ORCID Profile
0000-0002-4755-177X
Current Organisation
University College London
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Publisher: Elsevier BV
Date: 2019
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 06-2007
DOI: 10.1167/IOVS.06-1470
Abstract: Numerous genetic diseases and environmental stimuli affect optic nerve morphology. The purpose of this study was to identify the principal heritable components of visible optic nerve head structures in a population-based s le of twins. Fifteen optic nerve specialists viewed stereoscopic optic nerve head photographs (Stereo Viewer-II Pentax Corp., Tokyo, Japan) from 50 randomly selected monozygotic or dizygotic twin pairs. Before viewing, each expert was questioned about which optic nerve head traits they believed were inherited. After viewing a standardized teaching set, the experts indicated which twin pairs they thought were monozygotic. Participants were then questioned about how their decisions were reached. A rank-ordered Rasch analysis was used to determine the relative weighting and value applied to specific optic nerve head traits. The proportion of twin pairs for which zygosity was correctly identified ranged from 74% to 90% (median, 82%) across the panel. Experts who correctly identified the zygosity in more than 85% of cases placed most weighting on shape and size of the optic disc and cup, whereas experts with the lowest scores placed greater weighting on the optic nerve head vasculature in reaching their decisions. In determining the genetic components of the optic nerve head, the results of this study suggest that the shape and size of the optic disc and cup are more heritable and should receive a greater priority for quantification than should vascular features.
Publisher: BMJ
Date: 25-01-2021
DOI: 10.1136/BJOPHTHALMOL-2020-316218
Abstract: To examine the associations of air pollution with both self-reported age-related macular degeneration (AMD), and in vivo measures of retinal sublayer thicknesses. We included 115 954 UK Biobank participants aged 40–69 years old in this cross-sectional study. Ambient air pollution measures included particulate matter, nitrogen dioxide (NO 2 ) and nitrogen oxides (NO x ). Participants with self-reported ocular conditions, high refractive error ( −6 or +6 diopters) and poor spectral-domain optical coherence tomography (SD-OCT) image were excluded. Self-reported AMD was used to identify overt disease. SD-OCT imaging derived photoreceptor sublayer thickness and retinal pigment epithelium (RPE) layer thickness were used as structural biomarkers of AMD for 52 602 participants. We examined the associations of ambient air pollution with self-reported AMD and both photoreceptor sublayers and RPE layer thicknesses. After adjusting for covariates, people who were exposed to higher fine ambient particulate matter with an aerodynamic diameter .5 µm (PM 2.5 , per IQR increase) had higher odds of self-reported AMD (OR=1.08, p=0.036), thinner photoreceptor synaptic region (β=−0.16 µm, p=2.0 × 10 −5 ), thicker photoreceptor inner segment layer (β=0.04 µm, p=0.001) and thinner RPE (β=−0.13 µm, p=0.002). Higher levels of PM 2.5 absorbance and NO 2 were associated with thicker photoreceptor inner and outer segment layers, and a thinner RPE layer. Higher levels of PM 10 (PM with an aerodynamic diameter µm) was associated with thicker photoreceptor outer segment and thinner RPE, while higher exposure to NO x was associated with thinner photoreceptor synaptic region. Greater exposure to PM 2.5 was associated with self-reported AMD, while PM 2.5 , PM 2.5 absorbance, PM 10 , NO 2 and NO x were all associated with differences in retinal layer thickness.
Publisher: Springer Science and Business Media LLC
Date: 30-03-2020
Publisher: Public Library of Science (PLoS)
Date: 07-10-2016
Publisher: Hindawi Limited
Date: 09-06-2017
DOI: 10.1002/HUMU.23247
Abstract: Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of the meta-analysis using 1000GP to the meta-analysis results using HRC. Overall, we found that using HRC imputation significantly improved P values (P = 3.07 × 10
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 2008
DOI: 10.1167/IOVS.07-0866
Publisher: Public Library of Science (PLoS)
Date: 22-05-2015
Publisher: Springer Science and Business Media LLC
Date: 20-01-2020
Publisher: Springer Science and Business Media LLC
Date: 08-01-2019
DOI: 10.1038/S41467-018-07819-1
Abstract: Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Oxford University Press (OUP)
Date: 07-03-2013
DOI: 10.1093/HMG/DDT116
Publisher: Springer Science and Business Media LLC
Date: 21-05-2018
Publisher: BMJ
Date: 07-11-2022
Abstract: To investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population. We included 38 694 adults from 14 population-based and hospital-based studies from the European Eye Epidemiology consortium. We examined associations between the use of systemic medications and any prevalent AMD as well as any late AMD using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis. Between studies, mean age ranged from 61.5±7.1 to 82.6±3.8 years and prevalence ranged from 12.1% to 64.5% and from 0.5% to 35.5% for any and late AMD, respectively. In the meta-analysis of fully adjusted multivariable models, lipid-lowering drugs (LLD) and antidiabetic drugs were associated with lower prevalent any AMD (OR 0.85, 95% CI=0.79 to 0.91 and OR 0.78, 95% CI=0.66 to 0.91). We found no association with late AMD or with any other medication. Our study indicates a potential beneficial effect of LLD and antidiabetic drug use on prevalence of AMD across multiple European cohorts. Our findings support the importance of metabolic processes in the multifactorial aetiology of AMD.
Publisher: BMJ
Date: 26-02-2008
Abstract: To investigate the association of biometric and systemic variables with optic disc characteristics in Chinese Singaporean adults. Ocular, biometric and medical data including intraocular pressure, refractive error, keratometry, axial length (AL), anterior chamber depth, corneal and lens thickness as well as optic disc data (using planimetry of stereo-photographs) were obtained from 622 normal subjects aged > or = 40 years from the Tanjong Pagar glaucoma survey of Singapore. Disc area (DA) was positively associated with AL and height but was unrelated to corneal thickness. Following adjustment for IOP and sex, DA remained positively associated with AL, height and age. Neuroretinal rim area (RA) was also significantly and positively associated with AL and also with height. RA was negatively associated with IOP and was unrelated to blood pressure, history of diabetes, myocardial infarction, stroke or migraine. These data on a Chinese Singaporean population identify height and axial length of the globe as significantly associated with rim area of the disc. These features should be taken into account in statistical assessments of optic nerve head morphometry. This may improve the discriminative ability of image analysis to detect glaucomatous changes. In addition, we identified a statistically significant but small inverse association between rim area and IOP within the normal statistical range.
Publisher: BMJ
Date: 07-2013
Publisher: Springer Science and Business Media LLC
Date: 28-08-2015
DOI: 10.1038/EYE.2015.157
Publisher: Elsevier BV
Date: 09-2021
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-2008
DOI: 10.1167/IOVS.07-1397
Abstract: To estimate the heritability of the iridotrabecular angle width measured by anterior segment optical coherence tomography (ASOCT) in a classic twin study. Twins aged 8 to 16 years were identified from the Guangzhou Twin Registry. ASOCT was used to obtain one horizontal scan, and the images were analyzed with custom software. Angle width was represented by the angle opening distance (AOD) at the 500-microm anterior-to-scleral spur, as well as the angle recess area (ARA) and trabecular-iris space area (TISA) located 750 microm anterior to the scleral spur. Zygosity was confirmed by genotyping with 16 polymorphic markers in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling after adjustment for age and sex, with the Mx program. The mean age of the participants was 11.7 +/- 2.6 years in 305 monozygotic (MZ) and 11.8 +/- 2.4 years in 157 dizygotic (DZ) pairs. The intraclass correlation coefficients for the AOD, ARA, and TISA were 0.70, 0.75, and 0.72 in the MZ pairs and 0.34, 0.32, and 0.33 in the DZ pairs, respectively. A model with additive genetic (69.7% 95% CI: 63.9%-74.6%) and unique environmental effects (30.3% 95% CI: 25.4%-36.1%) was the most parsimonious for AOD. Similar results were identified for ARA and TISA. The variance in drainage angle width in Chinese children appears to be largely attributable to genetic effects, with a heritability of approximately 70%.
Publisher: Public Library of Science (PLoS)
Date: 18-10-2021
Publisher: BMJ
Date: 02-2019
DOI: 10.1136/BMJOPEN-2018-025077
Abstract: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc–macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and s le collection will be performed in subsets of 25 000 participants every 2–3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life.
Publisher: Elsevier BV
Date: 06-2022
Publisher: Elsevier BV
Date: 02-2015
Publisher: Elsevier BV
Date: 07-2023
Publisher: Springer Science and Business Media LLC
Date: 26-08-2012
DOI: 10.1038/NG.2390
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-06-2022
DOI: 10.1167/IOVS.63.6.29
Publisher: BMJ
Date: 26-02-2008
Abstract: To investigate the correlation between optic disc parameters and their association with demographic variables in a Chinese population. Disc data were obtained from 929 subjects aged > or = 40 years from the Tanjong Pagar glaucoma survey of Singapore, using a novel planimetric method of sequential stereo-photographs. Biometric data (refractive error, keratometry, axial length, anterior chamber depth, lens thickness) were used to calculate ocular magnification. Camera magnification was quantified with a model eye. A "normal" dataset of 622 subjects was generated by exclusion of subjects with abnormal results on psychophysical testing, an occludable angle or an intraocular pressure > 97.5th percentile in either eye. Median disc area (DA), cup area (CA), and rim area (RA) were 2.09 (range 1.28-4.01) mm2, 0.69 (0.01-1.90) mm2 and 1.38 (0.82-2.50) mm2, respectively. There was strong evidence of an association between DA and RA (Spearman's rho 0.624, p<0.001). DA and RA were significantly greater in men (median DA = 2.20 range 1.30-3.56 median RA, 1.45 range 0.85-2.30) than women (median DA, 2.00 range 1.28-4.01 median RA, 1.36 range 0.82-2.49, p women). Disc area (but not that of the rim) increases with age.
Publisher: Oxford University Press (OUP)
Date: 10-01-2017
DOI: 10.1093/HMG/DDW399
Publisher: Springer Science and Business Media LLC
Date: 11-01-2016
DOI: 10.1038/NG.3482
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.OPHTHA.2015.11.009
Abstract: To derive macular thickness measures and their associations by performing rapid, automated segmentation of spectral-domain optical coherence tomography (SD OCT) images collected and stored as part of the UK Biobank (UKBB) study. Large, multisite cohort study in the United Kingdom. Analysis of cross-sectional data. Adults from the United Kingdom aged 40 to 69 years. Participants had nonmydriatic SD OCT (Topcon 3D OCT-1000 Mark II Topcon GB, Newberry, Berkshire, UK) performed as part of the ocular assessment module. Rapid, remote, automated segmentation of the images was performed using custom optical coherence tomography (OCT) image analysis software (Topcon Advanced Boundary Segmentation [TABS] Topcon GB) to generate macular thickness values. We excluded people with a history of ocular or systemic disease (diabetes or neurodegenerative diseases) and eyes with reduced vision (<0.1 logarithm of the minimum angle of resolution) or with low SD OCT signal-to-noise ratio and low segmentation success certainty. Macular thickness values across 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields. The SD OCT scans of 67 321 subjects were available for analysis, with 32 062 people with at least 1 eye meeting the inclusion criteria. There were 17 274 women and 14 788 men, with a mean (standard deviation [SD]) age of 55.2 (8.2) years. The mean (SD) logarithm of the minimum angle of resolution visual acuity was -0.075 (0.087), and the refractive error was -0.071 (+1.91) diopters (D). The mean (SD) central macular thickness (CMT) in the central 1-mm ETDRS subfield was 264.5 (22.9) μm, with 95% confidence limits of 220.8 and 311.5 μm. After adjusting for covariates, CMT was positively correlated with older age, female gender, greater myopia, smoking, body mass index (BMI), and white ethnicity (all P < 0.001). Of note, macular thickness in other subfields was negatively correlated with older age and greater myopia. We report macular thickness data derived from SD OCT images collected as part of the UKBB study and found novel associations among older age, ethnicity, BMI, smoking, and macular thickness.
Publisher: Springer Science and Business Media LLC
Date: 05-01-2023
Publisher: Springer Science and Business Media LLC
Date: 13-05-2016
DOI: 10.1038/SREP25853
Abstract: Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7–15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E–08) and 2.3% (P = 6.9E–21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry s les (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4 P = 6.3E–04).
Publisher: Cold Spring Harbor Laboratory
Date: 26-07-2020
DOI: 10.1101/2020.07.20.20157180
Abstract: Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is often used to diagnose and manage multiple ophthalmic diseases including glaucoma. We present the first large-scale quantitative genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has previously been associated with glaucoma, and Mendelian randomisation confirms that inner retinal thickness, despite being a valid biomarker for the disease, is not on the same genetic causal pathway as glaucoma. Image analysis methods were used to extract overall retinal thickness at the fovea, representative of hypoplasia, with which three out of the 46 SNPs were associated. These SNPs have been previously linked with pigmentation, confirmed by their association with hair colour in the UK Biobank dataset. We additionally associate these three loci with visual acuity. In contrast to the already known Mendelian causes of severe foveal hypoplasia, our results suggest a previously unknown spectrum of foveal hypoplasia in the population, in part genetically determined, that has consequences on visual function.
Publisher: Wiley
Date: 09-09-2016
DOI: 10.1002/GEPI.21999
Abstract: Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 in iduals aged 25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10-25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated and in adults 20 loci were associated. Association with GRS increased with age β = 0.0016 per risk allele (P = 2 × 10
Publisher: Oxford University Press (OUP)
Date: 06-09-2019
DOI: 10.1093/HMG/DDZ193
Abstract: Optic nerve head morphology is affected by several retinal diseases. We measured the vertical optic disc diameter (DD) of the UK Biobank (UKBB) cohort (N = 67 040) and performed the largest genome-wide association study (GWAS) of DD to date. We identified 81 loci (66 novel) for vertical DD. We then replicated the novel loci in International Glaucoma Genetic Consortium (IGGC, N = 22 504) and European Prospective Investigation into Cancer–Norfolk (N = 6005) in general the concordance in effect sizes was very high (correlation in effect size estimates 0.90): 44 of the 66 novel loci were significant at P & 0.05, with 19 remaining significant after Bonferroni correction. We identified another 26 novel loci in the meta-analysis of UKBB and IGGC data. Gene-based analyses identified an additional 57 genes. Human ocular tissue gene expression analysis showed that most of the identified genes are enriched in optic nerve head tissue. Some of the identified loci exhibited pleiotropic effects with vertical cup-to-disc ratio, intraocular pressure, glaucoma and myopia. These results can enhance our understanding of the genetics of optic disc morphology and shed light on the genetic findings for other ophthalmic disorders such as glaucoma and other optic nerve diseases.
Publisher: Public Library of Science (PLoS)
Date: 15-07-2015
Publisher: Cold Spring Harbor Laboratory
Date: 03-02-2020
DOI: 10.1101/2020.01.30.927822
Abstract: We conducted a large multi-ethnic meta-analysis of genome-wide association studies for primary open-angle glaucoma (POAG) on a total of 34,179 cases vs 349,321 controls, and identified 127 independent risk loci, almost doubling the number of known loci for POAG. The majority of loci have broadly consistent effect across European, Asian and African ancestries. We identify a link, both genome-wide and at specific loci, between POAG and Alzheimer’s disease. Gene expression data and bioinformatic functional analyses provide further support for the functional relevance of the POAG risk genes. Several drug compounds target these risk genes and may be potential candidates for developing novel POAG treatments.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.OPHTHA.2012.04.020
Abstract: To summarize relevant evidence investigating the association between time spent outdoors and myopia in children and adolescents (up to 20 years). Systematic review and meta-analysis. Results from 7 cross-sectional studies were pooled in a meta-analysis. A further 16 studies (8 cross-sectional not meeting criteria for meta-analysis 7 prospective cohort studies 1 randomized, controlled trial [RCT]) were reported in the systematic review. The literature search included 4 databases (Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials [CENTRAL]), and reference lists of retrieved studies. Estimates of association were pooled using random effects meta-analysis. We summarized data examining the association between time spent outdoors and prevalent myopia, incident myopia, and myopic progression. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for myopia for each additional hour spent outdoors per week from a meta-analysis. The pooled OR for myopia indicated a 2% reduced odds of myopia per additional hour of time spent outdoors per week, after adjustment for covariates (OR, 0.981 95% CI, 0.973-0.990 P<0.001 I(2), 44.3%). This is equivalent to an OR of 0.87 for an additional hour of time spent outdoors each day. Three prospective cohort studies provided estimates of risk of incident myopia according to time spent outdoors, adjusted for possible confounders, although estimates could not be pooled, and the quality of studies and length of follow-up times varied. Three studies (2 prospective cohort and 1 RCT) investigated time spent outdoors and myopic progression and found increasing time spent outdoors significantly reduced myopic progression. The overall findings indicate that increasing time spent outdoors may be a simple strategy by which to reduce the risk of developing myopia and its progression in children and adolescents. Therefore, further RCTs are warranted to investigate the efficacy of increasing time outdoors as a possible intervention to prevent myopia and its progression.
Publisher: Oxford University Press (OUP)
Date: 14-06-2013
DOI: 10.1093/IJE/DYT086
Publisher: Public Library of Science (PLoS)
Date: 03-05-2012
Publisher: Public Library of Science (PLoS)
Date: 18-02-2015
Publisher: Elsevier BV
Date: 08-2013
Publisher: Elsevier BV
Date: 07-2015
Publisher: Springer Science and Business Media LLC
Date: 06-04-2016
DOI: 10.1038/NCOMMS11008
Abstract: Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry in iduals, we identify six novel loci ( FAM150B-ACP1 , LINC00340 , FBN1 , DIS3L-MAP2K1 , ARID2-SNAT1 and SLC14A2 ) associated with refractive error. In Asian populations, three genome-wide significant loci AREG , GABRR1 and PDE10A also exhibit strong interactions with education ( P .5 × 10 −5 ), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.
Publisher: BMJ
Date: 02-2021
DOI: 10.1136/BMJOPHTH-2020-000585
Abstract: There is contrasting evidence on the relationship between socioeconomic status (SES) and age-related macular degeneration (AMD), the most common cause of visual impairment (VI) in developed countries. This study examines the relationship between SES, cardiovascular risk factors and self-reported AMD. Over 500000 people participated in the UK Biobank study from 2006 to 2019, with sociodemographic data and clinical measurements collected using standardised procedures. Visual acuity was measured in 117907 participants with VI defined as LogMAR ≤0.3. We used logistic regression to examine the cross-sectional associations between SES and self-reported AMD. Self-reported AMD was available for 133339 participants aged 50 and older. People reporting AMD had higher academic qualifications, lower income, were unable to work due to disability, have higher BMI, diabetes and vascular heart disease after adjusting for age and sex. In a multivariable analysis, higher income was protective of AMD and economic inactivity due to disability increased the odds of AMD (2.02, 95% CI 1.13 to 3.61). Both associations were independent of cardiovascular factors, but was no longer significant after adjusting for VI. The association between education, employment and household income with AMD was independent of cardiovascular risk factors.
Publisher: Public Library of Science (PLoS)
Date: 06-03-2014
Publisher: Springer Science and Business Media LLC
Date: 15-08-2018
DOI: 10.1038/S41598-018-30004-9
Abstract: We evaluated the prevalence of visual impairment (VI) and blindness among Chinese adults in the Singapore Chinese Eye Study (SCES, 2009–2011), and compared the trends with the Tanjong Pagar Survey, Singapore (TPS), conducted a decade earlier. The SCES comprised of 3,353 Chinese adults aged ≥40 years (response rate, 72.8%). Participants underwent standardized examinations, including measurements of presenting, and best-corrected visual acuity (VA). Bilateral VI (VA 20/40 to ≥20/200) and blindness (VA 20/200) were defined based on the United States definition (better-seeing eye). Age-standardized prevalence was calculated using the 2010 Singapore Chinese Population Census. Primary causes and factors associated with VI and blindness were evaluated. In SCES, the age-standardized prevalence of presenting bilateral VI and blindness were 17.7% and 0.6%, respectively the age-standardised prevalence of best-corrected bilateral VI and blindness were 3.4% and 0.2%, respectively. The previous TPS reported similar rates of best-corrected bilateral VI (3.8%) and blindness (0.3%). In SCES, cataract remains the main cause for both best-corrected bilateral VI (76.0%) and blindness (50.0%). Older age, female, lower income, lower educational level, and smaller housing type were associated with presenting bilateral VI or blindness (all P ≤ 0.025). These findings will be useful for the planning of eye care services and resource allocation.
Publisher: Springer Science and Business Media LLC
Date: 03-11-2022
DOI: 10.1038/S41433-022-02298-7
Abstract: This study aims to describe the grading methods and baseline characteristics for UK Biobank (UKBB) participants who underwent retinal imaging in 2009–2010, and to characterise in iduals with retinal features suggestive of age-related macular degeneration (AMD), glaucoma and retinopathy. Non-mydriatic colour fundus photographs and macular optical coherence tomography (OCT) scans were manually graded by Central Administrative Research Facility certified graders and quality assured by clinicians of the Network of Ophthalmic Reading Centres UK. Captured retinal features included those associated with AMD (≥1 drusen, pigmentary changes, geographic atrophy or exudative AMD either imaging modality), glaucoma (≥0.7 cup-disc ratio, ≥0.2 cup-disc ratio difference between eyes, other abnormal disc features photographs only) and retinopathy (characteristic features of diabetic retinopathy with or without microaneurysms either imaging modality). Suspected cases of these conditions were characterised with reference to diagnostic records, physical and biochemical measurements. Among 68,514 UKBB participants who underwent retinal imaging, the mean age was 57.3 years (standard deviation 8.2), 45.7% were men and 90.6% were of White ethnicity. A total of 64,367 participants had gradable colour fundus photographs and 68,281 had gradable OCT scans in at least one eye. Retinal features suggestive of AMD and glaucoma were identified in 15,176 and 2184 participants, of whom 125 (0.8%) and 188 (8.6%), respectively, had a recorded diagnosis. Of 264 participants identified to have retinopathy with microaneurysms, 251 (95.1%) had either diabetes or hypertension. This dataset represents a valuable addition to what is currently available in UKBB, providing important insights to both ocular and systemic health.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2018
Publisher: Springer Science and Business Media LLC
Date: 31-08-2014
DOI: 10.1038/NG.3079
Publisher: Public Library of Science (PLoS)
Date: 12-05-2021
DOI: 10.1371/JOURNAL.PGEN.1009497
Abstract: Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2020
DOI: 10.1038/S42003-020-0802-Y
Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 in iduals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11 / FBLN2 rs2630445, RBP3 rs11204213) others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.
Publisher: Springer Science and Business Media LLC
Date: 24-02-2021
DOI: 10.1038/S41467-020-20851-4
Abstract: Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638 , CLIC5, SLC2A12, YAP1, MXRA5 , and SMAD6 . Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 19-04-2016
Publisher: Springer Science and Business Media LLC
Date: 14-05-2018
DOI: 10.1038/S41467-018-03646-6
Abstract: Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, % of the CCT-loci are near or within Mendelian disorder genes. These included FBN1 , ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus ( r = −0.62, P = 5.30 × 10 −5 ) but not between CCT and primary open-angle glaucoma ( r = −0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 2008
DOI: 10.1167/IOVS.07-1052
Abstract: To assess the heritability of anterior chamber depth (ACD) and relative anterior chamber depth (ACD/axial length, rACD) in Chinese in a classic twin study. Twins aged 7 to 15 years living in two local districts were recruited from the Guangzhou Twin Registry. Anterior chamber depth and axial length were measured by partial coherence laser interferometry. Zygosity in all same-sex twin pairs was confirmed by genotyping with 16 polymorphic markers. The phenotypes of the right eyes were used in analysis. Heritability was assessed by structural variance component genetic modeling. In total, 1126 twin participants were available for analysis, including 357 monozygotic (MZ) and 206 dizygotic (DZ) twin pairs. ACD increased with age (0.036 mm per year, P < 0.001) and 0.09 mm shallower in the girls than in the boys (P < 0.001). Age- and sex-adjusted intraclass correlation coefficients (ICCs) for ACD were 0.92 for the MZ and 0.50 for the DZ twins those for rACD were 0.89 for the MZ and 0.52 for the DZ twins. The best-fitting model yielded 90.1% (95% CI: 88.2%-91.7%) of additive genetic and 9.9% (95% CI: 8.3%-11.8%) of unique environmental effects for ACD and 89.2% (95% CI: 87.1%-90.9%) of additive genetic and 10.8% (95% CI: 9.1%-12.9%) of unique environmental effects for rACD. Additive genetic effects appear to be the major contributor to the variation of ACD and rACD in Chinese population. High heritability remained even when the data were corrected for the influence of myopia.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.OPHTHA.2019.08.015
Abstract: 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. Cross-sectional study. We included 42 044 participants in the UK Biobank. The mean age was 56 years. 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. Thicknesses of mRNFL, GCC, and GCIPL. 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 The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2015
Publisher: Springer Science and Business Media LLC
Date: 19-12-2015
DOI: 10.1007/S10654-015-0098-2
Abstract: The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in in idual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological s les, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.
Publisher: Public Library of Science (PLoS)
Date: 21-08-2013
Publisher: Springer Science and Business Media LLC
Date: 27-11-2019
DOI: 10.1038/S42003-019-0634-9
Abstract: A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG) intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is h ered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.
Publisher: Springer Science and Business Media LLC
Date: 04-04-2016
DOI: 10.1038/NG.3540
Abstract: Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.
Publisher: Elsevier BV
Date: 12-2017
Publisher: BMJ
Date: 25-06-2022
DOI: 10.1136/BJOPHTHALMOL-2020-317718
Abstract: 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). Cross-sectional study within the European Prospective Investigation of Cancer-Norfolk Eye Study, a large-scale cohort study in the UK. 314 study participants with POAG in either eye. 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. 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 .0001), and to have reported no problems with their eyesight (OR 0.03, 95% CI 0.01 to 0.10, p .0001). 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.
Publisher: Springer Science and Business Media LLC
Date: 04-11-2014
Publisher: Public Library of Science (PLoS)
Date: 02-10-2015
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Paul Foster.