Article

Catch the “comma,” spare the vision

Macular (paracentral) defects in patients with open-angle glaucoma are too easy to miss.

Early in the glaucomatous process, arcuate-like defects often appear in the macular (paracentral) region — an area vital for everyday activities, such as driving and reading.1,2 By macular region, we mean the central ±8° from fixation. This region represents only about 2% of the retinal area but contains more than 30% of the retinal ganglion cells.3

Robert Ritch, MD, our colleague and a well-known glaucoma specialist, first alerted us to these defects; he called them “comma-shaped” defects due to their appearance on 10-2 visual fields. Because the macular region is involved in activities essential to everyday life and thus to maintaining the patient’s independence, it is critical to recognize these defects as early as possible. Yet the tests most commonly used in the clinic can miss them.

Below we address two questions: why do the current tests typically used in clinical practice miss and/or underestimate these arcuate defects, and how can the clinician detect these defects with currently available technology?

WHAT IS AN ARCUATE DEFECT IN THE MACULA?

First, let’s illustrate what we mean by an “arcuate-like defect in the macular region.” Figure 1 shows a fundus photo with a pseudo-color map of the optical coherent tomography (OCT) thickness of the retinal ganglion cell plus inner plexiform (RGC+) layer for the average of a group of healthy eyes.4 Notice the thick ring of GCs around fixation, indicated by the orange plus symbol (+). This ring is due to the large number of GCs in this region and because those GCs closest to fixation are pushed to the side during development so that the foveola has only receptors and Müller cells.

Figure 2A (page 36) shows a similar GC+ thickness map for a patient with an arcuate defect near fixation in the superior visual field of the right eye, as seen on the 10-2 probability maps in panel B. Notice the missing region of the GC+ layer (white arrow in panel A), which corresponds to the arcuate (“comma-shaped”) defect on the 10-2 (black arrows in panel B).

Figure 1. A pseudo-color map of the average retinal ganglion cell plus inner plexiform (RGC+) thickness of a group of healthy eyes superimposed on a fundus photograph. The macular region, ±8° from fixation, falls within the black circle. The white line indicates the location of the OCT b-scan above.

Figure 2. A. A pseudo-color map of the RGC+ thickness as in Figure 1, but for an individual with an arcuate defect close to fixation. B. The total deviation and pattern deviation probability plots for this eye’s 10-2 visual field test. The arrows in both panels indicate corresponding locations.

TWO ASSUMPTIONS

Now let’s look at the anatomical basis for arcuate defects in the inferior macular region and the corresponding 10-2 superior visual field location. When told that these defects are relatively common, many clinicians are surprised. After all, they say, “I thought that damage near fixation occurred late in the glaucomatous process. Isn’t that why the 10-2 is used for cases of advanced glaucoma?”

The anatomical basis for this statement is based upon two commonly held beliefs. One, the temporal quadrant of the disc is thought to be less vulnerable to glaucomatous damage than are the inferior and superior quadrants.5 In fact, this appears to be true; the regions of the disc with the greatest damage are in the superior and inferior quadrants, as shown by the orange and green arcs in Figure 3 (page 36).6

Figure 3. A schematic of an anatomical model showing the relationship between the location of the RGC on the retina (circles) and the location where their axons enter the disc. The solid ellipse represents the disc and the dashed circle the location of the OCT circle scan. The regions of the superior and inferior disc most vulnerable to axon loss are labelled SVZ (superior vulnerability zone) and IVZ (inferior vulnerability zone). Notice the axons from the RGC in the inferior portion of the macula enter the IVZ. This portion of the disc is the macular vulnerability zone (MVZ).

Two, it was generally thought that the axons of the GCs of the macular region entered the temporal quadrant. We now know this is not strictly true.7 While the axons from the GCs in the superior macular region (blue circles in Figure 3) and the GCs from the maculo-papillary region (orange circles) enter the less vulnerable temporal quadrant of the disc, the axons from the GCs from the inferior portion of the macular (red circles) enter the most vulnerable portion of the disc, the inferior quadrant (green arc). We have called this portion of the disc the macular vulnerability zone (MVZ), and it is shown as the black arc in Figure 3.4,6,7

Consequently, the region of the disc most vulnerable to early damage (green arc in Figure 3) receives axons from the inferior macular, as well as from the inferior regions of the retina associated with the more classic inferior retina/superior visual field arcuate defects.

IT’S NOT TOO SOON TO CHECK

These macular arcuate defects associated with the MVZ are very common and occur early in the glaucomatous process. By “early” glaucoma, we mean an optic disc appearance consistent with glaucomatous optic neuropathy (GON) and a 24-2 visual field with a mean deviation (MD) better than -6 dB. Using this definition, we recently reported that 75% of 57 eyes with early glaucoma had damage in the MVZ.6 For example, the eye in Figure 2 had a 24-2 MD of -0.96 dB and thus would be classified as early glaucoma. While some eyes have very localized damage in the MVZ, in general the MVZ is often associated with damage throughout the inferior vulnerability zone (IVZ, Figure 3).6

Further, in addition to local damage, widespread damage often associated with glaucoma can affect the macula as well.8 Thus, the overwhelming majority of eyes will show early damage in the macula.

DETECTING MACULAR ARCUATE DEFECTS IN THE CLINIC

Typically, when evaluating patients for glaucoma, a 24-2 visual field is obtained, often along with an OCT scan of the disc. Both these tests can miss arcuate defects in the macula.6,9,10 The 24-2 does a particularly poor job,4,6 because the vulnerable region is poorly sampled by its 6-degree grid. Figure 4 (page 37) illustrates how a 24-2, which has test points spaced by 6 degrees, can completely miss a deep defect easily seen on the 10-2 test, which has test points spaced by 2 degrees. Thus, we recommend that clinicians either test all glaucoma or glaucoma-suspect patients with a visual field test pattern that includes a finer test grid in the macular area or perform both 24-2 and 10-2 tests within the first two visits.11

Figure 4. An example of a deep arcuate defect near fixation as seen on the 10-2 visual field (bottom panel), but missed by the 24-2 visual field test (upper panels) obtained on the same day.

While the OCT disc scan does a better job than the 24-2 in detecting these defects, it too can miss this damage.6,8,9 Thus, we also strongly recommend that a cube scan of the macular region be included in the initial OCT test. In some OCT instruments, this requires two cube scans — one centered on the macula and another centered on the disc. In other instruments, only a single scan is required as it includes both the macular and peripapillary regions.

For example, Figure 5 shows scans of the same eye from three OCT instruments. This eye has an arcuate defect near fixation as shown by the 10-2 in panel A. The arcuate defect is easily identified on the GC thickness and probability/deviation maps, as indicted by the black arrows within the green (GC thickness) and red (GC probability) rectangles. Given the difficulty in obtaining 24-2 and 10-2 in all patients in clinical practice, the results of the macular OCT cube scan can tailor the choice of which test strategy to perform on individual patients.

Figure 5. A. 10-2 visual field for a patient with an arcuate defect in the macula. B. Zeiss OCT report based on cube scans of both the macular and disc. C. Topcon OCT report based upon a wide-field scan including both the disc and macula. D. Heidelberg reports from a circle scan of the disc (left) and a cube scan of the macula. For panels B-D, the blue rectangle indicates the circumpapillary retinal nerve fiber thickness plot; the blue dashed rectangle the circumpapillary scan image; the green rectangle the ganglion cell (GC) thickness map (D, right) or GC+ inner plexiform map (C); and the red rectangle the GC+IPL probability/deviation map (B, C). The black arrows indicate corresponding regions of damage.

For more information, see references 4, 6 and 11 as well as the lecture series “How to identify glaucomatous damage on OCT scans,” found at http://hoodvisualscience.psych.columbia.edu .

SUMMARY

Both diffuse and local damage of the macula are very common early in the glaucomatous process. Arcuate defects near fixation are particularly important to detect but can be missed with common clinical tests (i.e., disc exams, 24-2 visual fields and OCT scans of the disc). On the other hand, they can be clearly identified with GC analysis of OCT macular scans and 10-2 visual fields. Both should be routinely used in the clinic. OM

REFERENCES

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  4. Hood DC, Raza AS, de Moraes CGV, Liebmann JM, Ritch R. Glaucomatous damage of the macula. Prog Ret Eye Res. 2013; 32:1-21.
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  9. Wang DL, Raza AS, de Moraes CG, Chen M, Alhadeff P, Jarukatsetphorn R, Ritch R, Hood DC. Central glaucomatous damage of the macula can be overlooked by conventional OCT retinal nerve fiber layer thickness analyses. Trans Vis Sci Tech. 2015;4:4. eCollection.
  10. Muhammad H, Fuchs TJ, De Cuir N, De Moraes CG, Blumberg DM, Liebmann JM, Ritch R, Hood DC. Hybrid deep learning on single wide-field optical coherence tomography scans accurately classifies glaucoma suspects. J Glaucoma 2017;26:1086-1094.
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