Shu Min Tang

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

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.

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

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.

PAX6 Gene Associated with High Myopia: A Meta-analysis

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.

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

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.

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

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.

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

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

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

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.

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

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

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

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