To summarize results, robust, continuous, repeatable, and clinically useful tracking on the lamina cribrosa was achieved in 96% of subjects tested in the clinical protocol. Examination of co-added disc circle OCT images found an improvement in 100% and 94% of the images for normal and glaucoma subjects. Analysis of the mean variation in disc edge position found an improvement in every subject. The variation in individual sets found an improvement in 82% and 77% of intra-visit sets and a reduction in standard deviation from greater than 2 to approximately 1 pixel for normal and glaucoma subjects. Similar analysis found an improvement in 93% and 94% of individual inter-visit sets and a variance reduction from nearly 3 to approximately 1 pixel for normal and glaucoma subjects.
As noted above, the purpose of the disc circle scans is to measure RNFL thickness for early diagnosis of glaucoma. Although preliminary analysis of RNFL thickness found no improvement due to tracking [12
], RNFL thickness may not be an appropriate measurement endpoint for the characterization of improvement due to tracking. This is because the effect of tracking may not be revealed within the typical RNFL standard deviation (≤10 μm with a ~120 μm mean). As seen in and , the shallow gradients of these layers render such measures less sensitive to transverse motion. This does not mean that tracking is not effective in obtaining more accurate RNFL metrics, and therefore potentially more sensitive and specific glaucoma diagnosis. Rather it means that an improvement should be made in the methodology of standard clinical RNFL measurements. For example, in other current (e.g., OCT III) and future systems, there is an improvement in both transverse and longitudinal image resolution. This should inevitably yield higher precision values for RNFL thickness. Also, as illustrated by and , an increase in the number of co-added images will significantly reduce speckle noise artifacts. This can only be accomplished with perfect registration from scan to scan. A 5% change in RNFL is significant loss. Without tracking, the effect of motion is masked by co-adding noisy scans. This constraint no longer exists with TOCT: boundaries will only become better defined by averaging because high image spatial frequencies are preserved with tracking.
In and , the overall appearance of the averaged circle scans with and without tracking is similar because the layer thickness does not change rapidly in the retinal plane. However, with tracking the most significant improvement is in resolving fine structure. Shadows of major retina vessels and often the vessels themselves can be clearly seen. Note that considerably greater structure in the underlying choroidal vessels is also evident. Further, there is a subtle enhancement of the contrast at the outer boundary of the RNFL. These features are easily understood because tracking causes successive images to align in the transverse directions to much better precision than the ~110-μm pixel size. The positions of fine scale features never shift. Further, to the extent that transverse motion is uncompensated, the vertical alignment algorithm will also induce errors without tracking.
Since only three radial scans (disc cup and macula) at any angle were collected and co-added, the reduction of speckle noise is not as dramatic in and . In , the true shape of the cup is distorted because of out-of-plane motion (see below). The disc cup edge in is broadened and blurred compared to . Without tracking, vertical alignment suffers somewhat from motion – tending to make boundaries visibly fuzzier. In , the foveal pit is not visible and the retinal boundary in this region blurred. Retinal layers visible on either side of the fovea (more clearly to the right) with tracking () are completely washed out in the non-tracking case (). Tracking thus provides a benefit by making low contrast boundary detection more robust. But this benefit may not be resolvable with only three scans. The effect lies within the standard deviation of the image noise statistics for so few scans, at least for good fixators. also illustrates one reason why extraction of edge and area information from the foveal pit is more difficult than that for the disc cup: because the pit area is much smaller and the edges more shallow (note the 5× reduction in scale of compared to ). The other primary reason is that the OCT signal is reduced in the foveal pit because of the absence of overlying layers that are more highly scattering and thus produce a clear demarcation of retinal edge.
The appearance of images co-added from 3 visits in is similar to the images co-added from single visits in and . Since this subject (normal subject 3) was a fairly good fixator and for the reasons discussed above, the appearance of some layers is preserved in the non-tracking co-added OCT image (). However, distinct layers of both the retina and choroid are blurred in the non-tracking image where they are clear and sharp in the tracking image (). Moreover, the location of blood vessels, denoted by their shadows, are preserved and enhanced in comparison to the single scan (). The effect of tracking as illustrated by the fundus images () is clear.
Before a full discussion of the quantitative analysis presented in –, one consideration of the method of data analysis alluded to in Section 4.3 must be fully explained. For many of the non-tracking scans, eye motion with a large vector component normal to the OCT scan was large enough to prohibit measurement of disc cup edge position. This large out-of-plane motion is illustrated in . In , an appropriate scan through the center of the disc is made. In the very next scan, , the motion was large enough so that no portion of the disc was scanned. show the co-added OCT and fundus images from this set. Obviously, the edge position of the disc cup cannot be measured for this large motion. Therefore, the entire set was thrown out. The effect of this is to make the standard deviation in – for the non-tracking cases artificially lower than is actually the case. Mild out-of-plane motion is also illustrated in the retinal edge position in run 3 of .
Figure 11 Large out-of-plane motion, common only in the non-tracking case, made co-addition of images and measurement of disc cup edge impossible. a. Single OCT scan centered on disc, b. Single OCT scan with large position error, c. Co-added OCT image from 3 individual (more ...)
It is clear from the results of the disc cup edge analysis presented in –, that there was a wide range of fixators in both the normal and glaucoma groups. This can be seen in the “NT avg” column, which displays the variation in disc cup edge under normal, non-tracking conditions. It should be emphasized that the standard deviation calculation made in these tables is a measure of the variance and is different from the peak-to-peak amplitude of eye motion estimated in Section 4 to be 0.5 deg (~150 μm) or 3 pixels for radial scans for a good fixator. The peak-to-peak amplitude can be several (i.e., 2–4) times larger than the standard deviation. Thus a range from 1.46 to 3.25 for normal subjects and 1.66 to 3.24 for glaucoma subjects for the standard deviation means a wide range of fixators were present in the sample, with the normal subjects slightly better fixators overall.
Although the overall standard deviation (i.e., mean for all sets) was reduced for all subjects when tracking was engaged, an improvement was found in only 82% and 77% of individual sets for normal and glaucoma subjects, respectively. Further examination of the data shows that the normal subjects that had particularly low percentages were generally the best fixators (). For example, the three best fixators (subjects 1, 10, and 6) had three of the four worst percentages. This leads to the obvious conclusion that tracking will be less useful for good fixators subject to the transverse image resolution. That is, if the amplitude of involuntary eye motion in a subject is lower than the pixel resolution of the imaging technique, then tracking can only improve position accuracy to the size of an individual pixel. In current and future high-bandwidth OCT systems, the limiting factor may be tracking accuracy rather than pixel resolution. For example, the current CZMI OCT III (Stratus) system uses 500 transverse pixels, or an improvement of 5 fold in resolution to ~12 μm, near the tracking accuracy found in other systems (<15 μm for TSLO [9
The limiting factor of pixel resolution on tracking performance can also be seen in the overall reduction in standard deviation from tracking to non-tracking. While the non-tracking standard deviation in disc cup edge position is correlated to the physiological factors that determine involuntary eye motion amplitude, the tracking standard deviation is limited by the image resolution. We expect that as the transverse pixel resolution is decreased to the limit of tracking accuracy, the variation in edge position will remain between 0.5 and 1 pixel for most subjects with tracking engaged, but will increase to the pixel equivalent for the range of fixators tested without tracking engaged (from approximately 0.5 deg or 150 μm for the best fixators).
Although there is a slight difference in disc cup edge position standard deviation between normal and glaucoma subjects, the degree to which this difference is significant is not known. Most of the problems may be traced to factors unrelated to tracking. For example, some glaucoma subjects had intra-ocular lenses (IOLs) that caused a drastic degradation of the OCT signal. Although this didn’t affect tracking robustness, it made extraction of information from poor OCT images difficult. There was also an increase in other problems with the glaucoma group that were not related to the performance of the TOCT system (e.g., subject attentiveness, etc.). As mentioned previously, there were also several subjects in the glaucoma group that had multiple tracking points within the optic nerve disc. These patients require particular attention from the operator. Many of these problems are inevitable in a clinical environment. It is expected that in further clinical testing with higher resolution OCT instruments, the tracker should give transverse scan alignment absolutely equivalent to the normal subjects – better than is possible for even the highest functioning fixators. It is under such circumstances that the clinical value of TOCT will be most evident.
When the data is re-sorted to compare disc cup edge variance between visits ( and ), it is clear that tracking is even more important to register images from visit to visit. An improvement in overall standard deviation was again seen in all subjects, with improvement in 93% and 94% of individual sets. This increased improvement results from the capability of the tracking system to continually return the OCT imaging beam to the same pixel coordinates. Conversely, without tracking, the operator is relied upon to locate the same disc cup position from the mediocre fundus image. (For macular scans, this degradation from visit to visit may not be as profound because the OCT scan automatically goes through the center of the fixation point, that is, the fovea). Thus, between visits with tracking engaged, the disc cup edge position variation is less than a fixed threshold (2 pixels) the same percentage of time as within visits (see “T<R” column in –). However, for the same fixed threshold with no tracking, the percentage drops considerable between visits compared to within visits (“NT<R” column in and compared to 2 and 3). This is also seen in the large increase from approximately 2 to 3 in the total non-tracking standard deviation. The slight increase in tracking standard deviation probably results from the accuracy of a calibration method (± 1 pixel), which was required to align coordinate axes of the OCT and tracker components of the TOCT. In a fully integrated system, we expect the tracking standard deviation to be identical within and between visits.
For the TOCT instrument, these results show a clear and significant enhancement of scan position accuracy and reproducibility for retinal tracking compared to fixation. Fine structure not readily resolved in single scans can easily be seen in averaged images. In the co-added images acquired without tracking, the finest scales are washed out – typically over three or more image pixels (over 300 microns at 110 microns per pixel, i.e., motion of ~1 deg). This motion occurs both laterally, and most problematically, in and out of the image plane. This blurring and distortion is particularly clear with scans through the disc with steep vertical features, at the fovea, and with circular scans with blood vessel and their shadows. The precise shape of cup, disc, and rim area is always certainly degraded by this effect. In multi-frame averages of circular scans around the disc, disc radial scans, and macular scans, the reduction in speckle noise is significant, while the fine structure is still clear. The vessel shadows line up perfectly in all tracked images taken over the hour-long visit duration in all subjects, boundaries are sharp, choroidal vessel structure is evident. For nearly all subjects, the effect of tracking is to make everyone a perfect fixator, regardless of age and eye motion characteristics. The observed level of transverse scan reproducibility appears to be consistent with the requirements for potential acquisition of high quality three-dimensional maps.