Visual Axis Opacity after Intraocular Lens Implantation in Children in the First 2 Years of Life: Findings from the IoLunder2 Cohort Study

Objective/ Purpose: Appropriate correction of aphakia is key to good outcomes. There may be clinical settings and populations where accessing or managing aphakic contact lenses is challenging. Strategies to target the increased risk of visual axis opacity (VAO) following primary IoL implantation in infancy are necessary. We describe the predictors of VAO following primary IoL implantation for unilateral or bilateral congenital or infantile cataract in children aged under 2 years. / Design: Population based (UK and Ireland) prospective inception cohort study undertaken through a national clinical network. / Participants: 105 children (57 bilateral cataract, 48 unilateral, total 162 eyes) undergoing primary IoL implantation in the first two years of life between January 2009 and December 2010. / Methods: Observational longitudinal study with multilevel, multivariable modelling to investigate associations between outcome of interest, and child and treatment specific factors including age, axial length, socioeconomic status, IoL model, and post operative steroid use. / Main outcome measures: Post operative proliferative and / or inflammatory visual axis opacity (VAO) requiring surgical correction. / Results: Visual axis opacity occurred in 67 eyes (45%), typically within the first post-operative year. Use of a three piece IoL model (odds ratio/OR 0.3, 95% confidence interval/CI 0.09 – 0.99, p=0.03), and increasing age at surgery (OR 0.97, 95% CI 0.95-0.99, p=0.02), were each independently protective against the development of proliferative VAO. Inflammatory VAO was independently associated with socioeconomic deprivation (OR 5.39, 95%CI 1.46 – 19.89, p=0.01). / Conclusions: Visual axis opacification is common following IoL implantation in early childhood. The findings of this prospective cohort study suggest that the use of three piece IoL models may reduce the risk of pseudophakic VAO in children aged under 2 years

Epidemiology of blindness in children

An estimated 1.4 million of the world’s children are blind. A blind child is more likely to live in socioeconomic deprivation, to be more frequently hospitalised during childhood and to die in childhood than a child not living with blindness. This update of a previous review on childhood visual impairment focuses on emerging therapies for children with severe visual disability (severe visual impairment and blindness or SVI/BL). For children in higher income countries, cerebral visual impairment and optic nerve anomalies remain the most common causes of SVI/BL, while retinopathy of prematurity (ROP) and cataract are now the most common avoidable causes. The constellation of causes of childhood blindness in lower income settings is shifting from infective and nutritional corneal opacities and congenital anomalies to more resemble the patterns seen in higher income settings. Improvements in maternal and neonatal health and investment in and maintenance of national ophthalmic care infrastructure are the key to reducing the burden of avoidable blindness. New therapeutic targets are emerging for childhood visual disorders, although the safety and efficacy of novel therapies for diseases such as ROP or retinal dystrophies are not yet clear. Population-based epidemiological research, particularly on cerebral visual impairment and optic nerve hypoplasia, is needed in order to improve understanding of risk factors and to inform and support the development of novel therapies for disorders currently considered ‘untreatable’

Temporal Trends in Childhood Uveitis: Using Administrative Health Data to Investigate the Impact of Health Policy and Clinical Practice

Background: We describe an investigation of temporal trends in the incidence of childhood uveitis-related hospital admissions, hospitalization being a robust indicator of disease severity. Methods: A population-based retrospective study using a hospitalization database, the Hospital Episode Statistics (HES) dataset, capturing data on care between 2013 and 2020. Primary outcomes were rates of pediatric hospital admissions for uveitis-related disorders. Results: During the study period, there were 3,258 reported uveitis-related hospital admissions of children aged 0 to 14 years, comprising 19% of all-age uveitis-related admissions. Anterior uveitis was the most common diagnosis. The annual incidence of childhood uveitis-related hospitalizations declined year on year from a peak incidence of 5.4 per 100,000 children (95% confidence interval 5.0–5.9) in 2015–2016 to 3.3 per 100,000 (95% CI 3.0–3.6) in 2019–2020. Over the same period, the national incidence of juvenile arthropathy-related admissions stayed stable. Conclusion: The decline in admissions nationally may reflect reduced incidence of uveitis complications with increasing use of immunosuppressive therapies

Visual impairment, severe visual impairment, and blindness in children in Britain (BCVIS2): a national observational study

Background: The WHO VISION 2020 global initiative against blindness, launched in 2000, prioritised childhood visual disability by aiming to end avoidable childhood blindness by 2020. However, progress has been hampered by the global paucity of epidemiological data concerning childhood visual disability. The British Childhood Visual Impairment and Blindness Study 2 (BCVIS2) was done to address this evidence gap. Methods: BCVIS2 was a prospective UK-wide, cross-sectional, observational study to establish an inception cohort of children newly diagnosed with visual impairment. Ophthalmologists and paediatricians reported cases from 89 hospitals and community centres across the UK. We included children aged 18 years or younger who were newly diagnosed with any condition causing impaired visual acuity to a level of 0·5 logMAR or worse (worse than 6/18 Snellen) in each eye, or equivalent vision as assessed by standard qualitative measures, between Oct 1, 2015, and Nov 1, 2016. Eligible children were notified simultaneously but independently by their managing ophthalmologists and paediatricians via the two national active surveillance schemes, the British Ophthalmological Surveillance Unit and the British Paediatric Surveillance Unit. Standardised detailed demographic, socioeconomic, and clinical data about detection, management, and treatment were collected at diagnosis and 1 year later. We calculated incidence estimates and relative rates by key sociodemographic factors. We did descriptive analyses of underlying ophthalmic disorders and non-ophthalmic comorbidities. Findings: 61 (7%) of 845 eligible children initially notified were ineligible at follow-up because of improved vision after treatment. Thus, the study sample comprised 784 children with permanent newly-diagnosed all-cause visual impairment, severe visual impairment, or blindness. 559 (72%) of 778 children had clinically significant non-ophthalmic impairments or conditions. 28 (4%) of 784 children died within a year after diagnosis of visual disability (all had underlying systemic disorders). Incidence of visual disability in the first year of life was 5·19 per 10 000 children (95% CI 4·71–5·72), almost ten times higher than among 1-to-4-year-olds and between 20 times and 100 times higher than in the older age groups. The overall cumulative incidence (or lifetime risk) of visual impairment, severe visual impairment, or blindness was 10·03 per 10 000 children (9·35–10·76). Incidence rates were higher for those from any ethnic minority group, the lowest quintile of socioeconomic status, and those born preterm or with low birthweight. 345 (44%) of 784 children had a single affected anatomical site. Disorders of the brain and visual pathways affected 378 (48%) of 784 children. Interpretation: BCVIS2 provides a contemporary snapshot of the heterogeneity, multi-morbidity, and vulnerability associated with childhood visual disability in a high-income country. These findings could facilitate developing and delivering health care and planning of interventional research. Our findings highlight the importance of including childhood visual disability as a sentinel event and metric in global child health initiatives. Funding: Fight for Sight, National Institute for Health Research, and Ulverscroft Foundation

Impact of persisting amblyopia on socio–economic, health and well–being outcomes in adult life: findings from the UK Biobank study

Objectives: This study aimed to investigate associations between persisting amblyopia into adulthood and its “real-life” impacts and inform the current debate about the value of childhood vision screening programs. Methods: Associations between persisting amblyopia and diverse socioeconomic, health, and well-being outcomes were investigated in multivariable-adjusted (sex, age, ethnicity, deprivation) regression models, with 126 400 participants (aged 40-70 years) of the UK Biobank with complete ophthalmic data. Analysis by age group (cohort 1, 60-70 years; cohort 2, 50-59 years; cohort 3, 40-49 years) assessed temporal trends. Results: Of 3395 (3%) participants with confirmed amblyopia, overall 77% (2627) had persisting amblyopia, declining from 78% in cohort 1 to 73% in cohort 3. The odds of persisting amblyopia were 5.91 (5.24-6.66) and 2.49 (2.21-2.81) times greater in cohort 1 and cohort 2, respectively, than cohort 3. The odds were also higher for more socioeconomically deprived groups and for white ethnicity. Reduced participation in sport, adverse general and mental health, and well-being were all independently associated with persisting amblyopia, with the strongest associations in the youngest cohorts. Associations with lower educational attainment and economic outcomes were only evident in the oldest cohort. Conclusions: There has been a decline in the overall frequency of persisting amblyopia since the introduction of universal child vision screening in the United Kingdom. Nevertheless, most adults treated for amblyopia in childhood have persisting vision deficits. There was no evidence that persisting amblyopia has vision-mediated effects on educational, employment-related, or economic outcomes. The observed adverse outcomes were largely those not directly mediated by vision. Patients undergoing treatment should be counseled about long-term outcomes

The Combined Impact Of IgLON Family Proteins Lsamp And Neurotrimin On Developing Neurons And Behavioral Profiles In Mouse

Cell surface neural adhesion proteins are critical components in the complex orchestration of cell proliferation, apoptosis, and neuritogenesis essential for proper brain construction and behavior. We focused on the impact of two plasticity-associated IgLON family neural adhesion molecules, Neurotrimin (Ntm) and Limbic system associated membrane protein (Lsamp), on mouse behavior and its underlying neural development. Phenotyping neurons derived from the hippocampi of Lsamp−/−, Ntm−/− and Lsamp−/−Ntm−/− mice was performed in parallel with behavioral testing. While the anatomy of mutant brains revealed no gross changes, the Ntm−/− hippocampal neurons exhibited premature sprouting of neurites and manifested accelerated neurite elongation and branching. We propose that Ntm exerts an inhibitory impact on neurite outgrowth, whereas Lsamp appears to be an enhancer of the said process as premature neuritogenesis in Ntm−/− neurons is apparent only in the presence of Lsamp. We also show interplay between Lsamp and Ntm in regulating tissue homeostasis: the impact of Ntm on cellular proliferation was dependent on Lsamp, and Lsamp appeared to be a positive regulator of apoptosis in the presence of Ntm. Behavioral phenotyping indicated test-specific interactions between Lsamp and Ntm. The phenotypes of single mutant lines, such as reduced swimming speed in Morris water maze and increased activity in the elevated plus maze, were magnified in Lsamp−/−Ntm−/− mice. Altogether, evidence both from behavioral experiments and cultured hippocampal cells show combined and differential interactions between Ntm and Lsamp in the formation of hippocampal circuits and behavioral profiles. We demonstrate that mutual interactions between IgLON molecules regulate the initiation of neurite sprouting at very early ages, and even cell-autonomously, independent of their regulation of cell-cell adhesion

Physical Activity and Hippocampal Sub-Region Structure in Older Adults with Memory Complaints.

BackgroundPhysical activity (PA) plays a major role in maintaining cognition in older adults. PA has been shown to be correlated with total hippocampal volume, a memory-critical region within the medial temporal lobe (MTL). However, research on associations between PA and MTL sub-region integrity is limited.ObjectiveTo examine the relationship between PA, MTL thickness, and its sub-regions, and cognitive function in non-demented older adults with memory complaints.MethodsTwenty-nine subjects aged ≥60 years, with memory complaints were recruited for this cross-sectional study. PA was tracked for 7 days using accelerometers, and average number of steps/day determined. Subjects were categorized into two groups: those who walked ≤4000 steps/day (lower PA) and those with >4000 steps/day (higher PA). Subjects received neuropsychological testing and 3T MRI scans. Nonparametric ANCOVAs controlling for age examined differences between the two groups.ResultsTwenty-six subjects aged 72.7(8.1) years completed the study. The higher PA group (n = 13) had thicker fusiform gyrus (median difference = 0.11 mm, effect size (ES) = 1.43, p = 0.001) and parahippocampal cortex (median difference = 0.12 mm, ES = 0.93, p = 0.04) compared to the lower PA group. The higher PA group also exhibited superior performance in attention and information-processing speed (median difference = 0.90, ES = 1.61, p = 0.003) and executive functioning (median difference = 0.97, ES = 1.24, p = 0.05). Memory recall was not significantly different between the two groups.ConclusionOlder non-demented individuals complaining of memory loss who walked >4000 steps each day had thicker MTL sub-regions and better cognitive functioning than those who walked ≤4000 steps. Future studies should include longitudinal analyses and explore mechanisms mediating hippocampal related atrophy

Casimir force between sharp-shaped conductors

Casimir forces between conductors at the sub-micron scale cannot be ignored in the design and operation of micro-electromechanical (MEM) devices. However, these forces depend non-trivially on geometry, and existing formulae and approximations cannot deal with realistic micro-machinery components with sharp edges and tips. Here, we employ a novel approach to electromagnetic scattering, appropriate to perfect conductors with sharp edges and tips, specifically to wedges and cones. The interaction of these objects with a metal plate (and among themselves) is then computed systematically by a multiple-scattering series. For the wedge, we obtain analytical expressions for the interaction with a plate, as functions of opening angle and tilt, which should provide a particularly useful tool for the design of MEMs. Our result for the Casimir interactions between conducting cones and plates applies directly to the force on the tip of a scanning tunneling probe; the unexpectedly large temperature dependence of the force in these configurations should attract immediate experimental interest

Vision screening in children:a retrospective study of social and demographic factors with regard to visual outcomes

BACKGROUND: Amblyopia and its risk factors have been demonstrated to be more common among children from low socioeconomic backgrounds. We sought to investigate this association in a region with orthoptic-delivered screening and whole population coverage, and to also examine the association of the Health Plan Indicator (HPI) with screening outcome. METHODS: Screening examination outcomes, postcodes and HPIs were extracted from the community child health database for every child who underwent preschool vision screening between March 2010 and February 2011 Tayside. We obtained the Scottish Index of Multiple Deprivation score for every child as a measure of area-based deprivation. We assessed the vulnerability/needs of the individual family through the HPI—‘Core’ (children and families receiving universal health visiting service), ‘Additional’ (receiving additional health/social support) and ‘Intensive’ (receiving high levels of support). The outcomes from follow-up examinations for those who failed screening were extracted from the orthoptic department database. RESULTS: 4365 children were screened during the year 2010–2011 of whom 523 (11.9%) failed. The odds of children from the least deprived socioeconomic group passing the visual screening test was 1.4 times higher than those from the most deprived socioeconomic group (OR 1.4, 95% CI 1.07 to 1.89, p=0.01). The odds of a child from a family assigned as ‘Intensive’ failing the preschool visual screening test was three times greater than the odds of a child from a family assigned as ‘Core’ (OR 3.59, 95% CI 1.6 to 7.8, p=0.001). CONCLUSIONS: We found that children from the most deprived backgrounds and those from unstable homes were more likely to fail preschool vision screening