The findings of this study suggest that progressive RNFL thickness changes were better detected on widefield OCT scans than from a derived circle scan of optic disc scans using a manual ROI approach after accounting for measurement variability and age-related changes. This highlights the potential advantages of using widefield scans to monitor progressive glaucomatous damage, which may be gained by evaluating a larger proportion of the entire RGC axonal tract as compared to a single location with a circumpapillary circle scan.
To fully appreciate the implications of the findings of this study, it is important to understand the longitudinal SNRs that were evaluated. Longitudinal SNRs provide a normalized measure of the age-adjusted rate of change in RNFL thickness for an eye divided by the standard deviation of test-retest differences. This measure is distinguished from conventional SNRs or z scores, which can be used to represent a normalized measure of the extent of change relative to variability, rather than the rate of change. As such, longitudinal SNRs are not intended to provide an estimate of whether an individual eye has progressed or not but rather are simply used to compare the different methods evaluated in this study.
Recognizing this interpretation, we note that no prior progression study, to our knowledge, has compared the performance of RNFL thickness measurements from a three-dimensional 12 × 9-mm widefield volume scan against those from a two-dimensional circumpapillary circle scan. Studies that have compared RNFL thickness measurements from the entire three-dimensional 6 × 6-mm optic disc scan against the circumpapillary circle scans have also been scarce and inconclusive. One study suggested that local event-based analysis of the RNFL thickness maps on such optic disc scans detected the greatest number of glaucoma eyes as having progressed compared to event- and trend-based analysis of cpRNFL thickness measurements,
9 whereas the results from another study suggested that trend-based analysis of the global cpRNFL thickness performed best.
12 However, neither study reported the statistical significance of these differences nor the specificities of these methods (required for equivalent comparisons), making it difficult to determine whether the analysis of the entire RNFL thickness map or cpRNFL thickness values is better based on those studies.
The improved ability for the progressive RNFL thickness changes to be detected on the widefield scans may be attributed to the greater reduction in measurement variability through averaging measurements over a substantially larger scanned area. The number of A-scans within the entire widefield scan (after excluding 1 mm from each edge) is nearly 20-fold that within the derived circle scan from the optic disc scan (averaged over a 100-μm annulus). It may also be attributed to the fact that progressive RNFL thickness change is more accurately captured when evaluated along a much larger portion of its entire axonal tract using the widefield scans, enhanced by the use of a manual ROI approach where a greater extent of information was available.
17,18 However, it remains to be determined how measurements from a single high-resolution, frame-averaged circle scan (e.g., those obtained using the Spectralis HRA+OCT device; Heidelberg Engineering GmbH, Heidelberg, Germany) performs against a widefield scan approach, and future studies are required to evaluate this.
The findings of this study underscore the potential advantage of using widefield scans for the challenging task of detecting progressive glaucomatous RNFL changes. The advantages of widefield scans have also been seen in recent studies that showed its improved ability to detect glaucomatous damage at cross-section.
14–16 This study also highlights the advantages of a ROI approach over the conventional use of the global cpRNFL thickness parameter,
17,18 gained by making full use of the OCT information available along with knowledge about the patterns of glaucomatous damage. However, it should be acknowledged that the comparisons between the average longitudinal SNRs of the methods performed in this study are meant to provide an evaluation of the potential value of each approach at the population-average level. The use of a dichotomized outcome measure of whether progression has occurred or not would have substantially diluted the statistical power to appreciate the true value of each method,
21 especially given that the majority of glaucoma eyes under routine clinical care often progress slowly.
22 Nonetheless, future studies are required to better understand the implications of these findings at the individual level, potentially through using trend- or event-based analyses of ROIs of longitudinal data (including a greater number of visits and follow-up duration) when compared to current methods. In addition, future studies are also required to determine the generalizability (performing intra- and intergrader assessments) of the manual ROI approach used in this study.
Several limitations of this study should be acknowledged when interpreting its findings. First, the age-related changes estimates were obtained in two different cohorts of healthy eyes. However, the sample size of both cohorts was relatively large (n ≥ 394), and therefore substantial differences in estimates of age-related changes are unlikely. Although longitudinal estimates of age-related change would have been more ideal compared to the cross-sectional estimates used in this study, it is unlikely that its use would significantly change the conclusions of this study since the same eyes were used to obtain the estimates for all three methods. Second, measurement variability estimates were also obtained in two different, but overlapping cohorts of glaucoma eyes. However, a total of 258 eyes were included for estimating the measurement variability of both the widefield and optic disc scans (representing 90% and 80% of the entire cohort, respectively), thus providing variability estimates from two very similar cohorts. It would also have been ideal if these estimates were obtained from a short-term test-retest cohort (rather than the intrasession estimates in this study), but this would also be unlikely to have changed the conclusions in this study given how the variability estimates were obtained from a very similar cohort of eyes. Third, progressive changes in the longitudinal group were only evaluated between two visits and over a relatively short duration, although increasing the number of visits and duration of follow-up would likely improve the precision of the change estimates without also altering the conclusions of this study. Finally, within-session estimates of measurement variability were used instead of short-term between-session estimates, which would be more representative of the extent of variability observed in a longitudinal cohort. Nevertheless, the within-session variability estimates were used when calculating the longitudinal SNRs for both the RNFL thickness changes from the widefield and optic disc scans (as a common denominator) and is thus unlikely to significantly affect the conclusions reached in this study.
In conclusion, the findings of this study using a manual ROI approach suggest that progressive RNFL changes in glaucoma eyes can be better detected using widefield OCT scans than derived circumpapillary circle scans from optic disc scans. These findings highlight potential advantages of using widefield scans for the challenging task of detecting disease progression in the clinical management of glaucoma.