GPA: A Better Way of Looking at Glaucoma

Nathan Radcliffe, MD

Traditionally, visual field assessment has required testing the patient, then comparing his results to a normative database. In the past, we often defined patients as having glaucoma when their visual field test was outside normal limits. But, as we all know, some patients have stellar visual field performance while others do not. In some situations, it may not be appropriate to compare a patient to a group of "normal" patients. Ideally, you should be able to compare that patient to his previous performance.

With the aid of Guided Progression Analysis (GPA) software from Carl Zeiss Meditec, we are finally able to address glaucoma in an ideal manner by evaluating it as a disease of change. More precisely, glaucoma is a disease of deterioration — of either visual function or of retinal nerve fiber tissue. The best way to manage glaucoma is to determine the rate at which the disease is changing — either functionally or structurally. Carl Zeiss Meditec has given us tools to evaluate change from both standpoints, using the same GPA language to evaluate perimetry with the Humphrey Field Analyzer (HFA), OCT and nerve fiber polarimetery.

We know there's a great deal of fluctuation inherent in glaucoma. There's fluctuation of intraocular pressure, of visual field performance, and to some extent, fluctuation (or noise) in some of the imaging test values. Glaucoma specialists minor in statistics; we know that one way to overcome fluctuation is to increase the rate at which we sample.

My strategy for detecting change, whether structural or functional, is to make multiple assessments. I begin by conducting two baseline visual field tests within a short time interval — anywhere between 6 weeks and 3 months of initial diagnosis. On average, I obtain two perimetric evaluations a year. There are patients at higher risk of progression and I assess them more frequently; likewise I assess stable patients less frequently.

Comparing Apples to Apples

With the overall strategy that Carl Zeiss Meditec has employed, you can use the same vocabulary to talk about visual fields and OCT, which is ideal because they're two different representations of the same disease process. In some cases, you may detect a glaucoma patient because of abnormal RNFL thickness compared to a normative database. In other cases, you may have a patient with normal RNFL thickness who is diagnosed with glaucoma because he has changed compared to his own baseline.

Using the GPA software on the Cirrus, we can evaluate the patient's loss of RNFL over time compared to his own baseline, which is a composite of two initial examinations. I've seen considerable variation in the thickness of the RNFL between healthy patients, so it makes much more sense to compare a patient to himself and his own historic baseline.

Additionally, we can use the visual field and optic nerve information together to perform structure-function assessments with greater sensitivity. I may, for example, have a patient with a borderline superior arcuate scotoma, which appears very early in the visual field test in her right eye.

When I am obtaining the OCT, I can lower my threshold for what I consider to be a glaucomatous defect, providing that it agrees with my functional assessment. So, by looking for a structure-function relationship using these two devices, I can determine that someone may have glaucoma even if she just has a borderline thinning in her RNFL—as long as it agrees with the borderline area of the visual field. Using the two devices together allows for greater sensitivity and specificity in diagnosis.

Similarly, you can see structure-function relationships in terms of progression. On the visual field test, the event–based GPA may tell you that a patient has possible progression in one area, and it can tell you this in as early as 3 visual field tests. You could obtain 2 more visual field tests to further clarify the likelihood of progression. Another strategy may be to repeat your OCT and look to see if there's been any deterioration in the corresponding region of nerve fiber layer.

Event and Trend Analysis

In general, there are two ways of telling whether a visual field or OCT has progressed: event-based and trend-based analysis. Both are available through GPA. The advantage to defining an event is that you can achieve it fairly quickly. For example, in the Early Manifest Glaucoma Trial, the investigators wanted a fairly sensitive measure of field progression, particularly since half of the patients in that study were randomized to placebo. For this study, they defined progression as at least three significantly progressing points at the same locations in three consecutive tests on the pattern deviation plot. This has now been incorporated into the HFA's GPA alert.¹ While this analysis can quickly tell us if the patient has progressed, it won't provide his rate of progression. A trend-based analysis takes longer to determine, but provides more information. You need at least four assessments for OCT; five for visual fields. You're calculating a slope or performing regression analysis and you need data for that. The advantages are that you can get information on the rate of field progression and also get a sense of variability by looking at the confidence intervals around that rate and the significance of the slope of progression.

Visual Field Index

The HFA measures the Visual Field Index (VFI), an age-adjusted and center-weighted assessment of the overall percentage of remaining visual field. This global index best answers the question, "Doctor, how much visual field do I have remaining?" It answers it in a way that reflects a patient's age and is also sensitive to the fact that central vision is more important to our patients than peripheral vision. In the visual cortex, central regions of vision are "weighted" by receiving a greater degree of cortical magnification. The relationship is linear and declines with eccentricity such that a region of visual field 1 degree more eccentric will receive about half of the visual cortex than the more central area.² Carl Zeiss Meditec took that same central weighting and applied that to the visual field, so the VFI better represents the functional importance of vision to your patient. Additionally, after several exams we can create a plot of a patient's VFI over time. The plot can tell you if the patient is losing vision and how quickly, along with a 5-year projection of total field remaining if the progression continues at the same rate. It will also tell you if the slope of that regression line is significant.

You can review this information with your patient to help him better understand his condition with intuitive and more concise language. I'm often surprised how two patients with similar VFI plots will feel differently about the projected loss of vision, and this information allows me to better engage my patients in a dialogue about their disease.

The bottom line is that we're closer now than ever to dealing with glaucoma on its own terms. By doing so, we can assess the rate at which our patient is deteriorating and adjust our therapy to that rate of change. OM

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Nathan Radcliffe, MD, is an assistant professor of ophthalmology and director of the glaucoma service atWeill Cornell Medical College and NewYork-Presbyterian Hospital in New York.

References

1. Bengtsson B, Lindgren A, Heijl A, Lindgren G,Asman P, Patella M. Perimetric probability maps to separate change caused by glaucoma from that caused by cataract. Acta Ophthalmol Scand. 1997;75:184-188.
2. Levi DM, Klein SA,Aitsebaomo AP. Vernier acuity, crowding, and cortical magnification. Vision Res 1985;25:963–977.

Monitoring Glaucoma Progression By Vincent Michael Patella, Vice President, Professional Affairs at Carl Zeiss Meditec As a result of work over the past decade, many doctors are becoming more interested in knowing how fast a patient is getting worse and whether or not it's a tolerable rate of change. In other words, given the patient's life expectancy and given his current state of vision, what is the risk that this patient will become visually disabled in his or her lifetime, assuming progression continues at the current rate? If there's significant risk of visual disability in his lifetime, then it may be necessary to adjust therapy. Treating glaucoma patients may become an activity in which you monitor staging, rates of change and life expectancy. In a typical scenario, the doctor makes the diagnosis that the patient has glaucoma, determines how much damage already exists, and decides what therapy is most appropriate. Then the question becomes one of determining if the patient is progressing under current therapy and, if so, how fast. Determining the rate of progression may require investment of considerable diagnostic effort over the first few years. Not all glaucoma patients progress at vision-threatening rates. Perhaps, 15-20% of patients may remain at significant risk of visual disability under their initial therapy. The other 80-85% may be fine with their treatment, needing continued monitoring but no urgent change in therapy. Under this new philosophy, the emphasis is on determining if this is the 1 patient in 6 who is progressing so rapidly that he needs more aggressive treatment. If they're not at high risk, you will, of course, continue to monitor their status. If they are progressing rapidly, then they'll have the benefit of being considered for early adjustments in therapy. This represents a real change in the way we think about glaucoma management, but it probably isn't very different from how other diseases are managed. The two techniques for quantitative progression assessment are change from baseline, also known as event detection, and rate of change. Any progression software should include both analyses. This is because detection of change from baseline is typically more sensitive than rate of change, whereas rate of change provides critical information to help judge whether the patient is at risk for vision loss during their life expectancy. Guided Progression Analysis (GPA) software from Carl Zeiss Meditec features both assessments. Carl Zeiss Meditec has created guided progression analysis software, which was launched for the Humphrey Field Analyzer (HFA), and the Cirrus HD-OCT. GPA software measures the rate of progression, which helps doctors determine if patients are in need of a change in therapy. It also helps determine if statistically significant progression has occurred since baseline. The HFA measures visual field sensitivity and, in the case of the Cirrus, we're measuring retinal nerve fiber layer (RNFL) thickness and optic nerve parameters. For both instruments, the goal of GPA is that the visual presentation identifies change that exceeds expected variability and after a certain number of measurements, tries to estimate the rate of change in parameters of interest for each instrument. GPA reflects a recent evolution in glaucoma management philosophy. This philosophy is evolving to emphasize that treatment decisions should be based upon the goal of minimizing the risk of visual disability in each patient's lifetime. This new strategy frontloads the therapeutic investment, so in essence, we're saying, let's spend some intensive effort evaluating our patients soon after initial treatment has begun. Is their disease now progressing quickly, slowly, or somewhere in between? Once we've figured out who they are, we can focus our healthcare resources on the fast progressors, and perhaps manage less aggressively those who have demonstrated over the course of their clinical management that they are at minimal risk.