A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance.

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology centers. Adequate conjunctival biopsies were stained with hematoxylin and eosin, Melan-A, SOX10, and PReferentially expressed Antigen in Melanoma. Digitized slides were uploaded on the SmartZoom platform and independently scored by 4 ocular pathologists to obtain a consensus score, before circulating to 14 expert eye pathologists for independent scoring. In total, 105 cases from 97 patients were evaluated. The initial consensus diagnoses using the WHO-EYE04 C-MIL system were as follows: 28 benign conjunctival melanoses, 13 low-grade C-MIL, 37 high-grade C-MIL, and 27 conjunctival MIS. Using this system resulted in 93% of the pathologists showing only fair-to-moderate agreement (kappa statistic) with the consensus score. The WHO-EYE05 C-MIL system (with high-grade C-MIL and MIS combined) improved consistency between pathologists, with the greatest level of agreement being seen with benign melanosis (74.5%) and high-grade C-MIL (85.4%). Lowest agreements remained between pathologists for low-grade C-MIL (38.7%). Regarding WHO-EYE05 C-MIL scoring and clinical outcomes, local recurrences of noninvasive lesions developed in 8% and 34% of the low- and high-grade cases. Invasive melanoma only occurred in 47% of the cases that were assessed as high-grade C-MIL. This extensive international collaborative study is the first to undertake a comprehensive review of the WHO-EYE05 C-MIL scoring system, which showed good interobserver agreement and reproducibility.

Intravenous Ketorolac Substantially Reduces Opioid Use and Length of Stay After Lumbar Fusion: A Randomized Controlled Trial.

STUDY DESIGN: A randomized, double-blinded, placebo-controlled trial. OBJECTIVE: To examine the effect of intravenous ketorolac (IV-K) on hospital opioid use compared with IV-placebo (IV-P) and IV acetaminophen (IV-A). SUMMARY OF BACKGROUND DATA: Controlling postoperative pain while minimizing opioid use after lumbar spinal fusion is an important area of study. PATIENTS AND METHODS: Patients aged 18 to 75 years undergoing 1 to 2 level lumbar fusions between April 2016 and December 2019 were included. Patients with chronic opioid use, smokers, and those on systemic glucocorticoids or contraindications to study medications were excluded. A block randomization scheme was used, and study personnel, hospital staff, and subjects were blinded to the assignment. Patients were randomized postoperatively. The IV-K group received 15 mg (age > 65) or 30 mg (age < 65) every six hours (q6h) for 48 hours, IV-A received 1000 mg q6h, and IV-P received normal saline q6h for 48 hours. Demographic and surgical details, opioid use in morphine milliequivalents, opioid-related adverse events, and length of stay (LOS) were recorded. The primary outcome was in-hospital opioid use up to 72 hours. RESULTS: A total of 171 patients were included (58 IV-K, 55 IV-A, and 58 IV-P) in the intent-to-treat (ITT) analysis, with a mean age of 57.1 years. The IV-K group had lower opioid use at 72 hours (173 ± 157 mg) versus IV-A (255 ± 179 mg) and IV-P (299 ± 179 mg; P = 0.000). In terms of opiate use, IV-K was superior to IV-A ( P = 0.025) and IV-P ( P = 0.000) on ITT analysis, although on per-protocol analysis, the difference with IV-A did not reach significance ( P = 0.063). When compared with IV-P, IV-K patients reported significantly lower worst ( P = 0.004), best ( P = 0.001), average ( P = 0.001), and current pain ( P = 0.002) on postoperative day 1, and significantly shorter LOS ( P = 0.009) on ITT analysis. There were no differences in opioid-related adverse events, drain output, clinical outcomes, transfusion rates, or fusion rates. CONCLUSIONS: By reducing opioid use, improving pain control on postoperative day 1, and decreasing LOS without increases in complications or pseudarthrosis, IV-K may be an important component of "enhanced recovery after surgery" protocols.

Differences in imaging and clinical characteristics are associated with higher rates of decompression-fusion versus decompression-alone in women compared to men for lumbar degenerative spondylolisthesis.

PURPOSE: The goals were to ascertain if differences in imaging/clinical characteristics between women and men were associated with differences in fusion for lumbar degenerative spondylolisthesis. METHODS: Patients had preoperative standing radiographs, CT scans, and intraoperative fluoroscopic images. Symptoms and comorbidity were obtained from patients; procedure (fusion-surgery or decompression-alone) was obtained from intraoperative records. With fusion surgery as the dependent variable, men and women were compared in multivariable logistic regression models with clinical/imaging characteristics as independent variables. The sample was dichotomized, and analyses were repeated with separate models for men and women. RESULTS: For 380 patients (mean age 67, 61% women), women had greater translation, listhesis angle, lordosis, and pelvic incidence, and less diastasis and disc height (all p ≤ 0.03). The rate of fusion was higher for women (78% vs. 65%; OR 1.9, p = 0.008). Clinical/imaging variables were associated with fusion in separate models for men and women. Among women, in the final multivariable model, less comorbidity (OR 0.5, p = 0.05), greater diastasis (OR 1.6, p = 0.03), and less anterior disc height (OR 0.8, p = 0.0007) were associated with fusion. Among men, in the final multivariable model, opioid use (OR 4.1, p = 0.02), greater translation (OR 1.4, p = 0.0003), and greater diastasis (OR 2.4, p = 0.0002) were associated with fusion. CONCLUSIONS: There were differences in imaging characteristics between men and women, and women were more likely to undergo fusion. Differences in fusion within groups indicate that decisions for fusion were based on composite assessments of clinical and imaging characteristics that varied between men and women.

Ultra-sensitive UV solar-blind optical wireless communications with an SiPM.

In this Letter, an SiPM with a dedicated cooling system suitable for receiving ultra-low-power solar-blind wavelengths is reported. This is designed to decrease the temperature of the detector from 21°C to -10°C, and the corresponding dark count rate (DCR) is reduced by approximately 10 dB. A 275 nm optical wireless communication (OWC) system is established using on-off-keying (OOK) modulation. Transmission rates ranging from 100 kbit/s to 2 Mbit/s are demonstrated with this cooled SiPM. The received power is as low as 30 pW (corresponding to 41.5 photons per bit) at a data rate of 1 Mbit/s and a bit error rate of 2.4 × 10-3.

Anion-Dependent Reactivity of Mono- and Dinuclear Boron Cations.

The dinuclear bis(N-heterocyclic carbene) borane adduct 2 rapidly reacts with tritylium salts at room temperature but the outcome is strongly impacted by the respective counter-ion. Using tritylium tetrakis(perfluoro-tert-butoxy)aluminate affords - depending on the solvent - either the bis(boronium) ion 4 or the hydride-bridged dication 5. In case of tritylium hexafluorophosphate, however, H/F exchange occurs between boron and phosphorus yielding the dinuclear BF3 adduct 3 along with phosphorus dihydride trifluoride. H/F exchange also takes place when using the mononuclear N-heterocyclic carbene BH3 adduct 6 and hence provides a facile route to PH2 F3 , which is usually synthesized in more complex reaction sequences regularly involving toxic hydrogen fluoride. DFT calculations shed light on the H/F exchange between the borenium ion and the [PF6 ]- counter-ion and the computed mechanism features only small barriers in line with the experimental observations.

Substrate-Selective Adhesion of Metal Nanoparticles to Graphene Devices.

Nanostructured electronic devices, such as those based on graphene, are typically grown on top of the insulator SiO2. Their exposure to a flux of small size-selected silver nanoparticles has revealed remarkably selective adhesion: the graphene channel can be made fully metallized, while the insulating substrate remains coverage-free. This conspicuous contrast derives from the low binding energy between the metal nanoparticles and a contaminant-free passivated silica surface. In addition to providing physical insight into nanoparticle adhesion, this effect may be of value in applications involving deposition of metallic layers on device working surfaces: it eliminates the need for masking the insulating region and the associated extensive and potentially deleterious pre- and postprocessing.

Design, Synthesis, and Application of Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the CXC Chemokine Receptor 2.

The inhibition of CXC chemokine receptor 2 (CXCR2), a key inflammatory mediator, is a potential strategy in the treatment of several pulmonary diseases and cancers. The complexity of endogenous chemokine interaction with the orthosteric binding site has led to the development of CXCR2 negative allosteric modulators (NAMs) targeting an intracellular pocket near the G protein binding site. Our understanding of NAM binding and mode of action has been limited by the availability of suitable tracer ligands for competition studies, allowing direct ligand binding measurements. Here, we report the rational design, synthesis, and pharmacological evaluation of a series of fluorescent NAMs, based on navarixin (2), which display high affinity and preferential binding for CXCR2 over CXCR1. We demonstrate their application in fluorescence imaging and NanoBRET binding assays, in whole cells or membranes, capable of kinetic and equilibrium analysis of NAM binding, providing a platform to screen for alternative chemophores targeting these receptors.

Emerging Need for PROMs to Measure the Impact of Spine Disorders on Overall Health and Well-being: Measuring Expectations as an Example for Lumbar Degenerative Spondylolisthesis.

Background: Assessing the impact of spine disorders such as lumbar degenerative spondylolisthesis (LDS) on overall health is a component of quality of care that may not be comprehensively captured by spine-specific and single-attribute patient-reported outcome measures (PROMs). Purpose: We sought to compare PROMs to the Lumbar Surgery Expectations Survey ("Expectations Survey"), which addresses multiple aspects of health and well-being, and to compare the relevance of surgeon-selected versus survey-selected Patient-Reported Outcomes Measurement Information System (PROMIS) items to LDS. Methods: In a cross-sectional study, 379 patients with LDS preoperatively completed the Expectations Survey, Numerical Rating Pain Scales, Oswestry Disability Index (ODI), and PROMIS computer-adaptive physical function, pain, and mental health surveys. Expectations Survey scores were compared to PROMs with correlation coefficients (indicating strengths of relationships) and probability values (indicating associations by chance). Surgeons reviewed physical function questions to identify those particularly relevant to LDS. Results: Patients' mean age was 67 years, 64% were women, and 83% had single-level and 17% had multiple-level LDS. Probability values between the Expectations Survey and PROMs were reliable, but strengths of relationships were only mild to moderate, indicating PROMs did not comprehensively capture the impact of LDS. None of the surgeon-selected PROMIS physical function questions were posed to patients. Conclusion: This cross-sectional study found PROMs to be reliably associated but not strongly correlated with the Expectations Survey, which addresses the whole-patient impact of LDS. New measures that complement PROMIS and ODI should be developed to capture the whole-person effects of LDS and permit attribution of LDS treatments to overall health.

Instability Missed by Flexion-Extension Radiographs Subsequently Identified by Alternate Imaging in L4-L5 Lumbar Degenerative Spondylolisthesis.

STUDY DESIGN: Cross-sectional preoperative and intraoperative imaging study of L4-L5 lumbar degenerative spondylolisthesis (LDS). OBJECTIVE: To determine if alternate imaging modalities would identify LDS instability that did not meet the criteria for instability based on comparison of flexion and extension radiographs. SUMMARY OF BACKGROUND DATA: Pain may limit full flexion and extension maneuvers and thereby lead to underreporting of true dynamic translation and angulation in LDS. Alternate imaging pairs may identify instability missed by flexion-extension. MATERIALS AND METHODS: Consecutive patients scheduled for surgery for single-level L4-L5 LDS had preoperative standing radiographs in the lateral, flexion, and extension positions, supine computed tomography (CT) scans, and intraoperative fluoroscopic images in the supine and prone positions after anesthesia but before incision. Instability was defined as translation ≥3.5 mm or angulation ≥11° between the following pairs of images: (1) flexion-extension; (2) CT-lateral; (3) lateral-intraoperative supine; (4) lateral-intraoperative prone; and (5) intraoperative supine-prone. RESULTS: Of 240 patients (mean age 68 y, 54% women) 15 (6%) met the criteria for instability by flexion-extension, and 225 were classified as stable. Of these 225, another 84 patients (35% of total enrollment) were reclassified as unstable by comparison of CT-lateral images (21 patients) and by lateral-intraoperative images (63 patients). Nine of the 15 patients diagnosed with instability by flexion-extension had fusion (60%), and 68 of the 84 patients reclassified as unstable by other imaging pairs had fusion (81%) ( P =0.07). The 84 reclassified patients were more likely to undergo fusion compared with the 141 patients who persistently remained classified as stable (odds ratio=2.6, 95% CI: 1.4-4.9, P =0.004). CONCLUSIONS: Our study provides evidence that flexion and extension radiographs underreport the dynamic extent of LDS and therefore should not be solely relied upon to ascertain instability. These findings have implications for how instability should be established and the extent of surgery that is indicated.

Complications and Revisions After Spine Surgery in Patients With Skeletal Dysplasia: Have We Improved?

STUDY DESIGN: Retrospective case series. OBJECTIVE: To report contemporary rates of complications and subsequent surgery after spinal surgery in patients with skeletal dysplasia. METHODS: A case series of 25 consecutive patients who underwent spinal surgery between 2007 and 2017 were identified from a single institution's skeletal dysplasia registry. Patient demographics, medical history, surgical indication, complications, and subsequent surgeries (revisions, extension to adjacent levels, or for pathology at a non-contiguous level) were collected. Charlson comorbidity indices were calculated as a composite measure of overall health. RESULTS: Achondroplasia was the most common skeletal dysplasia (76%) followed by spondyloepiphyseal dysplasia (20%); 1 patient had diastrophic dysplasia (4%). Average patient age was 53.2 ± 14.7 years and most patients were in excellent cardiovascular health (88% Charlson Comorbidity Index 0-4). Mean follow up after the index procedure was 57.4 ± 39.2 months (range). Indications for surgery were mostly for neurologic symptoms. The most commonly performed surgery was a multilevel thoracolumbar decompression without fusion (57%). Complications included durotomy (36%), neurologic complication (12%), and infection requiring irrigation and debridement (8%). Nine patients (36%) underwent a subsequent surgery. Three patients (12%) underwent a procedure at a non-contiguous anatomic zone, 3 (12%) underwent a revision of the previous surgery, and another 3 (12%) required extension of their previous decompression or fusion. CONCLUSIONS: Surgical complication rates remain high after spine surgery in patients with skeletal dysplasia, likely attributable to inherent characteristics of the disease. Patients should be counseled on their risk for complication and subsequent surgery.

Eating sustainably: Conviction or convenience?

Environmentally sustainable food consumption is one component of addressing climate change. Previous research has largely approached sustainable food consumption by investigating individual behaviors, without a broader conceptualization of what motivates food consumers to act sustainably. Using a representative sample of Indiana consumers, we explore sustainability across a range of food behaviors through latent class analysis, controlling for environmental attitudes, spatial access to food, and consumer demographics. This approach allows us to go beyond consumer segmentation analysis to explore how consumers conceptualize sustainable food behavior. The largest class of consumers (44% of the sample) appear either unwilling or unable to pay more for sustainability but are more likely to engage in sustainable behaviors that intersect with self-oriented attributes such as health benefits and lower cost. A second class (34%) consists of consumers who seem to be primarily motivated by the single issue of buying organic, are on average higher income, more educated, have better access to food, and are not opposed to paying for sustainability. Consumers in the smallest and most highly motivated group (9%) in terms of sustainability attitudes and self-perceived sustainability focus on local food production and are generally rural dwelling with less income. Only 13% of consumers engage in few to no sustainable behaviors, and these people notably exhibit the least sustainable attitudes. These findings illustrate the ways in which food sustainability is more nuanced than often characterized-much of it is driven by convenience and self-interest rather than reputation with respect to sustainability or conviction about environmental outcomes. This work also highlights how a combination of social, psychological, and spatial barriers exists and shape how different consumer groups conceptualize sustainable food consumption.

Acute development of spinal lumbar synovial facet cyst within 1 week after lumbar decompression: illustrative case.

BACKGROUND: Synovial facet cysts can sometimes develop in patients with lumbar spinal stenosis after decompressive laminectomy. The etiology of spinal lumbar synovial cysts is still unclear, but their formation is associated with underlying spinal instability, facet joint arthropathy, and degenerative spondylolisthesis. OBSERVATIONS: A 61-year-old-male patient presented with neurogenic claudication due to lumbar spinal stenosis. Radiographic studies showed grade I spondylolisthesis and radiological predictors of delayed spinal instability. He underwent lumbar decompression and shortly thereafter developed spinal instability and recurrent symptoms, with formation of a new spinal lumbar synovial facet cyst. He required revisional decompression, cyst excision, and posterolateral spinal fusion for definitive treatment. LESSONS: The literature reports postoperative spinal instability in up to one-third of patients with lumbar spinal stenosis and stable degenerative spondylolisthesis who undergo decompressive laminectomy. Close radiographic monitoring and early advanced imaging may be prudent in this patient population if they develop new postoperative neurological symptoms and show radiographic predictors of instability on preoperative imaging. Posterolateral spinal fusion with instrumentation should be considered in addition to lumbar decompression in this select group of patients who demonstrate radiographic predictors of delayed spinal instability if they are medically capable of tolerating a spinal fusion procedure.

Quantitative CT for Preoperative Assessment of Lumbar Degenerative Spondylolisthesis: The Unique Impact of L4 Bone Mineral Density on Single-Level Disease.

Background: Quantitative computed tomography (qCT) efficiently measures 3-dimensional vertebral bone mineral density (BMD), but its utility in measuring BMD at various vertebral levels in patients with lumbar degenerative spondylolisthesis (LDS) is unclear. Purpose: We sought to determine whether qCT could differentiate BMD at different levels of LDS, particularly at L4-L5, the most common single level for LDS. In addition, we sought to describe patterns of BMD for single-level and multiple-level LDS. Methods: We conducted a study of patients undergoing surgery for LDS who were part of a larger longitudinal study comparing preoperative and intraoperative images. Preoperative patients were grouped as single-level or multiple-level LDS, and qCT BMD was obtained for L1-S1 vertebrae. Mean BMD was compared with literature reports; in multivariable analyses, BMD of each vertebra was assessed according to the level of LDS, controlling for covariates and for BMD of other vertebrae. Results: Of 250 patients (mean age: 67 years, 64% women), 22 had LDS at L3-L4 only, 170 at L4-L5 only, 13 at L5-S1 only, and 45 at multiple levels. Compared with other disorders reported in the literature, BMD in our sample similarly decreased from L1 to L3 then increased from L4 to S1, but mean BMD per vertebra in our sample was lower. Nearly half of our sample met criteria for osteopenia. In multivariable analysis controlling for BMD at other vertebrae, lower L4 BMD was associated with LDS at L4-L5, greater pelvic incidence minus lumbar lordosis, and not having diabetes. In contrast, in similar multivariable analysis, greater L4 BMD was associated with LDS at L3-L4. Bone mineral density of L3 and L5 was not associated with LDS levels. Conclusion: In our sample of preoperative patients with LDS, we observed lower BMD for LDS than for other lumbar disorders. L4 BMD varied according to the level of LDS after controlling for covariates and BMD of other vertebrae. Given that BMD can be obtained from routine imaging, our findings suggest that qCT data may be useful in the comprehensive assessment of and strategy for LDS surgery. More research is needed to elucidate the cause-effect relationships among spinopelvic alignment, LDS, and BMD.

Development of fluorescent peptide G protein-coupled receptor activation biosensors for NanoBRET characterization of intracellular allosteric modulators.

G protein-coupled receptors (GPCRs) are widely therapeutically targeted, and recent advances in allosteric modulator development at these receptors offer further potential for exploitation. Intracellular allosteric modulators (IAM) represent a class of ligands that bind to the receptor-effector interface (e.g., G protein) and inhibit agonist responses noncompetitively. This potentially offers greater selectivity between receptor subtypes compared to classical orthosteric ligands. However, while examples of IAM ligands are well described, a more general methodology for assessing compound interactions at the IAM site is lacking. Here, fluorescent labeled peptides based on the Gα peptide C terminus are developed as novel binding and activation biosensors for the GPCR-IAM site. In TR-FRET binding studies, unlabeled peptides derived from the Gαs subunit were first characterized for their ability to positively modulate agonist affinity at the ß2 -adrenoceptor. On this basis, a tetramethylrhodamine (TMR) labeled tracer was synthesized based on the 19 amino acid Gαs peptide (TMR-Gαs19cha18, where cha = cyclohexylalanine). Using NanoBRET technology to detect binding, TMR-Gαs19cha18 was recruited to Gs coupled ß2 -adrenoceptor and EP2 receptors in an agonist-dependent manner, but not the Gi-coupled CXCR2 receptor. Moreover, NanoBRET competition binding assays using TMR-Gαs19cha18 enabled direct assessment of the affinity of unlabeled ligands for ß2 -adrenoceptor IAM site. Thus, the NanoBRET platform using fluorescent-labeled G protein peptide mimetics offers novel potential for medium-throughput screens to identify IAMs, applicable across GPCRs coupled to a G protein class. Using the same platform, Gs peptide biosensors also represent useful tools to probe orthosteric agonist efficacy and the dynamics of receptor activation.

Efficacy of bilateral temporal artery biopsies and sectioning of the entire block of tissue for the diagnosis of temporal arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis of medium and large sized blood vessels. The incidence is greater in women as compared to men (3:1) and most often occurs in the elderly. The most common symptoms are unilateral headaches, visual disturbances and scalp tenderness. If untreated, GCA may result in irreversible blindness. Prompt treatment is necessary to prevent progression of the disease, but accurate diagnosis is vital to prevent unwarranted side effects of the therapy. Temporal artery biopsy (TAB) remains the gold standard for diagnosis. TAB is an invasive procedure that can require up to 40 minutes to perform but is important for pathological confirmation. Variation amongst centers and practitioners exists in the type of biopsies performed. In 2013, a survey of over 1000 specialists showed that 37% recommended unilateral biopsy alone, 29% recommended initial unilateral biopsy with biopsy of the contralateral side if the first side is negative, 18% recommended bilateral biopsy in all cases, and 16% stated that their preference depended upon the degree of suspicion. Studies have shown that bilateral TAB can enhance diagnostic accuracy by 3 to 12.7%. Furthermore, temporal arteritis can involve the artery in a discontinuous fashion and there is no standardization of the number of sections or levels that should be examined in a segment of temporal artery. This study aims to shed light on the benefits of a bilateral temporal artery biopsy as well as to determine the optimum level for block sectioning for the diagnosis of temporal arteritis.

Oculopharyngeal Muscular Dystrophy Ptosis, Mueller's Muscle Involvement, and a Review of Management Over 34 Years.

PURPOSE: To review the management of the ptosis associated with oculopharyngeal muscular dystrophy (OPMD) from one author's experience over 34 years, demonstrate Mueller's muscle involvement in this disease, and how this impacts the preferred choice of surgery. METHODS: Retrospective, nonrandomized comparative case series. Forty patients with OPMD who underwent primary bilateral ptosis surgery through an anterior eyelid incision and had their Mueller's muscle biopsied (one side) and sent for histopathologic analysis were selected for chart review. The main outcome measure was the presence or absence of dystrophic changes in the biopsied Mueller's muscle. RESULTS: In 29/40 biopsies (72.5%), there were dystrophic changes and fatty infiltration of Mueller's muscle identified histopathologically. CONCLUSIONS: Mueller's muscle is involved in the dystrophic process more often than expected contributing to ptosis in the OPMD syndrome. A combined Mueller's-aponeurotic advancement is more effective at elevating the eyelid than simply advancing the aponeurosis when Mueller's is fatty infiltrated at the time of external levator advancement surgery in our experience. Management strategies for ptosis surgery in OPMD are reviewed. The age of onset, levator muscle function, previous ptosis repair, how debilitated the patient is with their disease process systemically, as well as the presence of other eye problems (e.g., dry eye, prior glaucoma filtering procedures, history of corneal surgery, laser refractive procedure) are important clinical considerations in patients with OPMD.

A rare case of intramuscular angioma involving the medial rectus muscle.

Benign benign vascular tumors (e.g., hemangiomas) and malformations are commonly encountered lesions in all ages of life, especially in infancy and childhood. Hemangiomas are considered to be proliferative vascular lesions while malformations are defects of embryonal vascular morphogenesis. Less than 1% of hemangiomas within the body occur in skeletal muscle and of these approximately 15% have been reported to occur in the head and neck musculature (e.g. masseter, trapezius, sternocleidomastoid, mylohyoid, temporalis muscles) Intramuscular angioma (the preferred term for lesions formerly known as intramuscular hemangiomas by WHO Tumors of Soft Tissue and Bone Classification, 5th edition 2020) (IA) occurring in the extraocular muscles or palpebral muscles (orbicularis oculi) are extremely rare with only a few case reports in the English literature. To date, all the extraocular muscles have reportedly been involved. With the case reported herein, the medial rectus muscle appears to be the most common extraocular muscle involved.

Recurrent Uveitis Related to Ibrutinib for Treatment of Chronic Lymphocytic Leukemia.

PURPOSE: We describe a case vision-threatening sclerouveitis as a probable adverse drug reaction to ibrutinib. METHODS: Case report. RESULTS: Ibrutinib is an inhibitor of Bruton's kinase which has shown success in the treatment of hematological malignancies such as chronic lymphocytic leukemia. Despite being generally well tolerated, recent studies have implicated ibrutinib in several adverse events affecting organs such as the heart, intestines, and the eyes. We present the case of a patient who developed severe sclerouveitis after approximately one year of ibrutinib therapy, and suggest this is a probable adverse drug reaction associated with ibrutinib in accordance with the Naranjo algorithm, highlighting the importance of prompt management of ocular symptoms in these patients.