Patient Management
Normal Tension Glaucoma: What We Know, What We Don't
Four specialists share the latest information.
By Jonathan S. Myers, M.D., Douglas J. Rhee, M.D., L. Jay Katz, M.D. and George L. Spaeth, M.D.

Only 30 years ago, leading figures in ophthalmology believed that normal tension glaucoma didn't exist. Today, we know that normal tension glaucoma affects between 6% and 65% of patients with glaucoma (depending on the population studied). Elevated intraocular pressure (IOP) is now considered a risk factor, not a requirement, for a glaucoma diagnosis. Clinicians have also become more adept at recognizing the ophthalmoscopic features of glaucoma, evaluating the appearance of the optic nerve rather than relying solely on elevated IOP.

Optic nerve of a patient with normal tension glaucoma. Note the disc hemorrhage at 10 o'clock and nerve fiber layer defects between 7 and 8 o'clock and 10 and 11 o'clock, as well as the inferior notch and incipient superior notch.

Diagnosing optic nerve change

In the past, clinicians were taught that basing a diagnosis on cupping and field loss, in the absence of elevated pressures, required neuroimaging to exclude compressive lesions of the optic nerve pathways. However, an important study by Greenfield et al. (published in Ophthalmology, Oct., 1998) showed that clinical judgment of optic nerve appearance was sufficient to make an accurate diagnosis. Optic nerves with typical glaucomatous features -- such as cupping or notching of the rim tissue, without disproportionate pallor in less affected areas (see photo, right) -- were correctly identified as glaucoma. Optic nerves with pallor and generalized atrophy, but no cupping, were correctly identified as neurologic pathologies requiring further diagnostic work-up.

Various patterns of glaucomatous optic nerve change, such as notching of the rim, concentric enlargement of the cup, or a more saucer-like excavation and atrophy of the tissue, have been noted. (Notching and saucer-like changes may be more common among patients with normal tension glaucoma.)

Discriminating optic nerve features include:

• Notches, or acquired pits of the optic nerve, are typically within 1 clock hour of the vertical poles on the nerve.
• Congenital pits of the optic nerve are often observed to be within 1 clock hour of the horizontal meridian and may be associated with serous retinal detachments.
• Congenital optic nerve colobomas are often found near the inferior pole, but can also be associated with colobomatous retinal or iris defects. They tend to remain stable over time.
• Drance, or disc, hemorrhages may portend progressive disease in any type of glaucoma, but they appear to be more common in normal tension glaucoma.

Note that congenitally large or anomalous optic nerves may masquerade as normal tension glaucoma.

Performing the work-up

The work-up for patients suspected of having glaucoma, based on optic nerve appearance -- without elevated pressures -- includes taking a detailed history and performing baseline ophthalmologic studies. The history should address:

• prior steroid use, to exclude the possibility of prior secondary elevated intraocular pressure that may have resolved, leaving a damaged, but stable disc
• past traumatic injuries, such as a hyphema, which could be responsible for a transient secondary glaucoma
• severe hypotension, associated with traumatic or surgical hemorrhage, which in rare cases may lead to an optic neuropathy that can mimic normal tension glaucoma
• a history of migraine or peripheral vasospasm such as Raynaud's phenomenon. These conditions have been associated with normal tension glaucoma.
• number of different tests can aid diagnosis:
• About half the patients in the Baltimore Eye Survey who were eventually diagnosed with primary open angle glaucoma had pressures less than 21 mm Hg when first examined. For that reason, patients suspected of having normal tension glaucoma should receive diurnal pressure monitoring, either during a single day of intraocular pressure measurements, or through a series of brief visits at different times over a period of days.
• Optic disc imaging using photographs or computerized analysis is still warranted and helpful, although none of the newer disc imaging technologies has been shown to be clearly superior to photographs for monitoring disease progression.
• Baseline visual field testing is crucial. In the Normal Tension Glaucoma Study, the vast majority of disease progression was detected by visual field changes, even with an expert panel monitoring nerve photographs regularly.

Reducing IOP

The Normal Tension Glaucoma Study showed a three-fold reduction in visual field deterioration when patients achieved a 30% reduction in IOP below pretreatment levels, compared to a control population. Pressure reduction can be achieved through topical agents, laser trabeculoplasty, or filtration surgery.

We usually offer patients a choice of topical medications or laser therapy as first treatment, with our goal being a 30% pressure reduction from the maximum pressure we've measured. Most patients choose medications, although laser trabeculoplasty can be cost-effective and convenient. Medications such as a selective alpha-2 agonist, prostaglandin analogs, and topical carbonic anhydrase inhibitors are typical first agents.

We usually reserve guarded filtration procedures, or trabeculectomies, for those demonstrating progression. (Non-penetrating surgeries don't achieve a low enough IOP for most of these patients.) However, filtration surgery for these patients is challenging because the therapeutic window is narrow.

Typically, anti-metabolites are used during filtration surgery to help achieve lower pressures. 5-fluorouracil, intra- or post-operatively, may be a milder first treatment than Mitomycin-C for patients who have no other risk factors for post-operative scarring.

Outlook: improving

Normal tension glaucoma continues to become easier to diagnose and manage. So far, IOP reduction remains the only treatment known to alter its progression. However, research in the areas of ocular hemodynamics and neuroprotection appear promising as viable treatment options for the future.

All four authors practice at Wills Eye Hospital in Philadelphia. Drs. Myers and Rhee are assistant attending surgeons; Dr. Katz and Dr. Spaeth are attending surgeons. Dr. Spaeth is also Louis J. Esposito Research Professor at Wills Eye Hospital/Jefferson Medical College.