Publications by authors named "Shu Min Tang"

22 Publications

  • Page 1 of 1

Association of polymorphisms in , and with myopia progression and polygenic risk prediction in children.

Br J Ophthalmol 2021 Apr 2. Epub 2021 Apr 2.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

Aims: To assess the association of single-nucleotide polymorphisms (SNPs) with myopia progression for polygenic risk prediction in children.

Methods: Six SNPs ( rs4373767, rs13382811, rs7744813, rs2073560, rs7839488 and rs524952) were analysed in 1043 school children, who completed 3-year follow-up, using TaqMan genotyping assays. SNP associations with progression in spherical equivalent (SE) were analysed by logistic regression. Polygenic risk scores (PRS) were applied for computing the sum of the risk alleles of multiple SNPs corresponding to myopia progression, weighted by the effect sizes of corresponding SNPs.

Results: rs524952 showed significant association with fast progression (OR=1.32, 95% CI 1.10 to 1.59; p=0.003) and rs7744813 had nominal association (OR=1.32, 95% CI 1.04 to 1.67; p=0.02). In quantitative traits locus analysis, rs524952 and rs7744813 were associated with progression in SE (β=-0.038 D/year, p=0.008 and β=-0.042 D/year, p=0.02) and axial elongation (β=0.016 mm/year, p=0.01 and β=0.017 mm/year, p=0.027). rs13382811 also showed nominal association with faster progression in SE (β=-0.041 D/year, p=0.02). PRS analysis showed that children with the highest PRS defined by rs13382811, rs7744813 and rs524952 had a 2.26-fold of increased risk of fast myopia progression (p=4.61×10). PRS was also significantly associated with SE progression (R=1.6%, p=3.15×10) and axial elongation (R=1.2%, p=2.6×10).

Conclusions: In this study, multi-tiered evidence suggested SNPs in , and as risk factors for myopia progression in children. Additional attention and appropriate interventions should be given for myopic children with high-risk PRS as defined by rs524952, rs7744813 and rs13382811.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318708DOI Listing
April 2021

Age Effect on Treatment Responses to 0.05%, 0.025%, and 0.01% Atropine: Low-Concentration Atropine for Myopia Progression Study.

Ophthalmology 2021 Jan 8. Epub 2021 Jan 8.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong SAR, China; Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China; Hong Kong Eye Hospital, Hong Kong SAR, China; Department of Ophthalmology, Hong Kong Children's Hospital, Hong Kong SAR, China. Electronic address:

Purpose: To investigate the effect of age at treatment and other factors on treatment response to atropine in the Low-Concentration Atropine for Myopia Progression (LAMP) Study.

Design: Secondary analysis from a randomized trial.

Participants: Three hundred fifty children aged 4 to 12 years who originally were assigned to receive 0.05%, 0.025%, or 0.01% atropine or placebo once daily, and who completed 2 years of the LAMP Study, were included. In the second year, the placebo group was switched to the 0.05% atropine group.

Methods: Potential predictive factors for change in spherical equivalent (SE) and axial length (AL) over 2 years were evaluated by generalized estimating equations in each treatment group. Evaluated factors included age at treatment, gender, baseline refraction, parental myopia, time outdoors, diopter hours of near work, and treatment compliance. Estimated mean values and 95% confidence intervals (CIs) of change in SE and AL over 2 years also were generated.

Main Outcome Measures: Factors associated with SE change and AL change over 2 years were the primary outcome measures. Associated factors during the first year were secondary outcome measures.

Results: In 0.05%, 0.025%, and 0.01% atropine groups, younger age was the only factor associated with SE progression (coefficient of 0.14, 0.15, and 0.20, respectively) and AL elongation (coefficient of -0.10, -0.11, and -0.12, respectively) over 2 years; the younger the age, the poorer the response. At each year of age from 4 to 12 years across the treatment groups, higher-concentration atropine showed a better treatment response, following a concentration-dependent effect (P <0.05 for each age group). In addition, the mean SE progression in 6-year-old children receiving 0.05% atropine (-0.90 diopter [D]; 95% CI, -0.99 to -0.82) was similar to that of 8-year-old children receiving 0.025% atropine (-0.89 D; 95% CI, -0.94 to -0.83) and 10-year-old children receiving 0.01% atropine (-0.92 D; 95% CI, -0.99 to -0.85). All concentrations were well tolerated in all age groups.

Conclusions: Younger age is associated with poor treatment response to low-concentration atropine at 0.05%, 0.025%, and 0.01%. Among concentrations studied, younger children required the highest 0.05% concentration to achieve similar reduction in myopic progression as older children receiving lower concentrations.
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http://dx.doi.org/10.1016/j.ophtha.2020.12.036DOI Listing
January 2021

Genetic associations of myopia severities and endophenotypes in children.

Br J Ophthalmol 2020 Aug 14. Epub 2020 Aug 14.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

Objective: To investigate the associations of multiple single-nucleotide polymorphisms (SNPs) with the severities and endophenotypes of myopia in children.

Methods: A total of 3300 children aged 5-10 years were recruited: 137 moderate and high myopia (SE≤-3.0D), 670 mild myopia (-3.0D-0.5D). 13 SNPs in 13 genes/loci were selected for genotyping in all subjects using TaqMan assays. Associations between each SNP with myopia severities and ocular traits (spherical equivalent (SE), axial length (AL) and corneal radius (CR)) were analysed.

Results: When compared with controls, SNPs rs4373767 (OR=1.15, p=0.038), rs7084402 (OR=1.18, p=0.005) and rs524952 (OR=1.14, p=0.025) showed nominal associations with overall myopia. rs4373767 and rs7084402 showed stronger associations with moderate and high myopia (rs4373767: OR=1.42, p=0.018; rs7084402: OR=1.33, p=0.025), while rs524952 had a stronger association with mild myopia (OR=1.14, p=0.025). rs524952 also showed a difference between emmetropia and hyperopia (p=0.018). In quantitative trait locus analysis, rs4373767, rs7744813 and rs524952 were correlated with both myopic SE (β=-0.09, p=0.03; β=-0.12, p=0.007; β=-0.13, p=0.0006, respectively) and AL (β=0.07, p=0.002; β=0.09, p=0.0008; β=0.07, p=0.0003, respectively). rs7839488 was correlated with both AL (β=0.07, p=0.005) and CR (β=0.02, p=0.006). Moreover, rs4373767-T (β=0.006; p=0.018), rs7744813-A (β=0.007; p=0.015) and rs524952-T (β=0.009; p=0.0006) were correlated with AL-CR ratio.

Conclusions And Relevance: and are genetic risk factors for moderate and high myopia, while and confer risk to excessive AL in children.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316728DOI Listing
August 2020

Association of WNT7B and RSPO1 with Axial Length in School Children.

Invest Ophthalmol Vis Sci 2020 08;61(10):11

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Purpose: To evaluate the association between single-nucleotide polymorphisms (SNPs) in the ZC3H11B, RSPO1, C3orf26, GJD2, ZNRF3, and WNT7B genes and myopia endophenotypes in children.

Methods: Seven SNPs identified in previous genome-wide association studies of axial length (AL) were genotyped in 2883 Southern Han Chinese children. Multiple linear regression analyses were conducted to evaluate the genotype association with AL, spherical equivalent (SE), corneal curvature (CC), and central corneal thickness (CCT).

Results: Two SNPs-namely, rs12144790 in RSPO1 (allele T, P = 0.0066, β = 0.062) and rs10453441 in WNT7B (allele A, P = 8.03 × 10-6, β = 0.103)-were significantly associated with AL. The association of rs4373767 in ZC3H11B (allele C, P = 0.030, β = -0.053) could not withstand the correction for multiple testing. WNT7B rs10453441 showed a strong association with CC (P = 1.17 × 10-14, β = 0.053) and with CCT (P = 0.0026, β = 2.65). None of the tested SNPs was significantly associated with SE. The C allele of SNP rs12321 in ZNRF3 was associated with CC (P = 0.0060, β = -0.018).

Conclusions: This study revealed that the RSPO1 SNP rs12144790 was associated with AL, whereas WNT7B rs10453441 was associated with AL, CC, and CCT in children. A novel association between ZNRF3 rs12321 and CC was discovered. Our data suggest that the RSPO1 and WNT7B genes might exert their effects on multiple aspects of eye growth during childhood. Potential differences in the genetic profiles of AL between children and adults should be explored in larger cohorts.
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http://dx.doi.org/10.1167/iovs.61.10.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441295PMC
August 2020

Differential Effects on Ocular Biometrics by 0.05%, 0.025%, and 0.01% Atropine: Low-Concentration Atropine for Myopia Progression Study.

Ophthalmology 2020 12 7;127(12):1603-1611. Epub 2020 Jun 7.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong SAR, China; Hong Kong Eye Hospital, Hong Kong SAR, China. Electronic address:

Purpose: To evaluate changes in ocular biometrics in groups receiving 0.05%, 0.025%, and 0.01% atropine compared with placebo over 1 year based on the Low-Concentration Atropine for Myopia Progression (LAMP) study.

Design: Double-blinded, randomized, placebo-controlled trial.

Participants: Three hundred eighty-three children aged 4 to 12 years who were assigned randomly to receive 0.05%, 0.025%, 0.01% atropine, or placebo once daily in both eyes and completed the first year of the LAMP study.

Methods: Cycloplegic spherical equivalent (SE), axial length (AL), corneal curvature (K), and anterior chamber depth (ACD) were measured by IOLMaster. Corneal astigmatism and lens power were calculated. The ocular biometric parameter changes were compared among groups. Contributions to SE progression from ocular parameters were determined and compared among groups.

Main Outcome Measures: Changes in ocular biometrics and their associations with the changes in SE.

Results: Over 1 year, changes in AL were 0.20 ± 0.25 mm, 0.29 ± 0.20 mm, 0.36 ± 0.29 mm, and 0.41 ± 0.22 mm in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P < 0.001), with a concentration-dependent response. Corneal power remained stable, and its changes were similar across all atropine concentrations: -0.02 ± 0.14 diopter (D), -0.01 ± 0.14 D, -0.01 ± 0.12 D, and 0.01 ± 0.14 D in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P = 0.10). Lens power decreased over time in each concentration, but its changes also were similar across all concentrations: -0.31 ± 0.43 D, -0.38 ± 0.47 D, -0.40 ± 0.43 D, and -0.41 ± 0.43 D in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P = 0.24). Changes in ACD remained similar across all concentrations (P = 0.41). The contributions to SE progression from the ocular biometric changes after adjusting for age and gender in each concentration were similar across all groups (P > 0.05).

Conclusions: Low-concentrations of atropine (0.05%, 0.025%, and 0.01%) have no clinical effect on corneal or lens power. Antimyopic effects of low-concentration atropine act mainly on reducing AL elongation, and therefore could reduce the risk of subsequent myopia complications.
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http://dx.doi.org/10.1016/j.ophtha.2020.06.004DOI Listing
December 2020

Independent Influence of Parental Myopia on Childhood Myopia in a Dose-Related Manner in 2,055 Trios: The Hong Kong Children Eye Study.

Am J Ophthalmol 2020 10 23;218:199-207. Epub 2020 May 23.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong; Hong Kong Eye Hospital, Hong Kong. Electronic address:

Purpose: To determine the effects on childhood myopia of parental myopia, parental education, children's outdoor time, and children's near work.

Design: Population-based cross-sectional study.

Methods: A total of 6,155 subjects in 2,055 family trios (1 child and both parents). Cycloplegic autorefraction was measured for children and noncycloplegic autorefraction for parents. Parental education, children's outdoor time, and near work were collected by questionnaires. Children were categorized into 10 groups based on parental myopia levels. Associations of the above factors with myopia were evaluated by regression analyses. The areas under the receiver operating characteristic curve (AUROCs) for myopia were evaluated.

Results: Mild parental myopia did not increase childhood myopia's risk, but the risk was 11.22-folds when both parents were highly myopic. Higher parental education (Father: OR 1.08, P = .046; Mother: OR 1.11, P = .001) and more reading time of children were risk factors (OR 1.21, P = .044). Reduced odds of myopia were associated with more time spent on outdoor activities (OR 0.78, P = .017). Notably, all these factors became insignificant after adjustment, except for parental myopia. Children with more severe parental myopia spent more time on reading, but less on electronic devices. Parental myopic status alone accounted for 11.82% of myopia variation in children. With age and parental myopia, the AUROC for myopia was 0.731.

Conclusions: Among parental and environmental factors, parental myopia confers, in a dose-related manner, the strongest independent effect on childhood myopia. Therefore children with high risk of myopia can be identified for early prevention, based on parental myopia data.
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http://dx.doi.org/10.1016/j.ajo.2020.05.026DOI Listing
October 2020

Two-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 2 Report.

Ophthalmology 2020 07 21;127(7):910-919. Epub 2019 Dec 21.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Purpose: To evaluate the efficacy and safety of 0.05%, 0.025%, and 0.01% atropine eye drops over 2 years to determine which is the optimal concentration for longer-term myopia control.

Design: Randomized, double-masked trial extended from the Low-Concentration Atropine for Myopia Progression (LAMP) Study.

Participants: Three hundred eighty-three of 438 children (87%) aged 4 to 12 years with myopia of at least -1.0 diopter (D) originally randomized to receive atropine 0.05%, 0.025%, 0.01%, or placebo once daily in both eyes in the LAMP phase 1 study were continued in this extended trial (phase 2).

Methods: Children in the placebo group (phase 1) were switched to receive 0.05% atropine from the beginning of the second-year follow-up, whereas those in the 0.05%, 0.025%, and 0.01% atropine groups continued with the same regimen. Cycloplegic refraction, axial length (AL), accommodation amplitude, photopic and mesopic pupil diameter, and best-corrected visual acuity were measured at 4-month intervals.

Main Outcome Measures: Changes in spherical equivalent (SE) and AL and their differences between groups.

Results: Over the 2-year period, the mean SE progression was 0.55±0.86 D, 0.85±0.73 D, and 1.12±0.85 D in the 0.05%, 0.025%, and 0.01% atropine groups, respectively (P = 0.015, P < 0.001, and P = 0.02, respectively, for pairwise comparisons), with mean AL changes over 2 years of 0.39±0.35 mm, 0.50±0.33 mm, and 0.59±0.38 mm (P = 0.04, P < 0.001, and P = 0.10, respectively). Compared with the first year, the second-year efficacy of 0.05% and 0.025% atropine remained similar (P >0.1), but improved mildly in the 0.01% atropine group (P = 0.04). For the phase 1 placebo group, the myopia progression was reduced significantly after switching to 0.05% atropine (SE change, 0.18 D in second year vs. 0.82 D in first year [P < 0.001]; AL elongated 0.15 mm in second year vs. 0.43 mm in first year [P < 0.001]). Accommodation loss and change in pupil size in all concentrations remained similar to the first-year results and were well tolerated. Visual acuity and vision-related quality of life remained unaffected.

Conclusions: Over 2 years, the efficacy of 0.05% atropine observed was double that observed with 0.01% atropine, and it remained the optimal concentration among the studied atropine concentrations in slowing myopia progression.
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http://dx.doi.org/10.1016/j.ophtha.2019.12.011DOI Listing
July 2020

High prevalence of myopia in children and their parents in Hong Kong Chinese Population: the Hong Kong Children Eye Study.

Acta Ophthalmol 2020 Jan 24. Epub 2020 Jan 24.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong.

Purpose: To determine the myopia prevalence in Hong Kong Chinese children and their parents.

Methods: It was a population-based cross-sectional study. A total of 4257 children aged 6-8 years, and 5880 parents were recruited in the Hong Kong Children Eye Study. Cycloplegic autorefraction was measured for children; and non-cycloplegic autorefraction for parents. Parental educational level, children's outdoor time, and near work were collected by validated questionnaires.

Results: In children aged 6-8 years, 25.0% were myopic, and among them, 12.7% for the 6-year-olds, 24.4% for the 7-year-olds and 36.1% for the 8-year-old. About 0.7% of children aged 8 years were high myopia. In all age groups, boys (their myopia rate: 13.9% at 6 years, 26.7% at 7 years, and 38.3% at 8 years) were more myopic than girls (11.3% at 6 years, 22.0% at 7 years, 33.4% at 8 years). Among parents, 72.2% were myopic (mother, 73.2%; father, 70.7%) and 13.5% high myopia (mother, 12.8%; father, 14.5%). It was observed that prevalence decreased with ages and increased with education level.

Conclusion: There is a strikingly high prevalence of myopia in Hong Kong children aged 6-8, much higher than that of other regions of China. Of note, the prevalence of children was similar to that in 15 years ago. Furthermore, the myopia prevalence of parents is high, and it had already increased in this cohort. Prevention of childhood myopia is important, likewise for visual complications from high myopia in adults.
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http://dx.doi.org/10.1111/aos.14350DOI Listing
January 2020

Effects of etanercept on the apoptosis of ganglion cells and expression of Fas, TNF-α, caspase-8 in the retina of diabetic rats.

Int J Ophthalmol 2019 18;12(7):1083-1088. Epub 2019 Jul 18.

Department of Ophthalmology, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.

Aim: To evaluate the effects of etanercept on the expression of Fas, tumor necrosis factor-alpha (TNF-α) and caspase-8 in the early stage of the apoptotic pathway in diabetic rats, and to explore the therapeutic effect of etanercept on diabetic retinopathy.

Methods: A total of 60 Sprague-Dawley (SD) rats were randomly and evenly divided into 3 groups with 20 rats each, including control group, and diabetic groups with or without treatment. Streptozotocin (STZ)-induced diabetic rats were established for diabetic groups. Blood glucose and body weight were measured weekly. All the rats were sacrificed at the 12wk after treatment. The expressions of Fas, TNF-α and caspase-8 in rat retina were quantitatively detected by PCR and Western blot. The leakage of Evan blue was adopted to measure the retinal vascular leakage quantitatively, and to compare it among different groups. TUNEL method was used to compare the amount of apoptotic bodies quantitatively in rat retina ganglion cells under electron microscope.

Results: The expressions of Fas, TNF-α and caspase-8 in each group were compared PCR and Western blot, in which the diabetic group with treatment was lower than those without treatment (<0.01), but all the diabetic groups were higher than the control group (<0.01). Evans blue leakage in the diabetic treatment group was lower than those without treatment (<0.01), but those in the control group was the lowest compared with the other two groups (<0.01). TUNEL method showed that the apoptotic bodies of retina in the diabetic treatment group was lower than those without treatment (<0.01), while those in the control group was the lowest compared with the other two groups (<0.01).

Conclusion: Etanercept can effectively reduce the expression of Fas, TNF-α and caspase-8, as well as the retinal leakage and retinal cell apoptosis in diabetic rats.
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http://dx.doi.org/10.18240/ijo.2019.07.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629802PMC
July 2019

Association of the and genes with myopia of different severities.

Br J Ophthalmol 2020 10 12;104(10):1472-1476. Epub 2019 Jul 12.

Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, New Territories, Hong Kong

Objective: To investigate the associations of single-nucleotide polymorphisms (SNPs) in the , and genes with severities of myopia in Chinese populations.

Methods: Based on previous myopia genome-wide association studies, five SNPs ( rs4373767, rs13382811, rs2730260, rs7839488 and 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 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 rs13382811 (allele T, OR=1.33, p=0.018) and 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 as a susceptibility gene for high and extreme myopia, and and 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.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314203DOI Listing
October 2020

Low-Concentration Atropine for Myopia Progression (LAMP) Study: A Randomized, Double-Blinded, Placebo-Controlled Trial of 0.05%, 0.025%, and 0.01% Atropine Eye Drops in Myopia Control.

Ophthalmology 2019 01 6;126(1):113-124. Epub 2018 Jul 6.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.

Purpose: Low-concentration atropine is an emerging therapy for myopia progression, but its efficacy and optimal concentration remain uncertain. Our study aimed to evaluate the efficacy and safety of low-concentration atropine eye drops at 0.05%, 0.025%, and 0.01% compared with placebo over a 1-year period.

Design: Randomized, placebo-controlled, double-masked trial.

Participants: A total of 438 children aged 4 to 12 years with myopia of at least -1.0 diopter (D) and astigmatism of -2.5 D or less.

Methods: Participants were randomly assigned in a 1:1:1:1 ratio to receive 0.05%, 0.025%, and 0.01% atropine eye drops, or placebo eye drop, respectively, once nightly to both eyes for 1 year. Cycloplegic refraction, axial length (AL), accommodation amplitude, pupil diameter, and best-corrected visual acuity were measured at baseline, 2 weeks, 4 months, 8 months, and 12 months. Visual Function Questionnaire was administered at the 1-year visit.

Main Outcome Measures: Changes in spherical equivalent (SE) and AL were measured, and their differences among groups were compared using generalized estimating equation.

Results: After 1 year, the mean SE change was -0.27±0.61 D, -0.46±0.45 D, -0.59±0.61 D, and -0.81±0.53 D in the 0.05%, 0.025%, and 0.01% atropine groups, and placebo groups, respectively (P < 0.001), with a respective mean increase in AL of 0.20±0.25 mm, 0.29±0.20 mm, 0.36±0.29 mm, and 0.41±0.22 mm (P < 0.001). The accommodation amplitude was reduced by 1.98±2.82 D, 1.61±2.61 D, 0.26±3.04 D, and 0.32±2.91 D, respectively (P < 0.001). The pupil sizes under photopic and mesopic conditions were increased respectively by 1.03±1.02 mm and 0.58±0.63 mm in the 0.05% atropine group, 0.76±0.90 mm and 0.43±0.61 mm in the 0.025% atropine group, 0.49±0.80 mm and 0.23±0.46 mm in the 0.01% atropine group, and 0.13±1.07 mm and 0.02±0.55 mm in the placebo group (P < 0.001). Visual acuity and vision-related quality of life were not affected in each group.

Conclusions: The 0.05%, 0.025%, and 0.01% atropine eye drops reduced myopia progression along a concentration-dependent response. All concentrations were well tolerated without an adverse effect on vision-related quality of life. Of the 3 concentrations used, 0.05% atropine was most effective in controlling SE progression and AL elongation over a period of 1 year.
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http://dx.doi.org/10.1016/j.ophtha.2018.05.029DOI Listing
January 2019

Vitamin D and its pathway genes in myopia: systematic review and meta-analysis.

Br J Ophthalmol 2019 01 17;103(1):8-17. Epub 2018 Jul 17.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

Objective: To conduct a systematic review and meta-analysis of the association of blood vitamin D (25-hydroxyvitamin D, 25(OH)D) concentration and vitamin D pathway genes with myopia.

Methods: We searched the MEDLINE and EMBASE databases for studies published up to 29 January 2018. Cross-sectional or cohort studies which evaluated the blood 25(OH)D concentration, blood 25(OH)D3 concentration or vitamin D pathway genes, in relation to risk of myopia or refractive errors were included. Standard mean difference (SMD) of blood 25(OH)D concentrations between the myopia and non-myopia groups was calculated. The associations of blood 25(OH)D concentrations and polymorphisms in vitamin D pathway genes with myopia using summary ORs were evaluated.

Results: We summarised seven studies involving 25 008 individuals in the meta-analysis. The myopia group had lower 25(OH)D concentration than the non-myopia group (SMD=-0.27 nmol/L, p=0.001). In the full analysis, the risk of myopia was inversely associated with blood 25(OH)D concentration after adjusting for sunlight exposure or time spent outdoors (adjusted odds ratio (AOR)=0.92 per 10 nmol/L, p<0.0001). However, the association was not statistically significant for the <18 years subgroup (AOR=0.91 per 10 nmol/L, p=0.13) and was significant only for 25(OH)D3 (likely to be mainly sunlight derived), but not total 25(OH)D (AOR=0.93 per 10 nmol/L, p=0.00007; AOR=0.91 per 10 nmol/L, p=0.15). We analysed four single nucleotide polymorphisms in the VDR gene from two studies; there was no significant association with myopia.

Conclusions: Lower 25(OH)D is associated with increased risk of myopia; the lack of a genetic association suggests that 25(OH)D level may be acting as a proxy for time outdoors.
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http://dx.doi.org/10.1136/bjophthalmol-2018-312159DOI Listing
January 2019

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

Br J Ophthalmol 2018 12 12;102(12):1736-1741. Epub 2018 Jul 12.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

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 locus showed a significant association with keratoconus (OR=2.22; 95% CI 1.42 to 3.45, p=4.30×10), 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 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.
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http://dx.doi.org/10.1136/bjophthalmol-2018-312218DOI Listing
December 2018

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

Br J Ophthalmol 2018 10 9;102(10):1336-1341. Epub 2018 Apr 9.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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 (OR=0.82, 95% CI 0.68 to 0.98; OR=0.67, 95% CI 0.47 to 0.94) and progression to severe ROP (OR=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.
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http://dx.doi.org/10.1136/bjophthalmol-2017-311576DOI Listing
October 2018

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

Br J Ophthalmol 2018 04 7;102(4):570-574. Epub 2018 Feb 7.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Aims: To investigate the association of the () 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 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 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; I=0%). In contrast, there was no significant association between the SNPs and high, moderate or mild myopia. No linear correlation was found between the SNPs and axial length.

Conclusion: This study provides additional evidence suggesting that the SNP rs644242 is associated with extreme myopia but not lower grade myopia. Thus, may be implicated in the development or progression into severe myopia. Further longitudinal studies are warranted.
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http://dx.doi.org/10.1136/bjophthalmol-2017-311327DOI Listing
April 2018

Refractive Errors and Concomitant Strabismus: A Systematic Review and Meta-analysis.

Sci Rep 2016 10 12;6:35177. Epub 2016 Oct 12.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.

This systematic review and meta-analysis is to evaluate the risk of development of concomitant strabismus due to refractive errors. Eligible studies published from 1946 to April 1, 2016 were identified from MEDLINE and EMBASE that evaluated any kinds of refractive errors (myopia, hyperopia, astigmatism and anisometropia) as an independent factor for concomitant exotropia and concomitant esotropia. Totally 5065 published records were retrieved for screening, 157 of them eligible for detailed evaluation. Finally 7 population-based studies involving 23,541 study subjects met our criteria for meta-analysis. The combined OR showed that myopia was a risk factor for exotropia (OR: 5.23, P = 0.0001). We found hyperopia had a dose-related effect for esotropia (OR for a spherical equivalent [SE] of 2-3 diopters [D]: 10.16, P = 0.01; OR for an SE of 3-4D: 17.83, P < 0.0001; OR for an SE of 4-5D: 41.01, P < 0.0001; OR for an SE of ≥5D: 162.68, P < 0.0001). Sensitivity analysis indicated our results were robust. Results of this study confirmed myopia as a risk for concomitant exotropia and identified a dose-related effect for hyperopia as a risk of concomitant esotropia.
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http://dx.doi.org/10.1038/srep35177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059633PMC
October 2016

Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis.

Sci Rep 2016 08 5;6:30732. Epub 2016 Aug 5.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.

The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed.
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http://dx.doi.org/10.1038/srep30732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974497PMC
August 2016

Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-analysis.

Ophthalmology 2016 06 4;123(6):1211-21. Epub 2016 Feb 4.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China. Electronic address:

Topic: Systematic review and meta-analysis of the genetic associations of primary angle-closure disease (PACD).

Clinical Relevance: To confirm the genetic biomarkers for PACD, including primary angle-closure glaucoma (PACG) and related phenotypes.

Methods: We searched in the MEDLINE and EMBASE databases for genetic studies of PACG or other PACD published from the start dates of the databases to May 11, 2015. We estimated the summary odds ratios (ORs) and 95% confidence intervals (CIs) for each polymorphism in PACG, primary angle-closure suspect (PACS), and primary angle-closure (PAC) using fixed- or random-effect models. We also performed sensitivity analysis to test the robustness of the results.

Results: Our literature search yielded 6463 reports. Among them, we identified 24 studies that fulfilled the eligibility criteria for meta-analysis, involving 28 polymorphisms in 11 genes/loci. We affirmed the association of PACG and combined PACS/PAC/PACG with 10 polymorphisms in 8 genes/loci, including COL11A1 (rs3753841-G, OR, 1.22; P = 0.00046), HGF (rs17427817-C, OR, 2.02; P = 6.9E-07; rs5745718-A, OR, 2.11; P = 9.9E-07), HSP70 (rs1043618, GG+GC, OR, 0.52; P = 0.0010), MFRP (rs2510143-C, OR, 0.66; P = 0.012; rs3814762-G, OR, 1.40; P = 0.0090), MMP9 (rs3918249-C, OR, 1.35; P = 0.034), NOS3 (rs7830-A, OR, 0.80; P = 0.036), PLEKHA7 (rs11024102-G, OR, 1.24; P = 8.3E-05), and PCMTD1-ST18 (rs1015213-A, OR, 1.59; P = 0.00013). Sensitivity analysis indicated that the results were robust.

Conclusions: In this study, we confirmed multiple polymorphisms in 8 genes/loci as genetic biomarkers for PACD, among which 3 were identified in a genome-wide association study (COL11A1, PLEKHA7, and PCMTD1-ST18), and 5 were identified in candidate gene studies (HGF, HSP70, MFRP, MMP9, and NOS3).
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http://dx.doi.org/10.1016/j.ophtha.2015.12.027DOI Listing
June 2016

Association of PEDF polymorphisms with age-related macular degeneration and polypoidal choroidal vasculopathy: a systematic review and meta-analysis.

Sci Rep 2015 Mar 30;5:9497. Epub 2015 Mar 30.

1] Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China [2] Department of Ophthalmology and Visual Sciences, Prince of Wales hospital, Hong Kong, China.

This study assesses the association of the pigment epithelium-derived factor (PEDF) gene with age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Publications in MEDLINE and EMBASE up to 21/08/2014 were searched for case-control association studies of PEDF with AMD and/or PCV. Reported studies giving adequate genotype and/or allele information were included. Pooled odds ratios (OR) and 95% confidence intervals (CI) of each polymorphism were estimated. Our literature search yielded 297 records. After excluding duplicates and reports with incomplete information, 8 studies were eligible for meta-analysis, involving 2284 AMD patients versus 3416 controls, and 317 PCV patients versus 371 controls. Four PEDF polymorphisms were meta-analyzed: rs1136287, rs12150053, rs12948385 and rs9913583, but none was significantly associated with AMD or PCV. The most-investigated polymorphism, rs1136287, had a pooled-OR of 1.02 (95% CI: 0.94-1.11, P = 0.64) for AMD. In subgroup analysis by ethnicity, no significant association was identified. Polymorphisms present in single report showed no association. Therefore, existing data in literature does not support the role of PEDF in the genetic susceptibility of AMD and PCV, although replication in specific populations is warranted. Since the pooled-sample size for PCV was small, there is a need of PEDF genotyping in larger samples of PCV.
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http://dx.doi.org/10.1038/srep09497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377572PMC
March 2015

Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis.

Sci Rep 2015 Mar 13;5:9091. Epub 2015 Mar 13.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.

As the role of hyperglycemia in the development of retinopathy of prematurity (ROP) has not been well established, a meta-analysis of the association between hyperglycemia and ROP was conducted. Studies were identified through literature search in MEDLINE and EMBASE up to June 20, 2014 with keywords related to "hyperglycaemia" and "ROP". Nine eligible studies involving 1939 neonates with 509 cases of ROP were included. Unadjusted analyses showed that hyperglycemia was significantly associated with ROP (Odds ratio [OR] = 4.16, P<0.0001). Comparing with the control, subjects in the ROP group had a significantly longer duration of hyperglycemia (Standardized mean difference [SMD] = 1.21, P< 0.0001), and higher mean glucose level. (SMD = 0.88, P = 0.0004) However, when combining the adjusted OR (after adjustment for birth weight, gestational age and other factors) provided from individual studies, only borderline significant association were observed on duration of hyperglycemia with ROP (adjusted OR 1.08, P = 0.03); and no significant association on mean glucose level with ROP (adjusted OR = 1.08, P = 0.15). Hence, hyperglycemia cannot be definitely considered as a risk factor for ROP, and further studies should adjust for potential confounding factors to clarify this association.
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http://dx.doi.org/10.1038/srep09091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357868PMC
March 2015

PAX6 gene associated with high myopia: a meta-analysis.

Optom Vis Sci 2014 Apr;91(4):419-29

*MBBS †MMed ‡MMedSc §MPhil ∥DPhil **PhD Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China (SMT, SSR, ALY, POST, CPP, LJC); and Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China (ALY, CPP, LJC).

Purpose: The PAX6 gene is among the most studied genes in high myopia, but reported findings of association studies on PAX6 and high myopia are inconsistent. We conducted a systematic review and meta-analysis to evaluate the association of PAX6 polymorphisms and high myopia.

Methods: All case-control association studies on PAX6 and high myopia reported in EMBASE and MEDLINE were retrieved. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for single-nucleotide polymorphisms (SNPs) that have been involved in at least two studies. Heterogeneity and publication bias analyses were also conducted.

Results: There were totally 63 publications on PAX6 and myopia. Among them, six articles met all the inclusion criteria, involving 3626 patients and 3262 controls of Asian ancestry. Five PAX6 SNPs, rs3026354, rs667773, rs2071754, rs644242, and rs3026393, were meta-analyzed in high myopia and two, rs667773 and rs644242, in extreme myopia. Single-nucleotide polymorphism rs644242 was associated with high myopia in the dominant model (OR = 0.87; 95% CI, 0.76 to 0.99; p = 0.035) and heterozygous model (OR = 0.85; 95% CI, 0.74 to 0.97; p = 0.019) and with extreme myopia in the dominant model (OR = 0.79; 95% CI, 0.65 to 0.95; p = 0.015), allelic model (OR = 0.81; 95% CI, 0.68 to 0.96; p = 0.014), and heterozygous model (OR = 0.80; 95% CI, 0.65 to 0.97; p = 0.024). However, the associations cannot withstand Bonferroni correction (p > 0.005). The other four SNPs did not show significant association with high myopia.

Conclusions: Meta-analysis of existing data revealed a suggestive association of PAX6 rs644242 with extreme and high myopia, which awaits validation in further studies. Nevertheless, PAX6 may only confer a small effect to myopia development.
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http://dx.doi.org/10.1097/OPX.0000000000000224DOI Listing
April 2014