Outcomes of centrally versus laterally based tarsoconjuctival pedicle flap reconstruction for large full thickness lower eyelid defects.

BACKGROUND: To compare the outcomes of two types of tarsoconjunctival pedicle flaps for reconstruction of large lower eyelid defects. METHODS: Retrospective medical record review of consecutive patients who underwent centrally-based or laterally-based tarsoconjunctival pedicle transconjunctival flap for lower eyelid reconstruction for defects greater than 50% of the lid margin. Full thickness skin grafts were used for anterior lamellar reconstruction in all cases. The primary outcome measure was eyelid position, function and satisfactory cosmesis. RESULTS: Forty-three patients were identified. Twenty-six patients underwent reconstruction with a centrally-based tarsoconjunctival pedicle flap; 17 patients underwent reconstruction with a laterally-based tarsoconjunctival pedicle flap. The average size of the lid defect was 77.7% (range 50-100%) in the central group and 75% (range 50-100%) in the lateral group (p=0.604). Mean follow up time was 61.5 weeks in the central group and 46.6 weeks in the lateral group (p=0.765). After division of the flap and during follow up, 27% of the centrally based group required revisional surgery with none in the laterally based group (p=0.03). 100% of the patients with centrally based flaps required second staged division of flap, whereas only 52% of patients with a laterally based flaps underwent second staged flap division. (p<0.001). CONCLUSION: Outcome suggests that for reconstruction of large lower lid defects requiring lid sharing procedures, both centrally and lateral-based procedures have equivalent functional outcome. However, the laterally based group has less need for revisional procedures and may not need a second stage division of the flap.

Looking beyond year 1 in the molecular era of pediatric brain tumor diagnosis: confirmatory testing of germline variants found on tumor sequencing.

Purpose: Somatic molecular profiling of pediatric brain tumors aids with the diagnosis and treatment of patients with a variety of high- and low-grade central nervous system neoplasms. Here, we report follow-up targeted germline evaluation for patients with possible germline variants following tumor only testing in the initial year in which somatic molecular testing was implemented at a single institution. Patients and Methods: Somatic testing was completed for all tumors of the central nervous system (CNS) undergoing diagnostic workup at Seattle Children's Hospital during the study period of November 2015 to November 2016. Sequencing was performed in a College of American Pathologists-accredited, Clinical Laboratory Improvements Amendments-certified laboratory using UW-OncoPlex™ assay (version 5), a DNA-based targeted next generation sequencing panel validated to detect genetic alterations in 262 cancer-related genes. We tracked subsequent clinical evaluation and testing on a subgroup of this cohort found to have potential germline variants of interest. Results: Molecular sequencing of 88 patients' tumors identified 31 patients with variants that warranted consideration of germline testing. To date, 19 (61%) patients have been tested. Testing confirmed germline variants for ten patients (31% of those identified for testing), one with two germline variants (NF1 and mosaic TP53). Eight (26%) patients died before germline testing was sent. One patient (13%) has not yet had testing. Conclusion: Clinically validated molecular profiling of pediatric brain tumors identifies patients who warrant further germline evaluation. Despite this, only a subset of these patients underwent the indicated confirmatory sequencing. Further work is needed to identify barriers and facilitators to this testing, including the role of genetic counseling and consideration of upfront paired somatic-germline testing.

The influence of orbital architecture on strabismus in craniosynostosis.

PURPOSE: To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis. METHODS: The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements. RESULTS: A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63%), Crouzon syndrome (13%), Apert syndrome (13%), and Pfeiffer syndrome (10%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups. CONCLUSIONS: In our small cohort, bony orbital dimensions, including the ratio of orbital height to width and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.

A comparison of proptosis reduction with teprotumumab versus surgical decompression based on fat-to-muscle ratio in thyroid eye disease.

PURPOSE: To explore if orbital fat-to-muscle ratio (FMR) is predictive of whether surgical decompression or teprotumumab leads to greater proptosis reduction in thyroid eye disease (TED). METHODS: A single-center retrospective cohort study comparing surgical decompression with teprotumumab according to FMR. All TED patients completing an 8-dose course of teprotumumab between January 2020 and September 2022 and all patients undergoing bony orbital decompression from January 2017 to December 2019 were included. Subjects were excluded if they were <18 years, received both surgical decompression and teprotumumab, or lacked orbital imaging. The primary exposure variable was teprotumumab or surgical decompression. The secondary exposure variable was baseline FMR. The primary outcome measure was change in proptosis (mm). RESULTS: Thirty-eight patients, mean age 53.5 years (±11.4), were included in the teprotumumab group and 160 patients, mean age 48 years (±11.1), in the surgical group. Average proptosis reduction after teprotumumab and surgical decompression was 3 mm (±1.44) and 5 mm (±1.75), respectively. The FMR was stratified at the median of 1.80. In subjects with FMR < 1.80, teprotumumab showed equivalent proptosis reduction compared to surgical decompression, -0.33 mm (SE 1.32) p = .802. In subjects with FMR ≥ 1.80, surgical decompression led to significantly more proptosis reduction than teprotumumab, 3.01 mm (SE 0.54), p < .001. CONCLUSIONS: Baseline FMR can be used to counsel patients as to proptosis reduction with teprotumumab versus surgery. Subjects with low FMR obtain comparable proptosis reduction with teprotumumab or surgery, whereas high FMR is associated with more significant proptosis reduction following surgery over teprotumumab.

A dose characterization study evaluating the pharmacodynamics and safety of a concentrated alfaxalone solution (4%) as an intramuscular sedative in dogs.

Alfaxalone is a commonly employed veterinary anaesthetic induction and sedation agent. A 4% w/v preserved, aqueous formulation of alfaxalone 'RD0387' (A4%) has recently been developed. To evaluate the sedative effects of A4%, three doses, 5 mg kg-1 (A5); 7.5 mg kg-1 (A7.5) and 10 mg kg-1 (A10) were administered intramuscularly into the epaxial musculature of six healthy adult mixed-breed dogs in an experimental, randomized, blinded, crossover study. Sedation time variables, quality of sedation (including onset of sedation and recovery), physiological variables, response to cephalic vein catheterization and frequency of undesirable events were recorded. Continuous variables were analysed between treatments (one-way ANOVA or restricted maximum likelihood modelling) and within treatments compared with baseline (Tukey's test). Categorical data were analysed between treatments (Kruskal-Wallis' test) and within treatments from baseline (Dunn's test). Significance was set at p < .05. All dogs became sedated (laterally recumbent) and sedation onset was significantly faster in groups A7.5 (9.8 ± 5.3 min) and A10 (9.1 ± 5.6 min) compared to A5 (25.6 ± 16.1 min) (p = .033, p = .027, respectively). Duration of sedation was significantly longer in A10 (168.5 ± 70.6 min) and A7.5 (143.8 ± 58 min) compared to A5 (63.8 ± 28.2 min) (p = .005 and p = .003, respectively). Dogs in A10 had a superior quality of onset of sedation compared to A5 (p = .028). Sedation scores and quality of recovery from sedation were not significantly different between doses. Two dogs (2/6) in A5 were insufficiently sedated for cephalic catheterization. Ataxia was the most frequently observed undesirable event with an overall frequency of 78% (14/18) and 89% (16/18) during sedation onset and recovery, respectively. Overall, A4% administered IM in dogs at 7.5 and 10 mg kg-1 resulted in sufficient sedation for IV catheterization in dogs. To improve the speed and quality of the sedation, it is recommended that future research focuses on combining A4% with other sedative or analgesic drugs.

Blepharospasm Secondary to Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson Disease: Clinical Characteristics and Management Outcomes.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for patients with motor symptoms of Parkinson disease but can be complicated by disabling blepharospasm and apraxia of eyelid opening (ALO). Currently, there is no clear consensus on optimal management, and addressing these issues is further hindered by systemic morbidity and resistance to treatments. We aim to describe the different phenotypes of these eyelid movement disorders, to report our management approach and patient responses to treatment. METHODS: A retrospective case series of all patients with blepharospasm/ALO secondary to STN-DBS that were treated at a tertiary center between 2011 and 2020. Data collected included date of Parkinson diagnosis, date of DBS surgery, date of development of blepharospasm/ALO symptoms, STN-DBS stimulation settings, and treatment given. Patients' symptoms before and after treatment were measured using the blepharospasm disability index and Jankovic Rating Scale. RESULTS: Five patients were identified with eyelid movement disorders secondary to STN-DBS. All patients had moderate-to-severe symptoms at presentation. Four patients received periocular botulinum toxin injections. Three patients underwent surgery in the form of frontalis suspension or direct brow lift with or without upper lid blepharoplasty. All reported an improvement in symptoms following treatment. CONCLUSIONS: A multimodality, patient-specific approach is required in the treatment of blepharospasm/ALO secondary to STN-DBS. Botulinum toxin injections can be effective, but patients may require surgery if toxin treatment alone becomes ineffective. Tailoring treatment to individual needs can result in a measurable improvement in symptoms.

Teprotumumab-related Cutaneous Hypersensitivity Reactions.

The authors report 4 cases of cutaneous hypersensitivity reactions developing in the course of teprotumumab treatment for thyroid eye disease. The onset of the cutaneous hypersensitivity reaction was also observed during the treatment course in all cases, between the second and fifth infusions. Teprotumumab-related cutaneous reactions suggest a possible immunogenic component of the monoclonal antibody and highlight the importance of close monitoring during treatment.

Reducing Surgical Risks in a Blepharoplasty.

Blepharoplasty is one of the commonest procedures performed for facial rejuvenation. The eyelids play a vital role in maintaining ocular surface integrity and visual functioning. Care must be taken to avoid complications that pose a risk to vision and ocular comfort. In addition, cosmetic complications can adversely affect patient satisfaction. Here the authors review the common complications encountered with blepharoplasty surgery and discuss how to minimize the risk of these and how to treat them if they do arise. With careful preoperative patient counseling, sound intraoperative technique, and appropriate postsurgical care, blepharoplasty remains a safe and well-tolerated procedure.

Evaluation of Depression and Anxiety in a Diverse Population With Thyroid Eye Disease Using the Nationwide NIH All of Us Database.

PURPOSE: To evaluate the prevalence of depression and anxiety among individuals with thyroid eye disease (TED) and identify sociodemographic risk factors using the NIH All of Us database. METHODS: Three hundred ninety eight cases with TED were compared with 1,592 controls with demographics matching the 2020 US Census. Primary outcomes were diagnosed depression or anxiety; Patient Health Questionnaire-9 (PHQ-9) scores and General Anxiety Disorder-7 (GAD-7) scores were included as secondary outcomes. We performed multivariable logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between TED and depression and anxiety. RESULTS: Patients with TED were more likely to have depression (OR 2.72, 95% CI 2.08-3.56, p < 0.001) and anxiety (OR 2.82, 95% CI 2.16-3.70, p < 0.001) than controls. In patients with TED, female gender was an independent risk factor for both depression (OR 1.72; 95% CI 1.00-5.07, p = 0.05) and anxiety (OR 2.17, 95% CI 1.25-3.85, p = 0.006). Unemployment (OR 1.72, 95% CI 1.03-2.94, p = 0.04) and lower income (OR 0.88 for income as a continuous variable, 95% CI 0.79-0.99, p = 0.03) were risk factors for anxiety. Risk factors for more severe depression as assessed by PHQ-9 included lower income (OR 0.70, 95% CI 0.57-0.85, p < 0.001), and protective factors included Black race (OR 0.12, 95% CI 0.02-0.45, p = 0.002). Lower income was associated with more severe anxiety as assessed by GAD-7 (OR 0.77, 95% CI 0.64-0.94, p = 0.009). CONCLUSIONS: Patients with TED were more likely to develop depression and anxiety compared with controls. This study highlights the psychosocial impact of TED and associated socioeconomic risk factors.

Ectopic Fibrous Dysplasia Presenting As a Well-Circumscribed Orbital Mass.

The authors present the case of a middle-aged woman with subacute progressive swelling of the OD associated with pain and severely limited duction in all gazes. MRI demonstrated a ~3 cm circumscribed mass in the extraconal space, which displaced and distorted the globe and impinged upon ocular adnexa. She underwent lateral orbitotomy with bone osteotomy to remove the mass, and subsequent histopathologic examination showed woven bone set within a fibrotic background, microscopic features of fibrous dysplasia. Fibrous dysplasia is characterized by abnormal scar-like bony proliferation, typically within a preexisting structure of the skeletal system. To the authors' knowledge, this represents the first example of fibrous dysplasia presenting as an orbital mass unconnected to the craniofacial skeleton.

Delayed hypersensitivity reaction from microneedling twenty years after silicone fillers.

Skin rejuvenation procedures have increasingly flooded the aesthetic market, one of which includes microneedling. In microneedling, multiple fine punctures of the skin are performed with a needle to induce neocollagenesis. Microneedling has increasingly been used to treat inflammatory acne, acne scarring, photodamaged skin, and even radiation dermatitis. We present a patient with a stable history of liquid injectable silicone (LIS) given 20 years prior who developed chronic periocular and facial hypersensitivity after undergoing microneedling at a medi-spa. Long-term steroids and immunosuppressants were needed for control. The patient's severe reaction and resistance to treatment highlights the potential complications of microneedling administered by a non-medical professional in the setting of prior injectable silicone.

Broad Antimicrobial Resistance in a Case of Relapsing Babesiosis Successfully Treated With Tafenoquine.

We describe a case of relapsing babesiosis in an immunocompromised patient. A point mutation in the Babesia microti 23S rRNA gene predicted resistance to azithromycin and clindamycin, whereas an amino acid change in the parasite cytochrome b predicted resistance to atovaquone. Following initiation of tafenoquine, symptoms and parasitemia resolved.

Associations Between Thyroid Eye Disease and Glaucoma Among Those Enrolled in the National Institutes of Health All of Us Research Program.

PURPOSE: To assess the association between thyroid eye disease (TED) and glaucoma. METHODS: Patients 18 years of age and over enrolled in the NIH All of Us Research Program, a nationwide cohort, were extracted. Those with conditions relating to TED were identified and compared with 2020 US Census-matched controls without a diagnosis of TED in a 1:4 ratio. The authors used Pearson's χ 2 tests to study demographics by TED status, and logistic regression to generate odds ratios and 95% confidence intervals to evaluate the association between TED and glaucoma (any type, including glaucoma suspect), using those without TED as the reference group. Multivariable models were adjusted for age, gender, race/ethnicity, eye doctor visits, and smoking status. RESULTS: A total of 393 cases of TED and 1,572 US Census-matched controls were identified. The median age of the cohort was 63 years (interquartile range: 48-73 years). Age, gender, and race/ethnicity varied by TED status ( p < 0.001). Overall, 114 (29.0%) of TED cases had a diagnosis of glaucoma, compared with 94 (6.0%) of non-TED controls. On bivariate logistic regression models, those diagnosed with TED were significantly more likely to be diagnosed with glaucoma compared with controls (odds ratio: 6.42; 95% confidence interval: 4.76-8.70; p < 0.001). This trend persisted on multivariable logistic regression controlling for confounding factors (odds ratio: 3.37; 95% confidence interval: 1.85-6.20 p < 0.001). CONCLUSIONS: Individuals with TED were significantly more likely to be diagnosed with glaucoma. Clinicians caring for patients with TED should be aware of this elevated risk and arrange glaucoma evaluation, accordingly.

Conjunctival Perivascular Epithelioid Cell Neoplasm With RBM10-TFE3 Fusion Presenting as Recurrent Subconjunctival Hemorrhage.

Subconjunctival hemorrhages commonly present to eye care professionals and are frequently regarded as benign self-limited conditions. In selected cases, subconjunctival hemorrhages can be a harbinger of more severe disease. Perivascular epithelioid cell tumors, or PEComas, are rare mesenchymal neoplasms believed to originate from perivascular myoid cells and are rarely present in ocular structures. We present a rare case of a conjunctival perivascular epithelioid cell tumor that initially presented with recurrent subconjunctival hemorrhage. To our knowledge, this is the first description of a PEComa with a RBM10-TFE3 gene fusion, only previously seen with renal cell carcinoma. Physicians should be aware of this rare condition, its location in the fornix and its presentation as a recurrent subconjunctival hemorrhage.

Differential effects of teprotumumab treatment based on fat-to-muscle ratio in patients with thyroid eye disease.

PURPOSE: To characterize the distribution of fat-to-muscle ratio (FMR) across patients with thyroid eye disease (TED) and to assess the association between FMR and therapeutic response to teprotumumab. METHODS: A retrospective cohort study of patients completing a full course of teprotumumab for TED between January 2020 and March 2022 at a single tertiary referral center. Patients without baseline orbital imaging were excluded. Quantitative analysis of FMR was performed by manual segmentation of patients' imaging using OsiriX software. The primary outcome measure was change in clinical measurement of proptosis. Linear regression modelled change in proptosis against FMR. Statistical significance was set at p < .05. RESULTS: Twenty-two patients (3 M:19F) were included with a mean age of 49.4 ± 15.5 years. The FMR ranged from 1.11 to 6.54, mean 3.15 ± 1.30. The data did not deviate from a normal distribution (Shapiro-Wilk test for normality, p = .18). Pre- and post-treatment average proptosis measurements were 21.72 ± 3.56 mm and 18.81 ± 3.07 mm, respectively. Univariable linear regression demonstrated a 0.78 ± 0.36 mm greater reduction in proptosis for every 1 unit decrease in FMR (p = .038). CONCLUSIONS: Contrary to the traditional dichotomous characterization of TED into type 1 and type 2 phenotypes, orbital FMR may represent a continuum of disease manifestation, more closely following a normal rather than bimodal distribution. Furthermore, pre-treatment FMR is associated with response to teprotumumab; those with lower FMR experiencing a greater reduction in proptosis. This has implications for patient selection and counselling regarding the expected treatment outcome.

Unravelling the Complex Anatomy of the Tear Trough and Lower Eyelid Folds: A Review of Cadaveric Studies in the Literature.

The lower eyelid tear trough deformity is a common cosmetic concern which is the result of multiple anatomic changes in the lower eyelid, usually resulting from age. A sound understanding of the underlying anatomy is vital to inform surgeons about the ideal treatment options for rejuvenation of this region and to minimize the risk of complications. Cadaveric studies provide unique insight into underlying anatomic changes. Here we review the relevant published cadaveric studies relating to the tear trough deformity and its treatment.