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.

Time outdoors, blood vitamin D status and myopia: a review.

BACKGROUND: Myopia is a major public health concern throughout the world and the prevalence has been increasing rapidly in recent years, especially in urban Asia. The "vitamin D hypothesis" has been raised recently because vitamin D may be a link between less time outdoors and increased risk of myopia. METHODS: We reviewed all studies published in English which examined the association of time outdoors and blood vitamin D status with myopia. RESULTS: The protective effect of time spent outdoors on the risk of myopia onset has been well-established with numerous observational studies and three trials published. Five studies reporting the association between the blood vitamin D status and the risk of myopia and two studies examining the variations in the vitamin D receptor as potential risk factors for myopia development were identified. Most of the current evidence was cross-sectional in nature and had not properly controlled important confounders in its analyses. The evidence supporting that vitamin D played a role in myopia development is weak and the mechanisms are unclear. CONCLUSIONS: At the current stage, it is still unclear whether blood vitamin D status regulates the onset or progression of myopia. Blood vitamin D status may only serve as a biomarker of outdoor exposure, which is the real protective factor for myopia.

Prospective associations of maternal betaine status with offspring weight and body composition at birth: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study.

BACKGROUND: Betaine supplementation results in lower body weight and fat mass and higher lean mass in animals and adult humans. However, the relation between maternal betaine status and offspring birth weight and body composition is less known. OBJECTIVE: The aim was to examine the association between maternal betaine status and neonatal birth size and adiposity in an Asian mother-offspring cohort. DESIGN: We included 955 pregnant women whose plasma betaine concentrations were measured at 26-28 wk of gestation. Neonatal anthropometric values were measured at birth, and abdominal adipose tissue compartments were assessed by MRI in a subset of infants (n = 307) in the first 14 d after birth. Multivariate general linear models were used to adjust for gestational age; fetal sex; and maternal age, height, education, ethnicity, prepregnancy body mass index, and plasma folate, vitamin B-12, and choline concentrations. RESULTS: The mean ± SD plasma concentration of betaine was 13.2 ± 2.7 µmol/L (range: 5.3-25.0 µmol/L). After adjustment for covariates, higher maternal plasma betaine was associated with lower birth weight (ß: -57.6 g; 95% CI: -109.9, -5.3 g), shorter birth length (ß: -0.29 cm per 5-µmol/L increment; 95% CI: -0.55, -0.03 cm), smaller head circumference (-0.20 cm; 95% CI: -0.38, -0.02 cm), smaller midupper arm circumference (-0.16 cm; 95% CI: -0.30, -0.03 cm), lower volumes of abdominal superficial subcutaneous adipose tissue (-4.53 mL; 95% CI: -8.70, -0.36 mL), and a higher risk of small-for-gestational-age birth (OR: 1.57; 95% CI: 1.05, 2.35). CONCLUSIONS: Higher maternal betaine status was generally associated with smaller infant birth size and less abdominal fat mass. Further studies are needed to replicate these findings and to understand their biological mechanisms. This study was registered at clinicaltrials.gov as NCT01174875.

Demographic Characteristics, Health Behaviors Before and During Pregnancy, and Pregnancy and Birth Outcomes in Mothers with Different Pregnancy Planning Status.

Studies on pregnancy intentions and their consequences have yielded mixed results. Here, we comprehensively analyzed the maternal characteristics, health behaviors before and during pregnancy, as well as pregnancy and birth outcomes, across three different pregnancy planning status in 861 women participating in an ongoing Asian mother-offspring cohort study. At 26-28 weeks' gestation, the women's intention and enthusiasm toward their pregnancy were used to classify their pregnancy into planned or unplanned, and unplanned pregnancy was further subdivided into mistimed or unintended. Data on maternal characteristics, health behaviors, and pregnancy outcomes up to that stage were recorded. After delivery, birth outcomes of the offspring were recorded. Linear and logistic regression analyses were performed. Overall, 56 % had a planned pregnancy, 39 % mistimed, and 5 % unintended. Compared to women who planned their pregnancy, women with mistimed pregnancy had higher body mass index and were more likely to have cigarette smoke exposure and less likely to have folic acid supplementation. At 26-28 weeks' gestation, unintended pregnancy was associated with increased anxiety. Neonates of mistimed pregnancy had shorter birth length compared to those of planned pregnancy, even after adjustment for maternal baseline demographics. These findings suggest that mothers who did not plan their pregnancy had less desirable characteristics or health behaviors before and during pregnancy and poorer pregnancy and birth outcomes. Shorter birth length in mistimed pregnancy may be attributed to maternal behaviors before or in the early stages of pregnancy, therefore highlighting the importance of preconception health promotion and screening for women of child-bearing age.

Infant Feeding Practices in a Multi-Ethnic Asian Cohort: The GUSTO Study.

The optimal introduction of complementary foods provides infants with nutritionally balanced diets and establishes healthy eating habits. The documentation of infant feeding practices in multi-ethnic Asian populations is limited. In a Singapore cohort study (GUSTO), 842 mother-infant dyads were interviewed regarding their feeding practices when the infants were aged 9 and 12 months. In the first year, 20.5% of infants were given dietary supplements, while 5.7% took probiotics and 15.7% homeopathic preparations. At age 9 months, 45.8% of infants had seasonings added to their foods, increasing to 56.3% at 12 months. At age 12 months, 32.7% of infants were given blended food, although 92.3% had begun some form of self-feeding. Additionally, 87.4% of infants were fed milk via a bottle, while a third of them had food items added into their bottles. At both time points, more than a third of infants were provided sweetened drinks via the bottle. Infants of Indian ethnicity were more likely to be given dietary supplements, have oil and seasonings added to their foods and consumed sweetened drinks from the bottle (p < 0.001). These findings provide a better understanding of variations in infant feeding practices, so that healthcare professionals can offer more targeted and culturally-appropriate advice.

Long-chain polyunsaturated fatty acid status during pregnancy and maternal mental health in pregnancy and the postpartum period: results from the GUSTO study.

OBJECTIVE: Studies have demonstrated a relationship between lower omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) status and anxiety and depression. It is uncertain whether similar associations occur in pregnant women, when anxiety and depression could have long-term effects on the offspring. We examined the associations between plasma LC-PUFA status during pregnancy and perinatal mental health. METHOD: At 26-28 weeks' gestation, plasma LC-PUFAs were measured in mothers of the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort study, who were recruited between June 2009 and September 2010. Maternal symptoms of anxiety and depression were assessed with the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3 months' postpartum. The STAI-state subscale was used as a continuous measure of current anxiety, while EPDS scores ≥ 15 during pregnancy or ≥ 13 postpartum were indicative of symptoms of probable depression. RESULTS: In adjusted regression analyses (n = 698), lower plasma total omega-3 PUFA concentrations (ß = -6.49 STAI-state subscale scores/unit increase of omega-3 fatty acid; 95% CI, -11.90 to -1.08) and higher plasma omega-6:omega-3 PUFA ratios (ß = 6.58 scores/unit increase of fatty acid ratio; 95% CI, 1.19 to 12.66), specifically higher arachidonic acid (AA):docosahexaenoic acid, AA:eicosapentaenoic acid, and AA:docosapentaenoic acid ratios, were associated with increased antenatal anxiety (P < .05 for all), but not postpartum anxiety. There was no association between plasma PUFAs and perinatal probable depression. CONCLUSIONS: No association was found with probable depression in pregnancy or postpartum. Lower plasma omega-3 fatty acids and higher omega-6:omega-3 fatty acid ratios were associated with higher antenatal anxiety, but not postpartum anxiety. Replication in other studies is needed to confirm the findings and determine the direction of causality. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01174875.

Developmental synchrony of thalamocortical circuits in the neonatal brain.

The thalamus is a deep gray matter structure and consists of axonal fibers projecting to the entire cortex, which provide the anatomical support for its sensorimotor and higher-level cognitive functions. There is limited in vivo evidence on the normal thalamocortical development, especially in early life. In this study, we aimed to investigate the developmental patterns of the cerebral cortex, the thalamic substructures, and their connectivity with the cortex in the first few weeks of the postnatal brain. We hypothesized that there is developmental synchrony of the thalamus, its cortical projections, and corresponding target cortical structures. We employed diffusion tensor imaging (DTI) and divided the thalamus into five substructures respectively connecting to the frontal, precentral, postcentral, temporal, and parietal and occipital cortex. T2-weighted magnetic resonance imaging (MRI) was used to measure cortical thickness. We found age-related increases in cortical thickness of bilateral frontal cortex and left temporal cortex in the early postnatal brain. We also found that the development of the thalamic substructures was synchronized with that of their respective thalamocortical connectivity in the first few weeks of the postnatal life. In particular, the right thalamo-frontal substructure had the fastest growth in the early postnatal brain. Our study suggests that the distinct growth patterns of the thalamic substructures are in synchrony with those of the cortex in early life, which may be critical for the development of the cortical and subcortical functional specialization.

Maternal PUFA status and offspring allergic diseases up to the age of 18 months.

Studies have suggested that maternal PUFA status during pregnancy may influence early childhood allergic diseases, although findings are inconsistent. We examined the relationship between maternal PUFA status and risk of allergic diseases in early childhood in an Asian cohort. Maternal plasma samples from the Growing Up in Singapore Towards Healthy Outcomes mother-offspring cohort were assayed at 26-28 weeks of gestation for relative abundance of PUFA. Offspring (n 960) were followed up from 3 weeks to 18 months of age, and clinical outcomes of potential allergic diseases (rhinitis, eczema and wheezing) were assessed by repeated questionnaires. Skin prick testing (SPT) was also performed at the age of 18 months. Any allergic disease with positive SPT was defined as having any one of the clinical outcomes plus a positive SPT. The prevalence of a positive SPT, rhinitis, eczema, wheezing and any allergic disease with positive SPT was 14·1 % (103/728), 26·5 % (214/808), 17·6 % (147/833), 10·9 % (94/859) and 9·4 % (62/657), respectively. After adjustment for confounders, maternal total n-3, n-6 PUFA status and the n-6:n-3 PUFA ratio were not significantly associated with offspring rhinitis, eczema, wheezing, a positive SPT and having any allergic disease with positive SPT in the offspring (P>0·01 for all). A weak trend of higher maternal n-3 PUFA being associated with higher risk of allergic diseases with positive SPT in offspring was observed. These findings do not support the hypothesis that the risk of early childhood allergic diseases is modified by variation in maternal n-3 and n-6 PUFA status during pregnancy in an Asian population.

Relations of plasma polyunsaturated Fatty acids with blood pressures during the 26th and 28th week of gestation in women of Chinese, Malay, and Indian ethnicity.

Observational and intervention studies have reported inconsistent results of the relationship between polyunsaturated fatty acids (PUFAs) and hypertension during pregnancy. Here, we examined maternal plasma concentrations of n-3 and n-6 PUFAs between the 26th and the 28th week of gestation in relation to blood pressures and pregnancy-associated hypertension.We used data from a birth cohort study of 751 Chinese, Malay, and Indian women. Maternal peripheral systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken from the brachial arm, and central SBP and pulse pressures (PPs) were derived from radial artery pressure waveforms between the 26th and the 28th week of gestation. Pregnancy-associated hypertension (including gestational hypertension and preeclampsia) was ascertained from medical records. Plasma phosphatidylcholine n-3 and n-6 PUFAs were measured by gas chromatography and expressed as percentage of total fatty acids.Peripheral SBP was inversely associated with total n-3 PUFAs [-0.51 (95% confidence interval, CI, -0.89 to -0.13) mm Hg] and long-chain n-3 PUFAs [-0.52 (CI -0.92 to -0.13) mmHg]. Similar but weaker associations were observed for central SBP and PP. Dihomo-γ-linolenic acid was marginally positively associated with peripheral SBP, central SBP, and PP, whereas linoleic acid and total n-6 PUFAs showed no significant associations with blood pressures. We identified 28 pregnancy-associated hypertension cases, and 1% increase in total n-3 PUFAs was associated with a 24% lower odds of pregnancy-associated hypertension (odds ratio 0.76; 95% CI 0.60 to 0.97). Maternal ethnicity modified the PUFAs-blood pressure relations, with stronger inverse associations with n-3 PUFAs in Chinese women, and stronger positive associations with n-6 PUFAs in Indian women (P values for interaction ranged from 0.02 to 0.07).Higher n-3 PUFAs at midgestation are related to lower maternal blood pressures and pregnancy-associated hypertension in Asian women, and the ethnicity-related variation between PUFAs and blood pressures deserves further investigation.

Dietary changes during pregnancy and the postpartum period in Singaporean Chinese, Malay and Indian women: the GUSTO birth cohort study.

OBJECTIVE: To examine changes in food consumption during pregnancy and the postpartum period in women of major Asian ethnic groups. DESIGN: Using interviewer-administered questionnaires, we assessed changes in food consumption during pregnancy (26-28 weeks' gestation) and the postpartum period (3 weeks after delivery) as compared with the usual pre-pregnancy diet. SETTING: Singapore. SUBJECTS: Pregnant women (n 1027) of Chinese, Malay and Indian ethnicity (mean age 30·4 (SD 5·2) years) who participated in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. RESULTS: During pregnancy, participants tended to increase their consumption of milk, fruit and vegetables and decrease their consumption of tea, coffee, soft drinks and seafood (all P < 0·001). Most participants reported adherence to traditional restrictions ('confinement') during the early postpartum period (Chinese: 94·8 %, Malay: 91·6 %, Indian: 79·6 %). During the postpartum period, participants tended to increase their consumption of fish and milk-based drinks and decrease their consumption of noodles, seafood, and chocolates and sweets (all P < 0·001). Ethnic differences in food consumption were pronounced during the postpartum period. For example, most Chinese participants (87·2 %) increased their ginger consumption during the postpartum period as compared with smaller percentages of Malays (31·8 %) and Indians (40·8 %; P for ethnic difference <0·001). Similar ethnic differences were observed for cooking wine/alcohol, herbs and spices, and herbal tea consumption. CONCLUSIONS: Marked changes in food consumption that reflect both modern dietary recommendations and the persistence of traditional beliefs were observed in Singaporean women during pregnancy and the postpartum period. Traditional beliefs should be considered in interventions to improve dietary intakes during these periods.

Automatic diagnosis of pathological myopia from heterogeneous biomedical data.

Pathological myopia is one of the leading causes of blindness worldwide. The condition is particularly prevalent in Asia. Unlike myopia, pathological myopia is accompanied by degenerative changes in the retina, which if left untreated can lead to irrecoverable vision loss. The accurate diagnosis of pathological myopia will enable timely intervention and facilitate better disease management to slow down the progression of the disease. Current methods of assessment typically consider only one type of data, such as that from retinal imaging. However, different kinds of data, including that of genetic, demographic and clinical information, may contain different and independent information, which can provide different perspectives on the visually observable, genetic or environmental mechanisms for the disease. The combination of these potentially complementary pieces of information can enhance the understanding of the disease, providing a holistic appreciation of the multiple risks factors as well as improving the detection outcomes. In this study, we propose a computer-aided diagnosis framework for Pathological Myopia diagnosis through Biomedical and Image Informatics(PM-BMII). Through the use of multiple kernel learning (MKL) methods, PM-BMII intelligently fuses heterogeneous biomedical information to improve the accuracy of disease diagnosis. Data from 2,258 subjects of a population-based study, in which demographic and clinical information, retinal fundus imaging data and genotyping data were collected, are used to evaluate the proposed framework. The experimental results show that PM-BMII achieves an AUC of 0.888, outperforming the detection results from the use of demographic and clinical information 0.607 (increase 46.3%, p<0.005), genotyping data 0.774 (increase 14.7%, P<0.005) or imaging data 0.852 (increase 4.2%, p=0.19) alone. The accuracy of the results obtained demonstrates the feasibility of using heterogeneous data for improved disease diagnosis through our proposed PM-BMII framework.

Morphology and microstructure of subcortical structures at birth: a large-scale Asian neonatal neuroimaging study.

This paper presents the growth pattern and sexual dimorphism of the thalamus and basal ganglia in a large-scale Asian neonatal cohort using both T2-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Our study observed a robust growth of the thalamus and basal ganglia (caudate, putamen, globus pallidus, and anterior limb of internal capsule) beyond the overall brain growth in the early postnatal period (36-43 weeks of the gestational age). Additionally, the microstructure of the two structures was integrated as reflected by an increase in fractional anisotropy (FA) and a decrease in axial and radial water diffusivities in the first few weeks of life. Sexual dimorphism was only observed in the whole brain growth and the left thalamic volume but not in the other volumes or DTI measures of the basal ganglia and thalamus at birth. Even though the pattern of sexual dimorphism in the total brain volume is present at birth and persists throughout postnatal brain development, sexual dimorphisms of the basal ganglia and thalamus differ from those found in later stages of brain development, indicating that regionally distinct patterns of postnatal brain development between males and females arise after birth.

Analgesic effect of supplemental intracameral lidocaine during phacoemulsification under topical anaesthesia: a randomised controlled trial.

AIMS: To determine the analgesic effect of supplemental intracameral lidocaine 1% during phacoemulsification under topical anaesthesia, and to assess the risk factors associated with pain. METHODS: In a double-masked, randomised, clinical trial, 506 patients undergoing phacoemulsification under topical anaesthesia were randomised to receive a supplemental intracameral injection of either 0.5 cc of 1% lidocaine (277 patients, 54.7%) or balanced salt solution (BSS) (229 patients, 45.3%). Patients were interviewed by a trained interviewer using a standardised questionnaire. The main outcome measure was intraoperative pain, scored on a visual analogue scale of 0-10. Logistic regression was performed to assess ORs. RESULTS: 125 of 277 patients (45.1%) experienced pain in the lidocaine group, compared with 123 of 229 patients (53.7%) in the BSS group. The proportion of patients who experienced pain was significantly lower in the intracameral lidocaine group compared with the BSS group (multivariate OR 0.68, 95% CI 0.47 to 0.97; p=0.034). The median pain score (range) was 0.0 for intracameral lidocaine group compared with 1.0 for BSS group (p=0.039). Pain was more common in females (54.3% vs 43.6%; OR 1.56), non-Chinese (62.3% vs 46.9%; OR 2.13) and those who had previous cataract surgery to the fellow eye (55.3% vs 44.7%; OR 1.61). CONCLUSION: The use of 0.5 cc of 1% intracameral lidocaine during phacoemulsification under topical anaesthesia significantly reduces pain experienced by patients. Risk factors for pain include females, non-Chinese and previous cataract surgery.

Visual experience during phacoemulsification under topical versus retrobulbar anesthesia: results of a prospective, randomized, controlled trial.

PURPOSE: To compare the subjective visual experience of cataract patients during phacoemulsification and intraocular lens implantation under topical anesthesia (TA) vs retrobulbar anesthesia (RA). DESIGN: Prospective, randomized, controlled trial. METHODS: Three hundred six cataract patients eligible for phacoemulsification and intraocular lens implantation were randomized to receive either TA or RA during surgery by one of three surgeons. The surgeons were familiar with both anesthetic techniques and operated on the patients using the technique to which the patients were randomized. A masked interviewer conducted in-person interviews with the patients using a standardized questionnaire about their intraoperative visual experience and their reaction to their visual experience between 30 minutes and 4 hours after the surgery. RESULTS: Two patients (one in each group) had intraoperative posterior capsule rupture and were excluded from analysis. There was no statistically significant difference between TA (n = 154) and RA (n = 150) groups, except that more males compared with females had TA (P = .03). More patients who had TA reported perception of light (P < .001) and colors (P < .001) and a change (either increase or decrease) in light brightness during the course of the surgery (P < .001). There was no statistically significant difference in the proportions of patients who saw movements, flashes, instruments, or the surgeon or medical staff during the operation and who found their visual sensations frightening in the two groups. However, 10.4% in the TA group and 9.3% in the RA group found their visual experience frightening. CONCLUSIONS: More patients undergoing cataract surgery under TA compared with RA reported perception of light, colors, and a change in light brightness. A significant proportion of patients in both groups found the visual experience frightening.