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.
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.
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.
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.
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.
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
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]
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
Clinical Context:
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.
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.
Clinical Context:
Nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production and possibly increasing outflow of aqueous humor.
Clinical Context:
Indicated for glaucoma. Selectively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors. Reduces IOP by reducing production of aqueous humor.
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.
Clinical Context:
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.
Mitchell V Gossman, MD, Partner and Vice President, Eye Surgeons and Physicians, PA; Medical Director, Central Minnesota Surgical Center; Clinical Associate Professor, University of Minnesota Medical School
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Martin B Wax, MD, Professor, Department of Ophthalmology, University of Texas Southwestern Medical School; Vice President, Research and Development, Head, Ophthalmology Discovery Research and Preclinical Sciences, Alcon Laboratories, Inc
Disclosure: Nothing to disclose.
Chief Editor
Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Additional Contributors
Baseer U Khan, MD,
Disclosure: Nothing to disclose.
Iqbal Ike K Ahmed, MD, FRCSC, Clinical Assistant Professor, Department of Ophthalmology, University of Utah
Disclosure: Nothing to disclose.
Jacqueline Freudenthal, MD, Co-Investigator, Ophthalmic Consultants Centre, Toronto
Disclosure: Nothing to disclose.
Khalid Hasanee, MD, Glaucoma and Anterior Segment Fellow, Department of Ophthalmology, University of Toronto
Disclosure: Nothing to disclose.
Neil T Choplin, MD, Adjunct Clinical Professor, Department of Surgery, Section of Ophthalmology, Uniformed Services University of Health Sciences
Kim KCY, Ahn AMD, Seong SGJ. Does redefining of high intraocular pressure (IOP) according to IOP distribution change prevalence of normal tension glaucoma in Korea? [abstract]. World Glaucoma Congress, 2009. Available at http://www.worldglaucoma.org/WGC/WGC2009/index.php. Accessed: July 24, 2009.
Paul T, Radcliffe N, Shimmio M. Reclassification of normal and high tension glaucoma eyes using corneal compensated IOP [abstract]. World Glaucoma Congress, 2009. Available at http://www.worldglaucoma.org/WGC2009/. Accessed: July 28, 2009.
Akopov E, Astakhov Y, Nefedova D. Retinal vessels calibrometry in normal pressure glaucoma evaluation [abstract]. World Glaucoma Congress, 2009. Available at http://www.worldglaucoma.org/WGC/WGC2009/index.php. Accessed: July 28, 2009.
Michelson G, Waerntges S, Engelhorn T, Doerfler A. Reduced optic radiation volume measured by DTI is correlated by arterial hypertension in normal tension glaucoma [abstract]. World Glaucoma Congress, 2009. Available at http://www.worldglaucoma.org/WGC/WGC2009/index.php. Accessed: July 28,2009.
[Guideline] Screening for glaucoma: recommendation statement. US Preventive Services Task Force. National Guideline Clearinghouse. 2005 Mar.
[Guideline] Primary open-angle glaucoma. American Academy of Ophthalmology. National Guideline Clearinghouse. 2005.
[Guideline] Comprehensive adult eye and vision examination. American Optometric Association. National Guideline Clearinghouse. 2005.
Takako Nakagami, Yoshio Yamazaki, Fukuko Hayamizu. Prognostic Factors for Progression of Visual Field Damage in Patients with Normal-Tension Glaucoma. Japanese Journal of Ophthalmology. January, 2006. Volume 50, Number 1:38-42.
Kurtz S, Haber I, Kesler A. Corneal Thickness Measurements in Normal-tension Glaucoma Workups: Is It Worth the Effort?. J Glaucoma. 2009 Apr 15 [Epub ahead of print].
Stewart WC, Reid KK. Incidence of systemic and ocular disease that may mimic low-tension glaucoma. J Glaucoma. 1992. 1:27-31.
