@article{Pontikos2019,
title = {Frequency and distribution of corneal astigmatism and keratometry features in adult life: Methodology and findings of the UK Biobank study},
author = {N Pontikos and et al},
url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218144},
year = {2019},
date = {2019-09-19},
journal = {PLOS One},
abstract = {This analysis included a subsample of 107,452 participants of the UK Biobank study who underwent an enhanced ophthalmic examination including autorefractor keratometry (Tomey RC 5000, Tomey Corp., Nagoya, Japan). Participants were recruited from across the United Kingdom between 2006 and 2010, and all were between 40 to 69 years. After quality control and applying relevant exclusions, data on corneal astigmatism on 83,751 participants were included for analysis. Potential associations were tested through univariable regression and significant parameters carried forward for multivariable analysis.

Results
In univariable analysis, the characteristics significantly associated with higher corneal astigmatism (P<0.001), by order of magnitude were, female gender, white ethnicity, lighter skin colour, use of UV protection, lower alcohol intake, lower corneal-compensated intraocular pressure (ccIOP), older age at completion of education, younger age, higher Townsend deprivation index, lower height and lower systolic blood pressure. After inclusion in the multivariable analysis, gender, skin colour, alcohol intake, age at completion of full-time education, ccIOP, age and Townsend deprivation score remained significant (all P<0.001). Increased corneal astigmatism was also found to be significantly associated with amblyopia or strabismus.

Conclusions
This analysis confirms previous associations with astigmatism such as younger age and female gender, and identified novel risk factors including lighter skin colour, lower alcohol intake, later age having completed full time education later, lower ccIOP and higher Townsend deprivation index. Further research is needed to investigate these novel associations.},
keywords = {10536, methodology, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Khawaja2019,
title = {Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort},
author = {A Khawaja },
url = {https://www.aaojournal.org/article/S0161-6420(19)31937-2/abstract},
year = {2019},
date = {2019-08-15},
journal = {Ophthalmology},
abstract = {Purpose
To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell–inner plexiform layer (GCIPL) thicknesses in a large cohort.

Design
Cross-sectional study.

Participants
We included 42 044 participants in the UK Biobank. The mean age was 56 years.

Methods
Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc.

Main Outcome Measures
Thicknesses of mRNFL, GCC, and GCIPL.

Results
We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: –0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61–0.30]; P = 1.1×10–8), greater social deprivation (most significant for GCIPL: –0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, –0.42 to –0.14]; P = 6.6×10–5), lower educational attainment (most significant for mRNFL: –0.36 μm for less than O level compared with degree level [95% CI, –0.45 to 0.26]; P = 2.3×10–14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: –1.65 μm [95% CI, –1.86 to –1.43]; P = 2.4×10–50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (–0.04 μm/mmHg [95% CI, –0.05 to –0.03]; P = 4.0×10–10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, –0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%).},
keywords = {36741, genetics, retinal thickness, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Zhang2019b,
title = {Associations with Corneal Hysteresis in a Population Cohort: Results from 96 010 UK Biobank Participants},
author = {B Zhang and et al},
url = {https://www.aaojournal.org/article/S0161-6420(19)30724-9/fulltext},
year = {2019},
date = {2019-07-05},
journal = {Ophthalmology},
abstract = {Purpose
To describe the distribution of corneal hysteresis (CH) in a large cohort and explore its associated factors and possible clinical applications.

Design
Cross-sectional study within the UK Biobank, a large cohort study in the United Kingdom.

Participants
We analyzed CH data from 93 345 eligible participants in the UK Biobank cohort, aged 40 to 69 years.

Methods
All analyses were performed using left eye data. Linear regression models were used to evaluate associations between CH and demographic, lifestyle, ocular, and systemic variables. Piecewise logistic regression models were used to explore the relationship between self-reported glaucoma and CH.


Main Outcome Measures
Corneal hysteresis (mmHg).

Results
The mean CH was 10.6 mmHg (10.4 mmHg in male and 10.8 mmHg in female participants). After adjusting for covariables, CH was significantly negatively associated with male sex, age, black ethnicity, self-reported glaucoma, diastolic blood pressure, and height. Corneal hysteresis was significantly positively associated with smoking, hyperopia, diabetes, systemic lupus erythematosus (SLE), greater deprivation (Townsend index), and Goldmann-correlated intraocular pressure (IOPg). Self-reported glaucoma and CH were significantly associated when CH was less than 10.1 mmHg (odds ratio, 0.86; 95% confidence interval, 0.79–0.94 per mmHg CH increase) after adjusting for covariables. When CH exceeded 10.1 mmHg, there was no significant association between CH and self-reported glaucoma.

Conclusions
In our analyses, CH was significantly associated with factors including age, sex, and ethnicity, which should be taken into account when interpreting CH values. In our cohort, lower CH was significantly associated with a higher prevalence of self-reported glaucoma when CH was less than 10.1 mmHg. Corneal hysteresis may serve as a biomarker aiding glaucoma case detection.},
keywords = {15008, corneal hysterisis, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Plotnikov2019b,
title = {A commonly occurring genetic variant within the NPLOC4-TSPAN10-PDE6G gene cluster is associated with the risk of strabismus},
author = {D Plotnikov and RL Shah and JN Rodrigues and PM Cumberland and JS Rahi and PG Hysi and D Atan and C Williams and JA Guggenheim},
url = {https://www.ncbi.nlm.nih.gov/pubmed/31073882},
year = {2019},
date = {2019-05-09},
journal = {Human genetics},
abstract = {Strabismus refers to an abnormal alignment of the eyes leading to the loss of central binocular vision. Concomitant strabismus occurs when the angle of deviation is constant in all positions of gaze and often manifests in early childhood when it is considered to be a neurodevelopmental disorder of the visual system. As such, it is inherited as a complex genetic trait, affecting 2-4% of the population. A genome-wide association study (GWAS) for self-reported strabismus (1345 cases and 65,349 controls from UK Biobank) revealed a single genome-wide significant locus on chromosome 17q25. Approximately 20 variants across the NPLOC4-TSPAN10-PDE6G gene cluster and in almost perfect linkage disequilibrium (LD) were most strongly associated (lead variant: rs75078292, OR = 1.26, p = 2.24E-08). A recessive model provided a better fit to the data than an additive model. Association with strabismus was independent of refractive error, and the degree of association with strabismus was minimally attenuated after adjustment for amblyopia. The association with strabismus was replicated in an independent cohort of clinician-diagnosed children aged 7 years old (116 cases and 5084 controls; OR = 1.85, p = 0.009). The associated variants included 2 strong candidate causal variants predicted to have functional effects: rs6420484, which substitutes tyrosine for a conserved cysteine (C177Y) in the TSPAN10 gene, and a 4-bp deletion variant, rs397693108, predicted to cause a frameshift in TSPAN10. The population-attributable risk for the locus was approximately 8.4%, indicating an important role in conferring susceptibility to strabismus.},
keywords = {17351, genetics, strabismus, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Huang2019,
title = {A Genome-Wide Association Study for Susceptibility to Visual Experience-Induced Myopia},
author = {Y Huang and CS Kee and PM Hocking and C Williams and SP Yip and JA Guggenheim and UK Biobank Eye and Vision Consortium and The CREAM Consortium.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30721303},
year = {2019},
date = {2019-01-01},
journal = {Investigative Ophtalmology and Visual Science},
abstract = {Purpose:
The rapid rise in prevalence over recent decades and high heritability of myopia suggest a role for gene-environment (G × E) interactions in myopia susceptibility. Few such G × E interactions have been discovered to date. We aimed to test the hypothesis that genetic analysis of susceptibility to visual experience-induced myopia in an animal model would identify novel G × E interaction loci.

Methods:
Chicks aged 7 days (n = 987) were monocularly deprived of form vision for 4 days. A genome-wide association study (GWAS) was carried out in the 20% of chicks most susceptible and least susceptible to form deprivation (n = 380). There were 304,963 genetic markers tested for association with the degree of induced axial elongation in treated versus control eyes (A-scan ultrasonography). A GWAS candidate region was examined in the following three human cohorts: CREAM consortium (n = 44,192), UK Biobank (n = 95,505), and Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4989).

Results:
A locus encompassing the genes PIK3CG and PRKAR2B was genome-wide significantly associated with myopia susceptibility in chicks (lead variant rs317386235, P = 9.54e-08). In CREAM and UK Biobank GWAS datasets, PIK3CG and PRKAR2B were enriched for strongly-associated markers (meta-analysis lead variant rs117909394, P = 1.7e-07). In ALSPAC participants, rs117909394 had an age-dependent association with refractive error (-0.22 diopters [D] change over 8 years, P = 5.2e-04) and nearby variant rs17153745 showed evidence of a G × E interaction with time spent reading (effect size -0.23 D, P = 0.022).

Conclusions:
This work identified the PIK3CG-PRKAR2B locus as a mediator of susceptibility to visually induced myopia in chicks and suggests a role for this locus in conferring susceptibility to myopia in human cohorts.},
keywords = {17351, genetics, myopia, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Shah2018,
title = {Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci},
author = {RL Shah and JA Guggenheim and UK Biobank Eye and Vision Consortium},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30306274},
year = {2018},
date = {2018-10-10},
journal = {Human Genetics},
abstract = {Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association studies for corneal and refractive astigmatism were performed in individuals of European ancestry (N = 86,335 and 88,005 respectively), with the mean corneal astigmatism or refractive astigmatism in fellow eyes analysed as a quantitative trait (dependent variable). Genetic correlation between the two traits was calculated using LD Score regression. Gene-based and gene-set tests were carried out using MAGMA. Single marker-based association tests for corneal astigmatism identified four genome-wide significant loci (P < 5 × 10-8) near the genes ZC3H11B (1q41), LINC00340 (6p22.3), HERC2/OCA2 (15q13.1) and NPLOC4/TSPAN10 (17q25.3). Three of these loci also demonstrated genome-wide significant association with refractive astigmatism: LINC00340, HERC2/OCA2 and NPLOC4/TSPAN10. The genetic correlation between corneal and refractive astigmatism was 0.85 (standard error = 0.068, P = 1.37 × 10-35). Here, we have undertaken the largest genome-wide association studies for corneal and refractive astigmatism to date and identified four novel loci for corneal astigmatism, two of which were also novel loci for refractive astigmatism. These loci have previously demonstrated association with axial length (ZC3H11B), myopia (NPLOC4), spherical equivalent refractive error (LINC00340) and eye colour (HERC2). The shared role of these novel candidate genes for astigmatism lends further support to the shared genetic susceptibility of myopia and astigmatism.},
keywords = {17351, eye, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Welikala2017,
title = {Automated arteriole and venule classification using deep learning for retinal images from the UK Biobank cohort.},
author = {RA Welikala and P Foster and PH Whincup and AR Rudnicka and CG Owen and DP Strachan and SA Barman and UK Biobank Eye and Vision Consortium.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28917120},
year = {2017},
date = {2017-09-08},
journal = {Computers in Biology and Medicine},
abstract = {The morphometric characteristics of the retinal vasculature are associated with future risk of many systemic and vascular diseases. However, analysis of data from large population based studies is needed to help resolve uncertainties in some of these associations. This requires automated systems that extract quantitative measures of vessel morphology from large numbers of retinal images. Associations between retinal vessel morphology and disease precursors/outcomes may be similar or opposing for arterioles and venules. Therefore, the accurate detection of the vessel type is an important element in such automated systems. This paper presents a deep learning approach for the automatic classification of arterioles and venules across the entire retinal image, including vessels located at the optic disc. This comprises of a convolutional neural network whose architecture contains six learned layers: three convolutional and three fully-connected. Complex patterns are automatically learnt from the data, which avoids the use of hand crafted features. The method is developed and evaluated using 835,914 centreline pixels derived from 100 retinal images selected from the 135,867 retinal images obtained at the UK Biobank (large population-based cohort study of middle aged and older adults) baseline examination. This is a challenging dataset in respect to image quality and hence arteriole/venule classification is required to be highly robust. The method achieves a significant increase in accuracy of 8.1% when compared to the baseline method, resulting in an arteriole/venule classification accuracy of 86.97% (per pixel basis) over the entire retinal image.},
keywords = {computer, imaging, methodology, Retinal, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Guggenheim2015,
title = {Role of Educational Exposure in the Association Between Myopia and Birth Order},
author = {MBBS PhD FRCOphth2 Jeremy A. Guggenheim PhD1; Cathy Williams},
url = {http://archopht.jamanetwork.com/article.aspx?articleid=2448580#Conclusions},
year = {2015},
date = {2015-10-08},
keywords = {15716, 375 eye, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Cumberland2015b,
title = {Frequency and Distribution of Refractive Error in Adult Life: Methodology and Findings of the UK Biobank Study},
author = {Phillippa M Cumberland and Yanchun Bao and Pirro G Hysi and Paul J Foster and Christopher Hammond Jugnoo J S Rahi and UK Biobank Eyes & Vision Consortium},
url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0139780},
year = {2015},
date = {2015-10-05},
journal = {PLOS one},
abstract = {Purpose

To report the methodology and findings of a large scale investigation of burden and distribution of refractive error, from a contemporary and ethnically diverse study of health and disease in adults, in the UK.
Methods

U K Biobank, a unique contemporary resource for the study of health and disease, recruited more than half a million people aged 40–69 years. A subsample of 107,452 subjects undertook an enhanced ophthalmic examination which provided autorefraction data (a measure of refractive error). Refractive error status was categorised using the mean spherical equivalent refraction measure. Information on socio-demographic factors (age, gender, ethnicity, educational qualifications and accommodation tenure) was reported at the time of recruitment by questionnaire and face-to-face interview.
Results

Fifty four percent of participants aged 40–69 years had refractive error. Specifically 27% had myopia (4% high myopia), which was more common amongst younger people, those of higher socio-economic status, higher educational attainment, or of White or Chinese ethnicity. The frequency of hypermetropia increased with age (7% at 40–44 years increasing to 46% at 65–69 years), was higher in women and its severity was associated with ethnicity (moderate or high hypermetropia at least 30% less likely in non-White ethnic groups compared to White).
Conclusions

Refractive error is a significant public health issue for the UK and this study provides contemporary data on adults for planning services, health economic modelling and monitoring of secular trends. Further investigation of risk factors is necessary to inform strategies for prevention. There is scope to do this through the planned longitudinal extension of the UK Biobank study.},
keywords = {669, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Rönnberg2014,
title = {The Effect of Functional Hearing Loss and Age on Long- and Short-term Visuospatial Memory: Evidence from the UK Biobank Resource},
author = {Jerker Rönnberg and Staffan Hygge and Gitte Keidser and Mary Rudner},
url = {http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00326/abstract},
year = {2014},
date = {2014-11-07},
journal = {Frontiers in Aging and Neuroscience},
volume = {6},
pages = {326},
abstract = {The UK Biobank offers cross-sectional epidemiological data collected on > 500 000 individuals in the UK between 40 and 70 years of age. Using the UK Biobank data, the aim of this study was to investigate the effects of functional hearing loss and hearing aid usage on visuospatial memory function. This selection of variables resulted in a sub-sample of 138 098 participants after discarding extreme values. A digit triplets functional hearing test was used to divide the participants into three groups: poor, insufficient and normal hearers. We found negative relationships between functional hearing loss and both visuospatial working memory (i.e., a card pair matching task) and visuospatial, episodic long-term memory (i.e., a prospective memory task), with the strongest association for episodic long-term memory. The use of hearing aids showed a small positive effect for working memory performance for the poor hearers, but did not have any influence on episodic long-term memory. Age also showed strong main effects for both memory tasks and interacted with gender and education for the long-term memory task. Broader theoretical implications based on a memory systems approach will be discussed and compared to theoretical alternatives.},
keywords = {3572, hearing, memory, vision},
pubstate = {published},
tppubtype = {article}
}

@article{Dawes2014b,
title = {Vision impairment and dual sensory problems in middle age.},
author = {P Dawes and C Dickinson and R Emsley and PN Bishop and KJ Cruickshanks and M Edmondson-Jones and A McCormack and H Fortnum and DR Moore and P Norman and K Munro},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24888710},
year = {2014},
date = {2014-05-29},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists).},
volume = {34},
number = {4},
pages = {479-88},
abstract = {PURPOSE:
Vision and hearing impairments are known to increase in middle age. In this study we describe the prevalence of vision impairment and dual sensory impairment in UK adults aged 40-69 years in a very large and recently ascertained data set. The associations between vision impairment, age, sex, socioeconomic status, and ethnicity are reported.
METHODS: This research was conducted using the UK Biobank Resource, with subsets of UK Biobank data analysed with respect to self-report of eye problems and glasses use. Better-eye visual acuity with habitually worn refractive correction was assessed with a logMAR chart (n = 116,682). Better-ear speech reception threshold was measured with an adaptive speech in noise test, the Digit Triplet Test (n = 164,770). Prevalence estimates were weighted with respect to UK 2001 Census data.
RESULTS:
Prevalence of mild visual impairment (VA >0.1 logMAR (6/7.5, 20/25) and ≥0.48 (6/18, 20/60)) and low vision (VA >0.48 (6/18, 20/60) and ≥1.3 (6/120, 20/400)) was estimated at 13.1% (95% CI 12.9-13.4) and 0.8% (95% CI 0.7-0.9), respectively. Use of glasses was 88.0% (95% CI 87.9-88.1). The prevalence of dual sensory impairment was 3.1% (95% CI 3.0-3.2) and there was a nine-fold increase in the prevalence of dual sensory problems between the youngest and oldest age groups. Older adults, those from low socioeconomic and ethnic minority backgrounds were most at risk for vision problems.
CONCLUSIONS:
Mild vision impairment is common in middle aged UK adults, despite widespread use of spectacles. Increased likelihood of vision impairment with older age and with ethnic minorities is of concern given ageing and more ethnically diverse populations. Possible barriers to optometric care for those from low socioeconomic and ethnic minority backgrounds may require attention. A higher than expected prevalence of dual impairment suggests that hearing and vision problems share common causes. Optometrists should consider screening for hearing problems, particularly among older adults.},
keywords = {166, eyesight, vision},
pubstate = {published},
tppubtype = {article}
}