Improving Glaucoma Diagnosis
Fourier domain OCT can help with early detection and disease management.
By Vikas Chopra, M.D.
As clinicians, we usually look at the optic nerve for signs of glaucoma, but Fourier domain OCT enables us to look for signs of glaucoma in the macula. This is important because glaucoma causes retinal ganglion cell (RGC) loss, and most of the eye's ganglion cells are present in the posterior pole. Loss of RGCs leads to nerve fiber layer (NFL) thinning and optic nerve cupping. Fourier domain OCT not only allows us to detect this measurable loss of RGCs and NFL surrounding the optic nerve, but also can detect their loss in the macula with newly developed algorithms.
Here, I'll discuss how Fourier domain OCT can help sharpen our diagnostic accuracy in glaucoma patients. I'll also review several cases that demonstrate the efficacy of this exciting technology.
Generational Leap
As mentioned earlier, OCT has taken another generational leap forward in the last few years. The RTVue-100 has 65 times the speed and twice the resolution of time domain OCT systems.
One of the limitations of using time domain OCT is that it under-samples the macula, acquiring 6 radial scans in about 2 seconds. The slower scans are applied in a spoke pattern, with up to 1.6 mm of space between each spoke in the periphery. As a result, the scans miss valuable information and produce a keyhole view of the fundus. It's possible to miss a lesion the size of the optic disc in the peripheral macula and not detect the loss of ganglion cells between the spokes.
In contrast, the high-speed RTVue completes the scan in less than 1 second, offering significant advantages in looking at the macula. The higher speed also results in higher definition and a stronger signal because of improved signal-to-noise ratio. Furthermore, motion artifact is absent or significantly reduced.
The high-speed, high-definition RTVue offers 5-micron resolution and allows us to perform retinal layer segmentation, as shown in Figure 1. This allows us to examine the inner retinal layers, which are preferentially affected in glaucoma. The three innermost retinal layers are labeled as the ganglion cell complex (GCC), which encompasses the NFL, the RGC layer and the inner plexiform layer.
More Sensitive Parameters
We know that macular retinal thinning is a relatively insensitive diagnostic parameter for glaucoma.1,2 One reason is that RGCs make up about one-third of the thickness of the macula. So if we measure total retinal thickness without retinal layer segmentation, we may miss signs of early glaucoma, since mild-to-moderate loss of RGCs may not be reflected clearly in the total retinal thickness measurement. Thus, the solution is to examine the inner retinal layer thickness instead of total retinal thickness, which leads to significantly improved sensitivity and specificity.
When using time domain OCT, which considers only 768 points over a 6-mm diameter, the slow speed and lower resolution can't provide an adequate scan of the macula.
Figure 1. The high resolution and definition of the RTVue-100 provides a detailed view of all the internal layers of the retina.
However, our group at the University of Southern California and a team at the University of Pittsburgh have shown that the RTVue can provide reliable macular scans through effective retinal segmentation and much wider macular mapping.3,4
We designed the Macular Map 7-mm (MM7) scan pattern specifically for glaucoma diagnosis for the RTVue. The MM7 scan considers 15,000 points in a 7-mm square area in the macula within 0.6 seconds.
The RTVue-100 allows us to view what we refer to as the ganglion cell complex (GCC). The OCT scans are processed to automatically provide GCC deviation maps.
Figure 2. The ganglion cell complex (GCC), which comprises the three innermost retinal layers (nerve fiber layer + ganglion cell layer + inner plexiform layer), becomes thinner in glaucomatous eyes.
Advanced Imaging for Glaucoma
Under the direction of David Huang, M.D., Ph.D., one of the co-inventors of OCT, we're leading an ongoing, multicenter, prospective longitudinal clinical trial — the Advanced Imaging for Glaucoma Study (AIGS) — funded by the National Institutes of Health. The goal is to develop and use advanced imaging technologies to improve glaucoma detection and management. Data from AIGS participants who had undergone both time domain and Fourier domain scans were evaluated to compare the novel macular scans developed by us with the commonly used peripapillary NFL scans. We evaluated their ability to differentiate glaucomatous eyes from normal eyes. To date, we've included the following:
■ 125 eyes of 65 normal patients
■ 76 eyes of 52 glaucoma suspects/preperimetric glaucoma patients
■ 112 eyes in 79 perimetric glaucoma patients.
| Applications in Glaucoma By Joel S. Schuman, M.D., F.A.C.S. |
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| The Optovue RTVue-100 takes a unique approach to imaging and quantifying the optic nerve, retinal nerve fiber layer and macula. Using scan patterns and algorithms developed at Doheny Eye Institute, this device can map the RNFL and optic nerve head contour in a single scan set called NHM4. The macula can be mapped with grid-like patterns concentrated in the fovea, and analysis includes segmentation of retinal layers. For glaucoma, comparisons can be made between the superior and the inferior inner retina. Early results for glaucoma discrimination using this technique are promising. Does This Patient Have Glaucoma? Here's an example of how I use Fourier domain technology in practice. A 70-year-old Caucasian woman who had normal intraocular pressures but a high cup-to-disc ratio in her right eye was referred to me. She'd received laser treatment, cryotherapy, pars plana vitrectomy, epiretinal membrane peeling for retinal tears and cataract surgery — all in the right eye. The question was whether she had glaucoma. Images from the OptoMap (Optos, Marlborough, Mass.) of the optic nerve in her right eye showed the chorioretinal scarring that could be visualized in the inferior temporal retinal periphery by indirect ophthalmoscopy, where the cryotherapy had been performed. The visual fields showed a dense superior arcuate defect in the right eye. The optic nerve clearly indicated damage, but it wasn't clear if this was from glaucoma or retinal insults and trauma from a retinal detachment repair. Her left eye had a full field and a normal appearance on Heidelberg Retinal Tomography (HRT) (Heidelberg Engineering, Vista, Calif.). The HRT revealed some borderline changes in the right eye, corresponding with the field loss. Time domain OCT showed fairly significant thinning of the RNFL that corresponded with the visual field defect. If we looked at the intraretinal layers, we would see the decrease in total retinal thickness, especially toward the area of the retinal hole and where she had received cryotherapy. If we looked at the NFL and the inner retinal complex of the affected eye, we would see significant thinning. The question was, were we looking at glaucoma or damage associated with retinal disease because of the macular hole, pars plana vitrectomy and membrane peeling? Taking a Detailed Look Mapping of the RNFL thickness on time domain OCT using software developed by Hiroshi Ishikawa from our group allowed segmentation of the RNFL and the macula for both eyes. We could see the RNFL thinness in the right eye. The outer retina of the right eye didn't look too bad, compared to that of the left eye. When we took the measurements using calipers, we could see that there wasn't much difference between eyes in the outer retina, while the RNFL and ganglion cell layers were significantly thinner in the eye in question. When we looked at the images produced by Fourier domain OCT, we could clearly see that the damage was at the level of the RNFL and the ganglion cell layer, as opposed to the outer retina. Therefore, this faster, higher-resolution imaging technology confirmed inner retinal damage, and suggested that this patient's findings were unlikely to be related to anything other than glaucomatous disease. |
Figure 3. The fractional deviation map is derived from the ganglion cell complex (GCC). The percentage of thinning is compared to the average normal retina.
As seen in Figure 2, the GCC becomes thinner in glaucomatous eyes. What we've derived from that information are several deviation maps, including one particularly useful map called the macular GCC (mGCC) deviation map (Figure 3).
From this map, we derive the fractional deviation map, which shows the percentage of thinning compared to what we find in the average, normal retina. We take a subject's map, subtract the normal map and divide it by the normal map to get an integral of deviation in areas of significant focal loss. Focal loss often occurs in early glaucoma, and it can be measured using Fourier domain OCT.
Figure 4. The macular GCC (mGCC) deviation map of this eye with perimetric glaucoma shows reduced GCC thickness and reduced focal loss volume (FLV), which corresponds well to the inferior rim loss on photos and superior visual field defects on perimetry.
The area of significant focal loss is marked by the red-hatch region seen in Figure 3. The volume of GCC loss within the focal loss area is a key diagnostic parameter called Focal Loss Volume (FLV). Glaucoma characteristically thins the GCC most in the inferior arcuate area.
Sample Uses of GCC Maps
In the case of a patient with perimetric glaucoma (Figure 4), we see that significant visual field loss corresponds to the patient's inferotemporal cupping. The glaucoma hemifield test is outside normal limits. The macular GCC deviation map shows an average thickness of 66 microns, which is significantly reduced. It also reveals a 9.7% loss of focal volume, representing a significant loss of RGCs.
Figure 5. This glaucoma suspect eye has superotemporal rim notching on the optic disc photograph. Visual field parameters are normal.
The patient shown in Figure 5 has preperimetric glaucoma, as shown by superotemporal rim notching on the optic disc photograph. The visual field test parameters, including the pattern standard deviation and the glaucoma hemifield test, are essentially normal. However, on the macular GCC map, we clearly see attenuation that matches the area of rim thinning on the disc. This GCC map quantifies this change as a 4.5% loss of focal volume.
Review of the visual field shows shallow defects of –5 dB to –6 dB on the pattern deviation map in the matching location. Note that the GCC is actually thicker than normal in some areas, and the average is normal in this case. Therefore, GCC loss is apparent only on the focal loss analysis. It's clear that we can use this technology to view the macula and monitor this patient.
Comparing OCT Parameters
We compared the macular thickness parameters of the RTVue and the time domain OCT and found that the RTVue provides greater diagnostic accuracy for assessment of macular ganglion cells, due to the RTVue's ability to look at retinal layer segmentation. The area under the operating curve is much greater for the RTVue, both in the perimetric and preperimetric glaucoma groups in a statistically significant manner.
Figure 6. An RTVue-100 scan of a patient with normal cups and normal nerve fiber layer is compared to an RTVue-100 scan of a glaucoma patient with advanced optic nerve cupping.
The RTVue also may improve repeatability compared to time domain OCT as found with higher intraclass correlation values. This is critical because of the potential it creates for tracking glaucoma over time. With improved repeatability, we may be able to detect true change, rather than simple variation.
Besides providing a novel means of macular mapping, the RTVue-100 performs optic nerve head mapping at 4 mm (NHM4 map) in less than 0.4 seconds with more than 9,500 A-scans. The NHM4 map describes optic disc morphology, measures peripapillary NFL (ppNFL) thickness and provides comparison with a normative database.
Evaluating Deviation Maps
Fourier domain OCT scan results from a patient with normal cups and a normal NFL on the left side are shown in comparison with a glaucoma patient with advanced optic nerve cupping on the right in Figure 6.
Figure 7 shows an optic nerve head ppNFL deviation map with a scan diameter around the optic nerve ranging from 2.5 mm to 4.0 mm. This is the same patient with perimetric glaucoma who was shown to have ganglion cell loss in the macula in Figure 4. Here, we can clearly see that the average NFL thickness is reduced to 49 microns around the optic nerve. Thus, we have confirmatory data with good concordance between the macular GCC scan and the optic nerve head ppNFL scan of the same patient.
Figure 7. This is an optic nerve head peripapillary NFL (ppNFL) deviation map with a scan diameter around the optic nerve ranging from 2.5 mm to 4.0 mm.
On the optic nerve head ppNFL deviation map of the preperimetric glaucoma patient (Figure 8), thinning in the supratemporal quadrant is clearly revealed. This is the same patient with preperimetric glaucoma who was shown to have RGC loss in the macula. The average NFL thickness is reduced to 54 microns around the optic nerve, also confirming the loss of macular focal volume seen in the macular GCC scan.
These data suggest that the RTVue may provide higher diagnostic accuracy for glaucoma diagnosis. However, a larger study is needed to confirm our findings and we're continuing to recruit for the AIG study. Again, this technology may improve repeatability and the potential to track glaucoma over time by looking at peripapillary and macular deviation maps.
Great Potential for Managing Glaucoma
The high-speed, high-resolution Fourier domain OCT provides clinicians and researchers better capabilities in the diagnosis and management of glaucoma. Fourier domain OCT is comparable to time domain OCT for glaucoma detection when using the optic nerve head ppNFL scans. However, the RTVue provides additional scan patterns of the macula that aren't found on the commercially available time domain OCT. The newly developed, wide-area macular scan with automatic retinal layer segmentation on the RTVue provides significantly greater diagnostic ability using mGCC compared to the total macular thickness by time domain machines.
Figure 8. A peripapillary NFL deviation map for a preperimetric glaucoma patient shows thinning in the supratemporal quadrant.
We're trying to determine if we can combine the ppNFL measurement and the GCC-FLV to create a global score that would help us determine a patient's risk for developing or having glaucoma. Also, in select cases, we may be able to use a macular scan instead of a ppNFL scan for glaucoma detection and follow-up, especially if we're unable to acquire a high-quality ppNFL scan. Thus, Fourier domain OCT, and the RTVue-100 in particular, hold great potential for earlier diagnosis and better management of glaucoma.
Vikas Chopra, M.D., is assistant professor of ophthalmology at the Keck School of Medicine at the University of Southern California and the Doheny Eye Institute.
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