A systematic review on the applicability of cell-free DNA level as an obesity biomarker.

Obesity has become a global health concern in recent decades. Utilizing biomarkers presents a promising approach to comprehensively monitor the progress of obesity and its associated health conditions. This review aims to synthesize the available evidence on the correlation between cfDNA level and obesity and to provide insights into the applicability of using cfDNA level as a tool for monitoring progression of obesity. Searches were performed in PubMed and Embase on April 1, 2022. Data and other relevant information were extracted and compiled into a structured table for further analysis. Among 1170 articles screened, 11 articles were included in this review and assessed qualitatively. The results demonstrated that existing evidence mainly focused on three populations, including healthy individuals, cancer patients and pregnant women. Majority of the studies on healthy individuals identified a significant association between cfDNA level and body weight status but not among cancer patients. Varying results were observed among pregnant women at different gestational trimesters. Our review summarized some preliminary evidence on the association between cfDNA level and obesity. More cohort studies in larger scale with comprehensive assessment have to be conducted to examine the applicability of cfDNA as a biomarker for severity and disease progression of obesity.

Colour perception develops throughout childhood with increased risk of deficiencies in children born prematurely.

AIM: To quantify the impact of prematurity on chromatic discrimination throughout childhood, from 2 to 15 years of age. METHODS: We recruited two cohorts of children, as part of the TrackAI Project, an international project with seven different study sites: a control group of full-term children with normal visual development and a group of children born prematurely. All children underwent a complete ophthalmological exam and an assessment of colour discrimination along the three colour axes: deutan, protan and trytan using a DIVE device with eye tracking technology. RESULTS: We enrolled a total of 1872 children (928 females and 944 males) with a mean age of 6.64 years. Out of them, 374 were children born prematurely and 1498 were full-term controls. Using data from all the children born at term, reference normative curves were plotted for colour discrimination in every colour axis. Pre-term children presented worse colour discrimination than full-term in the three colour axes (p < 0.001). Even after removing from the comparison, all pre-term children with any visual disorder colour discrimination outcomes remained significantly worse than those from full-term children. CONCLUSION: While colour perception develops throughout the first years of life, children born pre-term face an increased risk for colour vision deficiencies.

A systematic review and meta-analysis on the ocular characteristics in children and adolescents with neurodevelopmental disorders.

To conduct a systematic review and meta-analysis of the association between children and adolescents with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) and ocular characteristics. Systematic review with meta-analysis. Six databases (PubMed, Scopus, APA PsycInfo, Embase, EBSCOhost, and Cochrane library) were selected for a systematic literature search from database inception to July 2022. The observational studies assessing and reporting at least one outcome regarding ocular characteristics in children and adolescents with ADHD or ASD aged 6-17 were included. Studies in languages other than English, studies of adult or elderly human populations, and animal studies were excluded. The results were analyzed following the PRISMA guideline 2020. The findings of 15 studies, including 433 participants with ADHD, 253 participants with ASD, and 514 participants with typical development (TD), revealed that there were no significant differences in retinal nerve fiber layer, ganglion cell complex, and macular thickness between the ADHD group and the TD group. In subgroup analysis, significant differences in inferior ganglion cell (MD = - 3.19; 95% CI = [- 6.06, - 0.31], p = 0.03) and nasal macular thickness (MD = 5.88; 95% CI = [- 0.01, 11.76], p = 0.05) were detected between the ADHD group and the TD group. A significant difference in pupillary light reflex (PLR) was also observed between the ASD group and the TD group (MD = 29.7; 95% CI = [18.79, 40.63], p < 0.001). Existing evidence suggests a possible association between children and adolescents with ADHD or ASD and ocular characteristics. Given the limited number of studies, further research on a larger cohort is necessary to claim a possible diagnosis of ADHD or ASD through ocular characteristics.

Refractive Profile of Surgical Patients with Intermittent Exotropia: A Large-Sample Cross-Sectional Study in Southern China.

PURPOSE: To describe the refractive profile of surgical patients with intermittent exotropia (IXT) residing in southern China. METHODS: Medical records of patients who received strabismus surgery between June 2014 and August 2020 were retrospectively reviewed. Clinical data, including age, sex, refractive errors, preoperative angle of deviation, types of exotropia, accommodative convergence to accommodation ratio (AC/A ratio) and stereopsis, were investigated. RESULTS: A total of 2250 patients were included, and 93.6% of patients were younger than 30 years of age. The mean angle of exodeviation was 37.0 ± 14.7 prism degree (PD) and 37.5 ± 15.8 PD at distance and near, respectively. Mean spherical equivalent refraction (SER) values were -0.7 ± 2.4 D and -0.8 ± 2.5 D in the dominant eye and nondominant eye, respectively. Significant differences in SER were observed between the dominant eye and nondominant eye among children at 6 years old or younger. The percentage of myopia increased from 11.0% in children (≤6 years old) to 77.9% in teenagers (13-18 years of age). Significant positive associations between the magnitude of exodeviation and the magnitude of myopia were observed (p < 0.0001). Patients with convergence insufficiency type IXT (p < 0.0001) or AC/A < 2 (p < 0.05) showed a greater magnitude of myopia. The mild hyperopia group included a larger proportion of subjects showing a certain degree of stereopsis (p < 0.05). CONCLUSIONS: Myopia was present in more than half of our patients (51.2%), which is much higher than the percentage in the general population of southern China. Patients with convergence insufficiency, an AC/A ratio < 2, or a larger angle of deviation tended to have a greater magnitude of myopia.

The efficacy of physical exercise interventions on mental health, cognitive function, and ADHD symptoms in children and adolescents with ADHD: an umbrella review.

Background: A considerable number of published reviews have addressed the effects of physical exercise on mental health, cognitive function, or attention-deficit hyperactivity (ADHD) symptoms as outcomes in children and adolescents with ADHD. Their findings have often conflicted, therefore, there is an urgent need to synthesise a hierarchy of the evidence and examine the credibility of previous meta-analyses. To establish the robustness of these findings, we conducted an additional meta-analysis on a number of individual studies that were not covered in previous reviews but were suitable for inclusion in our own study. Methods: Three reviewers independently searched Web of Science, Psych INFO, Embase, Cochrane Library, PubMed, SPORTDiscus, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) for meta-analyses published between database inceptions to December 1, 2022. The individual studies were also screened from 1 January 2015 to 1 December 2022. We included meta-analyses and eligible individual studies that addressed the effects of exercise on at least one outcome of mental health, cognitive function, or ADHD symptoms in children and adolescents with ADHD. We excluded systematic reviews and articles that lacked sufficient data for a meaningful second analysis. The effect estimates (Hedges' g), 95% confidence interval (95% CI), 95% prediction interval (95% PI), small study effects, and excess significance bias were calculated. Finally, we categorised the meta-analyses based on the credibility of the evidence criteria and their quality using a Measurement Tool to Assess Systematic Reviews 2 checklist. This umbrella review was registered with PROSPERO, CRD42022361331. Findings: Of 181 listed review articles and 60 individual papers, 10 reviews and 12 individual articles were included in the meta-analyses. This yielded 37 meta-analyses based on 106 study estimates. Evidence was highly suggestive for the effectiveness of exercise (class II) for improving inattention (G = 0.92, 95% CI: 0.44-1.39, 95%), inhibitory control (G = 0.82, 95% CI: 0.52-1.13), and cognitive flexibility (G = 0.52, 95% CI: 0.32-0.72). However, evidence for the effectiveness of exercise on emotional, social, and working memory outcomes was weak, and these results were not significant for hyperactivity and behavioural functioning. Interpretation: Improvement of cognitive flexibility, inhibitory control, and inattention in children and adolescents with ADHD was highly suggested by exercise interventions. However, results were weak for other outcomes (emotional functioning, social functioning, and working memory). Further high-quality randomised controlled trials are, therefore, warranted to determine the effectiveness of exercise on weak outcomes. Funding: None.

Special Issue "Pediatric Eye Disease: Screening, Causes and Treatment".

Clinical manifestations and courses of eye diseases in children are profoundly variable, from minor irritations, pain, infections, inflammations, ocular misalignment, refractive errors and visual impairment, to permanent blindness [...].

Flipped Classroom Case Learning vs Traditional Lecture-Based Learning in Medical School Ophthalmology Education: A Randomized Trial.

PURPOSE: To address the problem of teaching noncore specialties, for which there is often limited teaching time and low student engagement, a flipped classroom case learning (FCCL) module was designed and implemented in a compulsory 5-day ophthalmology rotation for undergraduate medical students. The module consisted of a flipped classroom, online gamified clinical cases, and case-based learning. METHOD: Final-year medical students in a 5-day ophthalmology rotation were randomized to the FCCL or a traditional lecture-based (TLB) module. The outcomes of subjective assessments (student-rated anonymous Likert scale questionnaire, scale 1 to 5, and course and teaching evaluation, scale 1 to 6) and objective assessments (end-of-rotation and post-MBChB multiple-choice questions, scale 0 to 60) were compared between the 2 groups. RESULTS: Between May 2021 and June 2022, 216 students (108 in each group) completed the study. Compared with the TLB students, the students in the FCCL group rated various aspects of the course statistically significantly higher, including feeling more enthusiastic and engaged by the course and more encouraged to ask questions and participate in discussions (all P < .001). They also gave higher ratings for the instructional methods, course assignments, course outcomes, and course workload ( P < .001). They gave higher course and teaching evaluation scores to the tutors (5.7 ± 0.6 vs 5.0 ± 1.0, P < .001). The FCCL group scored higher than the TLB group on the end-of-rotation multiple-choice questions (53.6 ± 3.1 vs 51.8 ± 2.8, P < .001). When 32 FCCL students and 36 TLB students were reassessed approximately 20 weeks after the rotation, the FCCL group scored higher (40.3 ± 9.1) than the TLB group (34.3 ± 10.9, P = .018). CONCLUSIONS: Applying the FCCL module in ophthalmology teaching enhanced medical students' satisfaction, examination performance, and knowledge retention. A similar model may be suitable for other specialties.

Ophthalmic genetic counselling: emerging trends in practice perspectives in Asia.

Genetic counselling (GC) provides information to the patient and the family to make informed choices. Among the advanced Western countries and a few Asian countries, there are certified or trained professionals who perform GC. The Human Genome Project and next-generation sequencing diagnostics have provided an opportunity for increased genetic testing in the field of ophthalmology. The recent interventional therapeutic research strategies have also generated additional interest to seek GC globally, including in Asia. However, GC has several barriers to practise in the developing countries in Asia, namely, (a) shortage of qualified or trained genetic counsellors, (b) poor knowledge and reluctance in clinical adoption of genomics among the physicians in clinical practice, (c) overstretched public health services, and (d) negligible ophthalmic GC-related research and publications. The GC inadequacy in Asia is glaring in the most populous countries like China and India. Cultural differences, religious beliefs, misogyny, genetic discrimination, and a multitude of languages in Asia create unique challenges that counsellors in the West may only encounter with the immigrant minorities. Since there are currently 500 or more specific Mendelian genetic eye disorders, it is important for genetic counsellors to translate the genetic results at a level that the patient and family understand. There is therefore a need for governmental and healthcare organisations to train genetic counsellors in Asia and especially this practice must be included in the routine comprehensive ophthalmic care practice.

Development of oculomotor control throughout childhood: A multicenter and multiethnic study.

Although steady fixation is a key aspect of a proper visual function, it is only subjectively assessed in young and uncooperative children. In the present study, we characterize the development of fixational behavior throughout childhood in a large group of healthy children 5 months of age and up, recruited in five geographically diverse sites. In order to do it, we examined 802 healthy children from April 2019 to February 2020. Their oculomotor behavior was analyzed by means of an automated digital system, based on eye-tracking technology. Oculomotor outcomes were gaze stability, fixation stability and duration of fixations (for both long and short fixational tasks), and saccadic reaction time. Ninety-nine percent of all recruited children were successfully examined. Fixational and saccadic performance improved with age throughout childhood, with more pronounced changes during the first 2 years of life. Gaze and fixation tended to be more stable with age (p < 0.001 for most the outcomes), and saccades tended to be faster. In a multivariate analysis, including age and ethnicity as independent variables and adjusting by data quality, age was related with most fixational outcomes. Our automated digital system and eye-tracking data allow us to quantitatively describe the development of oculomotor control during childhood, assess visual fixation and saccadic performance in children 5 months of age and up, and provide a normative reference of fixational outcomes for clinical practice.

Early-life activities mediate the association between family socioeconomic status in early childhood and physical fitness in early adolescence.

The graded association between family socioeconomic status (SES) and physical fitness is evident, but little is known about the mechanism underlying this association. This study investigated the role of early-life activities as mediators of the longitudinal relationship between early-life SES and health-related physical fitness in 168 adolescents (51.2% boys; final mean age: 12.4 years old). In Wave 1 (2011-12), their parents completed questionnaires about family socioeconomic status (SES), parent-child activities, and child screen time. In Wave 2 (2014-15), participants' physical activity levels were assessed through parent proxy-reports. In Wave 3 (2018-19), a direct assessment of handgrip strength, standing long-jump, and 6-min walk test (6MWT) performance was conducted. After controlling for demographic factors, results of mediation analyses revealed that (a) Wave 1 SES predicted Wave 3 long-jump and 6MWT performance; (b) child physical activity level in Wave 2 mediated the relation between Wave 1 SES and standing long-jump performance in Wave 3; and (c) recreational parent-child activities and child screen time in wave 1 mediated the relation between Wave 1 SES and 6MWT performance in Wave 3. Our findings suggest that the type and frequency of early-life activities play a role in the graded association between childhood SES and physical fitness in adolescence.

Myopia incidence and lifestyle changes among school children during the COVID-19 pandemic: a population-based prospective study.

BACKGROUND: The impacts of social restrictions for COVID-19 on children's vision and lifestyle remain unknown. AIMS: To investigate myopia incidence, spherical equivalent refraction (SER) and lifestyle changes among schoolchildren during the COVID-19 pandemic. METHODS: Two separate longitudinal cohorts of children aged 6-8 years in Hong Kong were included. The COVID-19 cohort was recruited at the beginning of the COVID-19 outbreak, whereas the pre-COVID-19 cohort was recruited before the COVID-19 pandemic. All children received ocular examinations, and answered a standardised questionnaire relating to their lifestyle, including time spent on outdoor activities and near work, both at baseline and at follow-up visits. RESULTS: A total of 1793 subjects were recruited, of whom 709 children comprised the COVID-19 cohort with 7.89±2.30 months of follow-up, and 1084 children comprised the pre-COVID-19 cohort with 37.54±3.12 months of follow-up. The overall incidence was 19.44% in the COVID-19 cohort, and 36.57% in pre-COVID-19 cohort. During the COVID-19 pandemic, the change in SER and axial length was -0.50±0.51 D and 0.29±0.35 mm, respectively; the time spent on outdoor activities decreased from 1.27±1.12 to 0.41±0.90 hours/day (p<0.001), while screen time increased from 2.45±2.32 to 6.89±4.42 hours/day (p<0.001). CONCLUSIONS: We showed a potential increase in myopia incidence, significant decrease in outdoor time and increase in screen time among schoolchildren in Hong Kong during the COVID-19 pandemic. Our results serve to warn eye care professionals, and also policy makers, educators and parents, that collective efforts are needed to prevent childhood myopia-a potential public health crisis as a result of COVID-19.

Vulnerability and resilience in children during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is having a profound impact on the health and development of children worldwide. There is limited evidence on the impact of COVID-19 and its related school closures and disease-containment measures on the psychosocial wellbeing of children; little research has been done on the characteristics of vulnerable groups and factors that promote resilience. METHODS: We conducted a large-scale cross-sectional population study of Hong Kong families with children aged 2-12 years. Parents completed an online survey on family demographics, child psychosocial wellbeing, functioning and lifestyle habits, parent-child interactions, and parental stress during school closures due to COVID-19. We used simple and multiple linear regression analyses to explore factors associated with child psychosocial problems and parental stress during the pandemic. RESULTS: The study included 29,202 individual families; of which 12,163 had children aged 2-5 years and 17,029 had children aged 6-12 years. The risk of child psychosocial problems was higher in children with special educational needs, and/or acute or chronic disease, mothers with mental illness, single-parent families, and low-income families. Delayed bedtime and/or inadequate sleep or exercise duration, extended use of electronic devices were associated with significantly higher parental stress and more psychosocial problems among pre-schoolers. CONCLUSIONS: This study identifies vulnerable groups of children and highlights the importance of strengthening family coherence, adequate sleep and exercise, and responsible use of electronic devices in promoting psychosocial wellbeing during the COVID-19 pandemic.

A Longitudinal Study of the Relation between Childhood Activities and Psychosocial Adjustment in Early Adolescence.

BACKGROUND: Although an increasing body of research shows that excessive screen time could impair brain development, whereas non-screen recreational activities can promote the development of adaptive emotion regulation and social skills, there is a lack of comparative research on this topic. Hence, this study examined whether and to what extent the frequency of early-life activities predicted later externalizing and internalizing problems. METHODS: In 2012/13, we recruited Kindergarten 3 (K3) students from randomly selected kindergartens in two districts of Hong Kong and collected parent-report data on children's screen activities and parent-child activities. In 2018/19, we re-surveyed the parents of 323 students (aged 11 to 13 years) with question items regarding their children's externalizing and internalizing symptoms in early adolescence. Linear regression analyses were conducted to examine the associations between childhood activities and psychosocial problems in early adolescence. RESULTS: Early-life parent-child activities (ß = -0.14, p = 0.012) and child-alone screen use duration (ß = 0.15, p = 0.007) independently predicted externalizing problems in early adolescence. Their associations with video game exposure (ß = 0.19, p = 0.004) and non-screen recreational parent-child activities (ß = -0.14, p = 0.004) were particularly strong. CONCLUSIONS: Parent-child play time is important for healthy psychosocial development. More efforts should be directed to urge parents and caregivers to replace child-alone screen time with parent-child play time.

Impact of sleep duration, physical activity, and screen time on health-related quality of life in children and adolescents.

BACKGROUND: Existing studies on health-related quality of life (HRQoL) mainly covered single growth stages of childhood or adolescence and did not report on the trends in the relationships of HRQoL with sleep duration, physical activity, and screen time. This study aimed to establish the population norm of HRQoL in children and adolescents aged 6-17 years and examine the associations of screen time, sleep duration, and physical activity with HRQoL in this population. METHODS: We conducted a large-scale cross-sectional population-based survey study of Hong Kong children and adolescents aged 6 to 17 years. A representative sample of students were interviewed to assess their HRQoL using PedsQL and EQ-5D-Y-5L. Multivariable homoscedastic Tobit regression with linear form or restricted cubic spline of predictors was used to analyze the associations between screen time, sleep duration, and HRQoL. Multiple imputation by chained equations was performed to deal with missing data. RESULTS: A total of 7555 respondents (mean age 11.5, SD 3.2; 55.1% female) were sampled. Their EQ VAS scores, PedsQL physical summary scores, and psychosocial summary scores were positively correlated with sleep duration and moderate/vigorous activity but was negatively correlated with screen time. CONCLUSIONS: Children and adolescents who had longer exposure to screen, shorter sleep duration, and lower physical activity levels appeared to have poorer HRQoL as assessed by PedsQL and EQ-5D-Y-5L. Advice and guidance on screen time allocation for children and adolescents should be provided at the levels of school, community, and family.

Prevalence and predictors of myopic macular degeneration among Asian adults: pooled analysis from the Asian Eye Epidemiology Consortium.

AIMS: To determine the prevalence and predictors of myopic macular degeneration (MMD) in a consortium of Asian studies. METHODS: Individual-level data from 19 885 participants from four population-based studies, and 1379 highly myopic participants (defined as axial length (AL) >26.0 mm) from three clinic-based/school-based studies of the Asian Eye Epidemiology Consortium were pooled. MMD was graded from fundus photographs following the meta-analysis for pathologic myopia classification and defined as the presence of diffuse choroidal atrophy, patchy chorioretinal atrophy, macular atrophy, with or without 'plus' lesion (lacquer crack, choroidal neovascularisation or Fuchs' spot). Area under the curve (AUC) evaluation for predictors was performed for the population-based studies. RESULTS: The prevalence of MMD was 0.4%, 0.5%, 1.5% and 5.2% among Asians in rural India, Beijing, Russia and Singapore, respectively. In the population-based studies, older age (per year; OR=1.13), female (OR=2.0), spherical equivalent (SE; per negative diopter; OR=1.7), longer AL (per mm; OR=3.1) and lower education (OR=1.9) were associated with MMD after multivariable adjustment (all p<0.001). Similarly, in the clinic-based/school-based studies, older age (OR=1.07; p<0.001), female (OR=2.1; p<0.001), longer AL (OR=2.1; p<0.001) and lower education (OR=1.7; p=0.005) were associated with MMD after multivariable adjustment. SE had the highest AUC of 0.92, followed by AL (AUC=0.87). The combination of SE, age, education and gender had a marginally higher AUC (0.94). CONCLUSION: In this pooled analysis of multiple Asian studies, older age, female, lower education, greater myopia severity and longer AL were risk factors of MMD, and myopic SE was the strongest single predictor of MMD.

Association of the ZC3H11B, ZFHX1B and SNTB1 genes with myopia of different severities.

OBJECTIVE: To investigate the associations of single-nucleotide polymorphisms (SNPs) in the ZC3H11B, ZFHX1B, VIPR2, SNTB1 and MIPEP genes with severities of myopia in Chinese populations. METHODS: Based on previous myopia genome-wide association studies, five SNPs (ZC3H11B rs4373767, ZFHX1B rs13382811, VIPR2 rs2730260, SNTB1 rs7839488 and MIPEP rs9318086) were selected for genotyping in a Chinese cohort of 2079 subjects: 252 extreme myopia, 277 high myopia, 393 moderate myopia, 366 mild myopia and 791 non-myopic controls. Genotyping was performed by TaqMan assays. Allelic frequencies of the SNPs were compared with myopia severities and ophthalmic biometric measurements. RESULTS: The risk allele T of ZC3H11B SNP rs4373767 was significantly associated with high myopia (OR=1.39, p=0.007) and extreme myopia (OR=1.34, p=0.013) when compared with controls, whereas ZFHX1B rs13382811 (allele T, OR=1.33, p=0.018) and SNTB1 rs7839488 (allele G, OR=1.71, p=8.44E-05) were significantly associated with extreme myopia only. In contrast, there was no significant association of these SNPs with moderate or mild myopia. When compared with mild myopia, subjects carrying T allele of rs4373767 had a risk of progressing to high myopia (spherical equivalent ≤-6 dioptres) (OR=1.29, p=0.017). Similarly, the T allele of rs13382811 also imposed a significant risk to high myopia (OR=1.36, p=0.007). In quantitative traits analysis, SNPs rs4373767, rs13382811 and rs7839488 were correlated with axial length and refractive errors. CONCLUSIONS: We confirmed ZC3H11B as a susceptibility gene for high and extreme myopia, and ZFHX1B and SNTB for extreme myopia in Chinese populations. Instead of myopia onset, these three genes were more likely to impose risks of progressing to high and extreme myopia.

Comorbidity of dementia and age-related macular degeneration calls for clinical awareness: a meta-analysis.

AIM: To determine the association between dementia and age-related macular degeneration (AMD) using meta-analysis. METHODS: We searched in the MEDLINE, EMBASE, Web of Knowledge, PsycInfo and Cochrane database of systematic reviews for studies published from March 1959 to March 2018. We included cross-sectional, case-control and cohort studies that evaluated the association of dementia/Alzheimer's disease (AD) with AMD (as outcome) and the association of AMD with dementia/AD (as outcome). Studies that compared cognitive functions between AMD and controls were also included. The summary outcomes, namely odds ratio (OR), relative risk, mean differences and corresponding 95% CIs, were estimated using random effects models. We performed sensitivity analysis based on study quality and individual study effect to control for potential biases. RESULTS: Among 2159 citation records, we identified 21 studies consisting of 7 876 499 study subjects for meta-analysis. Patients with dementia (padjusted≤0.017, OR≥1.24, I2≤9%) or AD (p=0.001, ORunadjusted=2.22, I2=50%) were at risk for AMD, particularly for late AMD (padjusted<0.001, OR=1.37, I2=0). AMD was also significantly associated with increased risk of AD/cognitive impairment (padjusted=0.037, OR=2.42, I2=38%). Moreover, patients with AMD had poorer cognitive functions when compared with controls, including Mini-Mental State Examination (p<0.001, I2≤79%) and Trail Making Test A (p<0.001, I2=0). Sensitivity analysis and Egger's test indicated our results were less likely biased. CONCLUSIONS: A significant association between dementia/AD and AMD calls for greater clinical awareness. The cost-effectiveness of routine screening for the other condition in patients with primary diagnosis of dementia/AD or AMD requires further study.

Analysis of multiple genetic loci reveals MPDZ-NF1B rs1324183 as a putative genetic marker for keratoconus.

OBJECTIVE: To investigate the associations between 16 single-nucleotide polymorphisms (SNPs) in 14 genetic loci and keratoconus in an independent Chinese cohort. METHODS: This cross-sectional, case-control association study included a Chinese cohort of 133 patients with keratoconus and 371 control subjects. In a recent meta-analysis study, we identified association of 16 SNPs in 14 gene loci with keratoconus. In this study, we genotyped these 16 SNPs in all the patients and controls and analysed their association with keratoconus, its clinical severities and progression profiles. We also analysed the genotype-phenotype correlation between individual SNPs and steep keratometry, flat keratometry (Kf), average keratometry (Avg K) and best-fit sphere diameter (BFS) of the anterior and posterior corneal surface. RESULTS: Among the 16 selected SNPs, rs1324183 in the MPDZ-NF1B locus showed a significant association with keratoconus (OR=2.22; 95% CI 1.42 to 3.45, p=4.30×10-4), especially severe keratoconus (OR=5.10, 95% CI 1.63 to 15.93, p=0.005). The rs1324183 A allele was positively associated with anterior Kf (p=0.008), anterior Avg K (p=0.017), posterior Kf (p=0.01) and negatively associated with apex pachymetry (p=0.007) and anterior BFS (p=0.023) in keratoconus. The other 15 SNPs had no significant association with keratoconus or genotype-phenotype correlations. CONCLUSIONS: This study confirmed the association of SNP rs1324183 in MPDZ-NF1B with keratoconus and revealed the association of this SNP with keratoconus severity and corneal parameters. It is thus a putative genetic marker for monitoring the progression of keratoconus to a severe form and facilitating early intervention.

Association of antenatal steroid and risk of retinopathy of prematurity: a systematic review and meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the leading causes of childhood blindness. Use of antenatal steroid can reduce neonatal morbidity and mortality in preterm births, but its effect on ROP remained controversial. We aim to determine the association between antenatal steroid and risk of ROP by a systematic review and meta-analysis. METHODS: Reported studies on the association between antenatal steroid and risk of ROP or severe ROP were identified from MEDLINE and Embase databases from their inception to November 2016. Outcome measures were ORs with 95% CIs. Extracted data were pooled using a random-effect model or fixed-effect model where appropriate. Heterogeneity was assessed, and sensitivity analysis was performed. RESULTS: A total of 434 relevant studies were identified, and 28 studies were eligible for the meta-analysis, involving 20 731 neonates with 4202 cases of ROP. Among the 28 studies included, 13 studies provided data evaluating the association between antenatal steroid use and severe ROP, involving 4999 neonates with 792 cases of severe ROP. Antenatal steroid administration was associated with a reduced risk of ROP development (ORunadjusted=0.82, 95% CI 0.68 to 0.98; ORadjusted=0.67, 95% CI 0.47 to 0.94) and progression to severe ROP (ORunadjusted=0.58, 95% CI 0.40 to 0.86). CONCLUSION: Antenatal steroid administration is associated with a reduced risk of ROP development and progression to severe ROP. Our results strengthened the indications of antenatal steroid therapy to high-risk mothers giving preterm births, especially in low-income and middle-income countries where antenatal steroid are not yet widely used.

Association of the PAX6 gene with extreme myopia rather than lower grade myopias.

AIMS: To investigate the association of the paired box gene 6 (PAX6) with different severities of myopia. METHODS: A total of four haplotype-tagging single-nucleotide polymorphisms (SNPs; rs2071754, rs3026354, rs3026390 and rs628224) and two previously reported SNPs (rs644242 and rs662702) in the PAX6 gene were analysed in a Hong Kong Chinese cohort of 1288 myopia subjects (including 252 extreme myopia, 277 high myopia, 393 moderate myopia and 366 mild myopia) and 791 no myopia controls. Allelic association analyses were performed for individual SNPs in different subgroups of myopia and in combined myopia, followed by a meta-analysis of our current data with reported data on PAX6 in myopia. RESULTS: The association of tagging SNPs rs2071754 and rs644242 with extreme myopia could not withstand multiple correction (rs2071754: OR=1.25, P value=0.031; rs644242: OR=1.33, P value=0.032). In the meta-analysis, rs644242 showed an enhanced, significant association with extreme myopia (OR=1.27, 95% CI 1.10 to 1.46, P value=0.001; I2=0%). In contrast, there was no significant association between the PAX6SNPs and high, moderate or mild myopia. No linear correlation was found between the PAX6SNPs and axial length. CONCLUSION: This study provides additional evidence suggesting that the PAX6 SNP rs644242 is associated with extreme myopia but not lower grade myopia. Thus, PAX6 may be implicated in the development or progression into severe myopia. Further longitudinal studies are warranted.