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abnormal IOP. The traditionally used threshold of 21 mmHg as the line between normal and high IOP is an arbitrary distinction. It is based on an IOP level that is two standard deviations above the mean, for a Gaussian distribution of IOPs within a Caucasian population. Also, the exact mechanisms that cause POAG have not yet been clarified. Once these mechanisms become better elucidated, we may have some resolution to this debate. Regardless of how NTG is presently categorized, this debate underscores the likelihood that there are many unknown and variable factors that influence glaucomatous visual field loss.

Epidemiology

Population-based studies have shown NTG to be more common than originally expected, with a prevalence of 40–75% of individuals with newly diagnosed chronic open-angle glaucoma (Allingham et al., 2005). The prevalence varies with race and ethnicity, with the Japanese having a higher prevalence of NTG as a proportion of POAG (Shiose et al., 1991). When compared with high-pressure POAG, NTG occurs at an older age. Geijssen reported a mean age of 66.5 years for NTG patients in contrast to a younger mean age of 51.7 years for high-pressure POAG patients (Geijssen, 1991). Also, the mean age of NTG patients in the Low-Pressure Glaucoma Treatment Study was 64.9 years (Krupin et al., 2005).

Clinical features

Optic disk

There are several studies that demonstrate a difference in patterns of optic disk damage in NTG compared with POAG associated with high IOP. The neuroretinal rim has been shown to be thinner in NTG, especially inferiorly and infratemporally, when compared to POAG patients matched for total visual field loss (Simmons et al., 2004; Allingham et al., 2005). In addition, the retinal nerve fiber layer defects are more localized and central in NTG, while these defects tend to be

more diffuse and peripheral in POAG (Woo et al., 2003). This is in accordance with a previous report which showed that inferotemporal notching of the optic disk occurred more often in NTG in contrast to generalized cupping of the disk, which was associated with POAG (Caprioli and Spaeth, 1985). Some experts further divide NTG into two groups based on optic disk appearance: (1) focal ischemic glaucoma and (2) senile sclerotic glaucoma. The focal ischemic group has deep focal notching in the neural rim, while the senile sclerotic group has shallow pale sloping of the neuroretinal rim and is usually found in older patients with vascular disease (Simmons et al., 2004) (Figs. 1–4). It is important for the clinical ophthalmologist to realize, however, that any pattern of glaucomatous optic disk and nerve fiber layer damage can be seen with NTG.

Optic disk hemorrhage has been associated with NTG in several studies (Allingham et al., 2005; Krupin et al., 2005) and has also been shown to be a predictive factor for progression (Martus et al., 2005), pointing to vascular disease as a possible mechanism for this pathology (Fig. 5). One study found that in NTG an inferior area of peripapillary atrophy correlated with superior hemifield visual field damage, but a corresponding relationship was not found with superior peripapillary atrophy (Kawano et al., 2006) (Fig. 6). A clinician who sees either of these findings (disk hemorrhage or inferior peripapillary atrophy) in an NTG patient can expect to see visual field damage and should consider more aggressive treatment.

Visual field

There is some evidence that the visual field defects that are associated with NTG are more focal, deeper and occur earlier in the disease course when compared with POAG with higher IOP (Simmons et al., 2004; Allingham et al., 2005) (Figs. 1–7). While some studies have shown that the visual field defects are closer to fixation in NTG (Caprioli and Spaeth, 1984), there have been conflicting reports. This discrepancy may be due to different testing methods. Often the initial defect seen in NTG is a dense paracentral scotoma possibly encroaching on fixation (Simmons et al., 2004). This may be

due to a selection bias as patients are more likely to notice a central visual field defect than a peripheral visual field defect. Therefore, it is not unusual for patients with NTG to present with a complaint of central visual field loss.

Central corneal thickness

One small study has shown that the central corneal thickness (CCT) is significantly lower in NTG when it is compared to POAG and to age matched healthy subjects (Morad et al., 1998). The possible

implication of this study is that thinner CCT may lead to falsely low measurements of IOP and misdiagnosis of POAG patients as NTG. Alternatively, thinner CCT may intrinsically be related to an increased optic nerve susceptibility, for as yet unknown reasons.

Disease course

The disease course of NTG is highly variable, and ranges from long-term stability to slowly progressive to rapidly progressive. In addition, some NTG

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patients show episodic progression. The Collaborative Normal-Tension Glaucoma Study (CNTGS) demonstrates this variability well. In this study, 65% of NTG patients did not show any progression

despite not receiving any treatment. Conversely, 12% of NTG patients showed progression in spite of aggressive reduction of IOP by 30% (CNTGS, 1998a, b). There is, however, no reliable method for