pressure monitoring of patients with NTG, POAG and anterior ischemic optic neuropathy and found significantly lower nocturnal diastolic blood pressure and a significantly greater mean decrease in nocturnal diastolic blood pressure in NTG. In fact, they found an interesting relationship between systemic hypertension, visual field deterioration, and nocturnal hypotension: among patients taking medications for systemic hypertension, those who had progression of visual field defects had significantly greater drops in nocturnal blood pressure than those considered clinically stable. Another study by Hayreh et al. (1999) showed that patients who were using topical b-blockers had significantly greater dips in nocturnal diastolic blood pressure and patients with NTG receiving topical b-blockers had significant visual field progression more often than those not receiving b-blockers. In addition to vascular insufficiency, hematologic abnormalities, such as increased blood viscosity and hypercoagulability, have been associated with NTG. Magnetic resonance imaging studies in patients with NTG have shown an increased incidence of diffuse cerebral ischemia which is also consistent with a vascular etiology (Ong et al., 1995; Stroman et al., 1995).

Immune mechanisms

Other IOP-independent mechanisms of glaucomatous optic neuropathy are immunogenic etiologies. Several studies have shown that immune-related diseases occur at higher frequencies in patients with NTG (Cartwright et al., 1992; Wax et al., 1994; Romano et al., 1995). One study found that 30% of NTG patients had immune-related diseases compared to 8% of an ocular hypertension control group (Cartwright et al., 1992).

Despite some evidence linking ischemia and immunogenic mechanisms to glaucomatous optic neuropathy, current diagnostic and therapeutic procedures do not take these into consideration. Currently, the only proven modality for treatment of glaucoma is IOP reduction. Only with continued research will mechanisms of optic nerve damage in NTG be identified and the above factors more clearly elucidated. A better understanding of the various mechanisms causing

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glaucomatous nerve damage will allow for better and more targeted therapies.

Differential diagnosis

The differential diagnosis for NTG can be divided into two main categories, undetected high-tension glaucoma and nonglaucomatous optic nerve disease (Table 1).

Diagnostic evaluation

A medical history consisting of previous ocular diagnoses and treatments, family history, impact of visual function on daily living, and use of ocular and systemic medications should be obtained for each patient (Gaasterland et al., 2005). A history of previous hypotensive crises, such as myocardial infraction, shock, and hemorrhage, should also be elicited as this can cause visual field loss consistent with glaucoma but may be nonprogressive. A thorough medical history not only allows the clinician to effectively formulate a differential diagnosis but also brings to highlight any possible factors for noncompliance that may affect prognosis.

A complete ophthalmic physical examination should be performed on all new patients (Gaasterland et al., 2005). This includes pupil examination, slit-lamp anterior segment examination, IOP measurement, central corneal thickness, gonioscopy, optic nerve head and retinal nerve fiber layer evaluation, and visual field examination. The IOP should be measured with applanation tonometry before gonioscopy. If the patient is being dilated then IOP should be measured before and after dilation. If the disk damage does not correlate with the single IOP measurement then determining diurnal IOP fluctuations may be helpful. The optic nerve head and retinal nerve fiber layer evaluation should be performed with magnified stereoscopic visualization (slit-lamp biomicroscope) and preferably through a dilated pupil. IOP should be remeasured after dilation. Each time the optic nerve and retinal nerve fiber layer are examined it should be documented with photos or a detailed drawing. Automated static threshold perimetry is the recommended technique for evaluating the visual field.

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Table 1. Differential diagnosis of normal-tension glaucoma

Undetected high-tension glaucoma

POAG with wide diurnal IOP fluctuation

Intermittent IOP elevation J Angle-closure glaucoma J Glaucomatocyclitic crisis

Previous history of high IOP that has since normalized

‘‘Burnt-out’’ secondary glaucoma J Past history of steroid use

J Uveitic glaucoma

J Pigmentary glaucoma

J Past history of surgery or trauma

Use of medications that decrease IOP (masked IOP)

Tonometric error

Nonglaucomatous optic nerve disease

Compressive optic neuropathy J Vascular lesions

J Trauma J Tumors

–Pituitary tumors

–Optic nerve sheath meningioma

–Optic glioma

JGraves ophthalmopathy

Congenital anomalies

Hemodynamic shock optic neuropathy

Arteritic and nonarteritic ischemic optic neuropathy

Retinal disorders

Optic nerve drusen

Optic neuritis

Trauma

Methyl alcohol poisoning

Leber’s hereditary optic neuropathy

According to the Preferred Practice Patterns from the American Academy of Ophthalmology (Gaasterland et al., 2005), all follow-up glaucoma status evaluations should include a history and focused physical examination including visual acuity, slit-lamp biomicroscopy, and IOP with time of day measurement. Optic nerve head evaluation and documentation and visual field evaluation should be performed at the recommended intervals shown in Tables 2 and 3. Also gonioscopy should be performed periodically (every 1–5 years) if there is suspicion of an angleclosure component, shallowing of anterior chamber, or an unexplained rise in IOP.

Three common ancillary diagnostic tests for glaucoma are optical coherence tomography (OCT), nerve fiber layer polarimetry (GDx NFA), and confocal laser scanning tomography

Table 2. Recommended frequency of optic nerve head evaluation

Modified from Gaasterland et al. (2005).

Table 3. Recommended frequency of visual field evaluation

Modified from Gaasterland et al. (2005).

[Heidelberg Retinal Tomograph (HRT)]. Both OCT and GDx NFA analyze the thickness of the retinal nerve fiber layer. It is a known fact that reductions in retinal nerve fiber layer thickness precede visual field loss. In NTG patients with unilateral visual field defects, studies have shown that RNFL thinning is already present in fellow eyes (Kim et al., 2005). The HRT is a confocal laser scanning system that gives a quantitative assessment of the topography of the optic nerve head. Change in the topography of the optic nerve head, such as cupping and thinning of the neuroretinal rim, can precede measurable visual field defects in glaucoma. Since these tests are noninvasive and relatively comfortable for the patient, clinicians should consider adding the OCT, GDx, or HRT to their glaucoma evaluations as these ancillary tests may aid in detecting and following glaucomatous changes (Fig. 7).

If the clinical presentation is atypical, for example, unilateral or very asymmetric disease, decreased central visual acuity, or visual field loss not consistent with optic disk appearance, then further medical or neurological evaluation should be considered. Medical evaluation may consist of workup for anemia, cardiovascular disease, syphilis, and temporal arteritis. Routine neuroradiologic