Glaucoma Management

Gauging Success in Glaucoma Management

When it comes to IOP reduction, use science to answer the question: How low do you go?

BY BEN GADDIE, O.D., F.A.A.O. Louisville, Ky.

I have often noted that making the diagnosis of glaucoma is the more difficult component of management, not the treatment.

While technology provides us with more sophisticated data on our potential glaucoma patients, making a definitive diagnosis remains as much a science as an art. Clinically lowering intraocular pressure (IOP) is one area of glaucoma management that solid science has guided.

Glaucoma is typically a slow-moving disease, and some latency exists between the death of a retinal ganglion cell and the subsequent development of structural, and, later, functional deficit.

Given this fact, researchers may not determine the impact from changes in therapy that might reduce IOP for months or years.

We know that glaucoma has multi-factorial causes, yet IOP is the only factor we can modulate in its treatment. Because we stage our overall management success on the preservation of visual function and structural stabilization, this fact can sometimes make managing glaucoma feel aimless and frustrating. Oftentimes, we achieve success in lowering IOP but not in protecting the patient's visual function. Other times, the converse outcome prevails.

In this article, we'll examine a host of IOP-related treatment questions. These include:

• initial pressure-reduction percentages
• clinical implications of diurnal variations
• setting realistic pressure goals.

Set realistic target pressures

When beta-blockers were the mainstay of glaucoma therapy, we would hope for a 20% to 25% reduction in IOP as a target goal.

In the Ocular Hypertension Treatment Study, patients randomized to receive treatment for ocular hypertension had to achieve at least a 20% reduction in IOP to remain in the study.¹

As the Food and Drug Administration (FDA) has approved prostaglandin analogs (PGAs) as first-line glaucoma therapy, anecdotally it seems that the more-effective treatment changes our expectations of goal pressures. From that standpoint, we expect and set an approximate goal of 30% reduction of IOP in a patient who has an elevated IOP and open-angle glaucoma when we institute PGA treatment.

The glaucoma literature has supported a 30% reduction of IOP as of late, principally the Collaborative Normal-Tension Glaucoma Study. Although this study was inclusive only for normal tension glaucoma, the results showed that patients with normal tension glaucoma who achieved a 30% or greater reduction in IOP demonstrated glaucoma progression at a rate of 12% vs. 35% progression rates for untreated eyes.²

Something else to consider: The Early Management Glaucoma Trial demonstrated that every additional millimeter of pressure reduction resulted in a relative risk reduction of 10% to 11%.^3,4

The impact of CCT

It would be remiss not to mention a few potentially confounding factors surrounding the accuracy of IOP measurements.

Researchers and eyecare practitioners have long suspected that anomalies in central corneal thickness (CCT) cause inaccuracy with tonometry measurements. The medical literature highlighted the CCT influences on IOP in the 1970s.⁵ But, researchers and eyecare practitioners largely forgot the concept, as neither the medical literature, nor an eyecare practitioner widely disseminated it.

In any case, generally speaking, you can expect to see a diminished response to topical IOP-lowering agents among patients who have substantially thick corneas.⁵

Two important events occurred that brought the issue of CCT to center stage in the eyecare arena. The first was the explosive growth of blade-assisted LASIK and the realization that IOP decreased after the procedure. Biomechanical properties of the cornea are no doubt in play here.

Despite extensive work, there remains no consensus on which aspects of LASIK surgery cause the apparent reduction in IOP.

The Ocular Hypertension Treatment Study is the other event that exposed the importance of CCT.

This study underscored the importance of determining CCT in patients who have elevated IOP, and I've found that most eyecare practitioners have quickly adopted this concept.

The renewed interest in IOP has spurred some significant discoveries and questions. For example, one study elucidated that in glaucoma patients, IOP reaches its peak elevation while patients are lying down, during the sleep cycle.⁶ This concept is contrary to what we had always thought about the timing of daily IOP fluctuation.

In addition, several new tonometers have made their way into the U.S. market. For example, one of these tonometers has unchanged pre-and postoperative LASIK IOPs and may be less influenced by corneal biomechanical properties.^7,8

The thin cornea debate

Another area of interest and debate in glaucoma management is whether the presence of a thin cornea is an independent risk factor for progressive changes in glaucoma. Again, the studies in this area are split.

One study that analyzed all the relevant papers on progression based on CCT as a risk factor revealed that CCT is a strong predictor of conversion to glaucoma from ocular hypertension, but is not necessarily predictive of the risk of progression through the course of the disease.⁹

The role of IOP fluctuation

IOP fluctuation and the development or progression of glaucoma appear to be related.

In the Advanced Glaucoma Intervention Study, researchers recently reported that long-term IOP fluctuation is associated with visual field progression in patients who have low mean IOP but not in patients who have high mean IOP.¹⁰ This was a hot topic in 2007 and remains a difficult metric to study in a wide-scale manner.

Traditional diurnal/wake work thus far has shown only that the absolute level of the IOP, and not the amount of fluctuation, influences the risk of progression.

The results of the Early Manifest Glaucoma Trial revealed a relationship between high IOP and progression but not fluctuation of IOP and glaucoma progression.

A potential short-coming of these studies is the fact that the researchers didn't obtain 24-hour monitoring on these patients. It's possible that nocturnal fluctuation could contribute to progression. That work is ongoing.³

Eyecare practitioners are eager for the first continuous IOP monitoring tonometer. Prototypes have been implantable and contact lens-based, both with an external recording device.

If glaucoma patients can obtain IOP readings outside traditional office hours, these readings would be useful in enabling us to determine elevated IOP levels beyond that recorded in the clinic.

Until continuous IOP monitoring is available, ascertaining the true importance of IOP fluctuation on the rate of glaucoma progression remains difficult.

Set an algorithm

It's very important to obtain many IOP readings through multiple days and times of day prior to starting a patient on treatment for non-emergency glaucoma. For this reason, schedule patients for several appointments to assess their IOP, each at different times of the day.

Remember: Glaucoma patients can have drastic diurnal fluctuations. Therefore, a one-time reading prior to therapy is unacceptable.

The definition of meeting the target IOP clinically may differ somewhat, depending on the strength of the data obtained by tonometry. Therefore, it's important to not take IOP values as absolutes because they are only numbers, and glaucoma is a disease we can't effectively manage on IOP numbers alone. I've found that a minimum of three readings, taken at different times of day, enables me to decide on the best treatment for the patient.

If your patient doesn't quite reach goal pressure, be patient, and reassess his visual field more frequently during the first couple years of treatment. This allows you to detect the subset of patients who tend to progress and those who progress fast.

Choosing an initial drug class

The initial medication decision is an important factor in setting target or goal IOP. Some classes of medications are more likely than others to substantially lower IOP, and prudent class selection at the onset can often lead to monotherapy control around the target IOP.

The main classes of drugs to consider for first-line therapy include PGAs and beta-blockers. Most of the commercially available PGAs are FDA-approved for first-line use. Their efficacy, tolerability and ease of use have catapulted them to the head of the pack.

After choosing and instituting therapy with one of the PGAs, educate the patient on its use and potential side effects, so you can ensure medication compliance.

I personally prefer to have the patient use the PGA for four weeks prior to having him return for an IOP check, as I've found that most PGA samples last about four weeks. I also have the patient return with the bottle.

Keep in mind that the status of the bottle at return can often be a barometer of compliance. (When ascertaining compliance, consider that some medication will likely be wasted as the patient adapts to applying it to his eyes daily.)

I look for a 30% reduction in mean IOP (as best as I can determine what that mean is). Just as with other classes of topical glaucoma drugs, not every patient will respond to the PGA class of medication. Therefore, if a patient doesn't achieve at least a 20% to 25% reduction in IOP, I consider switching him to another drug within the same class.

Set the tone upfront

In explaining to patients why a medication switch is necessary, I use blood pressure, diabetes and cholesterol treatment as an analogy.

The medications we use to treat these conditions usually control the problem for a certain period of time and then lose their efficacy. When this happens, we adjust treatment and employ drugs that have a different mechanism of action. I explain to patients that the same thing occurs with glaucoma treatment.

Setting this tone up front is important so that patients aren't concerned when you switch their medication. After all, patients can only judge the success of their daily efforts to protect their eyes by knowing what their IOP numbers portend. OM

1. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that the topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002 Jun;120(6):701-13
2. Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J. Ophthalmol. 1998 Oct;126(4):487-497.
3. Bengtsson B, Leske MC, Hyman L, Heijl A. Fluctuation of intraocular pressure and glaucoma progression in the early manifest glaucoma trial. Ophthalmology. 2007 Feb;114(2):205-20 Epub 2006 Nov 13.
4. Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003 Jan;121(1):48-56.
5. Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol (Copenh). 1975 Mar;53(1):34-43.
6. Kida T, Liu JH, Weinreb Rn. Effect of 24-hour corneal biomechanical changes on intraocular pressure measurement. Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4422-6.
7. Pepose JS, Feigenbaum SK, Qazi MA, et al. Changes in corneal biomechanics and intraocular pressure following LASIK using static, dynamic, and noncontact tonometry. Am J Ophthalmol. 2007 Jan;143(1):39-4 Epub 2006 Oct 20
8. Shah S, Laiquzzaman M, Bhojwani R, Mantry S, Cunliffe I. Assessment of the biomechanical properties of the cornea with the ocular response analyzer in normal and keratoconic eyes. Invest Ophthalmol Vis Sci. 2007 Jul;48(7): 3026-3031.
9. Dueker DK, Singh K, Lin SC, et al. Corneal thickness measurement in the management of primary open-angle glaucoma: a report by the American Academy of Ophthalmology. Ophthalmology. 2007 Sep;114(9):1779-1787.
10. Caprioli J, Coleman AL. Intraocular Pressure Fluctuation: A Risk Factor for Visual Field Progression at Low Intraocular Pressures in the Advanced Glaucoma Intervention Study. Ophthalmology. 2007 Dec 13. [Epub ahead of print.]

Dr. Gaddie is in private practice in Louisville, KY, where he specializes in glaucoma. He is also an adjunct assistant professor of Optometry at Northeastern State University College of Optometry and a consultant to and speaker for Allergan. E-mail him at ibgaddie@bellsouth.net.