Electrical impedance spectroscopy for the characterization of skin barrier in atopic dermatitis.

BACKGROUND: Allergic disorders such as atopic dermatitis (AD) are strongly associated with an impairment of the epithelial barrier, in which tight junctions and/or filaggrin expression can be defective. Skin barrier assessment shows potential to be clinically useful for prediction of disease development, improved and earlier diagnosis, lesion follow-up, and therapy evaluation. This study aimed to establish a method to directly assess the in vivo status of epithelial barrier using electrical impedance spectroscopy (EIS). METHODS: Thirty-six patients with AD were followed during their 3-week hospitalization and compared with 28 controls. EIS and transepidermal water loss (TEWL) were measured in lesional and non-lesional skin. Targeted proteomics by proximity extension assay in serum and whole-genome sequence were performed. RESULTS: Electrical impedance spectroscopy was able to assess epithelial barrier integrity, differentiate between patients and controls without AD, and characterize lesional and non-lesional skin of patients. It showed a significant negative correlation with TEWL, but a higher sensitivity to discriminate non-lesional atopic skin from controls. During hospitalization, lesions reported a significant increase in EIS that correlated with healing, decreased SCORAD and itch scores. Additionally, EIS showed a significant inverse correlation with serum biomarkers associated with inflammatory pathways that may affect the epithelial barrier, particularly chemokines such as CCL13, CCL3, CCL7, and CXCL8 and other cytokines, such as IRAK1, IRAK4, and FG2, which were significantly high at admission. Furthermore, filaggrin copy numbers significantly correlated with EIS on non-lesional skin of patients. CONCLUSIONS: Electrical impedance spectroscopy can be a useful tool to detect skin barrier dysfunction in vivo, valuable for the assessment of AD severity, progression, and therapy efficacy.

Direct assessment of skin epithelial barrier by electrical impedance spectroscopy.

BACKGROUND: Many skin and mucosal inflammatory disorders, such as atopic dermatitis, have been associated with an impaired epithelial barrier function, which allows allergens, pollutants, or microbes to enter the tissue and activate the immune response. The aim of this study was to establish a method to directly assess in vivo the epidermal barrier function by electrical impedance (EI) spectroscopy. METHODS: Mice epidermal barrier was damaged by epicutaneous application of proteases and cholera toxin and by tape stripping. EI and transepidermal water loss (TEWL) were measured before and after the application. Additionally, histological analysis, immunofluorescence staining, and RT-PCR were performed on skin biopsies to evaluate the epithelial barrier. RESULTS: A few hours after papain application, a dose-dependent reduction of EI was detected, reflecting the decreased barrier function. At the same time, an increase of TEWL was observed, with a significant negative correlation with EI, demonstrating that EI changes were directly linked to barrier defects. Twenty-four and 48 hours after the treatment, EI starts to increase to background levels, indicating tissue healing and restoration of skin barrier. Barrier disruption was confirmed by histological analysis showing an impaired stratum corneum and higher cellular infiltration after papain application. In addition, immunofluorescence staining and RT-PCR showed downregulation of molecules involved in the barrier function, such as filaggrin, occludin, and claudin-1, and mRNA levels of filaggrin, loricrin, and involucrin. Comparable results were observed after tape stripping and cholera toxin treatment. CONCLUSION: Electrical impedance spectroscopy is a rapid and reliable diagnostic tool to detect skin barrier defects.

Some binocular advantages for planning reach, but not grasp, components of prehension.

Proficient (fast, accurate, precise) hand actions for reaching-to-grasp 3D objects are known to benefit significantly from the use of binocular vision compared to one eye alone. We examined whether these binocular advantages derive from increased reliability in encoding the goal object's properties for feedforward planning of prehension movements or from enhanced feedback mediating their online control. Adult participants reached for, precision grasped and lifted cylindrical table-top objects (two sizes, 2 distances) using binocular vision or only their dominant/sighting eye or their non-dominant eye to program and fully execute their movements or using each of the three viewing conditions only to plan their reach-to-grasp during a 1 s preview, with vision occluded just before movement onset. Various kinematic measures of reaching and grasping proficiency, including corrective error rates, were quantified and compared by view, feedback and object type. Some significant benefits of binocular over monocular vision when they were just available for pre-movement planning were retained for the reach regardless of target distance, including higher peak velocities, straighter paths and shorter low velocity approach times, although these latter were contaminated by more velocity corrections and by poorer coordination with object contact. By contrast, virtually all binocular advantages for grasping, including improvements in peak grip aperture scaling, the accuracy and precision of digit placements at object contact and shorter grip application times preceding the lift, were eliminated with no feedback available, outcomes that were influenced by the object's size. We argue that vergence cues can improve the reliability of binocular internal representations of object distance for the feedforward programming of hand transport, whereas the major benefits of binocular vision for enhancing grasping performance derive exclusively from its continuous presence online.

Gaze-grasp coordination in obstacle avoidance: differences between binocular and monocular viewing.

Most adults can skillfully avoid potential obstacles when acting in everyday cluttered scenes. We examined how gaze and hand movements are normally coordinated for obstacle avoidance and whether these are altered when binocular depth information is unavailable. Visual fixations and hand movement kinematics were simultaneously recorded, while 13 right-handed subjects reached-to-precision grasp a cylindrical household object presented alone or with a potential obstacle (wine glass) located to its left (thumb's grasp side), right or just behind it (both closer to the finger's grasp side) using binocular or monocular vision. Gaze and hand movement strategies differed significantly by view and obstacle location. With binocular vision, initial fixations were near the target's centre of mass (COM) around the time of hand movement onset, but usually shifted to end just above the thumb's grasp site at initial object contact, this mainly being made by the thumb, consistent with selecting this digit for guiding the grasp. This strategy was associated with faster binocular hand movements and improved end-point grip precision across all trials than with monocular viewing, during which subjects usually continued to fixate the target closer to its COM despite a similar prevalence of thumb-first contacts. While subjects looked directly at the obstacle at each location on a minority of trials and their overall fixations on the target were somewhat biased towards the grasp side nearest to it, these gaze behaviours were particularly marked on monocular vision-obstacle behind trials which also commonly ended in finger-first contact. Subjects avoided colliding with the wine glass under both views when on the right (finger side) of the workspace by producing slower and straighter reaches, with this and the behind obstacle location also resulting in 'safer' (i.e. narrower) peak grip apertures and longer deceleration times than when the goal object was alone or the obstacle was on its thumb side. But monocular reach paths were more variable and deceleration times were selectively prolonged on finger-side and behind obstacle trials, with this latter condition further resulting in selectively increased grip closure times and corrections. Binocular vision thus provided added advantages for collision avoidance, known to require intact dorsal cortical stream processing mechanisms, particularly when the target of the grasp and potential obstacle to it were fairly closely separated in depth. Different accounts of the altered monocular gaze behaviour converged on the conclusion that additional perceptual and/or attentional resources are likely engaged compared to when continuous binocular depth information is available. Implications for people lacking binocular stereopsis are briefly considered.

Tilted frames of reference have similar effects on the perception of gravitational vertical and the planning of vertical saccadic eye movements.

We investigated the effects of a tilted reference frame (i.e., allocentric visual context) on the perception of the gravitational vertical and saccadic eye movements along a planned egocentric vertical path. Participants (n = 5) in a darkened room fixated a point in the center of a circle on an LCD display and decided which of two sequentially presented dots was closer to the unmarked '6 o'clock' position on that circle (i.e., straight down toward their feet). The slope of their perceptual psychometric functions showed that participants were able to locate which dot was nearer the vertical with a precision of 1°-2°. For three of the participants, a square frame centered at fixation and tilted (in the roll direction) 5.6° from the vertical caused a strong perceptual bias, manifest as a shift in the psychometric function, in the direction of the traditional 'rod-and-frame' effect, without affecting precision. The other two participants showed negligible or no equivalent biases. The same subjects participated in the saccade version of the task, in which they were instructed to shift their gaze to the 6 o'clock position as soon as the central fixation point disappeared. The participants who showed perceptual biases showed biases of similar magnitude in their saccadic endpoints, with a strong correlation between perceptual and saccadic biases across all subjects. Tilting of the head 5.6° reduced both perceptual and saccadic biases in all but one observer, who developed a strong saccadic bias. Otherwise, the overall pattern and significant correlations between results remained the same. We conclude that our observers' saccades-to-vertical were dominated by perceptual input, which outweighed any gravitational or head-centered input.

A system for the management, display and integration of pre-hospital healthcare activity in the deployed environment.

AIM: To create and implement a system through which pre-hospital healthcare activity across an entire operational theatre could be made available in real-time to support healthcare delivery, governance and assurance activity. METHODS: An IT-based system was created that could display, manage and integrate the pre-hospital healthcare activity on Op HERRICK 18. The system was based on the Defence Medical Services Common Assurance Framework and run through Microsoft Office SharePoint. RESULTS: Pre-hospital healthcare activity was made available and visible across an operational theatre. This supported delivery, assurance and governance at any time. Activity from each medical facility could be integrated and display automatically improving theatre wide situational awareness. The availability of information resulted in a shift towards a more continuous process of assurance and governance rather than reliance on inherently threatening and increasingly intermittent inspection regimes. DISCUSSION: The ability to review healthcare activity remotely at anytime significantly improves the validity of assurance possible for a deployed force. Governance activity can be more responsive and less reliant on the fixed timescale and datasets of reports from outlying medical facilities. However, assurance and governance authorities must not allow such a wealth of information to impact local leadership and innovation through a perception of, or actual, micro-management.

Caesarean scar pregnancy presenting at 17 weeks with a journey involving an exploratory laparotomy, continuing pregnancy and delivery at 34 weeks: A case report.

Caesarean scar pregnancy (CSP) occurs when the gestational sac implants in the region of a scar from a previous caesarean delivery. CSP can lead to life-threatening complications, including severe haemorrhage, uterine rupture, placenta accreta spectrum (PAS) and hysterectomy. A 40-year-old woman with one previous caesarean was referred to the specialist centre at 17+1 weeks of gestation with concerns about CSP. At 19 weeks, she was admitted with abdominal pain. Due to raised body habitus, accurate ultrasound assessment was challenging, necessitating reliance on magnetic resonance imaging (MRI). The patient desired to continue the pregnancy, but due to pain and concerns about uterine rupture she consented to a laparotomy to potentially terminate the pregnancy. Findings during the laparotomy were reassuring, leading to the decision not to terminate the pregnancy. The patient remained hospitalised until delivery by caesarean-hysterectomy at 33+6 weeks. Histopathology confirmed the PAS diagnosis. This case highlights the importance of achieving early diagnosis and obtaining clear sonographic findings. It emphasises the pitfalls of relying on MRI due to its tendency to over-diagnose severity. It emphasises the urgency for improved training in this domain. Early sonographic diagnosis allows safer performance of termination of pregnancy. It also provides women who continue with the pregnancy useful prognostic signs to facilitate decisions on the optimal gestation for delivery. Determining optimal conservative management for CSP remains an ongoing challenge. This case emphasises the importance of multidisciplinary discussion, comprehensive patient counselling and involving patients in their care planning, to create an individualised and adaptable treatment plan.

Binocular vision enhances a rapidly evolving affordance priming effect: behavioural and TMS evidence.

Extensive research has suggested that simply viewing an object can automatically prime compatible actions for object manipulation, known as affordances. Here we explored the generation of covert motor plans afforded by real objects with precision ('pinchable') or whole-hand/power ('graspable') grip significance under different types of vision. In Experiment 1, participants viewed real object primes either monocularly or binocularly and responded to orthogonal auditory stimuli by making precision or power grips. Pinchable primes facilitated congruent precision grip responses relative to incongruent power grips, and vice versa for graspable primes, but only in the binocular vision condition. To examine the temporal evolution of the binocular affordance effect, participants in Experiment 2 always viewed the objects binocularly but made no responses, instead receiving a transcranial magnetic stimulation pulse over their primary motor cortex at three different times (150, 300, 450ms) after prime onset. Motor evoked potentials (MEPs) recorded from a pinching muscle were selectively increased when subjects were primed with a pinchable object, whereas MEPs from a muscle associated with power grips were increased when viewing graspable stimuli. This interaction was obtained both 300 and 450ms (but not 150ms) after the visual onset of the prime, characterising for the first time the rapid development of binocular grip-specific affordances predicted by functional accounts of the affordance effect.

Giant cell arteritis affecting the tongue: a case report and review of the literature.

UNLABELLED: Giant cell arteritis (GCA) is a systemic vasculitis with symptoms that could cause a patient to present to a general dental practitioner. A case of GCA that presented as headache, jaw claudication, unilateral visual loss and tongue ulceration leading to necrosis is reported and the literature reviewed, with an emphasis on dentally relevant aspects. It is vital that GCA is not overlooked in patients over the age of 50 with unexplained dental pain, tissue necrosis or jaw pain which may be misdiagnosed as a temporomandibular joint disorder. Early diagnosis and prompt treatment is the key to preventing visual loss. Early referral in such cases would be warranted. CLINICAL RELEVANCE: Dental clinicians may play a part in the early diagnosis of GCA by having a high index of suspicion for its symptoms in patients, so that devastating ischaemic consequences, such as irreversible visual loss, can be prevented.

Deficits in Reach Planning and On-Line Grasp Control in Adults With Amblyopia.

Purpose: Adults with amblyopia exhibit impairments when reaching to grasp three-dimensional objects. We examined whether their deficits derive from problems with feedforward planning of these prehension movements or in using visual feedback to control them on-line. Methods: Twenty-one adults with mild to severe anisometropic and/or strabismic amblyopia and reduced binocularity participated, along with 21 normally sighted age- and gender-matched controls. Subjects used their preferred hand to reach for, precision grasp, and then lift cylindrical table-top objects (two sizes, two distances) using binocular, dominant eye, or amblyopic/non-sighting eye vision just to plan their movements during a 1-second task preview with vision then occluded so feedback was absent or to plan and execute them (i.e., with visual feedback fully available). Kinematic and error measures of the timing and accuracy of the reach and grasp were quantified by view and feedback and compared by ANOVA. Results: The amblyopic adults performed generally worse than controls across all three views in both feedback conditions. With vision for planning only, their movement initiation and duration times were significantly increased, as were their initial reach times and error rates, especially when using the amblyopic eye alone, whatever its visual acuity loss. These relative planning deficits were only partially rectified with visual feedback available on-line. Relative grasp planning deficits were less evident in the amblyopia group, who instead produced significantly increased grip times and errors under binocular and amblyopic eye visual feedback conditions, although the subgroup with unmeasurable stereovision also formed wider (inaccurate) grasps across all conditions. Conclusions: Adults with amblyopia seem to have problems constructing reliable internal spatial representations for the feedforward planning of prehension, particularly with their affected eye and mainly affecting their reach, with additional deficits in on-line grasp control related to poor binocularity.

Practical limitations of emergency donor panels as a risk mitigation in small-scale short-term training team operations.

Haemostatic resuscitation with blood products has become the expected standard of care for trauma casualties. As UK Defence increases its deployment of small-scale, short-term training teams (STTTs) in Defence Engagement and influence operations, ever greater reliance is being placed on emergency donor panels (EDP) as a source of whole blood. This paper outlines the practical limitations of using EDPs as a risk mitigation in conventional STTTs which must be considered prior to every deployment.

Getting a grip: different actions and visual guidance of the thumb and finger in precision grasping.

We manipulated the visual information available for grasping to examine what is visually guided when subjects get a precision grip on a common class of object (upright cylinders). In Experiment 1, objects (2 sizes) were placed at different eccentricities to vary the relative proximity to the participant's (n = 6) body of their thumb and finger contact positions in the final grip orientations, with vision available throughout or only for movement programming. Thumb trajectories were straighter and less variable than finger paths, and the thumb normally made initial contact with the objects at a relatively invariant landing site, but consistent thumb first-contacts were disrupted without visual guidance. Finger deviations were more affected by the object's properties and increased when vision was unavailable after movement onset. In Experiment 2, participants (n = 12) grasped 'glow-in-the-dark' objects wearing different luminous gloves in which the whole hand was visible or the thumb or the index finger was selectively occluded. Grip closure times were prolonged and thumb first-contacts disrupted when subjects could not see their thumb, whereas occluding the finger resulted in wider grips at contact because this digit remained distant from the object. Results were together consistent with visual feedback guiding the thumb in the period just prior to contacting the object, with the finger more involved in opening the grip and avoiding collision with the opposite contact surface. As people can overtly fixate only one object contact point at a time, we suggest that selecting one digit for online guidance represents an optimal strategy for initial grip placement. Other grasping tasks, in which the finger appears to be used for this purpose, are discussed.

Quantification of free fetal DNA in multiple pregnancies and relationship with chorionicity.

OBJECTIVE: Free fetal DNA (ffDNA) in the maternal plasma appears to originate mainly from the trophoblast. We tested the hypothesis that ffDNA concentration is increased in multiple pregnancies where trophoblastic mass has been shown to be increased. METHODS: Quantitative real-time PCR was used to measure the plasma concentration of DYS14 in singleton and twin pregnancies with one or two male fetuses. Royston and Wright's regression method was used to relate ffDNA to gestational age in singleton controls; z-scores were calculated for the multiple pregnancy subgroups. RESULTS: Fifty-five singleton and 65 twin pregnancies (36 with one and 29 with two male fetuses) were analysed. There was significantly higher ffDNA concentration in twin pregnancies with two male fetuses compared with pregnancies with one male fetus. In cases with two male fetuses, there was no statistically significant difference between monochorionic and dichorionic pregnancies. CONCLUSIONS: There is higher ffDNA concentration in multiple pregnancies, and this must be taken into account for future quantitative ffDNA applications.

Cytoarchitectural differences are a key determinant of laminar projection origins in the visual cortex.

Regularity of laminar origin and termination of projections appears to be a common feature of corticocortical connections. We tested three models of this regularity, originally formulated for primate cerebral cortex, using quantitative data on the relative supragranular layer origins (SGN%) of 151 projections from 19 areas ( approximately 145,000 neurons) to four areas of cat extrastriate cortex. Predictive variables in the models were: hierarchical level differences (Barone et al., 2000), structural type differences (Barbas, 1986), and distances (Salin and Bullier, 1995) between areas. Global and local hierarchies of cat visual cortex were used to evaluate the hierarchical model. Ranking of areas by their cytoarchitectural differentiation (e.g., relative prominence of layer IV) allowed testing of the structural model, while the distance model was tested for the number of borders separating areas. Laminar projection origins correlated moderately with hierarchical differences, and poorly with border distances, but were strongly and consistently correlated with area differences in cytoarchitectural rank. Moreover, projection densities were moderately and negatively correlated with area distances and structural differences. Our findings suggest that the relative cytoarchitectural differentiation of cortical areas is the main determinant of laminar projection origins in cat visual cortex, and may underlie a general laminar regularity of mammalian cortical connections.

Oculomotor responses and visuospatial perceptual judgments compete for common limited resources.

While there is evidence for multiple spatial and attentional maps in the brain it is not clear to what extent visuoperceptual and oculomotor tasks rely on common neural representations and attentional mechanisms. Using a dual-task interference paradigm we tested the hypothesis that eye movements and perceptual judgments made to simultaneously presented visuospatial information compete for shared limited resources. Observers undertook judgments of stimulus collinearity (perceptual extrapolation) using a pointer and Gabor patch and/or performed saccades to a peripheral dot target while their eye movements were recorded. In addition, observers performed a non-spatial control task (contrast discrimination), matched for task difficulty and stimulus structure, which on the basis of previous studies was expected to represent a lesser load on putative shared resources. Greater mutual interference was indeed found between the saccade and extrapolation task pair than between the saccade and contrast discrimination task pair. These data are consistent with visuoperceptual and oculomotor responses competing for common limited resources as well as spatial tasks incurring a relatively high attentional cost.

pQCT- and Ultrasound-based Muscle and Fat Estimate Errors after Resistance Exercise.

PURPOSE: Resistance exercise increases blood flow, induces osmotic and hydrostatic fluid shifts during and immediately after exercise, and may trigger inflammatory responses for several days in the working muscle. The resultant muscle swelling can subsequently affect muscle size and quality assessments. However, the effects of muscle swelling on x-ray attenuation of adipose estimate errors are unknown. METHODS: Peripheral quantitative computed tomography (pQCT) and ultrasonography were used to assess muscle and adipose tissue properties of both upper arms before, 24, 48, and 72 h after unilateral resistance exercise. Recreationally active participants (n = 17) completed the exercise while their contralateral limb served as a control. RESULTS: Resistance exercise resulted in a significant increase in pQCT-derived muscle cross-sectional area (includes intermuscular adipose tissue [IMAT] area), muscle area (excludes IMAT area) and IMAT area, and ultrasound-derived muscle thickness at 24, 48, and 72 h. A significant decrease in pQCT-derived muscle density was also detected as well as an increase in ultrasound-derived echo intensity at 48 and 72 h. The changes in muscle area, IMAT area, and muscle density were significantly correlated with changes in echo intensity, whereas the changes in muscle cross-sectional area and IMAT area were significantly correlated with changes in muscle thickness. CONCLUSION: Unaccustomed resistance exercise can cause errors in pQCT- and ultrasound-based muscle and adipose estimates for at least 72 h. These errors are the result of muscle swelling likely caused by muscle blood flow and inflammation-dependent fluid shifts in muscle. These findings may have implications for measurements in other inflammatory conditions.

In vitro placenta barrier model using primary human trophoblasts, underlying connective tissue and vascular endothelium.

Fetal development may be compromised by adverse events at the placental interface between mother and fetus. However, it is still unclear how the communication between mother and fetus occurs through the placenta. In vitro - models of the human placental barrier, which could help our understanding and which recreate three-dimensional (3D) structures with biological functionalities and vasculatures, have not been reported yet. Here we present a 3D-vascularized human primary placental barrier model which can be constructed in 1 day. We illustrate the similarity of our model to first trimester human placenta, both in its structure and in its ability to respond to altered oxygen and to secrete factors that cause damage cells across the barrier including embryonic cortical neurons. We use this model to highlight the possibility that both the trophoblast and the endothelium within the placenta might play a role in the fetomaternal dialogue.

Preeclamptic placentae release factors that damage neurons: implications for foetal programming of disease.

Prenatal development is a critical period for programming of neurological disease. Preeclampsia, a pregnancy complication involving oxidative stress in the placenta, has been associated with long-term health implications for the child, including an increased risk of developing schizophrenia and autism spectrum disorders in later life. To investigate if molecules released by the placenta may be important mediators in foetal programming of the brain, we analysed if placental tissue delivered from patients with preeclampsia secreted molecules that could affect cortical cells in culture. Application of culture medium conditioned by preeclamptic placentae to mixed cortical cultures caused changes in neurons and astrocytes that were related to key changes observed in brains of patients with schizophrenia and autism, including effects on dendrite lengths, astrocyte number as well as on levels of glutamate and γ-aminobutyric acid receptors. Treatment of the placental explants with an antioxidant prevented neuronal abnormalities. Furthermore, we identified that bidirectional communication between neurons and astrocytes, potentially via glutamate, is required to produce the effects of preeclamptic placenta medium on cortical cells. Analysis of possible signalling molecules in the placenta-conditioned medium showed that the secretion profile of extracellular microRNAs, small post-transcriptional regulators, was altered in preeclampsia and partially rescued by antioxidant treatment of the placental explants. Predicted targets of these differentially abundant microRNAs were linked to neurodevelopment and the placenta. The present study provides further evidence that the diseased placenta may release factors that damage cortical cells and suggests the possibility of targeted antioxidant treatment of the placenta to prevent neurodevelopmental disorders.

Prehension deficits in amblyopia.

PURPOSE: Visual defects associated with amblyopia have been extensively studied, but their impact on the performance of everyday visuomotor tasks is unclear. This study evaluates eye-hand coordination (prehension) skills in adult amblyopes compared with normal subjects. METHODS: Twenty amblyopes (10 strabismic, 10 nonstrabismic) with different degrees of visual acuity loss (mild, moderate, or severe) and stereodeficiency (reduced or undetectable) participated, along with 20 matched control subjects. Subjects reached, precision grasped, and lifted cylindrical household objects (two sizes, four locations) using binocular vision or just the dominant or amblyopic (nondominant) eye, while the actions of the preferred hand were recorded. Various indices of prehension planning and online control were quantified for all trials (n = 48) performed under each viewing condition. RESULTS: Initial reaching behavior and grip shaping before object contact, which result from movement programming, were relatively normal in the amblyopic subjects, despite their vision losses. By contrast, they exhibited a range of deficits under both binocular and nondominant eye conditions in their final approach to the object (terminal reach) and when closing and applying a grasp. These impairments included prolonged execution times and more errors compared with control subjects, the extents of which covaried with the existing depth of amblyopia, although not with its underlying cause. CONCLUSIONS: Visuomotor adaptations in amblyopes are relatively minor and limited to aspects of movement planning. Their deficits in movement execution should benefit, however, from treatments that restore spatial acuity and binocularity to progressively normal levels and so deserve more explicit consideration when assessing therapeutic outcomes.