• Normal-Tension Glaucoma: When Normal Isn’t Good Enough

    By Miriam Karmel, Contributing Writer

    This article is from April 2006 and may contain outdated material.

    Not long ago, there was little impetus to treat patients with normal-tension glaucoma (NTG). Now there’s greater consensus about the need to lower IOP in patients with this unique glaucoma, which damages the optic nerve without an abnormal rise in pressure. “In the old days, some clinicians said, ‘Don’t bother to treat them. Nothing you do will help,’” said Peter A. Netland, MD, professor of ophthalmology, University of Tennessee.

    The Collaborative Normal-Tension Glaucoma Study (CNTGS) proved the “old days” wrong. It reported “unequivocally” that when IOP is lowered by 30 percent, progression of visual field loss is greatly reduced.

    “In this day and age, all we can do for NTG is lower the pressure,” said Leon W. Herndon, MD, associate professor of ophthalmology at Duke University. In many cases, the aim is single- digit control. “The only information we have is that lowering pressure makes sense with these patients.”

    Still, nearly a decade after the NTG report, questions remain about the disease that may affect one-fifth to one-third of the glaucoma patients in a typical American practice. The biggest questions, aside from etiology, which is unknown, are: How can you be sure of your diagnosis? And when do you initiate treatment?

    First Thing: Get the Diagnosis

    NTG is a diagnosis of exclusion, Dr. Netland said. “If you keep searching, many times you’ll find other causes that you may not see on the initial exam.”

    It’s a tricky diagnosis. “When glaucoma was considered to be a disease of elevated pressure, the diagnosis seemed to be easy,” said George L. Spaeth, MD, professor of ophthalmology, Wills Eye Hospital. But when it became clear that people with average pressures could have glaucoma, doctors started looking for other ways to diagnose NTG. “At the moment, the [optic] disc is in the ascendancy,” said Dr. Spaeth. But the disc can be difficult to read, he added.

    Below are tips for assessing patients suspected of having NTG, also known as low-tension glaucoma.

    What Dr. Spaeth rules out:

    • An affected visual field without a commensurate amount of optic nerve damage is a suspicious combination for an etiology other than NTG. It could signify an optic neuropathy due to multiple sclerosis or a pituitary tumor.
    • When the IOP in the two eyes is consistently symmetrical, but glaucomatous cupping of the disc is in only one eye, the patient almost certainly does not have active glaucoma. The difference between the two discs could signify an old steroid-induced glaucoma, glaucoma secondary to trauma or a pituitary tumor, disc anomaly, giant cell arteritis, or asymmetry in the size of the disc as a congenital anatomic variation.

    When Dr. Netland suspects NTG:

    • With a few exceptions, documented IOP is never higher than 21 mmHg.
    • NTG usually occurs over age 60. (Younger patients should arouse suspicion that something else is going on.)
    • A diagnosis of NTG is tentative until progressive visual field and optic nerve change is documented over time.
    • Disc hemorrhages have been found in higher prevalence in low-tension glaucoma. “If you see a disc hemorrhage in a person with low-tension glaucoma, that’s a sign of likely progression.”

    Limited Use of Imaging Devices

    If there’s a place for the newer imaging devices in NTG, the experts say that it’s limited. “You can’t just run a test and say they’re positive for low-tension glaucoma,” said Dr. Netland. “It’s still a clinical diagnosis.”

    Dr. Herndon agrees. “There are lots of fancy tests you can order. SWAP, NFL analyzer. To me, it boils down to: What does the nerve look like?” He looks for any contour changes to the optic nerve: notching or sloping of the cup, focal loss and nerve fiber layer dropout.

    Douglas R. Anderson, MD, a co- principal investigator of the CNTGS, urges caution when using these tests to diagnose NTG. “The clinician already observed something unusual about the optic nerve. That’s why the test was ordered,” he said. The machine confirms that the optic nerve is abnormal in some way, but doesn’t determine the nature of the abnormality, he said.

    Given that a diagnosis of glaucoma can be difficult when the IOP is normal, Dr. Anderson advised considering all clinical manifestations. For example, is there a large refractive error or anisometropia affecting both the visual field and disc appearance? Is the field defect consistent with a prechiasmal location of the disease, with cupping characteristic of glaucoma rather than other forms of optic atrophy in which pallor dominates?

    NTG is a clinical diagnosis, but the imaging devices give Dr. Netland more confidence in his initial diagnosis. He also uses pachymetry, which identifies patients with abnormally thin corneas; these could result in an underestimation of IOP.

    Dr. Herndon also measures corneal thickness in NTG patients who are getting worse. “If they have extremely thin corneas, that tells you to aim for lower pressures,” he said.

    To Treat or Not

    “Whether to treat is a separate question,” said Dr. Anderson, who is professor of ophthalmology at the Bascom Palmer Eye Institute at the University of Miami in Miami, Fla. Some doctors hasten to start treatment, while others “wait and see,” he said.

    After 40 years of clinical experience, Dr. Anderson stands comfortably in the latter camp, unless the glaucoma is in an advanced stage when discovered.

    Both approaches likely will have their advocates, at least until researchers discover which NTG patients are at risk of progression. While the CNTGS confirmed that treatment is effective, it didn’t resolve the question of which patients to treat.

    That’s an important consideration, since at least half of patients diagnosed with NTG were not treated, but did not progress during follow-up of five years or more. At the same time, one-sixth of the treated group continued to progress.

    Take a picture, then another. “The real test is whether the person continues to get worse,” Dr. Anderson said. “So if the vision is pretty normal, what’s the hurry about making the diagnosis or deciding to start treatment?” In mild cases, he advises taking a fundus photograph and scheduling six-month checkups to monitor progression. If there’s no change, there no need to treat, he said.

    However, if the vision is starting to deteriorate, or cupping worsens, treatment should be initiated.

    But save fixation. Dr. Herndon takes a slightly more aggressive approach. Like Dr. Anderson, he may follow some patients with no significant visual field defects. But if NTG patients have defects close to fixation, he is less likely simply to follow them. “If you lose fixation, then the patient is in a bad situation,” he said. “In the majority of patients, if you diagnose them with NTG, you’re going to want to treat.”

    How to Treat

    Treatment options are similar to those for primary open-angle glaucoma, Dr. Anderson said. “How you choose to lower the IOP depends on what is effective and tolerated by the patient.”

    Dr. Netland said prostaglandin analogs may be useful because they reduce IOP by increasing uveoscleral outflow, outside the conventional outflow facility. Theoretically, they lower IOP below the level achieved by other drugs, which go only as low as episcleral venous pressure, he said. That’s important for NTG treatment, which aims for pressures in the low teens or single digits.

    Calcium channel blockers have been evaluated for use in NTG patients. Dr. Netland uses them when conventional treatment fails. He said their use is described in an extensive body of literature, and prospective, randomized clinical trials in Japan have shown them to be effective. However, there is no endpoint, he said. “You’re not measuring IOP. You’re just trying to see if the patient doesn’t progress.” It makes sense, he said, to recommend them as a hypertensive medication of choice in patients who have systemic hypertension.

    Lowering IOP just the beginning? Treatment strategies are constantly evolving. Dr. Netland predicted that along with continued IOP lowering strategies, neuroprotective and vasoprotective drugs eventually may play a role in NTG management. In the meantime, he said, “It is useful to treat patients with low-tension glaucoma to lower their IOP.”

    When You’re Not Looking at NTG

    An estimated six percent of NTG suspects actually have a compressive tumor, Dr. Netland said. But you can’t order an MRI or CT scan on every patient who, despite normal pressure, is losing vision. When should you order one? The following set off alarms for Dr. Netland: asymmetry of the optic nerve, dyschromatopsia, age younger than 55 and optic nerve findings that don’t correspond to the visual field.

    Meridians matter. Dr. Herndon pays attention to visual defect patterns. Glaucoma defects are on a horizontal meridian. A visual field that respects the vertical meridian could indicate a neurological problem.

    Pale rim is a red flag. A pale optic nerve rim, one that’s not “nice and pink,” is another warning sign that it’s something other than NTG, Dr. Herndon said. Other clues include: headache, slurred speech, dizziness or “something that seems unusual. You don’t want to miss a compressive tumor of the optic nerve,” he said. “It’s important to have a high suspicion and low threshold for performing imaging.”

    Who’re You Calling Normal?

    There’s nothing normal about eyes with NTG, which is why Dr. Spaeth advocates a name change. This is more than a semantic quibble. The term can be confusing to patients, who wonder why they need treatment when their pressure is “normal,” Dr. Spaeth said.

    “Normal carries with it the implication of healthy, yet in NTG the pressure is not healthy.” Dr. Spaeth prefers saying, “The patient has glaucoma.” Then he further identifies the disease by the mechanism, such as open angle, or by a specific entity, such as exfoliation syndrome.