Regional trends and associated factors of childhood visual impairment: a case 1 study in Shandong province, China 2

Background: Visual impairment is a common child health problem. We hopes to analyze the 15 regional trend, related factors and spatial distribution of children's visual impairment in Shandong 16 province, to explore the spatial changes brought by time and their influencing factors, so as to 17 provide scientific basis for prevention of childhood visual impairment. 18 Methods: This study covers 5 complete cross-sectional surveys (Physical examination data in 19 Shandong province) from 2013 to 2017, involving about 29.24 million students. The 11 th International 20 Classification of Diseases was selected as the diagnostic standard. Spatial autocorrelation and hotspot 21 analysis methods in ArcGIS software were used to analyze spatial features. The associated factors were 22 analyzed by multinomial logistic regression. Results: The visual impairment prevalence showed a trend of decreasing first and then increasing 24 from 2013-2017, with slight changes. In terms of regional spatial differences, Weihai and Yantai have 25 the highest VI rates in all years, and there was a large-scale spatial aggregation phenomenon. The 26 southern low-value clusters, however, showed a weakening year by year. Further exploration revealed 27 that the per capita disposable income of rural households, the growth rate of gross domestic product, 28 total retail sales of consumer goods and number of full-time teachers were verified as risk factors for 29 regional visual impairment levels. 30 Conclusions: The slight rebound of the prevalence of visual impairment and the high rate in the 31 eastern and northern regions of Shandong province need more attention. It is suggested that relevant 32 departments should focus on the influence of regional economic and educational factors when 33 formulating relevant strategies.


Introduction 37
Childhood is considered to be one of the most critical stages of growth and development, which has 38 long been concerned from many aspects, such as the state, schools, families and individuals. How to 39 create a healthier growth environment for children in the current situation (increasingly complex living 40 environment) is an urgent problem to be solved. Among them, vision issues (such as visual impairment 41 (VI), myopia, amblyopia, etc.) are most common and prominent. As a window for one to understand 4 by 20%, and the risk of moderate to severe VI will even increase by 27% [1]. Meanwhile, compared 68 with normal children, visual impaired children are more likely to come from families with relatively 69 higher economic level [10]. In China, the direct cost per patient due to VI is US$ 6988.6 ± 10,834.3 per 70 year, of which 70% is direct medical expenses and only less than 30% can be reimbursed [13]. A recent

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German study also showed that VI and blindness have brought huge social burden (annual cost is about 72 EU€49.6 billion) [14]. Furthermore, if patients suffer from chronic diseases such as hypertension, the 73 risk of VI will be further increased [15]. The economic pressure brought by this multiple disease 74 burden is obvious.

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Globally, the number of visual impaired people among all ages reached about 285 million as early 76 as 2010 [2]. Moreover, the current problem of VI in China has a clear tendency to be younger. Albeit 77 the older age group still occupies the majority in general, the prevalence of younger group has 78 increased even more rapidly [1]. Therefore, this article will study the evolution of childhood vision 79 problems in Shandong province (about 100 million people), a representative province in China, based 80 on the VI prevalence of children aged 6-12. The aim was to find out the secular trend, regional 81 distribution characteristics and related risk factors through the analysis on the visual impaired 82 schoolchildren from 2013 to 2017, so as to provide data support for the next policy adjustment and

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According to the requirements of Health examination methods for primary and secondary schools 106 in Shandong province, all physical examinations procedures were carried out in accordance with 107 regulations and using standardized professional instruments. The data involved in this study were 108 obtained through physical measurements and did not involve laboratory examinations.

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According to the actual situation in China (i.e., the visual chart used in children's physical examination 121 does not involve the detection range of less than 6/60) and previous studies [1,20], in this study, visual 122 impairment was divided into mild and moderate-severe categories. Mild VI was defined as unaided 123 distance VA of worse than 6/12 (logMAR < 0.5) and that of equal to or better than 6/18 (logMAR ≥ 0.3) 124 in the worse eye, moderate to severe VI was defined as unaided distance VA worse than 6/18 (logMAR 125 < 0.3) in the worse eye.

Other Data 127
In terms of influencing factors, seven regional associated factors (obtained from the Shandong per capita disposable income of rural households (RPCDI). Meanwhile, in order to effectively reduce 135 the impact of population differences in different areas, this study weighted the regional associated 136 factors by their population (except GRGDP). In addition, based on the annual VI prevalence range and 137 the effect of mapping, the regional VI level was divided into 5 grades from low to high (ranging from 0% 138 to 35%, with every seven percentage points recorded as a level).

Statistical Analysis 140
Raw data was extracted through SQL Sever2017, and SPSS 22.0 was used to analyze the data. The 141 measurement data were described by the mean (standard deviation), and t-tests and linear correlation 142 were used for inter-group comparison. The counting data was expressed by the rate (%), and the 143 comparative analysis between groups was tested by chi-square tests. Furthermore, multinomial logistic

Spatial Analysis 147
ArcGIS 10.2 software was used to analyze spatial distribution, regional variation differences, etc. In 148 light of the distribution range of VI rates, this study artificially divided it into 5 levels. Besides, in order 149 to find out whether there is spatial clustering and its variation trend in the Shandong province, spatial

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The clustering of high and low values was obtained through hotspot analysis (calculation the 158 Getis-Ord Gi* statistic for each feature in a dataset). After a partial sum of a feature and its neighbors 159 was compared with the sum of all features, if the local sum was significantly different from the 160 expected local sum that it cannot be randomly generated, a statistically significant z-score will be 161 resulted. Based on the resultant z-scores and p-values, the location where the high-value or low-value 162 elements cluster in space can be illustrated.

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The Getis-Ord local statistic is given as： Where is the attribute value for feature , , is the spatial weight between feature and 165 , and： The * statistic returned for each feature in the dataset is the z-score. For statistically significant 167 positive z-scores, the larger the z-score is, the more intense the clustering of high values (hot spot). The

Patient and public involvement 170
No patients or public were involved in this study.

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The sample was from the physical examination data of primary and secondary school students in 173 Shandong province (2013-2017), and children aged 6-12 years old were selected as subjects (a total of 174 29 237 771, mean (SD) age: 9.06 (1.91) years; 53.96% were boys), which basically covers whole 175 school children in Shandong province. Among them, the sample size in these 5 years were 1 864 241, 5 176 859 099, 6 685 362, 7 065 383 and 7 763 686 respectively. Basic information of children in each city 177 can be found in Table 1.  188

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Compared with rural areas, urban regions had a higher VI prevalence, such as the overall rate 197 ( 2 =313936.581, p < 0.001), this gap was maintained at more than 6% every year. Meanwhile, the

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In terms of age, there was a strong linear-by-linear association between VI prevalence and age (e.g.

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Focusing on the regional distribution of mild and moderate-severe VI (yellow and purple dots) in 215 13 these maps, it was found that the aggregation phenomenon was prominent in the northeast of the 216 peninsula and areas around Jiaozhou Bay. In addition, the cluster of central counties has become more 217 and more distinct with the passage of time.

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Further, this study analyzed the spatial relationships that may exist between regional differences in 219 overall VI rates. The results (Table 3) illustrated that there was spatial aggregation of VI in Shandong 220 province.

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Combined with the maps of various years, the range of hot spots has been fluctuating slightly,

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while the accumulation of cold spots has shown a trend of weakening year by year, especially in

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Zaozhuang and Linyi cities. The results were shown in Figure 9-13.

Influencing factors Analysis 232
After the collinearity diagnostics, five types of regional economic associated factors and one social

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Studies have confirmed that RPCDI, GRGDP and FTT were risk factors for regional VI level.

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RPCDI played a role in promoting the "development" of regional VI in different grades, while the latter 242 two indexes only worked in the highest grade (compared with the level 1). Besides, CGTRS was also 243 verified as a risk factor (only in level 3). Nevertheless, GDP and GPBE showed no statistically 244 significant effect on the degree of VI. The results were shown in Table 4.

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As a large country with a population of 1.4 billion, China has an equally large number of children.

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Since the Two-Child policy was completely liberalized in early 2016, the number of newborns has 248 increased significantly. Meanwhile, the VI prevalence is also continuously rising [1]. In order to better

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Differences between urban and rural areas were also detected: The prevalence of the three VI was 274 higher in cities than that in countries. The gap in economic level has been considered as the main

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If subdivided by gender, the distribution characteristics (including total, mild and moderate to 313 severe VI) were highly consistent with the overall, and the results for boys and girls were similar.

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Therefore, this article does not further explore the gender differences in regional distribution.

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This study also included a variety of representative regional influencing factors, in order to 316 conduct a more comprehensive discussion on the reasons of the above problems. After adjusting for 317 confounding, through multiple logistic regression analysis, a total of three risk factors and one 318 protection factor were detected. They were: risk factors-RPCDI, GRGDP, CGTRS and FTT. When 319 the regional VI level reached the fifth grade, they played the most significant role (expect CGTRS).

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This means that compared with the underdeveloped areas, regions with higher RPCDI, GRGDP and

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FTT were more likely to develop into the regions with higher VI rate, and their risks were 2.540 (95%

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We suggested that future research should focus more on the teachers, so as to further explore the 343 specific causes of this association.

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This is the first systematic study on the visual impairment of children aged 6-12 in Shandong 345 province from 2013 to 2017, and the differences among them were expounded from various aspects.

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The sample involved in the study is huge, and the results are highly credible and regionally

Competing interests 379
The authors declare that they have no competing interests.

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The datasets generated and/or analysed during the current study are not publicly available due the data 382 is confidential, but are available from the corresponding author on reasonable request.

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Ethics approval and consent to participate 384 Ethics approval was not available in this cross-sectional study because we did not include any data of 385 students' personal information, including name, identity information, address, telephone number, etc.

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This study only showed the secondary aggregated data on county-level, therefore, waived off ethical 387 approval.

Consent of publication 389
Not applicable