DIAGNOSTICS
Overcoming Challenges in Detecting Glaucoma Progression
A new software tool may enhance your ability to identify and manage glaucoma.
By Murray Fingeret, O.D., New York, N.Y.

We can prevent significant vision loss for the more than two million Americans who have glaucoma if we properly monitor glaucoma progression -- particularly as it affects a patient's visual field. That's why it's important for us to recognize when it's necessary to step up treatment regimens.

This article will share ideas on how best to approach glaucoma detection and will review methods to monitor the progression of this disease.

Common challenges

It has long been recognized that a series of perimetry tests performed at regular intervals and compared over time provides significant insight into the progressive damage to a patient's visual field. However, clinicians have traditionally faced several challenges in assessing changes in relation to glaucoma progression. For instance, even when a clinician could determine the occurrence of a functional change, there was no objective way to confirm whether the change was a result of test variability or true disease progression.

Today, a new software tool called Glaucoma Progression Analysis, or GPA (developed for the Humphrey Field Analyzer II), will impact the way we manage glaucoma patients by enhancing our ability to quantify both the likelihood and the rate of disease progression.

Imaging is currently more important for the diagnosis of glaucoma than detecting progression. Scientists are developing software such as GPA for Carl Zeiss Meditec's OCT (optical coherence tomography) and for Laser Diagnostic Technologies' GDx nerve fiber analyzer that will provide probability analysis as to the significance when a practitioner finds progression. Any area may change because of variability, so we need to assess that the change is really glaucomatous. Imaging software that will allow us to use data gathered today in this analysis will be available soon.

Analyzing progress

The GPA software enables an easier and more precise way to monitor changes in the visual field by evaluating a series of SITA tests in a way that statistically assesses progression. The software can help clinicians determine new defects, or a deepening or enlargement of existing defects. Traditionally, there have been three main challenges in assessing perimetric evidence of glaucoma progression, all of which the GPA software helps to overcome.

Challenge 1: Manual comparison of printouts. Traditional tools required clinicians to manually compare individual test printouts taken over time. Comparing printouts to identify progression has always been an inexact art requiring a substantial amount of guesswork.

At the completion of a follow-up visual field test, a clinician can now simply select GPA from a list of options on the Humphrey Field Analyzer. The program requires a minimum of three visual field tests to run. It averages the first two fields to find a baseline. You can use older full-threshold fields as the baseline, but the analysis generally works with SITA fields. The software assists in selecting the baseline and follow-up exams to analyze, discarding any tests with low reliability, for instance, if a test has an abnormally high number of false positives.

Once the GPA establishes the baseline and follow-up exams, it performs an automated point-by-point analysis, making the comparison of visual field defects easier and more precise. It flags each point where it detects change with a small open triangle and it marks points where deep damage has already occurred with a small "x," and cannot be used to detect further damage.

When you perform a new follow-up exam, GPA compares the results to the baseline and to the last two fields performed, if available. It confirms change at each test, and when it flags points as getting worse a second time, you'll see a new symbol: a triangle filled in half way.

GPA analyzes the overall patterns of change and provides plain-language interpretations. When it flags the same three points as getting worse on two consecutive tests, it will mark a reading of "Possible Progression" on the field printout. When it notes significant degradation in three or more points in three consecutive exams, the software indicates "Likely Progression" on the printout.

When visually comparing printouts, a clinician may mistakenly determine that a patient is progressing. However, GPA technology will confirm whether the patient field is in fact stable. When five fields are available, GPA provides a quantifiable rate of change in dB each year.

Challenge 2: Test variability. Perhaps the biggest culprit that has traditionally hindered the recognition of true glaucoma progression has been variability among tests. In perimetry tests, all points have a small amount of variability; findings are rarely the same from test to test, even in a normal field. In addition, test/re-test variability is greater in glaucomatous eyes than in normal eyes. As a result, when manually comparing printouts, a test point may appear worse, but clinicians must "guess" whether the change was a result of variability or true progression. Today, the GPA software compensates for variability by drawing information from its database of glaucoma patient tests and retests.

The same scientists who led the Early Manifest Glaucoma Trial (EMGT) developed the technology in GPA. They incorporated new mathematical formulas to calculate the variability in patient testtaking by evaluating individuals who had glaucomatous field loss at 16 clinical sites. They obtained confidence limits by testing patients four times within a one-month period. In such a short time frame, you wouldn't expect glaucoma to progress, which allowed the scientists to analyze and quantify the amount of variability associated with glaucomatous field loss.

When evaluating field tests with GPA, we compare patient threshold values with the system's database of variability estimates. It flags any test point in a follow-up exam that worsens by an amount that exceeds the variability found in 95% of glaucomatous patient tests (p<0.05) as representing significant change at that test point. Points that change significantly and repeatedly indicate "progression."

However, even when using GPA, a clinician must be aware of the "learning effect" among patients. It may take a patient up to three visual field tests to establish a meaningful baseline, and it may be necessary to select different baseline exams than the ones the machine automatically chooses.

Challenge 3: Other media effects. In the past, it was also difficult to distinguish between reduced visual fields caused by glaucoma versus other conditions. GPA actually adjusts for visual field loss caused by other media, such as cataracts and pupil effects. This ensures a more accurate analysis and ultimately leads to a more appropriate treatment regimen.

The GPA software does this by using pattern rather than total deviation maps. Total deviation refers to change that affects the entire field, which can be a result of glaucoma, but also can result from a variety of other issues such as cataracts, a corneal scar or small pupils.

We associate pattern deviation loss, on the other hand, with localized or focal loss related to glaucoma. Pattern deviation maps detect glaucomatous change and ignore loss associated with other conditions.

Buddy up the GPA

By incorporating SITA examinations, pattern deviation and advanced progression algorithms, GPA accurately identifies degeneration of the visual field because of glaucomatous progression. However, it's not advisable to look at perimetry alone; instead use it in concert with IOP and structural assessment of the optic nerve and retinal nerve fiber layer to obtain a more comprehensive assessment of progression.

Future progression

Detecting the progression of visual field loss in glaucoma patients is important for effective long-term management of glaucoma patients. For years, clinicians have faced many challenges that have prevented them from performing this analysis accurately and objectively.

Today, software tools such as GPA take the guesswork out of perimetry, providing a means to eliminate the need for manual comparison, to compensate for variability and to reduce the effects of other conditions, so clinicians can determine whether new defects or a deepening of existing defects have occurred. IOP measurements and structural assessment are also important for observing advancing structural changes caused by glaucoma, and provide practitioners with complementary information to their perimetric data.

Detecting and stopping glaucoma progression is a key component to preserving patient vision and practitioners must remain diligent in monitoring visual field as well as structural changes that indicate progression despite current therapies. In the future, we'll continue to better understand the interplay between functional and structural changes to better serve our glaucoma patients.

Dr. Fingeret is chief of the Optometry Section, Brooklyn/St. Albans Campus, Department of Veterans Administration New York Harbor Health Care System. He is a clinical professor at the State University of New York College of Optometry, a fellow of the American Academy of Optometry, a member of the Glaucoma Advisory Committee of Prevent Blindness America, the National Academies of Practice and American Glaucoma Society. Dr. Fingeret is chair of the Glaucoma Diplomate committee of the American Academy of Optometry. 

CASE IN POINT

Figure 1.  Figure 2.  Figure 3. Through my experiences with glaucoma progression analysis (GPA) software, I've been able to differentiate between developing glaucoma, stable glaucoma and continued progression. New technologies such as GPA make the detection of visual field loss in glaucoma patients less challenging for clinicians, resulting in better long-term outcomes for our patients. The following is a patient case demonstrating my experiences with GPA software. Case History: Progression In this glaucoma patient, the SITA Standard visual field printouts for the right eye reveal an inferior arcuate scotoma. The fields are available from September 1996 through November 2003. The software shows that the patient is progressing over a period of time. The baseline page graphically reveals that there is progression with the mean deviation getting worse at a rate of 0.49 dB/year (see Figure 1, p. 28). This change could be the result of different causes including cataracts or glaucoma. From my clinical exam, I know that cataracts haven't progressed and that glaucoma is the cause for this change. Two points change in 1999, and one of those points is repeatable in 2000 (see Figure 2, p. 30). I note further change in 2001, though only one point has changed consistently (seen as the black triangle). By 2002, several points have changed on two consecutive fields. The message on the field reads "Possible Progression." While the patient's IOP was in the mid-teens, therapy was now advanced and the IOP lowered further. In 2003, I confirm change as a series of points got worse on three consecutive fields (see Figure 3, p. 31). While this patient has worsened as compared to the 1996/98 baseline examination, looking at the graph on the front sheet it appears that the change hasn't recently worsened. I can confirm this observation by resetting the baseline exams and using the 2001/2002 fields, which will then indicate whether progression is still occurring.