Visual demands in primary school classrooms

Purpose To quantify the visual function requirements to perform in a primary school classroom setting. Methods 33 classrooms of Years 5 and 6 (children aged 10-12 years) from 8 schools were included. The classroom activities undertaken for a full day (9am-3pm) were observed and a range of measurements recorded; text size and contrast of learning materials, habitual working distances (distance and near) and time spent performing various classroom tasks. These measures were used to calculate demands for distance and near visual acuity, contrast and sustained use of accommodation and vergence. Results The minimum resolution requirements for distance and near were 0.3±0.1 and 0.7±0.1 logMAR (using maximum viewing distances and smallest target sizes). Mean contrast levels of learning materials at distance and near were >70% (an average contrast reserve of 25:1). Near tasks (47%) dominated the academic tasks performed in the classroom followed by distance (29%), distance to near (15%) and computer-based (9%). On average, children maintained continuous near fixation for 23.2±4.7 minutes at a time and during distance-near tasks performed fixation changes 10±0.9 times per minute. The mean habitual near working distance was 22.9±1.3 cm, which corresponds to a 4.4±0.2 D accommodative demand and the vergence demand was 0.9±0.1Δ at distance and 21.9±1.1 Δ at near assuming an average pupillary distance of 56 mm. Conclusions The visual demands placed on children in modern classrooms were greater than those reported for traditional classrooms, likely due to inclusion of modern technologies. Relatively high levels of visual acuity, contrast processing and sustained accommodative-convergence are required to perform optimally in the classroom environment. These findings are important for determining evidence-based prescribing guidelines and developing paediatric vision screening protocols and referral criterion

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Simulated hyperopic anisometropia and reading, visual information processing and reading-related eye movement performance in children

Purpose: This study investigated the impact of simulated hyperopic anisometropia and sustained near work on performance of academic-related measures in children. Methods: Participants included 16 children (mean age: 11.1 ± 0.8 years) with minimal refractive error. Academic-related outcome measures included a reading test (Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (Developmental Eye Movement test). Performance was assessed with and without 0.75 D of imposed monocular hyperopic defocus (administered in a randomised order), before and after 20 minutes of sustained near work. Unilateral hyperopic defocus was systematically assigned to either the dominant or non-dominant sighting eye to evaluate the impact of ocular dominance on any performance decrements. Results: Simulated hyperopic anisometropia and sustained near work both independently reduced performance on all of the outcome measures (p0.05). A reduction of up to 12% in performance was observed across the range of academic-related measures following sustained near work undertaken during the anisometropic simulation. Conclusion: Simulated hyperopic anisometropia significantly impaired academic–related performance, particularly in combination with sustained near work. The impact of uncorrected habitual anisometropia on academic-related performance in children requires further investigation

Combining ganglion cell topology and data of patients with glaucoma to determine a structure-function map

PURPOSE - To introduce techniques for deriving a map that relates visual field locations to optic nerve head (ONH) sectors and to use the techniques to derive a map relating Medmont perimetric data to data from the Heidelberg Retinal Tomograph. METHODS - Spearman correlation coefficients were calculated relating each visual field location (Medmont M700) to rim area and volume measures for 10 degrees ONH sectors (HRT III software) for 57 participants: 34 with glaucoma, 18 with suspected glaucoma, and 5 with ocular hypertension. Correlations were constrained to be anatomically plausible with a computational model of the axon growth of retinal ganglion cells (Algorithm GROW). GROW generated a map relating field locations to sectors of the ONH. The sector with the maximum statistically significant (P RESULTS - The model of axon growth produced a 24-2 map that is qualitatively similar to existing maps derived from empiric data. When GROW was used in conjunction with normative data, 31% of field locations exhibited a statistically significant relationship. This significance increased to 67% (z-test, z = 4.84; P CONCLUSIONS - A computational model of axon growth and normalizing data by the fellow eye can assist in constructing an anatomically plausible map connecting visual field data and sectoral ONH data

A visual profile of Queensland Indigenous children

Purpose Little is known about the prevalence of refractive error, binocular vision, and other visual conditions in Australian Indigenous children. This is important given the association of these visual conditions with reduced reading performance in the wider population, which may also contribute to the suboptimal reading performance reported in this population. The aim of this study was to develop a visual profile of Queensland Indigenous children. Methods Vision testing was performed on 595 primary schoolchildren in Queensland, Australia. Vision parameters measured included visual acuity, refractive error, color vision, nearpoint of convergence, horizontal heterophoria, fusional vergence range, accommodative facility, AC/A ratio, visual motor integration, and rapid automatized naming. Near heterophoria, nearpoint of convergence, and near fusional vergence range were used to classify convergence insufficiency (CI). Results Although refractive error (Indigenous, 10%; non-Indigenous, 16%; p = 0.04) and strabismus (Indigenous, 0%; non-Indigenous, 3%; p = 0.03) were significantly less common in Indigenous children, CI was twice as prevalent (Indigenous, 10%; non-Indigenous, 5%; p = 0.04). Reduced visual information processing skills were more common in Indigenous children (reduced visual motor integration [Indigenous, 28%; non-Indigenous, 16%; p < 0.01] and slower rapid automatized naming [Indigenous, 67%; non-Indigenous, 59%; p = 0.04]). The prevalence of visual impairment (reduced visual acuity) and color vision deficiency was similar between groups. Conclusions Indigenous children have less refractive error and strabismus than their non-Indigenous peers. However, CI and reduced visual information processing skills were more common in this group. Given that vision screenings primarily target visual acuity assessment and strabismus detection, this is an important finding as many Indigenous children with CI and reduced visual information processing may be missed. Emphasis should be placed on identifying children with CI and reduced visual information processing given the potential effect of these conditions on school performanc

Foveal contrast processing of increment and decrement targets is equivalently reduced in glaucoma

Background:&nbsp;Psychophysical measurement of the function of individual precortical visual pathways (magnocellular, parvocellular and koniocellular) has enabled the development of sensitive tests for glaucoma and has enhanced understanding of its pathophysiology. Such pathways can be further subdivided into their &ldquo;On&rdquo; and &ldquo;Off&rdquo; components, which have anatomical and physiological asymmetries. This study investigated whether On and Off subdivisions of the magnocellular (M) pathway are differentially affected by glaucoma.Methods: 20 participants with glaucoma and 20 controls underwent two psychophysical procedures that have been shown to assess the M pathway (steady pedestal task) and its On and Off subdivisions (pedestal-delta-pedestal task) respectively. Luminance discrimination thresholds were measured foveally, using both increment and decrement stimuli.Results: The steady pedestal (undifferentiated M-pathway) task separated the glaucoma and control groups (p = 0.04) with equivalent outcomes for increment and decrement targets. The pedestal-delta-pedestal task (isolated On and Off M-pathway subdivisions) also differentiated between groups (p = 0.025), but the outcome was not dependent on which subdivision was isolated.Conclusions: This study found that increment and decrement targets can be used with equal effectiveness for detecting contrast processing deficits in early glaucoma. Outcomes further suggested that glaucoma affects On and Off subdivisions of the M-pathway equivalently.</div

Contrast sensitivity changes due to glaucoma and normal aging: Low-spatial-frequency losses in both magnocellular and parvocellular pathways

PURPOSE - To explore the effects of glaucoma and aging on low-spatial-frequency contrast sensitivity by using tests designed to assess performance of either the magnocellular (M) or parvocellular (P) visual pathways. METHODS - Contrast sensitivity was measured for spatial frequencies of 0.25 to 2 cyc/deg by using a published steady- and pulsed-pedestal approach. Sixteen patients with glaucoma and 16 approximately age-matched control subjects participated. Patients with glaucoma were tested foveally and at two midperipheral locations: (1) an area of early visual field loss, and (2) an area of normal visual field. Control subjects were assessed in matched locations. - An additional group of 12 younger control subjects (aged 20-35 years) were also tested. RESULTS - Older control subjects demonstrated reduced sensitivity relative to the younger group for the steady (presumed M)- and pulsed (presumed P)-pedestal conditions. Sensitivity was reduced foveally and in the midperiphery across the spatial frequency range. In the area of early visual field loss, the glaucoma group demonstrated further sensitivity reduction relative to older control subjects across the spatial frequency range for both the steady- and pulsed-pedestal tasks. Sensitivity was also reduced in the midperipheral location of "normal" visual field for the pulsed condition. CONCLUSIONS - Normal aging results in a reduction of contrast sensitivity for the low-spatial-frequency-sensitive components of both the M and P pathways. Glaucoma results in a further reduction of sensitivity that is not selective for M or P function. The low-spatial-frequency-sensitive channels of both pathways, which are presumably mediated by cells with larger receptive fields, are approximately equivalently impaired in early glaucoma