Voltage imaging and optogenetics reveal behaviour-dependent changes in hippocampal dynamics.

A technology that simultaneously records membrane potential from multiple neurons in behaving animals will have a transformative effect on neuroscience research1,2. Genetically encoded voltage indicators are a promising tool for these purposes; however, these have so far been limited to single-cell recordings with a marginal signal-to-noise ratio in vivo3-5. Here we developed improved near-infrared voltage indicators, high-speed microscopes and targeted gene expression schemes that enabled simultaneous in vivo recordings of supra- and subthreshold voltage dynamics in multiple neurons in the hippocampus of behaving mice. The reporters revealed subcellular details of back-propagating action potentials and correlations in subthreshold voltage between multiple cells. In combination with stimulation using optogenetics, the reporters revealed changes in neuronal excitability that were dependent on the behavioural state, reflecting the interplay of excitatory and inhibitory synaptic inputs. These tools open the possibility for detailed explorations of network dynamics in the context of behaviour. Fig. 1 PHOTOACTIVATED QUASAR3 (PAQUASAR3) REPORTS NEURONAL ACTIVITY IN VIVO.: a, Schematic of the paQuasAr3 construct. b, Photoactivation by blue light enhanced voltage signals excited by red light in cultured neurons that expressed paQuasAr3 (representative example of n = 4 cells). c, Model of the photocycle of paQuasAr3. d, Confocal images of sparsely expressed paQuasAr3 in brain slices. Scale bars, 50 µm. Representative images, experiments were repeated in n = 3 mice. e, Simultaneous fluorescence and patch-clamp recordings from a neuron expressing paQuasAr3 in acute brain slice. Top, magnification of boxed regions. Schematic shows brain slice, patch pipette and microscope objective. f, Simultaneous fluorescence and patch-clamp recordings of inhibitory post synaptic potentials in an L2-3 neuron induced by electrical stimulation of L5-6 in acute slice. g, Normalized change in fluorescence (ΔF/F) and SNR of optically recorded post-synaptic potentials (PSPs) as a function of the amplitude of the post-synaptic potentials. The voltage sensitivity was ΔF/F = 40 ± 1.7% per 100 mV. The SNR was 0.93 ± 0.07 per 1 mV in a 1-kHz bandwidth (n = 42 post-synaptic potentials from 5 cells, data are mean ± s.d.). Schematic shows brain slice, patch pipette, field stimulation electrodes and microscope objective. h, Optical measurements of paQuasAr3 fluorescence in the CA1 region of the hippocampus (top) and glomerular layer of the olfactory bulb (bottom) of anaesthetized mice (representative traces from n = 7 CA1 cells and n = 13 olfactory bulb cells, n = 3 mice). Schematics show microscope objective and the imaged brain region. i, STA fluorescence from 88 spikes in a CA1 oriens neuron. j, Frames from the STA video showing the delay in the back-propagating action potential in the dendrites relative to the soma. k, Sub-Nyquist fitting of the action potential delay and width shows electrical compartmentalization in the dendrites. Experiments in k-m were repeated in n = 2 cells from n = 2 mice.

Short-term outcomes of surgical treatment for primary ileocaecal Crohn's disease: Results of the Crohn's(urg) study, a multicentre, retrospective, comparative analysis between inflammatory and complicated phenotypes.

AIM: Recent evidence challenges the current standard of offering surgery to patients with ileocaecal Crohn's disease (CD) only when they present complications of the disease. The aim of this study was to compare short-term results of patients who underwent primary ileocaecal resection for either inflammatory (luminal disease, earlier in the disease course) or complicated phenotypes, hypothesizing that the latter would be associated with worse postoperative outcomes. METHOD: A retrospective, multicentre comparative analysis was performed including patients operated on for primary ileocaecal CD at 12 referral centres. Patients were divided into two groups according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. RESULTS: A total of 2013 patients were included, with 291 (14.5%) in the ICD group. No differences were found between the groups in time from diagnosis to surgery. CCD patients had higher rates of low body mass index, anaemia (40.9% vs. 27%, p < 0.001) and low albumin (11.3% vs. 2.6%, p < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3% vs. 93.1%, p = 0.001) and higher conversion rates (9.3% vs. 1.9%, p < 0.001). CCD patients had a longer hospital stay and higher postoperative complication rates (26.1% vs. 21.3%, p = 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1% vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgery (OR 3.44, p = 0.001) and the requirement for multiple intraoperative procedures (OR 8.39, p = 0.030). CONCLUSION: Indication for surgery in patients who present with an inflammatory phenotype of CD was associated with better outcomes compared with patients operated on for complications of the disease. There was no difference between groups in time from diagnosis to surgery.

Oculoplastic Management of an Eyelid Zipper Injury.

We present a case of a zipper injury to an upper eyelid in a pediatric patient. The zipper was successfully removed in the operating room by using a double-action bone cutter to cut the median footplate of the zipper and release the entrapped tissue. Zipper injuries are well-described in urology literature, however, limited case reports exist in ophthalmology literature. We review several methods for zipper removal and present special considerations for eyelid injuries.

Bilateral Congenital Nasolacrimal Duct Obstruction in Williams-Beuren Syndrome.

A 23-year-old patient with Williams-Beuren syndrome presented with ocular irritation and bilateral persistent tearing. Despite probing as an infant which showed bilateral nasolacrimal duct obstruction, dacryocystorhinostomy had been avoided due to the patient's syndromic supravalvular stenosis and related anesthesia risk. As the known diminished production of elastin in Williams-Beuren syndrome causes an array of associated vascular diseases, this case report hypothesizes that the lacrimal duct becomes obstructed through a similar mechanism. This case presents the unique findings of bilateral congenital nasolacrimal duct stenosis in a Williams-Beuren syndrome patient.

Standardized documentation and synoptic reporting of complex intestinal anatomy in enteric fistulation and intestinal failure.

AIM: In intestinal failure, delineation of both structure and function are key to controlling symptoms and planning further intervention. We have developed a template for developing an 'anatomy at a glance' patient-specific map to aid decision making and counselling. METHOD: A core dataset was developed and used to create an editable template to demonstrate the gastrointestinal tract, its relationship to the genitourinary tract, and specific anterior abdominal wall features. This was then used to create an anatomical template, specific to each patient, and stored in the electronic patient record and imaging archive. RESULTS: We have developed a technique for integration of multi-modal information into one diagram, easily referenced by the multidisciplinary team. Radiology, endoscopy and previous operation notes can be used to fill out a core dataset, which is then transposed into a standardized template. A worked example is shown. CONCLUSION: The mapping template has been successfully integrated into practice and aided decision making at all stages of the patient's therapeutic journey. It has been found helpful in planning routes of nutrition, preoperative optimization, surgical planning, interpreting postoperative imaging and managing patient expectations.

Topical Corticosteroid Use Associated With Increased Degree of Ptosis and Rate of Ptosis Repair Failure.

PURPOSE: To compare the degree of ptosis and the risk of ptosis repair failure among patients with and without a history of topical corticosteroid use. METHODS: Retrospective, case-controlled study examining topical corticosteroid use among adults with ptosis who underwent external levator advancement/resection (ELR) or Müller muscle conjunctival resection with at least 3 months postoperative follow-up. Comparative statistical analyses of surgical outcomes were performed amongst patients with and without history of topical corticosteroid use. RESULTS: A total of 240 patients (406 eyelids) met study criteria, of which 36 patients (44 eyelids) had history of topical corticosteroid use. Mean preoperative margin reflex distance was 0.20 mm and 0.58 mm for topical corticosteroid and non-corticosteroids users (p = 0.01). Mean preoperative levator function was 9.78 mm and 10.38 mm for topical corticosteroid and non-corticosteroid users (p = 0.02). The rate of ptosis repair failure was 30% and 16% in patients with and without a history of topical corticosteroid use (odds ratio 2.25, 95% confidence interval 1.10-4.55; p = 0.03). The rate of recurrence per surgical type in eyelids with and without history of topical corticosteroid use was: external levator advancement/resection 11/27 (41%) and 48/266 (18%) (odds ratio = 3.12, confidence interval 1.36-7.15 0; p = 0.01); Müller muscle conjunctival resection 2/17 (12%) and 9/96 (9%) (odds ratio 1.29, confidence interval 0.25-6.56; p = 0.76). CONCLUSIONS: Topical corticosteroid use is associated with more severe presenting ptosis and increased rates of ptosis repair failure. Compared to Müller muscle conjunctival resection, there is a significantly higher rate of ptosis repair failure in patients undergoing external levator advancement/resection.

Polytetrafluoroethylene frontalis suspension in blepharospasm with eyelid apraxia: an effective and well-tolerated adjunct to botulinum toxin therapy.

Purpose: To report the efficacy of polytetrafluoroethylene (PTFE) frontalis suspension for blepharospasm with eyelid apraxia and postoperative botulinum toxin requirements. Methods: Retrospective chart review of patients with blepharospasm and eyelid apraxia who underwent frontalis suspension. The primary outcome was a surgical success, defined by surgeon- and patient-reported success in postoperative eyelid opening. Comparative statistical analyses of botulinum toxin dosage and treatment intervals were performed amongst patients before and after frontalis suspension ptosis repair. Results: Five patients (10 eyelids) met the study criteria, of which 40% were female. Mean age was 63.2 years. All patients had successful surgical outcomes based on physician-reported and patient reported satisfaction with the postoperative eyelid opening. Average follow-up was 14 months. Preoperative botulinum toxin treatments averaged 80.4 units (range 32-110, SD 33.2) to the periocular region over an average of 9.6-week intervals. Postoperative botulinum toxin treatments averaged 61.4 units (range 24-110, SD 34.7) to the periocular region over an overage of 9.8-week intervals. No patients experienced postoperative exposure keratopathy, extrusion of the sling, or postoperative infection. Conclusions: Frontalis suspension using PTFE suture in the setting of blepharospasm with eyelid apraxia was found to be a safe and effective procedure. Frontalis suspension in this population is not a substitute for botulinum toxin treatment but may allow for reduced treatment dosage. Frontalis suspension appears to increase patient functionality with improved eyelid opening in patients with blepharospasm with eyelid apraxia.

Paediatric orbital and periorbital infections.

PURPOSE OF REVIEW: This study is a review of recent literature in the diagnosis and management of preseptal cellulitis, orbital cellulitis and dacryocystitis, including causative organisms, diagnosis and medical or surgical therapy and potential complications. RECENT FINDINGS: Advances in vaccination against Haemophilus influenzae B have resulted in a shift in the most common causative organisms of preseptal and orbital cellulitis. Management of orbital cellulitis has been advanced by adjuvant corticosteroids, and subperiosteal abscess volumes of more than 1250 ml has been shown as predictive for requiring potential surgical intervention. SUMMARY: Periorbital infections require prompt evaluation and management. Although the infectious organisms in both preseptal and orbital cellulitis include Staphylococcus/Streptococcus species, management may differ significantly on the basis of the nidus of infection, presenting signs and symptoms, and response to initial medical management.

Simulated Wound Assessment Using Digital Planimetry versus Three-Dimensional Cameras: Implications for Clinical Assessment.

BACKGROUND: Clinical management of wounds can benefit from objective measures of response to treatment. Wound surface area and volume are objective measures of wound healing. Using a synthetic wound model, we compare the accuracy and reproducibility of 2 commercially available 3-dimensional (3D) cameras against planimetry and water displacement. METHODS: Twelve ulcers of various sizes and colors were reproduced in modeling clay and cured. Five naive observers used digital planimetry, water displacement, Eykona camera (Fuel 3D, UK), and Silhouette camera (ARANZ, New Zealand) to measure the wounds. RESULTS: When compared with traditional planimetry, wound surface area measurement with Eykona and Silhouette tended to underestimate wounds by 1.7% and 3.7%, respectively. Spearman correlation coefficients were 0.94 (Eykona) and 0.92 (Silhouette). Intraclass correlations for planimetry and the 2 cameras were all 1. Eykona and Silhouette tended to underestimate wound volumes when compared with water displacement by 58% and 23%, respectively. Spearman correlation coefficients were 0.92 (Eykona) and 0.72 (Silhouette). Intraclass correlations for water displacement and the two cameras were all 1. DISCUSSION: Serial accurate objective area measurements are feasible as part of ongoing clinical assessment of wounds. 3D cameras are reliable but have not shown superior accuracy to manual planimetry, and financial concerns and IT integration may limit general clinical usage. Volume measurements of wounds are practicable as part of clinical care.

Pediatric orbital fractures.

PURPOSE OF REVIEW: The aim of this study was to summarize current evidence on the clinical presentation, evaluation, and management of pediatric orbital fractures. Recent trends in management strategies as well as emerging surgical techniques for pediatric orbital fracture repair are presented. RECENT FINDINGS: Although somewhat limited, growing bodies of evidence support a conservative approach with close follow up in pediatric orbital fractures. For those patients necessitating surgical repair, resorbable implants are increasingly preferred given their lack of donor site morbidity and a minimal impact on the developing craniofacial skeleton. There are emerging data reporting the use of three-dimensional (3D) printing-assisted approaches and intraoperative navigation; however, more research is needed to assess their applicability in the pediatric population. SUMMARY: There are few studies with large patient cohorts and long-term follow up given the rare incidence of pediatric orbital fractures, which restricts the generalizability of research on the topic. The studies available increasingly suggest that fractures without clinical evidence of entrapment can be managed conservatively with close follow up. A variety of reconstructive implants are available for those fractures necessitating repair. Donor site morbidity, availability, and need for additional procedures should all be factored into the reconstructive decision-making process.

Characteristics of Orbital Injuries Associated with Maxillofacial Trauma.

INTRODUCTION: The incidence of ocular injury associated with maxillofacial trauma remains poorly defined, with reported rates ranging from 0.8% to 92%. Our study aims to more accurately characterize ocular injuries associated with midface fractures. METHODS: We performed a retrospective review of 1677 patients from 2015 to 2020 with midface fractures at a Level I trauma center. Isolated nasal bone and frontal process of the maxilla fractures were excluded. Demographic information, mechanism of injury, need for surgery, and ophthalmologic findings were documented. Statistical analysis was conducted using SPSS. RESULTS: 773 patients between the ages of 15 and 92 were identified. Trauma most commonly resulted from assault (63.8%). The association between the mechanism of injury and ocular injury was statistically significant (p = 0.003), with 78.6% of gunshot wounds and 44.3% of assault patients having an ocular injury. The Ophthalmology service evaluated 62.6% of cases preoperatively. Minor ocular injury occurred in 36% of patients, including 46.1% of isolated orbital floor, and 28.2% of zygomaticomaxillary complex fractures. Major ocular injury occurred in 10.5% of patients. CONCLUSIONS: Over 10% of patients with midface fractures were found to have major ocular injuries. Ophthalmologic exams should be performed for all patients with midface fractures to guide clinical decision making and prevent further intraoperative ocular insults. LEVEL OF EVIDENCE: Level 4. This study represents a retrospective cohort study analyzing ocular injuries detected in patients presenting to a Level I trauma center with maxillofacial fractures between 2015 and 2020 Laryngoscope, 133:1624-1629, 2023.

Epidemiologic Differences and Management of Eyelid Lesions in the Pediatric Population.

PURPOSE: To report the relative incidence of excised pediatric eyelid lesions and describe the correlation between the clinical and pathology diagnosis. METHODS: This was a retrospective analysis of 137 consecutive pathology-confirmed eyelid lesions excised at a U.S. quaternary children's hospital system. Chalazion was excluded from this study. RESULTS: Benign non-cystic epithelial lesions comprised 48.2% of all excised lesions, followed by mesenchymal (14.6%) and cystic (10.2%) lesions. The most common lesions were molluscum contagiosum (21.9%) and verruca vulgaris (19.0%). Hispanic White race represented 62.0% of cases, followed by non-Hispanic White (23.3%) and Black (8.8%). There were no malignant lesions. A specific preoperative clinical diagnosis was attempted in 70.1% of cases. Of these, 60.4% had a matching histopathology. CONCLUSIONS: The authors report a higher proportion of molluscum contagiosum and verruca vulgaris when compared to the literature; these differences may suggest geographic variance, management preference, or a general increase in incidence. Correlation with pathology showed the clinical diagnosis of eyelid lesions can be challenging even for ophthalmologists. However, malignancy in pediatric eyelid lesions is rare and submission for histopathology may be safely omitted, except in cases with atypical features or suspicion for syndromic disease. The decision for surgery should be methodically approached and take into consideration the most likely diagnosis, natural history of the disease, sociopsychological impact, anesthesia risk, and resource burden. [J Pediatr Ophthalmol Strabismus. 2022;59(6):405-409.].

Eyelid Malposition after Blepharoplasty: An Ounce of Prevention.

Upper and lower eyelid blepharoplasty are common procedures performed to provide a more youthful and rejuvenated appearance. However, this seemingly straightforward procedure may result in lid malpositions, frustrating the patient and surgeon alike, which ultimately require further treatment. We review preoperative assessment pearls to avoid these lid malpositions, as well as options for treating any postoperative complications related to lid position. Many of the techniques discussed in this article, in addition to many other oculoplastic procedures, are available to view in Dr. Richard C. Allen's operative video library at: http://webeye.ophth.uiowa.edu/eyeforum/video/plastics/ .

Pilot Trial of Neuromuscular Stimulation in Human Subjects with Chronic Venous Disease.

INTRODUCTION: Neuromuscular stimulation (NMES) has been shown to improve peripheral blood flow in healthy people. We investigated the effect of bilateral leg NMES on the symptoms of chronic venous disease. METHODS: Forty subjects were recruited from four groups: healthy, superficial insufficiency, deep insufficiency, and deep obstruction. Haemodynamic venous measurements were taken from the right femoral vein with ultrasound, laser Doppler fluximetry from the left hand and foot. Devices were then worn for 4-6 hours per day, for 6 weeks. Haemodynamic measurements were repeated at week 6. Quality of life questionnaires were taken at week 0, 6 and 8. RESULTS: The mean age was 48.7, BMI 28.6kg/m2, and maximum calf circumference 39.0 cm. Twenty-four subjects were men. NMES increased femoral vein peak velocity, TAMV and volume flow by 55%, 20%, 36% at 20 minutes (all p<0.05), which was enhanced at week 6 (PV and TAMV p<0.05). Mean increases in arm and leg fluximetry were 71% and 194% (both p<0.01). Leg swelling was reduced by mean 252.7 mL (13%, p<0.05) overall; 338.9 mL (16%, p<0.05) in venous disease. For those with venous pathology, scores for disease specific and generic quality of life questionnaires improved. Those with C4-6 disease benefitted the most, with improvements in VDS score of 1, AVVQ of 6, and SF-12 of 10. CONCLUSION: NMES improves venous haemodynamic parameters in chronic venous disease, which is enhanced by regular use. NMES reduces leg oedema, improves blood supply to the skin of the foot, and may positively affect quality of life. CLINICAL TRIALS: This trial was registered with www.clinicaltrials.org.uk (NCT02137499).