Publications by authors named "Seang-Mei Saw"

448 Publications

New Polygenic Risk Score to Predict High Myopia in Singapore Chinese Children.

Transl Vis Sci Technol 2021 07;10(8):26

Singapore Eye Research Institute, Singapore.

Purpose: The purpose of this study was to develop an Asian polygenic risk score (PRS) to predict high myopia (HM) in Chinese children in the Singapore Cohort of Risk factors for Myopia (SCORM) cohort.

Methods: We included children followed from 6 to 11 years old until teenage years (12-18 years old). Cycloplegic autorefraction, ultrasound biometry, Illumina HumanHap 550, or 550 Duo Beadarrays, demographics, and environmental factors data were obtained. The PRS was generated from the Consortium for Refractive Error and Myopia genomewide association study (n = 542,934) and the Strabismus, Amblyopia, and Refractive Error in Singapore children Study (n = 500). The Growing Up in Singapore Towards healthy Outcomes Cohort study (n = 339) was the replication cohort. The outcome was teenage HM (≤ -5.00 D) with predictive performance assessed using the area under the curve (AUC).

Results: Mean baseline age ± SD was 7.85 ± 0.84 (n = 1004) and 571 attended the teenage visit; 23.3% had HM. In multivariate analysis, the PRS was associated with a myopic spherical equivalent with an incremental R2 of 0.041 (95% confidence interval [CI] = 0.010, 0.073; P < 0.001). AUC for HM (0.77 [95% CI = 0.71-0.83]) performed better (P = 0.02) with the PRS compared with a model without (0.72 [95% CI = 0.65, 0.78]). Children at the top 25% PRS risk had a 2.34-fold-greater risk of HM (95% CI = 1.53, 3.55; P < 0.001).

Conclusions: The new Asian PRS improved the predictive performance to detect children at risk of HM.

Translational Relevance: Clinicians may use the PRS with other predictive factors to identify high risk children and guide interventions to reduce the risk of HM later in life.
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http://dx.doi.org/10.1167/tvst.10.8.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322707PMC
July 2021

Near work, screen time, outdoor time and myopia in schoolchildren in the Sunflower Myopia AEEC Consortium.

Acta Ophthalmol 2021 Jun 17. Epub 2021 Jun 17.

Singapore Eye Research Institute, Singapore, Singapore.

Purpose: To examine the association between near work, screen time including TV and outdoor time with myopia in children from the Sunflower Myopia Asian Eye Epidemiology Consortium (AEEC).

Methods: We analysed AEEC cross-sectional data (12 241 children) on risk factors (near work, screen time including TV and outdoor time) and myopia of six population-based studies (China, Hong Kong and Singapore). Cycloplegic refraction and axial length (AL) measurements were included. Risk factors were determined using questionnaires. Data were pooled from each study, and multivariable regression analysis was performed to evaluate the associations between risks factors and myopia, spherical equivalent (SE) and AL.

Results: Among the included children, 52.1% were boys, 98.1% were Chinese and 69.7% lived in urban areas. Mean±standard deviation (SD) for age was 8.8 ± 2.9 years, for SE was -0.14 ± 1.8 D and for AL was 23.3 ± 1.1 mm. Myopia prevalence was 30.6%. In multivariate analysis, more reading and writing (OR = 1.17; 95% CI, 1.11-1.24), more total near work (OR = 1.05; 95% CI, 1.02-1.09) and less outdoor time (OR = 0.82, 95% CI, 0.75-0.88) were associated with myopia (p's < 0.05). These factors were similarly associated with SE and AL (p's < 0.05), except for total near work and AL (p = 0.15). Screen time including TV was not significantly associated with myopia (p = 0.49), SE (p = 0.49) or AL (p = 0.83).

Conclusion: In this study, increased reading and writing and decreased outdoor time were associated with myopia. Screen time may be a surrogate factor of near work or outdoor time, but further research is needed to assess its role as an independent risk factor for myopia.
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http://dx.doi.org/10.1111/aos.14942DOI Listing
June 2021

The longitudinal association between early-life screen viewing and abdominal adiposity-findings from a multiethnic birth cohort study.

Int J Obes (Lond) 2021 09 9;45(9):1995-2005. Epub 2021 Jun 9.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

Importance: Screen viewing in adults has been associated with greater abdominal adiposity, with the magnitude of associations varying by sex and ethnicity, but the evidence is lacking at younger ages. We aimed to investigate sex- and ethnic-specific associations of screen-viewing time at ages 2 and 3 years with abdominal adiposity measured by magnetic resonance imaging at age 4.5 years.

Methods: The Growing Up in Singapore Towards healthy Outcomes is an ongoing prospective mother-offspring cohort study. Parents/caregivers reported the time their child spent viewing television, handheld devices, and computer screens at ages 2 and 3 years. Superficial and deep subcutaneous and visceral abdominal adipose tissue volumes were quantified from magnetic resonance images acquired at age 4.5 years. Associations between screen-viewing time and abdominal adipose tissue volumes were examined by multivariable linear regression adjusting for confounding factors.

Results: In the overall sample (n = 307), greater total screen-viewing time and handheld device times were associated with higher superficial and deep subcutaneous adipose tissue volumes, but not with visceral adipose tissue volumes. Interactions with child sex were found, with significant associations with superficial and deep subcutaneous and visceral adipose tissue volumes in boys, but not in girls. Among boys, the increases in mean (95% CI) superficial and deep subcutaneous and visceral adipose tissue volumes were 24.3 (9.9, 38.7), 17.6 (7.4, 27.8), and 7.8 (2.1, 13.6) mL per hour increase in daily total screen-viewing time, respectively. Ethnicity-specific analyses showed associations of total screen-viewing time with abdominal adiposity only in Malay children. Television viewing time was not associated with abdominal adiposity.

Conclusion: Greater total screen-viewing time (and in particular, handheld device viewing time) was associated with higher abdominal adiposity in boys and Malay children. Additional studies are necessary to confirm these associations and to examine screen-viewing interventions for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.
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http://dx.doi.org/10.1038/s41366-021-00864-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611569PMC
September 2021

A Web-Based Time-Use Application to Assess Diet and Movement Behavior in Asian Schoolchildren: Development and Usability Study of My E-Diary for Activities and Lifestyle (MEDAL).

J Med Internet Res 2021 Jun 9;23(6):e25794. Epub 2021 Jun 9.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.

Background: Web-based time-use diaries for schoolchildren are limited, and existing studies focus mostly on capturing physical activities and sedentary behaviors but less comprehensively on dietary behaviors.

Objective: This study aims to describe the development of My E-Diary for Activities and Lifestyle (MEDAL)-a self-administered, web-based time-use application to assess diet and movement behavior-and to evaluate its usability in schoolchildren in Singapore.

Methods: MEDAL was developed through formative research and an iterative user-centric design approach involving small groups of schoolchildren (ranging from n=5 to n=15, aged 7-13 years). To test the usability, children aged 10-11 years were recruited from 2 primary schools in Singapore to complete MEDAL for 2 weekdays and 2 weekend days and complete a 10-item usability questionnaire.

Results: The development process revealed that younger children (aged <9 years) were less able to complete MEDAL independently. Of the 204 participants (118/204, 57.8% boys, and 31/201, 15.4% overweight) in the usability study, 57.8% (118/204) completed 3 to 4 days of recording, whereas the rest recorded for 2 days or less. The median time taken to complete MEDAL was 14.2 minutes per day. The majority of participants agreed that instructions were clear (193/203, 95.1%), that MEDAL was easy to use (173/203, 85.2%), that they liked the application (172/202, 85.1%), and that they preferred recording their activities on the web than on paper (167/202, 82.7%). Among all the factors evaluated, recording for 4 days was the least satisfactory component reported. Compared with boys, girls reported better recall ability and agreed that the time spent on completing 1-day entry was appropriate.

Conclusions: MEDAL appears to be a feasible application to capture diet and movement behaviors in children aged 10-12 years, particularly in the Asian context. Some gender differences in usability performance were observed, but the majority of the participants had a positive experience using MEDAL. The validation of the data collected through the application is in progress.
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http://dx.doi.org/10.2196/25794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262598PMC
June 2021

Assessment of the Macular Microvasculature in High Myopes With Swept Source Optical Coherence Tomographic Angiography.

Front Med (Lausanne) 2021 17;8:619767. Epub 2021 May 17.

Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore.

The risk of pathologic myopia (PM) increases with worsening myopia and may be related to retinal microvasculature alterations. To evaluate this, we analyzed the macular microvasculature of myopes with swept source-optical coherence tomographic angiography (SS-OCTA) in adolescent and young adult Singaporeans. This is a prevalent case-control study including 93 young Chinese from the Strabismus, Amblyopia and Refractive error in Singaporean children (STARS, = 45) study and the Singapore Cohort Study of Risk Factors for Myopia (SCORM, = 48) studies. Macular vessel density (VD) measurements were obtained from 3 × 3 mm SS-OCTA scans and independently assessed using ImageJ. These measurements were compared between individuals with non-high myopia [non-HM, = 40; SE >-5.0 diopter (D)] and HM (SE ≤-5.0D, = 53). The mean macular VD was 40.9 ± 0.6% and 38.2 ± 0.5% in the non-HM and HM, groups, respectively ( = 0.01 adjusted for age and gender). Mean FAZ area in the superficial layer was 0.22 ± 0.02 mm in the HM group, which was smaller compared to non-HM group (0.32 ± 0.03 mm, = 0.04). Mean deep FAZ area was similar between the two groups (0.45 ± 0.03 mm and 0.48 ± 0.04 mm in the HM and non-HM groups, respectively, = 0.70). VD was lower and superficial FAZ area was smaller, in adolescents and young adults with HM compared to non-HM. These findings require validation in prospective studies to assess their impact on the subsequent development of PM.
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http://dx.doi.org/10.3389/fmed.2021.619767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165745PMC
May 2021

IMI Risk Factors for Myopia.

Invest Ophthalmol Vis Sci 2021 04;62(5)

School of Optometry & Vision Sciences, Cardiff University, Cardiff, United Kingdom.

Risk factor analysis provides an important basis for developing interventions for any condition. In the case of myopia, evidence for a large number of risk factors has been presented, but they have not been systematically tested for confounding. To be useful for designing preventive interventions, risk factor analysis ideally needs to be carried through to demonstration of a causal connection, with a defined mechanism. Statistical analysis is often complicated by covariation of variables, and demonstration of a causal relationship between a factor and myopia using Mendelian randomization or in a randomized clinical trial should be aimed for. When strict analysis of this kind is applied, associations between various measures of educational pressure and myopia are consistently observed. However, associations between more nearwork and more myopia are generally weak and inconsistent, but have been supported by meta-analysis. Associations between time outdoors and less myopia are stronger and more consistently observed, including by meta-analysis. Measurement of nearwork and time outdoors has traditionally been performed with questionnaires, but is increasingly being pursued with wearable objective devices. A causal link between increased years of education and more myopia has been confirmed by Mendelian randomization, whereas the protective effect of increased time outdoors from the development of myopia has been confirmed in randomized clinical trials. Other proposed risk factors need to be tested to see if they modulate these variables. The evidence linking increased screen time to myopia is weak and inconsistent, although limitations on screen time are increasingly under consideration as interventions to control the epidemic of myopia.
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http://dx.doi.org/10.1167/iovs.62.5.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083079PMC
April 2021

IMI Prevention of Myopia and Its Progression.

Invest Ophthalmol Vis Sci 2021 04;62(5)

School of Optometry, Aston University, Birmingham, United Kingdom.

The prevalence of myopia has markedly increased in East and Southeast Asia, and pathologic consequences of myopia, including myopic maculopathy and high myopia-associated optic neuropathy, are now some of the most common causes of irreversible blindness. Hence, strategies are warranted to reduce the prevalence of myopia and the progression to high myopia because this is the main modifiable risk factor for pathologic myopia. On the basis of published population-based and interventional studies, an important strategy to reduce the development of myopia is encouraging schoolchildren to spend more time outdoors. As compared with other measures, spending more time outdoors is the safest strategy and aligns with other existing health initiatives, such as obesity prevention, by promoting a healthier lifestyle for children and adolescents. Useful clinical measures to reduce or slow the progression of myopia include the daily application of low-dose atropine eye drops, in concentrations ranging between 0.01% and 0.05%, despite the side effects of a slightly reduced amplitude of accommodation, slight mydriasis, and risk of an allergic reaction; multifocal spectacle design; contact lenses that have power profiles that produce peripheral myopic defocus; and orthokeratology using corneal gas-permeable contact lenses that are designed to flatten the central cornea, leading to midperipheral steeping and peripheral myopic defocus, during overnight wear to eliminate daytime myopia. The risk-to-benefit ratio needs to be weighed up for the individual on the basis of their age, health, and lifestyle. The measures listed above are not mutually exclusive and are beginning to be examined in combination.
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http://dx.doi.org/10.1167/iovs.62.5.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083117PMC
April 2021

Retinal photograph-based deep learning algorithms for myopia and a blockchain platform to facilitate artificial intelligence medical research: a retrospective multicohort study.

Lancet Digit Health 2021 05;3(5):e317-e329

Peking Union Medical College Hospital, Beijing, China.

Background: By 2050, almost 5 billion people globally are projected to have myopia, of whom 20% are likely to have high myopia with clinically significant risk of sight-threatening complications such as myopic macular degeneration. These are diagnoses that typically require specialist assessment or measurement with multiple unconnected pieces of equipment. Artificial intelligence (AI) approaches might be effective for risk stratification and to identify individuals at highest risk of visual loss. However, unresolved challenges for AI medical studies remain, including paucity of transparency, auditability, and traceability.

Methods: In this retrospective multicohort study, we developed and tested retinal photograph-based deep learning algorithms for detection of myopic macular degeneration and high myopia, using a total of 226 686 retinal images. First we trained and internally validated the algorithms on datasets from Singapore, and then externally tested them on datasets from China, Taiwan, India, Russia, and the UK. We also compared the performance of the deep learning algorithms against six human experts in the grading of a randomly selected dataset of 400 images from the external datasets. As proof of concept, we used a blockchain-based AI platform to demonstrate the real-world application of secure data transfer, model transfer, and model testing across three sites in Singapore and China.

Findings: The deep learning algorithms showed robust diagnostic performance with areas under the receiver operating characteristic curves [AUC] of 0·969 (95% CI 0·959-0·977) or higher for myopic macular degeneration and 0·913 (0·906-0·920) or higher for high myopia across the external testing datasets with available data. In the randomly selected dataset, the deep learning algorithms outperformed all six expert graders in detection of each condition (AUC of 0·978 [0·957-0·994] for myopic macular degeneration and 0·973 [0·941-0·995] for high myopia). We also successfully used blockchain technology for data transfer, model transfer, and model testing between sites and across two countries.

Interpretation: Deep learning algorithms can be effective tools for risk stratification and screening of myopic macular degeneration and high myopia among the large global population with myopia. The blockchain platform developed here could potentially serve as a trusted platform for performance testing of future AI models in medicine.

Funding: None.
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http://dx.doi.org/10.1016/S2589-7500(21)00055-8DOI Listing
May 2021

Visual field defects and myopic macular degeneration in Singapore adults with high myopia.

Br J Ophthalmol 2021 Apr 22. Epub 2021 Apr 22.

Singapore Eye Research Institute, Singapore

Aims: To characterise the association between visual field (VF) defects and myopic macular degeneration (MMD) in highly myopic adults without glaucoma.

Methods: Participants (n=106; 181 eyes) with high myopia (HM; spherical equivalent ≤-5.0 D or axial length (AL) ≥26 mm), after excluding glaucoma and glaucoma suspects, from the Singapore Epidemiology of Eye Diseases-HM study were included in this cross-sectional study. Humphrey VF (central 24-2 threshold), cup-disc ratio (CDR) and intraocular pressure (IOP) measurements were performed. Mean deviation (MD) and pattern SD (PSD), VF defects (normal or abnormal; p<0.05 in ≥3 non-edge contiguous locations) and pattern (eg, generalised sensitivity loss) were analysed. MMD presence was diagnosed from fundus photographs. Generalised estimating equations were used for analysing factors (MD, PSD, VF defects, CDR and IOP) associated with MMD.

Results: Mean age was 55.4±9.9 years and 51.9% were women (AL=26.7±1.1 mm). MMD eyes had lower MD (-3.8±2.9 dB vs -1.1±1.4 dB) and higher PSD (2.8±1.7 dB vs 1.7±0.6 dB). A higher percentage of MMD eyes (n=48) had abnormal VF (62.5% vs 28.6%; p<0.001) compared with no MMD (n=133 eyes). VF pattern in MMD eyes was significantly different from eyes without MMD (p=0.001) with greater generalised sensitivity loss (53.3% vs 10.5%) and arcuate defects (16.7% vs 10.5%). In multivariate analyses, MD (OR=1.52) and PSD (OR=1.67) were significantly (p=0.003) associated with MMD, but VF defects were not associated with MMD.

Conclusion: Highly myopic adults with MMD may have VF loss when compared with highly myopic patients without MMD even in adults without glaucoma.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318674DOI Listing
April 2021

Association of time outdoors and patterns of light exposure with myopia in children.

Br J Ophthalmol 2021 Apr 15. Epub 2021 Apr 15.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore

Background/aims: To evaluate the association of reported time outdoors and light exposure patterns with myopia among children aged 9 years from the Growing Up in Singapore Towards Healthy Outcomes birth cohort.

Methods: We assessed reported time outdoors (min/day), light exposure patterns and outdoor activities of children aged 9 years (n=483) with a questionnaire, the FitSight watch and a 7-day activity diary. Light levels, the duration, timing and frequency of light exposure were assessed. Cycloplegic spherical equivalent (SE), myopia (SE≤-0.5 D) and axial length (AL) of paired eyes were analysed using generalised estimating equations.

Results: In this study, 483 (966 eyes) multiethnic children (50.0% boys, 59.8% Chinese, 42.2% myopic) were included. Reported time outdoors (mean±SD) was 100±93 min/day, and average light levels were 458±228 lux. Of the total duration children spent at light levels of ≥1000 lux (37±19 min/day), 76% were spent below 5000 lux. Peak light exposure occurred at mid-day. Children had 1.7±1.0 light exposure episodes/day. Common outdoor activities were walks, neighbourhood play and swimming. Greater reported time outdoors was associated with lower odds of myopia (OR=0.82, 95% CI 0.70 to 0.95/hour increase daily; p=0.009). Light levels, timing and frequency of light exposures were not associated with myopia, SE or AL (p>0.05).

Conclusion: Reported time outdoors, light levels and number of light exposure episodes were low among Singaporean children aged 9 years. Reported time outdoors was protective against myopia but not light levels or specific light measures. A multipronged approach to increase time outdoors is recommended in the combat against the myopia epidemic.
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http://dx.doi.org/10.1136/bjophthalmol-2021-318918DOI Listing
April 2021

Rapid Myopic Progression in Childhood Is Associated With Teenage High Myopia.

Invest Ophthalmol Vis Sci 2021 04;62(4):17

Singapore Eye Research Institute, Singapore.

Purpose: The purpose of this study was to evaluate the association of childhood progression of spherical equivalent (SE) with high myopia (HM) in teenagers in the Singapore Cohort of Risk factors for Myopia (SCORM).

Methods: We included 928 SCORM children followed over a mean follow-up of 6.9 ± 1.0 years from baseline (6-11 years old) until their teenage years (12-19 years old). Cycloplegic autorefraction and axial length (AL) measurements were performed yearly. The outcomes in teenagers were HM (SE ≤ -5 diopter [D)], AL ≥ 25 mm, SE and AL. Three-year SE and AL progression in childhood and baseline SE and AL with outcomes were evaluated using multivariable logistic or linear regression models, with predictive performance of risk factors assessed using the area under the curve (AUC).

Results: At the last visit, 9.8% of teenagers developed HM and 22.7% developed AL ≥ 25 mm. In multivariate regression analyses, every -0.3 D/year increase in 3-year SE progression and every 0.2 mm/year increase in 3-year AL progression were associated with a -1.14 D greater teenage SE and 0.52 mm greater teenage AL (P values < 0.001). The AUC (95% confidence interval [CI]) of a combination of 3-year SE progression and baseline SE for teenage HM was 0.97 (95% CI = 0.95 - 0.98). The AUC of 3-year AL progression and baseline AL for teenage AL ≥ 25 mm was 0.91 (95% CI = 0.89 - 0.94).

Conclusions: Three-year myopia progression in childhood combined with baseline SE or AL were good predictors of teenage HM. Clinicians may use this combination of factors to guide timing of interventions, potentially reducing the risk of HM later in life.
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http://dx.doi.org/10.1167/iovs.62.4.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054625PMC
April 2021

Time spent outdoors in childhood is associated with reduced risk of myopia as an adult.

Sci Rep 2021 03 18;11(1):6337. Epub 2021 Mar 18.

Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Perth, Australia.

Myopia (near-sightedness) is an important public health issue. Spending more time outdoors can prevent myopia but the long-term association between this exposure and myopia has not been well characterised. We investigated the relationship between time spent outdoors in childhood, adolescence and young adulthood and risk of myopia in young adulthood. The Kidskin Young Adult Myopia Study (KYAMS) was a follow-up of the Kidskin Study, a sun exposure-intervention study of 1776 children aged 6-12 years. Myopia status was assessed in 303 (17.6%) KYAMS participants (aged 25-30 years) and several subjective and objective measures of time spent outdoors were collected in childhood (8-12 years) and adulthood. Index measures of total, childhood and recent time spent outdoors were developed using confirmatory factor analysis. Logistic regression was used to assess the association between a 0.1-unit change in the time outdoor indices and risk of myopia after adjusting for sex, education, outdoor occupation, parental myopia, parental education, ancestry and Kidskin Study intervention group. Spending more time outdoors during childhood was associated with reduced risk of myopia in young adulthood (multivariable odds ratio [OR] 0.82, 95% confidence interval [CI] 0.69, 0.98). Spending more time outdoors in later adolescence and young adulthood was associated with reduced risk of late-onset myopia (≥ 15 years of age, multivariable OR 0.79, 95% CI 0.64, 0.98). Spending more time outdoors in both childhood and adolescence was associated with less myopia in young adulthood.
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http://dx.doi.org/10.1038/s41598-021-85825-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973740PMC
March 2021

Is artificial intelligence a solution to the myopia pandemic?

Br J Ophthalmol 2021 06 12;105(6):741-744. Epub 2021 Mar 12.

Singapore National Eye Centre, Singapore

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http://dx.doi.org/10.1136/bjophthalmol-2021-319129DOI Listing
June 2021

Deep Learning Approach for Automated Detection of Myopic Maculopathy and Pathologic Myopia in Fundus Images.

Ophthalmol Retina 2021 Feb 18. Epub 2021 Feb 18.

Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address:

Purpose: To determine whether eyes with pathologic myopia can be identified and whether each type of myopic maculopathy lesion on fundus photographs can be diagnosed by deep learning (DL) algorithms.

Design: A DL algorithm was developed to recognize myopic maculopathy features and to categorize the myopic maculopathy automatically.

Participants: We examined 7020 fundus images from 4432 highly myopic eyes obtained from the Advanced Clinical Center for Myopia.

Methods: Deep learning (DL) algorithms were developed to recognize the key features of myopic maculopathy with 5176 fundus images. These algorithms were also used to develop a Meta-analysis for Pathologic Myopia (META-PM) study categorizing system (CS) by adding a specific processing layer. Models and the system were evaluated by 1844 fundus image. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to determine the performance of each DL algorithm. The rate of correct predictions was used to determine the performance of the META-PM study CS.

Main Outcome Measures: Four trained DL models were able to recognize the lesions of myopic maculopathy accurately with high sensitivity and specificity. The META-PM study CS also showed a high accuracy and was qualified to be used in a semiautomated way during screening for myopic maculopathy in highly myopic eyes.

Results: The sensitivity of the DL models was 84.44% for diffuse atrophy, 87.22% for patchy atrophy, 85.10% for macular atrophy, and 37.07% for choroidal neovascularization, and the AUC values were 0.970, 0.978, 0.982, and 0.881, respectively. The rate of total correct predictions from the META-PM study CS was 87.53%, with rates of 90.18%, 95.28%, 97.50%, and 91.14%, respectively, for each type of lesion. The META-PM study CS showed an overall rate of 92.08% in detecting pathologic myopia correctly, which was defined as having myopic maculopathy equal to or more serious than diffuse atrophy.

Conclusions: The novel DL models and system can achieve high sensitivity and specificity in identifying the different types of lesions of myopic maculopathy. These results will assist in the screening for pathologic myopia and subsequent protection of patients against low vision and blindness caused by myopic maculopathy.
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http://dx.doi.org/10.1016/j.oret.2021.02.006DOI Listing
February 2021

Annual Myopia Progression and Subsequent 2-Year Myopia Progression in Singaporean Children.

Transl Vis Sci Technol 2020 12 7;9(13):12. Epub 2020 Dec 7.

Singapore Eye Research Institute, Singapore.

Purpose: To investigate the association between 1-year myopia progression and subsequent 2-year myopia progression among myopic children in the Singapore Cohort Study of the Risk Factors for Myopia.

Methods: This retrospective analysis included 618 myopic children (329 male), 7 to 9 years of age (mean age, 8.0 ± 0.8) at baseline with at least two annual follow-up visits. Cycloplegic autorefraction was performed at every visit. Receiver operating characteristic (ROC) curves from multiple logistic regressions were derived for future fast 2-year myopia progression.

Results: Children with slow progression during the first year (slower than -0.50 diopter [D]/y) had the slowest mean subsequent 2-year myopia progression (-0.41 ± 0.33 D/y), whereas children with fast progression (faster than -1.25 D/y) in year 1 had the fastest mean subsequent 2-year myopia progression (-0.82 ± 0.30 D/y) ( for trend < 0.001). Year 1 myopia progression had the highest area under the curve (AUC) for predicting fast subsequent 2-year myopia progression (AUC = 0.77; 95% confidence interval [CI], 0.73-0.80) compared to baseline spherical equivalent (AUC = 0.70; 95% CI, 0.66-0.74) or age of myopia onset (AUC = 0.66; 95% CI, 0.61-0.70) after adjusting for confounders. Age at baseline alone had an AUC of 0.65 (95% CI, 0.61-0.69).

Conclusions: One-year myopia progression and age at baseline were associated with subsequent 2-year myopia progression in children 7 to 9 years of age.

Translational Relevance: Myopia progression and age at baseline may be considered by eye care practitioners as two of several factors that may be associated with future myopia progression in children.
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http://dx.doi.org/10.1167/tvst.9.13.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726587PMC
December 2020

Myopia.

Nat Rev Dis Primers 2020 12 17;6(1):99. Epub 2020 Dec 17.

Centre for Eye Research Australia, Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia.

Myopia, also known as short-sightedness or near-sightedness, is a very common condition that typically starts in childhood. Severe forms of myopia (pathologic myopia) are associated with a risk of other associated ophthalmic problems. This disorder affects all populations and is reaching epidemic proportions in East Asia, although there are differences in prevalence between countries. Myopia is caused by both environmental and genetic risk factors. A range of myopia management and control strategies are available that can treat this condition, but it is clear that understanding the factors involved in delaying myopia onset and slowing its progression will be key to reducing the rapid rise in its global prevalence. To achieve this goal, improved data collection using wearable technology, in combination with collection and assessment of data on demographic, genetic and environmental risk factors and with artificial intelligence are needed. Improved public health strategies focusing on early detection or prevention combined with additional effective therapeutic interventions to limit myopia progression are also needed.
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http://dx.doi.org/10.1038/s41572-020-00231-4DOI Listing
December 2020

Volumetric Choroidal Segmentation Using Sequential Deep Learning Approach in High Myopia Subjects.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1286-1289

Many ocular diseases are associated with choroidal changes. Therefore, it is crucial to be able to segment the choroid to study its properties. Previous methods for choroidal segmentation have focused on single cross-sectional scans. Volumetric choroidal segmentation has yet to be widely reported. In this paper, we propose a sequential segmentation approach using a variation of U-Net with a bidirectional C-LSTM(Convolutional Long Short Term Memory) module in the bottleneck region. The model is evaluated on volumetric scans from 40 high myopia subjects, obtained using SS-OCT(Swept Source Optical Coherence Tomography). A comparison with other U-Net-based variants is also presented. The results demonstrate that volumetric segmentation of the choroid can be achieved with an accuracy of IoU(Intersection over Union) 0.92.Clinical relevance- This deep learning approach can automatically segment the choroidal volume, which can enable better evaluation and monitoring at ocular diseases.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176184DOI Listing
July 2020

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

Br J Ophthalmol 2021 08 2;105(8):1140-1148. Epub 2020 Sep 2.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

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.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316648DOI Listing
August 2021

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

Br J Ophthalmol 2021 09 18;105(9):1196-1202. Epub 2020 Aug 18.

Department of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Germany.

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.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316475DOI Listing
September 2021

Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson.

Commun Biol 2020 07 31;3(1):410. Epub 2020 Jul 31.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM's Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development.
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http://dx.doi.org/10.1038/s42003-020-01137-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395727PMC
July 2020

Comparison of myopic progression in Finnish and Singaporean children.

Acta Ophthalmol 2021 Mar 24;99(2):171-180. Epub 2020 Jul 24.

Saw Swee Hock School of Public Health, National University of Singapore (NUS), Singapore.

Purpose: To compare 3-year myopic progression between Finnish and Singaporean children.

Methods: Myopic progression was compared between 9-year-old (mean age 9.7 ± 0.4 years, n = 92) and 11-year-old (mean age 11.7 ± 0.4 years, n = 144) Finnish (Finnish RCT) children and Singaporean children matched by age and refraction (SCORMMatched, n = 403) and 7- to 8-year-old Singaporean children matched only by refraction (SCORM Young, n = 186). Spherical equivalent (SE) was between -0.50 and -3.00 D. Refraction with cycloplegia was controlled annually for 3 years. Information on parental myopia, mother's education, time spent on near-work and outdoor time was gathered by parental questionnaire.

Results: Three-year myopic progression was -2.08 ± 0.96 D and -1.30 ± 0.69 D in the Finnish RCT and Singaporean SCORM Matched 9-year-olds, respectively, and -1.34 ± 0.78 D, and -0.52 ± 0.44 D in the 11-year-olds, respectively (p < 0.001 between all groups). Myopic progression was fastest (-2.69 ± 0.89 D) in the SCORM 7-year-olds and similar between the SCORM Matched 9-year-olds and Finnish RCT 11-year-olds (p = 0.55). The Finnish RCT and SCORM Matched children showed significant differences in both daily near-work time (1.8 ± 1.0 versus 3.4 ± 1.9 hours per day, p < 0.001) and outdoor time (2.6 ± 0.9 versus 0.5 ± 0.4 hours per day, p < 0.001). These differences did not, however, explain the differences in myopic progression between the groups. More time spent outdoors was associated with less myopic progression in the Finnish RCT (r = 0.17, p = 0.009) group only. In the whole materials, greater myopic progression was associated with younger age at baseline (p < 0.001), younger age was associated with mother's higher education (p < 0.001), and mothers higher education was associated with myopia in both parents (p < 0.001).

Conclusion: Age at baseline was the most significant factor associated with myopic progression. However, at the same age and with the same initial refraction, the Finnish and Singaporean children showed different myopic progression. This result remains unexplained. Thus, age of myopia onset should be considered when comparing myopic progression between different samples and conducting treatment trials. Parental myopia may be a weak indicator of heredity of myopia.
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http://dx.doi.org/10.1111/aos.14545DOI Listing
March 2021

Prevalence, risk factors and impact of posterior staphyloma diagnosed from wide-field optical coherence tomography in Singapore adults with high myopia.

Acta Ophthalmol 2021 Mar 29;99(2):e144-e153. Epub 2020 Jun 29.

Singapore Eye Research Institute, Singapore, Singapore.

Purpose: To investigate the prevalence and risk factors of posterior staphyloma using wide-field optical coherence tomography (WF-OCT) in adults with high myopia in Singapore.

Design: Population-based cross-sectional study.

Methods: Adults with spherical equivalent (SE) ≤ -5D in either eye at the first visit of Singapore Epidemiology of Eye Diseases study and Singapore Prospective Study Program study were recruited. Posterior staphyloma was diagnosed using WF-OCT (PLEX Elite9000, Carl Zeiss Meditec). Myopic macular degeneration (MMD), myopic traction maculopathy (MTM) and vision-related quality of life (VRQoL) were assessed using fundus photographs, DRI-Triton OCT (Topcon) and the Impact of Vision Impairment (IVI) questionnaire, respectively. Factors associated with posterior staphyloma were identified with multilevel, multivariable logistic regression. Impact of posterior staphyloma on MMD, MTM and visual function was analysed with multilevel, multivariable logistic regression and linear mixed model, respectively.

Results: Among the 225 eyes [mean SE = -6.5 ± 2.2 D, mean axial length (AL) = 26.2 ± 1.5 mm] of 117 participants (mean age = 60.3 ± 7.1 years), posterior staphyloma was detected in 47 (20.9%) eyes of 38 (32.5%) participants. Older age [odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10-1.26], more myopic SE (0.63; 0.51-0.77) and increased AL (2.51; 1.69-3.73) were associated with higher prevalence of posterior staphyloma (all p < 0.001). Adults with posterior staphyloma had higher odds of MMD (2.67; 1.23-5.82; p = 0.013), MTM (3.79; 1.13-12.68; p = 0.031) and worse IVI Reading (β = -1.44; -2.31 to 0.58; p = 0.001) scores.

Conclusions: About one in three adults with high myopia had posterior staphyloma, which was associated with increased odds of having myopic maculopathy and a detrimental impact on VRQoL.
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http://dx.doi.org/10.1111/aos.14527DOI Listing
March 2021

Characteristics of myopic traction maculopathy in myopic Singaporean adults.

Br J Ophthalmol 2021 04 23;105(4):531-537. Epub 2020 May 23.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore

Purpose: To investigate the characteristics, risk factors and visual impact of myopic traction maculopathy (MTM) among adults with myopia in Singapore.

Methods: We analysed 3316 myopic eyes of adults aged over 40 years who participated in the Singapore Epidemiology of Eye Diseases-2 study. Detailed questionnaires and ophthalmic examinations were conducted. A total of 2913 myopic eyes of 1639 subjects were graded for MTM by spectral-domain optical coherence tomography. MTM is defined as the presence of retinoschisis, lamellar or full-thickness macula hole and foveal retinal detachment. Fundus photographs were graded for myopic macular degeneration (MMD).

Results: Of these 2913 myopic eyes, the mean and SD of age was 60.1±8.0 years; the spherical equivalent (SE) was -2.5±2.3 D; and the axial length (AL) was 24.6±1.3 mm. MTM was found in 0.9% of myopic eyes and 7.3% of highly myopic eyes. In the multivariate analysis, myopic SE (p<0.001), longer AL (p<0.001), MMD (p=0.01) and epiretinal traction (p<0.001) were independent risk factors for MTM. MTM was not associated with age (p=0.38). MTM was significantly associated with poorer best-corrected visual acuity (BCVA) (p<0.01).

Conclusions: Our population-based study revealed that MTM was present in 0.9% of myopic eyes and 7.3% of highly myopic eyes. While greater myopic SE, longer AL, MMD and epiretinal traction are risk factors of MTM, age was not related to MTM. MTM has a negative effect on BCVA.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316182DOI Listing
April 2021

High Myopes in Singapore: 19-Year Progression from Childhood to Adulthood.

Ophthalmology 2020 12 21;127(12):1768-1770. Epub 2020 May 21.

Singapore Eye Research Institute, Singapore, Republic of Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Republic of Singapore; Duke-NUS Medical School, Singapore, Republic of Singapore. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2020.05.031DOI Listing
December 2020

Genome-Wide Association Study in Asians Identifies Novel Loci for High Myopia and Highlights a Nervous System Role in Its Pathogenesis.

Ophthalmology 2020 12 16;127(12):1612-1624. Epub 2020 May 16.

Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Department of Advanced Medicine for Ocular Diseases, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address:

Purpose: To identify novel susceptibility loci for high myopia.

Design: Genome-wide association study (GWAS) followed by replication and meta-analysis.

Participants: A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls).

Methods: We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses.

Main Outcome Measures: We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study.

Results: We identified 9 loci with genome-wide significance (P < 5.0 × 10). Three loci were previously reported myopia-related loci (ZC3H11B on 1q41, GJD2 on 15q14, and RASGRF1 on 15q25.1), and the other 6 were novel (HIVEP3 on 1p34.2, NFASC/CNTN2 on 1q32.1, CNTN4/CNTN6 on 3p26.3, FRMD4B on 3p14.1, LINC02418 on 12q24.33, and AKAP13 on 15q25.3). The GO analysis revealed a significant role of the nervous system related to synaptic signaling, neuronal development, and Ras/Rho signaling in the pathogenesis of high myopia.

Conclusions: The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.
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http://dx.doi.org/10.1016/j.ophtha.2020.05.014DOI Listing
December 2020

Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.

Eur J Epidemiol 2020 Jul 7;35(7):685-697. Epub 2020 May 7.

Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Lund University, 21741, Malmö, Sweden.

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (β = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (β = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (β = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.
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http://dx.doi.org/10.1007/s10654-020-00638-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867117PMC
July 2020

Six-Year Changes in Myopic Macular Degeneration in Adults of the Singapore Epidemiology of Eye Diseases Study.

Invest Ophthalmol Vis Sci 2020 04;61(4):14

.

Purpose: To examine the 6-year incidence, progression, associated risk factors, and impact of myopic macular degeneration (MMD) in a myopic population in Singapore.

Methods: We examined myopic (spherical equivalent ≤-0.5 diopters) adults (N = 2157 persons and 3661 eyes) who were phakic at baseline and participated in both baseline and 6-year follow-up visits of the Singapore Epidemiology of Eye Diseases study. Eye examinations, including visual acuity, subjective refraction and axial length (AL) measurements, were performed. MMD was graded from fundus photographs following the META-PM classification. Vision-related quality of life was assessed with Rasch-transformed scores from reading, mobility, and emotional domains of the Impact of Vision Impairment questionnaire.

Results: The 6-year eye-specific incidence of MMD among myopic eyes was 1.2% (95% CI, 0.9%-1.6%). Older age, worse spherical equivalent, and longer AL at baseline were associated with MMD incidence (all P < 0.001). The 6-year eye-specific progression of MMD in 288 eyes with baseline MMD was 17.0% (95% CI, 12.6%-21.4%). More severe MMD at baseline, worse spherical equivalent, and longer AL (all P < 0.05) were associated with MMD progression. Patients with Meta-PM categories 3 and 4 had worse best-corrected visual acuity and poorer vision-related quality of life outcomes than those without MMD (all P < 0.05).

Conclusions: Over a 6-year period, one in 80 myopic eyes developed MMD and one in six with existing MMD had MMD progression. Myopia severity and AL were strong predictors of MMD development and progression. Eyes with severe MMD were at higher risk of MMD progression than those with less severe MMD, and were associated with poorer visual acuity and vision-related quality of life.
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http://dx.doi.org/10.1167/iovs.61.4.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401489PMC
April 2020

Rationale and protocol for the 7- and 8-year longitudinal assessments of eye health in a cohort of young adults in the Raine Study.

BMJ Open 2020 03 25;10(3):e033440. Epub 2020 Mar 25.

Centre for Ophthalmology and Visual Science, University of Western Australia, Nedlands, Western Australia, Australia.

Introduction: Eye diseases and visual impairment more commonly affect elderly adults, thus, the majority of ophthalmic cohort studies have focused on older adults. Cohort studies on the ocular health of younger adults, on the other hand, have been few. The Raine Study is a longitudinal study that has been following a cohort since their birth in 1989-1991. As part of the 20-year follow-up of the Raine Study, participants underwent a comprehensive eye examination. As part of the 27- and 28-year follow-ups, eye assessments are being conducted and the data collected will be compared with those of the 20-year follow-up. This will provide an estimate of population incidence and updated prevalence of ocular conditions such as myopia and keratoconus, as well as longitudinal change in ocular parameters in young Australian adults. Additionally, the data will allow exploration of the environmental, health and genetic factors underlying inter-subject differential long-term ocular changes.

Methods And Analysis: Participants are being contacted via telephone, email and/or social media and invited to participate in the eye examination. At the 27-year follow-up, participants completed a follow-up eye screening, which assessed visual acuity, autorefraction, ocular biometry and ocular sun exposure. Currently, at the 28-year follow-up, a comprehensive eye examination is being conducted which, in addition to all the eye tests performed at the 27-year follow-up visit, includes tonometry, optical coherence tomography, funduscopy and anterior segment topography, among others. Outcome measures include the incidence of refractive error and pterygium, an updated prevalence of these conditions, and the 8-year change in ocular parameters.

Ethics And Dissemination: The Raine Study is registered in the Australian New Zealand Clinical Trials Registry. The Gen2 20-year, 27-year and 28-year follow-ups are approved by the Human Research Ethics Committee of the University of Western Australia. Findings resulting from the study will be published in health or medical journals and presented at conferences.

Trial Registration Number: ACTRN12617001599369; Active, not recruiting.
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http://dx.doi.org/10.1136/bmjopen-2019-033440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170556PMC
March 2020

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.

Commun Biol 2020 03 19;3(1):133. Epub 2020 Mar 19.

Department of Ophthalmology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.
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http://dx.doi.org/10.1038/s42003-020-0802-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081241PMC
March 2020

Association of Parental Myopia With Higher Risk of Myopia Among Multiethnic Children Before School Age.

JAMA Ophthalmol 2020 05;138(5):501-509

Southern California Eye Institute, CHA Hollywood Presbyterian Medical Center, Los Angeles.

Importance: Parental myopia is an important risk factor for preschool myopia in Asian children. Further investigation of the association between parental myopia and early-onset myopia risk in other racial/ethnic groups, such as African American and Hispanic white children, could improve understanding of the etiology and treatment of this condition.

Objective: To investigate the association of parental myopia with refractive error and ocular biometry in multiethnic children aged 6 to 72 months.

Design, Setting, And Participants: This cohort study pooled data from children in 3 population-based studies with comparable design from the US, Singapore, and Australia. Parental myopia was defined as the use of glasses or contact lenses for distance viewing by the child's biological parent(s). Multivariable regressions were conducted to assess the association of parental myopia. Data were collected from 2003 to 2011 and analyzed from 2017 to 2019.

Main Outcomes And Measures: Cycloplegic refraction and prevalence of myopia (spherical equivalent refractive error of≤-0.5 diopters [D]) in the more myopic eye.

Results: The analysis cohort included 9793 children, including 4003 Asian, 2201 African American, 1998 Hispanic white, and 1591 non-Hispanic white participants (5106 boys [52.1%]; mean [SD] age, 40.0 [18.9] months). Compared with children without parental myopia, the odds ratios for early-onset myopia were 1.42 (95% CI, 1.20-1.68) for children with 1 parent with myopia, 2.70 (95% CI, 2.19-3.33) for children with 2 parents with myopia, and 3.39 (95% CI, 1.99-5.78) for children with 2 parents with childhood-onset myopia. Even among children without myopia, parental myopia was associated with a greater ratio of axial length to corneal curvature radius (regression coefficient for myopia in both parents, 0.023; P < .001) and more myopic refractive error (regression coefficient for myopia in both parents, -0.20 D; P < .001). Effects of parental myopia were observed in all 4 racial/ethnic groups and across age groups except those younger than 1 year. However, parental myopia was not associated with the age-related trends of refractive error (regression coefficient for children without parental myopeia, 0.08; for children with 2 parents with myopia, 0.04; P = .31 for interaction) and ratio of axial length to corneal curvature radius (regression coefficient for children without parental myopeia, 0.031; for children with 2 parents with myopia, 0.032; P = .89 for interaction) beyond infancy.

Conclusions And Relevance: Parental myopia, especially childhood-onset parental myopia, was associated with a greater risk of early-onset myopia in Asian, Hispanic, non-Hispanic white, and African American children. The observed associations of parental myopia in children as early as 1 year of age and in children without myopia suggests that genetic susceptibility may play a more important role in early-onset myopia and that parental myopia may contribute to myopia in children by setting up a more myopic baseline before school age.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.0412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082765PMC
May 2020
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