Normal-Tension Glaucoma

The optic nerve head is supplied by a watershed vascular network from the short posterior ciliary arteries, making it vulnerable both to mechanical stress from elevated IOP and to reduced or unstable perfusion pressure. Normal-tension glaucoma (NTG) is a progressive optic neuropathy with the characteristic cupping and visual field loss of glaucoma, occurring despite intraocular pressure in the statistically normal range — implying that mechanisms beyond mechanical stress, particularly disrupted optic nerve head blood flow, contribute to axonal loss.¹

Primary vascular dysregulation (PVD) — a constitutional impairment of vascular tone regulation independent of structural vascular disease — is increasingly recognized as a central pathogenic contributor in a substantial proportion of NTG patients.¹ Proposed mechanisms include impaired autoregulation of optic nerve head perfusion, elevated endothelin-1 with relative nitric oxide deficiency, defective neurovascular coupling, mitochondrial dysfunction, oxidative stress, exaggerated nocturnal hypotension, and autonomic imbalance — sometimes termed Flammer syndrome when features extend beyond the eye.¹

NTG is typically asymptomatic until relatively advanced field loss develops. A vasculopathic phenotype may report cold extremities, migraine with aura, or other Flammer syndrome features — a useful clue prompting NTG consideration. Characteristic exam findings include optic disc hemorrhages, focal notch-type cupping, and central/paracentral visual field defects that can threaten central vision earlier than typical POAG.¹

Differential diagnosis includes POAG with undetected IOP peaks (missed on single measurements), compressive optic neuropathy (should be excluded, especially with pallor out of proportion to cupping or a field defect respecting the vertical midline), other causes of disc pallor/cupping (prior ischemic optic neuropathy, hereditary optic neuropathies), and physiologic large cup-disc ratio without progression.

Diagnosis requires confirming normal IOP on repeated measurements, ideally including diurnal curve assessment, alongside glaucomatous disc/RNFL and visual field findings. Non-glaucomatous causes of optic neuropathy should be reasonably excluded — neuroimaging is warranted in atypical presentations (disproportionate pallor, field defects respecting the vertical midline).

IOP reduction remains the only proven treatment for slowing NTG progression, following the same general principles as POAG management, even though IOP is already statistically normal. Minimally invasive glaucoma surgery (MIGS), alone or combined with cataract surgery, has shown efficacy: a meta-analysis found MIGS alone reduced IOP by approximately 2.6 mmHg and MIGS combined with phacoemulsification reduced IOP by approximately 2.1 mmHg, with meaningful reductions in medication burden and no significant difference between approaches.²

For patients with a PVD/vasculopathic phenotype, addressing vascular contributors is an emerging adjunctive strategy: optimizing nocturnal systemic blood pressure, lifestyle modification, and stress reduction are reasonable non-pharmacological measures, while calcium channel blockers, Ginkgo biloba extract, and endothelin receptor antagonists have shown benefit in selected cohorts, though robust randomized trial data are still needed before these become standard practice.¹

• Disc hemorrhages, focal notch-type cupping, and central/paracentral field defects point toward a PVD-associated NTG phenotype
• Excessive nocturnal systemic blood pressure lowering can worsen NTG by reducing optic nerve head perfusion overnight — review a patient's antihypertensive regimen and timing
• IOP reduction is still the only proven treatment for NTG — vascular-targeted therapies remain adjunctive
• Common pitfall: assuming a single 'normal' IOP measurement excludes glaucoma without considering diurnal fluctuation
• Common pitfall: failing to exclude compressive optic neuropathy in atypical presentations