eMedicine Specialties > Ophthalmology > Intraocular Pressure

Glaucoma, Low Tension

Iqbal Ike K Ahmed, MD, FRCSC, Clinical Assistant Professor, Department of Ophthalmology, University of Utah
Baseer U Khan, MD, Staff Physician, Department of Ophthalmology, University of Toronto, Canada; Khalid Hasanee, MD, Glaucoma and Anterior Segment Fellow, Department of Ophthalmology, University of Toronto

Updated: Jun 22, 2006

Introduction

Background

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.

Pathophysiology

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

Frequency

United States

Up to 15-25% of patients with POAG experience LTG. 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

An increased prevalence of LTG exists in Japan.

Mortality/Morbidity

Loss of peripheral vision is associated with LTG.

Race

An increased prevalence of LTG exists in Japan.

Sex

LTG is more common in females than in males.

Age

The mean age of patients with LTG is 60 years; they are older than patients with POAG.

Clinical

History

• Ocular history
• Steroid use
• Trauma
• Vasospasm
  • Raynaud syndrome
  • Migraines
• Coagulopathies - Previous blood loss or shocklike episode
• Systemic nocturnal hypotension (notably in older thin, Caucasian women)
• Autoimmune disorders (Patients often have evidence of other autoimmune diseases.)
• Systemic vascular disease
• Thyroid disease - Increased incidence of thyroid disease in patients with LTG (6 out 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

• Conduct general medical examination (eg, blood pressure, carotid arteries).
• Rule out ocular hypertension and POAG.
• Refractive error - Myopia
• Cornea
  • Keratic precipitates indicating uveitis
  • Krukenberg spindle indicating pigment dispersion
• Iris - Transillumination defects or pigment dusting indicating pigment dispersion
• Anterior chamber
  • By definition, LTG 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
• IOP
  • Perform diurnal curve (should be <22 mm Hg).
  • May be asymmetric
  • Higher IOP in left eye (related to blood flow from carotid arteries)
• Myopic - Greatest risk of progression
• Senile sclerotic - Older with vascular disease
• Focal ischemic - May be younger
• Optic disc in LTG 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
  • Disc hemorrhages
  • Acquired pit
• Retina - Arteriosclerotic changes indicating vascular disease
• Visual fields in LTG as compared to high-tension glaucoma (controversial)
  • Focal
  • Closer to fixation
  • Deeper
• Blood pressure - Nocturnal hypotension
• Carotid bruit indicating carotid insufficiency

Causes

LTG is associated with the following:

• Migraine
• Peripheral vasospasm, Raynaud syndrome
• Autoimmune disorders
• Systemic vascular disease (ie, atherosclerotic disease)
• Systemic nocturnal hypotension
• Sleep apnea (decreases oxygen saturation)

Differential Diagnoses

Other Problems to Be Considered

Intermittent IOP elevation
Burned-out glaucoma
Nonglaucomatous optic nerve
Congenital disc anomalies/cupping
Myopia with peripapillary atrophy
Optic nerve coloboma/pit
Vascular etiology
Carotid and ophthalmic artery occlusion
Previous blood loss or shocklike episode
Neurologic etiology
Hereditary optic neuropathy
Leber optic atrophy
Dominant or recessive optic atrophy
Tonometric error (thin cornea)

Workup

Laboratory Studies

• Perform blood tests
  • CBC (rule out anemia)
  • Erythrocyte sedimentation rate (ESR) rarely is elevated in LTG and typically is obtained in cases of decreased central acuity with a pale nerve to rule out anterior ischemic optic neuropathy (AION).
  • Rapid plasma reagent (RPR), fluorescein treponema antibody (FTA)
  • 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 LTG 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 this test is positive.
  • High-sensitivity C reactive protein is becoming the criterion standard for documenting both symptomatic and nonsymptomatic ischemic heart disease and is often positive in patients with LTG.
  • Mitochondrial testing for Leber (when indicated)

Imaging Studies

• 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 to CT scan because of its higher sensitivity.
  • Controversy exists as to whether neuroimaging should be performed routinely. Some advocate referral to neuroophthalmology if concerned.
  • Neuroimaging should be performed in any case 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
• If indicated, carotid Dopplers are recommended to rule out carotid insufficiency.
• When indicated, a chest x-ray is necessary to rule out sarcoidosis.

Other Tests

• To rule out nocturnal hypotension, 24-hour ambulatory blood pressure monitoring is advised.
• Diurnal tension curve: 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.
• Future diagnostic modalities - Ocular blood flow analysis
  • SLO - Retinal and choroidal, superficial optic nerve head
  • Doppler ultrasound - Carotid arteries
  • Confocal scanning laser Doppler flowmetry (Heidelberg Retinal Flowmetry) - Short PCA circulation, optic nerve head

Histologic Findings

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

Treatment

Medical Care

• The aim of IOP-lowering medications is for a reduction of at least 30%.

Surgical Care

• Argon laser trabeculoplasty (ALT): This procedure has minimal effects because the IOP is already in the reference range.
• Selective laser trabeculoplasty (SLT): This procedure is another alternative. SLT targets pigment-producing cells in the trabecular meshwork with less tissue destruction and scarring as compared to ALT.
• Trabeculectomy: If medical therapy is ineffective, adjunctive antimetabolite therapy likely is needed for postoperative IOP to be in the single digits. Significant risk of hypotony and endophthalmitis exists.

Consultations

• Neuroophthalmology consult to rule out compressive optic neuropathy (as indicated)

Diet

• 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.

Activity

• No restrictions on activity are indicated.

Medication

The goals of pharmacotherapy are to reduce IOP and morbidity and to prevent complications.

The aim of IOP-lowering medications is for a reduction of at least 30%. Nonselective beta-blockers (eg, timolol maleate, levobunolol) are controversial.

Medications for neuroprotection are as follows:

• Calcium channel blockers - Less progression
• 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 RGC 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

Alpha2-adrenergic agonists

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.

Dosing

Adult

1 gtt in affected eye(s) tid

Pediatric

Not established

Interactions

Coadministration with topical beta-blockers may further decrease IOP; tricyclic antidepressants may decrease effects of brimonidine; CNS depressants, such as barbiturates, opiates, and sedatives, may potentiate effects of brimonidine

Contraindications

Documented hypersensitivity; patients receiving MAOI therapy

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

May exacerbate or precipitate ocular irritation, topical sensitivity, vasovagal attack, and optic nerve ischemia in patients with advanced glaucomatous optic neuropathy

Carbonic anhydrase inhibitors

By slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport, it 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.

Dosing

Adult

1 gtt in affected eye(s) tid

Pediatric

Not established

Interactions

Coadministration with high-dose salicylate therapy may increase toxicity; may have additive systemic effects if patient is already on oral carbonic anhydrase inhibitors

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with chronic administration of dorzolamide; discontinue therapy and evaluate patient before restarting therapy

Beta-adrenergic blockers

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.

Dosing

Adult

1 gtt of 0.25% or 0.5% in affected eye(s) bid; if IOP is maintained at satisfactory levels, change dosage to 1 gtt in affected eye(s) qd; if clinical response not adequate, change dosage to 1 gtt of 0.5% solution in affected eye(s) bid; if IOP is still not at satisfactory level, consider concomitant therapy

Pediatric

Administer as in adults

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; bronchial asthma; sinus bradycardia; second- and third-degree AV block; severe chronic obstructive pulmonary disease; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Product may have sulfites, which may cause allergic-type reactions in susceptible patients; may exacerbate or precipitate heart block, asthma, chronic obstructive pulmonary disease, and mental changes (especially in elderly patients)

Levobunolol (AKBeta, Betagan)

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

Dosing

Adult

0.5% solution: 1-2 gtt in affected eye(s) qd
0.25% solution: 1-2 gtt in affected eye(s) bid
Severe or uncontrolled glaucoma: 0.5% solution bid; closely monitor patient; > 1 gtt (0.5% levobunolol) bid not shown to be more effective; if IOP not at satisfactory level on this regimen, concomitant therapy can be instituted; do not administer 2 or more topical ophthalmic beta-adrenergic blocking agents simultaneously

Pediatric

Not established

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; bronchial asthma; severe chronic obstructive pulmonary disease; sinus bradycardia; second- and third-degree AV block; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Beta-blockade may potentiate muscle weakness that is consistent with certain myasthenic symptoms (eg, diplopia, ptosis, generalized weakness); product may have sulfites, which may cause allergic-type reactions in certain susceptible persons

Betaxolol (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.

Dosing

Adult

1-2 gtt in affected eye(s) bid; consider concomitant therapy if IOP is not at satisfactory level

Pediatric

Not established

Interactions

May have additive systemic effects if patient is already on systemic beta-blockers

Contraindications

Documented hypersensitivity; bronchial asthma; severe chronic obstructive pulmonary disease; sinus bradycardia; second- and third-degree AV block; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Beta-blockade may potentiate muscle weakness consistent with myasthenic symptoms; product may have sulfites, which may cause hypersensitivity reactions in susceptible persons

Prostaglandin agonists

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.

Dosing

Adult

1 gtt in affected eye(s) hs; not to exceed 1 dose/d

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; signs of inflammation; pregnancy

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Commonly causes ocular hyperemia; may cause permanent increase in pigment to iris (ie, increases brown pigment) and eyelid; may increase eyelash growth; may cause bacterial keratitis; caution in uveitis or macular edema; do not instill if wearing contact lenses

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.

Dosing

Adult

Instill 1 gtt in affected eye(s) bid

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; signs of inflammation

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Commonly causes ocular hyperemia; may cause permanent increase in pigment to iris (ie, increases brown pigment) and eyelid; may increase eyelash growth; may cause bacterial keratitis; caution in uveitis or macular edema; do not instill if wearing contact lenses

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.

Dosing

Adult

Instill 1 gtt of 0.03% solution in affected eye(s) hs; not to exceed 1 dose/d

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; signs of inflammation

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

May cause permanent increase in pigment to iris (ie, increases brown pigment) and eyelid; may increase eyelash growth; may cause bacterial keratitis; caution in uveitis or macular edema; do not instill if wearing contact lenses

Latanoprost (Xalatan)

May decrease IOP by increasing outflow of aqueous humor.

Dosing

Adult

1 gtt (1.5 mcg) in affected eye(s) qd in evening; higher frequency administrations may decrease effectiveness

Pediatric

Not established

Interactions

Coadministration with eye drops containing the preservative thimerosal may reduce effects (administer at intervals of 5 min between applications)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Do not administer while wearing contact lenses; may increase brown pigment in iris and gradually change eye color (unknown effect)

Follow-up

Further Outpatient Care

• After obtaining baseline optic disc photos and/or analysis and visual fields, patients should receive regular follow-up care (ie, every 6 mo) to monitor for progression of this condition.

Complications

• Permanent loss of vision can occur if this condition is not detected early.

Patient Education

• For excellent patient education resources, visit eMedicine's Glaucoma Center. Also, see eMedicine's patient education articles Normal-Tension Glaucoma, Glaucoma Overview, Glaucoma FAQs, and Understanding Glaucoma Medications.

Miscellaneous

Medicolegal Pitfalls

• With excavation of the optic disc and changes of the visual field, identification of the cause is essential.

References

1. Abedin S, Simmons RJ, Grant WM. Progressive low-tension glaucoma: treatment to stop glaucomatous cupping and field loss when these progress despite normal intraocular pressure. Ophthalmology. Jan 1982;89(1):1-6. [Medline].

2. Fraunfelder FT, Roy FH. Current Ocular Therapy. Philadelphia: WB Saunders;2000: 488-9.

3. Hitchings RA. Low tension glaucoma--its place in modern glaucoma practice. Br J Ophthalmol. Aug 1992;76(8):494-6. [Medline].

4. Netland PA, Chaturvedi N, Dreyer EB. Calcium channel blockers in the management of low-tension and open-angle glaucoma. Am J Ophthalmol. May 15 1993;115(5):608-13. [Medline].

5. Stewart WC, Reid KK. Incidence of systemic and ocular disease that may mimic low-tension glaucoma. J Glaucoma. 1992;1:27-31.

6. Werner E. Progressive normal-tension glaucoma. I. Analysis. J Glaucoma. Dec 1996;5(6):422-6. [Medline].

Keywords

LTG, low-pressure glaucoma, optic neuropathy, intraocular pressure, primary open-angle glaucoma, POAG

Contributor Information and Disclosures

Author

Iqbal Ike K Ahmed, MD, FRCSC, Clinical Assistant Professor, Department of Ophthalmology, University of Utah
Iqbal Ike K Ahmed, MD, FRCSC is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Canadian Ophthalmological Society, and Ontario Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Baseer U Khan, MD, Staff Physician, Department of Ophthalmology, University of Toronto, Canada
Baseer U Khan, MD is a member of the following medical societies: Canadian Ophthalmological Society
Disclosure: Nothing to disclose.

Khalid Hasanee, MD, Glaucoma and Anterior Segment Fellow, Department of Ophthalmology, University of Toronto
Khalid Hasanee, MD is a member of the following medical societies: Canadian Medical Association, Canadian Ophthalmological Society, and Ontario Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Neil T Choplin, MD, Adjunct Clinical Professor, Department of Surgery, Section of Ophthalmology, Uniformed Services University of Health Sciences
Neil T Choplin, MD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, Association for Research in Vision and Ophthalmology, and California Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Martin B Wax, MD, Clinical Professor, Department of Ophthalmology, University of Texas Southwestern Medical School; Vice President, Ophthalmology Research and Development, Head, Ophthalmology Discovery Research, Alcon Labs, Inc
Martin B Wax, MD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Society for Neuroscience
Disclosure: Alcon Labs Salary Employment

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

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