ORCID Profile
0000-0003-0994-6196
Current Organisations
University of Western Australia
,
Garvan Institute of Medical Research
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Publisher: Springer Science and Business Media LLC
Date: 2021
DOI: 10.1007/S43630-020-00001-X
Abstract: This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive assessment (Photochemical and Photobiological Sciences, 2019, 18, 595–828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality human health terrestrial and aquatic ecosystems biogeochemical cycles and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.
Publisher: Springer Science and Business Media LLC
Date: 03-2023
DOI: 10.1007/S43630-023-00375-8
Abstract: This assessment by the Environmental Effects Assessment Panel (EEAP) of the Montreal Protocol under the United Nations Environment Programme (UNEP) evaluates the effects of ultraviolet (UV) radiation on human health within the context of the Montreal Protocol and its Amendments. We assess work published since our last comprehensive assessment in 2018. Over the last four years gains have been made in knowledge of the links between sun exposure and health outcomes, mechanisms, and estimates of disease burden, including economic impacts. Of particular note, there is new information about the way in which exposure to UV radiation modulates the immune system, causing both harms and benefits for health. The burden of skin cancer remains high, with many lives lost to melanoma and many more people treated for keratinocyte cancer, but it has been estimated that the Montreal Protocol will prevent 11 million cases of melanoma and 432 million cases of keratinocyte cancer that would otherwise have occurred in the United States in people born between 1890 and 2100. While the incidence of skin cancer continues to rise, rates have stabilised in younger populations in some countries. Mortality has also plateaued, partly due to the use of systemic therapies for advanced disease. However, these therapies are very expensive, contributing to the extremely high economic burden of skin cancer, and emphasising the importance and comparative cost-effectiveness of prevention. Photodermatoses, inflammatory skin conditions induced by exposure to UV radiation, can have a marked detrimental impact on the quality of life of sufferers. More information is emerging about their potential link with commonly used drugs, particularly anti-hypertensives. The eyes are also harmed by over-exposure to UV radiation. The incidence of cataract and pterygium is continuing to rise, and there is now evidence of a link between intraocular melanoma and sun exposure. It has been estimated that the Montreal Protocol will prevent 63 million cases of cataract that would otherwise have occurred in the United States in people born between 1890 and 2100. Despite the clearly established harms, exposure to UV radiation also has benefits for human health. While the best recognised benefit is production of vitamin D, beneficial effects mediated by factors other than vitamin D are emerging. For both sun exposure and vitamin D, there is increasingly convincing evidence of a positive role in diseases related to immune function, including both autoimmune diseases and infection. With its influence on the intensity of UV radiation and global warming, the Montreal Protocol has, and will have, both direct and indirect effects on human health, potentially changing the balance of the risks and benefits of spending time outdoors. Graphical abstract
Publisher: BMJ
Date: 17-07-2019
DOI: 10.1136/BJOPHTHALMOL-2018-312159
Abstract: To conduct a systematic review and meta-analysis of the association of blood vitamin D (25-hydroxyvitamin D, 25(OH)D) concentration and vitamin D pathway genes with myopia. We searched the MEDLINE and EMBASE databases for studies published up to 29 January 2018. Cross-sectional or cohort studies which evaluated the blood 25(OH)D concentration, blood 25(OH)D3 concentration or vitamin D pathway genes, in relation to risk of myopia or refractive errors were included. Standard mean difference (SMD) of blood 25(OH)D concentrations between the myopia and non-myopia groups was calculated. The associations of blood 25(OH)D concentrations and polymorphisms in vitamin D pathway genes with myopia using summary ORs were evaluated. We summarised seven studies involving 25 008 in iduals in the meta-analysis. The myopia group had lower 25(OH)D concentration than the non-myopia group (SMD=−0.27 nmol/L, p=0.001). In the full analysis, the risk of myopia was inversely associated with blood 25(OH)D concentration after adjusting for sunlight exposure or time spent outdoors (adjusted odds ratio (AOR)=0.92 per 10 nmol/L, p .0001). However, the association was not statistically significant for the years subgroup (AOR=0.91 per 10 nmol/L, p=0.13) and was significant only for 25(OH)D3 (likely to be mainly sunlight derived), but not total 25(OH)D (AOR=0.93 per 10 nmol/L, p=0.00007 AOR=0.91 per 10 nmol/L, p=0.15). We analysed four single nucleotide polymorphisms in the VDR gene from two studies there was no significant association with myopia. Lower 25(OH)D is associated with increased risk of myopia the lack of a genetic association suggests that 25(OH)D level may be acting as a proxy for time outdoors.
Publisher: Informa UK Limited
Date: 10-01-2013
DOI: 10.3109/13816810.2012.755632
Abstract: The Raine Eye Health Study (REHS) was conceived to determine the prevalence of and risk factors for eye disease in young adults, and to characterize ocular biometric parameters in a young adult cohort. This article summarizes the rationale and study design of REHS and outlines the baseline prevalence of ophthalmic disease in this population. The Western Australian Pregnancy Cohort (Raine) Study originated as a randomized-controlled trial of 2900 women recruited from the state's largest maternity hospital. Their offspring (N = 2868) have been followed at birth, ages 1, 2, 3, 5, 8, 10, 14, 17 and 20 years of age in a prospective cohort study. DNA has been collected from participants for genome-wide association studies. At the 20-year follow-up participants completed a comprehensive eye assessment that included visual acuity, orthoptic assessment and cycloplegic autorefraction, as well as several ocular biometric variables and multiple ophthalmic photographs of the anterior and posterior segments. A total of 1344 participants (51.3% male) were assessed over a 24-month period. For the majority of examined participants (85.5%) both parents were Caucasian, 63.3% had completed school year 12 or equivalent, 5.5% had myopia (spherical equivalent ≤-3 diopters) and 15 participants (1.2%) had unilateral or bilateral pterygia. Keratoconus, cataract, keratitis and uveitis were rare. The REHS design and methodology allow comparison with other population-based studies of eye disease. The study established the prevalence of eye disorders in a large s le of predominantly Caucasian young Australian adults.
Publisher: Wiley
Date: 13-01-2015
DOI: 10.1111/AOS.12644
Abstract: Astigmatism is a common cause of refractive error and is known to vary in prevalence with age. Although the search for genes associated with spherical refractive errors (especially myopia) has met with limited success, current efforts to identify genetic variants implicated in astigmatism development have been less rewarding. We aimed to assess the association between astigmatism and age to identify appropriate age cut‐offs for maximizing power in genetic studies of astigmatism. We performed a cross‐sectional analysis of right eye astigmatism data from four Australian‐based eye studies comprising 3841 participants aged 5–90 years. Measurements were performed under cycloplegia using an autorefractor, and in iduals with a history of cataract, refractive surgery or corneal pathology were excluded from the analysis. In addition to the magnitude and type (against‐the‐rule, with‐the‐rule, and oblique) of astigmatism, we calculated the vector components (J 0 , J 45 ) and evaluated the association of these outcome measures with age. The magnitude of refractive astigmatism ( RA ) remained relatively stable [mean ± SD (−0.44 D ± 0.50)] until in iduals reached the age of 50, thereafter increasing in average magnitude by approximately 1.00 D for those subjects aged 90. In contrast, corneal astigmatism ( CA ) remained relatively stable from childhood until the age of 80 (−0.76 D ± 0.61). The prevalence of clinically significant RA (≥1.00 D) increased with age and was highest in those aged years [55.1% (47.2–62.7%)]. Age was significantly associated with RA in adults [odds ratio ( OR ) = 1.04 per 1 year, p 0.001]. A weaker relationship was observed between CA and age ( OR = 1.007 per 1 year, p = 0.02). We have confirmed the previously documented association between RA and age. Our results indicate that most of the observed change occurs after the age of 50, providing a recommended cut‐off for participants in genetic studies of this refractive condition.
Publisher: Wiley
Date: 08-04-2015
DOI: 10.1111/AJR.12150
Abstract: This study aims to assess the current utilisation of a real-time teleophthalmology service for rural Western Australia (WA). Service evaluation by prospective audit. Includes general practices, optometrists, hospitals in rural WA and the Lions Eye Institute in Perth. Eighty-five patients from rural WA participating. Video consultation (VC) with a general ophthalmologist. Number of referring practitioners and their locations, software and imaging equipment used as well as the presentation, working diagnosis and follow-up plan for each consultation. Eighty-five participants took part in a total of 100 VCs in the 5-month data collection period. There were 49 men (58%) age range 7-92 years 31 identified as Indigenous Australian (37%). Participants were referred by optometrists (59%), hospital district medical officers (23%) and GPs (18%). Karratha (41%), Albany (20%) and Broome (14%) were the main VC locations. There were 31 different eye conditions managed red eye, acute vision loss, known glaucoma and abnormal retinal photographs were the main presentations. Skype was the commonly used software (71%). Images were provided in 63% of all VCs. The main equipment used included digital retinal cameras (56%), smartphones (25%) and digital slit l s (13%). An outpatient appointment with the ophthalmologist was recommended following 35 VCs. Optometrists used this service most frequently, despite a lack of financial incentive. Digital retinal cameras and smartphones were the most commonly used imaging modalities. Overall, real-time teleophthalmology was used in the management of a broad range of eye conditions and was a useful supplement to outreach ophthalmology services.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 14-09-2018
Publisher: Informa UK Limited
Date: 30-07-2020
Publisher: American Medical Association (AMA)
Date: 02-2022
Publisher: Cold Spring Harbor Laboratory
Date: 07-08-2014
DOI: 10.1101/007724
Abstract: A major bottleneck in biological discovery is now emerging at the computational level. Cloud computing offers a dynamic means whereby small and medium-sized laboratories can rapidly adjust their computational capacity. We benchmarked two established cloud computing services, Amazon Web Services Elastic MapReduce (EMR) on Amazon EC2 instances and Google Compute Engine (GCE), using publicly available genomic datasets (E.coli CC102 strain and a Han Chinese male genome) and a standard bioinformatic pipeline on a Hadoop-based platform. Wall-clock time for complete assembly differed by 52.9% (95%CI: 27.5-78.2) for E.coli and 53.5% (95%CI: 34.4-72.6) for human genome, with GCE being more efficient than EMR. The cost of running this experiment on EMR and GCE differed significantly, with the costs on EMR being 257.3% (95%CI: 211.5-303.1) and 173.9% (95%CI: 134.6-213.1) more expensive for E.coli and human assemblies respectively. Thus, GCE was found to outperform EMR both in terms of cost and wall-clock time. Our findings confirm that cloud computing is an efficient and potentially cost-effective alternative for analysis of large genomic datasets. In addition to releasing our cost-effectiveness comparison, we present available ready-to-use scripts for establishing Hadoop instances with Ganglia monitoring on EC2 or GCE.
Publisher: BMJ
Date: 03-2020
DOI: 10.1136/BMJOPEN-2019-033440
Abstract: Eye diseases and visual impairment more commonly affect elderly adults, thus, the majority of ophthalmic cohort studies have focused on older adults. Cohort studies on the ocular health of younger adults, on the other hand, have been few. The Raine Study is a longitudinal study that has been following a cohort since their birth in 1989–1991. As part of the 20-year follow-up of the Raine Study, participants underwent a comprehensive eye examination. As part of the 27- and 28-year follow-ups, eye assessments are being conducted and the data collected will be compared with those of the 20-year follow-up. This will provide an estimate of population incidence and updated prevalence of ocular conditions such as myopia and keratoconus, as well as longitudinal change in ocular parameters in young Australian adults. Additionally, the data will allow exploration of the environmental, health and genetic factors underlying inter-subject differential long-term ocular changes. Participants are being contacted via telephone, email and/or social media and invited to participate in the eye examination. At the 27-year follow-up, participants completed a follow-up eye screening, which assessed visual acuity, autorefraction, ocular biometry and ocular sun exposure. Currently, at the 28-year follow-up, a comprehensive eye examination is being conducted which, in addition to all the eye tests performed at the 27-year follow-up visit, includes tonometry, optical coherence tomography, funduscopy and anterior segment topography, among others. Outcome measures include the incidence of refractive error and pterygium, an updated prevalence of these conditions, and the 8-year change in ocular parameters. The Raine Study is registered in the Australian New Zealand Clinical Trials Registry. The Gen2 20-year, 27-year and 28-year follow-ups are approved by the Human Research Ethics Committee of the University of Western Australia. Findings resulting from the study will be published in health or medical journals and presented at conferences. ACTRN12617001599369 Active, not recruiting.
Publisher: Springer Science and Business Media LLC
Date: 14-11-2018
DOI: 10.1038/S41467-018-06649-5
Abstract: The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 in iduals. We confirm known loci including MTAP , PLA2G6 , and IRF4 , and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1 , PPARGC1B , HDAC4 , FAM208B, DOCK8 , and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk ( KITLG an exception), while many melanoma risk loci do not alter nevus count. For ex le, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.
Publisher: Springer Science and Business Media LLC
Date: 17-03-2021
DOI: 10.1038/S41598-021-85626-3
Abstract: Inflammation and cigarette smoking predispose to macular diseases, and choroidal and retinal thinning. We explored the choroidal and retinal thicknesses in young adults against their 7-year C-reactive protein (CRP) level trajectory and pack-years smoked. Participants from the Raine study, a longitudinal cohort study, had serum CRP levels analysed at the 14-, 17-, and 20-year follow-ups. Group-based trajectory modelling was used to classify participants according to their 7-year CRP levels. At the 20-year follow-up (at 18–22 years old), participants completed questionnaires on their smoking history, and underwent optical coherence tomography imaging to obtain their choroidal and retinal thicknesses at the macula. Three CRP trajectories were identified: consistently low CRP levels (78% of s le), increasing (11%), or consistently high (11%). 340 and 1035 participants were included in the choroidal and retinal thickness analyses, respectively. Compared to those in the “Low” trajectory group, participants in the “Increasing” and “High” groups had 14–21 μm thinner choroids at most macular regions. Every additional pack-year smoked was linked with a 0.06–0.10 μm thinner retina at the inner and outer macular rings, suggesting a dose-dependent relationship between smoking and thinner retinas. These associations may suggest that an increased risk of future visual impairment or eye disease associated with these risk factors may be present since young adulthood.
Publisher: Wiley
Date: 28-01-2015
DOI: 10.1002/GEPI.21886
Publisher: Elsevier BV
Date: 06-2020
Publisher: Springer Science and Business Media LLC
Date: 06-01-2013
DOI: 10.1038/NG.2506
Publisher: Wiley
Date: 19-08-2021
DOI: 10.1111/CEO.13980
Abstract: The prevalence of myopia is increasing globally including in Europe and parts of Asia but Australian data are lacking. This study aim described the change in myopia prevalence in middle‐aged Australian adults over approximately a 20‐year period. Two contemporary Western Australian studies (conducted in mid‐late 2010s): the coastal‐regional Busselton Healthy Ageing Study (BHAS) and the urban Gen1 of the Raine Study (G1RS) were compared to two earlier studies (early‐mid 1990s) in Australia: the urban Blue Mountains Eye Study (BMES) and urban/regional Melbourne Visual Impairment Project (MVIP). Refractive error was measured by autorefraction, vertometry, or subjective refraction. Participants (49–70 years) of European descent without self‐reported/diagnosed cataract, corneal disease, or refractive or corneal surgery were included. After exclusions, data were available from 2217, 1760, 700, 2987 and 756 participants from BMES, urban MVIP, regional MVIP, BHAS, and G1RS, respectively. The mean age ranged from 57.1 ± 4.6 years in the G1RS to 60.1 ± 6.0 years in the BMES 44–48% of participants were male. When stratified by location, the contemporary urban G1RS cohort had a higher age‐standardised myopia prevalence than the urban MVIP and BMES cohorts (29.2%, 16.4%, and 23.9%, p 0.001). The contemporary coastal‐regional BHAS had a higher age‐standardised myopia prevalence than the regional MVIP cohort (19.4% vs. 13.8%, p = 0.001). We report an increase in myopia prevalence in older adults in Australia born after World War ll compared to cohorts born before, accounting for urban/regional location. The prevalence of myopia remains relatively low in middle‐aged Australian adults.
Publisher: Wiley
Date: 10-01-2021
DOI: 10.1111/AOS.14709
Abstract: To investigate the relationship between time spent outdoors, at particular ages in childhood and adolescence, and myopia status in young adulthood using serum 25‐hydroxyvitamin D [25(OH)D] concentration as a biomarker of time spent outdoors. Participants of the Raine Study Generation 2 cohort had 25(OH)D concentrations measured at the 6‐, 14‐, 17‐ and 20‐year follow‐ups. Participants underwent cycloplegic autorefraction at age 20 years, and myopia was defined as a mean spherical equivalent −0.50 dioptres or more myopic. Logistic regression was used to analyse the association between risk of myopia at age 20 years and age‐specific 25(OH)D concentrations. Linear mixed‐effects models were used to analyse trajectory of 25(OH)D concentrations from 6 to 20 years. After adjusting for sex, race, parental myopia, body mass index and studying status, myopia at 20 years was associated with lower 25(OH)D concentration at 20 years (per 10 nmol/L decrease, odds ratio (aOR)=1.10, 95% CI: 1.02, 1.18) and a low vitamin D status [25(OH)D 50 nmol/L] at 17 years (aOR = 1.71, 95% CI: 1.06, 2.76) and 20 years (aOR = 1.71, 95% CI: 1.14, 2.56), compared to those without low vitamin D status. There were no associations between 25(OH)D at younger ages and myopia. In iduals who were myopic at 20 years had a 25(OH)D concentration trajectory that declined, relative to non‐myopic peers, with increasing age. Differences in 25(OH)D trajectory between in iduals with and without myopia were greater among non‐Caucasians compared to Caucasians. Myopia in young adulthood was most strongly associated with recent 25(OH)D concentrations, a marker of time spent outdoors.
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: 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: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-05-2020
DOI: 10.1167/TVST.9.6.29
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.JPEDS.2015.10.048
Abstract: To investigate whether being anesthesia administered at least once in early life influenced 3 main proxies of visual function: visual acuity, refractive error, and optic nerve health in young adulthood. At age 20 years, participants of the Western Australian Pregnancy Cohort Study had comprehensive ocular examinations including visual acuity, postcycloplegic refraction, and multiple scans of the optic disc. We identified in iduals who had at least 1 procedure requiring anesthesia during the first 3 years of life (between 1990 and 1994) and compared their visual outcomes with nonexposed in iduals. We excluded 40 participants with strabismus or other ophthalmic disease or surgery and 136 with non-European background. Of 834 participants, 15.2% (n = 127) were exposed to anesthesia at least once before age 3 years. In both exposed and nonexposed groups, median visual acuity (measured using the logarithm of the minimum angle of resolution [LogMAR] chart) was -0.06 LogMAR in the right eye and -0.08 LogMAR in the left eye (P > .05). Median spherical equivalent refractive error was +0.44 diopters (IQR -0.25, +0.63) and +0.31 diopters (IQR -0.38, +0.63) in the exposed and nonexposed group, respectively (P = .126). No difference was detected in mean global retinal nerve fiber layer thickness of the 2 groups (100.7 vs 100.1 μm, P = .830). We were unable to demonstrate an association of exposure to anesthesia as a child with reduced visual acuity or increased myopia or thinning of retinal nerve fiber layer. These findings support the view that anesthesia is unlikely to impair visual development, but further work is needed to establish whether more subtle defects are present and repeated exposures have any effects.
Publisher: Springer Science and Business Media LLC
Date: 03-2020
DOI: 10.1039/C9PP00240E
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 26-05-2022
DOI: 10.1167/IOVS.63.5.34
Publisher: BMJ
Date: 13-11-2020
DOI: 10.1136/BJOPHTHALMOL-2019-314675
Abstract: Myopia is an increasingly common condition that is associated with significant costs to in iduals and society. Moreover, myopia is associated with increased risk of glaucoma, retinal detachment and myopic maculopathy, which in turn can lead to blindness. It is now well established that spending more time outdoors during childhood lowers the risk of developing myopia and may delay progression of myopia. There has been great interest in further exploring this relationship and exploiting it as a public health intervention aimed at preventing myopia in children. However, spending more time outdoors can have detrimental effects, such as increased risk of melanoma, cataract and pterygium. Understanding how spending more time outdoors prevents myopia could advance development of more targeted interventions for myopia. We reviewed the evidence for and against eight facets of spending time outdoors that may protect against myopia: brighter light, reduced peripheral defocus, higher vitamin D levels, differing chromatic spectrum of light, higher physical activity, entrained circadian rhythms, less near work and greater high spatial frequency (SF) energies. There is solid evidence that exposure to brighter light can reduce risk of myopia. Peripheral defocus is able to regulate eye growth but whether spending time outdoors substantially changes peripheral defocus patterns and how this could affect myopia risk is unclear. Spectrum of light, circadian rhythms and SF characteristics are plausible factors, but there is a lack of solid evidence from human studies. Vitamin D, physical activity and near work appear unlikely to mediate the relationship between time spent outdoors and myopia.
Publisher: Springer Science and Business Media LLC
Date: 02-2018
DOI: 10.1039/C7PP90043K
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: 07-2015
DOI: 10.1038/NATURE14618
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: Springer Science and Business Media LLC
Date: 24-06-2019
Publisher: Wiley
Date: 08-2014
DOI: 10.1111/CEO.12394
Publisher: Wiley
Date: 08-2014
DOI: 10.1002/UOG.13399
Abstract: Through comprehensive ophthalmic examination of adult offspring we sought to determine the impact of multiple prenatal ultrasound scans on ocular development. 2743 pregnant women recruited to the Western Australian Pregnancy (Raine) Cohort study during 1989-1991 were randomized to receive at King Edward Memorial Hospital, Western Australia either multiple prenatal ultrasound scans and Doppler flow studies (intensive group) or a single ultrasound scan at 18 weeks' gestation. Neonatal birth weight of the offspring and other physical measurements were collected prospectively. At age 20 years, participants underwent a comprehensive ophthalmic examination including measurement of ocular biometry and visual acuity. Complete data were available for 1134 adult offspring participants. The mothers of 563 of these had been randomized to receive multiple prenatal ultrasound scans. The mean age of participants at follow-up was 20.0 years. There was no statistically significant difference between the two groups with regard to ocular biometric or visual outcomes, except for slightly higher intraocular pressure identified in in iduals exposed to multiple ultrasound scans (P = 0.034). Although infants in the intensive-ultrasound arm were more likely to have birth weights in the lower quartiles, this was not reflected in adult eye development. Axial length, lens thickness, corneal curvature and thickness and optic cup to disc ratio (a risk factor for glaucomatous optic neuropathy) were not significantly influenced by the more frequent ultrasound protocol. Prior to this study, there was a paucity of safety data for ultrasound with regard to eye development. We found that frequent in-utero exposure to ultrasound, including B-mode imaging and the use of spectral Doppler mode from 18 weeks' gestation, had no significant impact on visual outcomes or ocular biometry.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2012
Publisher: BMJ
Date: 2018
DOI: 10.1136/BMJOPEN-2017-020868
Abstract: Excessive and insufficient sun exposure during childhood have been linked to serious diseases in later life for ex le, insufficient sun exposure during childhood may increase the risk of developing myopia. The Kidskin-Young Adult Myopia Study (K-YAMS) is a follow-up of participants in the Kidskin Study, a non-randomised controlled trial that evaluated the effect of a 4-year educational intervention on sun-protection behaviours among primary school children in the late 1990s. Children who received the Kidskin intervention had lower levels of sun exposure compared with peers in the control group after 2 and 4 years of the intervention, but this was not maintained 2 years after the intervention had ceased. Thus, a follow-up of Kidskin Study participants provides a novel opportunity to investigate the associations between a childhood sun-exposure intervention and potentially related conditions in adulthood. The K-YAMS contacts Kidskin Study participants and invites them to participate using a variety of methods, such as prior contact details, the Australian Electoral Roll and social media. Self-reported and objective measures of sun-exposure and sun-protection behaviours are collected as well as a number of eye measurements including cycloplegic autorefraction and ocular biometry. Data will be analysed to investigate a possible association between myopic refractive error and Kidskin intervention group or measured sun exposure. The K-YAMS is approved by the Human Research Ethics Committee of the University of Western Australia (RA/4/1/6807). Findings will be disseminated via scientific journals and conferences. ACTRN12616000812392 Pre-results .
Publisher: Elsevier BV
Date: 05-2021
Publisher: Public Library of Science (PLoS)
Date: 13-04-2022
DOI: 10.1371/JOURNAL.PONE.0266909
Abstract: Changes in retinal thickness are common in various ocular diseases. Transverse magnification due to differing ocular biometrics, in particular axial length, affects measurement of retinal thickness in different regions. This study evaluated the effect of axial length and refractive error on measured macular thickness in two community-based cohorts of healthy young adults. A total of 2160 eyes of 1247 community-based participants (18–30 years 23.4% myopes, mean axial length = 23.6mm) were included in this analysis. Macular thickness measurements were obtained using a spectral-domain optical coherence tomography (which assumes an axial length of 24.385mm). Using a custom program, retinal thickness data were extracted at the 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) regions with and without correction for transverse magnificent effects, with the corrected measurements adjusting according to the participant’s axial length. Linear mixed models were used to analyse the effect of correction and its interaction with axial length or refractive group on retinal thickness. The raw measures (uncorrected for axial length) underestimated the true retinal thickness at the central macula, while overestimating at most non-central macular regions. There was an axial length by correction interaction effect in all but the nasal regions (all p .05). For each 1mm increase in axial length, the central macular thickness is overestimated by 2.7–2.9μm while thicknesses at other regions were underestimated by 0.2–4.1μm. Based on the raw thickness measurements, myopes have thinner retinas than non-myopes at most non-central macular. However, this difference was no longer significant when the corrected data was used. In a community-based s le, the raw measurements underestimate the retinal thickness at the central macula and overestimate the retinal thickness at non-central regions of the ETDRS grid. The effect of axial length and refractive error on retinal thickness is reduced after correcting for transverse magnification effects resulting from axial length differences.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 08-04-2022
Abstract: The human immune system displays substantial variation between in iduals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type-specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interin idual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interin idual variation in the immune system.
Publisher: American Medical Association (AMA)
Date: 04-2015
Publisher: Springer Science and Business Media LLC
Date: 27-07-2020
DOI: 10.1038/S41598-020-69524-8
Abstract: SIX1/SIX6 polymorphism has been shown to be associated with glaucoma. Studies have also found that, in older adults, retinal nerve fibre layer (RNFL) thickness is significantly thinned with each copy of the risk allele in SIX1/SIX6 . However, it is not known whether these genetic variants exert their effects in younger in iduals. Comparing a healthy young adult with an older adult cohort (mean age 20 vs 63 years), both of Northern European descent, we found that there was no significant RNFL thinning in each copy of the risk alleles in SIX1/SIX6 in the eyes of younger in iduals. The older cohort showed an unexpectedly thicker RNFL in the nasal sector with each copy of the risk allele for both the SIX1 (rs10483727) and SIX6 (rs33912345) variants. In the temporal sector, thinner RNFL was found with each copy of the risk allele in rs33912345 with a decrease trend observed in rs10483727. Our results suggest that SIX1/SIX6 gene variants exert their influence later in adult life.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2020
DOI: 10.1186/S12874-020-00996-Y
Abstract: Recent changes in communication technologies, including increased reliance on mobile phones and the internet, may present challenges and/or opportunities to re-engaging inactive study cohorts. We evaluate our ability to recruit participants for the Kidskin Young Adult Myopia Study (KYAMS), a follow-up of the Kidskin Study. KYAMS participants were recruited from the Kidskin Study, a sun exposure-intervention study for 5–6 year-olds running from 1995 to 1999 with most recent follow-up in 2005. From 2015 to 2019, the KYAMS used mail-outs, phone calls and social media to contact Kidskin Study participants. Multivariable logistic regression was used to identify variables associated with successful contact of a Kidskin Study participant or family member and KYAMS participation. Of 1695 eligible participants, 599 (35.5%) participants (or a family member) were contacted and 303 (17.9%) participated in the KYAMS. KYAMS participation was more likely in those who participated in the 2005 follow-up (odds ratio [OR] = 5.09, 95% confidence interval [CI]: 3.67–7.06) and had a mobile phone number on record (OR = 2.25, CI: 1.57–3.23). Of those contacted, participants who were the first point of contact (OR = 4.84, CI: 2.89–8.10) and who were contacted by letter in the first (OR = 6.53, CI: 3.35–12.75) or second (OR = 5.77, CI: 2.85–11.67) round were more likely to participate in the KYAMS, compared to contact by landline phone. We recruited approximately one-fifth of Kidskin Study participants for the KYAMS. Participants were more likely to participate in the KYAMS if they were contacted directly, rather than through a family member, and if they were contacted by invitation letter. ACTRN12617000812392 .
Publisher: Springer Science and Business Media LLC
Date: 14-01-2019
DOI: 10.1038/S41467-018-08078-W
Abstract: The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: Oxford University Press (OUP)
Date: 06-06-2017
DOI: 10.1093/IJE/DYX068
Publisher: Wiley
Date: 13-05-2020
DOI: 10.1111/CEO.13772
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-05-2021
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: Oxford University Press (OUP)
Date: 05-06-2015
DOI: 10.1093/HMG/DDV211
Abstract: Keratoconus is a degenerative eye condition which results from thinning of the cornea and causes vision distortion. Treatments such as ultraviolet (UV) cross-linking have proved effective for management of keratoconus when performed in early stages of the disease. The central corneal thickness (CCT) is a highly heritable endophenotype of keratoconus, and it is estimated that up to 95% of its phenotypic variance is due to genetics. Genome-wide association efforts of CCT have identified common variants (i.e. minor allele frequency (MAF) >5%). However, these studies typically ignore the large set of exonic variants whose MAF is usually low. In this study, we performed a CCT exome-wide association analysis in a s le of 1029 in iduals from a population-based study in Western Australia. We identified a genome-wide significant exonic variant rs121908120 (P = 6.63 × 10(-10)) in WNT10A. This gene is 437 kb from a gene previously associated with CCT (USP37). We showed in a conditional analysis that the WNT10A variant completely accounts for the signal previously seen at USP37. We replicated our finding in independent s les from the Brisbane Adolescent Twin Study, Twin Eye Study in Tasmania and the Rotterdam Study. Further, we genotyped rs121908120 in 621 keratoconus cases and compared the frequency to a s le of 1680 unscreened controls from the Queensland Twin Registry. We found that rs121908120 increases the risk of keratoconus two times (odds ratio 2.03, P = 5.41 × 10(-5)).
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.OPHTHA.2019.04.041
Abstract: Obstructive sleep apnea (OSA) is linked to increased glaucoma risk in middle-aged and older adults. However, little is known about associations between OSA and glaucoma-related optic disc parameters in young adults. We explored associations between overnight polysomnography-derived measures of OSA and the optic disc in young adults. Cross-sectional cohort study. Eight hundred forty-eight adults 19 to 22 years of age. Participants underwent an ophthalmic examination that included OCT imaging of the optic disc and measurements of intraocular pressure, axial length, and refractive error. Participants then underwent an overnight polysomnography study that obtained measurements of apnea-hypopnea index (AHI), peripheral oxygen saturation level, and number of cortical arousals from sleep. Based on the AHI results, participants were grouped into no OSA (AHI < 5 events/hour), mild OSA (AHI ≥ 5 and <15 events/hour), moderate OSA (AHI ≥ 15 and <30 events/hour), or severe OSA (AHI ≥ 30 events/hour). Neuroretinal rim area, horizontal and vertical widths, and peripapillary retinal nerve fiber layer (RNFL) thickness. The median AHI result across the study cohort was 2.2 events per hour (interquartile range, 1.0-4.4 events/hour). Based on the AHI results, 178 participants (21.0%) demonstrated OSA: 150 with mild OSA, 26 with moderate OSA, and 2 with severe OSA. In the unadjusted analyses, participants with OSA on average showed thinner peripapillary RNFL at the inferotemporal (P = 0.026) and superotemporal (P = 0.008) segments compared with those without OSA. Additionally, higher AHI results were associated with thinner RNFL superotemporally (P = 0.007). These findings remained significant after adjusting for gender, body mass index, ethnicity, and potential ocular confounders. There were no significant differences in optic disc measures between groups of OSA severity. Obstructive sleep apnea may be associated with preclinical thinning of the peripapillary RNFL in young adults. This suggests that an increased glaucoma risk already may be present in in iduals with OSA since young adulthood. Long-term follow-up of this cohort will allow further optic disc changes in relationship to polysomnography parameters to be documented and associations with future glaucoma diagnosis to be explored.
Publisher: BMJ
Date: 09-09-2015
DOI: 10.1136/BJOPHTHALMOL-2014-305498
Abstract: Previous studies have demonstrated a small but significant transient increase in intraocular pressure (IOP) in in iduals wearing certain types of swimming goggles. These findings suggested that wearing goggles could represent a significant risk factor for developing and/or worsening of glaucoma in people who swim regularly. The aim of this study was to determine if glaucoma prevalence is increased among adult swimmers. A comprehensive ocular examination was performed on 231 members of local swimming clubs and 118 non-swimmers. IOP was measured using iCARE tonometry and visual field testing was performed using Humphrey SITA fast 24-2. Retinal nerve fibre layer thickness was assessed using spectral domain optical coherence tomography. Based on measurements of IOP and visual fields, we did not detect any new cases of glaucoma in our cohort of frequent swimmers. Similarly, we found no difference in the thickness of the retinal nerve fibre layer between swimmers and non-swimmers the mean right global thickness (GT) was 94.0 μm (IQR 88.0, 100.3) vs 93.0 μm (IQR 89.0, 101.0), respectively (p=0.976), and the median left GT was 93.7 μm (IQR 88.0, 101) in both groups (p=0.799). These findings suggest that frequently wearing swim goggles does not lead to an increased risk of glaucoma over time in adults.
Publisher: American Medical Association (AMA)
Date: 06-2021
Publisher: Wiley
Date: 22-10-2022
DOI: 10.1111/OPO.12905
Abstract: Cross‐sectional studies have variably reported that poor sleep quality may be associated with myopia in children. Longitudinal data, collected over the ages when myopia develops and progresses, could provide new insights into the sleep‐myopia paradigm. This study tested the hypothesis that 12‐year trajectories of sleep behaviour from childhood to adolescence is associated with myopia during young adulthood. At the 5‐, 8‐, 10‐, 14‐ and 17‐year follow‐ups of the longitudinal Raine Study, which has been following a cohort since their birth in 1989–1992, participants' parents/guardians completed the Child Behaviour Checklist questionnaire (CBCL), which collected information on their child's sleep behaviour and quality. The CBCL includes six questions measuring sleep behaviour, which parents rated as 0 = not true, 1 = somewhat/sometimes true, or 2 = very/often true. Scores were summed at each follow‐up to form a composite “sleep behaviour score”. Latent Class Growth Analysis (LCGA) was used to classify participants according to their 12‐year trajectory of sleep behaviour. At the 20‐year follow‐up, an eye examination was performed which included cycloplegic autorefraction and axial length measurement. The LCGA identified three clusters of participants based on their trajectory of sleep behaviour: those with minimal' (43.6% of the total Raine Study s le), ‘declining’ (48.9%), or ‘persistent’ (7.5%) sleep problems. A total of 1194 participants had ophthalmic data and longitudinal sleep data available for analysis (47.2% female, 85.6% Caucasian). No significant differences were observed in regards to age, sex, ethnicity or ocular parameters between trajectory groups. Unadjusted and fully adjusted analyses demonstrated that sleep problem behaviour was not significantly associated with changes in refractive error, axial length or corneal radius. Our findings do not support the hypothesis that there is an association between sleep behaviour and myopia. Future longitudinal studies should explore sleep trajectory data pre‐ and post‐myopia diagnosis to confirm our results.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-07-2022
DOI: 10.1167/TVST.11.7.8
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-02-2019
Publisher: Asia Pacific Academy of Ophthalmology
Date: 2019
DOI: 10.22608/APO.2018329
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-10-2012
Publisher: Elsevier BV
Date: 02-2012
Publisher: Elsevier BV
Date: 09-2021
Publisher: Wiley
Date: 27-07-2016
DOI: 10.1111/CEO.12570
Abstract: P values associated with null hypothesis significance testing (NHST) are almost universal in the ophthalmic literature. A P value < 0.05 is traditionally considered 'significant'. This concept may deflect further thought about the veracity of the results. P values influence the publishability of the data and have flow-on effects for funding success and the direction of future research. Despite their importance, the problems inherent in P values have been recognized since their inception, and in more recent years have been increasingly highlighted in some scientific fields. In this review, we aim to bring the problems associated with P values and NHST to the attention of the ophthalmic research community. We do not offer a universal solution to the problem of determining the veracity of a scientific claim however, we demonstrate the need for caution in interpreting 'significant' P values by performing a Bayesian re-analysis of t-tests in the ophthalmic literature.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2021
DOI: 10.1038/S41598-021-85825-Y
Abstract: Myopia (near-sightedness) is an important public health issue. Spending more time outdoors can prevent myopia but the long-term association between this exposure and myopia has not been well characterised. We investigated the relationship between time spent outdoors in childhood, adolescence and young adulthood and risk of myopia in young adulthood. The Kidskin Young Adult Myopia Study (KYAMS) was a follow-up of the Kidskin Study, a sun exposure-intervention study of 1776 children aged 6–12 years. Myopia status was assessed in 303 (17.6%) KYAMS participants (aged 25–30 years) and several subjective and objective measures of time spent outdoors were collected in childhood (8–12 years) and adulthood. Index measures of total, childhood and recent time spent outdoors were developed using confirmatory factor analysis. Logistic regression was used to assess the association between a 0.1-unit change in the time outdoor indices and risk of myopia after adjusting for sex, education, outdoor occupation, parental myopia, parental education, ancestry and Kidskin Study intervention group. Spending more time outdoors during childhood was associated with reduced risk of myopia in young adulthood (multivariable odds ratio [OR] 0.82, 95% confidence interval [CI] 0.69, 0.98). Spending more time outdoors in later adolescence and young adulthood was associated with reduced risk of late-onset myopia (≥ 15 years of age, multivariable OR 0.79, 95% CI 0.64, 0.98). Spending more time outdoors in both childhood and adolescence was associated with less myopia in young adulthood.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-08-2018
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 23-07-2014
Abstract: To investigate the association between serum vitamin D levels and myopia in young adults. A total of 946 in iduals participating in the 20-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study were included in this study. Ethnicity, parental myopia, and education status were ascertained by self-reported questionnaire. A comprehensive ophthalmic examination was performed, including postcycloplegic autorefraction and conjunctival UV autofluorescence photography. Serum 25-hydroxyvitamin D₃ (25(OH)D₃) concentrations were determined using mass spectrometry. The association between serum 25(OH)D₃ concentrations and prevalent myopia was determined using multivariable logistic regression. Myopia was defined as mean spherical equivalent ≤ -0.5 diopters. Of the 946 participants, 221 (23.4%) had myopia (n = 725 nonmyopic). Myopic subjects had lower serum 25(OH)D₃ concentrations compared to nonmyopic participants (median 67.6 vs. 72.5 nmol, P = 0.003). In univariable analysis, lower serum 25(OH)D₃ concentration was associated with higher risk of having myopia (odds ratio [OR] for <50 vs. ≥50 nmol/L: 2.63 confidence interval [95% CI] 1.71-4.05 P < 0.001). This association persisted after adjustment for potential confounders, including age, sex, ethnicity, parental myopia, education status, and ocular sun-exposure biomarker score (adjusted OR 2.07 95% CI 1.29-3.32 P = 0.002). Myopic participants had significantly lower 25(OH)D₃ concentrations. The prevalence of myopia was significantly higher in in iduals with vitamin D deficiency compared to the in iduals with sufficient levels. Longitudinal studies are warranted to investigate whether higher serum 25(OH)D₃ concentration is protective against myopia or whether it is acting as a proxy for some other biologically effective consequence of sun exposure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-04-2020
Publisher: Springer Science and Business Media LLC
Date: 08-2022
DOI: 10.1186/S40662-022-00299-X
Abstract: To generate and validate a method to estimate axial length estimated (AL est ) from spherical equivalent (SE) and corneal curvature [keratometry (K)], and to determine if this AL est can replace actual axial length (AL act ) for correcting transverse magnification error in optical coherence tomography angiography (OCTA) images using the Littmann-Bennett formula. Data from 1301 participants of the Raine Study Gen2-20 year follow-up were ided into two datasets to generate (n = 650) and validate (n = 651) a relationship between AL, SE, and K. The developed formula was then applied to a separate dataset of 46 participants with AL, SE, and K measurements and OCTA images to estimate and compare the performance of AL est against AL act in correcting transverse magnification error in OCTA images when measuring the foveal avascular zone area (FAZA). The formula for AL est yielded the equation: AL est = 2.102K − 0.4125SE + 7.268, R 2 = 0.794. There was good agreement between AL est and AL act for both study cohorts. The mean difference [standard deviation (SD)] between FAZA corrected with AL est and AL act was 0.002 (0.015) mm 2 with the 95% limits of agreement (LoA) of − 0.027 to 0.031 mm 2 . In comparison, mean difference (SD) between FAZA uncorrected and corrected with AL act was − 0.005 (0.030) mm 2 , with 95% LoA of − 0.064 to 0.054 mm 2 . AL act is more accurate than AL est and hence should be used preferentially in magnification error correction in the clinical setting. FAZA corrected with AL est is comparable to FAZA corrected with AL act , while FAZA measurements using images corrected with AL est have a greater accuracy than measurements on uncorrected images. Hence, in the absence of AL act , clinicians should use AL est to correct for magnification error as this provides for more accurate measurements of fundus parameters than uncorrected images.
Publisher: Oxford University Press (OUP)
Date: 10-01-2017
DOI: 10.1093/HMG/DDW399
Publisher: Springer Science and Business Media LLC
Date: 31-08-2014
DOI: 10.1038/NG.3087
Publisher: Wiley
Date: 07-11-2015
DOI: 10.1111/CEO.12455
Abstract: Sun exposure is associated with several ophthalmic diseases, including pterygium which may develop in adolescence. This study reports the prevalence of pterygium and its associations in a large cohort of young Australian adults. Conjunctival ultraviolet autofluorescence, a biomarker of ocular sun exposure, has recently been characterized in some Australian populations. Cross-sectional population-based study. One thousand three hundred forty-four subjects aged 18-22 years in the Western Australian Pregnancy Cohort (Raine) Study. Standardized colour and ultraviolet autofluorescence photographs of the nasal and temporal conjunctiva were taken, and assessed for presence of pterygium and area of autofluorescence. Sun exposure and protective factors were assessed by structured questionnaire. Area of conjunctival ultraviolet autofluorescence in square millimetre (mm(2)) and presence of pterygium. Median total conjunctival autofluorescence was 44.2 mm(2) (interquartile range 20.2-69.8 mm(2)). Median conjunctival autofluorescence was higher in nasal than in temporal quadrants (23.8 mm(2) vs. 18.9 mm(2), P < 0.001), but did not differ according to age or gender. Higher body mass index was associated with lower levels of autofluorescence. Total autofluorescence increased with increasing time spent outdoors. Prevalence of pterygium was 1.2% (95% confidence interval 0.6-1.8%), and was associated with male gender (odds ratio 6.71, P = 0.012). Participants with pterygium had significantly more conjunctival autofluorescence than those without (median 73.4 mm(2) vs. 44.0 mm(2), P = 0.001). Conjunctival ultraviolet autofluorescence is associated with increased time spent outdoors, and increased prevalence of pterygium. The association of this biomarker with other ophthalmohelioses, including cataract, ocular surface squamous neoplasia and eyelid malignancy, has yet to be determined.
Publisher: Wiley
Date: 14-11-2018
DOI: 10.1111/CEO.13423
Abstract: Excessive ocular sun exposure is linked to various eye pathologies. Conjunctival ultraviolet autofluorescence (CUVAF) is a method of detecting sun-related conjunctival damage however, the custom-built camera system required is not readily available. We investigated whether blue laser autofluorescence (BAF) on a commonly used confocal scanning laser ophthalmoscope (cSLO) can be utilized to measure CUVAF area. Cross-sectional evaluation of a diagnostic technology at a medical research institute. Sixty-four participants recruited from three on-going observational eye studies in Western Australia. All participants had four images, two of each eye, captured using the CUVAF camera and BAF on the same day. Participants with pterygium or poor quality images were excluded from the analysis. Two graders measured CUVAF area in each image twice. CUVAF area measured by BAF was then compared to measurements determined with the conventional camera system. CUVAF area. After exclusions, 50 participants' images were analysed. Intra- and inter-observer repeatability were similar between the two systems. When comparing CUVAF area measured by BAF to the camera measurement, grader 1 had a mean difference of +1.00 mm BAF on a commercially available cSLO is a valid method for measuring CUVAF area. This finding provides broader opportunity for identifying, monitoring and educating patients with sun-exposure-related ocular conditions and for researching the ocular impacts of sun exposure.
Publisher: Informa UK Limited
Date: 05-09-2022
DOI: 10.1080/09286586.2021.1968005
Abstract: In 1989-1991, pregnant women completed questionnaires on their current smoking and alcohol drinking patterns. Following the birth of their offspring, information on household smokers was obtained between the 1- and 13-year follow-ups. At the 20-year follow-up, these offspring underwent an eye examination including optical coherence tomography imaging of the RNFL. Participants (n = 1,287) were 19-22 years old at time of eye examination. Most participants (77%) had no
Publisher: BMJ
Date: 23-11-2021
DOI: 10.1136/BJOPHTHALMOL-2021-320284
Abstract: Conjunctival ultraviolet autofluorescence (CUVAF) is a method of detecting conjunctival damage related to ultraviolet radiation exposure. In cross-sectional studies, CUVAF area is positively associated with self-reported time spent outdoors and pterygium and negatively associated with myopia however, longitudinal studies are scarce. To use a novel deep learning-based tool to assess 8-year change in CUVAF area in young adults, investigate factors associated with this change and identify the number of new onset pterygia. A deep learning-based CUVAF tool was developed to measure CUVAF area. CUVAF area and pterygium status were assessed at three study visits: baseline (participants were approximately 20 years old) and at 7-year and 8-year follow-ups. Participants self-reported sun protection behaviours and ocular history. CUVAF data were available for 1497 participants from at least one study visit 633 (43%) participants had complete CUVAF data. Mean CUVAF areas at baseline and the 7-year and 8-year follow-ups were 48.4, 39.3 and 37.7 mm 2 , respectively. There was a decrease in mean CUVAF area over time (change in total CUVAF area=−0.96 mm 2 per year (95% CI: −1.07 to –0.86)). For participants who wore sunglasses ≥1/2 of the time, CUVAF area decreased by an additional −0.42 mm 2 per year (95% CI: −0.72 to –0.12) on average. Fourteen (1.5%) participants developed a pterygium. In this young adult cohort, CUVAF area declined over an 8-year period. Wearing sunglasses was associated with a faster reduction in CUVAF area. Deep learning-based models can assist in accurate and efficient measurement of CUVAF area.
Publisher: Public Library of Science (PLoS)
Date: 23-09-2014
Publisher: Springer Science and Business Media LLC
Date: 23-02-2023
DOI: 10.1186/S13059-023-02873-5
Abstract: Using latent variables in gene expression data can help correct unobserved confounders and increase statistical power for expression quantitative trait Loci (eQTL) detection. The probabilistic estimation of expression residuals (PEER) and principal component analysis (PCA) are widely used methods that can remove unwanted variation and improve eQTL discovery power in bulk RNA-seq analysis. However, their performance has not been evaluated extensively in single-cell eQTL analysis, especially for different cell types. Potential challenges arise due to the structure of single-cell RNA-seq data, including sparsity, skewness, and mean-variance relationship. Here, we show by a series of analyses that PEER and PCA require additional quality control and data transformation steps on the pseudo-bulk matrix to obtain valid latent variables otherwise, it can result in highly correlated factors (Pearson's correlation r = 0.63 ~ 0.99). Incorporating valid PFs/PCs in the eQTL association model would identify 1.7 ~ 13.3% more eGenes. Sensitivity analysis showed that the pattern of change between the number of eGenes detected and fitted PFs/PCs varied significantly in different cell types. In addition, using highly variable genes to generate latent variables could achieve similar eGenes discovery power as using all genes but save considerable computational resources (~ 6.2-fold faster).
Publisher: Informa UK Limited
Date: 20-04-2017
DOI: 10.3109/13816810.2016.1164195
Abstract: Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant Mendelian disorder characterized by early onset cataracts and elevated levels of serum ferritin in the absence of iron overload. Numerous mutations associated with the development of HHCS have been reported in the 5' non-coding region of the ferritin light chain (FTL) gene in family studies. We present an FTL mutation in an Australian family with 10 HHCS-affected members spanning three generations. Blood and saliva s les were collected from affected and unaffected family members and DNA was extracted using commercially available kits (Qiagen). The complete sequencing of the iron-responsive element (IRE) of the FTL gene was analyzed using bi-directional genomic sequencing. A heterozygous single nucleotide substitution (c.-167 C>T) was identified in the proband and five affected family members (logarithm of the odds score [Z] = 3.61, recombination distance [θ = 0]). All affected in iduals had previously been found to have high ferritin levels and early onset cataracts. This is the first Australian report of the c.-167 C>T mutation in a large family with multiple affected in iduals. This finding raises the possibility that identification of HHCS mutations may be an effective means of disease detection and may aid in facilitating appropriate genetic counseling.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-03-2020
Publisher: Springer Science and Business Media LLC
Date: 16-04-2018
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.AJO.2016.03.008
Abstract: To characterize and quantify Bruch membrane opening (BMO)-based optic nerve head (ONH) parameters in a large, young and healthy, predominantly white population. Cross-sectional study and reliability analysis. The ONH of 1344 predominantly white subjects were imaged with spectral-domain optical coherence tomography (SD-OCT). A customized script, coded in Matlab, was used to manually segment and measure multiple BMO-based parameters of the ONH. Measurements were compared to those obtained with confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph HRT). Regression analysis was performed to assess the relationship between BMO parameters and other ocular and demographic variables. Mean BMO disc and neuroretinal rim (NRR) areas ranged from 0.94 to 4.06 mm(2) (mean 1.77 ± 0.38 mm(2)) and 0.94 to 3.99 mm(2) (mean 1.56 ± 0.31 mm(2)), respectively. When compared to the equivalent HRT measurements, SD-OCT-derived measures differed significantly for all comparable ONH parameters (P < .001). The limits of agreement computed from Bland-Altman plots comparing SD-OCT and HRT measurements showed suboptimal agreement between the techniques. Linear regression analysis demonstrated an effect of ethnicity, axial length, and refractive error on BMO-based parameters. We have quantified BMO-based parameters in a large cohort of young adults using SD-OCT. These data will be informative in constructing normative profiles for clinical and research purposes in glaucoma diagnosis and management.
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: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JID.2017.04.026
Abstract: Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait at genome-wide significance (P = 4.1 × 10
Publisher: Wiley
Date: 29-10-2012
Publisher: Elsevier BV
Date: 04-2020
Publisher: Elsevier BV
Date: 04-2021
Publisher: AMPCo
Date: 05-2014
DOI: 10.5694/MJA14.00086
Publisher: Springer Science and Business Media LLC
Date: 28-05-2018
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: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-03-2021
DOI: 10.1167/TVST.10.3.8
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 22-01-2019
DOI: 10.1167/TVST.8.1.13
Publisher: SPIE-Intl Soc Optical Eng
Date: 05-08-2016
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 23-12-2020
Publisher: Springer Science and Business Media LLC
Date: 21-02-2022
DOI: 10.1007/S43630-022-00176-5
Abstract: The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth’s surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1–67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change.
Publisher: Informa UK Limited
Date: 02-11-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2014
DOI: 10.1016/J.JCRS.2013.07.055
Abstract: To compare the monochromatic aberrations in a large cohort of 20-year-old Australians with differing levels of visual acuity and explore the relationship between these aberrations and refractive error. Lions Eye Institute, Perth, Western Australia, Australia. Cross-sectional analysis of a population-based cohort. Monochromatic aberrations were measured using a Zywave II wavefront aberrometer with natural pupils in a dark room. The logMAR corrected distance visual acuity (CDVA) was measured monocularly under normal illumination. Cycloplegic autorefraction was also performed. The study enrolled 2039 eyes of 1040 participants. Data from 1007 right eyes were analyzed. The median CDVA and spherical equivalent were -0.06 logMAR (interquartile range [IQR], -0.10 to 0.00) and +0.25 diopters (D) (IQR, -0.38 to 0.63), respectively. The median 6.0 mm higher-order aberration (HOA) was 0.58 μm (IQR, 0.44 to 0.79). Coma-like aberrations and 3rd-, 4th-, and 5th-order HOAs were significantly different between subjects with a CDVA of -0.10 logMAR or better and those with a CDVA worse than -0.10 logMAR. Fourth-order aberrations Z(4,-4) (P=.024) and Z(4,-2) (P=.029) and 2nd-order aberration Z(2,0) (P<.001) differed significantly between myopic eyes, emmetropic eyes, and hyperopic eyes. Subjects with higher myopia had slightly higher total HOAs. The HOAs in this population were marginally higher than previously reported values. The findings confirm there is a difference in monochromatic aberrations between different vision and refractive groups. Results in this study will benefit decision-making processes in the clinical setting.
Publisher: Springer Science and Business Media LLC
Date: 04-11-2014
Publisher: Springer Science and Business Media LLC
Date: 03-2019
DOI: 10.1039/C8PP90060D
Abstract: The Montreal Protocol has limited increases in the UV-B (280-315 nm) radiation reaching the Earth's surface as a result of depletion of stratospheric ozone. Nevertheless, the incidence of skin cancers continues to increase in most light-skinned populations, probably due mainly to risky sun exposure behaviour. In locations with strong sun protection programs of long duration, incidence is now reducing in younger age groups. Changes in the epidemiology of UV-induced eye diseases are less clear, due to a lack of data. Exposure to UV radiation plays a role in the development of cataracts, pterygium and possibly age-related macular degeneration these are major causes of visual impairment world-wide. Photodermatoses and phototoxic reactions to drugs are not uncommon management of the latter includes recognition of the risks by the prescribing physician. Exposure to UV radiation has benefits for health through the production of vitamin D in the skin and modulation of immune function. The latter has benefits for skin diseases such as psoriasis and possibly for systemic autoimmune diseases such as multiple sclerosis. The health risks of sun exposure can be mitigated through appropriate sun protection, such as clothing with both good UV-blocking characteristics and adequate skin coverage, sunglasses, shade, and sunscreen. New sunscreen preparations provide protection against a broader spectrum of solar radiation, but it is not clear that this has benefits for health. Gaps in knowledge make it difficult to derive evidence-based sun protection advice that balances the risks and benefits of sun exposure.
Publisher: Wiley
Date: 03-2021
DOI: 10.1002/CBIN.11572
Publisher: Wiley
Date: 26-10-2016
DOI: 10.1002/GEPI.21936
Publisher: Elsevier BV
Date: 04-2023
Publisher: Informa UK Limited
Date: 03-2015
DOI: 10.1111/CXO.12217
Abstract: The aim was to compare the power of spectacles donated to a recycled spectacle program to the custom-made spectacle refractive prescriptions dispensed in a developing country. Two hundred consecutive prescriptions were audited in an optical dispensary in Timor-Leste, a developing nation. These refractions were compared against measurements of 2,075 wearable donated spectacles. We determined how many of the 200 prescriptions could be matched to a donated spectacle measurement, how many donated spectacles could be tried for each prescription and how long it would take to find the matched spectacles. There were 1,854 donated spectacles identified as being suitable for comparison with the 200 refractive prescriptions. Twenty-nine out of 200 prescriptions (14.5 per cent) were matched to at least one pair of donated spectacles. Recycling all spectacles is not cost-effective in a developing country that has the ability to make custom-made spectacles and dispense ready-made spectacles.
Publisher: Elsevier BV
Date: 11-2014
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Seyhan Yazar.