Ophthalmology (Eye & Ear Hospital) - Research Publications

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    The WHO-ITU MyopiaEd Programme: A Digital Message Programme Targeting Education on Myopia and Its Prevention.
    Keel, S ; Govender-Poonsamy, P ; Cieza, A ; Faal, H ; Flitcroft, I ; Gifford, K ; He, M ; Khandekar, R ; Naidoo, K ; Oerding, M ; Ohno-Matsui, K ; Mariotti, S ; Wildsoet, C ; Wolffsohn, JS ; Wong, TY ; Yoon, S ; Mueller, A ; Dobson, R (Frontiers Media SA, 2022)
    The objective of this paper is to provide an overview of the World Health Organization - International Telecommunication Union MyopiaEd programme - a digital message programme targeting education on myopia and its prevention. The development of the MyopiaEd programme included 4 key steps: (1) Conceptualization and consultation with experts in the field of myopia, mHealth and health behavior change; (2) Creation of SMS message libraries and programme algorithm; (3) Review of the message libraries to ensure relevance to the target audience; and (4) Pre-testing amongst end-user groups to ensure that the design of the programme and the message content were understandable. After reviewing the available evidence and considering input of the experts, the aims, end users and key themes of the programme were finalized. Separate SMS-adapted message libraries were developed, reviewed and pre-tested for four target end-user groups; (1) general population involved in the care of children (2) parents or caregivers of children with myopia; (3) adolescents with myopia; and (4) adults with myopia. The message libraries are part of a comprehensive toolkit, developed through a consultative process with experts in digital health, to support implementation within countries. The development of the MyopiaEd programme aims to provide a basis for Member States and other stakeholders to develop, implement and monitor large-scale mHealth programmes. It is aimed at raising awareness of good eye care behaviors and addressing common reasons for non-compliance to spectacle wear. The next steps will involve adapting and evaluating the MyopiaEd programme in selected settings.
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    Association between digital smart device use and myopia: a systematic review and meta-analysis
    Foreman, J ; Salim, AT ; Praveen, A ; Fonseka, D ; Ting, DSW ; He, MG ; Bourne, RRA ; Crowston, J ; Wong, TY ; Dirani, M (ELSEVIER, 2021-12)
    BACKGROUND: Excessive use of digital smart devices, including smartphones and tablet computers, could be a risk factor for myopia. We aimed to review the literature on the association between digital smart device use and myopia. METHODS: In this systematic review and meta-analysis we searched MEDLINE and Embase, and manually searched reference lists for primary research articles investigating smart device (ie, smartphones and tablets) exposure and myopia in children and young adults (aged 3 months to 33 years) from database inception to June 2 (MEDLINE) and June 3 (Embase), 2020. We included studies that investigated myopia-related outcomes of prevalent or incident myopia, myopia progression rate, axial length, or spherical equivalent. Studies were excluded if they were reviews or case reports, did not investigate myopia-related outcomes, or did not investigate risk factors for myopia. Bias was assessed with the Joanna Briggs Institute Critical Appraisal Checklists for analytical cross-sectional and cohort studies. We categorised studies as follows: category one studies investigated smart device use independently; category two studies investigated smart device use in combination with computer use; and category three studies investigated smart device use with other near-vision tasks that were not screen-based. We extracted unadjusted and adjusted odds ratios (ORs), β coefficients, prevalence ratios, Spearman's correlation coefficients, and p values for associations between screen time and incident or prevalent myopia. We did a meta-analysis of the association between screen time and prevalent or incident myopia for category one articles alone and for category one and two articles combined. Random-effects models were used when study heterogeneity was high (I2>50%) and fixed-effects models were used when heterogeneity was low (I2≤50%). FINDINGS: 3325 articles were identified, of which 33 were included in the systematic review and 11 were included in the meta-analysis. Four (40%) of ten category one articles, eight (80%) of ten category two articles, and all 13 category three articles used objective measures to identify myopia (refraction), whereas the remaining studies used questionnaires to identify myopia. Screen exposure was measured by use of questionnaires in all studies, with one also measuring device-recorded network data consumption. Associations between screen exposure and prevalent or incident myopia, an increased myopic spherical equivalent, and longer axial length were reported in five (50%) category one and six (60%) category two articles. Smart device screen time alone (OR 1·26 [95% CI 1·00-1·60]; I2=77%) or in combination with computer use (1·77 [1·28-2·45]; I2=87%) was significantly associated with myopia. The most common sources of risk of bias were that all 33 studies did not include reliable measures of screen time, seven (21%) did not objectively measure myopia, and nine (27%) did not identify or adjust for confounders in the analysis. The high heterogeneity between studies included in the meta-analysis resulted from variability in sample size (range 155-19 934 participants), the mean age of participants (3-16 years), the standard error of the estimated odds of prevalent or incident myopia (0·02-2·21), and the use of continuous (six [55%] of 11) versus categorical (five [46%]) screen time variables INTERPRETATION: Smart device exposure might be associated with an increased risk of myopia. Research with objective measures of screen time and myopia-related outcomes that investigates smart device exposure as an independent risk factor is required. FUNDING: None.
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    Spatial Technology Assessment of Green Space Exposure and Myopia
    Yang, Y ; Chen, W ; Xu, A ; Zhao, L ; Ding, X ; Li, J ; Zhu, Y ; Chen, C ; Long, E ; Liu, Z ; Wang, X ; Li, X ; Zhang, X ; Jiang, Z ; He, H ; Wang, G ; Jin, L ; Liao, H ; Yun, D ; Yu-Wai-Man, P ; Yan, P ; Wang, R ; Li, Z ; Xie, Y ; Liu, Y ; Wang, X ; Zhang, Q ; Wang, J ; Nie, D ; Zhang, S ; Ting, DSW ; Wong, TY ; He, M ; Liu, Y ; Morgan, IG ; Lin, H (ELSEVIER SCIENCE INC, 2022-01)
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    Associations of retinal microvascular caliber with intermediate phenotypes of large arterial function and structure: A systematic review and meta-analysis
    Liu, M ; Wake, M ; Wong, TY ; He, M ; Xiao, Y ; Burgner, DP ; Lycett, K (WILEY, 2019-10)
    OBJECTIVE: Intermediate phenotypes of microcirculation (retinal microvascular caliber) are associated with cardiovascular (CV) risk factors and independently predict CV events. However, the effect of microcirculation variation on the vascular system is unclear. We conducted a systematic review and meta-analysis of observational studies to quantify associations of retinal microvascular caliber (arteriolar, venular caliber, arteriole-to-venule ratio) and preclinical CV measures (large arterial function and structure). METHODS: We identified studies in MEDLINE, EMBASE, and PubMed (1946 to March 2018) studying (a) general population samples and (b) patients with cardiometabolic disease. Study-specific correlation estimates were combined into meta-analysis where possible. RESULTS: Of 1294 studies identified, 26 met inclusion criteria (general population 16, patients 10), of which five studies were included in meta-analysis. Most studied middle-aged adults cross-sectionally, with one childhood study. Large arterial function and structure were predominantly assessed by pulse wave velocity and carotid intima-media thickness, respectively. Only arteriolar caliber was consistently associated with arterial function and structure, with stronger associations observed in cardiometabolic patients. Narrower (worse) arteriolar caliber was associated with faster (poorer) pulse wave velocity (correlation coefficient (r) -0.17, 95% CI -0.25 to -0.10) and greater (poorer) intima-media thickness (r -0.05, 95%CI -0.09 to -0.02) across all adult participants. CONCLUSIONS: Retinal arteriolar, but not venular caliber, was modestly associated with large arterial function and weakly associated with large arterial structure, with stronger evidence in patients with cardiometabolic disease. This suggests that preclinical changes in large arteries and the microcirculation have some shared but mainly unique pathways to associate with cardiovascular disease.
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    Associations of retinal microvascular caliber with large arterial function and structure: A population-based study of 11 to 12 year-olds and midlife adults
    Liu, M ; Lycett, K ; Wong, TY ; Grobler, A ; Juonala, M ; He, M ; Dwyer, T ; Burgner, D ; Wake, M (WILEY, 2020-08)
    OBJECTIVE: We examined associations between retinal microvascular and large arterial phenotypes to explore relationships between the micro- and macro-vasculature in childhood and midlife. METHODS: Participants were 1288 children (11-12 years, 50.9% female) and 1264 adults (mean age 44 years, 87.6% female) in a cross-sectional population-based study. Exposures were retinal arteriolar and venular caliber quantified from retinal images. Outcomes included arterial function (pulse wave velocity; carotid arterial elasticity) and structure (carotid intima-media thickness). Multivariable regression models were performed adjusting for age, sex, and family socioeconomic position. RESULTS: In children, one standard deviation wider arteriolar caliber was associated with slower pulse wave velocity (-0.15 SD, 95% CI -0.21, -0.09) and higher elasticity (0.13 SD, 95% CI 0.06, 0.20); per SD wider venular caliber was associated with faster pulse wave velocity (0.09 SD, 95% CI 0.03, 0.15) and lower elasticity (-0.07 SD, 95% CI -0.13, -0.01). The size of adult associations was approximately double. Wider arteriolar caliber was associated with smaller carotid intima-media thickness (-0.09 SD, 95% CI -0.16, -0.03) in adults but not children. Venular caliber and carotid intima-media thickness showed little evidence of association. CONCLUSIONS: Narrower retinal arterioles and wider venules are associated with large arterial function as early as mid-childhood. Associations strengthen by midlife and also extend to arterial structure, although effect sizes remain small.
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    Myopia - A 21st Century Public Health Issue (vol 60, pg1888, 2019)
    Resnikoff, S ; Jonas, JB ; Friedman, D ; He, M ; Jong, M ; Nichols, JJ ; Ohno-Matsui, K ; Smith, EL ; Wildsoet, CF ; Taylor, HR ; Wolffsohn, JS ; Wong, TY (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019-05)
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    Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium
    Li, Q ; Wojciechowski, R ; Simpson, CL ; Hysi, PG ; Verhoeven, VJM ; Ikram, MK ; Hoehn, R ; Vitart, V ; Hewitt, AW ; Oexle, K ; Makela, K-M ; MacGregor, S ; Pirastu, M ; Fan, Q ; Cheng, C-Y ; St Pourcain, B ; McMahon, G ; Kemp, JP ; Northstone, K ; Rahi, JS ; Cumberland, PM ; Martin, NG ; Sanfilippo, PG ; Lu, Y ; Wang, YX ; Hayward, C ; Polasek, O ; Campbell, H ; Bencic, G ; Wright, AF ; Wedenoja, J ; Zeller, T ; Schillert, A ; Mirshahi, A ; Lackner, K ; Yip, SP ; Yap, MKH ; Ried, JS ; Gieger, C ; Murgia, F ; Wilson, JF ; Fleck, B ; Yazar, S ; Vingerling, JR ; Hofman, A ; Uitterlinden, A ; Rivadeneira, F ; Amin, N ; Karssen, L ; Oostra, BA ; Zhou, X ; Teo, Y-Y ; Tai, ES ; Vithana, E ; Barathi, V ; Zheng, Y ; Siantar, RG ; Neelam, K ; Shin, Y ; Lam, J ; Yonova-Doing, E ; Venturini, C ; Hosseini, SM ; Wong, H-S ; Lehtimaki, T ; Kahonen, M ; Raitakari, O ; Timpson, NJ ; Evans, DM ; Khor, C-C ; Aung, T ; Young, TL ; Mitchell, P ; Klein, B ; van Duijn, CM ; Meitinger, T ; Jonas, JB ; Baird, PN ; Mackey, DA ; Wong, TY ; Saw, S-M ; Parssinen, O ; Stambolian, D ; Hammond, CJ ; Klaver, CCW ; Williams, C ; Paterson, AD ; Bailey-Wilson, JE ; Guggenheim, JA (SPRINGER, 2015-02)
    To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.
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    Comparison of Anterior Segment Optical Tomography Parameters Measured Using a Semi-Automatic Software to Standard Clinical Instruments
    Ang, M ; Chong, W ; Huang, H ; Tay, WT ; Wong, TY ; He, M-G ; Aung, T ; Mehta, JS ; Stieger, K (PUBLIC LIBRARY SCIENCE, 2013-06-04)
    OBJECTIVE: To compare anterior segment parameters measured using a semi-automatic software (Zhongshan Angle Assessment Program, ZAP) applied to anterior segment optical coherence tomography (AS-OCT) images, with commonly used instruments. METHODS: Cross-sectional study of a total of 1069 subjects (1069 eyes) from three population-based studies of adults aged 40-80 years. All subjects underwent AS-OCT imaging and ZAP software was applied to determine anterior chamber depth (ACD), central corneal thickness (CCT), anterior and keratometry (K) - readings. These were compared to auto-refraction, keratometry and ocular biometry measured using an IOLMaster, ultrasound pachymeter and auto-refractor respectively. Agreements between AS-OCT (ZAP) and clinical instrument modalities were described using Bland-Altman, 95% limits of agreement (LOA). RESULTS: The mean age of our subjects was 56.9±9.5 years and 50.9% were male. The mean AS-OCT (ZAP) parameters of our study cohort were: ACD 3.29±0.35 mm, CCT 560.75±35.07 µm; K-reading 46.79±2.72 D. There was good agreement between the measurements from ZAP analysis and each instrument and no violations in the assumptions of the LOA; albeit with a systematic bias for each comparison: AS-OCT consistently measured a deeper ACD compared to IOLMaster (95% LOA -0.24, 0.55); and a thicker CCT for the AS-OCT compared to ultrasound pachymetry (16.8±0.53 µm 95% LOA -17.3, 50.8). AS-OCT had good agreement with auto-refractor with at least 95% of the measurements within the prediction interval (P value <0.001). CONCLUSION: This study demonstrates that there is good agreement between the measurements from the AS-OCT (ZAP) and conventional tools. However, small systematic biases remain that suggest that these measurement tools may not be interchanged.
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    Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium
    Fan, Q ; Guo, X ; Tideman, JWL ; Williams, KM ; Yazar, S ; Hosseini, SM ; Howe, LD ; St Pourcain, B ; Evans, DM ; Timpson, NJ ; McMahon, G ; Hysi, PG ; Krapohl, E ; Wang, YX ; Jonas, JB ; Baird, PN ; Wang, JJ ; Cheng, C-Y ; Teo, Y-Y ; Wong, T-Y ; Ding, X ; Wojciechowski, R ; Young, TL ; Parssinen, O ; Oexle, K ; Pfeiffer, N ; Bailey-Wilson, JE ; Paterson, AD ; Klaver, CCW ; Plomin, R ; Hammond, CJ ; Mackey, DA ; He, M ; Saw, S-M ; Williams, C ; Guggenheim, JA (NATURE PORTFOLIO, 2016-05-13)
    Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).
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    Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error
    Fan, Q ; Verhoeven, VJM ; Wojciechowski, R ; Barathi, VA ; Hysi, PG ; Guggenheim, JA ; Hoehn, R ; Vitart, V ; Khawaja, AP ; Yamashiro, K ; Hosseini, SM ; Lehtimaki, T ; Lu, Y ; Haller, T ; Xie, J ; Delcourt, C ; Pirastu, M ; Wedenoja, J ; Gharahkhani, P ; Venturini, C ; Miyake, M ; Hewitt, AW ; Guo, X ; Mazur, J ; Huffman, JE ; Williams, KM ; Polasek, O ; Campbell, H ; Rudan, I ; Vatavuk, Z ; Wilson, JF ; Joshi, PK ; McMahon, G ; St Pourcain, B ; Evans, DM ; Simpson, CL ; Schwantes-An, T-H ; Igo, RP ; Mirshahi, A ; Cougnard-Gregoire, A ; Bellenguez, C ; Blettner, M ; Raitakari, O ; Kaehoenen, M ; Seppala, I ; Zeller, T ; Meitinger, T ; Ried, JS ; Gieger, C ; Portas, L ; van Leeuwen, EM ; Amin, N ; Uitterlinden, AG ; Rivadeneira, F ; Hofman, A ; Vingerling, JR ; Wang, YX ; Wang, X ; Boh, ET-H ; Ikram, MK ; Sabanayagam, C ; Gupta, P ; Tan, V ; Zhou, L ; Ho, CEH ; Lim, W ; Beuerman, RW ; Siantar, R ; Tai, E-S ; Vithana, E ; Mihailov, E ; Khor, C-C ; Hayward, C ; Luben, RN ; Foster, PJ ; Klein, BEK ; Klein, R ; Wong, H-S ; Mitchell, P ; Metspalu, A ; Aung, T ; Young, TL ; He, M ; Paerssinen, O ; van Duijn, CM ; Wang, JJ ; Williams, C ; Jonas, JB ; Teo, Y-Y ; David, AMM ; Oexle, K ; Yoshimura, N ; Paterson, AD ; Pfeiffer, N ; Wong, T-Y ; Baird, PN ; Stambolian, D ; Bailey-Wilson, JE ; Cheng, C-Y ; Hammond, CJ ; Klaver, CCW ; Saw, S-M ; Rahi, JS ; Korobelnik, J-F ; Kemp, JP ; Timpson, NJ ; Smith, GD ; Craig, JE ; Burdon, KP ; Fogarty, RD ; Iyengar, SK ; Chew, E ; Janmahasatian, S ; Martin, NG ; MacGregor, S ; Xu, L ; Schache, M ; Nangia, V ; Panda-Jonas, S ; Wright, AF ; Fondran, JR ; Lass, JH ; Feng, S ; Zhao, JH ; Khaw, K-T ; Wareham, NJ ; Rantanen, T ; Kaprio, J ; Pang, CP ; Chen, LJ ; Tam, PO ; Jhanji, V ; Young, AL ; Doering, A ; Raffel, LJ ; Cotch, M-F ; Li, X ; Yip, SP ; Yap, MKH ; Biino, G ; Vaccargiu, S ; Fossarello, M ; Fleck, B ; Yazar, S ; Tideman, JWL ; Tedja, M ; Deangelis, MM ; Morrison, M ; Farrer, L ; Zhou, X ; Chen, W ; Mizuki, N ; Meguro, A ; Makela, KM (NATURE PUBLISHING GROUP, 2016-04)
    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.