Clinical Update: Normal Tension Glaucoma
Become definitive in your glaucoma diagnosis and don't rely on elevated IOP alone. Consider these other factors.
BY DEEPAK GUPTA, O.D., F.A.A.O., Stamford, Conn.
When we think of glaucoma, almost everyone thinks of elevated
IOP. However, normal tension glaucoma (NTG) occurs in the absence of elevated
IOP. In this article, we'll review the unique characteristics of normal tension glaucoma.
Of the three million Americans who have glaucoma, the medical community estimates that roughly 25% have
NTG. The Collaborative Normal-Tension Glaucoma Treatment Study (CNTGS) defines it as glaucoma that demonstrates the following three characteristics:
1. No single IOP reading ever greater than 24 mmHg.
2. A median IOP reading of below 20 mmHg.
3. Nine out of 10 readings
22 mmHg or lower.
Depending on who you ask, NTG is either a separate disease entity or simply a variation of primary open angle glaucoma
(POAG), or "high tension" glaucoma. One of the more popular theories on the etiology of NTG is that it involves a basic weakness of the lamina
cribosa, which permits mechanical damage to ganglion cell axons even at statistically "normal" IOP values.
Another popular theory involves vascular risk factors that ultimately contribute to optic nerve hypoperfusion and ischemic damage. Much of this theory revolves around the observation that NTG patients have both decreased blood flow velocity and increased vascular resistance in the ophthalmic artery, central retinal artery and posterior ciliary arteries.
Telling the two apart
As is the case with
POAG, considerable variation exists in the clinical presentation of NTG. Even so, certain characteristics will help you differentiate between the two entities.
Most practitioners consider normal IOP to range between 10 mmHg and 21 mmHg, but realize that "normal" IOP refers to a statistical average and not to a disease-free state. The Baltimore Eye Survey emphasized this fact and found that that IOP isn't always elevated in glaucoma patients. This study underscores the fact that IOP isn't a sensitive indicator or predictor of the development of glaucoma.
One issue that's become critical because of studies such as the Baltimore Eye Survey is that you should always get an idea of your patient's diurnal curve when evaluating
IOP. For example, if your patient had normal IOPs for most of the 24 hours in a day, but suffered occasional IOP spikes, then she would have POAG instead of true
NTG. This is more than nomenclature -- it dramatically changes your management strategies.
Recent interest has focused on the role of corneal pachymetry in accurate IOP readings. Studies suggest that NTG patients have thinner corneas that may result in an underestimation of
IOP. One study found that when corneal thickness was compensated for, nearly one-third of patients originally diagnosed with NTG actually had
POAG. Changes in corneal thickness, however, don't explain all cases of NTG.
Optic nerve head changes.
The following are some subtle optic nerve head differences between NTG and
► Optic cups, on the average, are larger in NTG than in
POAG. Of course, some of this may be an artifact because doctors diagnose many patients with NTG later in the course of the disease. In addition, patients who have NTG will demonstrate an increased prevalence of focal notching or thinning of the neural retinal rim.
► Patients who have NTG demonstrate an increased incidence of peripapillary atrophy and/or scleral crescents. The development of peripapillary atrophy may indicate decreased perfusion to the peripapillary retina and possibly to the optic nerve as well. This may lead to progressive visual field loss in these patients.
► Disc hemorrhages are more common in patients who have
NTG. They usually indicate an infarct of the nerve fiber layer and are often associated with progressive visual field loss.
► A recent study found that patients who have NTG have a higher incidence of optic nerve pits. In these patients, acquired pits occur, often located at the inferior base of the cup, and are commonly associated with progressive visual field loss, often close to fixation.
Because both NTG and POAG are IOP-associated disease processes, there's some debate as to whether visual field differences between them exist. Although not conclusive, some evidence indicates that the optic nerve is more susceptible to focal damage in
NTG, so the field loss is more localized to one hemifield, has a steeper slope and is closer to fixation.
One study found that the left eye was twice as likely to have a visual field defect than the right eye in patients who have
NTG. This distinguished it from POAG, in which either eye has an equal chance of having a visual field defect. The most alarming aspect of the visual field analysis in NTG patients is that even with proper treatment and monitoring, they're more likely to have progressive visual field loss than those who have
Be on the alert
Patients who have NTG have certain identifiable risk factors which you should specifically screen for when taking a medical history on a suspected patient. For example, they have a high frequency of vascular diseases such as hypertension, coronary artery disease and diabetes. You should also ask them about vasospastic disorders such as migraine headache and Raynaud's Syndrome (tingling of the extremities), past history of extreme blood loss
(hemodynamic crisis) and abnormal blood coagulation or platelet disorders.
Patients who experience significant nocturnal hypotension (low blood pressure at night) may be at risk for NTG because this tends to reduce optic nerve perfusion and contribute to glaucomatous optic atrophy. In many patients, the use of antihypertensive medication at bedtime exacerbates the situation.
Sift through the clues
All clinical signs aside, you must realize that the diagnosis of NTG is a diagnosis of exclusion. Myriad diseases cause optic nerve damage, so rule them out before arriving at a diagnosis of
NTG. One of the most important and common things to rule out are optic nerve lesions, which may present with a similar visual field loss pattern as glaucoma. Although neuroimaging is not mandatory in every case of suspected
NTG, it's wise to consider it for young patients, those who have poor manifest refractions, patients who have visual field defects that respect either the horizontal or vertical midline, and those who've developed neuroretinal rim pallor.
Other things to rule out include anterior ischemic optic neuropathy, an old vein occlusion, toxic optic neuropathy and myopic discs.
NTG requires special care
The results of the 1998 CNTGS told us conclusively that reducing IOP does indeed help slow the progression of field loss in
NTG. The CNTGS was a randomized, controlled clinical trial designed to determine the importance of IOP in the pathogenic process of the disease. In it, researchers randomized patients into either a control (untreated) group or a treatment group in which IOP was lowered 30% from baseline by a combination of medical and/or surgical therapy. Thirty-five percent of the control group experienced visual field progression compared to only 12% of the treated group.
While this sounds encouraging, it also means that even in patients who achieved a 30% reduction in IOP (which is sometimes difficult in
NTG), 12% still suffered additional visual field loss. Despite that finding, the researchers'
ations were for a 30% reduction in IOP for NTG patients.
One of the difficult aspects of managing NTG patients is choosing which drug to start them on. It's much easier to achieve a 30% reduction in IOP in a POAG patient when the IOP is 28 mmHg, than a NTG patient whose highest IOP was
If it turns out that the vascular etiology of NTG is correct, then a medication that's least likely to affect the ocular blood flow and perfusion may be best in the initial management. For this reason, the CNTGS didn't use either beta blockers or alpha agonists as treatments.
The one exception to this rule is betaxolol
(Betoptic S), which doesn't negatively effect ocular perfusion because of its ability to cause
vasodilation. Some studies have even suggested that betaxolol may have a neuroprotective effect on ganglion cell death through its calcium-channel blocking function.
Using one of the prosta-glandin analogs is an excellent first choice for managing NTG patients. These drugs feature once-a-day dosing, excellent efficacy and no negative impact on ocular blood flow.
Another excellent choice is brimonidine
(Alphagan P), a selective alpha-2 agonist that may exhibit the added feature of
neuroprotection. Patients not responding to medical therapy may require an argon laser trabeculoplasty or selective laser trabeculoplasty to preserve vision. If those don't work, filtering surgery is another option.
Look into the future
Calcium-channel blockers have the potential to increase optic nerve perfusion and may one day become a viable treatment option for either NTG or POAG patients. To date, however, studies have failed to prove their efficacy in managing glaucoma.
One interesting therapy that may help NTG patients is Ginkgo
biloba. Early studies indicate that Ginkgo used as adjunctive therapy in patients who have progressive low-tension glaucoma has been of some benefit. Obviously, more research needs to be done.
Although we know a lot more than we once did about
NTG, we still have much to learn about this disorder. For now, lowering IOP remains the mainstay of therapy, but further research will one day improve our management of these patients.
References are available on request.
Calcium-channel blockers have
the potential to increase optic nerve perfusion and may become a viable treatment option for either NTG or POAG patients.Dr. Gupta
primary care optometry at Stamford Ophthalmology. You can reach him at email@example.com.
Optometric Management, Issue: December 2003