Is dietary Vitamin A associated with myopia from adolescence to young adulthood?

Purpose: Potential links may exist between vitamin A intake and myopia via various pathways. In this study, we examined the association between dietary vitamin A intake during adolescence and myopia in early adulthood. Methods: We performed a prospective analysis utilizing data collected from participants of the Raine Study Gen2. Dietary vitamin A intake, determined via food frequency questionnaires completed at ages 14, 17, and 20 years, was compared with ophthalmic measurements collected at year 20. Low vitamin A levels were defined as \u3c600 \u3eµg/day. Regression models were used to adjust for ocular sun exposure level, educational level, and parental myopia as potential confounders. Results: A total of 642 subjects were analyzed. Although those with adequate vitamin A intakes were less likely to be myopic (P = 0.03), this association became insignificant when adjusted for potential confounding factors in logistic regression modeling (odds ratio, 0.59; 95% confidence interval, 0.98–2.52; P = 0.06). Conclusions: There were no significant associations between total vitamin A intakes during adolescence and year 20 refractive errors after adjustment for confounders. Replication of this finding and further investigations are essential to rule out the suggestion that sufficient vitamin A intake during adolescence is associated with lower risk of myopia in early adulthood. Translational Relevance: Our findings are not definitive that ingesting foods high in vitamin A during childhood and adolescence does not have a role for preventing myopia in early adulthood

Low 25-Hydroxyvitamin D Concentration Is Not Associated With Refractive Error in Middle-Aged and Older Western Australian Adults

Purpose: To investigate the association between serum 25-hydroxyvitamin D (25[OH]D) concentration and refractive error in a community-based cohort of adults aged 46 to 69 years. Methods: Residents of the City of Busselton in Western Australia born between 1946 and 1964 were invited to participate. Participants underwent cycloplegic autorefraction and completed questionnaires on education, occupational sun exposure, and physical activity. Blood samples were collected and serum frozen at −80°C. Serum 25[OH]D concentration was measured by immunoassay. Data on 25[OH]D were deseasonalized and multivariate models built to analyze the association between 25[OH]D concentration and spherical equivalent and myopia, defined as spherical equivalent <−0.50 D. Results: After exclusions, data were available for 4112 participants. Serum 25[OH]D concentration was not associated with spherical equivalent or myopia after adjustment for confounding factors (β = −0.01, 95% confidence interval [CI]: −0.03 to −0.008, P = 0.25, and odds ratio = 1.02, 95% CI: 0.99 to 1.05, P = 0.12, respectively). When participants were classified into 25[OH]D groups of lower (<50 nmol/L), medium (≥50 to <75 nmol/L), and upper (≥75 nmol/L), the upper group had slightly greater myopic refractive error than the medium group (P = 0.02) but not the lower group, after adjustment for confounders. Conclusions: There was no substantial association between 25[OH]D levels and spherical equivalent or odds of myopia in this study. The association previously noted between low serum 25[OH]D level and myopia in younger Western Australians is not evident in later adulthood. Translational Relevance: This study provides further evidence suggesting that vitamin D levels are unrelated to myopia risk in adults and thus not a suitable target for myopia intervention

Incidence and prevalence of keratoconus based on Scheimpflug imaging

The prevalence of keratoconus (Belin/Ambrόsio Enhanced Ectasia Display Score ≥2.6 on Scheimpflug imaging) in a longitudinal, community cohort study from Western Australia was 3.4% (n=26/755). Keratoconus incidence over an 8-year period was 2.2% (n=15/669)

The effect of transverse ocular magnification adjustment on macular thickness profile in different refractive errors in community-based adults

Purpose 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. Methods 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. Results 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\u3c0.05). 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. Conclusion In a community-based sample, 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

Role of the TCF4 gene intronic variant in normal variation of corneal endothelium

PURPOSE: To identify early features of Fuchs endothelial dystrophy (FED) in carriers of the rs613872(G) transcription factor 4 gene (TCF4) aged 20 to 21 years. METHODS: Prospective cohort study of people aged 20 to 21 years previously enrolled in the Western Australia Pregnancy (Raine) Cohort. Specular microscopy was performed using a noncontact specular microscopy (EM-3000; Tomey, Nagoya, Japan). Individual genotype data were extracted from the genome-wide Illumina 660 Quad Array. Analysis of the association between the rs613872 risk allele in TCF4 and specular microscopic measurements was conducted. RESULTS: Association between the rs613872 risk allele and corneal endothelial cell density (CD) as well as the coefficient of variation in cell shape was the main outcome measure. Genotype and specular microscopic data were available for a total of 445 participants (46% women). The median CD was 2851 and 2850 cells per square millimeter in the right and left eyes, respectively. No significant differences between intereye variability in endothelial CD were seen (right eye to left eye correlation = 0.64); however, a significant difference in variability of endothelial CD between men and women was observed (male: OD, 2839 ± 124 cells/mm and OS, 2845 ± 124 cells/mm vs. female: OD, 2838 ± 134 cells/mm and OS, 2842 ± 132 cells/mm; OD, P = 0.0013 and OS, P = 0.0016). Eleven individuals were homozygous for the rs613872 risk allele. We found no association between rs613872 genotype and CD or coefficient of variation. One of 11 homozygous GG individuals was found to have a gutta in 1 sample field on specular microscopy, whereas 2 of 297 TT individuals also had a gutta each in 1 sample field. CONCLUSIONS: We were unable to detect an association between TCF4 rs613872 genotype and the variation in corneal endothelial CD or variation in cell morphology in a healthy young adult population. Copyrigh

Memoria de actividades: Año 2005

Purpose: In Bornholm eye disease, a defect in the splicing of transcripts from a variant OPN1LW opsin gene leads to a depletion in spliced transcript levels and, consequently, a reduction in photopigment in photoreceptors expressing the variant gene. Methods: Myopic and age-matched control subjects were drawn from the Western Australian Pregnancy Cohort (Raine) Study and the Norfolk Island Eye Study groups. The OPN1LW opsin gene was amplified using long-range PCR methodology and was fully sequenced. Expression of variant opsins was evaluated using quantitative PCR (qPCR). RNA secondary structure changes arising from identified variants were predicted by modeling. Results: Forty-two nucleotide sites were found to vary across the 111 subjects studied. Of these, 15 had not been previously reported, with three present only in myopic individuals. Expression of these variants in transfected human embryonic kidney (HEK293T) cells demonstrated that splicing efficiencies were not affected. However, gene transcripts from two of the three variants were significantly depleted. RNA secondary structure modeling predicted that these single nucleotide changes could affect RNA stability. Conclusions: None of the variants identified in myopic individuals appeared to alter the efficiency of transcript splicing. However, two resulted in a significant reduction in the number of spliced and unspliced transcripts, indicating an overall reduction in steady-state transcript stability. Such a change would be expected to result in a reduced amount of photopigment, and this may be a contributing factor in the development of myopia.</p

Investigating the long-term impact of a childhood sun-exposure intervention, with a focus on eye health: protocol for the Kidskin-Young Adult Myopia Study

Introduction Excessive and insufficient sun exposure during childhood have been linked to serious diseases in later life; for example, 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. Methods and analysis 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.A pilot study of the K-YAMS was funded by a Perpetual Impact Philanthropy Grant (IPAP2015/0230). The K-YAMS study is funded by a competitive, peer-reviewed Project Grant from the National Health and Medical Research Council (1121979). GL receives financial support through an Australia Government Research Training Program Scholarship. SY is supported by a National Health and Medical Research Council CJ Martin Early Career Fellowship. DC is supported by a National Health and Medical Research Council Research Fellowship GNT 1119339. RML is supported by a National Health and Medical Research Council Senior Research Fellowship (#1107343) and a Cancer Australia grant

Distribution of Axial Length in Australians of Different Age Groups, Ethnicities, and Refractive Errors

Treatments are available to slow myopic axial elongation. Understanding normal axial length (AL) distributions will assist clinicians in choosing appropriate treatment for myopia. We report the distribution of AL in Australians of different age groups and refractive errors

Re-engaging an inactive cohort of young adults: evaluating recruitment for the Kidskin Young Adult Myopia Study

Background: 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. Methods: KYAMS participants were recruited from the Kidskin Study, a sun exposure-intervention study for 5–6 yearolds 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. Results: 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. Conclusions: 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.The KYAMS was funded by grants from Perpetual Impact Philanthropy (IPAP2015/0230) and the National Health and Medical Research Council (1121979). GL receives financial support through an Australia Government Research Training Program Scholarship. SY is supported by a National Health and Medical Research Council (NHMRC) early career fellowship. RML is supported by a NHMRC Senior Research Fellowship (#1107343) and DAM is supported by a NHMRC Practitioner Fellowship

Genome-Wide Association Reveals Pigmentation Genes Play a Role in Skin Aging

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 (GWAS) 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 (p = 4.1 × 10-9); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (p = 8.8 × 10-13), and rs4268748 near MC1R (p = 1.2 × 10-15). At all three loci we highlight putative functionally relevant SNPs. There are a number of red hair/low pigmentation alleles of MC1R; we found that together these MC1R alleles explained 4.1% of variance in skin pattern damage. We also show that skin aging and reported experience of sunburns was proportional to the degree of penetrance for red hair of alleles of MC1R. Our work has uncovered genetic contributions to skin aging and confirmed previous findings, showing that pigmentation is a critical determinate of skin aging