Population screening for glaucoma in UK : current recommendations and future directions

Funding Information: APK is funded by a UKRI Future Leaders Fellowship and an Alcon Research Institute Young Investigator Award.Effective population screening for glaucoma would enable earlier diagnosis and prevention of irreversible vision loss. The UK National Screening Committee (NSC) recently published a review that examined the viability, effectiveness and appropriateness of a population-based screening programme for primary open-angle glaucoma (POAG). In our article, we summarise the results of the review and discuss some future directions that may enable effective population screening for glaucoma in the future. Two key questions were addressed by the UK NSC review; is there a valid, accurate screening test for POAG, and does evidence exist that screening reduces morbidity from POAG compared with standard care. Six new studies were identified since the previous 2015 review. The review concluded that screening for glaucoma in adults is not recommended because there is no clear evidence for a sufficiently accurate screening test or for better outcomes with screening compared to current care. The next UK NSC review is due to be conducted in 2023. One challenge for POAG screening is that the relatively low disease prevalence results in too many false-positive referrals, even with an accurate test. In the future, targeted screening of a population subset with a higher prevalence of glaucoma may be effective. Recent developments in POAG polygenic risk prediction and deep learning image analysis offer potential avenues to identifying glaucoma-enriched sub-populations. Until such time, opportunistic case finding through General Ophthalmic Services remains the primary route for identification of glaucoma in the UK and greater public awareness of the service would be of benefit.Publisher PDFPeer reviewe

Residential area deprivation and risk of subsequent hospital admission in a British population: the EPIC-Norfolk cohort.

OBJECTIVES:To investigate whether residential area deprivation index predicts subsequent admissions to hospital and time spent in hospital independently of individual social class and lifestyle factors. DESIGN:Prospective population-based study. SETTING:The European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) study. PARTICIPANTS:11 214 men and 13 763 women in the general population, aged 40-79 years at recruitment (1993-1997), alive in 1999. MAIN OUTCOME MEASURE:Total admissions to hospital and time spent in hospital during a 19-year time period (1999-2018). RESULTS:Compared to those with residential Townsend Area Deprivation Index lower than the average for England and Wales, those with a higher than average deprivation index had a higher likelihood of spending >20 days in hospital multivariable adjusted OR 1.18 (95% CI 1.07 to 1.29) and having 7 or more admissions OR 1.11 (95% CI 1.02 to 1.22) after adjustment for age, sex, smoking status, education, social class and body mass index. Occupational social class and educational attainment modified the association between area deprivation and hospitalisation; those with manual social class and lower education level were at greater risk of hospitalisation when living in an area with higher deprivation index (p-interaction=0.025 and 0.020, respectively), while the risk for non-manual and more highly educated participants did not vary greatly by area of residence. CONCLUSION:Residential area deprivation predicts future hospitalisations, time spent in hospital and number of admissions, independently of individual social class and education level and other behavioural factors. There are significant interactions such that residential area deprivation has greater impact in those with low education level or manual social class. Conversely, higher education level and social class mitigated the association of area deprivation with hospital usage

Towards modifying the genetic predisposition for glaucoma: An overview of the contribution and interaction of genetic and environmental factors

Glaucoma, the leading cause of irreversible blindness worldwide, is a complex human disease, with both genetic and environmental determinants. The availability of large-scale, population-based cohorts and biobanks, combining genotyping and detailed phenotyping, has greatly accelerated research into the aetiology of glaucoma in recent years. Hypothesis-free genome-wide association studies have furthered our understanding of the complex genetic architecture underpinning the disease, while epidemiological studies have provided advances in the identification and characterisation of environmental risk factors. It is increasingly recognised that the combined effects of genetic and environmental factors may confer a disease risk that reflects a departure from the simple additive effect of the two. These gene-environment interactions have been implicated in a host of complex human diseases, including glaucoma, and have several important diagnostic and therapeutic implications for future clinical practice. Importantly, the ability to modify the risk associated with a particular genetic makeup promises to lead to personalised recommendations for glaucoma prevention, as well as novel treatment approaches in years to come. Here we provide an overview of genetic and environmental risk factors for glaucoma, as well as reviewing the evidence and discussing the implications of gene-environment interactions for the disease

Differentiating glaucoma from chiasmal compression using optical coherence tomography: the macular naso-temporal ratio

BACKGROUND/AIMS: The analysis of visual field loss patterns is clinically useful to guide differential diagnosis of visual pathway pathology. This study investigates whether a novel index of macular atrophy patterns can discriminate between chiasmal compression and glaucoma. METHODS: A retrospective series of patients with preoperative chiasmal compression, primary open-angle glaucoma (POAG) and healthy controls. Macular optical coherence tomography (OCT) images were analysed for the macular ganglion cell and inner plexiform layer (mGCIPL) thickness. The nasal hemi-macula was compared with the temporal hemi-macula to derive the macular naso-temporal ratio (mNTR). Differences between groups and diagnostic accuracy were explored with multivariable linear regression and the area under the receiver operating characteristic curve (AUC). RESULTS: We included 111 individuals (31 with chiasmal compression, 30 with POAG and 50 healthy controls). Compared with healthy controls, the mNTR was significantly greater in POAG cases (β=0.07, 95% CI 0.03 to 0.11, p=0.001) and lower in chiasmal compression cases (β=-0.12, 95% CI -0.16 to -0.09, p<0.001), even though overall mGCIPL thickness did not discriminate between these pathologies (p=0.36). The mNTR distinguished POAG from chiasmal compression with an AUC of 95.3% (95% CI 90% to 100%). The AUCs when comparing healthy controls to POAG and chiasmal compression were 79.0% (95% CI 68% to 90%) and 89.0% (95% CI 80% to 98%), respectively. CONCLUSIONS: The mNTR can distinguish between chiasmal compression and POAG with high discrimination. This ratio may provide utility over-and-above previously reported sectoral thinning metrics. Incorporation of mNTR into the output of OCT instruments may aid earlier diagnosis of chiasmal compression

Prevalence of diabetic retinopathy in Indigenous and non-Indigenous Australians: a systematic review and meta-analysis

TOPIC: This systematic review and meta-analysis summarises evidence relating to the prevalence of diabetic retinopathy (DR) among Indigenous and non-Indigenous Australians. CLINICAL RELEVANCE: Indigenous Australians suffer disproportionately from diabetes-related complications. Exploring ethnic variation in disease is important for equitable distribution of resources and may lead to identification of ethnic-specific modifiable risk factors. Existing DR prevalence studies comparing Indigenous and non-Indigenous Australians have shown conflicting results. METHODS: This study was conducted following Joanna Briggs Institute guidance on systematic reviews of prevalence studies (PROSPERO ID: CRD42022259048). We performed searches of Medline (Ovid), EMBASE, and Web of Science until October 2021, using a strategy designed by an information specialist. We included studies reporting DR prevalence among diabetic patients in Indigenous and non-Indigenous Australian populations. Two independent reviewers performed quality assessments using a 9-item appraisal tool. Meta-analysis and meta-regression were performed using double arcsine transformation and a random-effects model comparing Indigenous and non-Indigenous subgroups. RESULTS: Fifteen studies with 8219 participants met criteria for inclusion. The Indigenous subgroup scored lower on the appraisal tool compared to the non-Indigenous subgroup (mean score 50% vs 72%, p=0.04). In the unadjusted meta-analysis, DR prevalence in the Indigenous subgroup (30.2% [95%CI: 24.9-25.7]) did not differ significantly (p=0.17) from the non-Indigenous subgroup (23.7% (95%CI: 16.8-31.4]). After adjusting for age and for quality, DR prevalence was higher in the Indigenous subgroup (p-values<0.01), with prevalence ratio point estimates ranging between 1.72-2.58, depending on the meta-regression model. For the secondary outcomes, prevalence estimates were higher in the Indigenous subgroup for diabetic macular oedema (8.7% vs 2.7%, p=0.02) and vision-threatening DR (8.6% vs 3.0%, p=0.03), but not for proliferative DR (2.5% vs 0.8%, p=0.07). CONCLUSION: Indigenous studies scored lower for methodological quality, raising the possibility that systematic differences in research practices may be leading to underestimation of disease burden. After adjusting for age and for quality, we found a higher DR prevalence in the Indigenous subgroup. This contrasts with a previous review which reported the opposite finding of lower DR prevalence using unadjusted pooled estimates. Future epidemiological work exploring DR burden in Indigenous communities should aim to address methodological weaknesses identified by this review

Topical Beta-Blockers and Cardiovascular Mortality: Systematic Review and Meta-Analysis with Data from the EPIC-Norfolk Cohort Study.

PURPOSE: To determine if topical beta-blocker use is associated with increased cardiovascular mortality, particularly among people with self-reported glaucoma. METHODS: All participants who participated in the first health check (N = 25,639) of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort (1993-2013) were included in this prospective cohort study, with a median follow-up of 17.0 years. We determined use of topical beta-blockers at baseline through a self-reported questionnaire and prescription check at the first clinical visit. Cardiovascular mortality was ascertained through data linkage with the Office for National Statistics mortality database. Hazard ratios (HRs) were estimated using multivariable Cox regression models. Meta-analysis of the present study's results together with other identified literature was performed using a random effects model. RESULTS: We did not find an association between the use of topical beta-blockers and cardiovascular mortality (HR 0.93, 95% confidence interval, CI, 0.67-1.30). In the 514 participants with self-reported glaucoma, no association was found between the use of topical beta-blockers and cardiovascular mortality (HR 0.89, 95% CI 0.56-1.40). In the primary meta-analysis of four publications, there was no evidence of an association between the use of topical beta-blockers and cardiovascular mortality (pooled HR estimate 1.10, 95% CI 0.84-1.36). CONCLUSION: Topical beta-blockers do not appear to be associated with excess cardiovascular mortality. This evidence does not indicate that a change in current practice is warranted, although clinicians should continue to assess individual patients and their cardiovascular risk prior to commencing topical beta-blockers.EPIC-Norfolk infrastructure and core functions are supported by grants from the Medical Research Council (G1000143) and Cancer Research UK (C864/A14136). The clinic for the third health examination was funded by Age UK Research into Ageing (262). Mr Khawaja is a Wellcome Trust Clinical Research Fellow. Mr Foster has received additional support from the Richard Desmond Charitable Trust (via Fight for Sight) and the Department for Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital and the UCL Institute of Ophthalmology for a specialist Biomedical Research Centre for Ophthalmology.This is the final version of the article. It first appeared from Taylor & Francis via http://dx.doi.org/10.1080/09286586.2016.1213301

Association Between Retinal Nerve Fiber Layer Thickness and Incident Dementia in the European Prospective Investigation into Cancer in Norfolk Cohort

BACKGROUND: Retinal nerve fiber layer (RNFL) thickness may reflect cerebral status. OBJECTIVE: This study assessed the relationship between RNFL thickness and incident all-cause dementia in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) Eye Study. METHODS: Glaucoma detection with variable corneal compensation (GDx-VCC) and Heidelberg Retinal Tomograph II (HRT II) derived global mean RNFL thickness from dementia-free participants at baseline within the EPIC-Norfolk Eye Study were analyzed. Incident dementia was identified through linkage to electronic medical records. Cox proportional hazard mixed-effects regression models adjusted for key confounders were used to examine the associations between RNFL thickness and incident dementia in four separate models. RESULTS: 6,239 participants were included with 322 cases of incident dementia and mean age of 67.5-years old, with 49.7% women (median follow-up 13.2-years, interquartile range (11.7 to 14.6 years). Greater RNFL thickness (GDx-VCC) was not significantly associated with a lower risk of incident dementia in the full adjusted model [HR per quartile increase 0.95; 95% CI 0.82-1.10]. Similarly, RNFL thickness assessed with HRT II was also not associated with incident dementia in any model (full adjusted model; HR per quartile increase: 1.06; [95% CI 0.93-1.19]. Gender did not modify any associations under study. CONCLUSION: GDx-VCC and HRT II derived RNFL thickness are unlikely to be useful predictors of incident dementia. Higher resolution optical imaging technologies may clarify whether there are useful relationships between neuro-retinal morphology and brain measures

A new tool for converting food frequency questionnaire data into nutrient and food group values: FETA research methods and availability.

OBJECTIVES: To describe the research methods for the development of a new open source, cross-platform tool which processes data from the European Prospective Investigation into Cancer and Nutrition Norfolk Food Frequency Questionnaire (EPIC-Norfolk FFQ). A further aim was to compare nutrient and food group values derived from the current tool (FETA, FFQ EPIC Tool for Analysis) with the previously validated but less accessible tool, CAFÉ (Compositional Analyses from Frequency Estimates). The effect of text matching on intake data was also investigated. DESIGN: Cross-sectional analysis of a prospective cohort study-EPIC-Norfolk. SETTING: East England population (city of Norwich and its surrounding small towns and rural areas). PARTICIPANTS: Complete FFQ data from 11 250 men and 13 602 women (mean age 59 years; range 40-79 years). OUTCOME MEASURES: Nutrient and food group intakes derived from FETA and CAFÉ analyses of EPIC-Norfolk FFQ data. RESULTS: Nutrient outputs from FETA and CAFÉ were similar; mean (SD) energy intake from FETA was 9222 kJ (2633) in men, 8113 kJ (2296) in women, compared with CAFÉ intakes of 9175 kJ (2630) in men, 8091 kJ (2298) in women. The majority of differences resulted in one or less quintile change (98.7%). Only mean daily fruit and vegetable food group intakes were higher in women than in men (278 vs 212 and 284 vs 255 g, respectively). Quintile changes were evident for all nutrients, with the exception of alcohol, when text matching was not executed; however, only the cereals food group was affected. CONCLUSIONS: FETA produces similar nutrient and food group values to the previously validated CAFÉ but has the advantages of being open source, cross-platform and complete with a data-entry form directly compatible with the software. The tool will facilitate research using the EPIC-Norfolk FFQ, and can be customised for different study populations.This study was supported by programme grants from the MRC Population Health Sciences Research Network (PHSRN), Cancer Research UK(C864/A8257) and the Medical Research Council (G0401527 and G1000143). NGF was supported by the Medical Research Council (MC_UP_A100_1003); APK is funded by a Wellcome Trust Clinical Research Fellowshi

Area deprivation and age related macular degeneration in the EPIC-Norfolk Eye Study.

OBJECTIVES: To investigate the relationship between area deprivation, individual socio-economic status (SES) and age related macular degeneration (AMD). STUDY DESIGN: Cross sectional study nested within a longitudinal cohort study. METHODS: Data were collected in the EPIC-Norfolk Eye Study by trained nurses, using standardized protocols and lifestyle questionnaires. The English Index of multiple deprivation 2010 (IMD) was derived from participants' postcodes. AMD was identified from standardized grading of fundus photographs. Logistic regression was used to examine associations between IMD, SES and AMD. RESULTS: 5344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD. Of 5182 participants with complete data, AMD was identified in 653 participants (12.60%, 95%CI = 11.7-13.5%). Multivariable logistic regression showed that people living in the most affluent 5% of areas had nearly half the odds of AMD compared to those living in comparatively more deprived areas (OR = 0.56, 95% CI = 0.36-0.89, P = 0.02), after adjusting for age, sex, education, social class and smoking. CONCLUSIONS: The authors found that living in the most affluent areas exerted a protective effect on AMD, independently of education and social class. Further investigation into underlying mechanisms will inform potential interventions to reduce health inequalities relating to AMD.EPIC-Norfolk infrastructure and core functions are supported by grants from the Medical Research Council (G0401527) and Cancer Research UK (C864/A8257). The clinic for the third health examination was funded by Age UK Research into Ageing grant (262). Dr Yip is a National Institute for Health Research (NIHR) Clinical Lecturer. Dr Khawaja is a Wellcome Trust Clinical Research Fellow. Michelle Chan is an MRC/RCOphth Clinical Training Felllow and has received additional support from the International Glaucoma Association. Professor Foster has received additional support from the Richard Desmond Charitable Trust (via Fight for Sight). Professor Foster and Tunde Peto received funding from the Department for Health through the award made by the NIHR to Moorfields Eye Hospital and the UCL Institute of Ophthalmology for a specialist Biomedical Research Centre for Ophthalmology. None of the funding organisations had a role in the design or conduct of the research.This is the final version. It was first published by Elsevier at http://www.publichealthjrnl.com/article/S0033-3506%2814%2900274-1/abstrac