Staying On Top of Glaucoma
The Real Efficacy program looks to prevent vision loss in glaucoma patients.
STEVEN SIMMONS, M.D.

There have been so many studies about glaucoma and so much knowledge gleaned from them, that it is difficult to keep abreast of all of the advancements in knowledge. For this reason, Drs. Louis Cantor, Robert Noecker, Leon Herndon, Ronald Gross and I developed the content for a program named the Real Efficacy (RE) program.

The RE program was developed to put all of the studies and knowledge to work. Designed to discuss a successful treatment strategy for glaucoma patients to prevent visual loss, the program's curriculum takes a three-pronged approach to education:

► Diagnose and treat early by focusing on both the structure of the optic nerve and functional vision.

► Aggressive lowering of IOP, reduction of IOP fluctuation and the establishment of dynamic, ambitious target pressures.

► Establishment of effective medical and surgical treatments to achieve target pressures and preserve visual function.

Developing A Sense of Urgency

Glaucoma is a disease characterized by progressive injury to the retinal ganglion cells (RGCs) and their axons. A key feature of the disease is a specific pattern of optic atrophy, or cupping, which goes hand in hand with visual loss.

Because it is a silent and painless disease, many patients and physicians feel that it is not necessary to treat with a sense of urgency. Unfortunately, this lack of urgency can lead to vision loss and eventually blindness.

To answer the question of how many patients with untreated glaucoma go blind, one must look no further then the West Indies study to understand the natural history of glaucoma. In this study, 205 patients from St. Lucia were diagnosed with glaucoma between the years of 1986 to 1987, and these patients were reexamined 10 years later. Some of the follow-up findings included:

► 16% of patients progressed to blindness in at least one eye over 10 years.

► 9% of these patients progressed to bilateral blindness.

► More than 50% of eyes that progressed to end-stage glaucoma had no or minimal visual function loss at baseline.

Identify and Treat Early

To be successful in avoiding the advanced visual loss secondary to glaucoma, it is critical that the disease be diagnosed early by identifying the structural damage that occurs with glaucoma prior to functional loss. A nerve fiber layer injury can be observed up to 6 years in advance of visual field defects.¹ The mean number of axons in a normal optic nerve is approximately 800,000 to 1.2 million.² Thirty-five percent to 40% of these optic nerve fibers can be lost without visual field.³

Visual field loss detected by standard automated perimetry (SAP) then does not characterize early disease, but rather more advanced disease. By the time visual field loss is detected by SAP, substantial structural damage already exists.^1,4 Functional loss may be detected earlier using more selective tests such as frequency doubling technology (FDT/Matrix) or shortwave automated perimetry (SWAP).⁴ By selecting a subset of RGCs, these visual field techniques reduce the redundancy present with SAP and as a result, can detect visual field loss 3 to 5 years earlier than SAP.

Optic Nerve is Key

As information and treatment methodology evolves, greater emphasis is being placed on glaucoma as an optic neuropathy with characteristic changes in the optic nerve that precede visual field damage. In fact, early glaucoma in the American Academy of Ophthalmology's (AAO) classification is explicitly glaucoma without visual field loss by SAP. As a result, it is critically important to integrate careful optic nerve evaluation into clinical practice.

Clinicians should use their optic nerve evaluation to categorize disease severity, which is important in setting treatment goals and target pressures. While the initial optic nerve evaluation is important, it is just as significant to continually reevaluate the nerve, to look for evidence of progression, and when noted, treatment and target pressures should be adjusted accordingly.

► handy reference tool for evaluating the optic nerve is the "5 R's" which was described by Robert Weinreb, M.D. These 5 R's include:

► Observing the scleral ring to identify the limits of the optic disc and its size

► Identifying the size of the rim

► Examining the retinal nerve fiber layer

► Examining the region of parapapillary atrophy

► Looking for retinal and optic disc hemorrhages

Identifying the glaucoma patient is only the first step in a successful treatment regimen. Once identified, it is critical that each individual patient be treated aggressively enough to avoid progressive visual loss.

Landmark National Eye Institute trials have shown the relationship between IOP and glaucomatous progression. These trials have also led to two major conclusions. One, it is critical to lower IOP aggressively, and two that it is vital to maintain a steady level of IOP without large fluctuations. The lower and more stable the IOP, the better chance of treating the disease successfully. When pressures were low enough and fluctuated the least, patients on average had no progression of their disease. These studies have shown that patients at all stages of glaucoma benefit from reducing IOP.

In treating newly diagnosed glaucoma patients, a target IOP should be established as a goal of therapy. This IOP goal should be independently set for each patient, depending on the extent of their disease, the level of their untreated IOP and their risk factors for progression (age, family history). But once set, it is vital this target pressure be reviewed and adjusted as needed over the course of treatment.

Based on clinical trial evidence and glaucoma experts' experience, guidelines for setting target pressures in glaucoma have been developed by leading ophthalmic and glaucoma organizations, such as AAO, Canadian Ophthalmology Society/Canadian Glaucoma Society, European Glaucoma Society and others.

These groups recommend a minimum initial target IOP reduction of 25% for glaucoma patients. However, more aggressive target pressure reductions of 30% to 40% are recommended for higher risk patients. Regardless of the initial number, the target pressure must be dynamic if it is to be a successful treatment goal in preventing visual loss.

The consequences of failing to achieve the target IOP can be significant, and some of the studies have suggested that for every 1 mm Hg rise in IOP, the risk of progression increases by 10%. With this in mind, clinicians must consider the most effective means by which they will be able to lower IOP in each patient.

From a medical therapy perspective, the most successful strategy is the building block approach where the patient is started on the strongest "foundation." Ideally, the target IOP can be achieved with one medication. Monotherapy improves patient compliance, decreases cost to the patient and reduces cumulative patient exposure to preservatives. It makes sense to evaluate the medications in the marketplace to determine which agent might be the most effective in achieving the target pressure for each patient you are treating. Randomized, controlled trials have shown that the most effective medications are the once-daily lipids Lumigan (bimatoprost, Allergan), Xalatan (latanoprost, Pfizer) and Travatan (travoprost, Alcon).

If your initial therapy choice does not achieve the target pressure, the question you are confronted with is, should you switch to a new therapy or simply add another. With the goal of reaching the target IOP using the minimal number of medications possible, patients benefit from switching to a more effective monotherapy rather than adding to a medication that is not effectively lowering IOP.

Quality of Life

Finally, it is important to incorporate your patient's priorities into your decision making when contemplating a therapy. Clinicians should take the time to understand the significant impact glaucoma has on a patient's quality of life. Once diagnosed with glaucoma, a patient's primary concern is preserving quality vision.

With patients being diagnosed at a younger age, there are an increasing number of patient life-years with glaucoma. The only way to treat these patients is to implement optimal therapies that preserve vision. Effective IOP lowering becomes more important for a larger number of patients. Physicians need to take to time to talk to their patients about the therapy they have chosen, how it can help and how it might affect them relative to transient side effects such as hyperemia, iris pigmentation or eyelash growth. This time spent will prepare patients to be compliant and help them to save their vision.

With early diagnosis and appropriate treatment, blindness can be prevented in glaucoma sufferers. The content of the RE program is designed to teach clinicians how to diagnose glaucoma earlier, and treat it more effectively with the ultimate goal of preserving our patients� sight so they can remain functional throughout their lives.

Steven Simmons, M.D., is co-director of the Glaucoma Consultants of the Capital Region in Albany, New York, and he is an associate clinical professor of ophthalmology at Albany Medical Center. He can be reached at (518) 475-7300 or glaucomaconsult@aol.com.

REFERENCES
1. Sommer A, et al. Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol. 1991;109:77-83.
2. Quigley HA, et al. Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. Arch Ophthalmol. 1982;100:135-146.
3. Kerrigan-Baumrind LA, et al. Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Invest Ophthalmol Vis Sci. 2000;42:1993-2003.
4. Bowd C, et al. Detecting early glaucoma by assessment of retinal nerve fiber layer thickness and visual function. Invest Ophthalmol Vis Sci. 2001;42:1993-2003.