How Low Must You Go?
New information can help you target the right IOP level in normal tension glaucoma.
Clinical Challenges with Eric Schmidt, O.D.

Last month I discussed how clinical studies guide us as to when, where and how to treat a branch retinal vein occlusion. This month, I'll share yet another study that offers advice about treating patients with normal tension glaucoma (NTG).

THE CASE: Ms. Willie was the youngest of six children, all female. "By the time I came around," she said, "my Daddy wanted a junior so he named me Willie, after him." She and I both chuckled. So began my relationship with Ms. Willie. When I finally got down to business, I realized that she would probably be a regular in my practice.

She was referred in as an NTG suspect with suspicious-looking optic nerves but pressure that never exceeded 19 mm Hg. Based on just those facts, I knew I'd need to see her at least three times before I could decide whether or not to treat.

At the first exam, Ms. Willie said her vision wasn't as clear as it used to be, but it wasn't seriously worse. She didn't indicate any other ocular problems, such as discomfort or redness. Systemically, Ms. Willie was taking only metoprolol (Lopressor) for hypertension.

In the exam chair

Through her hyperopic eyeglasses, Ms. Willie read 20/30 OD and OS; this didn't improve with the pinhole occluder or refraction. External tests were normal. The slit lamp revealed 1+ nuclear sclerosis OD and 1+ posterior subcapsular cataract and trace nuclear sclerosis OS. I judged her anterior chamber angles to be grade 2 OD and Grade 3 OS using the Van Herick method. Goldmann tonometry showed pressures of 17 mm Hg OD and OS. I placed a Sussman gonioscopy lens on her eyes and saw open angles, Grade 3, 360 degrees OU, but there were moderate amounts of iris processes throughout the angles.

Examination of the optic nerve heads showed disks that looked suspicious for glaucoma. I judged the cup-to-disk ratio to be .6/.65 OD and .65/.7 OS. Large laminar dots were visible in the base of the cup, and I noted a moderately large alpha zone surrounding both disks (see photo, below left).

Visual fields added further credence to the diagnosis of NTG. They revealed a classic inferior nasal step OD and a double arcuate scotoma that was denser below than above OS. But before initiating therapy for NTG, I wanted to get two or three more pressure readings. These would provide information as to whether the intraocular pressure (IOP) was peaking at a certain time of day, what the peak IOP was and whether the IOP was actually climbing into the abnormal range on occasion.

Over the next month, Ms. Willie's IOP ranged between 17 mm Hg and 22 mm Hg. During that time, Ms. Willie's physician added atorvastatin (Lipitor) to her drug regimen for hypercho-lesterolemia.

Shooting for a target

NTG usually presents more subtly than in this case. Because of the classic clinical picture here, it was easy to decide that treatment was indicated. I prescribed betaxolol 0.25% (Betoptic S) OU b.i.d. and set a target pressure of 15 mm Hg. The conventional wisdom in primary open-angle glaucoma has long been to set a 33% reduction in IOP as an initial target. In NTG, however, the target IOP wasn't always as clear. Most doctors never understood how low the IOP must go to prevent further optic nerve damage.

Recently though, the Collaborative Normal Tension Glau- coma Study (CNTGS) offered us an excellent guideline when deciding what target IOP to shoot for in NTG. This well-designed, multi-center study aimed to answer the question, "Does substantially lowering IOP slow the rate of glaucomatous optic nerve damage in NTG patients?" The results showed that lowering the IOP by 30% by any means effectively reduced disease progression. In fact, of those patients who met the goal of 30% IOP reduction, only 12% showed continued progression.

Factors to consider

So, a 30% reduction in IOP should be set for NTG patients. It's important to understand, though, that these following factors unrelated to pressure also affect NTG, and must be taken into account:

• One of the more widely accepted theories about the etiology of NTG is that these patients have decreased perfusion to the optic nerve, which causes loss of rim tissue even with normal IOP.
• Some NTG patients have faulty autoregulation of the microcirculation as compared to normal patients. This problem could contribute to "cupping" in the absence of high pressures.

Choosing our ammo

Non-selective beta-blockers are vasoconstrictors that reduce blood flow to the optic nerve. As such, they shouldn't be used to treat NTG. Betaxolol 0.25%, a cardio-selective beta-blocker, has been shown in studies to increase blood flow to the optic nerve head through vasodilation.

The newest anti-glaucoma drug, isopropyl unoprostone (Rescula), has also been shown to be a vasodilator and shows promise as a useful agent for treating NTG by increasing perfusion to the optic nerve head.

I kept Ms. Willie on betaxolol 0.25% b.i.d. for 3 months, but she never reached the target IOP of 15 mm Hg. Her IOP never fell below 17 mm Hg on that drop.

Though we were probably achieving some enhanced perfusion, I felt that the lackluster IOP response more than counteracted any perfusion effect. I discontinued the betaxolol 0.25% and prescribed latanoprost 0.005% (Xalatan) OU q.h.s. Latanoprost is a proven IOP reducer, but unlike beta-blockers, it doesn't have any negative vasoactive response, making it effective in many cases of NTG. It consistently lowered Ms. Willie's IOP to 16 mm Hg, but her visual field showed continued worsening. Her IOP needed to be lowered further.

I asked her to continue the latanoprost and added brimonidine tartrate 0.2% (Alphagan) OU b.i.d. Brimonidine tartrate is another effective IOP-reducing agent but also reportedly possesses neuroprotective capacities. Neuroprotective agents enhance the survival of retinal ganglion cells in ischemic or toxic situations, so brimonidine tartrate helps to control some of the non-pressure-related factors as well as reduce IOP.

On this combined therapy, Ms. Willie's IOP dropped to 12 mm Hg OU and has remained in that range. There's been no further degradation of her visual field, and she's tolerating both drops well. If for any reason her IOP begins to rise or the optic nerve heads show increasing cupping, I won't hesitate to add isopropyl unoprostone to the mix or consider an argon laser trabeculoplasty.

Parting shot

Up to 50% of all patients with glaucoma have NTG. NTG is notoriously difficult to diagnose, but as our knowledge of its pathology and clinical presentation increases, so does our ability to recognize it.

In NTG, it's important to understand the following:

• what we're trying to achieve with treatment (preservation of visual field)
• the role that non-pressure-related factors play
• how different anti-glaucoma agents affect the optic nerve and IOP differently.

The CNTGS also brings us new insight as to how pressure affects the optic nerve in NTG. By arming ourselves with all these data, we'll be better able to control this insidious disease.

Contributing Editor Eric Schmidt, O.D., is director of the Bladen Eye Center in Elizabethtown, N.C. He can be reached at KENZIEKATE@aol.com.