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.

KCNV2-associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3.

BACKGROUND/AIMS: To investigate genotype-phenotype associations in patients with KCNV2 retinopathy. METHODS: Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants-two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)-and parameters were compared. RESULTS: Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants. CONCLUSIONS: Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.

The Natural History of Leber Congenital Amaurosis and Cone-Rod Dystrophy Associated with Variants in the GUCY2D Gene.

OBJECTIVE: To describe the spectrum of Leber congenital amaurosis (LCA) and cone-rod dystrophy (CORD) associated with the GUCY2D gene and to identify potential end points and optimal patient selection for future therapeutic trials. DESIGN: International, multicenter, retrospective cohort study. SUBJECTS: Eighty-two patients with GUCY2D-associated LCA or CORD from 54 families. METHODS: Medical records were reviewed for medical history, best-corrected visual acuity (BCVA), ophthalmoscopy, visual fields, full-field electroretinography, and retinal imaging (fundus photography, spectral-domain OCT [SD-OCT], fundus autofluorescence). MAIN OUTCOMES MEASURES: Age of onset, evolution of BCVA, genotype-phenotype correlations, anatomic characteristics on funduscopy, and multimodal imaging. RESULTS: Fourteen patients with autosomal recessive LCA and 68 with autosomal dominant CORD were included. The median follow-up times were 5.2 years (interquartile range [IQR] 2.6-8.8 years) for LCA and 7.2 years (IQR 2.2-14.2 years) for CORD. Generally, LCA presented in the first year of life. The BCVA in patients with LCA ranged from no light perception to 1.00 logarithm of the minimum angle of resolution (logMAR) and remained relatively stable during follow-up. Imaging for LCA was limited but showed little to no structural degeneration. In patients with CORD, progressive vision loss started around the second decade of life. The BCVA declined annually by 0.022 logMAR (P < 0.001) with no difference between patients with the c.2513G>A and the c.2512C>T GUCY2D variants (P = 0.798). At the age of 40 years, the probability of being blind or severely visually impaired was 32%. The integrity of the ellipsoid zone (EZ) and that of the external limiting membrane (ELM) on SD-OCT correlated significantly with BCVA (Spearman ρ = 0.744, P = 0.001, and ρ = 0.712, P < 0.001, respectively) in those with CORD. CONCLUSIONS: Leber congenital amaurosis associated with GUCY2D caused severe congenital visual impairment with relatively intact macular anatomy on funduscopy and available imaging, suggesting long preservation of photoreceptors. Despite large variability, GUCY2D-associated CORD generally presented during adolescence, with a progressive loss of vision, and culminated in severe visual impairment during mid-to-late adulthood. The integrity of the ELM and EZ may be suitable structural end points for therapeutic studies of GUCY2D-associated CORD.

Feasibility and tolerability of ophthalmic virtual reality as a medical communication tool in children and young people.

PURPOSE: Virtual reality (VR) can be useful in explaining diseases and complications that affect children in order to improve medical communications with this vulnerable patient group. So far, children and young people's responses to high-end medical VR environments have never been assessed. METHODS: An unprecedented number of 320 children and young people were given the opportunity to interact with a VR application displaying original ophthalmic volume data via a commercially available tethered head-mounted display (HMD). Participants completed three surveys: demographics and experience with VR, usability and perceived utility of this technology and the Simulator Sickness Questionnaire. The second survey also probed participants for suggestions on improvements and whether this system could be useful for increasing engagement in science. RESULTS: A total of 206 sets of surveys were received. 165 children and young people (84 female) aged 12-18 years (mean, 15 years) completed surveys that could be used for analysis. 69 participants (47.59%) were VR-naïve, and 76 (52.41%) reported that they had previous VR experience. Results show that VR facilitated understanding of ophthalmological complications and was reasonably tolerated. Lastly, exposure to VR raised children and young people's awareness and interest in science. CONCLUSIONS: The VR platform used was successfully utilized and was well accepted in children to display and interact with volume-rendered 3D ophthalmological data. Virtual reality (VR) is suitable as a novel image display platform in ophthalmology to engage children and young people.

Dynamic volume-rendered optical coherence tomography pupillometry.

PURPOSE: To assess intrapupillary space (IPS) changes in healthy subjects with regard to decreased iris motility in patients with pseudoexfoliation glaucoma (PEXG) or non-arteritic anterior ischaemic optic neuropathy (NAION) in a feasibility study in a clinical environment. METHODS: Scotopic and photopic IPS measurements using three-dimensionally rendered swept-source optical coherence tomography (SS-OCT) data were obtained and compared for all subjects. Intrapupillary space (IPS) parameters were evaluated such as absolute volumetric differences, relative light response for volumetric ratios and pupillary ejection fraction (PEF) for functional contraction measurements. RESULTS: From a total of 122 IPS from 66 subjects, 106 IPS were eligible for comparison providing values for 72 normal, 30 PEXG and 4 NAION eyes. In healthy, PEXG and NAION subjects, scotopic overall mean IPS was 8.90, 3.45 and 4.16 mm3 , and photopic overall mean IPS was 0.87, 0.74 and 1.13 mm3 , respectively. Three-dimensional contractility showed a mean absolute difference of 8.03 mm3 for normals (defined as 100% contractility), 2.72 mm3 for PEXG (33.88% of normal) and 3.03 mm3 for NAION (38.50% of normal) with a relative light response ratio between scotopic and photopic volumes of 10.26 (100%), 4.69 (45.70%) and 3.67 (35.78%), respectively. Pupillary ejection fraction (PEF) showed a contractile pupillary emptying of 88.11% for normals, 76.92% for PEXG and 70.91% for NAION patients. CONCLUSION: This 3D pupillometry OCT assessment allows for quantitative measurements of pupil function, contractility and response to light. More specifically, PEF is presented as a potential (neuro)-pupillary outcome measure that could be useful in the monitoring of ophthalmic disorders that affect pupillary function.

KCNV2-Associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints-KCNV2 Study Group Report 2.

PURPOSE: To describe the detailed retinal phenotype of KCNV2-associated retinopathy. STUDY DESIGN: Multicenter international retrospective case series. METHODS: Review of retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), including qualitative and quantitative analyses. RESULTS: Three distinct macular FAF features were identified: (1) centrally increased signal (n = 35, 41.7%), (2) decreased autofluorescence (n = 27, 31.1%), and (3) ring of increased signal (n = 37, 44.0%). Five distinct FAF groups were identified based on combinations of those features, with 23.5% of patients changing the FAF group over a mean (range) follow-up of 5.9 years (1.9-13.1 years). Qualitative assessment was performed by grading OCT into 5 grades: (1) continuous ellipsoid zone (EZ) (20.5%); (2) EZ disruption (26.1%); (3) EZ absence, without optical gap and with preserved retinal pigment epithelium complex (21.6%); (4) loss of EZ and a hyporeflective zone at the foveola (6.8%); and (5) outer retina and retinal pigment epithelium complex loss (25.0%). Eighty-six patients had scans available from both eyes, with 83 (96.5%) having the same grade in both eyes, and 36.1% changed OCT grade over a mean follow-up of 5.5 years. The annual rate of outer nuclear layer thickness change was similar for right and left eyes. CONCLUSIONS: KCNV2-associated retinopathy is a slowly progressive disease with early retinal changes, which are predominantly symmetric between eyes. The identification of a single OCT or FAF measurement as an endpoint to determine progression that applies to all patients may be challenging, although outer nuclear layer thickness is a potential biomarker. Findings suggest a potential window for intervention until 40 years of age.

Efficacy and Incontinence Rates After Urethroplasty for Radiation-induced Urethral Stenosis: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the efficacy of urethroplasty and rates of de novo stress urinary incontinence (SUI) in the specific setting of radiation-induced urethral stenosis. METHODS: A systematic search of databases (PubMed and EMBASE) was performed between 1980-2019 (CRD42020144845). Inclusion criteria were: (1) prior pelvic radiotherapy; (2) surgical urethroplasty; (3) rates of successful treatment and/or SUI development and (4) total case number provided. The pooled summary of stenosis resolution rate and SUI were calculated using the random-effects model weighted by the inverse variance. Accessory analyses were performed by reconstructive technique and type of RT. RESULTS: Ninety-six studies were identified, of which 8 retrospective studies met inclusion criteria, comprising 256 patients. The proportion of cases treated with external beam RT (EBRT), brachytherapy (BT), or combination (EBRT+BT) were 52%, 33%, and 15%, respectively, of studies that specified modality. Most strictures involved the bulbomembranous region (n = 212; 83%). Sixty-one percent of cases (n = 157) entailed primary anastomosis, while the remainder underwent augmentation reconstruction (graft or flap). The mean follow-up time after urethroplasty varied from 10 to 50.5 months. The pooled stenosis resolution rate was 80% (95% CI: 74%-86%). There were no significant associations between stenosis resolution rate and reconstructive technique (rho=0.20, P = .74) or RT modality (rho=-0.31, P = .53). Fifty-three cases developed subsequent SUI, with a pooled complication rate of 19% (95% CI: 10%-31%). CONCLUSIONS: Urethroplasty after radiation-induced urethral stenosis is effective for 80% of cases, independent of prior RT modality or urethroplasty technique; however, 1 out of every 5 patients develops SUI post-procedure.

Optical coherence tomography (OCT) in neuro-ophthalmology.

Optical coherence tomography (OCT) is a non-invasive medical imaging technology that is playing an increasing role in the routine assessment and management of patients with neuro-ophthalmic conditions. Its ability to characterise the optic nerve head, peripapillary retinal nerve fibre layer and cellular layers of the macula including the ganglion cell layer enables qualitative and quantitative assessment of optic nerve disease. In this review, we discuss technical features of OCT and OCT-based imaging techniques in the neuro-ophthalmic context, potential pitfalls to be aware of, and specific applications in more common neuro-ophthalmic conditions including demyelinating, inflammatory, ischaemic and compressive optic neuropathies, optic disc drusen and raised intracranial pressure. We also review emerging applications of OCT angiography within neuro-ophthalmology.

KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1.

PURPOSE: To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults. STUDY DESIGN: This was a multicenter international clinical cohort study. METHODS: Review of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) recordings, incorporating the international standards, were reviewed and quantified and compared with age and recordings from control subjects. RESULTS: In total, 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before 12 years of age (range, 0-11 years). Decreased visual acuity was present in all patients, and 4 other symptoms were common: reduced color vision (78.6%), photophobia (53.5%), nyctalopia (43.6%), and nystagmus (38.6%). After a mean follow-up of 8.4 years, the mean best-corrected visual acuity (BCVA ± SD) decreased from 0.81 ± 0.27 to 0.90 ± 0.31 logarithm of minimal angle of resolution. Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the dark-adapted 0.01 ERG, dark-adapted 10 ERG a-wave, and LA 3.0 30 Hz and LA3 ERG b-waves were 55%, 21%, 48%, and 74%, respectively compared with control values. Peak times showed stability across 6 decades. CONCLUSION: In KCNV2-associated retinopathy, full-field ERGs are diagnostic and consistent with largely stable peripheral retinal dysfunction. Report 1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics.

Enhanced S-Cone Syndrome: Spectrum of Clinical, Imaging, Electrophysiologic, and Genetic Findings in a Retrospective Case Series of 56 Patients.

PURPOSE: To describe the detailed phenotype, long-term clinical course, clinical variability, and genotype of patients with enhanced S-cone syndrome (ESCS). DESIGN: Retrospective case series. PARTICIPANTS: Fifty-six patients with ESCS. METHODS: Clinical history, examination, imaging, and electrophysiologic findings of 56 patients (age range, 1-75 years) diagnosed with ESCS were reviewed. Diagnosis was established by molecular confirmation of disease-causing variants in the NR2E3 gene (n = 38) or by diagnostic full-field electroretinography findings (n = 18). MAIN OUTCOME MEASURES: Age at onset of visual symptoms, best-corrected visual acuity (BCVA), quantitative age-related electrophysiologic decline, and imaging findings. RESULTS: Mean age at onset of visual symptoms was 4.0 years, and median age at presentation was 20.5 years, with mean follow-up interval being 6.1 years. Six patients were assessed once. Disease-causing variants in NR2E3 were identified in 38 patients. Mean BCVA of the better-seeing eye was 0.32 logarithm of the minimum angle of resolution (logMAR) at baseline and 0.39 logMAR at follow-up. In most eyes (76% [76/100]), BCVA remained stable, with a mean BCVA change of 0.07 logMAR during follow-up. Nyctalopia was the most common initial symptom, reported in 92.9% of patients (52/56). Clinical findings were highly variable and included foveomacular schisis (41.1% [26/56]), yellow-white dots (57.1% [32/56]), nummular pigmentation (85.7% [48/56]), torpedo-like lesions (10.7% [6/56]), and circumferential subretinal fibrosis (7.1% [4/56]). Macular and peripheral patterns of autofluorescence were classified as (1) minimal change, (2) hypoautofluorescent (mild diffuse, moderate speckled, moderate diffuse, or advanced), or (3) hyperautofluorescent flecks. One patient showed undetectable electroretinography findings; quantification of main electroretinography components in all other patients revealed amplitude and peak time variability but with pathognomonic electroretinography features. The main electroretinography components showed evidence of age-related worsening over 6.7 decades, at a rate indistinguishable from that seen in unaffected control participants. Eighteen sequence variants in NR2E3 were identified, including 4 novel missense changes. CONCLUSIONS: Enhanced S-cone syndrome has a highly variable phenotype with relative clinical and imaging stability over time. Most electroretinography findings have pathognomonic features, but quantitative assessment reveals variability and a normal mean rate of age-related decline, consistent with largely nonprogressive peripheral retinal dysfunction.

Validation of virtual reality orbitometry bridges digital and physical worlds.

Clinical science and medical imaging technology are traditionally displayed in two dimensions (2D) on a computer monitor. In contrast, three-dimensional (3D) virtual reality (VR) expands the realm of 2D image visualization, enabling an immersive VR experience with unhindered spatial interaction by the user. Thus far, analysis of data extracted from VR applications was mainly qualitative. In this study, we enhance VR and provide evidence for quantitative VR research by validating digital VR display of computed tomography (CT) data of the orbit. Volumetric CT data were transferred and rendered into a VR environment. Subsequently, seven graders performed repeated and blinded diameter measurements. The intergrader variability of the measurements in VR was much lower compared to measurements in the physical world and measurements were reasonably consistent with their corresponding elements in the real context. The overall VR measurements were 5.49% higher. As such, this study attests the ability of VR to provide similar quantitative data alongside the added benefit of VR interfaces. VR entails a lot of potential for the future research in ophthalmology and beyond in any scientific field that uses three-dimensional data.

Juvenile Batten Disease (CLN3): Detailed Ocular Phenotype, Novel Observations, Delayed Diagnosis, Masquerades, and Prospects for Therapy.

PURPOSE: To characterize the retinal phenotype of juvenile neuronal ceroid lipofuscinosis (JNCL), highlight delayed and mistaken diagnosis, and propose an algorithm for early identification. DESIGN: Retrospective case series. PARTICIPANTS: Eight children (5 female) with JNCL. METHODS: Review of clinical notes, retinal imaging including fundus autofluorescence and OCT, electroretinography (ERG), and both microscopy and molecular genetic testing. MAIN OUTCOME MEASUREMENTS: Demographic data, signs and symptoms, visual acuity (VA), fundus autofluorescence and OCT findings, ERG phenotype, and microscopy/molecular genetics. RESULTS: Participants presented with rapid bilateral vision loss over 1 to 18 months, with mean VA deteriorating from 0.44 logarithm of the minimum angle of resolution (logMAR) (range, 0.20-1.78 logMAR) at baseline to 1.34 logMAR (0.30 logMAR - light perception) at last follow-up. Age of onset ranged from 3 to 7 years (mean, 5.3 years). The age at diagnosis of JNCL ranged from 7 to 10 years (mean, 8.3 years). Six children displayed eccentric fixation, and 6 children had cognitive or neurologic signs at the time of diagnosis (75%). Seven patients had bilateral bull's-eye maculopathy at presentation. Coats-like exudative vasculopathy, not previously reported in JNCL, was observed in 1 patient. OCT imaging revealed near complete loss of outer retinal layers and marked atrophy of the nerve fiber and ganglion cell layers at the central macula. An electronegative ERG was present in 4 patients (50%), but with additional a-wave reduction, there was an undetectable ERG in the remaining 4 patients. Blood film microscopy revealed vacuolated lymphocytes, and electron microscopy showed lysosomal (fingerprint) inclusions in all 8 patients. CONCLUSIONS: In a young child with bilateral rapidly progressive vision loss and macular disturbance, blood film microscopy to detect vacuolated lymphocytes is a rapid, readily accessible, and sensitive screening test for JNCL. Early suspicion of JNCL can be aided by detailed directed history and high-resolution retinal imaging, with subsequent targeted microscopy/genetic testing. Early diagnosis is critical to ensure appropriate management, counseling, support, and social care for children and their families. Furthermore, although potential therapies for this group of disorders are in early-phase clinical trial, realistic expectations are that successful intervention will be most effective when initiated at the earliest stage of disease.

Novel biomarker of sphericity and cylindricity indices in volume-rendering optical coherence tomography angiography in normal and diabetic eyes: a preliminary study.

PURPOSE: Preliminary to evaluate geometric indices (vessel sphericity and cylindricity) for volume-rendered optical coherence tomography angiography (OCTA) in healthy and diabetic eyes. METHODS: Twenty-six eyes of 13 healthy subjects and 12 eyes of patients with central ischemic, non-proliferative diabetic retinopathy were included. OCTA volume and surface area of the foveal vessels were measured and compared to determine OCTA sphericity and cylindricity indices and surface efficiency (SE). RESULTS: The overall average OCTA volume in healthy was 0.49 ± 0.09 mm3 (standard deviation [SD]), compared to 0.44 ± 0.07 mm3 (SD) in the diabetic eyes (difference in means 0.06 mm3, p = 0.054). The overall average OCTA surface area in the healthy eyes was 87.731 ± 9.51 mm2 (SD), compared to 76.65 ± 13.67 mm2 (SD) in the diabetic eyes (difference in means 11.08 mm2, p = 0.021). In relation to total foveolar tissue volume, the proportion of blood vessels was 22% in healthy individuals and only 20% in diabetics. The difference between the groups was more pronounced with respect to the total OCTA surface area, with a decrease of 13% in diabetics. A diabetic eye was most likely using geometric vessel indices analysis if the sphericity value was ≥ 0.190, with a cylindricity factor of ≥ 0.001. Reproducibility of the method was good. CONCLUSIONS: A method for OCTA surface area and volume measurements was developed. The application of the novel OCTA sphericity and cylindricity indices could be suitable as temporal biomarker to characterize stable disease or disease progression and may contribute to a better understanding in the evolution of diabetic retinopathy.

Pelvic Insufficiency Fractures After External Beam Radiation Therapy for Gynecologic Cancers: A Meta-analysis and Meta-regression of 3929 Patients.

PURPOSE: To estimate the overall rate, symptomatic proportion, and most common sites of pelvic insufficiency fracture (PIF) after external beam radiation therapy for gynecologic cancers based on posttreatment computed tomography, magnetic resonance imaging, positron emission tomography, or bone scintigraphy. METHODS AND MATERIALS: A systematic search of databases (PubMed and EMBASE) was performed (CRD42019125679). The pooled summary of overall PIF and the proportion of symptomatic cases were calculated using the random-effects model weighted by the inverse variance. A multivariate meta-regression was performed to evaluate potential sources of heterogeneity regarding PIF fractures. RESULTS: Twenty-one studies met the inclusion criteria (total 3929 patients). Five hundred four patients developed PIF, translating to an overall rate of 14% (95% confidence interval, 10%-18%, based on 21 studies). Among these cases with PIF, the proportion of symptomatic patients was 61% (95% confidence interval, 52%-69%, based on 14 studies). The total number of PIFs was 704 (mean, 1.72 PIFs per each patient to develop PIF, based on 14 studies). More recent series (P = .0074) and the use of intensity modulated radiation therapy (P = .0299) were associated with lower fracture rates. The most common fracture sites were sacroiliac joint (39.7%), body of the sacrum (33.9%), pubis (13%), lumbar vertebra (7%), iliac bone (2.8%), acetabulum (2.1%), and femoral head/neck (1.5%). The median time to fracture was 7.1 to 19 months after radiation therapy. CONCLUSIONS: The incidence of PIF after radiation therapy for gynecologic cancers is high (14%), with the majority affecting the sacral bone or joint (73.6%), although this risk appears to be lower with intensity modulated radiation therapy. Posttreatment bone surveillance is warranted in this population because nearly 40% of patients were asymptomatic at the time of PIF diagnosis.

Validation of automated artificial intelligence segmentation of optical coherence tomography images.

PURPOSE: To benchmark the human and machine performance of spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) image segmentation, i.e., pixel-wise classification, for the compartments vitreous, retina, choroid, sclera. METHODS: A convolutional neural network (CNN) was trained on OCT B-scan images annotated by a senior ground truth expert retina specialist to segment the posterior eye compartments. Independent benchmark data sets (30 SDOCT and 30 SSOCT) were manually segmented by three classes of graders with varying levels of ophthalmic proficiencies. Nine graders contributed to benchmark an additional 60 images in three consecutive runs. Inter-human and intra-human class agreement was measured and compared to the CNN results. RESULTS: The CNN training data consisted of a total of 6210 manually segmented images derived from 2070 B-scans (1046 SDOCT and 1024 SSOCT; 630 C-Scans). The CNN segmentation revealed a high agreement with all grader groups. For all compartments and groups, the mean Intersection over Union (IOU) score of CNN compartmentalization versus group graders' compartmentalization was higher than the mean score for intra-grader group comparison. CONCLUSION: The proposed deep learning segmentation algorithm (CNN) for automated eye compartment segmentation in OCT B-scans (SDOCT and SSOCT) is on par with manual segmentations by human graders.

MORPhA Scale: Behavioral and electroencephalographic validation of a rodent anesthesia scale.

BACKGROUND: Laboratory practice commonly implies rodent anesthesia. Such is instrumental not only for animal welfare, but also for standardized assessment of new anesthetics. NEW METHOD: We developed and validated a grading system for a temporal follow-up of anesthesia. The Minho Objective Rodent Phenotypical Anesthesia (MORPhA) scale was tested in mice (C57BL/6 J) and rats (Wistar-Han) anesthetized with ketamine/dexmedetomidine (ket/dex). The scale comprises 12 behavioral readouts organized in 5 stages - (i) normal/(ii) hindered voluntary movement, elicited response to (iii) non-noxious/(iv) noxious stimuli and (v) absence of response - evaluated at regular time-points. Progression across stages was monitored by electroencephalography (EEG) in rats during anesthesia induction and reversal (atipamezole) and during induction with a second anesthetic drug (pentobarbital). RESULTS: Higher anesthetic doses decreased the time to reach higher levels of anesthesia during progression, while increasing the time to regain waking behavior during reversal in both mice and rats. A regular decrease in high frequencies (low and high gamma) power was observed as the MORPhA score increased during anesthesia induction, while the opposite pattern was observed during emergence from anesthesia through reversion of dex effect. COMPARISON WITH EXISTING METHODS: Degree of anesthesia in laboratory rodents is normally evaluated by testing loss of reflexes. While these are useful endpoint assessments, they are of limited application to study induction/reversal kinetics or factors affecting individual susceptibility. MORPhA allows graded standardized assessment of this progression in a biologically-relevant fashion. CONCLUSIONS: The devised anesthetic scale is of simple application and provides a semi-quantifiable readout of anesthesia induction/reversal.

Open anterograde anatomic radical retropubic prostatectomy technique: description of the first fiftyfive procedures.

INTRODUCTION: Robotic-assisted radical prostatectomy is the leading surgical technique and was discussed in Pasadena Consensus Panel (1). The goal of this study is to present the results of the first fifty-five patients submitted to Anterograde Anatomic Radical Retropubic Prostatectomy technique (R2PA2), without adding complexity or cost. MATERIALS AND METHODS: Fifty-five eligible men with localized prostate cancer underwent R2PA2 from January, 2016 to December, 2017. The technique was previously described (2): the main surgical steps were anterograde dissection, ligation of the dorsal vascular complex without dividing, preservation of the bladder neck, nerve sparing, preservation of Denonvilliers' fascia and confection of the running suture anastomosis. All patients were operated on by second-year residents. RESULTS: All procedures were completed as planned, but one converted to retrograde prostatectomy (mean duration, 163.40 minutes; hospital stay, 4 days with 4.20 days of drainage; indwelling vesical catheterization of 9.80 days). Positive surgical margin was found in six T2 staging patient (10.90%) and five T3 (9.10%). Biochemical PSA recurrence occurred in three patients (5.50%). Twenty-four (43.60%) were continent immediately after indwelling catheter removal, seventeen (30.90%) did not wear a pad at one postoperative month while eighteen (30%) used only one safety pad. Five minor complications occurred. CONCLUSION: We were able to perform R2PA2 allowing men who do not have access to this new technology to be operated on with the same technique used in robotic surgery. This method was reproducible by low-volume prostate cancer surgeons; help inexperienced surgeons to develop skills valuable to future training with robotic techniques. ACKNOWLEDGEMENTS This work was supported by the FAPERJ - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. Secretaria de Estado de Ciência, Tecnologia e Inovação do Governo do Estado do Rio de Janeiro, Brazil, and Pedro Ernesto University Hospital of the State University of Rio de Janeiro, Brazil. Available at: http://www.intbrazjurol.com.br/video-section/20180421_Carrerette_et_al.

Analysis of Physiological and Kinematic Demands of Wheelchair Basketball Games-A Review.

Seron, BB, Oliveira de Carvalho, EM, and Greguol, M. Analysis of physiological and kinematic demands of wheelchair basketball games-A review. J Strength Cond Res 33(5): 1453-1462, 2019-In wheelchair basketball (WB), knowledge of the specificities of the game is essential for efficient planning of training strategies for high performance. This study aimed to review the literature concerning studies that have investigated physiological and kinematic measures during WB games. The literature search took place in 4 electronic databases: Scopus, MEDLINE-PubMed, SPORTDiscus, and CINAHL. The inclusion criteria for this review were as follows: (a) articles that evaluated the behavior of physiological and kinematic variables during WB games; (b) athletes aged at least 18 years; and (c) participants with a minimum of 1 year in the modality practice. The selected studies (n = 16) were divided into 2 groups: physiological analysis (n = 11) and kinematic analysis (n = 5). In analyzing the studies, it was observed that the WB game is very demanding in relation to cardiovascular requirements (∼65% of the time is spent in zones of high heart rate [HR] intensity and 70% of V[Combining Dot Above]O2peak). Edwards and Stagno methods seem to be adequate for the control of internal loads imposed on WB players, and moderate correlations were found between rating of perceived exertion measures and HR-based methods. Considering the methodological limitations, kinematic analysis in WB games is rather inconsistent (distance traveled between 2.6 and 5 km; average speed between 1.8 and 2.0 m·s; maximum speed = 4 m·s). Despite the gaps observed in this context, the execution of rotational movements seems to have great relevance for WB. We can conclude that different methods have been adequate for the internal load control in WB games. However, the results of the external demands are not enough to determine a profile nor to serve as parameters for the training prescription for athletes of the modality.

Effects of aerobic and resistance training on the cardiorespiratory fitness of young people with Down Syndrome / Efeitos do treinamento aeróbio e resistido na capacidade cardiorrespiratória de jovens com Síndrome de Down

Abstract The aim of this study was to investigate the effects of 12 weeks of aerobic and resistance training on the maximal and submaximal cardiorespiratory fitness of young people with Down Syndrome (DS). Forty-one individuals of both sexes with Down syndrome (age, 15.51±2.70 y) were divided into three groups: CG (control group) with 10 participants; ATG group (aerobic training group) with 16 participants; and RTG (resistance training group) with 15 participants. The training program lasted 12 weeks, with frequency of 3 days a week for ATG and two RTG, and duration of 50 minutes per session. Aerobic training consisted of exercise on a treadmill/bike at intensity between 50 and 70% of reserve heart rate, while resistance training was composed of nine exercises performed on three sets of 12 maximum repetitions for each exercise. Aerobic and resistance training were not able to increase peak oxygen uptake. However, there was an increase in the maximum ventilation and a decrease of submaximal heart rate only for groups who participated in the training program. Moreover, the aerobic group increased work capacity after training. Training programs led to an improvement in cardiac efficiency during submaximal activities and increased maximum ventilation, which demonstrates a cardiorespiratory improvement

Resumo Objetivou-se investigar o efeito de 12 semanas de treinamento aeróbio e resistido na capacidade cardiorrespiratória máxima e submáxima de jovens com Síndrome de Down (SD). Quarenta e um indivíduos de ambos os gêneros com Síndrome de Down (idade, 15,51±2.70 anos) foram divididos em três grupos: GC (grupo controle) com 10 participantes; GTA (grupo treino aeróbio) com 16 participantes; e GTR (grupo treino resistido) com 15 participantes. O programa de treinamento teve duração de 12 semanas, com frequência de 3 dias por semana para o GTA e duas para o GTR, com duração de 50 minutos por sessão. O treino aeróbio era realizado na esteira/ bicicleta ergométrica com intensidade entre 50 e 70% da frequência de reserva, enquanto o treino resistido era composto de nove exercícios que eram realizados em três series de 12 repetições para cada exercício. O treino aeróbio e resistido não foram capazes de aumentar o consumo máximo de oxigênio. Entretanto, houve um aumento na ventilação máxima e diminuição na frequência cardíaca submáxima para os dois grupos que participaram dos programas de treinamento. Além disso, o GTA aumentou a capacidade de trabalho. Os programas de treinamento promoveram uma melhora na eficiência cardíaca durante atividades submáximas e aumento na ventilação máxima, o que demostra uma melhora na capacidade cardiorrespiratória.