Estimating the Distribution of True Rates of Visual Field Progression in Glaucoma.

Purpose: The purpose of this study was to estimate the distribution of the true rates of progression (RoP) of visual field (VF) loss. Methods: We analyzed the progression of mean deviation over time in series of ≥ 10 tests from 3352 eyes (one per patient) from 5 glaucoma clinics, using a novel Bayesian hierarchical Linear Mixed Model (LMM); this modeled the random-effect distribution of RoPs as the sum of 2 independent processes following, respectively, a negative exponential distribution (the "true" distribution of RoPs) and a Gaussian distribution (the "noise"), resulting in a skewed exGaussian distribution. The exGaussian-LMM was compared to a standard Gaussian-LMM using the Watanabe-Akaike Information Criterion (WAIC). The random-effect distributions were compared to the empirical cumulative distribution function (eCDF) of linear regression RoPs using a Kolmogorov-Smirnov test. Results: The WAIC indicated a better fit with the exGaussian-LMM (estimate [standard error]: 192174.4 [721.2]) than with the Gaussian-LMM (192595 [697.4], with a difference of 157.2 [22.6]). There was a significant difference between the eCDF and the Gaussian-LMM distribution (P < 0.0001), but not with the exGaussian-LMM distribution (P = 0.108). The estimated mean (95% credible intervals, CIs) "true" RoP (-0.377, 95% CI = -0.396 to -0.359 dB/year) was more negative than the observed mean RoP (-0.283, 95% CI = -0.299 to -0.268 dB/year), indicating a bias likely due to learning in standard LMMs. Conclusions: The distribution of "true" RoPs can be estimated with an exGaussian-LMM, improving model accuracy. Translational Relevance: We used these results to develop a fast and accurate analytical approximation for sample-size calculations in clinical trials using standard LMMs, which was integrated in a freely available web application.

Face-down positioning or posturing after pars plana vitrectomy for macula-involving rhegmatogenous retinal detachments.

BACKGROUND: A macula-involving rhegmatogenous retinal detachment (RRD) is one of the most common ophthalmic surgical emergencies and causes significant visual morbidity. Pars plana vitrectomy (PPV) with gas tamponade is often performed to repair primary macula-involving RRDs with a high rate of anatomical retinal reattachment. It has been advocated by some ophthalmologists that face-down positioning after PPV and gas tamponade helps reduce postoperative retinal displacement. Retinal displacement can cause metamorphopsia and binocular diplopia. OBJECTIVES: The primary objective of this review is to determine whether face-down positioning reduces the risk of retinal displacement following PPV and gas tamponade for primary macula-involving RRDs. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 11), MEDLINE (January 1946 to 28 November 2022), Embase.com (January 1947 to 28 November 2022), PubMed (1948 to 28 November 2022), Latin American and Caribbean Health Sciences Literature database (1982 to 28 November 2022), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 28 November 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which face-down positioning was compared with no positioning or another form of positioning following PPV and gas tamponade for primary macula-involving RRDs. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for the prespecified outcomes using the GRADE approach. MAIN RESULTS: We identified three RCTs (369 eyes of 368 participants) that met the eligibility criteria. Two RCTs provided data on postoperative retinal displacement, one reported on postoperative distortion and quality of life outcomes, two on postoperative best-corrected visual acuity (BCVA) in logMAR, and two on postoperative ocular adverse events such as outer retinal folds. Study characteristics and risk of bias All the trials involved predominantly male participants (range: 68% to 72%). Only one trial provided race and ethnicity information, was registered on a trial registry, and reported funding sources. Using the RoB 2 tool, we assessed the risk of bias for proportion of eyes with retinal displacement, mean change in visual acuity, objective distortion scores, quality of life assessments, and ocular adverse events, with most domains judged to be at low risk of bias. Findings Immediate face-down positioning may result in a lower proportion of participants with postoperative retinal displacement compared with support-the-break positioning at six months (risk ratio [RR] 0.73, 95% confidence interval [CI] 0.54 to 0.99; 1 RCT; 239 eyes of 239 participants; very low certainty evidence). One study found no evidence of a difference in BCVA at three months when comparing postoperative face-up with face-down positioning with or without perfluorocarbon liquid (mean difference [MD] -0.03, 95% CI -0.09 to 0.02; I2 = 0; 56 eyes of 56 participants; very low certainty evidence). Immediate face-down positioning appears to have little to no effect on postoperative distortion scores at week 26 (MD 1.80, 95% CI -1.92 to 5.52; 1 RCT; 219 eyes of 219 participants; very low certainty evidence) and postoperative quality of life assessment scores at week 26 (MD -1.80, 95% CI -5.52 to 1.92; 1 RCT; 217 eyes of 217 participants; very low certainty evidence). Adverse events One study that enrolled 262 participants with macula-involving RRDs suggested that immediate face-down positioning after PPV and gas tamponade may reduce the ocular adverse event of postoperative outer retinal folds at six months (RR 0.39, 95% CI 0.17 to 0.90; 1 RCT; 262 eyes of 262 participants; very low certainty evidence) and binocular diplopia (RR 0.20, 95% CI 0.04 to 0.90; 1 RCT; 262 eyes of 262 participants; very low certainty evidence) compared with support-the-break positioning. Immediate face-down positioning may increase the ocular adverse event of elevated intraocular pressure compared with support-the-break positioning (RR 1.74, 95% CI 1.11 to 2.73; 1 RCT; 262 eyes of 262 participants; very low certainty evidence). Another study found no evidence of a difference in postoperative outer retinal folds when comparing face-down versus face-up positioning at one and three months (RR 1.00, 95% CI 0.50 to 2.02; RR 1.00, 95% CI 0.28 to 3.61; 1 RCT; 56 eyes of 56 participants; very low certainty evidence). No studies reported non-ocular adverse events. AUTHORS' CONCLUSIONS: Very low certainty evidence suggests that immediate face-down positioning after PPV and gas tamponade may result in a reduction in postoperative retinal displacement, outer retinal folds, and binocular diplopia, but may increase the chance of postoperative raised intraocular pressure compared with support-the-break positioning at six months. We identified two ongoing trials that compare face-down positioning with face-up positioning following PPV and gas tamponade in participants with primary macula-involving RRDs, whose results may provide relevant evidence for our stated objectives. Future trials should be rigorously designed, and investigators should analyze outcome data appropriately and report adequate information to provide evidence of high certainty. Quality of life and patient preferences should be examined in addition to clinical and adverse event outcomes.

The Double Layer Sign Is Highly Predictive of Progression to Exudation in Age-Related Macular Degeneration.

PURPOSE: The presences of a double layer sign (DLS) and a shallow irregular retinal pigment epithelium (RPE) elevation (SIRE) were investigated using spectral domain-OCT (SD-OCT) imaging to determine their ability to predict progression to exudative macular neovascularization (eMNV) in the unaffected fellow eyes (study eye) of participants with age-related macular degeneration (AMD) with newly diagnosed unilateral eMNV. DESIGN: Retrospective, reanalysis of SD-OCT scans of study eyes from the Early Detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU). PARTICIPANTS: The EDNA study repository of SD-OCT scans was assessed for inclusion. Cases with incomplete data sets, low quality scans, or exhibiting other pathology were excluded, which resulted in 459 eligible cases. METHODS: Spectral domain-OCT volume scans of study eyes were graded for irregular elevation of the RPE (IE), with length, and height measurements made on the most affected B-scan. Eyes with heterogeneous reflectivity within the IE were classified as exhibiting the DLS. Eyes with DLS where the length of separation between RPE and Bruch's membrane was ≥ 1000 µm in length and < 100 µm in height were subclassified as SIRE. MAIN OUTCOME MEASURES: Hazard of progression to eMNV for DLS and SIRE. RESULTS: Of the 459 eyes, 268 had IE, of which 101 were DLS-like and 51 also fulfilled criteria for SIRE. Over the 3 years FU period, 104 (23%) eyes progressed to eMNV. After an FU of 18 months, a significantly higher proportion of study eyes (P < 0.001) with IE, DLS, and SIRE developed eMNV compared with those without these features (IE: 17% vs. no IE 6.3%; DLS: 23% vs. no DLS 9.9%; SIRE: 22% vs. no SIRE 11%). In the adjusted Cox regression models, a significantly greater hazard of progression (P < 0.001) was associated with the presence of IE (adjusted hazard ratio [HR], 3.01; 95% confidence interval [CI], 1.88-4.82), DLS (adjusted HR, 3.41; 95% CI, 2.26-5.14), or SIRE (adjusted HR, 2.83; 95% CI, 1.68-4.75). CONCLUSION: The DLS is a highly sensitive predictor of progression to eMNV, and the use of SIRE does not improve predictability. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Identifying the severity of diabetic retinopathy by visual function measures using both traditional statistical methods and interpretable machine learning: a cross-sectional study.

AIMS/HYPOTHESIS: To determine the extent to which diabetic retinopathy severity stage may be classified using machine learning (ML) and commonly used clinical measures of visual function together with age and sex. METHODS: We measured the visual function of 1901 eyes from 1032 participants in the Northern Ireland Sensory Ageing Study, deriving 12 variables from nine visual function tests. Missing values were imputed using chained equations. Participants were divided into four groups using clinical measures and grading of ophthalmic images: no diabetes mellitus (no DM), diabetes but no diabetic retinopathy (DM no DR), diabetic retinopathy without diabetic macular oedema (DR no DMO) and diabetic retinopathy with DMO (DR with DMO). Ensemble ML models were fitted to classify group membership for three tasks, distinguishing (A) the DM no DR group from the no DM group; (B) the DR no DMO group from the DM no DR group; and (C) the DR with DMO group from the DR no DMO group. More conventional multiple logistic regression models were also fitted for comparison. An interpretable ML technique was used to rank the contribution of visual function variables to predictions and to disentangle associations between diabetic eye disease and visual function from artefacts of the data collection process. RESULTS: The performance of the ensemble ML models was good across all three classification tasks, with accuracies of 0.92, 1.00 and 0.84, respectively, for tasks A-C, substantially exceeding the accuracies for logistic regression (0.84, 0.61 and 0.80, respectively). Reading index was highly ranked for tasks A and B, whereas near visual acuity and Moorfields chart acuity were important for task C. Microperimetry variables ranked highly for all three tasks, but this was partly due to a data artefact (a large proportion of missing values). CONCLUSIONS/INTERPRETATION: Ensemble ML models predicted status of diabetic eye disease with high accuracy using just age, sex and measures of visual function. Interpretable ML methods enabled us to identify profiles of visual function associated with different stages of diabetic eye disease, and to disentangle associations from artefacts of the data collection process. Together, these two techniques have great potential for developing prediction models using untidy real-world clinical data.

Scleral Buckle, Vitrectomy, or Combined Surgery for Inferior Break Retinal Detachment: Systematic Review and Meta-Analysis.

TOPIC: To compare outcomes of scleral buckle (SB), pars plana vitrectomy (PPV), and combined PPV-SB to treat rhegmatogenous retinal detachments (RRDs) with inferior retinal breaks (IRBs). CLINICAL RELEVANCE: Rhegmatogenous retinal detachments with IRBs are not uncommon; their management is challenging with higher risk of failure. There is no consensus about their treatment, specifically whether SB, PPV, or PPV-SB should be performed. METHODS: Systematic review and meta-analysis. Randomized controlled trials, case-control, and prospective/retrospective series (if n > 50) in English were eligible. Medline, Embase, and Cochrane databases were searched up to January 23, 2023. Standard systematic review methods were followed. The following outcomes at 3 (± 1) and 12 (± 3) months were evaluated: number of eyes with retinal reattachment after ≥ 1 surgeries, change in best-corrected visual acuity from preoperative to postoperative levels, and number of eyes with improvement of > 10 and > 15 ETDRS letters after surgery. Authors of eligible studies were asked for individual participant data (IPD) and IPD meta-analysis was undertaken. Risk of bias was assessed using National Institutes of Health study quality assessment tools. This study was registered prospectively in PROSPERO (CRD42019145626). RESULTS: A total of 542 studies were identified: 15 were eligible and included and 60% were retrospective. Individual participant data was obtained from 8 studies (1017 eyes). Given that only 26 patients had received SB alone, these data were not considered in the analysis. There was no evidence for differences between treatment groups (PPV versus PPV-SB) in the probability of having a flat retina at 3 or 12 months postoperatively after 1 (P = 0.067; odds ratio [OR], 0.47; P = 0.408; OR 2.55; respectively) or > 1 (OR, 0.54; P = 0.21; OR, 0.89; P = 0.926; respectively) surgery. Pars plana vitrectomy-SB showed less improvement in vision postoperatively at 3 months (estimate, 0.18; 95% confidence interval, 0.01-0.35; P = 0.044), but this difference was no longer observed at 12 months (estimate, -0.07; 95% confidence interval, -0.27, 0.13; P = 0.479). CONCLUSION: Available evidence suggests a lack of benefit of adding SB to PPV to treat RRDs with IRBs. Evidence, however, comes mainly from retrospective series and, thus, despite the large number of eyes included, should be interpreted with caution. Further research is needed. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Stress and cataract surgery: A nationwide study evaluating surgeon burnout.

BACKGROUND: We aimed to evaluate the nationwide prevalence of stress induced burnout among cataract surgeons. We believe that knowledge of these factors can help formulate a solution to this underreported problem. METHODS: A three-part nationwide cross-sectional survey was disseminated with via the Royal College of Ophthalmologists (RCOphth) in the United Kingdom(UK). All consultants, trainees and specialty doctors and associate specialists(SAS) were invited to participate. We evaluated burnout using the Maslach Burnout Inventory (MBI). Logistic regression modelling was completed to look at factors linked to high level burnout in certain domains. RESULTS: A total of 406 respondents completed our survey. Prevalence of cataract surgery-related high burnout was estimated at 3.45% (Section A and/or B) and 40% within Personal Accomplishment (PA)(Section C of the MBI). Multiple factors were associated with increased burnout within PA: Increasing age: 61+ OR: 2.99 (1.02-8.78, p = 0.05), Number of cataract operations completed: >3000 OR 2.98 (1.03-8.64, p = 0.04), Lists per week: 2: OR 2.99 (1.38-6.47, p < 0.01), 2.5: OR 8.95 (2.58-31.02, p < 0.01), 3 or more: OR 2.64 (1.07-6.54, p = 0.04). Sleeping 8 h or more was found to be protective OR 0.52 (0.28-0.96, p = 0.04). 17% of respondents indicated they would be willing to give up cataract surgery if given the opportunity. CONCLUSION: The prevalence of stress induced burnout by cataract surgery appears to be present in a minority of surgeons. There appears to be a significant reduction in the feeling of personal achievement within the profession. A large proportion of this cohort appears to be willing to give up surgical responsibilities.

Prevalence and risk factors for age-related macular degeneration in a population-based cohort study of older adults in Northern Ireland using multimodal imaging: NICOLA Study.

PURPOSE: To report prevalence and risk factor associations for age-related macular degeneration (AMD) and AMD features from multimodal retinal grading in a multidisciplinary longitudinal population-based study of aging in Northern Ireland. STUDY DESIGN: Population-based longitudinal cohort study. METHODS: Retinal imaging at the Norther Ireland Cohort for the Longitudinal Aging Study health assessment included stereo Colour Fundus Photography (CFP) (Canon CX-1, Tokyo, Japan) and Spectral-Domain Optical Coherence Tomography (SD-OCT) ((Heidelberg Retinal Angopgraph (HRA)+OCT; Heidelberg Engineering, Heidelberg, Germany). Medical history and demographic information was obtained during a home interview. Descriptive statistics were used to describe the prevalence of AMD and individual AMD features. Multiple imputation followed by multiple regression modelling was used to explore risk factor associations including relationships with AMD genetic risk score. RESULTS: Retinal images from 3386 participants were available for analysis. Mean age of the sample was 63.4 (SD 9.01, range: 36-99). Population weighted prevalence of AMD using colour grading in those over 55 years was: no drusen: 6 0.4%; drusen <63 µm: 15.9%; drusen 63-125 µm: 13.7%; drusen >125 µm or pigmentary changes: 8.3%; late AMD: 1.6%. Prevalence of AMD features in those over 55 years was: OCT drusen 27.5%, complete outer retinal pigment epithelium and outer retinal atrophy (cRORA) on OCT was 4.3%, reticular drusen 3.2% and subretinal drusenoid deposits 25.7%. The genetic risk score was significantly associated with drusen and cRORA but less so for SDD alone and non-significant for hyperpigmentation or vitelliform lesions. CONCLUSIONS: Multimodal imaging-based classification has provided evidence of some divergence of genetic risk associations between classical drusen and SDD. Our findings support an urgent review of current AMD severity classification systems.

Modelling ready-made spectacle coverage for children and adults using a large global database.

BACKGROUND/AIMS: To model the suitability of conventional ready-made spectacles (RMS) and interchangeable-lens ready-made spectacles (IRMS) with reference to prescribing guidelines among children and adults using a large, global database and to introduce a web-based application for exploring the database with user-defined eligibility criteria. METHODS: Using refractive power and interpupillary distance data for near and distance spectacles prescribed to children and adults during OneSight clinics in 27 countries, from 2 January 2016 to 19 November 2019, we modelled the expected suitability of RMS and IRMS spectacle designs, compared with custom-made spectacles, according to published prescribing guidelines. RESULTS: Records of 18 782 presbyopic adult prescriptions, 70 619 distance adult prescriptions and 40 862 paediatric prescriptions were included. Globally, 58.7%-63.9% of adults could be corrected at distance with RMS, depending on the prescribing cut-off. For presbyopic adult prescriptions, coverage was 44.1%-60.9%. Among children, 51.8% were eligible for conventional RMS. Coverage for all groups was similar to the above for IRMS. The most common reason for ineligibility for RMS in all service groups was astigmatism, responsible for 27.2% of all ineligible adult distance prescriptions using the strictest cut-off, 31.4% of children's prescriptions and 28.0% of all adults near prescriptions globally. CONCLUSION: Despite their advantages in cost and convenience, coverage delivered by RMS is limited under current prescribing guidelines, particularly for children and presbyopic adults. Interchangeable designs do little to remediate this, despite extending coverage for anisometropia. Our free application allows users to estimate RMS coverage in specific target populations.

Assessment of the Classification of Age-Related Macular Degeneration Severity from the Northern Ireland Sensory Ageing Study Using a Measure of Dark Adaptation.

Purpose: To assess the differences in rod-mediated dark adaptation (RMDA) between different grades of age-related macular degeneration (AMD) severity using an OCT-based criterion compared with those of AMD severity using the Beckman color fundus photography (CFP)-based classification and to assess the association between the presence of subretinal drusenoid deposits (SDDs) and RMDA at different grades of AMD severity using an OCT-based classification. Design: Cross-sectional study. Participants: Participants from the Northern Ireland Sensory Ageing study (Queen's University Belfast). Methods: Complete RMDA (rod-intercept time [RIT]) data, CFP, and spectral-domain OCT images were extracted. Participants were stratified into 4 Beckman groups (omitting late-stage AMD) and 3 OCT-based groups. The presence and stage of SDDs were identified using OCT. Main Outcome Measures: Rod-intercept time data (age-corrected). Results: Data from 459 participants (median [interquartile range] age, 65 [59-71] years) were stratified by both the classifications. Subretinal drusenoid deposits were detected in 109 eyes. The median (interquartile range) RMDA for the Beckman classification (Beckman 0-3, with 3 being intermediate age-related macular degeneration [iAMD]) groups was 6.0 (4.5-8.7), 6.6 (4.7-10.5), 5.7 (4.4-7.4), and 13.2 (6-21.1) minutes, respectively. OCT classifications OCT0-OCT2 yielded different median (interquartile range) values: 5.8 (4.5-8.5), 8.4 (5.2-13.3), and 11.1 (5.3-20.1) minutes, respectively. After correcting for age, eyes in Beckman 3 (iAMD) had statistically significantly worse RMDA than eyes in the other Beckman groups (P ≤ 0.005 for all), with no statistically significant differences between the other Beckman groups. Similarly, after age correction, eyes in OCT2 had worse RMDA than eyes in OCT0 (P ≤ 0.001) and OCT1 (P < 0.01); however, there was no statistically significant difference between eyes in OCT0 and eyes in OCT1 (P = 0.195). The presence of SDDs was associated with worse RMDA in OCT2 (P < 0.01) but not in OCT1 (P = 0.285). Conclusions: Eyes with a structural definition of iAMD have delayed RMDA, regardless of whether a CFP- or OCT-based criterion is used. In this study, after correcting for age, the RMDA did not differ between groups of eyes defined to have early AMD or normal aging, regardless of the classification. The presence of SDDs has some effect on RMDA at different grades of AMD severity.

Children who idiopathically toe-walk have greater plantarflexor effective mechanical advantage compared to typically developing children.

PURPOSE: The effective mechanical advantage (EMA) of the plantarflexor muscles is important for gait function and is likely different from typical in equinus gait. However, this has never been quantified for children who idiopathically toe-walk (ITW), despite being routinely altered through clinical intervention. METHODS: This study quantified the Achilles tendon and ground reaction force (GRF) moment arms, and the plantarflexor EMA of 5 children who ITW and 14 typically developing (TD) children, whilst walking on an instrumented treadmill. RESULTS: There was no difference in the Achilles tendon moment arm length throughout stance between groups (p > 0.05). Children who ITW had a significantly greater GRF moment arm length in early stance (20-24% p = 0.001), but a significantly shorter GRF moment arm length during propulsion (68-74% of stance; p = 0.013) than TD children. Therefore, children who ITW had a greater plantarflexor EMA than TD children when active plantarflexion moments were being generated (60-70% of stance; p = 0.007). Consequently, it was estimated that children who ITW required 30% less plantarflexor muscle force for propulsion. CONCLUSION: Clinical decision making should fully consider that interventions which aim to restore a typical heel-toe gait pattern risk compromising this advantageous leverage and thus, may increase the strength requirements for gait.

Associations between self-reported periodontal disease and nutrient intakes and nutrient-based dietary patterns in the UK Biobank.

AIM: To examine the cross-sectional associations between single nutrient intakes and posteriori nutrient-based dietary patterns and periodontal disease risk in a subset of the UK Biobank cohort. MATERIALS AND METHODS: Dietary data were collected by 24-h dietary recall on up to five separate occasions over 16 months. A touchscreen questionnaire was used to collect oral health information. Participants were considered at high risk of periodontal disease if they reported having painful gums and/or bleeding gums and/or loose teeth. Principal component analysis identified four nutrient-based dietary patterns from 20 nutrients. Logistic regression was used to estimate the odds ratio of periodontal disease risk for single nutrients and nutrient-based dietary patterns. RESULTS: A total of 9476 participants (mean age 56.2 years [SD 8.0]) were included in the analysis. Higher intakes of vitamin B6, B12, C, and E, folate, iron, potassium, magnesium, polyunsaturated fatty acids, and total sugar were associated with a lower risk of periodontal disease. Higher intake of saturated fat was associated with an increased risk. A dietary pattern characterized by high micronutrients and fibre intake was associated with low risk of periodontal disease. CONCLUSION: Within this sample of middle-aged and older adults, a "high micronutrient and fibre" dietary pattern was associated with reduced risk of periodontal disease.

Testing the performance of risk prediction models to determine progression to referable diabetic retinopathy in an Irish type 2 diabetes cohort.

BACKGROUND /AIMS: To evaluate the performance of existing prediction models to determine risk of progression to referable diabetic retinopathy (RDR) using data from a prospective Irish cohort of people with type 2 diabetes (T2D). METHODS: A cohort of 939 people with T2D followed prospectively was used to test the performance of risk prediction models developed in Gloucester, UK, and Iceland. Observed risk of progression to RDR in the Irish cohort was compared with that derived from each of the prediction models evaluated. Receiver operating characteristic curves assessed models' performance. RESULTS: The cohort was followed for a total of 2929 person years during which 2906 screening episodes occurred. Among 939 individuals followed, there were 40 referrals (4%) for diabetic maculopathy, pre-proliferative DR and proliferative DR. The original Gloucester model, which includes results of two consecutive retinal screenings; a model incorporating, in addition, systemic biomarkers (HbA1c and serum cholesterol); and a model including results of one retinopathy screening, HbA1c, total cholesterol and duration of diabetes, had acceptable discriminatory power (area under the curve (AUC) of 0.69, 0.76 and 0.77, respectively). The Icelandic model, which combined retinopathy grading, duration and type of diabetes, HbA1c and systolic blood pressure, performed very similarly (AUC of 0.74). CONCLUSION: In an Irish cohort of people with T2D, the prediction models tested had an acceptable performance identifying those at risk of progression to RDR. These risk models would be useful in establishing more personalised screening intervals for people with T2D.

Vision impairment and traffic safety outcomes in low-income and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Road traffic injuries are a major public health concern and their prevention requires concerted efforts. We aimed to systematically analyse the current evidence to establish whether any aspects of vision, and particularly interventions to improve vision function, are associated with traffic safety outcomes in low-income and middle-income countries (LMICs). METHODS: We did a systematic review and meta-analysis to assess the association between poor vision and traffic safety outcomes. We searched MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials in the Cochrane Library from database inception to April 2, 2020. We included any interventional or observational studies assessing whether vision is associated with traffic safety outcomes, studies describing prevalence of poor vision among drivers, and adherence to licensure regulations. We excluded studies done in high-income countries. We did a meta-analysis to explore the associations between vision function and traffic safety outcomes and a narrative synthesis to describe the prevalence of vision disorders and adherence to licensure requirements. We used random-effects models with residual maximum likelihood method. The systematic review protocol was registered on PROSPERO, CRD-42020180505. FINDINGS: We identified 49 (1·8%) eligible articles of 2653 assessed and included 29 (59·2%) in the various data syntheses. 15 394 participants (mean sample size n=530 [SD 824]; mean age of 39·3 years [SD 9·65]; 1167 [7·6%] of 15 279 female) were included. The prevalence of vision impairment among road users ranged from 1·2% to 26·4% (26 studies), colour vision defects from 0·5% to 17·1% (15 studies), and visual field defects from 2·0% to 37·3% (ten studies). A substantial proportion (range 10·6-85·4%) received licences without undergoing mandatory vision testing. The meta-analysis revealed a 46% greater risk of having a road traffic crash among those with central acuity visual impairment (risk ratio [RR] 1·46 [95% CI 1·20-1·78]; p=0·0002, 13 studies) and a greater risk among those with defects in colour vision (RR 1·36 [1·01-1·82]; p=0·041, seven studies) or the visual field (RR 1·36 [1·25-1·48]; p<0·0001, seven studies). The I2 value for overall statistical heterogeneity was 63·4%. INTERPRETATION: This systematic review shows a positive association between vision impairment and traffic crashes in LMICs. Our findings provide support for mandatory vision function assessment before issuing a driving licence. FUNDING: None.

In vivo operating lengths of the gastrocnemius muscle during gait in children who idiopathically toe-walk.

NEW FINDINGS: What is the central question of this study? What are the in vivo operating lengths of the gastrocnemius muscle in children who idiopathically toe-walk? What is the main finding and its importance? Children who idiopathically toe-walk operate at more plantarflexed positions but at longer fascicle lengths than typically developing children during gait. However, these ranges utilised during gait correspond to where children who idiopathically toe-walk are optimally strong. This should be considered when prescribing clinical treatments to restore typical gait. ABSTRACT: Children who idiopathically toe-walk (ITW) habitually operate at greater plantarflexion angles than typically developing (TD) children, which might result in shorter, sub-optimal gastrocnemius fascicle lengths. However, currently no experimental evidence exists to substantiate this notion. Five children who ITW and 14 TD children completed a gait analysis, whilst gastrocnemius fascicle behaviour was simultaneously quantified using ultrasound. The moment-angle (hip, knee and ankle) and moment-length (gastrocnemius) relationships were determined from isometric maximum voluntary contractions (MVC) on an isokinetic dynamometer combined with ultrasound. During gait, children who ITW operated at more plantarflexed angles (Δ = 20°; P = 0.013) and longer muscle fascicle lengths (Δ = 12 mm; P = 0.008) than TD children. During MVC, no differences in the peak moment of any joint were found. However, peak plantarflexor moment occurred at significantly more plantarflexed angles (-16 vs. 1°; P = 0.010) and at longer muscle fascicle lengths (44 vs. 37 mm; P = 0.001) in children who ITW than TD children. Observed alterations in the moment-angle and moment-length relationships of children who ITW coincided with the ranges used during gait. Therefore, the gastrocnemius muscle in children who ITW operates close to the peak of the force-length relationship, similarly to TD children. Thus, this study indicates that idiopathic toe-walking is truly an ankle joint pathology, and children who ITW present with substantial alterations in the gastrocnemius muscle functional properties, which appear well adapted to the characteristic demands of equinus gait. These findings should be considered when prescribing clinical treatments to restore typical gait.

A new phylodynamic model of Mycobacterium bovis transmission in a multi-host system uncovers the role of the unobserved reservoir.

Multi-host pathogens are particularly difficult to control, especially when at least one of the hosts acts as a hidden reservoir. Deep sequencing of densely sampled pathogens has the potential to transform this understanding, but requires analytical approaches that jointly consider epidemiological and genetic data to best address this problem. While there has been considerable success in analyses of single species systems, the hidden reservoir problem is relatively under-studied. A well-known exemplar of this problem is bovine Tuberculosis, a disease found in British and Irish cattle caused by Mycobacterium bovis, where the Eurasian badger has long been believed to act as a reservoir but remains of poorly quantified importance except in very specific locations. As a result, the effort that should be directed at controlling disease in badgers is unclear. Here, we analyse densely collected epidemiological and genetic data from a cattle population but do not explicitly consider any data from badgers. We use a simulation modelling approach to show that, in our system, a model that exploits available cattle demographic and herd-to-herd movement data, but only considers the ability of a hidden reservoir to generate pathogen diversity, can be used to choose between different epidemiological scenarios. In our analysis, a model where the reservoir does not generate any diversity but contributes to new infections at a local farm scale are significantly preferred over models which generate diversity and/or spread disease at broader spatial scales. While we cannot directly attribute the role of the reservoir to badgers based on this analysis alone, the result supports the hypothesis that under current cattle control regimes, infected cattle alone cannot sustain M. bovis circulation. Given the observed close phylogenetic relationship for the bacteria taken from cattle and badgers sampled near to each other, the most parsimonious hypothesis is that the reservoir is the infected badger population. More broadly, our approach demonstrates that carefully constructed bespoke models can exploit the combination of genetic and epidemiological data to overcome issues of extreme data bias, and uncover important general characteristics of transmission in multi-host pathogen systems.

Anatomic-Functional Correlates in Lesions of Retinal Vein Occlusion.

Purpose: To evaluate anatomic-functional associations at sites of retinal lesions in retinal vein occlusion (RVO). Methods: This pilot, prospective, observational study was conducted at the Northern Ireland Clinical Research Facility (NICRF) of Queen's University and the Belfast Health and Social Care Trust, Northern Ireland, between August 1, 2018, and September 30, 2019. The study included 10 treatment-naïve patients with RVO (10 RVO eyes and 10 fellow eyes). There were 81 points/sites assessed for each eye at baseline; six patients were re-assessed 6 months after anti-vascular endothelial growth factor therapy at the same locations. We investigated associations between retinal sensitivity and presence of structural RVO lesions, including retinal ischemia, hemorrhages, intraretinal fluid (IRF) and subretinal fluid outside the foveal/parafoveal regions. Comparisons were made between RVO eyes and fellow eyes at baseline, and between RVO eyes at baseline and at 6 months after treatment. Regression models were used to investigate anatomic-functional associations. Results: At baseline, strong associations were found between reduced retinal sensitivity and presence of ischemia (estimate = -2.08 dB; P < 0.001), intraretinal fluid (estimate = -7.82 dB; P < 0.001), and subretinal fluid (estimate = -8.66 dB; P < 0.001). Resolution of subretinal fluid but not intraretinal fluid was associated with improved function (estimate = 2.40 dB [P = 0.022]; estimate = 1.16 dB [P = 0.228], respectively). However, reperfusion of ischemic retina, observed in 31 of 486 points (6%) 6 months after anti-vascular endothelial growth factor therapy, was associated with a further decrease in retinal sensitivity (estimate = -2.34 dB; P = 0.035). Conclusions: Retinal sensitivity was decreased at sites of RVO lesions. Decreased function at sites of retinal ischemia did not recover after treatment, even when reperfusion occurred.

Muscle architecture and passive lengthening properties of the gastrocnemius medialis and Achilles tendon in children who idiopathically toe-walk.

Children who idiopathically toe-walk (ITW) habitually operate at greater plantarflexion angles and thus, at shorter muscle-tendon unit (MTU) lengths than typically developing (TD) children. Therefore, it is often assumed that habitual use of the gastrocnemius muscle in this way will cause remodelling of the muscle-tendon architecture compared to TD children. However, the gastrocnemius muscle architecture of children who ITW has never been measured. It is essential that we gain a better understanding of these muscle-tendon properties, to ensure that appropriate clinical interventions can be provided for these children. Five children who ITW (age 8 ± 2 years) and 14 TD children (age 10 ± 2 years) participated in this study. Ultrasound was combined with isokinetic dynamometry and surface electromyography, to measure muscle architecture at common positions and passive lengthening properties of the gastrocnemius muscle and tendon across full range of motion. Regardless of which common condition groups were compared under, both the absolute and normalised to MTU muscle belly and fascicle lengths were always longer, and the Achilles tendon length was always shorter in children who ITW than TD children (p < 0.05; large effect sizes). The passive lengthening properties of the muscle and tendon were not different between groups (p > 0.05); however, passive joint stiffness was greater in children who ITW at maximum dorsiflexion (p = 0.001) and at a joint moment common to all participants (p = 0.029). Consequently, the findings of this pilot study indicate a remodelling of the relative MTU that does not support the concept that children who ITW commonly experience muscle shortening. Therefore, greater consideration of the muscle and tendon properties are required when prescribing clinical interventions that aim to lengthen the MTU, and treatments may be better targeted at the Achilles tendon in children who ITW.