Low-Tension Glaucoma

Low-tension glaucoma (LTG) is a chronic optic neuropathy that affects adults. Its features parallel primary open-angle glaucoma (POAG), including characteristic optic disc cupping and visual-field loss, with the exception of a consistently normal intraocular pressure (IOP), ie, less than 22 mm Hg.[1] Although the upper limit of "normal" is fuzzy and arbitrary, cases of low-tension glaucoma tend not to be with truly low pressures but rather with pressures considered to be in the moderate or upper-normal range, however "normal" is defined.

Low-tension glaucoma is an optic neuropathy with chronic loss of retinal ganglion cells (RGC) due to a genetic hypersensitivity to IOP. Low-tension glaucoma also is due to vascular factors, including vasospasm and ischemia.

Frequency

United States

Up to 15-25% of patients with POAG experience low-tension glaucoma. According to the Baltimore Eye Study, 50% of individuals with glaucomatous disc and visual-field changes had an IOP of less than 21 mm Hg on a single visit, and 33% had an IOP of less than 21 mm Hg on 2 measurements.

International

The prevalence of low-tension glaucoma is higher in Japan and Korea.[2]

Mortality/Morbidity

Loss of peripheral vision is associated with low-tension glaucoma.

Race

The prevalence of low-tension glaucoma is higher in Japan and Korea.[2]

Sex

Low-tension glaucoma is more common in females than in males.

Age

The mean age of patients with low-tension glaucoma is 60 years; they typically are older than patients with POAG.

For excellent patient education resources, visit eMedicineHealth's Eye and Vision Center. Also, see eMedicineHealth's patient education articles Normal-Tension Glaucoma, Glaucoma Overview, Glaucoma FAQs, and Glaucoma Medications.

The history of low-tension glaucoma (LTG) may include the following:

• Ocular history

• Steroid use

• Trauma

• Vasospasm (see below)

  • Raynaud syndrome

  • Migraine headaches

• Coagulopathies - Previous blood loss or shocklike episode

• Systemic nocturnal hypotension (notably in older thin, white women)

• Autoimmune disorders (evidence of other autoimmune diseases common)

• Systemic vascular disease

• Thyroid disease - Increased incidence of thyroid disease in patients with low-tension glaucoma (6 of 25 patients in 1 series)

• Sleep apnea (particularly in heavy men)

• Alzheimer disease - Associated with mild increase in cup-to-disc ratio

• Family history of glaucoma or optic neuropathy

Physical examination findings in low-tension glaucoma (LTG) may include the following:

• Conduct general medical examination (eg, blood pressure, carotid arteries).

• Exclude ocular hypertension and POAG

• Refractive error - Myopia

• Cornea (see below)

  • Central corneal thickness thinner in normal-tension glaucoma[3] in correlation with severity

  • Keratic precipitates indicating uveitis

  • Krukenberg spindle indicating pigment dispersion

• Iris - Transillumination defects or pigment dusting indicating pigment dispersion

• Anterior chamber (see below)

  • By definition, low-tension glaucoma has an open, normal-appearing angle.

  • Rule out angle closure and angle recession.

• Lens - Glaucomflecken indicating previous IOP elevation, probably secondary to acute angle closure

• Posterior synechiae

• Peripheral anterior synechiae

• Intraocular pressure (see below)

  • Perform diurnal curve (should be < 22 mm Hg).

  • May be asymmetric

  • Higher IOP in left eye (related to blood flow from carotid arteries)

    • IOP fluctuation leads to greater visual-field progression in normal-tension glaucoma[3]

    • Other - Corneal compensated IOP using the Ocular Response Analyzer[4]

• Myopic - Greatest risk of progression

• Senile sclerotic - Older with vascular disease

• Focal ischemic - May be younger

• Optic disc in low-tension glaucoma as compared to high-tension glaucoma (controversial)

• Larger discs

• Peripapillary disc atrophy (particularly beta zone)

• Thin disc rims; more commonly shows notching, more sloping of cup

• Narrow vessels in peripapillary area, independent of stage of the disease[5]

• Disc hemorrhages[6]

• Acquired pit

• Retina - Arteriosclerotic changes indicating vascular disease

• Visual fields in low-tension glaucoma as compared to high-tension glaucoma (controversial)

• Focal

• Closer to fixation

• Deeper

• Blood pressure - Nocturnal hypotension

• Carotid bruit indicating carotid insufficiency

Low-tension glaucoma is associated with the following:

• Migraine

• Peripheral vasospasm, Raynaud syndrome

• Generalized peripheral vascular endothelial dysfunction[7]

• Ocular circulation insufficiency (lower ocular pulse amplitude)[7]

• Increased resistance index in the central retinal artery (role in progression of visual field defect)[8]

• Impaired vascular autoregulation (prolonged arteriovenous venous passage time in relation to ocular perfusion)[9]

• Autoimmune disorders

• Systemic vascular disease (ie, atherosclerotic disease, cerebrovascular insufficiency)[10]

• Systemic nocturnal hypotension

• Sleep apnea (decreases oxygen saturation)

Permanent loss of vision can occur if low-tension glaucoma is not detected early.

Blood tests in low-tension glaucoma (LTG) that may be considered depending on the clinical presentation include the following:

• Order a CBC count to rule out anemia.
• Erythrocyte sedimentation rate (ESR) rarely is elevated in low-tension glaucoma and typically is obtained in cases of decreased central acuity with a pale nerve to rule out anterior ischemic optic neuropathy (AION) depending on the tempo of vision loss.
• Order rapid plasma reagent (RPR) and fluorescein treponema antibody (FTA) testing.
• Checking for the presence of antinuclear antibody (ANA) is recommended to rule out collagen-vascular and autoimmune diseases. Screening for extractable nuclear antigens (ie, Ro, La, Sm) also is recommended to rule out autoimmune diseases.
• Serum immunofixation for monoclonal gammopathy is indicated. Approximately 10% of patients with low-tension glaucoma have monoclonal gammopathy (paraproteinemia), which represents a benign condition two thirds of the time. However, lymphoproliferative disorders (ie, cancers) need to be ruled out by a hemato-oncology specialist if results from this test are positive.
• Mitochondrial testing for Leber optic neuropathy
• Anticardiolipin antibody (ACA) testing should be performed, and an increased level is considered a risk factor for visual-field defect progression. ^[11]

Optic nerve head and/or retinal nerve fiber analysis

Optic nerve head and/or retinal nerve fiber analysis may be helpful in diagnosing and monitoring progression of glaucomatous optic neuropathy.

Analyze optic nerve head with confocal scanning laser ophthalmoscopy (SLO), eg, Heidelberg Retinal Tomograph, or optical coherence topography (OCT).

Analyze retinal nerve fiber with confocal SLO, OCT, or scanning laser polarimetry (GDx). Often, retinal nerve fiber layer changes may occur before any changes on visual-field testing. Most often, nerve fiber layer thinning occurs first in the superior and inferior poles.

Neuroimaging of orbits and head

MRI is the preferred imaging modality compared with CT scanning because of its higher sensitivity in ruling out tumors that cause compressive optic neuropathy.[12]

Controversy exists as to whether neuroimaging should be performed routinely. Consider referral to a neurophthalmologist upon doubt.

Neuroimaging should be performed in any patient with the following:

• Markedly asymmetric disease
• Increased optic disc pallor relative to cupping
• Unusual visual-field defects, particularly those with respect to the vertical midline
• Rapid progression of visual fields
• Rapid progression of optic neuropathies
• Dyschromatopsia
• Afferent papillary defect with mild cupping

Carotid Doppler testing

If indicated, carotid Doppler testing is recommended to rule out carotid insufficiency.

Chest radiography

Chest radiography may be considered to rule out sarcoidosis.

To rule out nocturnal hypotension, 24-hour ambulatory blood pressure monitoring or sleep study may be considered.

The diurnal tension curve may need to be determined. Although IOP may be normal during an examination, the patient may have intermittent spikes in IOP throughout the day that may explain optic nerve and visual field damage and diagnose the condition as primary open-angle glaucoma.

Multifocal electroretinograms (mfERGs) provides an index of identification for a glaucomatous optic neuropathy in normal-tension glaucoma.[13]

Future diagnostic modalities - Ocular blood flow analysis (see below)

• Scanning laser ophthalmoscopy - Retinal and choroidal, superficial optic nerve head
• Doppler ultrasonography - Carotid arteries
• Confocal scanning laser Doppler flowmetry (Heidelberg Retinal Flowmetry) - Short posterior ciliary artery circulation, optic nerve head
• Diffuse tension MRI (DTI) - Reduction of the optic radiation volume in patients with normal-tension glaucoma, in relation to arterial hypertension and cerebral microangiopathy stage ^[14]

Findings include posterior deformation of the cribriform plate, with compression of the lamina due to direct deformation by secondary vascular compression, resulting in glial atrophy.

In low-tension glaucoma (LTG), the aim of IOP-lowering medications is for a reduction of at least 30%.

Also see the following clinical guideline summaries:

• US Preventive Services Task Force - Screening for glaucoma: recommendation statement[15]

• American Academy of Ophthalmology - Primary open-angle glaucoma[16]

• American Optometric Association - Comprehensive adult eye and vision examination[17]

Argon laser trabeculoplasty (ALT): This procedure may have minimal effect because the intraocular pressure (IOP) is already in the reference range.

Selective laser trabeculoplasty (SLT): SLT targets pigment-producing cells in the trabecular meshwork with less tissue destruction and scarring compared with ALT.

Trabeculectomy: If medical therapy is ineffective, adjunctive antimetabolite therapy likely is needed for postoperative IOP to be in the single digits. A higher risk of hypotony and endophthalmitis exists when targeting extremely low pressures that may be needed to retard or prevent progression of field loss.

Neurophthalmologist consultation can be ordered to rule out compressive optic neuropathy (as indicated).

An increase in salt intake may be recommended if the patient's diastolic blood pressure is significantly lower than the systolic blood pressure (ie, >70 mm Hg). However, controversy exists regarding this recommendation. Exercise caution in those patients with vascular or cardiac disease.

No restrictions on activity are indicated.

After obtaining baseline optic disc photos and/or analysis and visual fields, patients should receive regular follow-up care (eg, at least every 6 months) to monitor for progression of field loss and optic nerve tissue in low-tension glaucoma (LTG).

Evaluate risk factors for defective visual-field progression linked to the following 4 independent predictive factors determined by the Canadian Glaucoma Study[22] :

• Abnormal anticardiolipin antibody level

• Higher mean intraocular pressure (IOP) at follow up

• Higher baseline age

• Female sex

The goals of pharmacotherapy are to reduce IOP and morbidity and to prevent complications. The goal of therapy with IOP-lowering medications is for a reduction of at least 30%. Nonselective beta-blockers (eg, timolol maleate, levobunolol) are controversial because as visual-field progression is possibly due to secondary aggravated nocturnal arterial hypotension.[18, 19] A systematic review and meta-analysis of 15 randomized clinical trials studying IOP-lowering agents for treatment of normal-tension glaucoma determined that latanoprost, bimatoprost, and timolol were most effective.[20]

Medications for neuroprotection are as follows:

• Calcium channel blockers - Less progression[21]

• Betaxolol - Improved choroidal flow, better visual-field preservation

• Dorzolamide - Increased retinal blood flow velocity in humans

• Brimonidine - Increased retinal ganglion cell survival in rat optic nerve crush injury

Future medications include the following:

• N -methyl-D-aspartate (NMDA) receptor antagonist (Memantine) - Prevents binding of glutamate and resultant calcium influx; blocks rat ganglion cells from glutamate toxicity in rats and blocks toxic level of glutamate in vitreous

• Serotonin S2 receptor antagonist (Naftidrofuryl) - Arteriolar vasodilation, improved blood flow in Raynaud syndrome

• Glutamate antagonists

• Monoamine oxidase inhibitors (Deprenyl) - Neuroprotection in rat crush model

• Neurotrophic factors (Neurotrophins) - Retard apoptosis in cell culture

• Free radical scavengers - Ginkgo biloba extract scavenges free radicals and nitric oxide, improves blood flow (60-120 mg bid)

• Cannabinoids (marijuana) - Reduces IOP with NMDA antagonist and antioxidant activity

Class Summary

Decrease IOP pressure by reducing aqueous humor production.

Brimonidine (Alphagan)

Selective alpha2-receptor that reduces aqueous humor formation and may increase uveoscleral outflow or inhibit inflow.

Class Summary

By slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport, may inhibit carbonic anhydrase in the ciliary processes of the eye. This effect may decrease aqueous humor secretion, reducing IOP.

Dorzolamide (Trusopt)

Used concomitantly with other topical ophthalmic drug products to lower IOP. If more than 1 ophthalmic drug is being used, administer the drugs at least 10 min apart. Reversibly inhibits carbonic anhydrase, reducing hydrogen ion secretion at renal tubule and increasing renal excretion of sodium, potassium bicarbonate, and water to decrease production of aqueous humor.

Class Summary

The exact mechanism of ocular antihypertensive action is not established, but it appears to be a reduction of aqueous humor production or inhibition of inflow.

Timolol ophthalmic (Timoptic XE, Timoptic, Blocadren)

May reduce elevated and normal IOP with or without glaucoma by inhibiting inflow.

Levobunolol (AKBeta, Betagan)

Nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production and possibly increasing outflow of aqueous humor.

Betaxolol ophthalmic (Betoptic)

Indicated for glaucoma. Selectively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors. Reduces IOP by reducing production of aqueous humor.

Class Summary

For reduction of IOP in patients intolerant to other IOP-lowering medications or who do not respond optimally to other IOP-lowering medications.

Travoprost ophthalmic solution (Travatan)

Prostaglandin F2-alpha analog. Selective FP prostanoid receptor agonist believed to reduce IOP by increasing uveoscleral outflow. Used to treat open-angle glaucoma or ocular hypertension.

Unoprostone ophthalmic solution (Rescula)

Prostaglandin F2-alpha analog. Selective FP prostanoid receptor agonist believed to reduce IOP by increasing uveoscleral outflow. Used to treat open-angle glaucoma or ocular hypertension.

Bimatoprost ophthalmic solution (Lumigan)

A prostamide analogue with ocular hypotensive activity. Mimics the IOP-lowering activity of prostamides via the prostamide pathway. Used to reduce IOP in open-angle glaucoma or ocular hypertension.

Latanoprost (Xalatan, Xelpros)

May decrease IOP by increasing outflow of aqueous humor.