GPA: A Better Way of Looking at Glaucoma

By 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), and OCT with the Cirrus™.

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 few as 3 visual field tests. You could obtain two 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.

The HFA measures the Visual Field Index™ (VFI™), an age-adjusted and center-weighted assessment of the overall percentage of the remaining visual field. This global index best answers the question, “Doctor, how much visual field do I have remaining?” HFA answers this question 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 one 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 being able to deal 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. ■

Nathan Radcliffe, MD, is a cataract and glaucoma surgeon at the New York Eye Surgery Center and is a clinical assistant professor of ophthalmology and director of the glaucoma service at NYU Langone Ophthalmology Associates.

References

GPA Summary Report — Sample Case
Likely progression

This is an example of a patient with statistically significant and possibly clinically significant progression. This patient’s visual field loss is measurably progressing based upon the GPA alert and the VFI slope. The patient may be at significant risk of further visual loss in the future. These findings must be considered in the context of patient life expectancy and also relative to the possible risks associated with any contemplated escalation in treatment.

 

1. VFI slope is pronounced, showing a decrease of almost 23% over the past 5 years.

 

 

1. Patient was 87 years old at the time of the most recent test.

 

 

1. Event analysis (GPA Alert) indicates “Likely Progression”.