The biometric parameters of aniso-astigmatism and its risk factor in Chinese preschool children: the Nanjing Eye Study

doi:10.21203/rs.3.rs-33135/v2

Backgrounds: Aniso-astigmatism may hinder normal visual development in preschool children. Knowing its prevalence, biometric parameters and risk factors is fundamental to children eye care. The purpose of this study was to determine the biometric components of aniso-astigmatism and associated maternal risk factors in Chinese preschool children.

Methods: In the population-based, prospective cohort Nanjing Eye Study, children were measured for noncycloplegic refractive error using an autorefractor and for biometric parameters using an optical low-coherent reflectometry. The difference of total astigmatism (TA) between both eyes was calculated using cylinder power (non-vectorial aniso-TA was defined as ≥1.00 Dioptre Cylinder [DC] between both eyes) and by vector analysis (vectorial aniso-TA was defined as a difference of ≥0.5 in J₀ or J₄₅ between both eyes which is equivalent to 1.00 DC). The prevalence of aniso-TA was presented. Interocular biometric parameters were compared between with vs. without aniso-astigmatism group. In addition, risk factors were determined using multivariate logistic regression model.

Results: Of 1131 children (66.90±3.38 months, 53.31% male), the prevalence of non-vectorial aniso-TA was 1.95% (95% Confidence Interval (CI)=1.14%-2.75%), while the prevalence of vectorial aniso-TA was twice as common as non-vectorial aniso-TA, neither varying with sex or age. With aniso-TA eyes were more asymmetric in axial length and corneal curvature radius than without aniso-TA eyes. In multivariate logistic regression model, 5-min Apgar score less than 7 was significantly associated with higher risk of aniso-TA (vectorial aniso-TA: Odds Ratio (OR)=6.42, 95%CI=2.63-15.69, P<0.001; non-vectorial aniso-TA: OR=4.99, 95%CI=1.41-17.68, P=0.01）. Being twin or triple was significantly associated with higher risk of vectorial aniso-CA (OR=2.43, 95%CI=1.05-5.60, P=0.04). Pre-term delivery (OR=2.60, 95%CI=1.09-6.15, P=0.03) and post-term delivery (OR=3.61, 95%CI=1.31-9.96, P=0.01) were significantly associated with higher risk of vectorial aniso-CA.

Conclusions: Both corneal curvature radius and axial length asymmetry were correlated with aniso-TA. Children with 5-min Apgar score<7 were more likely to have aniso-TA, while twin or triple, pre-term or post-term delivery were more likely to have vectorial aniso-CA.

Ophthalmology

aniso-astigmatism

Apgar score

preschool children

population-based study

Astigmatism occurs when incident light rays do not converge at a single focal point [1]. It can lead to substantial visual dysfunction due to visual torsion, metamorphosis, asthenopia and reduced accommodation response [2,3]. Some studies suggest astigmatism may also be associated with myopia progression [4,5]. Anisometropia is an interocular asymmetry in refraction that can be associated with strabismus, amblyopia, aniseikonia, and reduced stereopsis [6-9]. Vision In Preschoolers Study Group (VIP) has demonstrated that non-vectorial aniso-astigmatism was more related with unilateral amblyopia than isometropia [10]. Thus aniso-astigmatism may bring damage to visual development in preschool children.

Previous studies have been focusing on risk factors for astigmatism [11-13]. Maternal smoking during pregnancy, caesarean section, darker iris colour, Hispanic, African American, and Asian race might be risks factor of astigmatism. Few studies explore the risk factors for aniso-astigmatism except the Sydney Myopia Study and the Shandong Children Eye Study [14,15]. It remains unclear whether maternal factors are associated with aniso-astigmatism in Chinese preschool children. Furthermore, vectorial feature of astigmatism was rarely considered while analyzing the risk factors for aniso-astigmatism [10,16,17]. However, initial oblique astigmatism is more likely to be associated with amblyopia than orthogonal astigmatism, even with a small degree [18,19]. Thus, cylinder axis should not be neglected.

The aim of this study was to describe the characteristics of aniso-TA using cylinder power and by vector analysis, to compare the interocular biometric parameters between with aniso-astigmatism group and without aniso-astigmatism group and to determine risk factors for aniso-astigmatism including vectorial aniso-total astigmatism (vectorial aniso-TA), non-vectorial aniso-TA, vectorial aniso-corneal astigmatism (vectorial aniso-CA) and vectorial aniso-residual astigmatism (vectorial aniso-RA) in a population-based Nanjing Eye Study (NES).

Study design

The NES is an ongoing population-based open cohort study, designed to prospectively observe the onset and progression of childhood ocular diseases in eastern China. All study procedures were approved by the institutional review board in The First Affiliated Hospital with Nanjing Medical University and were conducted according to the tenets of the Declaration of Helsinki. Written consent was obtained from the parents or guardians of all children. This study comprised 61- to 72-month-old children enrolled in kindergarten in the Yuhuatai District of Nanjing City in East China. Data from eye examinations and questionnaire presented in this paper were collected in 2017.

Ocular examinations and questionnaires

All children underwent comprehensive eye examinations, including noncycloplegic autorefraction of both eyes of each participant (Cannon RF10; Canon, Tokyo, Japan) and measurement of biometric parameters by the optic low-coherent reflectometer (LenStar LS-900; Haag-Streit AG, Koeniz, Switzerland). Biometric parameters refer to central corneal thickness (CCT), corneal radius (CR), anterior chamber depth (ACD), lens thickness (LT) and axial length (AL). A comprehensive questionnaire was distributed to legal guardians of each child. The examining procedures and content of the questionnaire have been described in detail previously [20,21]. The Apgar score is the most widely recognized index used to report the health status of a newborn [22], which is usually obtained by evaluating the following 5 items: appearance (color), pulse (heart rate), grimace response (reflexes), activity (muscle tone) and respiration (breathing rate and effort) at one, five and ten minutes after delivery, with the range being 0–10 [23]. In particular, the 5-minute Apgar score is often regarded as representing and was categorized as normal (≥7) and abnormal (<7) in this study.

Definition

Definition and calculations of TA, CA and RA were described in previous publications. To decompose vectorial aniso-astigmatism, the vector method modified by Thibos was used for the following calculations [24]:

where SE is the spherical equivalent, S is sphere, C is the cylinder in minus format, A is the cylinder axis, J₀ and J₄₅ are the horizontal or vertical and oblique vectors of the cylinder, respectively.

The difference of TA between both eyes was calculated using cylinder power (non-vectorial aniso-TA was defined as ≥1.00 Dioptre Cylinder [DC] between both eyes) and by vector analysis (vectorial aniso-TA was defined as a difference of ≥0.5 in J₀ or J₄₅ between both eyes which is equivalent to 1.00 DC) [16]. Similar definition applied to aniso-CA and aniso-RA. Aniso-J_0t and aniso-J_45t are J₀ and J₄₅ of vectorial aniso-TA. Aniso-J_0c and aniso-J_45c are J₀ and J₄₅ of vectorial aniso-CA. Aniso-J_0r and aniso-J_45r are J₀ and J₄₅ of vectorial aniso-CA. Group A included children with vectorial aniso-TA, and the others belonged to group B. Group C included children with vectorial aniso-CA, and the others belonged to group D. Group E included children with vectorial aniso-RA, and the others belonged to group F. Group G included children with non-vectorial aniso-TA, and the others belonged to group H.

Statistical analysis

The Statistical Package for the Social Sciences (SPSS V.13.0; IBM, Chicago, IL, USA) was used for all statistical analyses. Characteristics of children included in the analysis were compared to those excluded due to missing data in questionnaire using two-sample t-test for comparisons of means and chi-square test for comparison of proportions. Prevalence variations by sex and age were assessed using chi-square test. Spearman correlation coefficient (ρ) was used to evaluate the relationships between the components of aniso-astigmatism. Comparisons of interocular difference in biometric parameters were performed between children with vs. without vectorial aniso-astigmatism (Mann-Whitney U test). Comparisons of distribution of each candidate risk factor were performed between groups using two-sample t-tests for continuous variables and chi-square tests for categorical variables. All factors with P <0.05 were included into multivariate logistic regression models. The forward variable selection was performed to determine statistically significant risk factors for each type of aniso-astigmatism. Odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated from multivariate logistic regression models. All statistical tests were two-sided and P less than 0.05 was considered statistically significant.

Prevalence of aniso-TA

Among 2300 eligible preschoolers, 1920 (participation rate 83.48%) children were examined,404 children were uncooperative and no refraction measurements or biometric parameters from right or left eyes were obtained after several attempts. Guardians of 385 children did not complete the questionnaires, leaving 1131 children (58.90% of eligible participants) included in this study.

There were no significant differences in characteristics of children (including age, gender, prevalence rate of aniso-TA) between children included in the analysis and those excluded from analysis due to missing data in questionnaire.

The mean (± SD) age was 66.90 ± 3.38 months and 53.31% of participants were boys. Han nationality children (1117, 98.76%) constituted the majority of the population. The prevalence of TA ≥1.00 DC was 12.56% (95% CI=10.62% to 14.49%) in right eye and 12.73% (95% CI=10.79% to 14.68%) in left eye. Table 1 shows the prevalence of aniso-TA stratified by sex and age. The prevalence of non-vectorial aniso-TA was 1.95%, while the prevalence of vectorial aniso-TA was 3.89%. Neither non-vectorial aniso-TA nor vectorial aniso-TA varied with sex or age (all P>0.05). Forty-four children had vectorial aniso-TA. Of them, twenty-six children had aniso-J_0t ≥ 0.5, twenty-four children had aniso-J_45t ≥ 0.5, and six children had both. In addition, the prevalence of non-vectorial aniso-TA ≥2.00 DC was 0.18% and none had non-vectorial aniso-TA ≥3.00 DC.

Table 1. Prevalence of aniso- total astigmatism stratified by sex and age.
Characteristics	N (%)	Vectorial aniso-TA^* N (%, 95% CI)	P	Non-vectorial aniso-TA^# N (%, 95% CI)	P
Sex			0.77		0.74
Boys	603 (53.3%)	22 (3.65%, 2.15 - 5.15)		13 (2.16%, 0.99 - 3.32)
Girls	528 (46.7%)	22 (4.17%, 2.46 - 5.88)		9 (1.70%, 0.60 - 2.81)
Age (month)			0.82		0.71
61 - 66	546 (48.3%)	20 (3.66%, 2.08 - 5.24)		12 (2.20%, 0.95 - 3.43)
67 - 72	685 (51.7%)	24 (3.50%, 2.12 - 4.88)		10 (1.71%, 0.66 - 2.76)
Total	1131 (100%)	44 (3.89%, 2.76 - 5.02)		22 (1.95%, 1.14 - 2.75)

^* Vectorial aniso-TA was defined as a difference of ≥ 0.5 in J₀ or J₄₅ between the two eyes.
^# Non-vectoral aniso-TA was defined as the difference of ≥ 1.0 diopter cylinder in absolute cylinder between the two eyes regardless of axis.
N, number; CI, confidence interval.

The components of vectorial aniso-astigmatism

There was a statistically significant association between aniso-J₀_tand aniso-J₀_c(ρ=0.15, P<0.001), and also between aniso-J₄₅_tand aniso-J₄₅_c (ρ=0.11, P<0.001). There was a statistically significant association between aniso-J₀_tand aniso-J₀_r (ρ=0.22, P<0.001), and also between aniso-J₄₅_tand aniso- J₄₅_r (ρ=0.11, P<0.001).

Comparison between groups towards interocular biometric parameters

Table 2 shows comparisons of interocular differences in ocular biometric parameters between groups with vs. without aniso-astigmatism. Absolute value of interocular differences in AL, mean CR, AL/CR, CCT, ACD, LT were calculated. The absolute value of interocular differences in AL, CR and AL/CR, ACD were significantly different between group A and group B (P=0.001, P<0.001, P=0.001, and P=0.01 respectively). The absolute value of interocular differences in CR and AL/CR were significantly different between group C and group D (both P<0.001), which were also significantly different between group E and group F (both P<0.001). The absolute value of interocular differences in AL, CR and AL/CR were significantly different between group G and group H (P<0.001, P=0.001, and P<0.001 respectively).

Table 2. Comparisons of interocular differences in ocular biometric parameters between groups with vs. without aniso-astigmatism.

AL (mm)

MCR (mm)

AL/CR

CCT (mm)

ACD (mm)

LT (mm)

Mean ± SD

P

Mean ± SD

P

Mean ± SD

P

Mean ± SD

P

Mean ± SD

P

Mean ± SD

P

Vectorial aniso-TA group (N)

0.001

<0.001

0.001

0.19

0.01

0.09

Group A (44)

0.19 ± 0.24

0.12 ± 0.09

0.05 ± 0.05

9.50 ± 17.17

0.09 ± 0.09

0.10 ± 0.10

Group B (1087)

0.11 ± 0.14

0.07 ± 0.07

0.03 ± 0.03

7.59 ± 14.27

0.06 ± 0.08

0.07 ± 0.09

Vectorial aniso-CA group (N)

0.89

<0.001

0.30

0.79

0.78

Group C (278)

0.11 ± 0.14

0.11 ± 0.09

0.04 ± 0.04

7.54 ± 14.74

0.06 ± 0.07

0.08 ± 0.09

Group D (853)

0.11 ± 0.14

0.06 ± 0.06

0.03 ± 0.03

7.70 ± 14.29

0.06 ± 0.08

0.07 ± 0.10

Vectorial aniso-RA group (N)

0.48

<0.001

0.36

0.42

0.87

Group E (273)

0.12 ± 0.15

0.11 ± 0.09

0.04 ± 0.04

7.95 ± 15.18

0.06 ± 0.07

0.07 ± 0.08

Group F (858)

0.11 ± 0.14

0.06 ± 0.06

0.03 ± 0.03

7.57 ± 14.14

0.06 ± 0.08

0.08 ± 0.10

Non-vectorial aniso-TA group (N)

<0.001

0.001

<0.001

0.97

0.81

0.68

Group G (22)

0.28 ± 0.30

0.13 ± 0.09

0.06 ± 0.06

8.95 ± 17.20

0.06 ± 0.06

0.07 ± 0.09

Group H(1109)

0.10 ± 0.14

0.07 ± 0.07

0.03 ± 0.03

7.63 ± 14.34

0.06 ± 0.08

0.07 ± 0.09

All numbers showed in this table were calculated as absolute values of interocular deviation with a form of mean ± standard deviation.
AL, axial length; MCR,mean corneal curvature radius; CCT, central corneal thickness; ACD, anterior chamber depth; LT, lens thickness; SD, standard deviation; N, number.

Risk factors for aniso-astigmatism

Comparisons for each risk factor between group A and group B were shown in sTable 1. Children in group A were more likely to have abnormal 5 min-Apgar score (P<0.001) and parental astigmatism (P=0.03) than those in group B. In the multivariate analysis, two variables remained significantly associated with vectorial aniso-TA: 5 min-Apgar score and parental astigmatism. Children with 5min-Apgar score lower than 7 were 6.42 times as likely to have vectorial aniso-TA as children with normal Apgar score (95%CI=2.63-15.69, P<0.001). Children with parental astigmatism were 2.03 times as likely to have vectorial aniso-TA as children without parental astigmatism (95%CI=1.09-3.79, P=0.03).

Comparisons for each risk factor between group C and group D were shown in sTable 2. Children in group C were more likely to have older father at child birth (P=0.047), pre-term delivery (P=0.01), more outdoor activity (P=0.03) and being twin or triple (P=0.03) than those in group D. In the multivariate logistic regression analysis, two variables remained significantly associated with vectorial aniso-CA: being twin or triple and term delivery (Table 3). Children being twin or triple were 2.43 times as likely to have vectorial aniso-CA as those being monotocous (95%CI=1.05-5.60, P=0.04). Pre-term delivery (OR=2.60, 95%CI=1.09-6.15, P=0.03) and post-term delivery (OR=3.61, 95%CI=1.31-9.96, P=0.01) were more likely to have vectorial aniso-CA than full-term delivery.

Table 3. Independent Risk Factors for vectorial aniso-CA from Multivariate Logistic Regression

	Multivariate analysis
Risk factors	Adjusted OR	95% CI	P
Twin or triple (Yes vs No)	2.43	1.05-5.60	0.04
Term delivery
Full-term	Reference
Pre-term	2.60	1.09-6.15	0.03
Post-term	3.61	1.31-9.96	0.01

OR, odds ratio; CI, confidence interval.

Comparisons for each risk factor between group E and group F were shown in sTable 3 and no statistically significant difference was found. Likewise, no statistically significant variable was found to be associated with vectorial aniso-RA in the multivariate logistic regression analysis. Comparisons for each risk factor between group G and group H were shown in sTable 4. Children in group G were more likely to have younger paternal age at child birth, (P=0.049) abnormal 5 min-Apgar score (P=0.03) than those in group H. In the multivariate logistic regression analysis, only 5 min-Apgar score remained significantly associated with non-vectorial aniso-TA. Children with 5min-Apgar score lower than 7 were 4.99 times as likely to have non-vectorial aniso-TA as children with normal Apgar score (95%CI=1.41-17.68, P=0.01).

Table 4. Studies of aniso-astigmatism among young children.
Author	Year	Location	Age	Sample size	Definition	Prevalence
The Sydney Myopia Study^[14]	2006	Sydney, Australia	6 years	1765	≥ 1.0DC	1.60%
Dobson et al.^[26]	2008	Tohono O’odham, American	4 - 13 years	1041	≥ 1.0DC	15%
The Northern Ireland Childhood Errors of Refraction Study^[27]	2013	Northern Ireland, England	6 - 7 years	661	≥ 1.0DC	7.70%
	2013	Northern Ireland, England	12 - 13 years	389	≥ 1.0DC	5.60%
The Sydney Paediatric Eye Disease Study^[29]	2013	Sydney, Australia	6 - 72 months	2090	≥ 1.0DC	Overall 3%
						European-Caucasian 1.9%
						East-Asian 5.2%
						South-Asian 3.6%
						Middle-Eastern 3.3%
The Multi-Ethnic Pediatric Eye Disease Study^[17]	2010	California, America	6 - 72 months	Hispanic American, 3030	≥ 1.0DC	5.60%
				Hispanic American, 3030	≥ 0.50 in J₀/ J₄₅	10.40%
				African American, 2994	≥ 1.0DC	4.50%
				African American, 2994	≥ 0.50 in J₄₅/ J₄₅	11.90%
The Shandong Children Eye Study^[15]	2015	Shandong, China	4 - 18 years	6025	≥ 1.0DC	3.70%
Yamashita et al.^[28]	1997	Rural area of southwestern Japan	6 years	350	≥ 1.0DC	2.6%
			7 years			2.3%
			8 years			2.0%
			9 years			3.4%
			10 years			3.7%
			11 years			4.3%

This study describes, for the first time to our knowledge, the prevalence of aniso-TA using both non-vectorial aniso-TA and vectorial aniso-TA in Chinese preschool children. The prevalence of vectorial aniso-TA was twice as common as non-vectorial aniso-TA, which did not vary with sex and age. The prevalence of aniso-TA was much lower than that of TA.

Prevalence of aniso-TA from previous studies on similar age population was shown in Table 4. These studies reported different prevalence rate, which might be due to different ethnicity, age, and whether vectorial analysis was used. We compared the prevalence of non-vectorial aniso-TA with previous studies defined as ≥1.0DC. The prevalence of non-vectorial aniso-TA in the present study was lower than that found in the Tohono O’odham Native American children, in the Northern Ireland Childhood Errors of Refraction (NICER) study and in the rural area of southwestern Japan [25-27]. However, it was higher than that in the Sydney Myopia Study, and similar to that in the Sydney Paediatric Eye Disease Study [14,28]. Among these studies, the prevalence of non-vectorial aniso-TA found in the Tohono O’odham Native American children was the highest, in accordance with the population’s high TA prevalence [25,29]. When compared with the Shandong Children Eye Study, which was also carried out among Chinese children, the prevalence in this study was lower [15]. Our previous study also showed the TA prevalence was lower than that from The Shandong Children Eye Study [20,30]. Few studies revealed the prevalence of vectorial aniso-TA. The prevalence of vectorial aniso-TA in the present study was lower than that found in the Multi-Ethnic Pediatric Eye Disease Study (MEPEDS) [16]. In their study, vectorial aniso-TA was twice as common as non-vectorial aniso-TA，similar with our results. Children in MEPEDS were African American and Hispanic, who also showed higher TA prevalence. The difference between non-vectorial aniso-TA prevalence and vectorial aniso-TA prevalence was reasonable as vectorial aniso-TA took astigmatic axis into consideration.

Whatever definition was used, aniso-TA was associated not only with increased interocular differences in CR, but also with AL, possibly due to the relationship among aniso-TA and anisometropia. A similar correlation was reported by Huynh et al [14], O'Donoghue et al [26], Singh et al [31], and Hameshi et al [32]. These studies showed non-vectorial aniso-CA was associated with non-vectorial aniso-TA. This finding is in agreement with our knowledge that most aniso-TA of the eyes is due to corneal issues. Interestingly, we found interocular differences in ACD were associated with vectorial aniso-TA. The finding is in accordance with Hameshi et al, but contradicts with the results of the NICER Study [26,32]. Vectorial aniso-CA and vectorial aniso-RA can only be explained by interocular differences in CR.

Genetic factor plays an important role in the development of astigmatism. Accordingly, this study revealed that parental astigmatism was a risk factor for vectorial aniso-TA. Previous genetic studies on astigmatism provided contradicting results on the genetic contribution to astigmatism. Wixson concluded that both parents seemed to play roles in determining the corneal power characteristics of the child. Early twin studies showed that the correlations between monozygotic twins and those between dizygotic twins for astigmatism were not significantly different, which indicated low genetic contribution to astigmatism. However, some other twin studies drew different conclusions, with the estimated heritability ranging from 30% to 60%. A meta-analysis of five Asian cohorts identifies PDGFRA as a susceptibility locus for CA [21]. Similarly, previous studies have obtained contradicting results on genetic contribution to aniso-astigmatism. Recently, a population-based twin study showed that the correlation between monozygotic twins for aniso-CA were significantly different from dizygotic twins [33]. A study in Korea found that intraclass correlation coefficients for spherical equivalent and ocular biometrics were significantly higher in monozygotic twins compared with singleton, with greater consistency and conformity [34]. However, another study did not find any significantly difference between children being twin or siblings in refractive error, corneal curvature, ACD and CCT [35].

Interestingly, our study found that being twin or triple increased the risk for vectorial aniso-CA. Further investigations may be needed to clarify the ocular developmental difference between twin or triple and singleton. Our study demonstrated that children with a 5-min Apgar score<7 had a higher likelihood of developing aniso-TA at 5- to 6- years compared to those with an Apgar score of 7–10 (within the normal range), while pre-term or post-term delivery were risk factors for vectorial aniso-CA. A previous study found asymmetrical growth restriction in perterm-born children [36]. Dubois reported structural asymmetries of perisylvian regions in the preterm newborn [37]. Additionally, several studies have revealed abnormal nervous system function in preterm born children. Michalczuk suggested that Apgar score seemed to be a predicting factor for developmental rate of brain function in children with history of prematurity [38]. Teli found that low 5-minute Apgar score in very perterm infants hindered corpus callosum microstructural development [39]. Moreover, eye growth is parellel to neurodevelopment. White matter changes were found in children with anisometropic amblyopia [40]. It has also been reported that low 5-minute Apgar score increased the risk of reduced vision in children [41]. The Sydney Myopia Study found that paternal age>35 years was accociated with non-vectorial aniso-TA in unadjusted analyses. After multivariable adjustment, breast feeding had a significant protective association (P=0.02) with non-vectorial aniso-TA. In our study, neither paternal age>35 years or breast feeding was a risk factor for non-vectorial aniso-TA. To sum up, intrauterine hypoplasia and poor birth condition may be associated with asymmeric whole body development, neurodevelopment, and asymmeric visual and refractive development such as aniso-astigmatism. Further work is required to clarify the developmental mechanism behind these associations.

The strengths of this study include its population-based design, large sample size, and standardized examination protocols performed by an expert team, risk factors during pregnancy and early childhood. Our analyses are different from most previous studies by considering vectorial features of aniso-astigmatism. The limitation of this study is that some eligible children were not included into the anaysis due to missing data in questionnaire or refractive error measures, and the risk factor data collected through questionnaire may be subjective and biased. This study is also limited in the use of refraction data under noncyloplegic condition.

In summary, in the 61- to 72-month-old children in the Yuhuatai District, the prevalence of non-vectorial aniso-TA was 1.95%, while the prevalence of vectorial aniso-TA was twice as common as non-vectorial aniso-TA. Both CR and AL asymmetry were correlated with aniso-TA. Children with 5-min Apgar score<7 were more likely to have aniso-TA, while twin or triple, pre-term or post-term delivery were more likely to have vectorial aniso-CA.

TA: Total Astigmatism; CA: Corneal Astigmatism; RA: Resiual Astigmatism; DC: Dioptre Cylinder; CCT: Central Corneal Thickness; CR: Corneal Radius; ACD: Anterior Chamber Depth; LT: Lens Thickness; AL: Axial Length.

Ethics approval and consent to participate

This study followed the tenets of the Declaration of Helsinki and was approved by the ethics committee of the Nanjiing Medical University. Written consent was obtained from the parents or guardians of all children.

Consent to publish

Not Applicable.

Availability of data and materials

Data can be shared upon request.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was funded by The National Natural Science Foundation of China (Grant No. 81673198；No. 81803258); the Natural Science Foundation of Jiangsu Province (Grant No. BK20161595); Jiangsu Province’s Key Provincial Talents Program (Grant No. QNRC2016563). The sponsor or funding organization had no role in the design or conduct of this research.

Authors’ Contributions

Study concept and design (DH, HZ, XC); data collection (HT, QH, YW, RL, QS, XZ1 and XZ2, with XZ1 corresponding to Xiaoyan Zhao); analysis and interpretation of data (HT, QH, ZW); drafting of the manuscript (HT, QH, ZW); critical revision of the manuscript (HL); supervision (HL). All authors read and approved the final manuscript.

Acknowledgements

The authors would like to thank the children, their parents or legal guardians, and all the members of the Maternal and Child Healthcare Hospital of Yuhuatai District, Nanjing, China, for their helpful advice and support. The authors would also like to thank Xin Xu, a statistician in Nanjing Medical University for her statistical help.

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sTable 1. Distribution of Risk Factors in Children With vs. Without Vectorial Aniso-Total Astigmatism

Risk Factors	Group A (N=44)	Group B (N=1087)	P-value
Mean (± SD) age (month)	67.07 ± 2.99	66.89 ± 3.40	0.053
Gender: male (%)	22 (50%)	581 (53.45%)	0.77
Mean (± SD) paternal age at child birth (year)	26.91 ± 3.78	27.83 ± 4.84	0.24
Mean (± SD) maternal age at child birth (year)	25.75 ± 3.13	26.15 ± 3.96	0.21
Paternal myopia: yes (%)	16 (36.36%)	389 (35.79%)	0.94
Maternal myopia: yes (%)	23(52.27%)	426(39.19%)	0.09
Parental astigmatism: yes (%)	18 (40.91%)	270 (24.84%)	0.03
Mode of pregnancy: assisted (%)	5 (11.36%)	182 (16.74%)	0.46
Term delivery			0.07
Full-term	40 (90.91%)	979 (90.06%)
Pre-term	4 (9.09%)	55 (5.06%)
Post-term	0 (0%)	53 (4.88%)
Mean (± SD) birth weight (kilogram)	3.19 ± 0.53	3.35 ± 0.52	0.76
5-min Apgar score: abnormal (%)	7 (15.91%)	30 (2.76%)	<0.001
Delivery mode			0.96
Vaginal	25 (56.82%)	610 (56.12%)
Vaginal transferring to cesarean	3 (6.82%)	87 (8.00%)
Cesarean	16 (36.36%)	390 (35.88%)
Oxygen uptake after birth: yes (%)	6 (13.64%)	63 (5.80%)	0.07
Second or third child: yes (%)	6 (13.64%)	213 (19.60%)	0.43
Twin or triple: yes (%)	1 (2.27%)	23 (2.12%)	0.94
Feeding patterns			0.36
Exclusive breastfeeding	19 (43.18%)	525 (48.30%)
Partial breastfeeding	18 (40.91%)	464 (42.69%)
Formula feeding	7 (15.91%)	98 (9.01%)
Second-hand smoke exposure during pregnancy: yes (%)	9 (20.45%)	148 (13.62%)	0.29
Maternal working during pregnancy: yes (%)	19 (43.18%)	505 (46.46%)	0.79
Mean (± SD) outdoor activity (hour)	2.03 ± 0.78	2.25 ± 1.42	0.054
Mean (± SD) mid-working distance activity (hour)	4.69 ± 2.14	4.79 ± 3.53	0.59
Mean (± SD) near-work activity (hour)	1.21 ± 0.89	1.55 ± 1.68	0.25

Group A: children with vectorial aniso-total astigmatism; Group B: children with vectorial aniso-total astigmatism

sTable 2. Distribution of Risk Factors in Children With vs. Without Vectorial Aniso-Corneal Astigmatism

Risk Factors	Group C (N=278)	Group D (N=873)	P-value
Mean (± SD) age (month)	66.85 ± 3.38	66.91 ± 3.39	0.98
Gender: male (%)	135 (48.56%)	468 (42.20%)	0.08
Mean (± SD) paternal age at child birth (year)	28.00 ± 4.40	27.73 ± 4.93	0.047
Mean (± SD) maternal age at child birth (year)	26.20 ± 3.55	26.12 ± 4.05	0.15
Paternal myopia: yes (%)	99 (35.61%)	306 (35.87%)	0.99
Maternal myopia: yes (%)	108 (38.85%)	341 (39.98%)	0.79
Parental astigmatism: yes (%)	76 (27.34%)	212 (24.85%)	0.46
Mode of pregnancy: assisted (%)	53 (19.06%)	134 (15.71%)	0.22
Term delivery			0.01
Full-term	252 (90.65%)	767 (89.92%)
Pre-term	20 (7.19%)	39 (4.57%)
Post-term	6 (2.16%)	47 (5.51%)
Mean (± SD) birth weight (kilogram)	3.29 ± 0.56	3.36 ± 0.50	0.33
5-min Apgar score: abnormal (%)	13 (4.68%)	24 (2.81%)	0.19
Delivery mode			0.39
Vaginal	157 (56.47%)	478 (56.04%)
Vaginal transferring to cesarean	17 (6.12%)	73 (8.56%)
Cesarean	104 (37.41%)	302 (35.40)
Oxygen uptake after birth: yes (%)	22 (7.91%)	47 (5.51%)	0.19
Second or third child: yes (%)	52 (18.70%)	167 (19.58%)	0.82
Twin or triple: yes (%)	11 (3.96%)	13 (1.52%)	0.03
Feeding patterns			0.28
Exclusive breastfeeding	124 (44.60%)	420 (49.24%)
Partial breastfeeding	130 (46.76%)	352 (41.27%)
Formula feeding	24 (8.63%)	81 (9.50%)
Second-hand smoke exposure during pregnancy: yes (%)	39 (14.03%)	118 (13.83%)	0.94
Maternal working during pregnancy: yes (%)	129 (46.40%)	395 (46.31%)	0.98
Mean (± SD) outdoor activity (hour)	2.32 ± 1.71	2.21 ± 1.28	0.03
Mean (± SD) mid-working distance activity (hour)	4.97 ± 4.10	4.73 ± 3.25	0.88
Mean (± SD) near-work activity (hour)	1.48 ± 1.83	1.55 ± 1.60	0.98

Group C: children with vectorial aniso-corneal astigmatism; Group D: children with vectorial aniso-corneal astigmatism

sTable 3. Distribution of Risk Factors in Children With vs. Without Vectorial Aniso-Residual Astigmatism.

Risk Factors	Group E (N=273)	Group F (N=858)	P-value
Mean (± SD) age (month)	66.73 ± 3.37	66.95 ± 3.39	0.74
Gender: male (%)	140 (51.28%)	463 (53.96%)	0.48
Mean (± SD) paternal age at child birth (year)	27.79 ± 4.58	27.80 ± 4.87	0.45
Mean (± SD) maternal age at child birth (year)	26.13 ± 3.68	26.15 ± 4.00	0.50
Paternal myopia: yes (%)	94 (34.43%)	311 (36.25%)	0.64
Maternal myopia: yes (%)	107 (39.19%)	342 (39.86%)	0.90
Parental astigmatism: yes (%)	74 (27.11%)	214 (24.94%)	0.53
Mode of pregnancy: assisted (%)	49 (17.95%)	138 (16.08%)	0.53
Term delivery			0.19
Full-term	248 (90.84%)	771 (89.86%)
Pre-term	17 (6.23%)	42 (4.90%)
Post-term	8 (2.93%)	45 (5.24%)
Mean (± SD) birth weight (kilogram)	3.33 ± 0.53	3.34 ± 0.51	0.83
5-min Apgar score: abnormal (%)	12 (4.40%)	25 (2.91%)	0.32
Delivery mode			0.58
Vaginal	146 (53.48%)	489 (56.99%)
Vaginal transferring to cesarean	24 (8.79%)	66 (7.70%)
Cesarean	103 (37.73%)	303 (35.31%)
Oxygen uptake after birth: yes (%)	20 (7.33%)	49 (5.71%)	0.41
Second or third child: yes (%)	49 (17.95%)	170 (19.81%)	0.55
Twin or triple: yes (%)	6 (2.20%)	18 (2.10%)	0.92
Feeding patterns			0.69
Exclusive breastfeeding	131 (47.99%)	413 (48.14%)
Partial breastfeeding	120 (43.96%)	120 (13.99%)
Formula feeding	22 (8.06%)	22 (2.56%)
Second-hand smoke exposure during pregnancy: yes (%)	40 (14.65%)	117 (13.64%)	0.75
Maternal working during pregnancy: yes (%)	131 (47.99%)	393 (45.80%)	0.58
Mean (± SD) outdoor activity (hour)	2.22 ± 1.39	2.25 ± 1.40	0.94
Mean (± SD) mid-working distance activity (hour)	4.96 ± 4.51	4.73 ± 3.09	0.27
Mean (± SD) near-work activity (hour)	1.60 ± 2.30	1.51 ± 1.40	0.11

Group E: children with vectorial aniso-residual astigmatism; Group F: children with vectorial aniso-residual astigmatism

sTable 4. Distribution of Risk Factors in Children With vs. Without Non-Vectorial Aniso-Total Astigmatism

Risk Factors	Group G (N=22)	Group H (N=1109)	P-value
Mean (± SD) age (month)	66.50 ± 2.92	66.91 ± 3.40	0.15
Gender: male (%)	13 (59.09%)	590 (53.20)	0.74
Mean (± SD) paternal age at child birth (year)	26.91 ± 2.72	27.82 ± 4.83	0.049
Mean (± SD) maternal age at child birth (year)	25.77 ± 3.10	26.15 ± 3.95	0.51
Paternal myopia: yes (%)	10 (45.45%)	395 (35.62%)	0.47
Maternal myopia: yes (%)	11 (50.00%)	438 (39.50%)	0.44
Parental astigmatism: yes (%)	9 (40.91%)	279 (25.16%)	0.15
Mode of pregnancy: assisted (%)	7 (31.82%)	180 (16.23%)	0.10
Term delivery			0.99
Full-term	20 (90.90%)	999 (90.08%)
Pre-term	1 (4.55%)	58 (5.23%)
Post-term	1 (4.55%)	52 (4.69%)
Mean (± SD) birth weight (kilogram)	3.39 ± 0.43	3.34 ± 0.52	0.34
5-min Apgar score: abnormal (%)	3 (13.64%)	34 (3.07%)	0.03
Delivery mode			0.16
Vaginal	8 (36.36%)	627 (56.54%)
Vaginal transferring to cesarean	3 (13.64%)	87 (7.84%)
Cesarean	11 (50.00%)	395 (35.62%)
Oxygen uptake after birth: yes (%)	3 (13.64%)	66 (5.95%)	0.30
Second or third child: yes (%)	2 (9.09%)	217 (19.57%)	0.33
Twin or triple: yes (%)	1 (4.55%)	23 (2.07%)	0.96
Feeding patterns			0.33
Exclusive breastfeeding	8 (36.36%)	536 (48.33%)
Partial breastfeeding	10 (45.46%)	472 (42.56%)
Formula feeding	4 (18.18%)	101 (9.11%)
Second-hand smoke exposure during pregnancy: yes (%)	2 (9.09%)	155 (13.98%)	0.73
Maternal working during pregnancy: yes (%)	11 (50.00%)	513 (46.26%)	0.89
Mean (± SD) outdoor activity (hour)	1.82 ± 0.63	2.25 ± 1.41	0.07
Mean (± SD) mid-working distance activity (hour)	4.47 ± 1.90	4.80 ± 3.51	0.35
Mean (± SD) near-work activity (hour)	1.29 ± 0.85	1.54 ± 1.67	0.32

Group G: children with non-vectorial aniso-total astigmatism; Group H: children with non-vectorial aniso-total astigmatism

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The biometric parameters of aniso-astigmatism and its risk factor in Chinese preschool children: the Nanjing Eye Study

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