Response to the letter re "CPAP therapy reduces oxidative stress in patients with glaucoma and OSAS and improves the visual field".
Response to the letter re "CPAP therapy reduces oxidative stress in patients with glaucoma and OSAS and improves the visual field".
复制标题
对“CPAP 治疗可减少青光眼和 OSAS 患者的氧化应激并改善视野”的信件的回应。
DOI：
10.1007/s00417-020-04824-3
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Nakazawa T.
中科院分区：
文献类型：
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作者：
Himori N;Nakazawa T.
我们感谢特恩布尔博士和海特马博士对我们工作的评论。我们的研究招募了患有阻塞性睡眠呼吸暂停综合征的青光眼患者，他们的进展在CPAP治疗开始之前和之后都是可靠的。CPAP前的进展是基于两年期间5组或更多可靠的HFA数据，而CPAP后的进展是基于5组或更多的1.5年期间的数据。所有患者每天使用CPAP至少4小时，在研究期间没有停止使用CPAP。对所有患者进行全夜多导睡眠监测，测量CPAP前、后的呼吸暂停低通气指数。高度近视的受试者没有被排除在外，反映了近视不影响青光眼进展的报道[1]。尽管OSAS对氧化应激的影响可能还没有完全确定，但有证据表明OSAS与青光眼有关。此前，我们发现患有OSAS的青光眼患者比没有OSAS的类似患者进展更快(以及更高的氧化应激)[2]。其他以前的报告也表明，OSAS可能导致青光眼，特别是NTG[3，4]，OSAS会加速青光眼的进展[5，6]。此外，CPAP可以改善OSAS对眼睛的许多影响。CPAP可降低交感神经系统的活动[7]和内皮素-1的水平[8]。交感神经活动和内皮素-1都促进血管收缩，这表明CPAP减轻了OSAS引起的视盘和视网膜的血管收缩。此外，长期的研究发现，作为OSAS的主要特征，间歇性呼吸暂停和缺氧会促进全身氧化应激[9]。缺氧会增加ROS水平，降低线粒体复合体I的活性，并减少抗氧化剂[10]。呼吸暂停会增加交感神经系统的活动[11]。这种活动可以引起系统性动脉高压，激活肾素-血管紧张素-醛固酮系统，释放内皮素-1和其他促进氧化应激的分子[8，12]。最后，间歇性缺氧通过上调核因子kappa-β(增加肿瘤坏死因子水平)和激活缺氧诱导因子-1来促进全身炎症[13]。也有证据表明，CPAP可以减轻氧化应激。CPAP显著降低了一种氧化应激的尿标记物[14]，并逆转了OSAS对炎症、氧化应激和降低的一氧化氮修复能力的影响[15]。我们还想指出，直到最近，人们还认为CPAP在使用过程中会导致眼压升高，因此在OSAS合并青光眼的患者中是禁忌的。这一禁忌症改变了，因为发现即使在呼吸暂停期间眼压显著下降，CPAP也不会增加眼压[16]。有鉴于此，我们认为报告CPAP在OSAS和青光眼患者中的潜在益处是很重要的。然而，我们承认我们的研究不是随机的，没有对照组，主要由NTG患者组成。因此，需要更多的研究，特别是在青光眼类型广泛的研究人群中，才能证实我们的发现。
We thank Dr. Turnbull and Dr. Heitmar for their comments on our work. Our study recruited glaucoma patients with OSAS whose progression was reliably known both before and after the start of CPAP therapy. Pre-CPAP progression was assessed based on 5 or more sets of reliable HFA data from a 2-year period, and post-CPAP progression was assessed on 5 or more sets of data from a 1.5-year period. All patients used CPAP daily for at least 4 h and did not cease CPAP use during the study period. The apnea-hypopnea index was measured both pre-and post-CPAP in all patients with full-night comprehensive polysomnography. Subjects with high myopia were not excluded, reflecting reports that myopia does not influence glaucoma progression [1]. Although the effect of OSAS on oxidative stress may not be fully established, there is evidence that OSAS is associated with glaucoma. Previously, we found that glaucoma patients with OSAS had faster progression (as well as higher oxidative stress) than similar patients without OSAS [2]. Other previous reports have also shown that OSAS can contribute to glaucoma, especially NTG [3, 4] and that OSAS accelerates glaucoma progression [5, 6]. Furthermore, CPAP can ameliorate many of the effects of OSAS on the eye. CPAP reduces the activity of the sympathetic nervous system [7] and the level of endothelin-1 [8]. Sympathetic nervous activity and endothelin-1 both promote vasoconstriction, suggesting that CPAP mitigates OSAS-induced vasoconstriction in the optic disc and retina.Moreover, there is a long history of studies finding evidence that intermittent apnea and hypoxia, key features of OSAS, promote systemic oxidative stress [9]. Hypoxia increases ROS levels, decreases mitochondrial complex I activity, and decreases antioxidants [10]. Apnea increases sympathetic nervous system activity [11]. This activity can induce systemic arterial hypertension, activating the renin-angiotensin-aldosterone system and releasing endothelin-1 and other molecules that promote oxidative stress [8, 12]. Finally, intermittent hypoxia promotes systemic inflammation, both by upregulating nuclear factor kappa-β, which increases TNF levels, and by activating hypoxia-inducible factor-1 [13]. There is also evidence that CPAP can reduce oxidative stress. CPAP significantly lowers a urinary marker of oxidative stress [14] and reverses the effects of OSAS on inflammation, oxidative stress, and decreased nitric oxide repair capacity [15]. We would also like to point out that until relatively recently, it was thought that CPAP could induce elevated IOP during use and it was therefore contraindicated in OSAS patients with glaucoma. This contraindication changed with findings that even though IOP fell significantly during apnea, CPAP did not increase IOP [16]. In light of this, we consider that it is important to report the potential benefits of CPAP in patients with OSAS and glaucoma. Nevertheless, we acknowledge that our study was not randomized, had no control group, and was primarily composed of NTG patients. Therefore, additional research, especially in a study population with a broad range of glaucoma types, will be needed to confirm our findings.