Autoregulation and Systemic Blood Pressure: A New View of Normal Tension Glaucoma

描述（由申请人提供）：关于正常张力性青光眼的主流假设是，正常张力性青光眼的进行性视野丧失是眼压升高的结果。我们将探索另一种假设，即正常张力性青光眼的视野丧失主要与全身性低血压，特别是夜间低血压有关，而与眼压无关。此外，我们假设正常紧张性青光眼的视野缺陷是由于全身低血压超过了自我调节的下限，导致缺血和视野丧失而发生的。因此，随着正常紧张性青光眼的进展，进行性缺血性损伤和视野丧失是周期性和潜伏性夜间低血压发作的结果。85例正常张力性青光眼；也就是说，对于眼压<21毫米汞柱的视野缺损患者，本研究的主要目的是确定体压低于正常体压20毫米汞柱的患者是否可以预测随访12个月后患者的纵向视野丧失。夜间低血压定义为平均动脉压低于患者通常平均动脉压20毫米汞柱以上。基线评估将包括基本的人口学和临床特征。然后，患者将在48小时内用动态记录设备监测血压，并进行扫描激光断层扫描（海德堡视网膜断层扫描）、光学相干断层扫描和视盘立体照片。在6个月和12个月的随访间隔，参与者还将进行眼科检查，视野测试（Humphrey 24-2），扫描激光断层扫描（海德堡视网膜断层扫描），光学相干断层扫描和重复48小时动态血压。眼压、药物和间隔事件也将被记录下来。在6个月和12个月时，通过共聚焦激光扫描断层扫描（Heidelberg视网膜断层扫描）、光学相干断层扫描、立体照片和视野（Humphrey 24-2）的纵向变化来评估视野丧失。判定结果的眼科医生将不知道患者的动态血压状况，测量血压的技术人员也不知道眼科测量结果。数据分析需要许多不同的多变量技术（主成分、光谱和小波分析）来首先定义结果（血压和视野）的测量，以及（多变量贝叶斯）分层分析来模拟数据的纵向性质。项目的叙述

DESCRIPTION (provided by applicant): The dominant hypothesis about normal tension glaucoma is that progressive visual field loss in normal tension glaucoma is a result of elevated intra-ocular pressures. We will explore an alternative hypothesis that visual field loss in normal tension glaucoma is primarily related to systemic hypotension, specifically nocturnal hypotension, not to intra-ocular pressures. Further, we hypothesize that the visual field defects in normal tension glaucoma occur because systemic hypotension exceeds the lower limit of autoregulation resulting in ischemia and field loss. Thus, as normal tension glaucoma progresses, progressive ischemic damage and visual field loss is a result of periodic and insidious nocturnal hypotensive episodes. Among 85 patients with normal tension glaucoma; that is, patients who have visual field deficits with intra-ocular pressures <21 mm Hg, the principal objective of this study is to determine whether systemic blood pressures >20 mm Hg below the patient's usual systemic pressure predicts longitudinal within-patient visual field loss over 12 months of follow-up. Nocturnal hypotension will be defined as mean arterial pressure that falls more than 20 mm Hg below the patients' usual mean arterial pressure. The baseline evaluation will include basic demographic and clinical characteristics. Patients will then have their blood pressures monitored with an ambulatory recording device over the course of 48 hours and will have scanning laser tomography (Heidelberg retinal tomography), optical coherence tomography, and stereo photographs of the optic disc. At 6 and 12 months of follow up intervals, participants will also have ophthalmologic exams, visual field testing (Humphrey 24-2), scanning laser tomography (Heidelberg retinal tomography), optical coherence tomography and repeat 48 hour ambulatory blood pressure. Intra ocular pressures, medications and interval events will also be documented. Visual field loss will be assessed by longitudinal within patient changes in confocal laser scanning tomography (Heidelberg Retinal tomography), optical coherence tomography, stereo photographs and visual fields (Humphrey 24-2) performed at 6 and 12 months. The ophthalmologists adjudicating the outcomes will be blinded to the patient's ambulatory blood pressure status, as will the technicians measuring blood pressure be blinded to the ophthalmologic measures. The data analysis requires many different multivariate techniques (principal component, spectral and wavelet analysis) to first define measures of outcome (for blood pressure and visual fields), as well as a (multivariate Bayesian) hierarchical analysis to model the longitudinal nature of the data.Project Narrative The effects of glaucoma can be potentially devastating, and include blindness. Of the three million Americans currently suffering from glaucoma, one sixth of patients with glaucoma have normal tension glaucoma. Among patients with normal tension glaucoma, this study will assess the role of hypotension and systemic autoregulation in progression of visual field abnormalities. This study hopes to contribute a further understanding of the relation of hypotension and intraocular pressures to the development of this disease.