By Joshua D. Stein, MD, MS, and Pratap Challa, MD
Edited by Ingrid U. Scott, MD, MPH, and Sharon Fekrat, MD
This article is from February 2007 and may contain outdated material.
Normal-tension glaucoma (NTG) is a form of open-angle glaucoma characterized by glaucomatous optic neuropathy in patients with IOP measurements consistently lower than 21 mmHg. Although NTG was once thought to be uncommon, the Beaver Dam Eye Study reported that nearly one-third of glaucoma patients can be classified as having NTG.1 Other studies have suggested that as many as two-thirds of Japanese patients with glaucoma have NTG.2
The etiology of NTG is unclear. Contributing factors may include vasospastic events, hypoperfusion, nocturnal hypotension, hypercoagulability and increased blood viscosity, and genetic factors. NTG has also been associated with migraine headaches, Raynaud’s phenomenon, diffuse cerebral ischemia and various autoimmune disorders.
Distinguishing NTG From Primary Open-Angle Glaucoma
Patients with NTG or primary open-angle glaucoma (POAG) present with open angles on gonioscopy, cupping of the optic nerve head and visual field loss. However, NTG has several distinguishing features. As the name implies, NTG patients have a higher propensity for optic nerve damage at relatively low levels of IOP. Visual field defects typically appear deeper, steeper and closer to fixation in patients with NTG than in patients with POAG. Also, the amount of visual field loss in NTG tends to be greater than one would expect on the basis of optic nerve appearance alone. As with other forms of glaucoma, patients with NTG who have asymmetrical IOP readings demonstrate greater visual field damage in the eye with the higher IOP. On ophthalmoscopy, patients with NTG tend to have more localized defects of the retinal nerve fiber layer and an increased propensity for optic disc hemorrhages compared with patients with POAG.
Significance of Disc Hemorrhages in Patients With NTG
Several studies have found a link between the presence of disc hemorrhages and NTG. Although uncommon, the presence of a disc, or Drance, hemorrhage can be a worrisome sign that the patient’s glaucoma is poorly controlled and that the patient will likely experience progression of loss in visual fields over the next 17 to 20 months.3 In a study of patients with NTG, Rasker and colleagues observed visual field progression of 8.2 percent per year among patients with disc hemorrhages compared with 3.6 percent per year among those without disc hemorrhages.4 Other investigators have noted that the presence of a disc hemorrhage not only signifies a risk of damage to the involved eye but may also predict damage to the contralateral eye.5
Assessing for the presence of a disc hemorrhage should be part of the routine ophthalmologic examination, and when a hemorrhage is found, optic nerve head photography should be performed for documentation.
Differential Diagnosis
NTG is a diagnosis of exclusion, and other ocular or systemic disorders need to be considered in the differential diagnosis.
Other types of glaucoma. Various forms of glaucoma present with intermittently elevated IOP simulating NTG. Burned-out open-angle glaucoma, a condition characterized by glaucomatous damage that occurred from years of elevated IOP that has since normalized, can simulate NTG. Other forms of glaucoma simulating NTG include POAG with diurnal IOP fluctuations, intermittent angle-closure glaucoma and secondary open-angle glaucomas, such as pigmentary glaucoma, when exercise or other activities result in IOP spikes that are not apparent on routine ophthalmological examination.
Thin central corneas. Also, patients with POAG who have thin central corneas, including those who have undergone refractive surgery, may have falsely low IOP readings that mimic NTG.
Other disorders of the optic nerve. Disorders of the optic nerve not caused by IOP elevations—including ischemic optic neuropathy, Leber’s hereditary optic neuropathy, optic nerve drusen, optic pits and compressive lesions of the optic nerve—should also be considered in the differential diagnosis.
Systemic disorders. Syphilis, tuberculosis, sarcoidosis and multiple sclerosis, for example, must be ruled out since they produce optic neuropathies that may mimic glaucoma.
Systemic drugs. Medications such as ethambutol and isoniazid can damage the optic nerve and cause optic neuropathy in a patient with normal IOP.
Because NTG is a bilateral condition, patients with unilateral optic neuropathy should be evaluated for other conditions affecting only one eye.
Workup
An evaluation to determine whether a patient has NTG should be done with a thorough history-taking. Specifically, the physician should inquire whether the patient has any systemic medical conditions associated with NTG, assess the types of medications the patient is taking, and determine whether there is a family history of glaucoma or NTG, whether the patient’s history is positive for ocular trauma or surgery, or whether the patient has symptoms suggesting elevated IOP from angle closure.
To exclude other conditions, the physician should perform a complete ophthalmologic examination, which should include BCVA, color vision, pupillary examination, tonometry, pachymetry, gonioscopy, standardized automated perimetry and a detailed evaluation of the optic nerve and nerve fiber layer. A diurnal IOP curve should be obtained to confirm that the patient is not developing IOP spikes at other times of the day that are resulting in glaucomatous optic neuropathy.
Adjunctive tests to rule out other conditions that mimic NTG include auscultation and palpation of the carotid arteries, exophthalmometry, 24-hour blood pressure monitoring, and laboratory testing for infectious or inflammatory conditions that can cause optic neuropathy.
Neuroimaging and consultation with a neuro-ophthalmologist may be necessary—especially if perimetry suggests that damage is further posterior in the visual pathway; if the optic nerve demonstrates more pallor than cupping; or if the patient is younger than 65 years of age and demonstrates rapid progression of optic nerve damage or marked asymmetry of damage between the two optic nerves.
Optic nerve head photography is important to document the status of the optic nerve at baseline and for future comparisons. Serial visual field testing and optic nerve and retinal nerve fiber layer imaging are useful to identify progression over time.
Treatment
It is important to identify and treat any underlying medical conditions associated with NTG, such as anemias, arrhythmias, hypothyroidism, autoimmune diseases and migraine headaches. The Collaborative Normal Tension Glaucoma Study demonstrated that a 30 percent reduction in IOP can prevent progression of visual field loss in half of patients with documented progression or a fixation threat.6
Pharmacologic treatment. Topical agents that can be used to reduce the IOP include prostaglandin analogs, alpha2 agonists, carbonic anhydrase inhibitors and miotics. Beta-blockers can also be used to lower the IOP; however, there is some controversy over whether they decrease perfusion and whether they should be used as first-line agents. Some studies have suggested that alpha2 agonists such as brimonidine may have additional neuroprotective effects on the optic nerve, but no conclusive evidence is available to date. Calcium channel blockers may be useful as adjunctive medical treatment, and studies are under way to assess the effectiveness of memantine in patients with NTG.
Surgical treatment. If medications are ineffective or if patient adherence to the recommended medical regimen is an issue, another option is laser trabeculoplasty. Patients who continue to progress despite maximum tolerated medical therapy may require filtration surgery.
The target IOP for patients with NTG is the IOP at which no further structural or functional disease progression is observed. NTG can be challenging to diagnose and manage; however, with effective IOP control, progression of visual field loss can be minimized.
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1 Klein, B. E. et al. Ophthalmology 1992;99(10):1499–1504.
2 Shiose, Y. et al. Jpn J Ophthalmol 1991;35(2):133–155.
3 Ishida, K. et al. Am J Ophthalmol 2000;127(6):707–714.
4 Arch Ophthalmol 1997;115(10):1257–1262.
5 Jonas, J. B. et al. Ophthalmology 2002;109(11):2078–2083.
6 Am J Ophthalmol 1998;126(4):498–505.
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Dr. Stein is a glaucoma fellow and Dr. Challa is an assistant professor of ophthalmology. Both are at Duke University.