Eyes on CVI: Eye movements unveil distinct visual search patterns in Cerebral Visual Impairment compared to ADHD, dyslexia, and neurotypical children.

Visual search problems are often reported in children with Cerebral Visual Impairment (CVI). To tackle the clinical challenge of objectively differentiating CVI from other neurodevelopmental disorders, we developed a novel test battery. Visual search tasks were coupled with verbal and gaze-based measurements. Two search tasks were performed by children with CVI (n: 22; mean age (SD): 9.63 (.46) years) ADHD (n: 32; mean age (SD): 10.51 (.25) years), dyslexia (n: 28; mean age (SD): 10.29 (.20) years) and neurotypical development (n: 44; mean age (SD): 9.30 (.30) years). Children with CVI had more impaired search performance compared to all other groups, especially in crowded and unstructured displays and even when they had normal visual acuity. In-depth gaze-based analyses revealed that this group searched in overall larger areas and needed more time to recognize a target, particularly after their initial fixation on the target. Our gaze-based approach to visual search offers new insights into the distinct search patterns and behaviours of children with CVI. Their tendency to overlook targets whilst fixating on it, point towards higher-order visual function (HOVF) deficits. The novel method is feasible, valid, and promising for clinical differential-diagnostic evaluation between CVI, ADHD and dyslexia, and for informing individualized training.

Outcome measures in Angelman syndrome.

BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children's functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials. AIM: Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype. METHODS: The study sample consisted of 28 children with AS aged 2-18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored. RESULTS: Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD). CONCLUSIONS: Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition. TRIAL REGISTRATION: Registered d.d. 23-04-2020 under number 'NL8550' in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075.

Effect of ethnic diversity on the saccadic reaction time among healthy Indian and Dutch adults.

Eye movement perimetry (EMP) expresses the decline in visual field (VF) responsiveness based on the deviation in saccadic reaction times (SRTs) from their expected age-similar responses (normative database). Since ethnic dissimilarities tend to affect saccade parameters, we evaluated the effect of such a factor on SRT and its interaction with age, stimulus eccentricity, and intensity. 149 healthy adults, spread into five age groups, drawn from Indian and Dutch ethnicities underwent a customized EMP protocol integrated with a saccade task from which the SRTs to 'seen' visual stimuli were computed. The EMP test had a total of 54 coordinates (five stimulus eccentricities) tested using Goldmann size III visual stimuli presented at four stimulus intensity (SI) levels against a constant background. Considering SRT as a dependent variable, a Generalized Linear Mixed Model analysis was conducted that revealed a statistically significant (p < 0.001) influence of ethnicity and interaction between the tested factors (ethnicity × age × stimulus eccentricity × intensity). However, during the post hoc analysis, out of the 100 possible pair-wise comparisons, only 6% (minor proportion) of the estimates showed statistical significance. Hence, the ethnic-specific differences need not be accounted for while implementing EMP in a diverse set of populations instead a collective database might serve the purpose.

The integrated brain network that controls respiration.

Respiration is a brain function on which our lives essentially depend. Control of respiration ensures that the frequency and depth of breathing adapt continuously to metabolic needs. In addition, the respiratory control network of the brain has to organize muscular synergies that integrate ventilation with posture and body movement. Finally, respiration is coupled to cardiovascular function and emotion. Here, we argue that the brain can handle this all by integrating a brainstem central pattern generator circuit in a larger network that also comprises the cerebellum. Although currently not generally recognized as a respiratory control center, the cerebellum is well known for its coordinating and modulating role in motor behavior, as well as for its role in the autonomic nervous system. In this review, we discuss the role of brain regions involved in the control of respiration, and their anatomical and functional interactions. We discuss how sensory feedback can result in adaptation of respiration, and how these mechanisms can be compromised by various neurological and psychological disorders. Finally, we demonstrate how the respiratory pattern generators are part of a larger and integrated network of respiratory brain regions.

Detection of visual field defects using Eye Movement Pediatric Perimetry in children with intracranial lesions: feasibility and applicability.

The study aimed at evaluating the feasibility of Eye Movement Pediatric Perimetry (EMPP) among children in detecting Visual Field Defects (VFDs) associated with Intracranial Lesions (IL). Healthy controls (n = 35) and patients diagnosed with IL (n = 19) underwent a comprehensive clinical evaluation followed by a Goldmann Visual Field (GVF) and a customised EMPP protocol. During EMPP, all the participants were encouraged to fixate on a central target and initiate Saccadic Eye Movement (SEM) responses towards randomly appearing peripheral stimuli. The SEM responses were recorded using an eye-tracking device and further inspected to calculate Performance Scores (PS), Saccadic Reaction Times (SRTs), and an EMPP Index (EMPI). The mean age (years) of the controls and cases were 7.3 (SD: 1.5) and 9.4 (SD: 2.4) respectively. Among the controls, the older children (≥7 years) showed statistically significantly faster SRTs (p = 0.008) compared to the younger group. The binocular EMPP measurements compared between the controls and the cases revealed no statistically significant differences in PS (p = 0.34) and SRT (p = 0.51). EMPP failed in 4 children because of data loss or unacceptably poor PS whereas GVF failed in 7 children due to unreliable subjective responses. Of the 16 reports, with regard to the central 30-degree VF, 63% of the outputs obtained from both methods were comparable. EMPP is a reliable method to estimate and characterise the central 30-degree VF in greater detail in children with IL. EMPP can supplement the conventional methods, especially in those children who fail to complete a long duration GVF test.

Clinical Utility of Eye Tracking in Assessing Distractibility in Children with Neurological Disorders or ADHD: A Cross-Sectional Study.

This study aims to investigate distractibility quantified by recording and analyzing eye movements during task-irrelevant distraction in children with and without ADHD and in children with and without neurological disorders. Gaze behavior data and press latencies of 141 participants aged 6−17 that were collected during a computerized distraction paradigm with task-irrelevant stimuli (IDistrack) were analyzed. Children using attention-regulating medication were excluded from participation. Data were analyzed for subgroups that were formed based on the presence of neurological disorders and the presence of ADHD separately. Participants with ADHD and participants with neurological disorders spent less time fixating on the target stimuli compared to their peers without ADHD (p = 0.025) or their peers without neurological disorders (p < 0.001). Participants with and without ADHD had equal press latencies (p = 0.79). Participants with neurological disorders had a greater press latency compared to their typically developing peers (p < 0.001). Target fixation duration shows a significant association with parent-reported attention problems (r = −0.39, p < 0.001). We conclude that eye tracking during a distraction task reveals potentially valid clinical information that may contribute to the assessment of dysfunctional attentional processes. Further research on the validity and reliability of this paradigm is recommended.

Early Screening of Visual Processing Dysfunctions in Children Born Very or Extremely Preterm.

Introduction: Children with early brain damage or dysfunction are at risk of developing cerebral visual impairment (CVI), including visual processing dysfunctions (VPD), which currently remain largely undetected until school age. Our aim was to systematically screen for possible VPD in children born very or extremely preterm from 1 to 2 years corrected age (CA) and to evaluate the effectiveness of early referral. Method: We included N = 48 children born < 30 weeks from 1 year CA. They underwent a two-step VPD screening based on (1) neurological signs indicative of visual brain damage evaluated by neonatologists and/or pediatric neurologist and (2) a functional assessment of visual orienting functions (VOF) with an eye tracking-based test. If at least one of these assessments was abnormal for their age, the children were classified as a risk of VPD and referred to undergo conventional visual diagnostics: ophthalmic exam and visual function assessment (VFA). At 2 years CA, VOF screening was repeated and neurodevelopment was assessed. Results: 18 children (38%) were classified as at risk of VPD at 1 year CA. 7 children had abnormal neurological signs, 5 children had abnormal VOF, and 6 children had both. Subsequent ophthalmic exams (N = 14) showed severe hypermetropia in 21% and strabismus in 14%. VFA (N = 10) showed abnormal visual function and behavior in only 1 child. At 2 years CA, the total group showed an increase in abnormal VOF. Whereas the children at risk showed some normalization, the group without VPD risk at 1 year CA showed deterioration of VOF. Neurodevelopmental outcome did not clearly differ between risk groups. Conclusion: Our findings show a substantial risk of VPD during visual screening (in 38%) at 1 year CA, but relatively few deficits on subsequent conventional ophthalmic exams and VFA. The data suggest that most conventional visual diagnostic methods at this young age are not related to the established VPD risks. VOF assessment should be used complimentary to these methods. The fact that at 2 years CA the number of children with a VPD risk based on abnormal VOF increased argues for more extensive and continuous screening in risk groups, at least until school age.

Activated PI3Kδ syndrome, an immunodeficiency disorder, leads to sensorimotor deficits recapitulated in a murine model.

The phosphoinositide-3-kinase (PI3K) family plays a major role in cell signaling and is predominant in leukocytes. Gain-of-function (GOF) mutations in the PIK3CD gene lead to the development of activated PI3Kδ syndrome (APDS), a rare primary immunodeficiency disorder. A subset of APDS patients also displays neurodevelopmental delay symptoms, suggesting a potential role of PIK3CD in cognitive and behavioural function. However, the extent and nature of the neurodevelopmental deficits has not been previously quantified. Here, we assessed the cognitive functions of two APDS patients, and investigated the causal role of the PIK3CD GOF mutation in neurological deficits using a murine model of this disease. We used p110δE1020K knock-in mice, harbouring the most common APDS mutation in patients. We found that APDS patients present with visuomotor deficits, exacerbated by autism spectrum disorder comorbidity, whereas p110δE1020K mice exhibited impairments in motor behaviour, learning and repetitive behaviour patterning. Our data indicate that PIK3CD GOF mutations increase the risk for neurodevelopmental deficits, supporting previous findings on the interplay between the nervous and the immune system. Further, our results validate the knock-in mouse model, and offer an objective assessment tool for patients that could be incorporated in diagnosis and in the evaluation of treatments.

A haploscope based binocular pupillometer system to quantify the dynamics of direct and consensual Pupillary Light Reflex.

This study described the development of a haploscope-based pupillometer for the parametrization of the Pupillary Light Reflex (PLR), and its feasibility in a set of 30 healthy subjects (light or dark-colored irides) and five patients diagnosed with Relative Afferent Pupillary Defect (RAPD). Our supplementary aim focused on evaluating the influence of iris colour on the PLR to decide whether a difference in PLR parameters should be anticipated when this system is used across ethnicities. All the participants underwent a customized pupillometry protocol and the generated pupil traces, captured by an eye tracker, were analyzed using exponential fits to derive PLR parameters. A Pupil Response Symmetry (PRS) coefficient was calculated to predict the presence of RAPD. The mean (SD) Initial PD during dilation (3.2 (0.5) mm) and the minimum PD during constriction (2.9 (0.4) mm) in the light iris group had a statistically significant (p < 0.001) higher magnitude compared to the dark iris group. The normal limits of the PRS coefficient ranged from - 0.20 to + 1.07 and all RAPD patients were outside the calculated normal limits. This proposed system, analysis strategies, and the tested metrics showed good short-term repeatability and the potential in detecting pupil abnormalities in neuro-ophthalmic diseases.

Slowed Saccadic Reaction Times in Seemingly Normal Parts of Glaucomatous Visual Fields.

Purpose: In eye movement perimetry, peripheral stimuli are confirmed by goal-directed eye movements toward the stimulus. The saccadic reaction time (SRT) is regarded as an index of visual field responsiveness, whereas in standard automated perimetry (SAP), the visual field sensitivity is tested. We investigated the relation between visual field sensitivity and responsiveness in corresponding locations of the visual field in healthy controls and in patients with mild, moderate and advanced glaucoma. Materials and Methods: Thirty-four healthy control subjects and 42 glaucoma patients underwent a 54-point protocol in eye movement perimetry (EMP) and a 24-2 SITA standard protocol in a Humphrey Field Analyzer. The visual field points were stratified by total deviation sensitivity loss in SAP into 6 strata. A generalized linear mixed model was applied to determine the influence of the various factors. Results: The generalized linear mixed model showed that the mean SRT increased with increasing glaucoma severity, from 479 ms in the control eyes to 678 ms in the eyes of patients with advanced glaucoma (p < 0.001). Mean SRTs significantly increased with increasing SAP sensitivity loss. Even at the locations where no sensitivity loss was detected by SAP (total deviation values greater or equal than 0 dB), we found lengthened SRTs in mild, moderate and advanced glaucoma compared to healthy controls (p < 0.05) and in moderate and advanced glaucoma compared to mild glaucoma (p < 0.05). At locations with total deviation values between 0 and -3 dB, -3 and -6 dB and -6 and -12 dB, we found similar differences. Conclusions: The lengthened SRT in areas with normal retinal sensitivities in glaucomatous eyes, i.e., planning and execution of saccades to specific locations, precede altered sensory perception as assessed with SAP. Better understanding of altered sensory processing in glaucoma might allow earlier diagnosis of emerging glaucoma.

To Explore the Predictive Power of Visuomotor Network Dysfunctions in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: Research into Alzheimer's disease has shifted toward the identification of minimally invasive and less time-consuming modalities to define preclinical stages of Alzheimer's disease. METHOD: Here, we propose visuomotor network dysfunctions as a potential biomarker in AD and its prodromal stage, mild cognitive impairment with underlying the Alzheimer's disease pathology. The functionality of this network was tested in terms of timing, accuracy, and speed with goal-directed eye-hand tasks. The predictive power was determined by comparing the classification performance of a zero-rule algorithm (baseline), a decision tree, a support vector machine, and a neural network using functional parameters to classify controls without cognitive disorders, mild cognitive impaired patients, and Alzheimer's disease patients. RESULTS: Fair to good classification was achieved between controls and patients, controls and mild cognitive impaired patients, and between controls and Alzheimer's disease patients with the support vector machine (77-82% accuracy, 57-93% sensitivity, 63-90% specificity, 0.74-0.78 area under the curve). Classification between mild cognitive impaired patients and Alzheimer's disease patients was poor, as no algorithm outperformed the baseline (63% accuracy, 0% sensitivity, 100% specificity, 0.50 area under the curve). COMPARISON WITH EXISTING METHODS: The classification performance found in the present study is comparable to that of the existing CSF and MRI biomarkers. CONCLUSION: The data suggest that visuomotor network dysfunctions have potential in biomarker research and the proposed eye-hand tasks could add to existing tests to form a clear definition of the preclinical phenotype of AD.

Saccadic reaction time in mirror image sectors across horizontal meridian in eye movement perimetry.

In eye movement perimetry (EMP), the saccadic reaction time (SRT) to 'seen' visual stimuli are delayed in glaucoma. Evaluating SRT behaviour in hemi-field sectors could refine its clinical implication. The development phase included 60 controls retrospectively and for the test cohort in evaluation phase, another 30 healthy subjects and 30 glaucoma patients were recruited prospectively. The SRTs were used to calculate the normative limits within 5 predefined hemi-field sectors. Scores were assigned to probabilities for SRT at the level of 5%, 2.5% 1% and 0.5%. Per sector pair, a probability score limit (PSL) was calculated at each of the four levels and were compared with the scores obtained from the test cohort. The classification accuracy 'normal versus abnormal' was assessed for PSL in EMP and compared with glaucoma hemi-field test in standard automated perimetry. We found no statistically significant differences in SRTs between the mirror sectors in healthy subjects. The PSL at 2.5% had moderate classification accuracy with a specificity of 77% and sensitivity 70%. This could be suggestive of an SRT delay in the overall visual field in glaucoma.

Early visuospatial attention and processing and related neurodevelopmental outcome at 2 years in children born very preterm.

BACKGROUND: The ability to perceive and process visuospatial information is a condition for broader neurodevelopment. We examined the association of early visuospatial attention and processing with later neurodevelopmental outcome in very preterm infants. METHODS: Visuospatial attention and processing was assessed in 209 children (<30 weeks gestation) using an easy applicable eye tracking-based paradigm at 1 and 2 years. Average reaction times to fixation (RTF) on specific visual stimuli were calculated, representing time needed for overall attention (Cartoon stimuli) and processing (Motion and Form stimuli). Associations between RTFs and various measures of development at 2 years including cognitive and motor development (Bayley Scales of Infant and Toddler Development-Third edition; Bayley-III), language (Lexi test) and behavior (Child Behavior Checklist) were examined. RESULTS: At 1 year, 100 ms slower Cartoon and Motion RTFs were associated with lower cognitive Bayley-III scores (-4.4 points, 95%CI: -7.4; -1.5 and -1.0 points, -1.8; -0.2, respectively). A 100 ms slower Cartoon RTF was associated with a 3.5 (-6.6; -0.5) point decrease in motor Bayley-III score. CONCLUSIONS: Visuospatial attention and motion processing at 1 year is predictive of overall cognitive and motor development 1 year later. The nonverbal eye tracking-based test can assist in early detection of preterm children at risk of adverse neurodevelopment. IMPACT: Visuospatial attention and processing at 1 year corrected age is predictive for overall cognitive and motor development 1 year later in preterm infants. First study to relate early visuospatial attention and processing with later neurodevelopmental outcome in preterm children. Early detection of preterm children at risk of adverse neurodevelopment, which allows for more timely interventions.

Remodeling of Rat M. Gastrocnemius Medialis During Recovery From Aponeurotomy.

Aponeurotomy is a surgical intervention by which the aponeurosis is transsected perpendicularly to its longitudinal direction, halfway along its length. This surgical principle of aponeurotomy has been applied also to intramuscular lengthening and fibrotomia. In clinics, this intervention is performed in patients with cerebral palsy in order to lengthen or weaken spastic and/or short muscles. If the aponeurotomy is performed on the proximal aponeurosis, as is the case in the present study, muscle fibers located distally from the aponeurosis gap that develops lose their myotendinous connection to the origin. During recovery from this intervention, new connective (scar) tissue repairs the gap in the aponeurosis, as well as within the muscle belly. As a consequence, the aponeurosis is longer during and after recovery. In addition, the new connective tissue is more compliant than regular aponeurosis material. The aim of this study was to investigate changes in muscle geometry and adaptation of the number of sarcomeres in series after recovery from aponeurotomy of the proximal gastrocnemius medialis (GM) aponeurosis, as well as to relate these results to possible changes in the muscle length-force characteristics. Aponeurotomy was performed on the proximal aponeurosis of rat muscle GM and followed by 6 weeks of recovery. Results were compared to muscles of a control group and those of a sham-operated group. After recovery from aponeurotomy, proximal and distal muscle fiber lengths were similar to that of the control group. The mean sarcomere length from fibers located proximally relative to the aponeurosis gap remained unchanged. In contrast, fibers located distally showed 16-20% lower mean sarcomere lengths at different muscle lengths. The number of sarcomeres in series within the proximal as well as distal muscle fibers was unchanged. After recovery, muscle length-force characteristics were similar to those of the control group. A reversal of proximal-distal difference of fibers mean sarcomere lengths within muscles during recovery from aponeurotomy is hypothesized to be responsible for the lack of an effect. These results indicate that after recovery from aponeurotomy, geometrical adaptations preserved the muscle function. Moreover, it seems that the generally accepted rules of adaptation of serial sarcomere numbers are not applicable in this situation.

Brain Damage and Visuospatial Impairments: Exploring Early Structure-Function Associations in Children Born Very Preterm.

BACKGROUND: To provide insight into early neurosensory development in children born very preterm, we assessed the association between early structural brain damage and functional visuospatial attention and motion processing from one to two years corrected age. METHODS: In 112 children born at less than 32 weeks gestational age, we assessed brain damage and growth with a standardized scoring system on magnetic resonance imaging (MRI; 1.5 Tesla) scans performed at 29 to 35 weeks gestational age. Of the children with an MRI scan, 82 participated in an eye tracking-based assessment of visuospatial attention and motion processing (Tobii T60XL) at one year corrected age and 59 at two years corrected age. RESULTS: MRI scoring showed good intra- and inter-rater reproducibility. At one year, 10% children had delayed attentional reaction times and 23% had delayed motion reaction times. Moderate to severe brain damage significantly correlated with slower visuospatial reaction times. At two years, despite attention and motion reaction times becoming significantly faster, 20% had delayed attentional reaction times and 35% had delayed motion reaction times, but no correlations with MRI scores were found. The presence of structural brain damage was associated with abnormal functional performance over age. CONCLUSIONS: The present study indicates an association between moderate to severe brain damage and visuospatial attention and motion processing dysfunction at one year corrected age. This provides a new perspective on comprehensive MRI scoring and quantitative functional visuospatial assessments and their applicability in children born very preterm in their first years of life.

Visual Field Plots: A Comparison Study Between Standard Automated Perimetry and Eye Movement Perimetry.

PRéCIS:: This eye movement perimetry (EMP) study describes the development of saccadic reaction time (SRT)-based visual field plots, which could effectively display the presence, location, and extent of glaucomatous defects and support clinical decision-making. PURPOSE: EMP is capable of discriminating normal from glaucomatous visual field defects on the basis of average delays in SRTs. To classify the presence and extent of age-corrected visual field defects, it is required to create SRT-based probability maps. AIM: The aim of this study was to create visual field probability plots based on SRTs and to evaluate their clinical applicability by 2 glaucoma specialists. MATERIALS AND METHODS: The development phase included 95 controls segregated into 5 age-bins to estimate normative limits of SRT. Next, for the testing phase, a set of 28 healthy subjects and 24 glaucoma patients were recruited who underwent standard automated perimetry (SAP) and EMP visual field testing. Fifty-two SAP and EMP plots were presented to 2 glaucoma specialists to classify them as normal or abnormal and to identify the defect location and pattern as 1 or more of 7 predefined categories. RESULTS: The glaucoma specialists showed a sensitivity of 100% and a specificity of 93% and 96% for identifying normal versus abnormal visual field. For specialists 1 and 2, 85% and 92%, respectively, of EMP reports were assigned to the same category as SAP. The reports that did not agree with SAP were graded to a higher defect pattern. The intermethod agreement for specialists 1 and 2 was κ 0.92 and 0.96, respectively. CONCLUSION: SRT-based visual field probability plots provided a comprehensive summary of an individual's visual field status and showed comparable clinical applicability to that of SAP plots.

Early intervention for children at risk of visual processing dysfunctions from 1 year of age: a randomized controlled trial protocol.

BACKGROUND: An increasing number of children are suffering from brain damage-related visual processing dysfunctions (VPD). There is currently a lack of evidence-based intervention methods that can be used early in development. We developed a visual intervention protocol suitable from 1 year of age. The protocol is structured, comprehensive and individually adaptive, and is paired with quantitative outcome assessments. Our aim is to investigate the effectiveness of this first visual intervention program for young children with (a risk of) VPD. METHODS: This is a single-blind, placebo-controlled trial that is embedded within standard clinical care. The study population consists of 100 children born very or extremely preterm (< 30 weeks) at 1 year of corrected age (CA), of whom 50% are expected to have VPD. First, children undergo a visual screening at 1 year CA. If they are classified as being at risk of VPD, they are referred to standard care, which involves an ophthalmic and visual function assessment and a (newly developed) visual intervention program. This program consists of a general protocol (standardized and similar for all children) and a supplement protocol (adapted to the specific needs of the child). Children are randomly allocated to an intervention group (starting upon inclusion at 1 year CA) or a control group (postponed: starting at 2 years CA). The control group will receive a placebo treatment. The effectiveness of early visual intervention will be examined with follow-up visual and neurocognitive assessments after 1 year (upon completion of the direct intervention) and after 2 years (upon completion of the postponed intervention). DISCUSSION: Through this randomized controlled trial we will establish the effectiveness of a new and early visual intervention program. Combining a general and supplement protocol enables both structured comparisons between participants and groups, and custom habilitation that is tailored to a child's specific needs. The design ensures that all included children will benefit from participation by advancing the age at which they start receiving an intervention. We expect results to be applicable to the overall population of children with (a risk of) VPD early in life. TRIAL REGISTRATION: Netherlands Trial Register: NTR6952. Registered 19 January 2018.

Effect of Age, Sex, Stimulus Intensity, and Eccentricity on Saccadic Reaction Time in Eye Movement Perimetry.

PURPOSE: In eye movement perimetry (EMP), the extent of the visual field is tested by assessing the saccades using an eye tracker. The aim of the present study was to determine the effects of age and sex of the subjects, the eccentricity and intensity of the peripheral stimuli on saccadic reaction time (SRT), and the interaction between these parameters in healthy participants. METHODS: Healthy participants aged between 20 to 70 years underwent a complete ophthalmic examination and an EMP test. SRT was determined from detected peripheral stimuli of four intensity levels. A multilevel mixed-model analysis was used to verify the influence of subject and stimulus characteristics on SRT within the tested visual field. RESULTS: Ninety-five subjects (mean age 43.0 [15.0] years) were included. Age, stimulus intensity, and eccentricity had a statistically significant effect on SRT, not sex. SRTs were significantly faster with increasing stimulus intensity and decreasing eccentricity (P < 0.001). At the lowest stimulus intensity of 192 cd/m2, a significant interaction was found between age and eccentricity. CONCLUSIONS: The current study demonstrated significant SRT dependence across the visual field measured up to 27°, irrespective of sex. The presented SRT values may serve as a first normative guide for EMP. TRANSLATIONAL RELEVANCE: This report of SRT interaction can aid in refining its use as a measure of visual field responsiveness.

Eye Movement Perimetry and Frequency Doubling Perimetry: clinical performance and patient preference during glaucoma screening.

PURPOSE: To evaluate the screening accuracy of an Eye Movement Perimetry (EMP) in comparison with Frequency Doubling Perimetry (FDP) and to investigate the patient preference and perception towards these visual field screening methods. METHODS: A total of 104 healthy subjects (mean age (SD) of 48 (14) years) and 73 glaucoma patients (mean age (SD) of 52 (13) years) were recruited. All the participants underwent a comprehensive ophthalmic evaluation including the 24-2 SITA standard protocol on the Humphrey Field Analyzer (HFA). This was followed by the 26-point protocol in EMP and the C-20-1 protocol in FDP. During EMP, all subjects were instructed to fixate a central target and to look at the detected peripheral target, followed by refixation of the central target and Saccadic Reaction Time (SRT) towards each of the "seen" stimuli was calculated. Next, a questionnaire was administered to evaluate the patient preference and perception towards the perimetry techniques. Mean SRTs and Robin scores were used to plot Receiver Operating Characteristics (ROC) curves to determine the screening accuracies. From the questionnaire survey, the frequency distributions of the responses were calculated. RESULTS: Robin score and SRT were significantly increased in glaucoma patients in comparison with the age-matched healthy subjects (p < 0.001). The ROC analysis revealed comparable Area Under the Curve (AUC) values (0.95, p = 0.81) with a specificity of 95.2% for FDP and 96.2% for EMP with a sensitivity of 87.7%. Thirty-seven percent of the older age group (≥ 40 years) and 65% of severe glaucoma patients showed preference for EMP over FDP. CONCLUSIONS: This study results indicate that the customized protocol in EMP provides efficient and rapid means of screening visual field defects in glaucoma, which compared well with FDP. Elderly healthy participants and patients with moderate and severe glaucomatous defects preferred EMP as it permitted natural reflexive eye movements thereby resembling a real-life test setting.

Gestalt Perception in Children With Visual Impairments: Item-Specific Performance and Looking Behavior.

Visual closure is the ability to visualize a complete whole when an incomplete picture is presented. The aim of the present study was to investigate the Kaufman Gestalt closure task in children with cerebral and ocular visual impairments. Looking behavior was assessed by an eye tracker system to quantify the number and duration of fixations. We found that children with visual impairments due to cerebral damage show weaker Gestalt perception and had different looking patterns than children with ocular or without visual impairments. Children with brain damage performed significantly worse on the animate items than the group without brain damage.