Long-term Effect of Dual-focus Contact Lenses on Myopia Progression in Children: A 6-year Multicenter Clinical Trial.

SIGNIFICANCE: Treatment of myopic children with a dual-focus soft contact lens (DFCL; MiSight 1 day) produced sustained slowing of myopia progression over a 6-year period. Significant slowing was also observed in children switched from a single vision control to treatment lenses (3 years in each lens). PURPOSE: This study aimed to evaluate the effectiveness of DFCLs in sustaining slowed progression of juvenile-onset myopia over a 6-year treatment period and assess myopia progression in children who were switched to a DFCL at the end of year 3. METHODS: Part 1 was a 3-year clinical trial comparing DFCLs with a control contact lens (Proclear 1 day) at four investigational sites. In part 2, subjects completing part 1 were invited to continue for 3 additional years during which all children were treated with MiSight 1 day DFCLs (52 and 56 from the initially treated [T6] and control [T3] groups, respectively). Eighty-five subjects (45 [T3] and 40 [T6]) completed part 2. Cyclopleged spherical equivalent refractive errors (SEREs) and axial lengths (ALs) were monitored, and a linear mixed model was used to compare their adjusted change annually. RESULTS: Average ages at part 2 baseline were 13.2 ± 1.3 and 13.0 ± 1.5 years for the T6 and T3 groups, respectively. Slowed myopia progression in the T6 group observed during part 1 was sustained throughout part 2 (mean ± standard error of the mean: change from baseline SERE [in diopters], -0.52 ± 0.076 vs. -0.51 ± 0.076; change in AL [in millimeters], 0.28 ± 0.033 vs. 0.23 ± 0.033; both P > .05). Comparing progression rates in part 2 for the T6 and T3 groups, respectively, indicates that prior treatment does not influence efficacy (SERE, -0.51 ± 0.076 vs. -0.34 ± 0.077; AL, 0.23 ± 0.03 vs. 0.18 ± 0.03; both P > .05). Within-eye comparisons of AL growth revealed a 71% slowing for the T3 group (3 years older than part 1) and further revealed a small subset of eyes (10%) that did not respond to treatment. CONCLUSIONS: Dual-focus soft contact lenses continue to slow the progression of myopia in children over a 6-year period revealing an accumulation of treatment effect. Eye growth of the initial control cohort with DFCL was slowed by 71% over the subsequent 3-year treatment period.

HOXA9 is a novel myopia risk gene.

PURPOSE: A recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-ß that is a risk factor for myopia. We speculate HOXA9 may participate in myopia development. METHODS: The Singapore GUSTO birth cohort provides data on children's cycloplegic refraction measured at age of 3 years and their methylation profile based on the umbilical cord DNA. The HOXA9 expression levels were measured in the eyes of mono-ocular form deprivation myopia in mice. The plasmid with the mouse HOXA9 cDNA was constructed and then transfected to mouse primary retinal pigment epithelial (RPE) cells. The expression levels of myopia-related genes and cell proliferation were measured in the HOXA9-overexpressed RPE cells. RESULTS: A total of 519 children had data on methylation profile and cycloplegic refraction. The mean spherical equivalent refraction (SE) was 0.90D. Among 8 SE outliers (worse than -2D), 7 children had HOXA9 hypomethylation. The HOXA9 levels in the retina of myopic eyes was 2.65-fold (p = 0.029; paired t-test) higher than the uncovered fellow eyes. When HOXA9 was over-expressed in the RPE cells, TGF-ß, MMP2, FGF2 and IGF1R expression levels were dose-dependently increased by HOXA9. However, over-expression of HOXA9 had no significant influence on IGF1 or HGF expression. In addition, HOXA9 also increased RPE proliferation. CONCLUSION: Based on the human, animal and cellular data, the transcription factor HOXA9 may promote the expression of pro-myopia genes and RPE proliferation, which eventually contribute to myopia development.

A 3-year Randomized Clinical Trial of MiSight Lenses for Myopia Control.

SIGNIFICANCE: Results of this randomized, double-masked clinical trial demonstrate the effectiveness of the MiSight soft contact lens in slowing myopia progression over multiple years. PURPOSE: The purpose of this study was to quantify the effectiveness of MiSight daily disposable soft contact lens in slowing the progression of juvenile-onset myopia. METHODS: Myopic children (spherical equivalent refraction, -0.75 to -4.00 D; astigmatism, <1.00 D) aged 8 to 12 years with no prior contact lens experience were enrolled in a 3-year, double-masked, randomized clinical trial at four investigational sites in four countries. Subjects in each group were matched for age, sex, and ethnicity and were randomized to either a MiSight 1-day contact lens (test) or Proclear 1-day (control; omafilcon A) and worn on a daily disposable basis. Primary outcome measures were the change in cycloplegic spherical equivalent refraction and axial length. RESULTS: Of the subjects enrolled, 75.5% (109/144) completed the clinical trial (53 test, 56 control). Unadjusted change in spherical equivalent refraction was -0.73 D (59%) less in the test group than in the control group (-0.51 ± 0.64 vs. -1.24 ± 0.61 D, P < .001). Mean change in axial length was 0.32 mm (52%) less in the test group than in the control group (0.30 ± 0.27 vs. 0.62 ± 0.30 mm, P < .001). Changes in spherical equivalent refraction and axial length were highly correlated (r = -0.90, P < .001). Over the course of the study, there were no cases of serious ocular adverse events reported. Four asymptomatic corneal infiltrative (one test, three control) events were observed at scheduled study visits. CONCLUSIONS: Results of this clinical trial demonstrate the effectiveness of the MiSight daily disposable soft contact lens in slowing change in spherical equivalent refraction and axial length.

Is there a link between passive smoke exposure and early-onset myopia in preschool Asian children?

PURPOSE: To investigate the association of passive tobacco smoke exposure with early-onset myopia among three-year-old children in Singapore. METHODS: Pregnant mothers who attended their first trimester clinic at two major maternity units were recruited into the GUSTO birth cohort. The current analysis comprised 572 three-year-old children, who underwent cycloplegic autorefraction and axial length (AL) measurements. Myopia was defined as spherical equivalent (SE) of ≤-0.50 dioptres (D). Either parent completed questionnaires describing their child's exposure to passive smoke at six months, one and two years of age. RESULTS: There were 197 children (36.2%) who were exposed to passive smoke from birth to before six months. Compared to non-exposed children, children exposed to any passive smoke from birth to before six months experienced greater myopia prevalence (adjusted OR = 2.79; 95% CI: 1.24-6.29; p = 0.01). The odds of myopia in a child was greater if a smoker smokes at home, in the family car, or in the presence of the child (adjusted OR = 3.95; 95% CI: 1.41-11.09; p < 0.01) compared to non-exposed child. In contrast to myopia, childhood exposure to passive smoke did not systematically shift mean values for SE or AL. CONCLUSIONS: In this prospective birth cohort study, we found that childhood exposure to passive smoke from birth to before six months slightly increased the risk of early-onset myopia. This may indicate a delayed response to passive smoke exposure before six months and the development of myopia at three years of age. Our study is limited by the small number of myopic children at this young age. Thus, larger prospective studies using more objective cotinine level measures are required to fully establish and understand the influence of tobacco smoke on refractive development in older children.

Eye size and shape in newborn children and their relation to axial length and refraction at 3 years.

PURPOSE: To determine if eye size and shape at birth are associated with eye size and refractive error 3 years later. METHODS: A subset of 173 full-term newborn infants from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort underwent magnetic resonance imaging (MRI) to measure the dimensions of the internal eye. Eye shape was assessed by an oblateness index, calculated as 1 - (axial length/width) or 1 - (axial length/height). Cycloplegic autorefraction (Canon Autorefractor RK-F1) and optical biometry (IOLMaster) were performed 3 years later. RESULTS: Both eyes of 173 children were analysed. Eyes with longer axial length at birth had smaller increases in axial length at 3 years (p < 0.001). Eyes with larger baseline volumes and surface areas had smaller increases in axial length at 3 years (p < 0.001 for both). Eyes which were more oblate at birth had greater increases in axial length at 3 years (p < 0.001). Using width to calculate oblateness, prolate eyes had smaller increases in axial length at 3 years compared to oblate eyes (p < 0.001), and, using height, prolate and spherical eyes had smaller increases in axial length at 3 years compared to oblate eyes (p < 0.001 for both). There were no associations between eye size and shape at birth and refraction, corneal curvature or myopia at 3 years. CONCLUSIONS: Eyes that are larger and have prolate or spherical shapes at birth exhibit smaller increases in axial length over the first 3 years of life. Eye size and shape at birth influence subsequent eye growth but not refractive error development.

A cluster randomised controlled trial evaluating an incentive-based outdoor physical activity programme to increase outdoor time and prevent myopia in children.

PURPOSE: To evaluate an incentive-based intervention to increase time spent outdoors among children in a 9-month cluster randomised controlled trial. METHODS: Two hundred and eighty-five children aged 6-12 years of age were randomised to the intervention (n = 147) or control arm (n = 138) in the Family incentive trial (FIT). The FIT intervention comprised of targeted education on myopia and good eye care habits, structured weekend outdoor activities and incentives for children to increase their daily steps via pedometers. The main outcome measure was outdoor time, measured by the WHO questionnaire and a 1-week diary. RESULTS: Interim analysis at 6 months showed a significant increase in mean outdoor time per week in the intervention arm (14.75 h week(-1) ) compared to the control arm (12.40 h week(-1) ) as measured by the questionnaire (p = 0.04). However, greater outdoor time was not statistically significant at the end of the trial (15.95 h week(-1) vs 14.34 h in the control group (p = 0.29). CONCLUSIONS: There was an increase in outdoor time for children in the incentive-based physical activity outdoor program after 6 months but not at the end of the trial. Further larger school trials with better compliance with the intervention and longer duration could be conducted to evaluate clinical outcomes such as myopic shifts.

Does sunlight (bright lights) explain the protective effects of outdoor activity against myopia?

In the following point-counterpoint article, internationally-acclaimed myopia researchers were challenged to defend the two opposing sides of the topic defined by the title; their contributions, which appear in the order, Point followed by Counterpoint, were peer-reviewed by both the editorial team and an external reviewer. Independently of the invited authors, the named member of the editorial team provided an Introduction and Summary, both of which were reviewed by the other members of the editorial team. By their nature, views expressed in each section of the Point-Counterpoint article are those of the author concerned and may not reflect the views of all of the authors.

Atropine Ophthalmic Solution to Reduce Myopia Progression in Pediatric Subjects: The Randomized, Double-Blind Multicenter Phase II APPLE Study.

PURPOSE: The purpose of this study was to assess the dose-response effects of low-dose atropine on myopia progression and safety in pediatric subjects with mild-to-moderate myopia. METHODS: This phase II, randomized, double-masked, placebo-controlled study compared the efficacy and safety of atropine 0.0025%, 0.005%, and 0.01% with placebo in 99 children, aged 6-11 years, with mild-to-moderate myopia. Subjects received 1 drop in each eye at bedtime. The primary efficacy endpoint was change in spherical equivalent (SE), while secondary endpoints included changes in axial length (AL) and near logMAR (logarithm of the minimum angle of resolution) visual acuity and adverse effects. RESULTS: The mean±SD changes in SE from baseline to 12 months in the placebo and atropine 0.0025%, 0.005%, and 0.01% groups were -0.55±0.471, -0.55±0.337, -0.33±0.473, and -0.39±0.519 D, respectively. The least squares mean differences (atropine-placebo) in the atropine 0.0025%, 0.005%, and 0.01% groups were 0.11 D ( P =0.246), 0.23 D ( P =0.009), and 0.25 D ( P =0.006), respectively. Compared with placebo, the mean change in AL was significantly greater for atropine 0.005% (-0.09 mm, P =0.012) and 0.01% (-0.10 mm, P =0.003). There were no significant changes in near visual acuity in any of the treatment groups. The most common ocular adverse events were pruritus and blurred vision, each occurring in 4 (5.5%) atropine-treated children. Changes in mean pupil size and amplitude of accommodation were minimal. CONCLUSIONS: Atropine doses of 0.005% and 0.01% effectively reduced myopia progression in children but no effect was noted with 0.0025%. All doses of atropine were safe and well tolerated.

Axial length elongation profiles from 3 to 6 years in an Asian paediatric population: the Growing Up in Singapore Towards Healthy Outcomes birth cohort study (GUSTO).

AIMS: To determine axial length (AL) elongation profiles in children aged 3-6 years in an Asian population. METHODS: Eligible subjects were recruited from the Growing Up in Singapore Towards Healthy Outcomes birth cohort. AL measurement was performed using IOLMaster (Carl Zeiss Meditec, Jena, Germany) at 3 and 6 years. Anthropometric measurements at birth, cycloplegic refraction at 3 and 6 years, questionnaires on the children's behavioural habits at 2 years and parental spherical equivalent refraction were performed. Multivariable linear regression model with generalised estimating equation was performed to determine factors associated with AL elongation. RESULTS: 273 eyes of 194 children were included. The mean AL increased from 21.72±0.59 mm at 3 years to 22.52±0.66 mm at 6 years (p<0.001). Myopic eyes at 6 years had greater AL elongation (1.02±0.34 mm) compared with emmetropic eyes (0.85±0.25 mm, p=0.008) and hyperopic eyes (0.74±0.16 mm, p<0.001). The 95th percentile limit of AL elongation was 1.59 mm in myopes, 1.34 mm in emmetropes and 1.00 mm in hyperopes. Greater birth weight (per 100 g, ß=0.010, p=0.02) was significantly associated with greater AL elongation from 3 to 6 years, while parental and other behavioural factors assessed at 2 years were not (all p≥0.08). CONCLUSION: In this preschool cohort, AL elongates at an average length of 0.80 mm from 3 to 6 years, with myopes demonstrating the greatest elongation. The differences in 95th percentile limits for AL elongation between myopes, emmetropes and hyperopes can be valuable information in identifying myopia development in preschool children.

Let Us Avoid a 'Myopic View' in Times of COVID-19.

The COVID-19 pandemic has affected people from almost all facets of life and it's impact is extremely palpable among students. In this review paper, we discuss about the risk factors for myopia progression that were exacerbated by the pandemic, which are supported by evidence from studies published recently. It is imperative that measures are put in place to address the rising incidence of myopia so as to prevent the impending myopia pandemic.

Highlights from the 2019 International Myopia Summit on 'controversies in myopia'.

Myopia is an emerging public health issue with potentially significant economic and social impact, especially in East Asia. However, many uncertainties about myopia and its clinical management remain. The International Myopia Summit workgroup was convened by the Singapore Eye Research Institute, the WHO Regional Office for the Western Pacific and the International Agency for the Prevention of Blindness in 2019. The aim of this workgroup was to summarise available evidence, identify gaps or unmet needs and provide consensus on future directions for clinical research in myopia. In this review, among the many 'controversies in myopia' discussed, we highlight three main areas of consensus. First, development of interventions for the prevention of axial elongation and pathologic myopia is needed, which may require a multifaceted approach targeting the Bruch's membrane, choroid and/or sclera. Second, clinical myopia management requires co-operation between optometrists and ophthalmologists to provide patients with holistic care and a tailored approach that balances risks and benefits of treatment by using optical and pharmacological interventions. Third, current diagnostic technologies to detect myopic complications may be improved through collaboration between clinicians, researchers and industry. There is an unmet need to develop new imaging modalities for both structural and functional analyses and to establish normative databases for myopic eyes. In conclusion, the workgroup's call to action advocated for a paradigm shift towards a collaborative approach in the holistic clinical management of myopia.

Visual acuity outcomes with SA60D3, SN60D3, and ZM900 multifocal IOL implantation after phacoemulsification.

PURPOSE: To assess the near and distance visual acuity achieved with implantation of the ReSTOR SA60D3 and SN60D3 (Alcon Laboratories Inc) and Tecnis ZM900 (Abbott Medical Optics [AMO]) multifocal intraocular lens (IOL) after cataract surgery. METHODS: This is a retrospective study of 108 eyes of 54 patients who underwent uneventful bilateral phacoemulsification of cataract and IOL implantation at an ophthalmic center in Singapore by a single surgeon. Inclusion criteria were visually significant cataracts, corneal astigmatism <2.00 diopters, and no other ocular diseases. Patients received the SA60D3, SN60D3, or ZM900 multifocal IOL in both eyes. Binocular near and distance visual acuity outcomes were assessed 3 months after second-eye surgery. RESULTS: No difference in mean postoperative uncorrected and best spectacle-corrected visual acuity for distance among the groups was noted. The ZM900 lens was significantly better than both ReSTOR lenses for uncorrected near vision with 96.7% achieving N5 compared to 75% of SA60D3 patients and 83.3% of SN60D3 patients (P=.003). For distance corrected near vision, 100% of ZM900 patients achieved N5 compared to 83.3% for each the SA60D3 and SN60D3 IOLs (P=.005). No significant difference between both ReSTOR lenses for near vision was noted. CONCLUSIONS: All three IOLs provide similar uncorrected and best corrected distance visual acuity. However, the ZM900 IOL provides better binocular distance corrected and uncorrected near acuity than the SA60D3 or SN60D3. The ZM900 IOL group was more myopic preoperatively compared to the other two groups, which may be a contributing factor.

Case control study of risk factors and ophthalmological outcomes of very low birth weight infants with Type 1 retinopathy of prematurity.

INTRODUCTION: We evaluated the risk factors associated with Type 1 retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants and compared ophthalmologic outcomes between cases with Type 1 ROP who received treatment and gestational age-matched controls with mild or no ROP not requiring treatment. METHODS: This was a retrospective case-control study of VLBW infants born in National University Hospital, Singapore, from January 2001 to December 2013. 17 cases with Type 1 ROP were each matched for gestational age with controls who had either mild (below Stage 2) or no ROP. Antenatal, perinatal and postnatal variables, as well as childhood ophthalmologic outcomes, were collected from their clinical records and analysed. RESULTS: The number of packed cell transfusions and highest fraction of inspired oxygen given at weeks 7-10 were found to be statistically significant on multivariate analysis (p = 0.045 and p = 0.049, respectively). None of the infants had blindness or retinal detachment, and there were no significant differences in refractive errors between the groups at 1-4 years of age. Strabismus at four years of age was more common in the group with Type 1 ROP (p = 0.023). CONCLUSION: Increased episodes of blood transfusions and chronic lung disease requiring high oxygen supplementation at 7-10 weeks of life are significant risk factors associated with Type 1 ROP in VLBW infants in our study. Strabismus at four years is more common in this group of patients. This study highlights the importance of long-term ophthalmologic surveillance for these high-risk children.

Maternal Lutein and Zeaxanthin Concentrations in Relation to Offspring Visual Acuity at 3 Years of Age: The GUSTO Study.

Lutein and zeaxanthin play important roles in visual functions, but their influence on early visual development is unclear. We related maternal lutein and zeaxanthin concentrations during pregnancy to offspring visual acuity (VA) in 471 mother-child pairs from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Maternal concentrations of plasma lutein and zeaxanthin were determined at delivery. We measured uncorrected distance of VA in 3-year old children using a LEA Symbols chart; readings were converted to the logarithm of Minimum Angle of Resolution (logMAR), with >0.3 logMAR indicating poor VA. Associations were examined using linear or Poisson regression adjusted for confounders. The median (inter-quartile range) of maternal lutein and zeaxanthin concentrations were 0.13 (0.09, 0.18) and 0.09 (0.07, 0.12) µmol/L, respectively. A total of 126 children had poor VA. The highest tertile of maternal zeaxanthin concentration was associated with 38% lower likelihood of poor VA in children (95% CI: 0.42, 0.93, p-Trends = 0.02). Higher maternal lutein concentrations were associated with a lower likelihood of poor VA in children (RR 0.60 (95% CI: 0.40, 0.88) for middle tertile; RR 0.78 (95% CI: 0.51, 1.19) for highest tertile (p-Quadratic = 0.02)). In conclusion, lutein and zeaxanthin status during pregnancy may influence offspring early visual development; but the results require confirmation with further studies, including more comprehensive measurements of macular functions.

In-utero epigenetic factors are associated with early-onset myopia in young children.

OBJECTIVES: To assess whether epigenetic mechanisms affecting gene expression may be involved in the pathogenesis of early-onset myopia, we performed genome-wide DNA methylation analyses of umbilical cord tissues, and assessed any associations between CpG site-specific methylation and the development of the disorder when the children were 3 years old. METHODS: Genome-wide DNA methylation profiling of umbilical cord samples from 519 Singaporean infants involved in a prospective birth cohort 'Growing Up in Singapore Towards healthy Outcomes' (GUSTO) was performed using the Illumina Infinium HumanMethylation450K chip microarray. Multivariable logistic regression models were used to assess any associations between site-specific CpG methylation of umbilical cord tissue at birth and myopia risk in 3 year old children, adjusting for potential confounders. Gene expression of genes located near CpG sites that demonstrated statistically significant associations were measured in relevant ocular tissues using human and mouse fetal and adult eye samples. RESULTS: We identified statistically significant associations between DNA methylation levels at five CpG sites and early-onset myopia risk after correcting for multiple comparisons using a false discovery rate of 5%. Two statistically significant CpG sites were identified in intergenic regions: 8p23(p = 1.70×10-7) and 12q23.2(p = 2.53×10-7). The remaining 3 statistically significant CpG sites were identified within the following genes: FGB (4q28, p = 3.60×10-7), PQLC1 (18q23, p = 8.9×10-7) and KRT12 (17q21.2, p = 1.2×10-6). Both PQLC1 and KRT12 were found to be significantly expressed in fetal and adult cornea and sclera tissues in both human and mouse. CONCLUSIONS: We identified five CpG methylation sites that demonstrate a statistically significant association with increased risk of developing early-onset myopia. These findings suggest that variability in the neonatal cord epigenome may influence early-onset myopia risk in children. Further studies of the epigenetic influences on myopia risk in larger study populations, and the associations with adulthood myopia risk are warranted.

Patterns of Daily Outdoor Light Exposure in Australian and Singaporean Children.

PURPOSE: Myopia is rising in prevalence in many locations, and there is evidence that outdoor light exposure is a major environmental factor playing a role in myopia development. This study examined the patterns of daily light exposure in similarly aged children from two geographic locations (Australia and Singapore) known to exhibit differences in myopia prevalence. METHODS: Wearable light sensors were used to assess daily light exposure in 69 Singaporean children aged 8 to 12 years (mean, 9.2 ± 1.1) and 43 Australian children aged 10 to 12 years (mean, 11.3 ± 0.6). The mean daily time exposed to bright outdoor light (>1000 lux) and the number and duration of daily episodes of outdoor exposure were examined. RESULTS: Patterns of daily outdoor light exposure differed substantially between Australia and Singapore. Australian children (105 ± 42 min/d) experienced significantly longer daily outdoor light exposure than Singaporean children (61 ± 40 min/d; P = 0.005), with the largest differences found on weekdays during school hours. Australian children (6.9 ± 1.5 episodes per day) had more frequent daily episodes of outdoor light exposure compared with Singaporean children (4.6 ± 1.5; P = 0.02); however, there was no significant difference in the mean duration of these episodes between countries (P = 0.54). CONCLUSIONS: Children living in Singapore were exposed to significantly less daily outdoor light than Australian children, and these differences may be one of several factors contributing to the differences in myopia prevalence typically found between these populations. TRANSLATIONAL RELEVANCE: Knowledge of these light exposure patterns may assist in the design of outdoor interventions, including school programs, to increase outdoor time in urban Asian populations.

Sleep Duration in Infants Was Not Associated With Myopia at 3 Years.

PURPOSE: To investigate the association of sleep duration and quality at 12 months and myopia at 3 years. DESIGN: Cohort study. METHODS: The Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort recruited pregnant women at 2 major public maternity hospitals (n = 1236). We included 376 children of Chinese, Malay, and Indian ethnicity who had completed caregiver questionnaires on the child's sleep at 12 months of age [Brief Infant Sleep Questionnaire (BISQ)] and also completed cycloplegic autorefraction and eye axial length (AL) measurement at 3 years of age. Data on total sleep duration and number of night wakings were collected by BISQ. Univariable and multivariable regression models adjusting for potential confounders (age, sex, ethnicity, parental myopia, maternal education level, outdoor time, near work, and height) were used. RESULTS: Thirteen (3.5%) participants were myopic and mean spherical equivalent (SE) was 0.89 diopters (D) (SD 0.88) at 3 years. Total sleep duration and number of night wakings at 12 months were not associated with SE at 3 years (P > 0.05). The total sleep duration (P = 0.07) and number of night wakings (P = 0.49) were not associated with AL in the multivariate model. Total sleep duration in tertile 2 was not associated with AL (P = 0.11) compared with tertile 1. Only total sleep duration in tertile 3 was associated with longer AL (P = 0.006), but there was no association with SE. CONCLUSIONS: Sleep duration and quality at 12 months of age were not associated with refractive error at 3 years.

Diet and risk of myopia in three-year-old Singapore children: the GUSTO cohort.

BACKGROUND: To investigate the relationship between dietary intakes at six, nine and 12 months and risk of myopia in three-year-old children in a birth cohort. METHODS: Three hundred and seventeen children from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study were included. Dietary intake at six, nine and 12 months of age was ascertained using either 24-hour recalls or three-day food diaries completed by parents. Cycloplegia was achieved with three drops of one per cent cycloplentolate instilled at five minute intervals. Cycloplegic autorefraction and axial length (AL) were measured at three years of age with a table-mounted autorefractor and optical biometer, respectively. Myopia was defined as spherical equivalent (SE) of ≤ -0.50 D. Associations of dietary intake with SE, AL and myopia were examined by single dietary factor models using two multivariable regression models. Model 1 included adjusting for age, gender and total energy intake. Model 2 included additional adjustments for ethnicity, time spent outdoors, maternal education and parental myopia. RESULTS: In the single dietary factor adjusted models, dietary intakes at six, nine and 12 months were not associated with SE, AL and myopia. In model 1, protein, fat and carbohydrate intakes were not associated with SE, AL and myopia at any of the three time points (p > 0.05). In model 2, protein, fat and carbohydrate intakes were not associated with SE, AL and myopia at any of the three time points (p > 0.05). CONCLUSIONS: In this study, there was no evidence that diet at ages six, nine and 12 months was related to SE, AL or myopia at age three years. Further prospective studies with larger sample sizes are needed to understand the influence of diet on eye development in young children.

Macular Ganglion Cell and Retinal Nerve Fiber Layer Thickness in Children With Refractive Errors-An Optical Coherence Tomography Study.

PURPOSE: To study the distribution of macular ganglion cell-inner plexiform layer (GC-IPL) thickness and peripapillary retinal nerve fiber layer (RNFL) thickness in children with refractive errors. MATERIALS AND METHODS: Two hundred forty-three healthy eyes from 139 children with refractive error ranging from -10.00 to +5.00 D were recruited from the National University Hospital Eye Surgery outpatient clinic. After a comprehensive ocular examination, refraction, and axial length (AL) measurement (IOLMaster), macular GC-IPL and RNFL thickness values were obtained with a spectral domain Cirrus high definition optical coherence tomography system (Carl Zeiss Meditec Inc.). Only scans with signal strength of >6/10 were included. Correlation between variables was calculated using the Pearson correlation coefficient. A multivariate analysis using mixed models was done to adjust for confounders. RESULTS: The mean spherical equivalent refraction was -3.20±3.51 D and mean AL was 24.39±1.72 mm. Average, minimum, superior, and inferior GC-IPL were 82.59±6.29, 77.17±9.65, 83.68±6.96, and 81.64±6.70 µm, respectively. Average, superior, and inferior peripapillary RNFL were 99.00±11.45, 123.20±25.81, and 124.24±22.23 µm, respectively. Average, superior, and inferior GC-IPL were correlated with AL (ß=-2.056, P-value 0.000; ß=-2.383, P-value 0.000; ß=-1.721, P-value 0.000), but minimum GC-IPL was not (ß=-1.056, P-value 0.115). None of the RNFL parameters were correlated with AL. CONCLUSIONS: This study establishes normative macular GC-IPL and RNFL thickness in children with refractive errors. Our results suggest that high definition optical coherence tomography RNFL parameters and minimum GC-IPL are not affected by AL or myopia in children, and therefore warrants further evaluation in pediatric glaucoma patients.

Axial Length/Corneal Radius of Curvature Ratio and Myopia in 3-Year-Old Children.

PURPOSE: This study investigated the association of axial length (AL) to corneal radius of curvature (CRC) ratio with spherical equivalent (SE) in a 3-year old Asian cohort. METHODS: Three-hundred forty-nine 3-year old Asian children from The Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort study underwent AL and CRC measurements with a noncontact ocular biometer and cycloplegic refraction using an autorefractor. The ratio of AL to CRC (AL/CRC) was calculated for all the participants, and subsequently AL, CRC, and AL/CRC were analyzed in relationship to SE. RESULTS: The SE showed better correlation with AL/CRC (Spearman's correlation coefficient, ρ = -0.53; 95% confidence interval [CI]: -0.66; -0.49; P < 0.001) compared to either AL or CRC alone ([ρ = -0.36; 95% CI: -0.51 to 0.51; P = 0.01] and [ρ = 0.05; 95% CI: -0.04 to 0.17; P = 0.34], respectively). Mean AL/CRC was 2.91 ± 0.06 among myopes and decreased to 2.79 ± 0.06 among hyperopes. Axial length to corneal radius of curvature was strongly correlated with SE in myopes (ρ = -0.78; 95% CI: -3.76; -0.79; P = < 0.001), but not in emmetropes and hyperopes ([ρ = -0.39; 95% CI: -10.73; -0.57; P = 0.01] and [ρ = -0.18; 95% CI: -17.28; 12.42; P = 0.38], respectively). Linear regression adjusted for gender and ethnicity showed a 0.74-diopter shift in SE towards myopia with every 0.1 increase in AL/CRC ratio (P < 0.001, r2 = 0.33). CONCLUSION: The correlation between SE and AL/CRC is stronger than that between AL or CRC alone. This suggests that in a research setting, when cycloplegic refraction is difficult to perform on 3-year-old children, AL/CRC may be the next best reference for refractive error. TRANSLATIONAL RELEVANCE: In the research setting, AL/CRC may be the next best reference for refractive error over AL alone when cycloplegic refraction is unavailable in 3-year old children.