Normal Tension Glaucoma (NTG)

Definition

• IOP consistently ≤ 21 mmHg on diurnal testing
• Open anterior chamber angle on gonioscopy
• Characteristic glaucomatous optic nerve cupping
• Visual field defects consistent with nerve appearance
• No features of secondary glaucoma or a non-glaucomatous cause

• Kanski's Clinical Ophthalmology, 10th ed., p. 386

Pathogenesis

• Robbins Pathologic Basis of Disease, p. 1223

Risk Factors

• Age - tends to be older than POAG patients (may reflect delayed diagnosis)
• Sex - higher prevalence in females in some studies
• Race - significantly more common in Japanese individuals
• Family history - OPTN gene (optineurin) mutations identified in some NTG cases
• Low CCT - thinner corneas than POAG
• Vascular conditions - migraine, Raynaud phenomenon, diabetes, carotid insufficiency, hypercoagulability
• Systemic hypotension - nocturnal BP dips >20% are particularly important; beta-blockers taken at bedtime may worsen this
• Obstructive sleep apnoea - impairs ocular perfusion
• Myopia - associated with glaucoma and progression
• Thyroid disease - may be more common
• Low serum retinol
• Autoantibodies

Clinical Features

• Optic nerve head tends to be larger on average
• Acquired optic disc pits and focal nerve fibre layer defects are more common
• Splinter haemorrhages on the disc margin are more frequent - they are associated with a greater likelihood of progression and are often missed without disc photography
• Peripapillary atrophic changes may be more prevalent
• Pallor disproportionate to cupping should raise suspicion of an alternative (non-glaucomatous) diagnosis

Fig. Bilateral advanced glaucomatous damage in NTG (right eye shown) - Kanski's Clinical Ophthalmology, 10th ed.

• Denser, more localised, and closer to fixation than in POAG
• A dense nasal paracentral defect is typical
• Same pattern types as POAG (arcuate, etc.) but with above features
• Wills Eye Manual, p. 561

Differential Diagnosis

1. Angle closure - rule out by dark-room gonioscopy
2. Low CCT causing spuriously low IOP readings (post-refractive surgery, corneal ectasia)
3. POAG with wide diurnal IOP fluctuation - diurnal phasing required; nocturnal spikes require home monitoring or in-patient assessment
4. Previous masking by systemic beta-blockers started after glaucomatous damage
5. Spontaneously resolved glaucoma (pigmentary, traumatic, steroid-induced)
6. Shock-related optic neuropathy - from acute blood loss, MI, bypass surgery; visual loss should not progress
7. Neurological compressive lesions - optic nerve/chiasmal compression (neuroimaging mandatory if visual fields suggest non-glaucomatous pattern, if colour vision is disturbed, or in young patients)
8. AION (arteritic or non-arteritic) - may mimic NTG exactly; check ESR/CRP if GCA suspected
9. Other optic neuropathies - inflammatory, infiltrative, drug-induced (e.g., ethambutol), Leber hereditary optic neuropathy, dominant optic atrophy

Workup

• Vasospasm (migraine, Raynaud), hypotensive episodes (surgery, haemorrhage), prior steroid use, ocular trauma/uveitis, GCA symptoms, cardiovascular risk factors

• Repeat IOP - diurnal curve (phasing); consider supine IOP
• Gonioscopy - rule out angle closure, angle recession, PAS
• Visual fields (perimetry at 6-monthly intervals initially)
• OCT - RNFL thinning (thinner in NTG)
• Colour plates (Ishihara/HRR) - rule out optic neuropathy
• Blood pressure monitoring - 24-hour ambulatory BP; look for nocturnal dipping
• Carotid Dopplers - assess ocular blood flow
• CT or MRI - to exclude compressive lesions, especially if visual acuity reduced, colour vision affected, or fields suggest non-glaucomatous pattern
• FBC, ESR, CRP (if GCA or inflammatory cause suspected)
• Lipid profile, glucose, thrombophilia screen if vascular risk suspected

Treatment

The Collaborative Normal Tension Glaucoma Study (CNTGS)

• Demonstrated progression on serial perimetry
• Advanced glaucomatous damage, especially if central vision is threatened
• Long life expectancy
• Disc haemorrhages (marker of higher progression risk)

Medical Treatment

Surgical Treatment

• Consider if progression occurs despite IOP in the low teens
• Trabeculectomy with antimetabolite (MMC or 5-FU) is usually required to achieve sufficiently low target pressure

Non-IOP-Directed Measures

• Systemic vascular control - optimise management of diabetes, hypertension, hyperlipidaemia
• Nocturnal BP dips - reduce antihypertensive dose (especially bedtime dosing); consider increased salt intake (in consultation with cardiologist)
• Calcium-channel blockers (e.g., nimodipine) - for vasospasm; advocated by some authorities
• Head-up sleeping position (30°) - mean IOP is ~20% lower than flat position; beneficial in at least one-third of patients
• Regular exercise - encouraged
• Avoid head-stand yoga - transiently raises IOP
• Ginkgo biloba (40 mg TID) - may confer some benefit in selected cases
• Neuroprotection - no agent of proven benefit yet; memantine showed no benefit in clinical trials

Prognosis & Progression

• Approximately 50% of untreated patients remain stable at 5-7 years
• Progression is more likely with: disc haemorrhages, female sex, lower IOP at baseline (paradoxically), migraine, myopia, and nocturnal hypotension
• The EMGT confirms low blood pressure as an independent risk factor for progression
• Splinter haemorrhages are the strongest clinical marker of ongoing progression

Recent Evidence (PubMed, 2025)

• A 2025 Cochrane systematic review (PMID 41370133) on prognostic factors in open-angle glaucoma progression confirms that low perfusion pressure, disc haemorrhages, and thin RNFL are the strongest predictors of progression.
• A 2025 meta-analysis (PMID 40340860) found that microinvasive glaucoma surgery (MIGS), alone or combined with phacoemulsification, is effective at achieving IOP reduction in NTG patients.

• Kanski's Clinical Ophthalmology: A Systematic Approach, 10th ed., pp. 385-388
• Wills Eye Manual, Office and Emergency Room Diagnosis, pp. 561-562
• Robbins & Cotran Pathologic Basis of Disease, p. 1223