Primary Vascular Dysregulation in Normal-Tension Glaucoma: Pathophysiology and Management

Area of Science:

• Ophthalmology
• Vascular Biology
• Neuroscience

Background:

• Normal-tension glaucoma (NTG) is a progressive optic neuropathy not solely caused by high intraocular pressure (IOP).
• Primary vascular dysregulation (PVD), a condition affecting blood vessel tone, is increasingly implicated in NTG pathogenesis.
• Understanding PVD's role is crucial for developing novel NTG treatment strategies beyond IOP reduction.

Purpose of the Study:

• To review the evidence linking PVD to NTG.
• To explore the underlying mechanisms of PVD in NTG.
• To evaluate current and emerging management strategies for PVD-related NTG.

Main Methods:

• A comprehensive narrative review of peer-reviewed literature was conducted.
• Databases searched include PubMed, MEDLINE, EMBASE, and Cochrane from 1985 to March 2026.
• Included studies: RCTs, observational cohorts, case-control studies, systematic reviews, and basic science investigations.

Main Results:

• PVD involves impaired optic nerve head perfusion, elevated endothelin-1, nitric oxide deficiency, and autonomic imbalance.
• PVD-associated NTG presents with optic disc hemorrhages, focal cupping, and visual field defects despite controlled IOP.
• Treatments like calcium channel blockers and Ginkgo biloba extract show benefit; lifestyle modifications are also key.

Conclusions:

• PVD is a significant, actionable factor in many NTG cases.
• A multimodal approach integrating IOP control with vascular strategies is recommended for PVD-NTG.
• Further RCTs in phenotypically defined PVD-NTG populations are needed for definitive guidelines.