Primary Vascular Dysregulation in Normal-Tension Glaucoma: Pathophysiology and Management
Abstract
Normal-tension glaucoma (NTG) is a progressive optic neuropathy occurring in the absence of elevated intraocular pressure (IOP), implying that mechanisms beyond mechanical stress drive axonal loss. Primary vascular dysregulation (PVD), a constitutional impairment of vascular tone regulation independent of structural disease, is increasingly recognized as a central pathogenetic contributor to NTG. This review examines the evidence linking PVD to NTG, explores underlying mechanisms, and evaluates current and emerging management strategies targeting vascular dysregulation. A comprehensive narrative review of peer-reviewed literature was conducted using PubMed, MEDLINE, EMBASE, and Cochrane databases from 1985 to March 2026. Search terms included: normal-tension glaucoma, primary vascular dysregulation, Flammer syndrome, ocular blood flow, endothelin-1, calcium channel blockers, optic nerve head ischemia, autoregulation, and neurovascular coupling. Studies including randomized controlled trials, prospective observational cohorts, case-control studies, systematic reviews, and seminal basic science investigations were selected for inclusion based on relevance and quality. PVD encompasses impaired autoregulation of optic nerve head (ONH) perfusion, elevated endothelin-1 (ET-1) levels with relative nitric oxide (NO) deficiency, defective neurovascular coupling, mitochondrial dysfunction, oxidative stress, exaggerated nocturnal hypotension, and autonomic nervous system imbalance.…
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