交感兴奋下脉络膜改变与学龄期儿童近视相关性的人群流行病学研究

Prevalence of myopia is high in Chinese children. Our previous research found that myopia increases sharply from 5.2% at 6 years old to 14.3% at 7 years old after school entrance, and reaches 52.2% at 10 years old. Education and myopia onset are closely related in school children. Although their relationship is widely acknowledged, the pathway how education lead to myopia onset is not clear, thus impeding early myopia control. We presume that the continuous activation of children's sympathetic nervous system under the exam-oriented education system in China, leading to change of choroidal thickness could be the possible pathway. Literatures showed activation of sympathetic nervous system could lead to thinning of choroidal thickness by constricting choroidal vessels and contracting non-vascular smooth muscle cells. In addition, our previous research found choroidal thickness is thinner in myopic children than in emmetropic children. Moreover, a number of studies regarded change of choroidal thickness as an importance connection between defocus signal and change of retina and axial length during myopia onset and progression. Therefore, the present study plan to conduct a 2-year cohort study in the primary school children of junior grade who had been documented previously and were under regular follow-up. This study tries to elucidate association between change of subfoveal and perifoveal choroidal thickness under activation of sympathetic nervous system and myopia onset, and tries to obtain a sympathetic activation related indicator (quantified by urinary catecholamines) for predicting myopia onset in children, in order to provide new.evidences to alleviate the high prevalence of myopia caused by education.

我国儿童近视患病率居高不下。我们前期研究发现近视患病率在6岁时为5.2%，7岁入学后剧增至14.3%，至10岁时已达52.2%，明确教育因素与儿童近视发病密切相关。尽管这点已被公认，但教育导致近视发病的机制仍不清楚，影响了近视的早期防控。我们推测：应试教育模式造成儿童全身交感神经持续兴奋，导致脉络膜改变是可能的作用途径。理由是既往研究显示交感兴奋可收缩脉络膜血管和平滑肌细胞导致其变薄；而我们前期研究发现儿童近视患眼较正视眼脉络膜明显较薄；且近期研究多认为脉络膜改变是离焦后视网膜平面和眼轴长度变化的重要环节。为此，本研究拟对前期已建档并定期随访的低年级儿童进行为期2年的前瞻性队列研究，阐明全身交感兴奋后黄斑区中心凹下及中心凹旁脉络膜厚度改变与学龄期儿童近视发病之间的相关性，确定导致脉络膜改变的交感兴奋界值（用尿儿茶酚胺来量化），探讨其预测近视发生的可能，为缓解教育相关的近视高发提供新的资料。

我国儿童近视患病率居高不下。交感兴奋对眼底组织，特别是脉络膜的调节作用：交感神经支配眼部脉络膜血管以及脉络膜上腔内的非血管平滑肌细胞，直接调节脉络膜血管以及脉络膜上腔内的非血管平滑肌细胞的收缩与舒张，可能是脉络膜厚度改变的主要原因，而脉络膜厚度变薄是儿童近视发生发展的重要危险信号。本课题以这些发现为基础，通过对低年级学龄儿童进行前瞻性队列研究，通过收集并检测儿童尿液中肾上腺素、去甲肾上腺素及多巴胺的含量，首次阐明了儿童交感兴奋与脉络膜厚度呈负相关，并在动物实验中得到验证。稳健回归结果显示肾上腺素与平均脉络膜厚度、除了上方及鼻侧外部的脉络膜外，其他黄斑区脉络膜厚度均与其呈显著负相关。去甲肾上腺素主要与上方内侧的脉络膜厚度呈负相关。交感兴奋公因子与颞侧及上方内侧、上方外侧的脉络膜呈负相关。交感兴奋与儿童眼轴存在正相关，横断面研究显示去甲肾上腺素与右眼、左眼眼轴显著相关（Spearman检验, P=0.034和0.017），相关系数分别为0.126和0.141，但队列研究显示因果关联尚不明确。结果提示交感兴奋能引起脉络膜变薄，但程度可能不足以导致屈光度数或眼轴的长期改变。本项目研究成果对儿童近视的发病机制研究提供了新的证据。项目研究成果在Acta Ophthalmologica等期刊发表论文5篇，培养博士研究生1名。