Effectiveness of early spectacle intervention on visual outcomes in babies at risk of cerebral visual impairment: a parallel group, open-label, randomised clinical feasibility trial protocol.

INTRODUCTION: Hypoaccommodation is common in children born prematurely and those with hypoxic ischaemic encephalopathy (HIE), with the potential to affect wider learning. These children are also at risk of longer-term cerebral visual impairment. It is also well recognised that early intervention for childhood visual pathology is essential, because neuroplasticity progressively diminishes during early life. This study aims to establish the feasibility and acceptability of conducting a randomised controlled trial to test the effectiveness of early near vision correction with spectacles in infancy, for babies, at risk of visual dysfunction. METHODS AND ANALYSIS: This is a parallel group, open-label, randomised controlled (feasibility) study to assess visual outcomes in children with perinatal brain injury when prescribed near vision spectacles compared with the current standard care-waiting until a problem is detected. The study hypothesis is that accommodation, and possibly other aspects of vision, may be improved by intervening earlier with near vision glasses. Eligible infants (n=75, with either HIE or <29 weeks preterm) will be recruited and randomised to one of three arms, group A (no spectacles) and two intervention groups: B1 or B2. Infants in both intervention groups will be offered glasses with +3.00 DS added to the full cycloplegic refraction and prescribed for full time wear. Group B1 will get their first visit assessment and intervention at 8 weeks corrected gestational age (B1) and B2 at 16 weeks corrected gestational age. All infants will receive a complete visual and neurodevelopmental assessment at baseline and a follow-up visit at 3 and 6 months after the first visit. ETHICS AND DISSEMINATION: The South-Central Oxford C Research Ethics Committee has approved the study. Members of the PPI committee will give advice on dissemination of results through peer-reviewed publications, conferences and societies. TRIAL REGISTRATION NUMBER: ISRCTN14646770, NCT05048550, NIHR ref: PB-PG-0418-20006.

Prognostic value of transient pattern visual evoked potentials in children with cerebral visual impairment.

AIM: To investigate whether pattern reversal visual evoked potentials (PRVEPs) could predict future visual acuity in infants with cerebral visual impairment (CVI). METHOD: Fifty-five children (27 males, 28 females) with severe CVI seen in the ophthalmology department of a specialist children's hospital were identified retrospectively. Behavioural visual acuity and visual evoked potentials (VEPs) at presentation (time 1, T1) were compared with final visual acuity at late preschool/early school age (time 2, T2). Predictors of visual acuity at T2 were identified using univariate and multivariate logistic and linear regression analysis. RESULTS: Median age was 14 months at T1 (range: 6-44mo) and 63 months at T2 (range: 29-150mo). The presence of a PRVEP produced by a check width of 50' (minutes of arc) or smaller (T1) predicted (p=0.05) the presence of measurable preferential looking acuity at T2. The presence of PRVEP to check widths of 25' or smaller (T1) predicted (p=0.02) better preferential looking acuity (logMAR-equivalent) scores at T2. The latter association was independent of presenting acuity at T1. INTERPRETATION: The presence of PRVEPs to check widths of 50' and 25' in infancy provided useful information. VEPs in young children with CVI may have prognostic value regarding future acuity.

Exploratory Investigation of Brain MRI Lesions According to Whole Sample and Visual Function Subtyping in Children With Cerebral Visual Impairment.

Background: There is limited research on brain lesions in children with cerebral visual impairment (CVI) of heterogeneous etiologies and according to associated subtyping and vision dysfunctions. This study was part of a larger project establishing data-driven subtypes of childhood CVI according to visual dysfunctions. Currently there is no consensus in relation to assessment, diagnosis and classification of CVI and more information about brain lesions may be of potential diagnostic value. Aim: This study aimed to investigate overall patterns of brain lesions and associations with level of visual dysfunction and to compare the patterns between the classification subgroups in children with CVI. Methods: School-aged children with CVI received ophthalmological and neuro-psychological/developmental assessments to establish CVI-related subtyping. Other pediatric information was collected from medical records. MRI scans were coded according to a semi-quantitative template including brain regions (right hemisphere, left hemisphere, visual pathways) and summed for total scores. Non-parametric analyses were conducted. Results: 28 children had clinical brain MRI scans available [44% of total sample, Group A (lower severity of visual dysfunctions) n = 16, Group B (higher severity) n = 12]. Total brain scores ranged between 0 and 18 (Group A mdn = 7, IQR = 0.8-10.0, Group B mdn = 10, IQR = 6.5-11.8) and were widespread across regions. 71 per cent had post-geniculate visual pathway damage. The median total brain and hemisphere scores of Group B were higher than subgroup A but differences did not reach statistical significance. No statistically significant associations were found between brain scores and vision variables (acuity, contrast sensitivity). Conclusion: This study found a spread of lesions across all regions on the brain scans in children with congenital CVI. The majority had damage in the postgeniculate visual pathways and visual cortex region suggesting this is an area of interest and potentially informative for diagnosis. However the subtyping classification did not show differences in number or region of lesions though the trend was higher toward Group B. This study confirms the complex diffuse and variable nature of brain lesions in children with congenital CVI, many of whom have other neurological impairments.

Visual function subtyping in children with early-onset cerebral visual impairment.

AIM: To develop a data-driven subgrouping method to identify and profile subtypes of early-onset childhood cerebral visual impairment (CVI). METHOD: Sixty-three children with suspected or diagnosed congenital CVI were recruited (28 males, 35 females, median age=8y, range=5-16y). Cognitive, basic, and higher-order vision functions were assessed and quality of life, functional vision questionnaire, neurodevelopmental, and ophthalmological data were collected. Cluster analysis and other statistical analyses were undertaken to determine and validate the subgrouping. RESULTS: Forty-three participants completing the full test battery were included in cluster analysis, revealing two subgroups. Group A1 (n=15) showed selective visual perception and visuomotor deficits. Group A2 (n=28) showed more severe and broader visual perception and visuomotor deficits, and variable visual acuity. A third, lower-functioning group, Group B (n=20), was differentiated and showed significant visual acuity reduction compared with Group A (p<0.001, V=0.69). External validation showed significant cooccurring ophthalmological (e.g. strabismus p<0.001, V=0.59) and motor impairment differences (χ2 =16.26, p<0.001, V=0.51) between the three groups. All groups had lowered parent-reported quality of life and everyday functional vision. INTERPRETATION: Statistical analyses revealed three subgroups with differentiated vision function characteristics on a gradient of severity. The subgrouping method provides the first steps in developing a novel classification system to underpin future clinical diagnostics and profiling of early-onset CVI. WHAT THIS PAPER ADDS: Three data-driven subgroups of vision function deficits were identified. A similar severity gradient was shown in cooccurring cognitive and neurodevelopmental deficits. Reported quality of life and functional vision difficulties were low across all groups.

Mother-infant interactions with infants with congenital visual impairment and associations with longitudinal outcomes in cognition and language.

BACKGROUND: This study investigated mother-infant interactions, including maternal maintaining of infant attentional focus and sensitivity, with infants with congenital severe and profound visual impairment (VI) and the association with developmental trajectories from one to three years. METHOD: Fifty-five infants and mothers were video-recorded playing together with a standard set of toys at Time 1 (T1) mean age 12.95 months (8.13-17.05 months). Maintain was categorized as the mother following and maintaining the child's focus, and Sensitivity, the mother's responsiveness and contingency to infant behaviour. Vision level was measured using the Near Detection Scale. Cognition and language were measured at T1, 12 months later (T2) and 24 months later (T3) using the Reynell-Zinkin Scales. RESULTS: Cross-sectional analyses showed that mothers of infants with severe VI (basic form vision) produced higher rates of Maintain compared to those with children with profound VI (light perception at best). Linear mixed-effects models examining developmental progression from T1 to T3 (controlling for vision level) showed an average increase of 5 DQ points (CI 95%: 1.03-9.08) in verbal comprehension for higher Sensitivity. No significant findings were found for Maintain. CONCLUSIONS: The findings suggest that mother-infant interactions (maternal Maintain) are associated with level of vision at infancy, but only maternal Sensitivity has a long-term positive association with advances in verbal comprehension from infancy to about three years. They highlight the need for incorporating strategies related to parent-infant interactions, including increased sensitivity, into early intervention for children with visual impairment.

Detection vision development in infants and toddlers with congenital vision disorders and profound-severe visual impairment.

AIM: To investigate detection vision development in infants and toddlers with congenital disorders of the peripheral visual system (CDPVS) and severe to profound visual impairment (SVI/PVI). METHOD: This was a longitudinal observational investigation of a cohort of infants with CDPVS (entry age 8-16mo) followed up 12 months later. Detection vision (Near Detection Scale [NDS]) and resolution acuity (Keeler Acuity Cards [KAC]) were assessed at each time point. Relationships between detection vision, resolution acuity, and age were investigated. RESULTS: The study cohort comprised 80 children (39 females, 41 males), mean age 13 months (Time 1) and 26 months (Time 2); 22 (27.5%) with PVI (light perception at best) and 58 (72.5%) with SVI (basic 'form' vision) at Time 1. All children achieved a measure with the NDS, however only 35 per cent and 56 per cent at Time 1 and Time 2 respectively did so on KAC. Those with PVI at Time 1 showed no further improvement at Time 2, but 87 per cent of children with SVI showed improvement in vision. The median change in NDS score was 1.0 (range 1-7, SD 1.68). INTERPRETATION: Vision development continues after 12 months of age in many toddlers if they have basic 'form' vision. A measure of detection vision is feasible in very young children when resolution acuity measurement is not achievable. WHAT THIS PAPER ADDS: The Near Detection Scale (NDS) can measure low levels of vision when acuity is not otherwise measurable. Vision can improve in toddlers with severe visual impairment who have some 'form' vision. Infants with light perception at best by 12 months are unlikely to show improvement in vision. There is a moderate negative relationship between the NDS and resolution acuity results.

Brain structure in children with congenital visual disorders and visual impairment.

AIM: To examine if congenital visual impairment is associated with differences in brain anatomy in children. METHOD: Ten children (8-12y) with congenital disorders of the peripheral visual system with severe visual impairment (SVI; >0.8 logMAR) or mild-to-moderate visual impairment (MVI; 0.6-0.8 logMAR) were compared to 21 typically sighted comparison (TSC) children. Thalamus volume, grey matter density, white matter microstructure, and integrity of visual tracts were investigated in SVI, MVI, and TSC groups with anatomical and diffusion-weighted magnetic resonance imaging. RESULTS: Compared to the TSC group, the SVI group had lower white matter integrity in tracts of the visual system (optic radiations: SVI 0.35±0.015, TSC 0.39±0.007 [p=0.022]; posterior corpus callosum: SVI 0.37±0.019; TSC 0.42±0.009 [p=0.033]) and lower left thalamus volume (SVI 4.37±0.087; TSC 4.99±0.339 [p=0.015]). Neuroanatomical differences were greater in the SVI group, while no consistent differences between the MVI and TSC group were observed. INTERPRETATION: Posterior tracts of the visual system are compromised in children with congenital visual impairment versus those who are typically sighted. The severity of visual input appears to have affected neuroanatomical development as significant reductions were only found in the SVI group. WHAT THIS PAPER ADDS: Severe visual impairment in mid-childhood is associated with reduced integrity of visual pathways and reduced thalamus volume.

Cerebral Visual Impairment and Clinical Assessment: The European Perspective.

This paper summarizes the multidisciplinary pediatric assessment methods of 3 European centers for identifying and assessing cerebral visual impairment in childhood. It describes a comprehensive neurodevelopmental assessment evaluation in which visual aspects play an important part. Developmental trajectories and the heterogeneity of the clinical picture are emphasized. Multidisciplinary ophthalmology and neurodisability/neurology teamwork together with the parent and teachers, to reach an integrated and individualized perspective for the individual child, are described. This comprehensive assessment is the starting point for habilitation programs and interventions, that can support and meet the child's needs and help them reach their optimal potential. Future developments in classification of the cerebral visual impairment conditions, building on the child's individual assessment profile, will further enhance the direction of clinical, educational, and research progress.

Home-based early intervention in infants and young children with visual impairment using the Developmental Journal: longitudinal cohort study.

AIM: To investigate the effects of home-based early intervention in children with severe visual impairment (SVI) using the Developmental Journal for babies and young children with visual impairment (DJVI). METHOD: A longitudinal observational study was undertaken with a national cohort (OPTIMUM) of infants with congenital disorders of the peripheral visual system (CDPVS) and profound-SVI; and followed up after 12 months and 24 months. Intervention was categorized according to the practitioner diary records of their usual practice over 12 months from baseline comparing those receiving the DJVI and those receiving 'Other Support'. Outcome measures of cognition and language, behaviour difficulties, parenting stress, and satisfaction with parent-practitioner partnership were collected. RESULTS: In the 54 children (26 males, 28 females, baseline mean age 13.5mo, SD 2.3mo, range 8-17mo) with 'total' CDPVS (including 16 'complex' and 38 'simple' with or without known brain disorder respectively), linear mixed effects pointed towards acceleration in sensorimotor understanding and expressive language especially in the 'simple' subsample (11.72 developmental quotient, 95% confidence interval -1.17 to 24.61, p>0.05) in those receiving the DJVI. Vision level also predicted outcomes (p<0.05). The DJVI group showed improvements in behavioural withdrawal (η2 =0.20, p=0.02, 'simple') and parenting stress (d=0.78, d=0.92, p=0.02 total and 'simple' respectively) and perceived practitioner-parent relationship (η2 =0.16, p=0.01). INTERPRETATION: Infants and young children with visual impairment receiving home-based early intervention using the DJVI with a structured developmental approach had better outcomes than those receiving 'other' home-based early interventions. Moderate to large effect improvements were found in child cognition and language, behaviour and parenting stress and the perceived practitioner-parent relationship, although cognition did not reach 5% significance level. WHAT THIS PAPER ADDS: Early intervention using the Developmental Journal for babies and young children with visual impairment was associated with enhanced developmental outcomes compared to other approaches. Improvements were also found in child behaviour, parenting stress, and perceived parent practitioner outcomes. Type and complexity of visual impairment also influenced outcomes.

INTERVENCIÓN TEMPRANA DOMICILIARIA EN LACTANTES Y NIÑOS PEQUEÑOS CON DISCAPACIDAD VISUAL USANDO EL DIARIO DE DESARROLLO: ESTUDIO LONGITUDINAL DE COHORTE: OBJETIVO: Investigar los efectos de la intervención temprana en el hogar en niños con discapacidad visual grave utilizando el Diario de Desarrollo para bebés y niños pequeños con discapacidad visual (DJVI). MÉTODO: Se realizó un estudio observacional longitudinal con una cohorte nacional (OPTIMUM) de bebés con trastornos congénitos del sistema visual periférico (CDPVS) y discapacidad visual profunda-severa; y seguimiento después de 12 meses y 24 meses. La intervención se categorizó de acuerdo con los registros del diario de desarrollo del médico en su práctica habitual más de 12 meses desde el inicio, comparando los que recibieron el DJVI y los que recibieron "otro apoyo". Se recopilaron las medidas de resultado de la cognición y el lenguaje, las dificultades de comportamiento, el estrés de los padres y la satisfacción con la asociación entre padres y profesionales. RESULTADOS: En los 54 niños (26 varones, 28 mujeres, edad media de referencia 13,5 meses, DS 2,3 meses, rango 8-17 meses) con CDPVS 'total' (incluidos 16 'complejo' y 38 'simple' con o sin trastorno cerebral conocido respectivamente), los efectos mixtos lineales apuntan hacia la aceleración en la comprensión sensoriomotora y el lenguaje expresivo, especialmente en la submuestra "simple" (cociente de desarrollo 11,72, intervalo de confianza del 95% -1,17 a 24,61, p>0,05) en los que recibieron el DJVI. El nivel de visión también predijo resultados (p <0,05). El grupo DJVI mostró mejoras en la abstinencia conductual (η2 =0,20, p=0,02, 'simple') y el estrés parental (d=0,78 − d=0,92, p=0,02 total y 'simple' respectivamente) y la relación percibida entre el médico y el padre (η2 =0,16, p=0,01). INTERPRETACIÓN: Los bebés y niños pequeños con discapacidad visual que recibieron una intervención temprana en el hogar utilizando el DJVI, con un enfoque de desarrollo estructurado, tuvieron mejores resultados que los que recibieron "otras" intervenciones tempranas en el hogar. Se encontraron mejoras de efecto moderado a grande en la cognición infantil y el lenguaje, el comportamiento y el estrés parental y la relación percibida entre el médico y el padre, aunque la cognición no alcanzó el nivel de significación del 5%.

INTERVENÇÃO PRECOCE DOMICILIAR EM LACTENTES E CRIANÇAS JOVENS COM DEFICIÊNCIA VISUAL USANDO O DEVELOPMENTAL JOURNAL: ESTUDO DE COORTE LONGITUDINAL: OBJETIVO: Investigar os efeitos da intervenção precoce domiciliar em crianças com deficiência visual severa usando o Developmental Journal para lactentes e crianças jovens com deficiência visual (DJDV). METODO: Um estudo observacional longitudinal foi realizado com uma coorte nacional (OPTIMUM) de crianças com distúrbios congênitos do sistema visual periférico (DCSVP) e deficiência visual grave-profunda, estes foram acompanhados após 12 meses e 24 meses. A intervenção foi categorizada de acordo com os registros diários do profissional de sua prática habitual ao longo de 12 meses, a partir de uma linha de base, comparando aqueles que receberam a DJDV e os que receberam "outro suporte". Resultados dos testes de cognição e linguagem, dificuldades de comportamento, estresse parental e satisfação com a parceria entre pais e profissionais, foram coletados. RESULTADOS: Nas 54 crianças (26 do sexo masculino e 28 do feminino, média de idade na linha de base de 13,5 meses; DP 2,3 meses; variação de 8 a 17 meses) com DCSVP total (incluindo 16 'complexos' e 38 'simples' com ou sem distúrbio cerebral conhecido, respectivamente), efeitos mistos lineares apontaram para um avanço na compreensão sensório-motora e de linguagem expressiva, especialmente, no subgrupo 'simples' (11,72 quociente de desenvolvimento, IC 95% -1,17 a 24,61; p>0,05) naqueles que receberam o DJDV. Nível visual também foi preditivo dos desfechos (p<0,05). O grupo DJDV apresentou melhora no comportamento de retraimento social (η2 =0,20; p=0,02; 'simples'), no estresse parental (d=0,78 − d=0,92; p=0,02 total e 'simples', respectivamente) e na percepção do relacionamento profissional-pais (η2 =0,16; p=0,01). INTERPRETAÇÃO: Lactentes e crianças jovens com deficiência visual que recebem intervenção domiciliar precoce usando a DJVI com uma abordagem de desenvolvimento estruturado tiveram resultados melhores do que aqueles que receberam "outras" intervenções precoces em casa. Melhorias com efeito de moderado a grande foram encontradas na cognição e linguagem, no comportamento infantil e estresse parental, e no relacionamento percebido entre pais e profissionais, embora a cognição não tenha alcançado nível de significância de 5%.

Adaptive behaviour and quality of life in school-age children with congenital visual disorders and different levels of visual impairment.

BACKGROUND: Adaptive behaviours are vital skills that allow individuals to function independently and are potentially amenable to behavioural interventions. Previous research indicated that adaptive behaviours are reduced in children and adolescents with severe to profound VI, but it was unclear if this was also the case for children with mild to moderate VI. AIM: The aim of the study was to assess differences in adaptive behaviour in children with congenital visual disorders and different levels of visual impairment and their influence on quality of life and everyday strengths and difficulties. METHODS AND PROCEDURES: Questionnaires about adaptive behaviour, strengths and difficulties, and quality of life were completed by parents of school-age children with severe-to-profound VI (S/PVI, n = 9, 0.9 logMAR - light perception only), mild-to-moderate VI (MVI, n = 9, 0.1-0.7 logMAR), or typical sight (control, n = 18, -0.3 to 0.1 logMAR). Differences in questionnaire domains by the severity of VI and relationships between adaptive behaviour and quality of life were analysed in general linear models. OUTCOMES AND RESULTS: The questionnaire ratings indicated reduced adaptive behaviour, more difficulties, and reduced quality of life in children with S/PVI compared to typically-sighted peers. Effects were smaller for children with MVI, but indicated a significant reduction in quality of life compared to typically-sighted children. The effect of visual impairment on quality of life in school was partially mediated by adaptive behaviour. CONCLUSION AND IMPLICATION: Severe congenital visual impairment affects adaptive behaviour in children with verbal abilities in the typical range. This effect is less pronounced in children with mild-to-moderate VI, but still impacts on quality of life, particularly in school.

Executive abilities in children with congenital visual impairment in mid-childhood.

The role of vision and vision deprivation in the development of executive function (EF) abilities in childhood is little understood; aspects of EF such as initiative, attention orienting, inhibition, planning and performance monitoring are often measured through visual tasks. Studying the development and integrity of EF abilities in children with congenital visual impairment (VI) may provide important insights into the development of EF and also its possible relationship with vision and non-visual senses. The current study investigates non-visual EF abilities in 18 school-age children of average verbal intelligence with VI of differing levels of severity arising from congenital disorders affecting the eye, retina, or anterior optic nerve. Standard auditory neuropsychological assessments of sustained and divided attention, phonemic, semantic and switching verbal fluency, verbal working memory, and ratings of everyday executive abilities by parents were undertaken. Executive skills were compared to age-matched typically-sighted (TS) typically-developing children and across levels of vision (mild to moderate VI [MVI] or severe to profound VI [SPVI]). The results do not indicate significant differences or deficits on direct assessments of verbal and auditory EF between the groups. However, parent ratings suggest difficulties with everyday executive abilities, with the greatest difficulties in those with SPVI. The findings are discussed as possibly reflecting increased demands of behavioral executive skills for children with VI in everyday situations despite auditory and verbal EF abilities in the typical range for their age. These findings have potential implications for clinical and educational practices.

Parenting stress, anxiety, and depression in mothers with visually impaired infants: a cross-sectional and longitudinal cohort analysis.

AIM: This study examined cross-sectional and longitudinal patterns of parenting stress, adult anxiety, and depression in mothers of children with profound or severe visual impairment (PVI or SVI) at 1 year and 2 years of age. METHOD: Mothers of a national longitudinal cohort (OPTIMUM Project) of infants with congenital disorders of the peripheral visual system and PVI (light perception at best) or SVI (basic 'form' vision of non-light reflecting objects) participated. Infant age at baseline (T1 ) was 8 to 16 months. Mothers completed the Parenting Stress Index - Short Form and the Hospital Anxiety and Depression Scale at T1 (n=79) and at follow-up 12 months later (T2 ) (n=73). RESULTS: Mothers of the total group had higher parenting stress levels (34.6% in clinical range) than community normative data at T1 (p=0.017). Mothers of infants in the PVI subgroup had elevated stress at T1 (p=0.014) and T2 (p=0.009). The PVI subgroup was also elevated in the Difficult Child subscale at T2 (p=0.001). Within-sample differences in parenting stress between the visual impairment subgroups were found at T2 only: the PVI subgroup scored higher than the SVI subgroup (p=0.029). Adult anxiety and depression in the total group were not elevated compared with community normative data at T1 and T2 ; however, higher parenting stress was related to raised adult anxiety and depression levels at T1 and T2 (p=0.001). Regression analysis found parenting stress and lower child vision level (T1 ) predicted parenting stress (T2 ) (p=0.001; 42% variance). INTERPRETATION: Mothers of 1-year-old infants with visual impairment showed raised risk for parenting stress, which continued to be elevated for children with PVI and those perceived as 'difficult' at 2 years. This was also a psychological risk, with greater adult anxiety and depression in those mothers with raised parenting stress. The clinical significance is that identification of parenting stress and targeted parenting, and behavioural support of the child in the first years of life is highly indicated. WHAT THIS PAPER ADDS: Mothers of infants with visual impairment are at increased risk of parenting stress. Parenting stress was higher in mothers of children with profound visual impairment than those with severe visual impairment. High levels of parenting stress and lower infant vision at 1 year of age predicted higher parenting stress at 2 years of age.

Is there consensus in defining childhood cerebral visual impairment? A systematic review of terminology and definitions.

The childhood condition of visual difficulties caused by brain damage, commonly termed cortical or cerebral visual impairment (CVI), is well established but has no internationally accepted definition. Clarification of its core features is required to advance research and clinical practice. This systematic review aimed to identify the definitions of childhood CVI in the original scientific literature to describe and critically appraise a consensual definition of the condition. MEDLINE, EMBASE, PsychINFO, CINAHL and AMED databases were searched in January 2017. Studies were included if they (1) were published original research, (2) contained a childhood CVI sample, (3) contained a definition of CVI and (4) described their CVI identification/diagnostic method. Thematic analysis identified concepts within definitions and narrative synthesis was conducted. Of 1150 articles, 51 met inclusion criteria. Definitions were subdivided according to detail (descriptive definition, description not reaching definition status and diagnostic/operationalising criteria). Three themes concerning visual deficits, eye health and brain integrity were identified (each containing subthemes) and analysed individually across definitions. The most common themes were 'visual impairment' (n=20), 'retrochiasmatic pathway damage'(n=13) and 'normal/near normal eye health' (n=15). The most consensual definition identified here may not be the best quality for advancing our understanding of CVI. We argue for the alternative definition: CVI is a verifiable visual dysfunction which cannot be attributed to disorders of the anterior visual pathways or any potentially co-occurring ocular impairment. We propose reporting guidelines to permit comparison across studies and increase the evidence base for more reliable clinical assessment and diagnosis.

Frontal EEG asymmetry and later behavior vulnerability in infants with congenital visual impairment.

OBJECTIVE: Young children with congenital visual impairment (VI) are at increased risk of behavioral vulnerabilities. Studies on 'at risk' populations suggest that frontal EEG asymmetry may be associated with behavioral risk. We investigated frontal asymmetry at 1year (Time 1), behavior at 2years (Time 2) and their longitudinal associations within a sample of infants with VI. Frontal asymmetry in the VI sample at 1year was also compared cross-sectionally to an age-matched typically sighted (TS) group. METHODS: At Time 1, 22 infants with VI and 10 TS infants underwent 128-channel EEG recording. Frontal asymmetry ratios were calculated from power spectral density values in the alpha frequency band. At Time 2, Achenbach Child Behavior Checklist data was obtained for the VI sample. RESULTS: 63.6% of the VI sample and 50% of the TS sample showed left frontal asymmetry; no significant difference in frontal asymmetry was found between the two groups. 22.7% of the VI sample had subclinical to clinical range 'internalizing' behavior difficulties. Greater left frontal asymmetry at one year was significantly associated with greater emotionally reactive scores at two years within the VI sample (r=0.50, p=0.02). CONCLUSIONS: Left frontal asymmetry correlates with later behavior risk within this vulnerable population. SIGNIFICANCE: These findings make an important first contribution regarding the utility of frontal EEG asymmetry as a method to investigate risk in infants with VI.

Event-related potential response to auditory social stimuli, parent-reported social communicative deficits and autism risk in school-aged children with congenital visual impairment.

Communication with visual signals, like facial expression, is important in early social development, but the question if these signals are necessary for typical social development remains to be addressed. The potential impact on social development of being born with no or very low levels of vision is therefore of high theoretical and clinical interest. The current study investigated event-related potential responses to basic social stimuli in a rare group of school-aged children with congenital visual disorders of the anterior visual system (globe of the eye, retina, anterior optic nerve). Early-latency event-related potential responses showed no difference between the VI and control group, suggesting similar initial auditory processing. However, the mean amplitude over central and right frontal channels between 280 and 320ms was reduced in response to own-name stimuli, but not control stimuli, in children with VI suggesting differences in social processing. Children with VI also showed an increased rate of autistic-related behaviours, pragmatic language deficits, as well as peer relationship and emotional problems on standard parent questionnaires. These findings suggest that vision may be necessary for the typical development of social processing across modalities.

Functional vision and cognition in infants with congenital disorders of the peripheral visual system.

AIM: To investigate how vision relates to early development by studying vision and cognition in a national cohort of 1-year-old infants with congenital disorders of the peripheral visual system and visual impairment. METHOD: This was a cross-sectional observational investigation of a nationally recruited cohort of infants with 'simple' and 'complex' congenital disorders of the peripheral visual system. Entry age was 8 to 16 months. Vision level (Near Detection Scale) and non-verbal cognition (sensorimotor understanding, Reynell Zinkin Scales) were assessed. Parents completed demographic questionnaires. RESULTS: Of 90 infants (49 males, 41 females; mean 13mo, standard deviation [SD] 2.5mo; range 7-17mo); 25 (28%) had profound visual impairment (light perception at best) and 65 (72%) had severe visual impairment (basic 'form' vision). The Near Detection Scale correlated significantly with sensorimotor understanding developmental quotients in the 'total', 'simple', and 'complex' groups (all p<0.001). Age and vision accounted for 48% of sensorimotor understanding variance. Infants with profound visual impairment, especially in the 'complex' group with congenital disorders of the peripheral visual system with known brain involvement, showed the greatest cognitive delay. INTERPRETATION: Lack of vision is associated with delayed early-object manipulative abilities and concepts; 'form' vision appeared to support early developmental advance. This paper provides baseline characteristics for cross-sectional and longitudinal follow-up investigations in progress. A methodological strength of the study was the representativeness of the cohort according to national epidemiological and population census data.

Story discourse and use of mental state language between mothers and school-aged children with and without visual impairment.

BACKGROUND: Lack of sight compromises insight into other people's mental states. Little is known about the role of maternal language in assisting the development of mental state language in children with visual impairment (VI). AIMS: To investigate mental state language strategies of mothers of school-aged children with VI and to compare these with mothers of comparable children with typically developing vision. To investigate whether the characteristics of mother-child discourse were associated with the child's socio-communicative competence. METHODS & PROCEDURES: Mother-child discourse with twelve 6-12-year-old children with VI was coded during a shared book-reading narrative and compared with 14 typically sighted children matched in age and verbal ability. OUTCOMES & RESULTS: Mothers of children with VI elaborated more and made significantly more references to story characters' mental states and descriptive elaborations than mothers of sighted children. Mental state elaborations of mothers in the VI group related positively with the level produced by their children, with the association remaining after mothers' overall verbosity and children's developmental levels were controlled for. Frequency of maternal elaborations, including their mental state language, was related to socio-communicative competence of children with VI. CONCLUSIONS & IMPLICATIONS: The findings offer insights into the potential contribution of maternal verbal scaffolding to mentalistic language and social-communicative competences of children with VI.

Reduced ventral cingulum integrity and increased behavioral problems in children with isolated optic nerve hypoplasia and mild to moderate or no visual impairment.

OBJECTIVES: To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified. PATIENTS AND METHODS: Eleven children with isolated optic nerve hypoplasia (mean age 5.9 years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11 of whom also completed behavioral assessments. Fractional anisotropy images were processed using tract-based spatial statistics. Partial correlation between ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and child behavioral checklist scores (controlled for age at scan and sex) was performed. RESULTS: Children with optic nerve hypoplasia had significantly higher scores on the child behavioral checklist (p<0.05) than controls (4 had scores in the clinically significant range). Ventral cingulum, corpus callosum and optic radiation fractional anisotropy were significantly reduced in children with optic nerve hypoplasia. Right ventral cingulum fractional anisotropy correlated with total and externalising child behavioral checklist scores (r = -0.52, p<0.02, r = -0.46, p<0.049 respectively). There were no significant correlations between left ventral cingulum, corpus callosum or optic radiation fractional anisotropy and behavioral scores. CONCLUSIONS: Our findings suggest that children with optic nerve hypoplasia and mild to moderate or no visual impairment require behavioral assessment to determine the presence of clinically significant behavioral problems. Reduced structural integrity of the ventral cingulum correlated with behavioral scores, suggesting that these white matter abnormalities may be clinically significant. The presence of reduced fractional anisotropy in the optic radiations of children with mild to moderate or no visual impairment raises questions as to the pathogenesis of these changes which will need to be addressed by future studies.

Effect of growth hormone deficiency on brain structure, motor function and cognition.

The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone <6.7 µg/l) and idiopathic short stature (peak growth hormone >10 µg/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth hormone deficiency [peak growth hormone <6.7 µg/l (mean 3.5 µg/l)] and 14 controls (mean 8.4 years of age) with idiopathic short stature [peak growth hormone >10 µg/l (mean 15 µg/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth hormone deficiency had lower Full-Scale IQ (P < 0.01), Verbal Comprehension Index (P < 0.01), Processing Speed Index (P < 0.05) and Movement-Assessment Battery for Children (P < 0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P < 0.03) and insulin-like growth factor binding protein-3 (P < 0.02) standard deviation scores in isolated growth hormone deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P < 0.01) were significantly smaller; and corticospinal tract (bilaterally; P < 0.045, P < 0.05) and corpus callosum (P < 0.05) fractional anisotropy were significantly lower in the isolated growth hormone deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and corpus callosum fractional anisotropy with Full-Scale IQ and Processing Speed Index. In patients with isolated growth hormone deficiency, white matter abnormalities in the corpus callosum and corticospinal tract, and reduced thalamic and globus pallidum volumes relate to deficits in cognitive function and motor performance. Follow-up studies that investigate the course of the structural and cognitive deficits on growth hormone treatment are now required to confirm that growth hormone deficiency impacts significantly on brain structure, cognitive function and motor performance.