正常眼压性青光眼与睡眠呼吸事件的相关性研究

Relationship between normal-tension glaucoma and sleep-breathing events

背景正常眼压性青光眼（NTG）是原发性开角型青光眼中的一个重要类型，非眼压依赖因素对本病的影响已受到广泛关注，而近期一些研究发现睡眠呼吸暂停综合征患者青光眼发病率较高，提示两者之间有一定的内在联系。目的探讨NTG患者睡眠呼吸事件的发生频率和强度及其与青光眼进展的关系。方法采用前瞻性病例对照研究设计，纳入2011—2012年于北京大学第三医院眼科就诊的NTG患者20例作为NTG组，纳入同期年龄和性别匹配的18名健康志愿者作为正常对照组，所有受试者进行视野、海德堡共焦激光眼底断层扫描仪（HRT）检查、OCT检查以及多导睡眠监测（PSG），采用SPSS17．0统计学软件对两组之间受试者的各睡眠呼吸参数测量值的差异进行Mann—WhitneyU检验或独立样本t检验，对受试者睡眠呼吸事件参数测量值与平均视网膜神经纤维层（RNFL）厚度及视杯容积的关系进行Spearman秩相关分析和Pearson相关分析，确定NTG患者睡眠呼吸事件与青光眼相关指标的关系。结果两个组间受试者的临床基线特征，包括年龄、性别、身高、体质量及体质量指数（BMI）的差异均无统计学意义（P〉0．05）。NTG组受试者测量的呼吸暂停低通气指数（AHI）、低通气指数（HI）和呼吸暂停指数（AI）均明显高于正常对照组，差异均有统计学意义（U=89．000，P=0．007；U=91．000，P=0．008；U=89．000，P=0．007），睡眠呼吸事件中关于时间的相关参数均明显长于正常对照组（P〈0．05），而睡眠觉醒期和睡眠中动脉血氧饱和度均低于正常对照组，差异均有统计学意义（t=-3．480，P=0．001；t=-3．255，P=0．002）。两个组间受试者睡眠平均心率、睡眠最低心率、睡眠最高心率的差异均无统计学意义（t=-0．133，P=0．895；t=-0．906，P=0．371；t=-0．164，P=0．871）。HRT测量的NTG患者平均RNFL厚度为（188．16±98．29）μm，与最低睡眠动脉血氧饱和度[（85．55±6．58）％]呈中度正相关（r=0．552，P=0．022），与AHI、AI均呈中度负相关（r=-0．530，P=0．019；r=-0．517，P=0．024），但HI与RNFL厚度无明显相关性（r=-0．399，P=0．091）。OCT测量的NTG患者视杯容积为（0．580±0．215）μm^3，与AHI、AI、HI均呈中度正相关（r=0．584，P=0．018；r=0．670，P=0．005；r=0．544，P=0．034），而与睡眠最低动脉血氧饱和度间无明显相关性（r=-0．493，P=0．052）。结论NTG患者睡眠呼吸事件发生的概率及强度均较正常人增加，可能在一定程度上与NTG的发病有关，同时对NTG患者的神经修复过程有不良影响。

Background Normal-tension glaucoma （NTG） is a common form of open-angle glaucoma throughout the world and additional intraoeular pressure （IOP）-independent factors take increasing importance in NTG. Some recent studies found that patients with obstructive sleep apnea syndrome had a high prevalence of NTG. Objective The aim of this study was to determine the relationship between NTG and sleep-breathing events. Methods A prospective cases-controlled trial was designed. This trial protocol was approved by the Ethic Committee of Peking University Third Hospital. Written informed consent was obtained from each subject prior to entering into the study cohort. Twenty NTG patients were included in Peking University Third Hospital in 2011-2012, and 18 normal volunteers were enrolled in the same duration. Perimetry,retinal nerve fibrous layer （RNFL） thickness by Heidelberg confocal laser scanner （HRT）,volume of optical disc by OCT and polysomnography （PSG） in night were performed on all the subjects. The difference of all the PSG sleep parameters were compared using Mann-Whitney U test or independent sample t test, and the correlations of PSG sleep parameters with RNFL and volume of optical disc in the NTG patients were analyzed by Spearman rank correlation and Pearson correlation analysis of SPSS 17.0 software. Results The demographic baseline of the subjects was no significant difference between the NTG group and the normal control group, including age, gender, height, weight and body mass index（BMI） （all at P〉0.05 ）. Apnea hypopnea index （AHI） ,hypopnea index （HI） and apnea index （AI） were significantly higher （ U = 89. 000, P = 0. 007; U= 91. 000, P = 0. 008; U= 89. 000 ,P = 0, 007 ） , and the time-related parameters of apnea sleep events were longer in the NTG group than those in the normal control group （all at P〈0.05 ）. In the NTG group ,lowest sleep SaO2 of both waking and sleeping states was significant declined in comparison with the normal control group （ t = -3. 480, P = 0.001 ; t = -3. 255, P = 0. 002 ）. The mean heart rate, lowest heart rate and highest heart rate in sleeping state were insignificantly differences between the two groups （ t = -0. 133, P = 0. 895 ; t = -0. 906, P = 0. 371 ; t = -0. 164, P = 0. 871）. The mean RNFL thickness was （lgg. 16±9%. 29 ] μm in the NTG group and showed a moderate positive correlation with the lowest sleep SaO2 of sleeping state （ [ 85.55 ±6.58 1% ） （ r = 0. 552, P = 0. 022 ） and moderate negative correlations with AHI,AI（r=-0. 530,P=0. 019; r=-0. 517 ,P=0. 024）. No significant correlation was seen between the RNFL thickness and HI （r=-0. 399 ,P=0. 091 ）. The volume of optical disk was （0. 580±0. 215） μm3 and presented moderate positive correlations with AHI, AI, HI （ r = 0. 584, P = 0. 018 ; r = 0. 670, P = 0. 005 ; r = 0. 544,P=0. 034）. However, there was no significant correlation between volume of optical disk and the lowest sleep SaO2 of sleeping state （ r = - 0. 493, P = 0. 052 ）. Conclusions The probability and intensity of sleep-breathing events have increasing trends in NTG patients,which probably is associated with the pathogenesis and advancement of NTG. The abnormality of PSG sleep parameters plays adverse effect on the repair process of optical nerve of NTG patients.