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. Author manuscript; available in PMC: 2022 Sep 1.
Published in final edited form as: Am J Ophthalmol. 2021 Feb 21;229:26–33. doi: 10.1016/j.ajo.2021.02.015

Qualitative Evaluation of the 10-2 and 24-2 Visual Field Tests for Detecting Central Visual Field Abnormalities in Glaucoma

Adi Orbach 1, Ghee Soon Ang 1, Andrew S Camp 2, Derek S Welsbie 2, Felipe A Medeiros 3, Christopher A Girkin 4, Massimo A Fazio 4, Won Hyuk 2, Robert N Weinreb 2, Linda M Zangwill 2,#, Zhichao Wu 1,5,#
PMCID: PMC8379296  NIHMSID: NIHMS1711460  PMID: 33626360

INTRODUCTION

Visual field testing remains one of the most important tools for the diagnosis and monitoring of glaucoma. Its results are crucial for estimating the current level and future risk of functional impairment for individuals affected by this disease.1,2 Although visual field damage in glaucoma predominantly affects the peripheral field in most patients, glaucomatous damage to the central field has been found to occur more often than conventionally expected, and even in the early stages of this disease.3 In addition, the central visual field is an important predictor of vision-related quality of life.4–6 Therefore, being able to detect glaucomatous central visual field damage effectively is important in the clinical management of glaucoma patients.

Numerous studies have suggested that targeted testing of the central visual field region (e.g. the 10-2 strategy on the Humphrey Field Analyzer [HFA]; Carl Zeiss Meditec, Dublin, CA)6–10 or adding additional test locations within this region to conventional stimulus patterns (such as done with the new 24-2C testing strategy on the HFA)11,12 could improve the detection of central visual field abnormalities. However, none of these studies have compared the newly proposed approaches with conventional strategies at topographically equivalent locations, and at matched specificities.

Instead, we observed recently that pattern standard deviation (PSD) values derived from 10-2 tests and the topographically equivalent central 12 locations of 24-2 tests (C24-2) performed similarly at detecting central visual field abnormalities in a large cohort of eyes with either a glaucomatous optic nerve appearance or ocular hypertension.13 Other recent studies have also confirmed our findings of a similar performance of the 10-2 and C24-2 PSD in smaller cohorts.14,15 However, we cautioned about the interpretation of these findings, given that PSD values are not typically used in isolation to detect visual field abnormalities in clinical practice. Indeed, a recent study showed how the reliance on summary measures may result in under-detection of glaucomatous damage on optical coherence tomography (OCT) imaging, when compared to an expert qualitative evaluation of the imaging results.16 This difference is likely due to the fact that summary measures may be unable to identify distinguishing patterns known to be associated with glaucomatous damage.

We thus hypothesized that a qualitative evaluation of the visual field results could provide a more effective and clinically relevant means for understanding the potential advantages of 10-2 visual field testing for detecting central visual field abnormalities. As such, this study sought to compare the performance of the 10-2 and 24-2 visual field tests for detecting central visual field abnormalities based on an expert qualitative evaluation of its results.

METHODS

This study included participants that were examined in two prospective observational studies of optic nerve structure and visual function in glaucoma – the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES)17 – and these studies were conducted in adherence with the Declaration of Helsinki and to the Health Insurance Portability and Accountability Act. Institutional review board approvals were obtained from all sites included in these studies and written informed consent was obtained from all participants.

The full description of all the testing procedures for these studies have been provided in a previous publication.17 Briefly, all participants underwent a medical history review, best-corrected visual acuity measurements, slit lamp biomicroscopy, dilated fundus examination and optic disc stereophotography, and intraocular pressure (IOP) and pachymetry measurements at annual intervals. Visual field testing for the participants included in this study was performed using the Swedish Interactive Thresholding Algorithm Standard 24-2 and 10-2 strategy on the HFA II-i (Carl Zeiss Meditec, Dublin, CA) at approximately semi-annual intervals.

This study included eyes with a glaucomatous optic nerve appearance (based on masked grading of stereophotographs by at least two graders, using a methodology described further previously17) or ocular hypertension (defined as having an IOP of 22 mm Hg or more) as cases and healthy eyes as controls in a cross-sectional study. The controls included eyes from healthy participants who were otherwise unremarkable on a comprehensive ophthalmological examination and with an IOP less than 22 mm Hg. All participants were recruited from optometry or ophthalmology clinics, or from the general population through advertisements or community presentations. All eyes in the case and control groups were required to also have a best-corrected visual acuity of 20/40 or better, open angles on gonioscopy and participants had to be 18 years of age or older. Participants with any other ocular or systemic disease that could affect the optic nerve head, or the visual field, were excluded from this study. Note that visual field results were not used for classifying eyes as either cases or controls, to avoid potential biases in evaluating the performance of the 10-2 and C24-2 results (which could occur if information from the latter could be used to define the diagnostic categories).

Visual Field Testing

Eyes included in this study were all required to have reliable 10-2 and 24-2 visual field tests that were performed on the same day, and unreliable tests were defined as those with >33% fixation loss, >33% false negative errors (except when the mean deviation [MD] was worse than −12 dB), or >15% false positive errors. Tests with artifacts such as inappropriate fixation, fatigue, inattention or learning effects, eyelid or rim artifacts, or evidence that the results were affected by a condition other than glaucoma (e.g. homonymous hemianopia), were excluded. The assessment of these artifacts were performed by experienced graders at the University of California, San Diego (UCSD) Visual Field Assessment Center.18

Qualitative Evaluation of Visual Field Test Results

In order to compare the performance of the 10-2 and 24-2 visual fields at topographically matched regions, only the results of the central 12 locations of the 24-2 visual field (termed C24-2) was made visible for the qualitative evaluation. An example of the 10-2 and C24-2 reports generated for the qualitative evaluation is shown in Figure 1. All the visual field reports were then de-identified and presented in a randomized order in a custom-written program, and each report was graded for the probability of the presence of visual field damage in the central visual field region consistent with glaucomatous damage. This grading was performed along a continuous scale (0 to 100%), with higher values indicating a higher graded probability of central visual field abnormalities. Four experienced glaucoma specialists (AO, GSA, ASC and DSW) graded all the visual field reports.

Figure 1:

Figure 1:

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Example of the 24-2 (left) and 10-2 visual field reports (right) used in this study, with the results of only the central 12 locations shown for the 24-2 visual field test to ensure that only the topographically matched locations to the 10-2 test are shown.

Statistical Analysis

The performance of the qualitative evaluation of the 10-2 and C24-2 visual field test results for detecting the cases was compared using a Wald test of the difference in their sensitivity at 95% specificity (i.e. based on a cut-off of the graded probabilities that led to 5% of the controls being flagged as abnormal), using a bootstrap resampling procedure (n = 1000 resamples).19 Of interest, the performance of the qualitative grading was also compared with the performance of the pattern standard deviation (PSD) measure (calculated using methods as described in further detail previously13), similarly using a Wald test for the 10-2 and C24-2 visual field tests separately. The agreement between the cases detected by these two methods at 95% specificity was also examined using Cohen’s kappa.

RESULTS:

Participant Characteristics

A total of 523 eyes with a glaucomatous optic nerve appearance or ocular hypertension from 300 participants were included as cases, and these participants were on average 70 ± 11 years old (range, 27 to 99 years old). Another 107 eyes from 67 healthy participants were included as controls, and these participants were on average 64 ± 11 years old (range, 34 to 95 years old). The characteristics of these eyes based on the 24-2 and 10-2 visual fields are summarized in Table 1. Amongst the eyes included as cases, 272 (52%) eyes had a Glaucoma Hemifield Test (GHT) result that was “Outside Normal Limits” and 309 (59%) eyes had a PSD value at a probability of <5% based on the whole 24-2 visual field test. In addition, 408 (78%) eyes had an 24-2 visual field MD ≥ −6 dB, 55 (11%) eyes had an MD < −6 dB and ≥ −12 dB, and 60 eyes had an MD < −12 dB.

Table 1:

Visual field characteristics and qualitative grading results of the eyes in this study, with all values presented as median (interquartile range; 25th to 75th percentile).

Controls (n = 107 eyes) Cases (n = 523 eyes)
24-2 VF 10-2 VF 24-2 VF 10-2 VF
MD −0.26 (−1.44 to 0.72) 0.17 (−1.17 to 0.83) −1.76 (−4.98 to 0.09) −1.25 (−4.42 to 0.25)
PSD 1.78 (1.52 to 2.32) 0.83 (0.69 to 1.10) 2.33 (1.67 to 6.20) 1.11 (0.79 to 3.64)
Graded Probability of Central Visual Field Abnormalities (%)*
  Grader 1 2 (0 to 2) 2 (0 to 3) 2 (0 to 65) 4 (2 to 80)
  Grader 2 5 (5 to 5) 5 (5 to 5) 5 (5 to 50) 5 (5 to 50)
  Grader 3 10 (0 to 25) 0 (0 to 10) 25 (10 to 100) 10 (0 to 50)
  Grader 4 0 (0 to 10) 5 (0 to 20) 10 (0 to 60) 10 (5 to 70)
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Notes: VF = visual field; MD = mean deviation, PSD = pattern standard deviation

*

= along a 0–100% scale. Note: only the central 12 locations for the 24-2 VF were shown during the qualitative grading process.

Qualitative Grading Results

The median qualitatively graded probabilities of central visual field abnormalities were similar between the case eyes with a glaucomatous optic nerve appearance or ocular hypertension and the control eyes for the C24-2 (e.g. 2% and 2% respectively for Grader 1) and 10-2 visual fields (e.g. 4% and 2% respectively for Grader 1), reflecting how the case group had a large proportion of eyes with central visual field graded as being relatively normal. Instead, the 75th percentile of the graded probabilities showed a greater expected difference between the case and control groups for the C24-2 (e.g. 65% vs. 2% respectively for Grader 1) and 10-2 visual fields (e.g. 80% and 3% respectively for Grader 1). Of interest, the cut-offs of the graded probabilities used to determine sensitivity at 95% specificity for the 10-2 and C24-2 visual field tests (or the 95th percentile of the graded probabilities in the control group) were 20% and 20% respectively for Grader 1, 25% and 15% respectively for Grader 2, 75% and 50% respectively for Grader 3, and 60% and 30% respectively for Grader 4.

Diagnostic Performance of the 10-2 and C24-2 Visual Field Qualitative Grading

Based on the qualitative grading of the visual field test results, there was no significant difference in the sensitivity of detecting the cases at 95% specificity between the 10-2 and C24-2 visual fields (P ≥ 0.25 for all graders). The absence of a significant difference remained when considering only cases with a 24-2 visual field MD of ≥ −6 dB (P ≥ 0.27 for all graders), or ≥ −12 dB (P ≥ 0.24 for all graders); these findings are summarized in Table 2. There were also no significant differences when examining only cases with an MD < −6 dB and ≥−12 dB (all P ≥ 0.19), or cases with an MD < −12 dB (all P ≥ 0.43).

Table 2:

Sensitivity (%) of detecting cases (eyes with a glaucomatous optic nerve appearance or ocular hypertension) at 95% specificity based on a qualitative grading of the 10-2 and central 12 locations of the 24-2 visual field test (C24-2).

10-2 VF 24-2 VF Difference* (95% CI) P-Value
MD ≥ −6 dB (n = 515) Grader 1 15.2 12.7 2.5 (−9.7 to 14.6) 0.69
Grader 2 11.8 16.4 −4.7 (−16.5 to 7.2) 0.45
Grader 3 8.8 10.0 −1.2 (−14.6 to 12.1) 0.86
Grader 4 12.3 18.1 −5.9 (−16.6 to 4.8) 0.27
MD ≥ −12 dB (n = 570) Grader 1 23.8 22.5 1.3 (−11.3 to 13.9) 0.84
Grader 2 19.2 25.3 −6.0 (−19.7 to 7.6) 0.37
Grader 3 14.0 17.5 −3.5 (−23.2 to 16.3) 0.72
Grader 4 19.2 26.1 −6.9 (−18.7 to 4.9) 0.24
All Eyes (n = 630) Grader 1 32.2 31.4 1.0 (−10.6 to 12.6) 0.87
Grader 2 27.9 33.8 −5.9 (−18.3 to 6.5) 0.37
Grader 3 18.9 25.8 −6.9 (−34.1 to 20.3) 0.60
Grader 4 27.9 34.6 −6.7 (−19.0 to 5.6) 0.25
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Notes: VF = visual field; MD = mean deviation of the 24-2 visual field test; n = total number of eyes in the case and control groups

*

= difference between 10-2 and 24-2 visual field; CI = confidence interval.

Comparison of Visual Field Qualitative Grading to PSD

At 95% specificity, there was also no significant difference in the sensitivity of the 10-2 and C24-2 PSD for detecting the cases (35.9% vs. 35.4%; P = 0.90), as reported previously.13 Of interest, there was no significant difference between the sensitivity of detecting cases when using the qualitative evaluation (25.8% to 34.6% for Graders 1 to 4; Table 2) and PSD measure (35.4%) for the C24-2 visual fields for all graders (all P ≥ 0.39) and 10-2 visual field for Grader 1 (P = 0.29). However, the PSD measure had significantly higher sensitivity (35.9%) than the qualitative evaluation for the 10-2 visual field for Grader 2 (27.9%), Grader 3 (18.9%) and Grader 4 (27.9%; all P ≤ 0.016); these findings are summarized in Table 3.

Table 3:

Comparison between qualitative grading and pattern standard deviation (PSD) values for the 10-2 visual field test and central 12 locations of the 24-2 (C24-2) visual field test.

10-2 VF Qualitative Evaluation vs. PSD C24-2 VF Qualitative Evaluation vs. PSD
P-Value for Sensitivity* κ for agreement % Cases in Agreement P-Value for Sensitivity* κ for agreement % Cases in Agreement
Grader 1 0.29 0.87 94.1 0.27 0.87 94.1
Grader 2 0.011# 0.80 91.2 0.77 0.85 93.1
Grader 3 0.015# 0.54 81.1 0.39 0.72 88.2
Grader 4 0.016# 0.79 90.1 0.83 0.82 91.6
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Notes:

*

= for difference of detecting cases at 95% specificity

#

= sensitivity of the qualitative evaluation significantly lower compared to PSD at P < 0.05; κ = Cohen’s kappa.

Based on the descriptions by Landis & Koch,20 there was also near-perfect or almost near-perfect agreement between the cases detected at 95% specificity qualitative evaluation and PSD measure for the 10-2 (κ ≥ 0.79) and C24-2 visual fields (κ ≥ 0.82) for all graders except Grader 3, whose evaluation showed moderate agreement for the 10-2 (κ = 0.54) and substantial agreement (κ = 0.72) for the C24-2 visual fields. These findings are summarized in Table 3, with the proportion of cases in agreement cases detected using the qualitative evaluation and PSD values for each type of visual field test also presented, and the level of agreement between the two approaches illustrated in Figure 2.

Figure 2:

Figure 2:

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Proportional Venn diagram illustrating the level of agreement between the number of cases (eyes with, suspected or at risk of having glaucoma) that were detected at 95% specificity based on a qualitative evaluation by Grader 1 of the 10-2 (left) and central 12 locations of the 24-2 visual fields (VF; right) or their pattern standard deviation values.

DISCUSSION

This study demonstrated that the ability to detect central visual field abnormalities as not significantly different in eyes with, suspected or at risk of having glaucoma based on a qualitative evaluation of the 10-2 test and central twelve locations of the 24-2 test. Furthermore, we observed that there was frequently near-perfect agreement between the eyes detected by the qualitative evaluation and PSD values by both testing strategies. These findings suggest that the increased sampling density provided by the 10-2 test did not result in a significant improvement in detecting central visual field abnormalities, despite using a qualitative method of assessment that reflects more closely how clinicians evaluate the central visual field test points.

These findings of this study are consistent with recent studies demonstrating that PSD values from the 10-2 and central 12 locations of the 24-2 test performed similarly at detecting central visual field abnormalities.13–15 The often near-perfect agreement between the eyes detected by the qualitative evaluation and PSD values further explained why there were no significant differences in the performance of the 10-2 and 24-2 tests in view of those previous findings. These findings are also consistent with another study that showed that even visual field testing at twice the sampling density of the 10-2 strategy did not result in a significant improvement in the ability to detect glaucomatous visual field abnormalities compared to the sampling density of the 24-2 test.21

The findings that a qualitative evaluation of the visual field results performed no better (and in fact, significantly worse in three out of four glaucoma specialists) than the summary measure of PSD is in contrast to recent observations that a qualitative evaluation was more effective at detecting glaucomatous damage on OCT imaging.16 These findings may be due to the fact that the visual field results – even at the sampling density of the 10-2 test – does not contain a sufficient level of spatial resolution for a qualitative evaluation to exploit for identifying known patterns consistent with glaucomatous damage. This may be further exacerbated by the known variability of this test, which can often result in false-positive presence of visual field abnormalities.22

Nonetheless, these findings should still not be taken to imply that 10-2 visual field testing is not useful in the early detection of glaucomatous central visual field abnormalities. The value of the increased sampling density provided by this testing strategy could be potentially realized when examined alongside structural information,3,15 or by using emerging artificial intelligence methods. However, until the value of 10-2 testing is clearly established, caution should be applied when considering its routine incorporation into glaucoma management given: (i) the potential impact on already limited healthcare resources if additional testing is routinely performed, and (ii) the potential delay in the time taken to detect visual field progression23,24 in the non-central regions if 10-2 tests are performed in lieu of a conventional 24-2 testing strategy (due to a reduced frequency of testing by the latter). These issues could be overcome by the use of testing strategies that include more test locations in the central visual field region.11,12 However, it is unlikely that the addition of a limited number of test locations would result in significant improvements in detecting central visual field abnormalities if a 10-2 strategy (with a greater sampling density) does not already provide such improvements. In addition, it remains to be established whether 10-2 testing strategy might be more useful than the 24-2 strategy for detecting progressive central visual field loss when taking a similar qualitative evaluation approach as performed in this study. We have previously observed that the 10-2 strategy only provided minimal improvements to the C24-2 for the time to detect progression based on trend-based analyses of the summary measure of MD,22 but a qualitative evaluation may enable a greater level of improvement.

A notable limitation of this study is that the 10-2 and 24-2 visual field tests were compared in their ability to discriminate eyes with, suspected or at risk of having glaucoma from healthy eyes. These are two groups that were not specifically defined based on whether glaucomatous damage that should result in central visual field abnormalities was present or not. However, they represent two groups that would have a distinctly different risk for having glaucomatous central visual field abnormalities, and thus still provide a useful assessment of these two testing strategies. Future studies comparing the performance of the 10-2 and 24-2 visual field tests when defining groups based on the presence of central glaucomatous damage based on OCT imaging are required. It should also be noted that this study primarily included eyes (78% of cases) with glaucomatous optic neuropathy or ocular hypertension with early visual field abnormalities (24-2 MD ≥ −6 dB) or without an abnormal 24-2 visual field test result. The interpretation of the comparison between the 10-2 and C24-2 should be made in recognition of the characteristics of this cohort, and the performance of these two tests could differ when evaluating eyes with more severe visual field loss. Of interest, the sensitivity for detecting central visual fields abnormalities was non-significantly higher with the C24-2 compared to 10-2 tests based on the qualitative evaluation for all four graders (P ≥ 0.26) when evaluating the 115 (22%) eyes with more severe glaucoma (MD < −6 dB). In addition, the graders in this study were presented only with the central points of the 24-2 VF, which may not be generalizable to clinical practice where the central points of the 24-2 may or may not be looked at as closely as in this study. Furthermore, all graders included in this study were experienced glaucoma specialists, and they may therefore not represent the broader community of eye care practitioners (other glaucoma specialists, general ophthalmologists or optometrists) who may have utilized the 10-2 and C24-2 visual field tests differently. However, our inclusion of experienced glaucoma specialists as graders in this study enabled us to more effectively examine if there is information inherently present in the 10-2 visual field test that could be exploited by experts to improve the detection of visual field abnormalities. Finally, we did not examine the repeatability of the qualitative assessment performed by these glaucoma specialists, as this assessment – whilst informative – would not have affected the main outcome evaluated in this study.

In conclusion, this study demonstrated that the ability to detect central visual field loss in eyes with, suspected or at risk of having glaucoma was not significantly different based on an expert qualitative evaluation of the 10-2 or central 12 locations of the 24-2 visual field test results. These findings should not be taken to mean that the 10-2 testing strategy is not useful for characterizing the central visual field in eyes with glaucoma, but it highlights the need for the value-add of this strategy to be established clearly before considering its incorporation into the routine management of glaucoma patients.

This study whether central visual field abnormalities could be more effectively detected on the 10-2 test compared to the topographically-matched central 12 locations of the 24-2 test based on an expert qualitative evaluation by four glaucoma specialists. The findings showed that the performance of both methods was similar, suggesting that the increased sampling of the 10-2 test may not provide significant improvements over the 24-2 test for detecting visual field abnormalities.

ACKNOWLEDGEMENTS

a. Funding Support: Supported in part by National Institutes of Health/National Eye Institute Grants EY021818 (FAM) EY011008, EY14267, EY027510, EY019869 (LMZ) and EY029058 (RNW), and Core Grant P30EY022589; EY026574 (LMZ); Eye Sight Foundation of Alabama (MAF, CAG) and Research to Prevent Blindness (New York, NY; MAF, CAG, RNW), P30EY003039; grants for participants’ glaucoma medications from Alcon, Allergan, Pfizer, Merck, and Santen; a National Health & Medical Research Council Early Career Fellowship (#1104985, ZW). The sponsors or funding organizations had no role in the design or conduct of this research. Trial Registration: clinicaltrials.gov Identifier: NCT00221923.

Footnotes

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b. Financial Disclosure(s): Adi Orbach: None; Ghee Soon Ang: None; Andrew S. Camp: None; Derek S. Welsbie: None; Felipe A. Medeiros: Financial support – Alcon Laboratories (Fort Worth, TX), Bausch & Lomb (Garden City, NY), Carl Zeiss Meditec (Jena, Germany), Heidelberg Engineering (Heidelberg, Germany), Merck (White House Station, NJ), Allergan (Irvine, CA), Topcon (Livermore, CA), Reichert (Dewey, NY), National Eye Institute (Bethesda, MD); Research support – Alcon Laboratories (Fort Worth, TX), Allergan (Irvine, CA), Carl Zeiss Meditec (Jena, Germany), Reichert (Dewey, NY); Consultant – Allergan (Irvine, CA), Carl-Zeiss Meditec, (Jena, Germany), Novartis (Basel, Switzerland); Christopher A. Girkin: Financial Support – National Eye Institute, EyeSight Foundation of Alabama, Research to Prevent Blindness, Heidelberg Engineering, GmbH; Massimo A. Fazio: Financial Support – National Eye Institute, EyeSight Foundation of Alabama, Research to Prevent Blindness, Heidelberg Engineering, GmbH; Christopher A. Girkin: Financial Support – National Eye Institute, EyeSight Foundation of Alabama, Research to Prevent Blindness, Heidelberg Engineering, GmbH; Robert N. Weinreb: Financial support – Heidelberg Engineering, Carl Zeiss Meditec, Konan, Optovue, Centervue, National Eye Institute, Research to Prevent Blindness; Consultant – Aerie Pharmaceuticals, Allergan, Bausch & Lomb, Eyenovia, Nicox, Novartis; Linda M. Zangwill: Financial Support – National Eye Institute, Carl Zeiss Meditec Inc., Heidelberg Engineering GmbH, Optovue Inc., Topcon Medical Systems Inc.; Consultant – Merck; Recipient – Optovue, Topcon Medical Systems. Zhichao Wu: None.

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