2d:I[856015,["/_next/static/immutable/chunks/1xzisbplk9czp.js","/_next/static/immutable/chunks/3j2i1faptc_-9.js","/_next/static/immutable/chunks/0fma7nlq6immz.js","/_next/static/immutable/chunks/08tq8rmv423j5.js","/_next/static/immutable/chunks/1chr5wkk3j58k.js","/_next/static/immutable/chunks/37kmmh_zm4dov.js","/_next/static/immutable/chunks/311zvdjfxff-f.js","/_next/static/immutable/chunks/1a_hqhrsle_n_.js"],"default"] 2e:T61fb,

Summary Table

Feature	Detail
Risk Factors	Japanese/Asian descent, female sex, age > 40, family history of glaucoma, migraine, Raynaud phenomenon, nocturnal hypotension, cardiovascular disease, thin central corneal thickness, disc hemorrhages, obstructive sleep apnea
Etiology	Optic neuropathy with progressive retinal ganglion cell loss despite statistically "normal" intraocular pressure (IOP consistently ≤ 21 mmHg); likely driven by vascular dysregulation, impaired optic nerve head perfusion, and individual susceptibility to pressure-related damage
Patient Presentation	Insidious, painless, progressive visual field loss; often detected incidentally on routine eye exam; patient may report difficulty with reading or peripheral vision late in disease
Classic Physical Exam	Open anterior chamber angle on gonioscopy; IOP ≤ 21 mmHg on multiple readings (including diurnal curve); optic disc cupping with increased cup-to-disc ratio, focal notching (especially inferotemporal), disc hemorrhages (Drance hemorrhages), peripapillary atrophy, nerve fiber layer defects
Key Diagnostic Results	Visual field testing (standard automated perimetry) showing arcuate scotomas, paracentral scotomas, or nasal steps; OCT showing retinal nerve fiber layer (RNFL) thinning; IOP consistently ≤ 21 mmHg across diurnal measurements; pachymetry revealing thin corneas
Management	IOP-lowering therapy remains the mainstay (target: 30% reduction from baseline); prostaglandin analogs as first-line; if progression continues despite IOP reduction, consider adjunctive agents, address vascular risk factors, or refer for surgical options
Keywords	"Normal IOP with glaucomatous disc changes," "disc hemorrhage," "paracentral scotoma," "thin cornea," "Raynaud phenomenon with visual field loss," "low-tension glaucoma"

1. Pathophysiology

Normal tension glaucoma (NTG) is classified as a subtype of primary open-angle glaucoma (POAG) in which the defining paradox is progressive optic nerve damage occurring at an IOP that falls within the statistically normal range (≤ 21 mmHg). This challenges the traditional understanding that elevated IOP is the sole driver of glaucomatous damage and shifts the focus toward non-pressure-dependent mechanisms.The predominant theory involves vascular dysregulation at the optic nerve head. In NTG patients, the autoregulatory mechanisms that maintain stable blood flow to the optic disc are impaired. When systemic blood pressure drops, particularly during sleep (nocturnal hypotension), perfusion pressure to the optic nerve head falls below a critical threshold, resulting in ischemic injury to the retinal ganglion cells. This explains the strong association with Raynaud phenomenon and migraine, both of which reflect systemic vasospastic tendencies. The concept of optic nerve perfusion pressure, defined as the difference between mean arterial pressure and IOP, is central here. Even a "normal" IOP can be relatively too high for an optic nerve that is already underperfused.

A second contributing mechanism involves mechanical susceptibility of the lamina cribrosa. In some NTG patients, the connective tissue architecture of the lamina cribrosa is structurally weaker, meaning even normal levels of IOP can produce axonal compression and disruption of axoplasmic flow. This leads to retinal ganglion cell apoptosis through mechanisms analogous to high-pressure glaucoma but at a lower threshold.

Additionally, there is growing evidence for translaminar pressure gradient abnormalities. The pressure difference between the intraocular compartment (IOP) and the retrolaminar cerebrospinal fluid (CSF) pressure determines the net mechanical stress on the lamina. NTG patients have been found to have lower intracranial pressure (ICP), which means the translaminar gradient is higher even when IOP is normal, effectively producing the same axonal stress as elevated IOP would in a patient with normal ICP.

Finally, oxidative stress, glutamate excitotoxicity, and autoimmune-mediated damage to retinal ganglion cells have been proposed as additional IOP-independent pathways. These mechanisms are less firmly established but are under active investigation and occasionally appear in exam questions framed around "non-IOP-dependent risk factors."

The clinical consequence of all these mechanisms is the same: progressive, irreversible loss of retinal ganglion cell axons leading to characteristic optic disc cupping and visual field defects that are often more centrally located (paracentral scotomas) compared to the more peripheral arcuate defects seen in high-pressure POAG.

2. Classification and Clinical Manifestation

NTG is not traditionally subclassified into formal stages the way some diseases are, but it is critical to understand where it sits within the glaucoma classification and how its clinical features differ from related conditions.

Glaucoma Classification

Type	Angle	IOP	Key Feature
Primary Open-Angle Glaucoma (POAG)	Open	Elevated (> 21 mmHg)	Most common glaucoma; IOP-driven damage
Normal Tension Glaucoma (NTG)	Open	≤ 21 mmHg	Glaucomatous damage at normal IOP
Ocular Hypertension (OHT)	Open	Elevated (> 21 mmHg)	High IOP but no optic nerve damage or field loss
Primary Angle-Closure Glaucoma	Closed/Narrow	Usually elevated	Pupillary block mechanism; acute or chronic
Secondary Glaucoma	Variable	Usually elevated	Due to identifiable cause (trauma, steroids, uveitis, neovascularization)

Clinical Manifestations of NTG

Feature	Detail
Symptoms	Asymptomatic until late; may notice paracentral vision loss, reading difficulty, or "missing spots"
IOP	Consistently ≤ 21 mmHg (must be confirmed with diurnal IOP curve or multiple readings)
Anterior chamber angle	Open on gonioscopy
Optic disc	Cupping (increased cup-to-disc ratio), focal notching (inferotemporal rim thinning is characteristic), disc hemorrhages (Drance hemorrhages, more common in NTG than high-pressure POAG)
Peripapillary changes	Beta-zone peripapillary atrophy, RNFL wedge defects visible on red-free photography or OCT
Visual field defects	Paracentral scotomas and arcuate defects that tend to be closer to fixation compared to POAG; nasal steps also seen
Systemic associations	Migraine, Raynaud phenomenon, nocturnal systemic hypotension, cardiovascular disease, obstructive sleep apnea

The clinical pearl here is that disc hemorrhages and paracentral scotomas closer to fixation are hallmark features that should raise suspicion for NTG over typical POAG on a vignette.

3. Diagnostic Workup

Diagnostic Summary Table

Test	Role	Key Findings
Goldmann applanation tonometry	Measure IOP (best initial)	IOP ≤ 21 mmHg on multiple occasions including diurnal curve
Pachymetry	Measure central corneal thickness (CCT)	Thin CCT may cause underestimation of true IOP; thin cornea is itself a risk factor for NTG
Gonioscopy	Assess anterior chamber angle	Confirms open angle (mandatory to rule out angle closure)
Dilated fundus exam / Slit lamp with 78D or 90D lens	Optic disc assessment	Cupping, focal rim thinning/notching, disc hemorrhages, peripapillary atrophy
Standard automated perimetry (SAP) (e.g., Humphrey 24-2 or 10-2)	Visual field testing	Paracentral scotomas, arcuate defects, nasal steps
OCT of RNFL and ganglion cell complex	Structural assessment	RNFL thinning, ganglion cell-inner plexiform layer thinning, often preceding detectable field loss
Diurnal IOP curve / 24-hour IOP monitoring	Rule out IOP spikes	Some "NTG" patients have occult IOP spikes at night or early morning
Neuroimaging (MRI brain/orbits with contrast)	Rule out compressive lesion	Indicated when visual field loss is atypical, unilateral, or rapidly progressive
Blood pressure monitoring (especially nocturnal)	Evaluate vascular risk	Nocturnal dips in BP correlate with progression

The best initial step when glaucomatous disc changes are observed is to confirm the IOP with Goldmann applanation tonometry on multiple occasions. A single normal reading is insufficient because IOP fluctuates throughout the day. A diurnal curve (measurements taken at different times including early morning) is essential to ensure there are no occult pressure spikes that would reclassify the patient as having standard POAG.

Pachymetry is a required adjunct. Central corneal thickness directly affects the accuracy of tonometry. A thin cornea will cause Goldmann tonometry to underestimate the true IOP, meaning some patients labeled as "NTG" may actually have a higher true IOP. Conversely, thin corneal thickness has been shown in the Ocular Hypertension Treatment Study (OHTS) and the Collaborative Normal-Tension Glaucoma Study (CNTGS) to be an independent risk factor for glaucomatous progression.

Gonioscopy is non-negotiable. Every patient with suspected glaucoma must have their angle assessed to exclude angle-closure mechanisms, pigment dispersion, or pseudoexfoliation that might explain the disc damage.

Visual field testing with standard automated perimetry (Humphrey visual field, typically 24-2 strategy) is the functional gold standard for documenting the pattern and severity of field loss. In NTG, the 10-2 test (which focuses on the central 10 degrees) is particularly valuable because paracentral defects closer to fixation are more common than in high-pressure POAG and may be missed on a 24-2 test.

OCT provides objective, quantitative measurement of the RNFL and ganglion cell layer and is invaluable for detecting early structural damage before visual field loss becomes clinically apparent on perimetry.

A critical diagnostic consideration: always rule out non-glaucomatous causes of optic disc cupping and visual field loss. If the presentation is atypical (unilateral, rapidly progressive, visual field defect respecting the vertical midline suggesting a neurologic rather than glaucomatous pattern, or presence of pallor out of proportion to cupping), MRI of the brain and orbits must be obtained to exclude compressive lesions such as pituitary adenomas, meningiomas, or aneurysms. This is a high-yield exam trap.

4. Management and Treatment

Management Summary Table

Situation	Treatment	Details
First-line IOP lowering	Prostaglandin analog (e.g., latanoprost 0.005%)	One drop to affected eye(s) once daily at bedtime; target 30% IOP reduction from baseline
Second-line / adjunctive	Topical beta-blocker (e.g., timolol 0.5%)	One drop twice daily; avoid in asthma, COPD, bradycardia
	Topical alpha-2 agonist (e.g., brimonidine 0.2%)	One drop two to three times daily
	Topical carbonic anhydrase inhibitor (e.g., dorzolamide 2%)	One drop two to three times daily
Refractory to medical therapy	Selective laser trabeculoplasty (SLT)	Can be used as primary or adjunctive therapy
Progressive despite maximal medical/laser therapy	Trabeculectomy or glaucoma drainage device	Surgical IOP reduction
Vascular risk factor modification	Avoid excessive nocturnal hypotension	Review antihypertensive regimen; avoid aggressive nighttime BP lowering; address sleep apnea

Despite the IOP being "normal," the Collaborative Normal-Tension Glaucoma Study (CNTGS) demonstrated that lowering IOP by 30% from baseline significantly reduces the rate of visual field progression. This established IOP reduction as the evidence-based treatment for NTG, even though the IOP is already within the statistically normal range. The target is not a fixed number but a 30% reduction from the individual's baseline.

Prostaglandin analogs (latanoprost, travoprost, bimatoprost) are first-line because they provide the greatest IOP-lowering efficacy (25-33% reduction), have a favorable once-daily dosing schedule (administered at bedtime), and have minimal systemic side effects. Counsel patients about potential local effects: iris pigmentation changes (particularly in hazel or green eyes), periorbital fat atrophy, and eyelash growth.

If a prostaglandin analog alone does not achieve the target, adjunctive agents are added. Topical timolol is a common second agent (one drop of 0.5% twice daily), but it must be used cautiously. Avoid timolol in patients with asthma, COPD, second- or third-degree heart block, or decompensated heart failure. Brimonidine and dorzolamide are alternatives, often used as fixed-combination drops to reduce the burden of multiple medications.

Selective laser trabeculoplasty (SLT) is an effective option that can be offered as a primary treatment or as an adjunct. It carries minimal risk and can be repeated if the effect wanes over time.

For patients who continue to progress despite maximal tolerated medical and laser therapy, trabeculectomy (filtration surgery) is considered. This creates a new drainage pathway for aqueous humor, further lowering IOP, but carries risks of hypotony, bleb-related infection, and cataract formation.

An often-overlooked component of NTG management involves systemic vascular optimization. Patients on antihypertensive medications who demonstrate nocturnal hypotension should have their dosing schedule reviewed in coordination with their primary care physician. Aggressive nighttime blood pressure lowering can worsen optic nerve perfusion and accelerate NTG progression. This does not mean stopping antihypertensives, but rather adjusting the timing (e.g., switching evening doses to morning) to avoid excessive nocturnal dips. Obstructive sleep apnea should be screened for and treated with CPAP if present.

5. Differential Diagnosis and Distractors

Differential Diagnosis	Why It Is Similar	Key Discriminator
Primary open-angle glaucoma (POAG)	Same disc cupping, RNFL thinning, and visual field defects	IOP is elevated (> 21 mmHg) in POAG; NTG has consistently normal IOP
Compressive optic neuropathy (e.g., pituitary adenoma, meningioma)	Can cause optic disc pallor/cupping with visual field loss and normal IOP	Visual field defect in compressive lesions typically respects the vertical midline (bitemporal hemianopia for chiasmal lesions); pallor out of proportion to cupping; MRI reveals the lesion
Anterior ischemic optic neuropathy (AION)	Optic disc edema (acute) followed by pallor; visual field loss; associated with vascular risk factors	AION presents with sudden, painless vision loss and disc edema acutely; NTG is insidious; AION disc shows pallor rather than cupping; altitudinal field defect rather than arcuate scotoma
Optic neuritis	Visual field loss and optic nerve pathology	Painful eye movements, younger patient (often female), associated with multiple sclerosis; disc edema or retrobulbar (normal-appearing disc acutely); NTG is painless and chronic
Physiologic cupping	Large cup-to-disc ratio on fundoscopy	Cup-to-disc ratio is symmetric bilaterally, no progressive change, normal visual fields, and normal RNFL on OCT
Chronic angle-closure glaucoma	Progressive disc cupping and field loss at normal-appearing IOP (may have intermittent closures)	Gonioscopy reveals a narrow or closed angle; peripheral anterior synechiae may be present; NTG angle is open

6. Traps and High-Yield Pearls

The most common way students miss questions on NTG is by assuming that a normal IOP rules out glaucoma. This is the fundamental conceptual trap. When a vignette describes progressive visual field loss with optic disc cupping and normal IOP, the instinct to look for a non-glaucomatous diagnosis is strong, but the correct answer is almost always NTG, provided the angle is open, the visual field pattern is glaucomatous (not hemianopic), and neuroimaging has been considered.

The second major trap involves failing to order neuroimaging when the presentation is atypical. A young patient with unilateral disc pallor, a visual field defect that respects the vertical midline, or rapid progression should prompt an MRI before accepting the diagnosis of NTG. Test writers love to include a pituitary adenoma masquerading as NTG.

A third pitfall is not understanding pachymetry. Some questions will present a patient with "normal IOP" who actually has a thin cornea. The student must recognize that the measured IOP is artificially low, and the true IOP may be higher. This does not automatically convert the diagnosis to POAG, but it is a testable concept about the limitations of Goldmann tonometry.

Finally, remember that the treatment for NTG is still IOP lowering, even though the IOP is normal. Students sometimes hesitate to choose "lower the IOP" when the pressure is 14 mmHg, but the CNTGS data clearly supports this approach. The target is a relative 30% reduction from baseline, not an absolute threshold. If the baseline IOP is 16 mmHg, the target becomes approximately 11 mmHg.

The core competency being tested across NTG questions is the ability to recognize that glaucomatous damage is not solely defined by elevated IOP, to distinguish NTG from compressive and vascular optic neuropathies, and to apply evidence-based IOP-lowering treatment even in the absence of elevated pressure.

1e:["$","$L2d",null,{"article":{"id":"da001a00-fa5e-4197-84fe-e7d713411221","title":"Normal Tension Glaucoma","content":"$2e","category":"Oftalmologi","created_at":"2026-05-12T04:48:05.333637+00:00","status":"published","subcategory":null},"questionCount":1,"sections":[{"id":"section-pathophysiology","num":"01","title":"Pathophysiology"},{"id":"section-classification-and-clinical-manifestation","num":"02","title":"Classification and Clinical Manifestation"},{"id":"section-diagnostic-workup","num":"03","title":"Diagnostic Workup"},{"id":"section-management-and-treatment","num":"04","title":"Management and Treatment"},{"id":"section-differential-diagnosis-and-distractors","num":"05","title":"Differential Diagnosis and Distractors"},{"id":"section-traps-and-high-yield-pearls","num":"06","title":"Traps and High-Yield Pearls"}],"hasSummaryTable":true}]