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

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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.