We have shown that using OCT information to automatically choose half of the locations in the visual field for testing, while leaving the other half fixed, identifies more abnormal points in the visual field than using a fixed pattern (either rectangular or polar).
Using structural information to determine the placement of VF stimuli is not a new idea. Previously, in the FOP scheme
1, locations were added to a standard test grid manually by the examiner based on retinal photos. We purport that our method has two advantages: first, it is fully automatic, requiring no manual location selection; and second, we do not increase the number of test points relative to a standard grid approach.
An alternative approach to FOP for choosing VF locations based on structural damage could be to predict the visual field from retinal images,
21,22 and use the prediction as a guide for stimulus placement. Zhu et al.
23 predicted visual fields using RNFL thickness as measured by the scanning laser polarimetry using a Bayesian radial basis model. Using this model, the mean absolute prediction rate for VF sensitivities was found to be 2.9 dB with a standard deviation of 3.7 dB.
21 While the Zhu et al.
23 model for prediction of VF sensitivity exists, no work has been done on using the model as a basis for location selection in a perimetric test. This could be a fruitful area of investigation, and may improve upon our simple heuristics based on OCT sectors used in the defect-based method.
The individualized map between OCT and VF locations used in this study is developed based on a computational model. In order to validate the individualized map, we need to physically measure and observe an individual's retinal nerve fiber (RNF) arrangements in the retina. However, using current imaging technologies, it is not feasible to directly observe an individual's RNF arrangement. Although, there are several recent advancements in adaptive optics imaging technologies that enable in vivo imaging of RNF arrangements in retina, at present using adaptive optics–scanning light ophthalmoscopy is only possible to measure superficial RNF arrangements and it takes about 40 minutes (including short breaks) to image a 20° × 1° rectangular portion of retina.
24 However, the individualized map used in this study has been shown to have good agreement with maps derived from visual inspection and subsequent hand tracing of RNFL trajectories,
25,26 and unlike other maps, the individualized map enables customization for each individual using an individual's biometric data. Improvements in mapping between clinical structural measures and VF space should only improve our defect-based method.
In this dataset, for patient 15 (
Table) the fixed grids (24-2, P59 and P49) found more abnormal locations than the defect-based method. This individual had both a superior and inferior RNFL defect. The defect-based method placed all of its 26 variable location points in the superior (based on the most damaged OCT sector) and so had none left to allocate into the inferior field. However, the schemes that sampled the field on a regular grid had locations in both scotomas. Increasing the number of variable locations allowed would work well for this participant; however, in this study, we chose our parameters a priori rather than finding the best fit for our dataset. It would be ideal to have a dataset against which we could optimize the various heuristics and parameters chosen here, and another dataset to validate these choices. Collecting visual fields at a resolution of 2° is laborious and demanding on the volunteers; therefore, this ideal situation may not be possible.
Participant 1 had an early macular defect that was not detected by the peripapillary RNFL scan, but did show up on a 10-2 field and the suprathreshold tests. Because the peripapillary RNFL scan was normal, the defect-based method failed to allocate additional VF locations in the macula region. Evidence for an inability to detect the macular RNFL thinning by peripapillary RNFL scans is scattered throughout the literature.
27–29 Tan et al.
29 studied the diagnostic ability of peripapillary RNFL and macular scans to identify macular defects. They found in 78 glaucoma eyes with central perimetric defects, both peripapillary RNFL and macular scans identified a macular defect on 65% of eyes, 13% of eyes had macular defects identified only by peripapillary RNFL scans and 9% of eyes had macular defects only on macular scans (
Fig. 7 in Tan et al.
29). Based on this, the defect-based method will fail to allocate VF locations to the macular region in the 9% of cases with macular defects (those with normal peripapillary scans). In order to avoid this scenario, a future defect-based method may be feasible that is based on a combination of macular thickness scans and peripapillary scans, possibly with higher weighting given to macular thickness scans to detect central VF defects.
Participant 3 had a superior RNFL defect but their suprathreshold visual field and HFA visual fields did not show any corresponding inferior VF defect. There is apparent structure-function discordance in this individual. There are several reasons for the structure-function discordance, which includes variability associated with structure and functional measures, individual differences in structure-function mapping, using fixed ONH sector sizes,
10 the dynamic range of structural and functional instruments, instrument floor effect, etc. (for detailed review, please see Refs.
17,
30, and
31). The defect-based method depends on the existence of a predictable structure-function relationship in glaucoma. If there is significant discordance between structure and function like in participant 1 and 3, then the defect-based method will break down. Perhaps in these cases, regular test patterns that sample the visual field uniformly in VF space have an advantage, although in our data, that is not obvious as the regular patterns generally fail to do better than random patterns (
P < 0.05).
While in this manuscript we are not proposing a specific perimetric thresholding procedure that would make use of the locations identified by defect-based sampling, there are at least three areas of consideration for the development of such a procedure. First, any VF procedure that tests at locations that may differ from patient to patient increases the burden of clinical interpretation of the VF output over the current “one size fits all” situation. The 24-2 and G patterns are well established in clinical practice, allowing experienced clinicians to quickly glean information from their display. There is an extra burden on clinicians to interpret VF data with varying locations for different patients. This might be overcome by presenting data in a standard format using interpolation, or 3D displays, but this requires further work specific to different tests.
Second, the defect-based sampling method is designed to increase the likelihood of spatial sampling damaged locations in the visual field, and these areas of the visual field have high variability when tested with existing thresholding algorithms.
32 Testing in these regions should increase the sensitivity of a test in detecting glaucoma compared with one that tests on a fixed grid. However, it is not clear if testing in these regions, instead of testing in regions that do not have a corresponding RNFL deficit, will increase sensitivity for monitoring glaucomatous change. Perhaps getting more reliable threshold estimates in areas of the visual field that are deteriorating but have higher dB values than those obtained in a damaged area would be preferable. Determining how to use the locations identified by the defect-based method in a VF test requires further study.
Third, the magnitude of test–retest variability in the selection of locations that may arise from variability in OCT parameters from one visit to the next is not entirely clear, and may vary between instruments and will depend upon the use of follow-up image alignment features within individual OCT platforms. Various parameters like low signal strength, sample density, low RNFL thickness, media opacity, pupil size, OCT segmentation errors, eye movements, and position of scan circle are known to affect the RNFL thickness measurement.
33–36
The uniform sampling method does not improve the number of abnormal VF locations identified compared to the other methods. The uniform method proposed in this experiment samples the visual field as evenly as possible around the ONH within the constraints of these visual fields. Note: to truly sample evenly around the ONH requires stimulus placement in areas quite dissimilar to the most common way of sampling the visual field using a rectangular grid, in which stimulus placement extends only six degrees temporal to the blind spot. We similarly collected our ground truth visual fields without these locations; hence there are not adequate VF locations in the temporal VF region to map evenly around the ONH.
The visual fields that were used to test our VF sampling models were collected using a suprathreshold test strategy for several reasons. First, in order to assess the utility of the spatial sampling strategies, only a classification of “normal” or “abnormal” is required for each VF location. We could have measured fields using a threshold approach, but for the purpose of evaluating the sampling methods, would then have reduced the dataset to normal/abnormal using a total deviation classification or similar approach anyhow. Given the large amount of data that needed to be collected (the 2° grid has approximately 7 times the VF locations as a standard 24-2 pattern), the use of a suprathreshold approach was most pragmatic. The total test visit time was approximately 2 hours (customized VF test, Humphrey VF test, imaging, and axial length measurements), with the customized VF test containing 386 locations taking on average 29 ± 3 minutes (excluding breaks) to complete. It should be noted that the suprathreshold visual field is not the part of the defect-based sampling method, but was measured to provide test data to enable the main study (analysis of different sampling strategies) to be performed. The defect-based method described in this study is relevant to any test strategy/algorithm (e.g., SITA, Zippy Estimation of Sequential Testing [ZEST], staircase, screening procedures etc.).
We evaluated the defect-based method on 23 subjects. Although, the number of participants is not large, the amount of VF information collected in each participant was almost seven times more than that collected in regular clinics. In addition to this, the 23 participants used in our study represented a substantial variety of spatial patterns of glaucomatous VF loss ranging from minimal damage to extensive loss (
Supplementary Fig. S1, 24-2 grayscale ordered by MD). We deliberately selected patients with a range of VF defects that could arise due to RNFL thickness loss.
A limitation of the defect-based sampling method is that it ignores some regions of the visual field that are not associated with an OCT deficit.
Figure 6A shows the locations that are definitely chosen (black dots), but it is feasible that there might be large areas not sampled. This should not be a problem for diagnosis of glaucoma, as the defect-based method generally finds abnormal VF locations; but it may be a problem for monitoring the progressive deterioration of normal points. Whether the information lost in not testing the OCT-normal regions of a fixed grid is compensated by the information gained by testing abnormal locations chosen by the defect-based method for determining glaucomatous progression requires further investigation. A second limitation of the defect-based sampling method is that locations are chosen based on individual RNFL thickness, so any VF defects that do not involve RNFL thickness loss may not be selected as a region of interest. Therefore, this approach is really targeted toward glaucomatous VF damage.
In conclusion, structural information can be used to locate more abnormal points in an individual's visual field than current fixed-grid patterns in common use without increasing the number of locations examined.