ePCR, and categorized as definitive NFOOD, probable NFOOD, or non-OOD. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the most prevalent CAD and ePCR variables were calculated. We used a machine learning technique-Random-Forests (RF) modeling-to optimize our ability to accurately predict NFOOD cases within census blocks. Results: Of 37,960 9-1-1 calls, clinical review identified 158 NFOOD cases (0.4%), of which 123 (77.8%) were definitive and 35 (22.2%) were probable cases. Overall, 106 (67.1%) received naloxone from the EMS responder at the scene. As a predictor of NFOOD, naloxone administration by paramedics had 67.1% sensitivity, 99.6% specificity, 44% PPV, and 99.9% NPV. Using CAD variables alone achieved a sensitivity of 36.7% and specificity of 99.7%. Combining ePCR variables with CAD variables increased the diagnostic accuracy with the best RF model yielding 75.9% sensitivity, 99.9% specificity, 71.4% PPV, and 99.9% NPV. Conclusion: CAD problem type variables and naloxone administration, used alone or in combination, had sub-optimal predictive accuracy. However, a Random Forests modeling approach improved accuracy of identification, which could foster improved surveillance and intervention efforts. We identified the set of NFOODs that EMS encountered in a year and may be useful for future surveillance efforts.

Comparing factual recall of tapped vs. handwritten text.

As a result of the rushed transition to remote teaching because of the COVID-19 pandemic, teachers have suddenly been forced to design mobile-assisted language learning (MALL; m-learning) activities, mostly for the first time in their careers. However, it is imperative that instructors realize that the challenge is greater than simply converting paper-based assignments into a digital format. There has been very little research done examining the cognitive effects of writing on a smartphone, compared to writing on paper. The current study therefore sought to examine how recollection of content differed depending on the medium used for notetaking. A population of 138 Japanese university students of English-as-a-Foreign-Language (EFL) were asked to transcribe a short text, either by paper or by smartphone, and then quizzed on the content immediately afterwards. Students who wrote the text by hand were found to have significantly greater recollection of the content compared to those who had 'tapped' on smartphones. These results follow precursor research which indicated that Japanese students compose significantly slower on their phones in English (Lee, 2020b), and wrote significantly less in writing tasks (Lee, 2019, 2020a) than handwriting counterparts.

Orbital Hemorrhagic Necrosis, Globe Rupture, and Death From Intraorbital Injection of 1% Sodium Deoxycholate in a Murine Model.

PURPOSE: Deoxycholic acid (DCA) 1% is an injectable detergent indicated for submental fat reduction, although clinically it is being injected off-label for orbital fat prolapse. It is known to cause severe inflammation, local nerve dysfunction, and tissue necrosis, all of which could be catastrophic in the orbit and periocular region. This study evaluated the effects of periocular DCA on orbital and ocular adnexal tissues in a murine model. METHODS: Mice were treated via split-face intraorbital injections, subcutaneous injections, and topical cornea application with DCA versus phosphate-buffered saline. Whole heads were fixed, decalcified, and sectioned for orbital histology after 1-7 days. Matched pairs of human globes and mouse globes were immersed in either phosphate-buffered saline or 1% DCA for 72 hours. RESULTS: Six of 11 mice receiving intraorbital DCA injections died within minutes. Surviving mice developed severe orbital inflammatory necrosis. All orbits injected with phosphate-buffered saline were clinically and histologically normal. Six mice were treated with lower concentrations of DCA and all developed variable amounts of orbital inflammation, hemorrhage, and globe necrosis. Mice receiving subcutaneous DCA injection to the lower eyelid showed inflammatory necrosis, edema, and lid malposition. Topical application of DCA to mouse corneas caused no external or histologic changes. Human and mouse globes immersed ex vivo in DCA developed corneal edema and cataract formation without observable scleral changes. CONCLUSION: Intraorbital and periocular injection of DCA can cause devastating complications in a murine model, and significant caution is advised for off-label use in the periocular region.

Orbital Bony Reconstruction With Presized and Precontoured Porous Polyethylene-Titanium Implants.

PURPOSE: Complex bony orbital defects are reconstructively challenging due to loss of intraoperative anatomical landmarks and adjacent support. Presized and precontoured porous polyethylene-titanium implants (Medpor Titan 3D Orbital Floor Implant) are designed to reestablish normal orbital floor and medial wall anatomy and are modeled after anatomically averaged orbits. This is the first study to report clinical outcomes with this implant. METHODS: This retrospective case series reviewed clinical data and outcomes for patients undergoing orbital reconstruction with a presized and precontoured porous polyethylene-titanium orbital implant from January 2016 to June 2018. RESULTS: A total of 34 orbits of 33 patients were identified (mean age: 43 ± 16 years, 70% men). Most bony defects were a result of trauma and included large orbital floor deformities (100%), medial wall defects (74%), disrupted inferomedial struts (68%), and broken posterior ledges (82%). Symptomatic diplopia (73%) and enophthalmos (89%, mean: 3.7 ± 2.1 mm) were common preoperatively. Many cases were revisions (44%). Mean follow up was 7.8 ± 6.7 months. All patients had improved globe positioning, enophthalmos, and hypoglobus. Seven patients had persistent postoperative diplopia: 6 responded to prism therapy and 1 required strabismus surgery. One patient required retrobulbar hematoma drainage and 1 patient required implant explantation due to chronic infection. CONCLUSIONS: Commercially available presized and precon toured porous polyethylene-titanium implants are useful for complex orbital bony defects and can achieve functional improve ments in diplopia, enophthalmos, and extraocular motility with a low incidence of postoperative complications or revisional surgery.

Bilateral Poorly Differentiated Adenocarcinoma of the Lacrimal Gland With Tumor Regression After Treatment With Pembrolizumab.

An 85-year-old man presented with a 6-month history of worsening left proptosis and painless ophthalmoplegia. Imaging revealed an extensive intraconal and extraconal tumor extending to the level of the optic foramen, as well as the scalp, cheek, and the nasal bridge. Incisional biopsy was consistent with lacrimal gland adenocarcinoma. The patient underwent a left orbital exenteration followed by immunotherapy with pembrolizumab. The treatment was stopped prematurely after 5 cycles due to development of autoimmune colitis. Four months later, the patient developed new contralateral disease in the right orbit and an incisional biopsy again showed lacrimal gland adenocarcinoma. Following the incisional biopsy, no further treatment was administered, but over the ensuing 6 months, there was dramatic spontaneous regression of the tumor both clinically and radiographically. At 28 months, the patient is still alive with relatively stable disease.

A Modified Hughes Flap for Correction of Refractory Cicatricial Lower Lid Retraction With Concomitant Ectropion.

INTRODUCTION: Correction of lower eyelid retraction commonly involves one or more techniques, including recession of the eyelid retractors, spacer grafts, horizontal lid tightening, and midface lifting. However, patients presenting with cicatricial lower lid retraction following prior eyelid surgery often have scarring and concomitant ectropion or entropion that cause unpredictable wound healing, recicatrization, and suboptimal outcomes. The modified Hughes tarsoconjunctival flap is typically used to repair full-thickness eyelid defects. Prior reports describe treating refractory lower lid retraction with a modified Hughes flap placed beneath the tarsus after full-thickness blepharotomy. We present our experience with a novel surgical technique for treating refractory cicatricial lower lid retraction using a modified Hughes flap above the tarsus after excision of the scarred lid margin. METHODS: Three patients were treated using this technique. The upper edge of the lower eyelid and associated scar tissue are excised. A modified Hughes flap is mobilized and secured above the posterior lamellar remnant. A full-thickness skin graft is placed over the flap. The flap is divided 4-5 weeks later. RESULTS: This surgical technique was employed in all 3 cases. All cases were revisional, with 2 having extensive multioperative histories with multiple unsuccessful reconstructions and lid retraction repairs. All patients had improvement in cicatricial eyelid retraction, lagophthalmos, exposure keratopathy, and resolution of concomitant cicatricial ectropion. CONCLUSIONS: The technique of using a modified Hughes flap to reconstruct above the tarsus with excision of the scarred lid margin was effective in correcting refractory cicatricial lower lid retraction. This procedure can be considered in multioperative cases in which traditional techniques for lower lid retraction repair have failed. Reconstructing a new lid margin reduces the risk of recicatrization and suboptimal results.

Orbital cholesterol granuloma: A report and discussion of orbital findings.

PURPOSE: To report a case of orbital cholesterol granuloma and discuss the orbital findings seen in this entity. OBSERVATION: A 38-year-old male presented with an 8-month history of progressive left upper lid ptosis and hypoglobus. Clinical examination was significant for 3 mm of hypoglobus and restricted supraduction in the left eye. Contrasted computed tomography imaging revealed a well-circumscribed lesion in the superotemporal orbit causing extensive bone erosion that appeared to arise from the lacrimal gland. An incisional biopsy was performed, and histopathological evaluation demonstrated fibrovascular tissue surrounding a mixture of histiocytes and cholesterol clefts, consistent with a cholesterol granuloma. CONCLUSIONS AND IMPORTANCE: Orbital cholesterol granulomas are rare lesions that are predominantly found in the superotemporal orbit. These lesions can be associated with marked bony changes in the superotemporal fossa that can be mistaken for a lacrimal gland neoplasm; however, bony erosion is a hallmark of this lesion and should be considered on the differential diagnosis of any lacrimal gland mass with extensive bony erosion.

Odontogenic choristoma presenting as dermolipoma.

A 5-year-old otherwise healthy girl presented to the oculoplastic service with a painless superotemporal subconjunctival mass in the left eye. Visual acuity was within normal limits, and there was no evidence of proptosis or orbital enlargement. Excision was performed to remove the anterior portion of the mass for alleviation of symptoms. On histopathological analysis, the mass was comprised of fibroadipose tissue consistent with dermolipoma and contained a hard nodule found to be a calcified tooth. In the periocular region, odontogenic choristoma (tooth) is a rare lesion, and has been reported to occur within teratomas, dermoid cysts, and displaced oral embryonic epithelium. We describe an unusual case of a tooth occurring within a sporadic dermolipoma. The clinical presentation, examination, management, and histopathology are reviewed.