This study demonstrated that a qualitative evaluation of OCT imaging results allows eyes with perimetric glaucoma to be detected with a high degree of accuracy, performing better than a conventional metric of global cpRNFL thickness. Furthermore, at least four of the seven eyes with perimetric glaucoma that were missed by the qualitative evaluation on OCT imaging showed visual field results that could be considered inconclusive for glaucomatous damage. This suggests that the actual accuracy might be even higher than we reported. In any case, these findings underscore the potential of OCT imaging in the clinical management of patients with glaucoma.
Previous studies have consistently suggested that OCT imaging does not perform any better than does a careful qualitative evaluation of optic disc stereophotographs for detecting glaucoma eyes with repeatable visual field defects when relying on conventional summary metrics like global circumpapillary RNFL thickness.
1–5 Instead, this study demonstrates that applying a similar careful qualitative approach toward evaluating OCT imaging results substantially improves the detection of glaucomatous damage compared to using a summary metric. This should not be surprising. In the same way that the presence, extent, nature, and details of glaucomatous damage visible on a clinical examination of the optic disc are insufficiently represented by a summary metric such as a cup-to-disc ratio, characteristics of glaucomatous damage visible on OCT imaging are likewise insufficiently represented by a metric of global cpRNFL thickness.
Indeed, these findings are in agreement with a previous study
7 that demonstrated how the ability to detect glaucomatous damage was improved by scoring RNFL defects based on the RNFL thickness deviation plots of OCT optic disc scans. However, our study is distinguished by also considering patterns of loss on the RNFL thickness plots in addition to the deviation plots and we evaluated macular OCT scans as well. This process may improve the ability to detect subtle glaucomatous defects, especially those that may not fall outside normative limits (and thus be present on the deviation plots) due to healthy interindividual variability. It may also improve the ability to correctly discriminate between normal variations in neuroretinal thickness (which may result in arcuate-like abnormalities on the optic disc RNFL thickness plots, for instance) and true glaucomatous defects.
6
Our findings also agree with our previous studies,
8,9 although there are some key differences in the methodology and thus its interpretation. For instance, the judgment of whether an eye was abnormal or not (used for defining the reference standard) in our first study
8 was performed by three glaucoma specialists who were provided with a commercial OCT report, optic disc stereophotographs, and a 24-2 visual field test. In our second study,
9 the reference standard was determined by two glaucoma specialists who were given a widefield OCT report and its interpretation by the grader (similar to a neurosurgeon being provided with results by a radiologist), along with the patient chart information, optic disc stereophotographs, and 24-2 and 10-2 visual field results. An important limitation with evaluating the qualitative approach with a reference standard that depends on using the OCT imaging results as well is the risk of overestimating its diagnostic performance, since both the technique studied and the reference standard evaluate the same source of information (although the latter includes other information as well).
Another important methodological difference was the participants examined; our previous studies
8,9 included only eyes with abnormal or suspicious-appearing optic discs and with a 24-2 visual field MD > −6 dB. Consequently, the eyes judged as being normal were used as the control group instead of the use of healthy eyes, as in this study. The eyes included in our previous studies are more likely to represent the challenging cases faced daily by glaucoma specialists in clinical practice, whereas the eyes included in this study (including a larger proportion of healthy participants) might be more akin to those seen in a general ophthalmology setting. In either case, the inclusion of a large sample of healthy participants in this study is relevant given the relatively low prevalence of glaucoma.
19 In addition, ensuring that a diagnostic technique has a high level of specificity is paramount because the initiation of lifelong treatment, let alone the diagnosis of glaucoma, can adversely affect an individual.
20,21
On the other hand, it is also crucial that a diagnostic technique like the qualitative approach of evaluating OCT imaging results not miss eyes with severe visual field loss. Indeed, we observed in this study that only 7 out of 156 eyes (4.5%) with perimetric glaucoma were missed by the qualitative evaluation of OCT imaging, although only one of these seven eyes had a 24-2 visual field MD worse than −6 dB. It is essential to note that while the use of a visual field endpoint for defining perimetric glaucoma is clinically relevant, it is by no means perfect because this endpoint can be reached simply as a result of measurement variability or factors unrelated to glaucomatous damage. In fact, a previous study demonstrated that 12% of the visual field tests in eyes with ocular hypertension (requiring three consecutive abnormal visual field tests based on the GHT and PSD results) after the visual endpoint was reached showed normal results.
15 For this reason, we presented the visual field results of the seven eyes missed by the qualitative evaluation of the OCT imaging results to the clinical and scientific community so that they may determine the significance of those visual field abnormalities for themselves. Our observations were that there was no compelling evidence of glaucomatous visual field damage in at least four of these eyes and that further investigations into the visual field abnormalities observed in the remaining three eyes are warranted. We thus believe that the diagnostic performance of the qualitative evaluation of the OCT results might be higher than we actually report.
Whereas the presence of glaucomatous damage in the majority of the seven eyes missed by the qualitative approach was somewhat inconclusive, the same was not true for many of the 21 eyes (13.5%) missed when using the global cpRNFL thickness parameter but detected by the qualitative OCT evaluation. This can be clearly seen in the two examples shown in
Figure 1, where the inferior-temporal RNFL defect associated with macular RGC+ abnormalities in both eyes were missed by the global parameter. Missing cases with obvious disease—especially disease that often affects the macula,
6,17 which is a part of the retina that is crucial for vision-related quality of life
22 and daily functioning
13—is problematic, and hence we caution against a reliance on a global thickness metric alone.
Nonetheless, the key implication of the findings of this study is clear: the full potential of OCT imaging can be realized through a careful qualitative evaluation of the wealth of information it provides during the clinical management of patients with glaucoma. This careful evaluation took a median of 11 seconds to perform in this study and often took no longer than 1 minute even in challenging cases (such as eyes with suspected glaucoma), highlighting its feasibility in real-world clinical practice. Furthermore, the results highlight the potential utility of using the qualitative evaluation of OCT imaging results for defining the presence of glaucomatous damage in clinical research, although further studies are required to validate such an approach. In particular, it would be important to establish whether this method can accurately predict clinically relevant outcomes longitudinally in eyes without repeatable visual field loss (such as the those with suspected glaucoma in our study).
12,23 The continuous scale used for grading the probability of glaucomatous damage in this study is also useful for clinical research since it allows sensitivities to be compared at matched specificities, accounting for differences between graders. In addition, continuous measures tend to be more powerful than categorized measures, as useful information can be lost through the categorization process.
24
An important limitation should be recognized when interpreting the results of this study, namely that an observer with extensive experience in the evaluation of the OCT imaging results (DCH)
6 performed all the grading in this study, although previous work indicated others, including those without a medical degree, could be trained to perform as well.
6,8 In any case, it remains to be determined whether a similar diagnostic performance with the qualitative approach can be achieved currently in clinical practice or whether a knowledge gap exists. However, one of the authors in this study (ZW) also achieved the same diagnostic performance when undertaking the same evaluation, but the results were not included because the author was not masked to the proportion of healthy and glaucoma eyes included in the study (but otherwise performed all the grading in the same manner). Of interest, there was a near-perfect agreement between the grading by this author (ZW) and the single observer in this study (DCH;
κ = 0.93 ± 0.04;
P < 0.001) for the healthy and perimetric glaucoma eyes, but studies are needed to further establish the interobserver agreement for this method and are indeed underway in our lab. Nonetheless, this study demonstrates a proof in principle that OCT imaging can be a powerful tool in the detection of glaucomatous damage, and the use of other novel measures (e.g., RNFL volume deviation
25) or artificial intelligence (e.g., deep learning methods
26) could make better use of its information beyond the current conventional summary metric of global cpRNFL thickness. Future studies are also needed to determine whether a qualitative evaluation also performs better than such summary metrics when evaluating eyes that are difficult to judge, such as those with high myopia or macrodiscs and eyes with preperimetric glaucoma.
In conclusion, this study demonstrated that a qualitative evaluation of the OCT imaging results allowed a detection of glaucoma eyes with repeatable visual field abnormalities with a high level of accuracy, superior to that achieved by a global thickness parameter. These findings show the potential of OCT imaging in clinical management of patients with glaucoma when making full use of the information that it provides.