Introducing the 24-2C Visual Field Test in Neuro-Ophthalmology

The Humphrey 24-2C visual field test is a modified 24-2 visual field test that incorporates 10 additional test points in the central 10° of vision. This study compares the new 24-2C test to the standard Humphrey 10-2 visual field test in patients presenting for neuro-ophthalmology evaluation to evaluate its ability to detect central visual field defects.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Introducing the 24-2C Visual Field Test in NeuroOphthalmology Maya L. M. Yamane, MD, Jeffrey G. Odel, MD Purpose: The Humphrey 24-2C visual field test is a modified 24-2 visual field test that incorporates 10 additional test points in the central 10° of vision. This study compares the new 24-2C test to the standard Humphrey 10-2 visual field test in patients presenting for neuro-ophthalmology evaluation to evaluate its ability to detect central visual field defects. Methods: Twenty-five neuro-ophthalmology patients (42 eyes) underwent both 24-2C and 10-2 visual field testing using the Humphrey perimeter. The number of flagged total deviation (TD) and pattern deviation (PD) points of the 10 added test points of the 24-2C were compared with the corresponding 10-2 fields at the P , 5%, P , 2%, and P , 1% significance levels. The total number of flagged TD points were further analyzed by diagnosis. An experienced neuro-ophthalmologist evaluated all visual fields, commenting on the added value for clinical practice. Results: There was no significant difference between the number of flagged TD and PD points of the 10 extra 24-2C points and corresponding 10-2 points at all significance levels. When analyzed by diagnosis, there was no significant difference in the number of flagged TD points in patients with optic neuritis, ischemic optic neuropathy, optic atrophy, and no neuro-ophthalmic disease. The added 24-2C points aided in identifying visual field defects and areas of spared central vision and had similar diagnostic value as the 10-2. Conclusions: The 24-2C is able to detect visual field loss in the central 10° that corroborates with loss detected in the 10-2 pattern. The 24-2C exhibits potential to be used as a Columbia University (MLMY), Vagelos College of Physicians & Surgeons, New York, New York; Shiley Eye Institute and Viterbi Family Department of Ophthalmology (MLMY), University of California, San Diego, La Jolla, California; and Department of Ophthalmology (JGO), Columbia University Irving Medical Center, NewYorkPresbyterian Hospital, New York, New York. Funding and support was obtained from the Columbia University Vagelos College of Physicians and Surgeons Scholarly Project Program and Friedman Award. The authors report no conflicts of interest. Address correspondence to Maya L.M. Yamane, MD, Shiley Eye Institute, 9415 Campus Point Drive Rm 257, MC 0946, La Jolla, CA 92093-0946; E-mail: [e-mail] e606 hybrid between the 24-2 and 10-2 to better evaluate visual field defects. Journal of Neuro-Ophthalmology 2021;41:e606–e611 doi: 10.1097/WNO.0000000000001157 © 2020 by North American Neuro-Ophthalmology Society BACKGROUND S tandard automated perimetry is the most common perimetric test used in clinical practice for the evaluation of optic neuropathies. It is subject to patient and disease-related sources of variability, which can make the interpretation of results challenging. The introduction of the Swedish Interactive Threshold Algorithm (SITA), a method of automated perimetry, has significantly reduced testing times, but participant fatigue and testing variability is a continual challenge (1). To address this problem, recently, the SITA Fast algorithm was modified to produce SITA Faster, whose changes include lowering starting stimulus intensities based on age, using normal values obtained from SITA Fast to adjust the threshold at which to stop further testing at a given location, and elimination of false negative and blind spot catch trials (1). In addition, to reduce the number of visual field tests per patient, a new pattern, the 24-2C has been developed for the Humphrey Visual Field Analyzer 3.0 (Carl Zeiss, Meditec, Inc., Dublin, CA) using the SITA Faster protocol (1). The 24-2 and 10-2 are 2 commonly used visual field patterns; the 24-2 measures the central 24° of the visual field and contains 54 test points that are 6° apart, whereas the 10-2 pattern measures the central 10° of the visual field with 68 points that are 2° apart. The area and source of visual field loss often determines which test a patient will undergo, as multiple tests on a given eye during one evaluation is impractical. Given that the 24-2 test supplies only 4 test points in the central 8° of vision, the region that corresponds to the macula, the 24-2 test is limited in its Yamane and Odel: J Neuro-Ophthalmol 2021; 41: e606-e611 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution ability to detect macular damage (2–7). The macula is vital for high acuity vision including face recognition and reading. Although it is less than 2% of the retina by area, it contains over 30% of retinal ganglion cells (2,7,8). The 102 test, although able to detect central vision loss with increased sensitivity, does not evaluate vision more peripheral to the central 10°. With the intention of better characterizing central vision loss while maintaining the 24° radius range, the 24-2C pattern (Fig. 1A) adds 10 test points from the 10-2 to the 24-2 within the central 10° of the visual field in areas previously determined to be vulnerable to glaucomatous damage (9). These 10 points are included at the end of the 24-2 test. Prior research using the 24-2C pattern has focused on glaucomatous vision loss (10). However, pathologies of the optic nerve and visual pathways can also affect central vision (11). In this study, we therefore compared the new 24-2C visual field test with the standard 10-2 test in patients presenting for routine neuro-ophthalmology evaluation. We quantitatively assessed the difference in vision deficits detected via the 24-2C and 10-2 patterns and qualitatively explored how the 24-2C affects clinical diagnostics. METHODS This prospective study was approved by the Columbia University Irving Medical Center Institutional Review Board. It adheres to the tenets of the Declaration of Helsinki and the Health Insurance Portability and Accountability Act. All participants gave written informed consent to participate in the study. Patients who routinely undergo visual field testing were recruited from a neuroophthalmology practice at an academic institution between January and March 2019. Inclusion criteria for participation was age 18–95, best-corrected visual acuity of 20/125 or better, and suspected pathology that involved central vision. Participants underwent a 24-2C visual field test with the SITA Faster protocol and a 10-2 visual field test with the SITA Fast protocol using the Humphrey visual field analyzer 3.0. The order of visual field testing was randomized. Participants also underwent routine clinical examination by an experienced neuro-ophthalmologist. Quantitative Field Analysis Visual fields with a #33% fixation loss rate, #20% false negative rate, and #15% false positive rate were included. The SITA Faster protocol does not compute fixation losses via the Heijl–Krakau method (1); therefore, the use of fixation losses as a reliability parameter was not applicable for the 24-2C and relied solely on gaze tracking. The reliability parameters and test duration were compared using a generalized estimating equation. The 10 points added to the standard 24-2 pattern in the central 10° of vision to create the 24-2C pattern were comYamane and Odel: J Neuro-Ophthalmol 2021; 41: e606-e611 pared with the corresponding 10 points in the 10-2 pattern for each eye (Fig. 1B). Outcomes examined were the total number of flagged points in the total deviation plot (TD) for the 24-2C and 10-2, the total number of flagged points in the pattern deviation (PD) plot, and the difference between the total number of flagged points in the 2 visual field tests. We defined the difference between the number of flagged points as number of 10–2 flagged points minus the number of 24–2C flagged points. The total number of flagged points represents the number of flagged points at the P , 5% significance level; this was further subcategorized by the number of flagged points at P , 2% and P , 1% significance levels for both TD and PD plots. Means for the outcomes were estimated with models fit using a generalized estimating equation with an exchangeable correlation structure. We then tested whether this mean difference was different from 0. Given that each pair of visual field tests is not completely independent (i.e., some patients obtained testing on both of their eyes), the assumption of independence from many simple statistical methods is most likely violated. Correlated data methods, such as mixed models or generalized estimating equations, are thus likely more appropriate. However, for patients with nonarteritic anterior ischemic optic neuropathy (NAION), our model estimation was diverging (correlation . 1). In this group of patients, there were only 2 eyes from the same patient, so the outcomes for this patient were averaged to create a single test point and descriptive statistics and a t test were used. We performed a subanalysis based on neuro-ophthalmic diagnosis: no neuro-ophthalmic disease, optic neuritis/ multiple sclerosis, NAION, idiopathic intracranial hypertension (IIH)/papilledema, optic atrophy of unknown cause, glaucoma, stroke, or optic nerve head drusen. Qualitative Field Analysis To explore the clinical implications, de-identified 24-2C and 10-2 visual fields were presented to an experienced neuro-ophthalmologist. While looking only at the 24-2C test, he/she commented on the type of visual field defect present, what disease entity this visual field defect might represent, and the added value of the extra 10 central points. Afterward, he was shown the 10-2 test, and again commented on the type of visual field defect present. RESULTS Quantitative Field Analysis A total of 25 patients including 42 eyes (mean age 54.8, SD 19.4, range 25–81) with a visual acuity of 20/70 or better underwent 24-2C and 10-2 visual field testing. The 10-2 visual fields had a significantly lower false positive (1.09% vs. 2.57%, P = 0.043) and false negative (1.15% vs. 3.89% P = 0.002) rate and took a significantly longer time to e607 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. A. A sample of the 24-2C visual field test of a right eye. B. The 24-2C and 10-2 TD and PD plots of a left eye. The points highlighted in the 24-2C are the 10 points added to the 24-2. The corresponding 10 points are highlighted in the 10-2 pattern. complete than the 24-2C test (average of 3:58 vs. 3:09 minutes, P , 0.001) (Table 1). The average mean deviation (MD) for the SITA Faster 24-2C tests was e608 25.15 dB (SD 7.69, range 230.62–3.5); the average MD for the SITA Fast 10-2 tests was 24.8 dB (SD 6.06, range 223.46–1.9). Yamane and Odel: J Neuro-Ophthalmol 2021; 41: e606-e611 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Mean (SE) values for the fixation loss rate, false positive rate, false negative rate, and test duration of the 24-2C and 10-2 tests Reliability Parameters Fixation loss rate False positives False negatives Test duration 24-2C N/A 2.57 (0.67) 3.89 (0.84) 188.70 (12.01) n 10–2 42 4.98 42 1.09 39 1.15 42 237.78 n Difference (10-2–24-2C) n (1.40) (0.39) (0.49) (13.87) 42 42 39 42 N/A 21.54 (0.76) 20.27 (0.89) 49.41 (8.71) 95% CI P Value 42 N/A N/A 42 23.03 to 20.05 0.043 39 24.48 to 20.99 0.002 42 32.35 to 66.47 ,0.001 The values of the 24-2C were subtracted from the 10-2 to represent the difference. CI, confidence interval. There was no significant difference between the number of flagged TD and PD points of the 10 central 24-2C and corresponding 10-2 points at the P , 5%, P , 2%, and P , 1% significance levels (Table 2 and 3). The TD difference was 0.08 (SE 0.27) at the P , 5% significance level, 0.08 (0.32) at the P , 2% significance level, and 0.16 (0.35) at the P , 1% significance level (Table 2). The PD difference was 20.007 (0.29) at the P , 5% significance level, 20.09 (0.30) at the P , 2% significance level, and 20.10 (0.29) at the P , 1% significance level (Table 3). The values in the 24-2C column are representative of the mean difference from 0 of the number of flagged TD or PD points, respectively. At all significance levels, these were statistically significant (not shown), indicating that the 242C expectedly picked up more flagged points in the central 10° than the 24-2 would have alone. Table 4 shows the average number of total flagged TD points for each visual field test and the difference subdivided by diagnosis. There was no significant difference between the number of flagged points in the 10-2 and 24-2C for eyes without neuroophthalmic disease (P = 0.433), optic neuritis/MS (P = 0.736), NAION (P = 0.182), and optic atrophy of unknown cause (P = 0.438). Notably, the 10-2 detected a significantly increased number of flagged points than the 24-2C in patients in IIH/ papilledema (P = 0.003). There was insufficient sample size of patients with glaucoma, stroke, and optic nerve head drusen to compute a meaningful average and difference of flagged points. paracentral or cecocentral scotomas, whereas the 24-2C detected more arcuate and altitudinal defects (Table 5). The following is example commentary: • “The 24-2C clearly demonstrates an upper central arcuate defect which would have only been hinted at by scattered 5% points.” • “The extra points bring out that there really is an upper and lower arcuate abnormality.” • “The 24-2C points were helpful in identifying the upper arcuate defect, but not essential.” • “The 10-2 in addition to the 24-2C helps to identify papillomacular involvement.” • “The extra points help define the central scotoma.” • “The extra points highlight the central sparing and provide a good substrate for follow-up.” • “There is no extra diagnostic information, but good definition of the spared area of the visual field.” • “The 24-2C helps identify remaining central vision and directs you to a 10-2. The 24-2 would underestimate the spared area.” Although helpful in identifying visual field defects, there were no cases in which having the extra points resulted in a change in clinical diagnosis. There were 9 cases in which the extra points were noted not to be helpful. It was mentioned that the addition of more points temporally would aid in the identification of cecocentral scotomas. Qualitative Field Analysis CONCLUSION Expert visual field analysis revealed the following visual field defects: pure central scotomas, paracentral or cecocentral scotomas, arcuate defects, nasal steps, altitudinal defects, hemianopic defects, general depression, and central depression (Table 5). The 10-2 detected a greater number of The existing 24-2 visual field test is limited in its ability to detect macular damage, and prior research has consequently suggested test points to add to the 24-2 to enhance its sensitivity (2–5,7,9,12,13). For example, Hood et al and Chen TABLE 2. Mean (SE) values for the number of flagged TD points for the 24-2C and 10-2 fields, and the difference in flagged points between the 10-2 and 24-2C, at the P , 5%, P , 2%, and P , 1% thresholds #Flagged TD at P , 5% #Flagged TD at P , 2% #Flagged TD at P , 1% 24-2C n 10–2 n Difference (10-2–24-2C) n 95% CI P Value 4.16 (0.71) 3.15 (0.69) 2.45 (0.63) 42 42 42 4.28 (0.73) 3.28 (0.69) 2.58 (0.63) 42 42 42 0.08 (0.27) 0.08 (0.32) 0.16 (0.35) 42 42 42 20.45 to 0.61 20.53 to 0.70 20.52 to 0.83 0.767 0.791 0.651 CI, confidence interval. Yamane and Odel: J Neuro-Ophthalmol 2021; 41: e606-e611 e609 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 3. Mean (SE) values for the number of flagged PD points for the 24-2C and 10-2 fields, as well as the difference in flagged points between the 10-2 and 24-2C, at the P , 5%, P , 2%, and P , 1% thresholds #Flagged PD at P , 5% #Flagged PD at P , 2% #Flagged PD at P , 1% 24-2C n 10–2 n Difference (10-2–24-2C) n 95% CI P Value 2.26 (0.44) 1.82 (0.39) 1.43 (0.31) 41 41 41 2.23 (0.39) 1.72 (0.38) 1.38 (0.36) 41 41 41 20.007 (0.29) 20.09 (0.30) 20.10 (0.29) 41 41 41 20.57 to 0.56 20.68 to 0.49 20.67 to 0.46 0.982 0.754 0.723 CI, confidence interval. et al showed that the 24-2 can miss superior arcuate defects, where localized and deep defects are in glaucoma, and that test points at (21°, 5°) and (1°, 5°) are promising to detect this (7,13). Ehrlich et al showed a statistically significant increase in sensitivity and true positives of the 24-2 when 16 points from the 10-2 were added, regardless of whether these points were added symmetrically or based on areas frequently flagged as abnormal in visual field testing (3). To date, there is limited research on the effectiveness of the 24-2C test. In one study by Callan et al, 25 normal and 25 glaucoma subjects took a 24-2, 24-2C, and 10-2 test on one eye. The 24-2C was able to detect a significantly increased number of flagged points in the central 10° of TD and PD plots compared with the 24-2 in participants with glaucoma (10). In another similar study, 60 glaucomatous eyes from 60 patients underwent 24-2C and 10-2 testing, and here they found that the number of flagged TD and PD defects were statistically equivalent at P , 5%, P , 2%, and P , 1% for the 24-2C and 10-2 tests, indicating analogous central defects picked up by these 2 tests (14). Although neuro-ophthalmology relies heavily on visual field testing, there is limited research in this area on nonglaucomatous optic neuropathies. To the best of our knowledge, our study is the first to evaluate the 24-2C in this patient population. Here, we show that the 24-2C detected more abnormal points in the central 10° of vision than the 24-2 would have alone, given that the average number of flagged points for TD and PD plots at all threshold levels had a significant P value. The 24-2C also detected a statistically similar number of abnormal points in the TD and PD plots at all threshold levels when compared with the corresponding 10-2 points. This was consistent for diagnoses of optic neuritis/MS, NAION, optic atrophy, and those who presented for neuroophthalmic evaluation but ended up not having a neuroophthalmic diagnosis. IIH/papilledema was the only case in which the 10-2 detected more abnormal points. The SITA Faster protocol automatically turns off fixation checks via the blind spot and false negative catch trials but retains gaze tracking (1). For this study, we opted to turn on false negative monitoring. Our data shows an increased false positive and false negative rate in the 24-2C SITA Faster compared with the 10-2 SITA Fast. Although perhaps not directly comparable, the 24-2 SITA Faster test has been shown to have a higher (although not significantly so) false positive rate than the 24-2 SITA Fast, which is higher than that of the SITA Standard. The SITA Faster 24-2 also took significantly less time than the 10-2 in our study. Expert neuro-ophthalmologist commentary revealed 3 themes. First, in comparison to the standard 24-2, the TABLE 4. Mean (SE) values for the total number (P , 5%) of flagged TD points for the 24-2C and 10-2 fields, and the difference in flagged points between the 10-2 and 24-2C, by diagnosis Diagnosis No neuro-ophthalmic disease Optic neuritis/MS NAION IIH/Papilledema Optic atrophy (unknown cause) Glaucoma Stroke Optic nerve head drusen Total TD Points Flagged 24-2C n Total TD Points Flagged 10-2 n Difference (10-2–24-2C) n 95% CI 0.80 (0.57) 8 0.53 (0.40) 8 20.26 (0.33) 8 (20.89 to 0.38) 0.433 2.53 9.88 1.38 6.17 9 5 8 7 3.0 (0.74) 9.35 (0.38) 1.75 (0.97) 6.77 (1.56) 9 5 8 7 0.31 (0.92) 20.50 (0.29) 0.38 (0.13) 0.51 (0.66) 9 5 8 7 (21.49 to 2.12) (21.42 to 0.42) (0.13 to 0.62) (20.78 to 1.80) 0.736 0.182 0.003 0.438 (0.69) (0.13) (0.90) (1.65) P Value Insufficient sample size (n = 2) Insufficient sample size (n = 2) Insufficient sample size (n = 1) CI, confidence interval; NAION, nonarteritic anterior ischemic optic neuropathy; IIH, idiopathic intracranial hypertension. e610 Yamane and Odel: J Neuro-Ophthalmol 2021; 41: e606-e611 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 5. Count of various visual field defects seen in the 24-2C and 10-2 visual fields 24-2C 10–2 Pure Central Paracentral or Cecocentral 2 2 2 5 Nasal Arcuate Step Altitudinal Hemianopic 13 11 2 1 2 0 extra points in the 24-2C helped to identify and define visual field defects, especially central arcuate defects and central scotomas. Second, the 24-2C helped to identify papillomacular involvement. Third, the 24-2C was especially helpful in identifying a spared area of central vision. In conclusion, we sought to answer the question of what additional information the extra 10 points of the 24-2C test provide, whether the 24-2C can serve has a hybrid between the 24-2 and 10-2, and how this may be applied clinically. The 24-2C is able to detect more visual field loss in the central 10° than the 24-2 test, and this visual loss corresponds to loss detected in the 10-2 pattern. From a clinical perspective, the extra points in the 24-2C especially helped to identify central arcuate defects, central scotomas, papillomacular damage and spared areas of central vision that the 24-2 alone would not have picked up on; this can be particularly useful for clinical monitoring of remaining vision. Although additional points did not influence the presumed clinical diagnosis, the 24-2C exhibits potential to be used as a hybrid between the 24-2 and 10-2 to evaluate visual field defects, especially in situations that require testing of both central and peripheral vision. For this reason, and its shorter test duration than the 10-2, the 24-2C may be an especially good screening test. The limitations of the current study and avenues for further exploration include: (1) The test-retest variability of the 24-2C is not currently known. (2) Although the 24-2C and 10-2 procedures were reported to have similar detection characteristics for central visual field loss, it is currently not clear whether the 2 procedures will have similar abilities to determine visual field change (progression or improvement). (3) Although qualitatively assessed, a quantitative approach to reveal the pattern and shape of visual field loss would be of interest in the future. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. L. M. Yamane and J. G. Odel; b. Acquisition of data: M. L. M. Yamane and J. G. Odel; c. Analysis and interpretation of data: M. L. M. Yamane and J. G. Odel. Category 2: a. Drafting the manuscript: M. L. M. Yamane; b. Revising it for intellectual content: M. L. M. Yamane and J. G. Odel. Category 3: a. Final approval of the completed manuscript: M. L. M. Yamane and J. G. Odel. 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