MOSAIC Clinical Trial Statistical Analysis Plan Primary Analysis v1.2

The Myopia Outcome Study of Atropine Treatment in Children (MOSAIC) is an investigator-led, double-masked randomised controlled trial of nightly atropine 0.01% eye drops compared to nightly placebo eye drops. A previously published protocol paper outlines the rationale, objective and sample size calculation for the study.1 A total of 250 participants were enrolled in the study and were randomised 2:1 to active treatment and placebo, respectively. This document outlines the plan for analysis of the 24-month outcomes of the MOSAIC

Will treating progressive myopia overwhelm the eye care workforce? A workforce modelling study

Purpose Treatments for myopia progression are now available, but implementing these into clinical practice will place a burden on the eye care workforce. This study estimated the full-time equivalent (FTE) workforce required to implement myopia control treatments in the UK and Ireland. Methods To estimate the number of 6- to 21-year-olds with myopia, two models utilising separate data sources were developed. The examination-based model used: (1) the number of primary care eye examinations conducted annually and (2) the proportion of these that are for myopic young people. The prevalence-based model used epidemiological data on the age-specific prevalence of myopia. The proportion of myopic young people progressing ≥0.25 dioptres (D)/year or ≥0.50 D/year was obtained from Irish electronic health records and the recommended review schedule from clinical management guidelines. Results Using the examination and prevalence models, respectively, the estimated number of young people with myopia was 2,469,943 and 2,235,713. The extra workforce required to provide comprehensive myopia management for this target population was estimated at 226–317 FTE at the 0.50 D/year threshold and 433–630 FTE at the 0.25 D/year threshold. Extra visits required for myopia control treatment represented approximately 2.6% of current primary eye care examinations versus 13.6% of hospital examinations. Conclusions Implementing new myopia control treatments in primary care settings over the medium-term is unlikely to overwhelm the eye care workforce completely. Further increases to workforce, upskilling of current workforce and tools to reduce chair time will help to ensure sustainability of the eye care workforce into the future

Choroidal Thickness Profiles and Associated Factors in Myopic Children

SIGNIFICANCE: This study addresses the lack of choroidal thickness (ChT) profile information available in European children and provides a baseline for further evaluation of longitudinal changes in ChT profiles in myopic children as a potential biomarker for myopia treatment and identifying children at risk of myopic progression. PURPOSE: This study aimed to investigate ChT profiles and associated factors in myopic children. METHODS: Baseline data of 250 myopic children aged 6 to 16 years in the Myopia Outcome Study of Atropine in Children clinical trial were analyzed. Choroidal thickness images were obtained using swept-source optical coherence tomography (DRI-OCT Triton Plus; Topcon Corporation, Tokyo, Japan). The macula was divided into nine Early Treatment of Diabetic Retinopathy Study locations with diameters of 1, 3, and 6 mm corresponding to the central fovea, parafoveal, and perifoveal regions. Multiple linear regression models were used to investigate determinants of ChT. RESULTS: Choroidal thickness varied across themacular Early Treatment of Diabetic Retinopathy Study locations (P \u3c .001): thickest in the perifoveal superior region (mean ± standard deviation, 249.0 ± 60.8 μm) and thinnest in the perifoveal nasal region (155.1 ± 50.3 μm). On average, ChT was greater in all parafoveal (231.8 ± 57.8 μm) compared with perifoveal (218.1 ± 49.1 μm) regions except superiorly where the ChT was greater in the perifoveal region. Longer axial length and higher myopic spherical equivalent refraction were consistently associated with thinner ChT at all locations in the multiple linear regression models. Asian race was significantly associated with thinner ChT only at parafoveal and perifoveal superior regions after Bonferroni correction (P = .004 and P = .001, respectively). CONCLUSIONS: Choroidal thickness was thinnest in the nasal macular region and varied systematically across all macular locations, with axial length and spherical equivalent refraction being the strongest determinants of ChT. Longitudinal evidence will need to evaluate whether any differences in ChT profiles are predictive of myopic progression and to determine the role of ChT measurements in identifying myopic children most in need of myopia control treatment

Regional variations and temporal trends of childhood myopia prevalence in Africa: A systematic review and meta-analysis

Purpose: To provide contemporary and future estimates of childhood myopia prevalence in Africa. Methods: A systematic online literature search was conducted for articles on childhood (≤18 years) myopia (spherical equivalent [SE] ≤ −0.50D; high myopia: SE ≤ −6.00D) in Africa. Population-or school-based cross-sectional studies published from 1 Jan 2000 to 30 May 2021 were included. Meta-analysis using Freeman–Tukey double arcsine transformation was performed to estimate the prevalence of childhood myopia and high myopia. Myopia prevalence from subgroup analyses for age groups and settings were used as baseline for generating a prediction model using linear regression. Results: Forty-two studies from 19 (of 54) African countries were included in the meta-analysis (N = 737,859). Overall prevalence of childhood myopia and high myopia were 4.7% (95% CI: 3.3%–6.5%) and 0.6% (95% CI: 0.2%–1.1%), respectively. Estimated prevalence across the African regions was highest in the North (6.8% [95% CI: 4.0%–10.2%]), followed by Southern (6.3% [95% CI: 3.9%–9.1%]), East (4.7% [95% CI: 3.1%–6.7%]) and West (3.5% [95% CI: 1.9%–6.3%]) Africa. Prevalence from 2011 to 2021 was approximately double that from 2000 to 2010 for all studies combined, and between 1.5 and 2.5 times higher for ages 5–11 and 12–18 years, for boys and girls and for urban and rural settings, separately. Childhood myopia prevalence is projected to increase in urban settings and older children to 11.1% and 10.8% by 2030, 14.4% and 14.1% by 2040 and 17.7% and 17.4% by 2050, respectively; marginally higher than projected in the overall population (16.4% by 2050). Conclusions: Childhood myopia prevalence has approximately doubled since 2010, with a further threefold increase predicted by 2050. Given this trajectory and the specific public health challenges in Africa, it is imperative to implement basic myopia prevention programmes, enhance spectacle coverage and ophthalmic services and generate more data to understand the changing myopia epidemiology to mitigate the expanding risk of the African population

A systematic review of clinical practice guidelines for childhood glaucoma

Objective: To conduct a systematic review to identify and critically appraise clinical practice guidelines on the assessment, diagnosis and management of childhood glaucoma. Methods and analysis: A systematic literature search of databases and professional websites for clinical practice guidelines published on eye conditions between 2010 and April 2020 in English was conducted. Identified guidelines were screened for relevance to childhood glaucoma and exclusion criteria applied. Guidelines that passed the screening and quality appraisal with the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and, if they achieved a mean score of ≥45 and ≥3 on subsets of 9 and 5 AGREE II items, respectively, were selected for inclusion and data extracted using a standardised form. Results: Following screening and critical appraisal, three guidelines were included for data extraction. None of the three guidelines was specifically developed for childhood glaucoma. A consistent recommendation was that children should undergo some form of eye screening examination or a comprehensive eye assessment to detect paediatric eye disease. Children at high risk of childhood glaucoma should undergo additional screening. One clinical practice guideline recommended interventions for childhood glaucoma consisting of tube surgery and topical beta-blockers or carbonic anhydrase inhibitors. Recommended interventions for childhood glaucoma were based on low-quality to moderate-quality evidence or expert opinion. Conclusion: Based on our selection criteria, we did not identify any high-quality clinical practice guidelines specifically targeted at childhood glaucoma. This is compounded by the lack of high-quality evidence on childhood glaucoma

Low 25-Hydroxyvitamin D Concentration Is Not Associated With Refractive Error in Middle-Aged and Older Western Australian Adults

Purpose: To investigate the association between serum 25-hydroxyvitamin D (25[OH]D) concentration and refractive error in a community-based cohort of adults aged 46 to 69 years. Methods: Residents of the City of Busselton in Western Australia born between 1946 and 1964 were invited to participate. Participants underwent cycloplegic autorefraction and completed questionnaires on education, occupational sun exposure, and physical activity. Blood samples were collected and serum frozen at −80°C. Serum 25[OH]D concentration was measured by immunoassay. Data on 25[OH]D were deseasonalized and multivariate models built to analyze the association between 25[OH]D concentration and spherical equivalent and myopia, defined as spherical equivalent <−0.50 D. Results: After exclusions, data were available for 4112 participants. Serum 25[OH]D concentration was not associated with spherical equivalent or myopia after adjustment for confounding factors (β = −0.01, 95% confidence interval [CI]: −0.03 to −0.008, P = 0.25, and odds ratio = 1.02, 95% CI: 0.99 to 1.05, P = 0.12, respectively). When participants were classified into 25[OH]D groups of lower (<50 nmol/L), medium (≥50 to <75 nmol/L), and upper (≥75 nmol/L), the upper group had slightly greater myopic refractive error than the medium group (P = 0.02) but not the lower group, after adjustment for confounders. Conclusions: There was no substantial association between 25[OH]D levels and spherical equivalent or odds of myopia in this study. The association previously noted between low serum 25[OH]D level and myopia in younger Western Australians is not evident in later adulthood. Translational Relevance: This study provides further evidence suggesting that vitamin D levels are unrelated to myopia risk in adults and thus not a suitable target for myopia intervention

A systematic review of clinical practice guidelines for childhood glaucoma.

OBJECTIVE: To conduct a systematic review to identify and critically appraise clinical practice guidelines on the assessment, diagnosis and management of childhood glaucoma. METHODS AND ANALYSIS: A systematic literature search of databases and professional websites for clinical practice guidelines published on eye conditions between 2010 and April 2020 in English was conducted. Identified guidelines were screened for relevance to childhood glaucoma and exclusion criteria applied. Guidelines that passed the screening and quality appraisal with the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and, if they achieved a mean score of ≥45 and ≥3 on subsets of 9 and 5 AGREE II items, respectively, were selected for inclusion and data extracted using a standardised form. RESULTS: Following screening and critical appraisal, three guidelines were included for data extraction. None of the three guidelines was specifically developed for childhood glaucoma. A consistent recommendation was that children should undergo some form of eye screening examination or a comprehensive eye assessment to detect paediatric eye disease. Children at high risk of childhood glaucoma should undergo additional screening. One clinical practice guideline recommended interventions for childhood glaucoma consisting of tube surgery and topical beta-blockers or carbonic anhydrase inhibitors. Recommended interventions for childhood glaucoma were based on low-quality to moderate-quality evidence or expert opinion. CONCLUSION: Based on our selection criteria, we did not identify any high-quality clinical practice guidelines specifically targeted at childhood glaucoma. This is compounded by the lack of high-quality evidence on childhood glaucoma

The effect of transverse ocular magnification adjustment on macular thickness profile in different refractive errors in community-based adults

Purpose Changes in retinal thickness are common in various ocular diseases. Transverse magnification due to differing ocular biometrics, in particular axial length, affects measurement of retinal thickness in different regions. This study evaluated the effect of axial length and refractive error on measured macular thickness in two community-based cohorts of healthy young adults. Methods A total of 2160 eyes of 1247 community-based participants (18–30 years; 23.4% myopes, mean axial length = 23.6mm) were included in this analysis. Macular thickness measurements were obtained using a spectral-domain optical coherence tomography (which assumes an axial length of 24.385mm). Using a custom program, retinal thickness data were extracted at the 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) regions with and without correction for transverse magnificent effects, with the corrected measurements adjusting according to the participant’s axial length. Linear mixed models were used to analyse the effect of correction and its interaction with axial length or refractive group on retinal thickness. Results The raw measures (uncorrected for axial length) underestimated the true retinal thickness at the central macula, while overestimating at most non-central macular regions. There was an axial length by correction interaction effect in all but the nasal regions (all p\u3c0.05). For each 1mm increase in axial length, the central macular thickness is overestimated by 2.7–2.9μm while thicknesses at other regions were underestimated by 0.2–4.1μm. Based on the raw thickness measurements, myopes have thinner retinas than non-myopes at most non-central macular. However, this difference was no longer significant when the corrected data was used. Conclusion In a community-based sample, the raw measurements underestimate the retinal thickness at the central macula and overestimate the retinal thickness at non-central regions of the ETDRS grid. The effect of axial length and refractive error on retinal thickness is reduced after correcting for transverse magnification effects resulting from axial length differences

Systematic review of clinical practice guidelines for uveitis

To facilitate the integration of eye care into universal health coverage, the WHO is developing a Package of Eye Care Interventions (PECI). Development of the PECI involves the identification of evidence-based interventions from relevant clinical practice guidelines (CPGs) for uveitis.A systematic review of CPGs published on uveitis between 2010 and March 2020 was conducted. CPGs passing title and abstract and full-text screening were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and data on recommended interventions extracted using a standard data extraction sheet.Of 56 CPGs identified as potentially relevant from the systematic literature search, 3 CPGs underwent data extraction following the screening stages and appraisal with the AGREE II tool. These CPGs covered screening for, monitoring and treating juvenile idiopathic arthritis (JIA)-associated uveitis, the use of adalimumab and dexamethasone in treating non-infectious uveitis, and a top-level summary of assessment, differential diagnosis and referral recommendations for uveitis, aimed at primary care practitioners. Many of the recommendations were based on expert opinion, though some incorporated clinical study and randomised controlled trial data.There is currently sparse coverage of the spectrum of disease caused by uveitis within CPGs. This may partially be due to the large number of conditions with diverse causes and clinical presentations covered by the umbrella term uveitis, which makes numerous sets of guidelines necessary. The limited pool of CPGs to select from has implications for clinicians seeking guidance on clinical care strategies for uveitis.</jats:p

Investigating the long-term impact of a childhood sun-exposure intervention, with a focus on eye health: protocol for the Kidskin-Young Adult Myopia Study

Introduction Excessive and insufficient sun exposure during childhood have been linked to serious diseases in later life; for example, insufficient sun exposure during childhood may increase the risk of developing myopia. The Kidskin-Young Adult Myopia Study (K-YAMS) is a follow-up of participants in the Kidskin Study, a non-randomised controlled trial that evaluated the effect of a 4-year educational intervention on sun-protection behaviours among primary school children in the late 1990s. Children who received the Kidskin intervention had lower levels of sun exposure compared with peers in the control group after 2 and 4 years of the intervention, but this was not maintained 2  years after the intervention had ceased. Thus, a follow-up of Kidskin Study participants provides a novel opportunity to investigate the associations between a childhood sun-exposure intervention and potentially related conditions in adulthood. Methods and analysis The K-YAMS contacts Kidskin Study participants and invites them to participate using a variety of methods, such as prior contact details, the Australian Electoral Roll and social media. Self-reported and objective measures of sun-exposure and sun-protection behaviours are collected as well as a number of eye measurements including cycloplegic autorefraction and ocular biometry. Data will be analysed to investigate a possible association between myopic refractive error and Kidskin intervention group or measured sun exposure.A pilot study of the K-YAMS was funded by a Perpetual Impact Philanthropy Grant (IPAP2015/0230). The K-YAMS study is funded by a competitive, peer-reviewed Project Grant from the National Health and Medical Research Council (1121979). GL receives financial support through an Australia Government Research Training Program Scholarship. SY is supported by a National Health and Medical Research Council CJ Martin Early Career Fellowship. DC is supported by a National Health and Medical Research Council Research Fellowship GNT 1119339. RML is supported by a National Health and Medical Research Council Senior Research Fellowship (#1107343) and a Cancer Australia grant