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

Cross Sectional and Longitudinal Associations between Cardiovascular Risk Factors and Age Related Macular Degeneration in the EPIC-Norfolk Eye Study.

PURPOSE: To examine the cross sectional and longitudinal relationship between cardiovascular risk factors and age-related macular degeneration (AMD) in a large British cohort study. METHODS: The EPIC Norfolk Eye study is nested in a larger prospective cohort study. Data on cardiovascular risk factors were collected at baseline (1993-1997) and follow up (2006-2011) via clinical examination, validated lifestyle questionnaires and serum blood samples. AMD was ascertained using standardised grading of fundus photographs at the follow up. Logistic regression was used to examine associations between baseline and follow up risk factors with AMD. RESULTS: 5,344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD in participants with mean age of 67.4 years old (range 44-91) at diagnosis. There were 28 cases of late AMD (0.5%, 95% confidence interval (CI)=0.3-0.8%) and 645 cases of early AMD (12.1%, 95%CI=11.2-13.0.%). In multivariable analysis, older people with higher levels of baseline high density lipoprotein- cholesterol (HDL-C ) and C-reactive protein (CRP) were more likely to have any signs of AMD, after adjusting for sex, education, smoking, and systolic blood pressure. In cross sectional analysis, only older age and higher HDL were significantly associated with AMD. CONCLUSIONS: We have found that older age and higher levels of CRP and HDL-C were associated with increased odds of AMD in this population in the longitudinal analysis, but older age and HDL-C, not CRP was significantly associated with AMD in the cross sectional analysis. The prevalence of AMD in this cohort was low compared to other cohorts in Europe, the US and Australia, and probably reflects the some selection biases in follow up participation as well as the low rate of smoking among our healthy participants.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 Fellow 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.This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013256

Glaucoma and intraocular pressure in EPIC-Norfolk Eye Study: cross sectional study.

Objectives To report the distribution of intraocular pressure (IOP) by age and sex and the prevalence of glaucoma.Design Community based cross sectional observational study.Setting EPIC-Norfolk cohort in Norwich and the surrounding rural and urban areas.Participants 8623 participants aged 48-92 recruited from the community who underwent ocular examination to identify glaucoma.Main outcome measures Prevalence and characteristics of glaucoma, distribution of IOP, and the sensitivity and specificity of IOP for case finding for glaucoma.Results The mean IOP in 8401 participants was 16.3 mm Hg (95% confidence interval 16.2 mm Hg to 16.3 mm Hg; SD 3.6 mm Hg). In 363 participants (4%), glaucoma was present in either eye; 314 (87%) had primary open angle glaucoma. In the remaining participants, glaucoma was suspected in 607 (7%), and 863 (10.0%) had ocular hypertension. Two thirds (242) of those with glaucoma had previously already received the diagnosis. In 76% of patients with newly diagnosed primary open angle glaucoma (83/107), the mean IOP was under the threshold for ocular hypertension (21 mm Hg). No one IOP threshold provided adequately high sensitivity and specificity for diagnosis of glaucoma.Conclusions In this British community, cases of glaucoma, suspected glaucoma, and ocular hypertension represent a large number of potential referrals to the hospital eye service. The use of IOP for detection of those with glaucoma is inaccurate and probably not viable

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.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 Research into Ageing (262). Genotyping was funded by the Medical Research Council (MC_PC_13048). Mr Khawaja is supported by a Moorfields Eye Charity grant. Miss Chan is a joint Medical Research Council/Royal College of Ophthalmologists Research Fellow, and received additional support from the International Glaucoma Association. Professor 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

Retinal Nerve Fiber Layer Measures and Cognitive Function in the EPIC-Norfolk Cohort Study

$\textbf{Purpose.}$ We examined the relationship between retinal nerve fiber layer (RNFL) thickness and cognitive function in a population of older British adults. $\textbf{Methods.}$ Participants of the European Prospective Investigation of Cancer (EPIC) Norfolk cohort study underwent ophthalmic and cognitive assessment. Measurements of RNFL thickness were made using the Heidelberg Retina Tomograph (HRT). Cognitive testing included a short form of the Mini-Mental State Examination (SF-MMSE), an animal naming task, a letter cancellation task, the Hopkins Verbal Learning Test (HVLT), the National Adult Reading Test (NART), and the Paired Associates Learning Test. Multivariable linear regression models were used to assess associations of RNFL thickness with cognitive test scores, adjusted for age, sex, education level, social class, visual acuity, axial length, and history of cataract surgery. $\textbf{Results.}$ Data were available from 5563 participants with a mean age of 67 years. A thicker HRT-derived RNFL thickness was associated with better scores for the SF-MMSE (0.06; 95% confidence interval [CI], [0.02, 0.10], P = 0.005), HVLT (0.16, 95% CI [0.03, 0.29]; P = 0.014), and NART (0.24, 95% CI [0.46, 0.02], P = 0.035). The associations of RNFL thickness with SF-MMSE and HVLT remained significant following further adjustment for NART. $\textbf{Conclusions.}$ We found a significant association between HRT-derived RNFL thickness and scores from cognitive tests assessing global function, recognition, learning, episodic memory, and premorbid intelligence. However, the associations were weak and not currently of predictive value. Further research is required to confirm and clarify the nature of these associations, and identify biological mechanisms.We would like to thank Mr Pak S. Lee for the training of research clinic nursing staff and equipment maintenance. 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 Research into Ageing (262). Mr Khawaja was a Wellcome Trust Clinical Research Fellow during the study. Professor 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. None of the funding organisations had a role in the design or conduct of the research.This is the final version of the article. It first appeared from the Association for Research in Vision and Ophthalmology via http://dx.doi.org/10.1167/iovs.16-1906

Retinal Nerve Fiber Layer Measures and Cognitive Function in the EPIC-Norfolk Cohort Study.

PURPOSE: We examined the relationship between retinal nerve fiber layer (RNFL) thickness and cognitive function in a population of older British adults. METHODS: Participants of the European Prospective Investigation of Cancer (EPIC) Norfolk cohort study underwent ophthalmic and cognitive assessment. Measurements of RNFL thickness were made using the Heidelberg Retina Tomograph (HRT). Cognitive testing included a short form of the Mini-Mental State Examination (SF-MMSE), an animal naming task, a letter cancellation task, the Hopkins Verbal Learning Test (HVLT), the National Adult Reading Test (NART), and the Paired Associates Learning Test. Multivariable linear regression models were used to assess associations of RNFL thickness with cognitive test scores, adjusted for age, sex, education level, social class, visual acuity, axial length, and history of cataract surgery. RESULTS: Data were available from 5563 participants with a mean age of 67 years. A thicker HRT-derived RNFL thickness was associated with better scores for the SF-MMSE (0.06; 95% confidence interval [CI], [0.02, 0.10], P = 0.005), HVLT (0.16, 95% CI [0.03, 0.29]; P = 0.014), and NART (-0.24, 95% CI [-0.46, -0.02], P = 0.035). The associations of RNFL thickness with SF-MMSE and HVLT remained significant following further adjustment for NART. CONCLUSIONS: We found a significant association between HRT-derived RNFL thickness and scores from cognitive tests assessing global function, recognition, learning, episodic memory, and premorbid intelligence. However, the associations were weak and not currently of predictive value. Further research is required to confirm and clarify the nature of these associations, and identify biological mechanisms.We would like to thank Mr Pak S. Lee for the training of research clinic nursing staff and equipment maintenance. 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 Research into Ageing (262). Mr Khawaja was a Wellcome Trust Clinical Research Fellow during the study. Professor 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. None of the funding organisations had a role in the design or conduct of the research.This is the final version of the article. It first appeared from the Association for Research in Vision and Ophthalmology via http://dx.doi.org/10.1167/iovs.16-1906

A framework for understanding shared substrates of airway protection

Deficits of airway protection can have deleterious effects to health and quality of life. Effective airway protection requires a continuum of behaviors including swallowing and cough. Swallowing prevents material from entering the airway and coughing ejects endogenous material from the airway. There is significant overlap between the control mechanisms for swallowing and cough. In this review we will present the existing literature to support a novel framework for understanding shared substrates of airway protection. This framework was originally adapted from Eccles' model of cough28 (2009) by Hegland, et al.42 (2012). It will serve to provide a basis from which to develop future studies and test specific hypotheses that advance our field and ultimately improve outcomes for people with airway protective deficits

Risk factors for previously undiagnosed primary open-angle glaucoma: the EPIC-Norfolk Eye Study.

BACKGROUND AND AIM: Undiagnosed glaucoma is an invisible but important public health issue. At least half of glaucoma cases are estimated to be undiagnosed in western populations. The aim of this study is to examine risk factors for previously undiagnosed primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study within the European Prospective Investigation of Cancer-Norfolk Eye Study, a large-scale cohort study in the UK. PARTICIPANTS: 314 study participants with POAG in either eye. METHODS: Logistic regression was used to examine associations with previously undiagnosed POAG compared with previously diagnosed POAG. The factors examined included sociodemographic, ocular, physical and economic factors that could be barriers to eye care access. RESULTS: 217 participants had previously diagnosed POAG and 107 participants were newly diagnosed with POAG during the study. After adjusting for covariables, the factors significantly associated with previously undiagnosed POAG were: a lower pretreatment intraocular pressure (IOP) (OR 0.71/mm Hg, 95% CI 0.63 to 0.80, p<0.0001), and to have reported no problems with their eyesight (OR 0.03, 95% CI 0.01 to 0.10, p<0.0001). CONCLUSIONS: The risk factors for previously undiagnosed POAG identified in this study highlight the over-reliance on IOP level in glaucoma screening and the risk of missing glaucoma among lower IOP cases. It also suggests a role in improving glaucoma awareness in the community

Risk factors for previously undiagnosed primary open-angle glaucoma: the EPIC-Norfolk Eye Study.

BACKGROUND AND AIM: Undiagnosed glaucoma is an invisible but important public health issue. At least half of glaucoma cases are estimated to be undiagnosed in western populations. The aim of this study is to examine risk factors for previously undiagnosed primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study within the European Prospective Investigation of Cancer-Norfolk Eye Study, a large-scale cohort study in the UK. PARTICIPANTS: 314 study participants with POAG in either eye. METHODS: Logistic regression was used to examine associations with previously undiagnosed POAG compared with previously diagnosed POAG. The factors examined included sociodemographic, ocular, physical and economic factors that could be barriers to eye care access. RESULTS: 217 participants had previously diagnosed POAG and 107 participants were newly diagnosed with POAG during the study. After adjusting for covariables, the factors significantly associated with previously undiagnosed POAG were: a lower pretreatment intraocular pressure (IOP) (OR 0.71/mm Hg, 95% CI 0.63 to 0.80, p<0.0001), and to have reported no problems with their eyesight (OR 0.03, 95% CI 0.01 to 0.10, p<0.0001). CONCLUSIONS: The risk factors for previously undiagnosed POAG identified in this study highlight the over-reliance on IOP level in glaucoma screening and the risk of missing glaucoma among lower IOP cases. It also suggests a role in improving glaucoma awareness in the community

Retinal Vasculometry Associations With Glaucoma: Findings From the European Prospective Investigation of Cancer-Norfolk Eye Study.

PURPOSE: To examine retinal vasculometry associations with different glaucomas in older British people. DESIGN: Cross-sectional study. METHODS: A total of 8,623 European Prospective Investigation into Cancer-Norfolk Eye study participants were examined, who underwent retinal imaging, ocular biometry assessment, and clinical ascertainment of ocular hypertensive or glaucoma status (including glaucoma suspect [GS], high-tension open-angle glaucoma [HTG], and normal-tension glaucoma [NTG]). Automated measures of arteriolar and venular tortuosity, area, and width from retinal images were obtained. MainOutcomeMeasures: Associations between glaucoma and retinal vasculometry outcomes were analyzed using multilevel linear regression, adjusted for age, sex, height, axial length, intraocular and systemic blood pressure, and within-person clustering, to provide absolute differences in width and area, and percentage differences in vessel tortuosity. Presence or absence of within-person-between-eye differences in retinal vasculometry by diagnoses were examined. RESULTS: A total of 565,593 vessel segments from 5,947 participants (mean age 67.6 years, SD 7.6 years, 57% women) were included; numbers with HTG, NTG, and GS in at least 1 eye were 87, 82, and 439, respectively. Thinner arterioles (-3.2 μm; 95% confidence interval [CI] -4.4 μm, -1.9 μm) and venules (-2.7 μm; 95% CI -4.9 μm, -0.5 μm) were associated with HTG. Reduced venular area was associated with HTG (-0.2 mm2; 95% CI -0.3 mm2, -0.1 mm2) and NTG (-0.2 mm2; 95% CI -0.3 mm2, -0.0 mm2). Less tortuous retinal arterioles and venules were associated with all glaucomas, but only significantly for GS (-3.9%; 95% CI -7.7%, -0.1% and -4.8%; 95% CI -7.4%, -2.1%, respectively). There was no evidence of within-person-between-eye differences in retinal vasculometry associations by diagnoses. CONCLUSIONS: Retinal vessel width associations with glaucoma and novel associations with vessel area and tortuosity, together with no evidence of within-person-between-eye differences in retinal vasculometry, suggest a vascular cause of glaucoma