Circadian fluctuation of mean ocular perfusion pressure is a consistent risk factor for normal-tension glaucoma

PURPOSE: To investigate systemic and ocular hemodynamic risk factors for glaucomatous damage in eyes with normal tension glaucoma (NTG). METHODS: Each patient with diagnosed NTG underwent 24-hour monitoring of intraocular pressure (IOP) and blood pressure (BP), scanning laser polarimetry (GDx-VCC), and a Humphrey visual field (HVF) examination. Multivariate regression models were used to evaluate potential risk factors: age, spherical equivalent, central corneal thickness (CCT), mean/peak in-hospital IOP, circadian IOP fluctuation, average mean arterial pressure (MAP), circadian MAP fluctuation, and circadian fluctuation of mean ocular perfusion pressure (MOPP). Functional outcome variables for glaucomatous damage were mean deviation (MD), pattern SD (PSD), and Advanced Glaucoma Intervention Study (AGIS) score. Anatomic outcome variables were TSNIT (temporal, superior, nasal, inferior, and temporal) average, superior average, inferior average, and nerve fiber indicator (NFI) on GDx-VCC. RESULTS: One hundred thirteen eyes of 113 patients met the inclusion criteria. In the multivariate regression models, larger circadian MOPP fluctuation was significantly associated with decreased MD, increased PSD, and increased AGIS score among functional outcome variables and with reduced TSNIT average, reduced inferior average, and increased NFI among anatomic outcome variables. Larger MAP fluctuation was associated with decreased MD, increased PSD, reduced TSNIT average, reduced inferior average, and increased NFI. CCT was not associated with any outcome variable. CONCLUSIONS: Of the functional and anatomic outcome variables, circadian MOPP fluctuation was the most consistent clinical risk factor for glaucoma severity in eyes with NTG. This finding may suggest an etiology of NTG as a chronic ischemic end organ disease.