Study of Optimal Perimetric Testing In Children (OPTIC): Development and feasibility of the kinetic perimetry reliability measure (KPRM)

INTRODUCTION: Interpretation of perimetric findings, particularly in children, relies on accurate assessment of test reliability, yet no objective measures of reliability exist for kinetic perimetry. We developed the kinetic perimetry reliability measure (KPRM), a quantitative measure of perimetric test reproducibility/reliability and report here its feasibility and association with subjective assessment of reliability. METHODS: Children aged 5-15 years, without an ophthalmic condition that affects the visual field, were recruited from Moorfields Eye Hospital and underwent Goldmann perimetry as part of a wider research programme on perimetry in children. Subjects were tested with two isopters and the blind spot was plotted, followed by a KPRM. Test reliability was also scored qualitatively using our examiner-based assessment of reliability (EBAR) scoring system, which standardises the conventional clinical approach to assessing test quality. The relationship between KPRM and EBAR was examined to explore the use of KPRM in assessing reliability of kinetic fields. RESULTS: A total of 103 children (median age 8.9 years; IQR: 7.1 to 11.8 years) underwent Goldmann perimetry with KPRM and EBAR scoring. A KPRM was achieved by all children. KPRM values increased with reducing test quality (Kruskal-Wallis, p=0.005), indicating greater testretest variability, and reduced with age (linear regression, p=0.015). One of 103 children (0.97%) demonstrated discordance between EBAR and KPRM. CONCLUSION: KPRM and EBAR are distinct but complementary approaches. Though scores show excellent agreement, KPRM is able to quantify withintest variability, providing data not captured by subjective assessment. Thus, we suggest combining KPRM with EBAR to aid interpretation of kinetic perimetry test reliability in children

A Common Glaucoma-risk Variant of SIX6 Alters Retinal Nerve Fiber Layer and Optic Disc Measures in a European Population: The EPIC-Norfolk Eye Study

PURPOSE: A common missense variant in the SIX6 gene (rs33912345) is strongly associated with primary open-angle glaucoma (POAG). We aimed to examine the association of rs33912345 with optic disc and retinal nerve fiber layer (RNFL) measures in a European population. METHODS: We examined participants of the population-based EPIC-Norfolk Eye Study. Participants underwent confocal laser scanning tomography (Heidelberg Retina Tomograph II, HRT) to estimate optic disc rim area and vertical cup-disc ratio (VCDR). Scanning laser polarimetry (GDxVCC) was used to estimate average RNFL thickness. The mean of right and left eye values was considered for each participant. Genotyping was performed using the Affymetrix UK Biobank Axiom Array. Multivariable linear regression with the optic nerve head parameter as outcome variable and dosage of rs33912345 genotype as primary explanatory variable was used, adjusted for age, sex, disc area, axial length and intraocular pressure. We further repeated analyses stratified into age tertiles. RESULTS: In total, 5433 participants with HRT data and 3699 participants with GDxVCC data were included. Each "C" allele of rs33912345 was associated with a smaller rim area (-0.030▒mm [95% CI -0.040, -0.020], P=5.4×10), a larger VCDR (0.025 [95% CI 0.017, 0.033], P=3.3×10) and a thinner RNFL (-0.39▒μm [95% CI -0.62, -0.15], P=0.001). The RNFL association was strongest in the oldest age tertile, whereas rim area and VCDR associations were strongest in the youngest and oldest age tertiles. CONCLUSIONS: The protein coding SIX6 variant rs33912345, previously associated with POAG, has a functional effect on glaucoma-associated optic nerve head traits in Europeans

Assessing the outcomes of participatory research: protocol for identifying, selecting, appraising and synthesizing the literature for realist review

<p>Abstract</p> <p>Background</p> <p>Participatory Research (PR) entails the co-governance of research by academic researchers and end-users. End-users are those who are affected by issues under study (<it>e.g.</it>, community groups or populations affected by illness), or those positioned to act on the knowledge generated by research (<it>e.g.</it>, clinicians, community leaders, health managers, patients, and policy makers). Systematic reviews assessing the generalizable benefits of PR must address: the diversity of research topics, methods, and intervention designs that involve a PR approach; varying degrees of end-user involvement in research co-governance, both within and between projects; and the complexity of outcomes arising from long-term partnerships.</p> <p>Methods</p> <p>We addressed the above mentioned challenges by adapting realist review methodology to PR assessment, specifically by developing inductively-driven identification, selection, appraisal, and synthesis procedures. This approach allowed us to address the non-uniformity and complexity of the PR literature. Each stage of the review involved two independent reviewers and followed a reproducible, systematic coding and retention procedure. Retained studies were completed participatory health interventions, demonstrated high levels of participation by non-academic stakeholders (<it>i.e.</it>, excluding studies in which end-users were not involved in co-governing throughout the stages of research) and contained detailed descriptions of the participatory process and context. Retained sets are being mapped and analyzed using realist review methods.</p> <p>Results</p> <p>The librarian-guided search string yielded 7,167 citations. A total of 594 citations were retained after the identification process. Eighty-three papers remained after selection. Principle Investigators (PIs) were contacted to solicit all companion papers. Twenty-three sets of papers (23 PR studies), comprising 276 publications, passed appraisal and are being synthesized using realist review methods.</p> <p>Discussion</p> <p>The systematic and stage-based procedure addressed challenges to PR assessment and generated our robust understanding of complex and heterogeneous PR practices. To date, realist reviews have focussed on evaluations of relatively uniform interventions. In contrast our PR search yielded a wide diversity of partnerships and research topics. We therefore developed tools to achieve conceptual clarity on the PR field, as a beneficial precursor to our theoretically-driven synthesis using realist methods. Findings from the ongoing review will be provided in forthcoming publications.</p

A population-based cohort study on sun habits and endometrial cancer

Background:No large cohort study has examined the risk of endometrial cancer in relation to sun exposure.Methods:A population-based cohort study of 29 508 women who answered a questionnaire in 1990-92, of whom 24 098 responded to a follow-up enquiry in 2000-02. They were followed for an average of 15.5 years.Results:Among the 17 822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. We used a multivariate Cox regression analysis adjusting for age and other selected demographic variables to determine the risk of endometrial cancer. Women using sun beds >3 times per year reduced their hazard risk (HR) by 40% (0.6, 95% confidence interval (CI) 0.4-0.9) or by 50% when adjusting for body mass index or physical activity (HR 0.5, 95% CI 0.3-0.9), and those women who were sunbathing during summer reduced their risk by 20% (HR 0.8 95% CI 0.5-1.5) compared with women who did not expose themselves to the sun or to artificial sun (i.e., sun beds).Conclusion:Exposure to artificial sun by the use of sun beds >3 times per year was associated with a 40% reduction in the risk of endometrial cancer, probably by improving the vitamin D levels during winter.British Journal of Cancer advance online publication, 23 June 2009; doi:10.1038/sj.bjc.6605149 www.bjcancer.com

Active microrheology and simultaneous visualization of sheared phospholipid monolayers

Two-dimensional films of surface-active agents—from phospholipids and proteins to nanoparticles and colloids—stabilize fluid interfaces, which are essential to the science, technology and engineering of everyday life. The 2D nature of interfaces present unique challenges and opportunities: coupling between the 2D films and the bulk fluids complicates the measurement of surface dynamic properties, but allows the interfacial microstructure to be directly visualized during deformation. Here we present a novel technique that combines active microrheology with fluorescence microscopy to visualize fluid interfaces as they deform under applied stress, allowing structure and rheology to be correlated on the micron-scale in monolayer films. We show that even simple, single-component lipid monolayers can exhibit viscoelasticity, history dependence, a yield stress and hours-long time scales for elastic recoil and aging. Simultaneous visualization of the monolayer under stress shows that the rich dynamical response results from the cooperative dynamics and deformation of liquid-crystalline domains and their boundaries

Reliability of the TekScan MatScan® system for the measurement of plantar forces and pressures during barefoot level walking in healthy adults

<p>Abstract</p> <p>Background</p> <p>Plantar pressure systems are increasingly being used to evaluate foot function in both research settings and in clinical practice. The purpose of this study was to investigate the reliability of the TekScan MatScan^®system in assessing plantar forces and pressures during barefoot level walking.</p> <p>Methods</p> <p>Thirty participants were assessed for the reliability of measurements taken one week apart for the variables maximum force, peak pressure and average pressure. The following seven regions of the foot were investigated; heel, midfoot, 3^rd-5^thmetatarsophalangeal joint, 2^ndmetatarsophalangeal joint, 1^stmetatarsophalangeal joint, hallux and the lesser toes.</p> <p>Results</p> <p>Reliability was assessed using both the mean and the median values of three repeated trials. The system displayed moderate to good reliability of mean and median calculations for the three analysed variables across all seven regions, as indicated by intra-class correlation coefficients ranging from 0.44 to 0.95 for the mean and 0.54 to 0.97 for the median, and coefficients of variation ranging from 5 to 20% for the mean and 3 to 23% for the median. Selecting the median value of three repeated trials yielded slightly more reliable results than the mean.</p> <p>Conclusions</p> <p>These findings indicate that the TekScan MatScan^®system demonstrates generally moderate to good reliability.</p

Specification of progression in glaucomatous visual field loss, applying locally condensed stimulus arrangements

The goal of this work was to (i) determine patterns of progression in glaucomatous visual field loss, (ii) compare the detection rate of progression between locally condensed stimulus arrangements and conventional 6° × 6° grid, and (iii) assess the individual frequency distribution of test locations exhibiting a local event (i.e., an abrupt local deterioration of differential luminance sensitivity (DLS) by more than -10dB between any two examinations). The visual function of 41 glaucomatous eyes of 41 patients (16 females, 25 males, 37 to 75 years old) was examined with automated static perimetry (Tuebingen Computer Campimeter or Octopus 101-Perimeter). Stimuli were added to locally enhance the spatial resolution in suspicious regions of the visual field. The minimum follow-up was four subsequent sessions with a minimum of 2-month (median 6-month) intervals between each session. Progression was identified using a modified pointwise linear regression (PLR) method and a modified Katz criterion. The presence of events was assessed in all progressive visual fields. Eleven eyes (27%) showed progression over the study period (median 2.5 years, range 1.3–8.6 years). Six (55%) of these had combined progression in depth and size and five eyes (45%) progressed in depth only. Progression in size conformed always to the nerve fiber course. Seven out of 11 (64%) of the progressive scotomata detected by spatially condensed grids would have been missed by the conventional 6° × 6° grid. At least one event occurred in 64% of all progressive eyes. Five of 11 (46%) progressive eyes showed a cluster of events. The most common pattern of progression in glaucomatous visual fields is combined progression in depth and size of an existing scotoma. Applying individually condensed test grids remarkably enhances the detection rate of glaucomatous visual field deterioration (at the expense of an increased examination time) compared to conventional stimulus arrangements

Eye movements and reading in glaucoma: observations on patients with advanced visual field loss

Purpose To investigate the relationship between reading speed and eye movements in patients with advanced glaucomatous visual field (VF) defects and age-similar visually healthy people. Methods Eighteen patients with advanced bilateral VF defects (mean age: 71, standard deviation [SD]: 7 years) and 39 controls (mean age: 67, SD: 8 years) had reading speed measured using short passages of text on a computer set-up incorporating eye tracking. Scanpaths were plotted and analysed from these experiments to derive measures of ‘perceptual span’ (total number of letters read per number of saccades) and ‘text saturation’ (the distance between the first and last fixation on lines of text). Another eye movement measure, termed ‘saccadic frequency’ (total number of saccades made to read a single word), was derived from a separate lexical decision task, where words were presented in isolation. Results Significant linear association was demonstrated between perceptual span and reading speed in patients (R2=0.42) and controls (R2=0.56). Linear association between saccadic frequency during the LDT and reading speed was also found in patients (R2=0.42), but not in controls (R2=0.02). Patients also exhibited greater average text saturation than controls (P=0.004). Conclusion Some, but not all, patients with advanced VF defects read slower than controls using short text passages. Differences in eye movement behaviour may partly account for this variability in patients. These patients were shown to saturate lines of text more during reading, which may explain previously-reported difficulties with sustained reading

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

ROBINS-I: a tool for assessing risk of bias in non-randomized studies of interventions

Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I ("Risk Of Bias In Non-randomised Studies-of Interventions"), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies