Normal Tension Glaucoma: How low should we go?

Normal tension glaucoma (NTG) is a term used to describe typical optic nerve cupping and visual field loss in the face of an intraocular pressure (IOP) in the normal range for the population (10-21 mmHg). Features such as optic nerve pallor, young age, central vision loss, or neurologic signs should prompt an appropriate workup, including imaging, but in a typical case, a specific etiology is rarely found. In one sense NTG may be a disease of increased optic nerve susceptibility to a relatively normal IOP. But can we define all NTG in the same way? If not, how do we separate them out?

The source of optic nerve damage in this disease is largely unknown, but vascular and mechanical factors have been implicated. A mechanical weakness in the optic nerve could lead to decreased resistance within the optic nerve head and susceptibility to even normal IOP. A defect in autoregulation of blood vessels could result in a poor compensatory response in some individuals to elevated IOP. Nocturnal hypotension could play a role in some cases, and nighttime dosing of systemic antihypertensives should be examined carefully. Intraocular pressure reduction reduces the incidence of progressive nerve damage in NTG patients as a whole, though some patients appear to have an IOP-independent mechanism for their glaucoma.

Much of our knowledge of the course of normal tension glaucoma comes from the multicenter Collaborative Normal Tension Glaucoma Study (CNGTS). About half of untreated patients with NTG progressed over 7 years in this study¹. That is a considerable risk, if you compare with the 10% of ocular hypertensives who develop glaucoma within 5 years. But this leaves roughly half of cases which developed glaucoma-like optic nerve damage at some point in life and remained stable for 7 years without treatment. In addition, lowering the pressure in a NTG patient by a similar percentage required of other glaucoma patients may be considerably more difficult and fraught with risk. Is there any way to separate these patients out? If not, who do we treat?

Some predictive factors for progression were pulled out of the CNTGS analysis. Progression was MORE COMMON in women, patients with migraines, and the presence of disc hemorrhages². Progression occurred MORE QUICKLY in women, especially those with migraines. Another paper from the CNGTS reported that patients with disc hemorrhages at baseline and cardiovascular risk factors were LESS LIKELY TO BENEFIT FROM TREATMENT, while women and patients with family history of glaucoma were MORE LIKELY to benefit³. In other words, patients with cardiovascular risk factors and disc hemorrhages may have a less pressure dependent process (hypothesis).

The CNTGS authors caution that given the considerable proportion of nonprogressors, the natural history must be carefully considered before deciding on surgery. Medical therapy may be easily justified in many cases. Adequate, multiple baseline pressure readings are crucial to determine a goal. A diurnal curve may reveal higher peaks in the IOP. A monocular trial may be particularly helpful in deciding on whether a particular medical therapy is helpful and tolerable to the patient. Pachymetry in these instances may help reset the bar for medical therapy, especially if a thin cornea is discovered. A patient achieving a pressure lowering from 12 to 8 will have achieved a 33% pressure reduction. As prostaglandins work via uveoscleral outflow, there may be particular advantage when working around episceral venous pressure. The neuroprotective effects of brimonidine have yet to be demonstrated, though a multicenter clinical trial is under way. Laser trabeculoplasty may be disappointing in patients with low starting pressures.

If a patient is inexorably deteriorating, surgery should be strongly considered. However, further deterioration of pressure in the face of an ostensibly well-controlled IOP (near episcleral venous pressure) should be regarded with healthy skepticism. Visual fields should be repeated several times before deterioration is confirmed. The time course of the progression, the life expectancy of the patient, the sight in the fellow eye, and the severity of disease in each eye should also be considered.

References:

1. Anderson DR, Drance SM, Schulzer M; Collaborative Normal-Tension Glaucoma Study Group. Natural history of normal-tension glaucoma. Ophthalmology. 2001 Feb;108(2):247-53.
2. Drance S, Anderson DR, Schulzer M; Collaborative Normal-Tension Glaucoma Study Group. Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol. 2001 Jun;131(6):699-708.
3. Anderson DR, Drance SM, Schulzer M; Collaborative Normal-Tension Glaucoma Study Group. Factors that predict the benefit of lowering intraocular pressure in normal tension glaucoma. Am J Ophthalmol. 2003 Nov;136(5):820-9.

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