A new static visual field test algorithm: the Ambient Interactive ZEST (AIZE).

Visual field (VF) test is one of the most vital tests in the diagnosis of glaucoma and to monitor the disease worsening. In the past couple of decades, the standard automated perimetry (SAP) test takes a major role in VF test for glaucoma patients. The SAP has been demanded to finish a test in short time without sacrificing accuracy. In this study, we developed and evaluated the performance of a new perimetric algorithm (ambient interactive zippy estimation by sequential testing (ZEST): AIZE) by computer simulation. AIZE is a modification of the ZEST procedure that utilizes the spatial information (weighted likelihood: WL) of neighboring test locations, which varies from the distance to the tested location, to estimate a visual threshold. Ten glaucomatous and 10 normal empirical visual field (VF) test results were simulated with five error conditions [(3% false positives (FP), 3% false negatives (FN)), (9% FP, 9% FN), (15% FP, 15% FN), (3% FP, 15% FN), (15% FP, 3% FN)]. The total number of test presentations and the root mean square error (RMSE) of the estimated visual sensitivities were compared among AIZE, the non-weighted test (WL = 0) and the fixed-weighted test (WL = 0.33). In both glaucomatous (G) and normal (N) VFs, the fixed-weighted test had the lowest number of test presentations (median G 256, N 139), followed by the AIZE (G 285, N 174) and the non-weighted test (G 303, N 195). The RMSE of the fixed-weighted test was lower (median 1.7 dB) than that of the AIZE (1.9 dB) and the non-weighted test (1.9 dB) for normal VFs, whereas the AIZE had a lower RMSE (3.2 dB) than the fixed-weighted test (4.5 dB) and the non-weighted test (4.0 dB) for glaucomatous VFs. Simulation results showed that AIZE had fewer test presentations than the non-weighted test strategy without affecting the accuracy for glaucomatous VFs. The AIZE is a useful time saving test algorithm in clinical settings.

Measurement of Fixational Eye Movements With the Head-Mounted Perimeter Imo.

Purpose: Although visual field testing is conducted with the subject gazing at a fixation target, constant minute eye movements, called fixational eye movements, do occur during fixation. We examined dynamic changes in fixational eye movements associated with stimulus presentation during visual field testing. Methods: We used the head-mounted perimeter imo, which is capable of measurement under binocular conditions, with the frame rate of its fixation monitoring camera improved to 300 Hz, to assess fixational eye movements in 18 healthy individuals. We measured changes in fixational eye movements during testing under monocular and binocular conditions and analyzed these changes based on the bivariate contour ellipse area (BCEA). We also assessed the changes in the horizontal and vertical microsaccade rates separately. Results: Both the BCEA and horizontal microsaccade rates were higher at 400 to 600 msec after stimulus presentation than during stimulus presentation (P < 0.01). Additionally, the BCEA and vertical microsaccade rates were significantly lower in the binocular condition than in the monocular condition (P < 0.01 and P < 0.05, respectively). We did not observe a significant correlation between the test locations and microsaccade direction during visual field testing. Conclusions: Fixational eye movements, especially vertical microsaccade rates, were lower in the binocular condition than in the monocular condition. Visual field testing under binocular conditions is a useful method for suppressing fixational eye movements and stabilizing the fixation during testing and may improve the reliability of the test results. Translational Relevance: Visual field testing under binocular conditions can make the fixation more stable during the testing compared with monocular conditions.

Effect of Sensitivity Disparity Between the Two Eyes on Pointwise Monocular Sensitivity Under Binocular Viewing in Patients With Glaucoma.

PRCIS: A difference between monocular sensitivities measured with and without occlusion was observed in glaucoma. Monocular sensitivity without occlusion could have been affected differently by binocular interaction due to the sensitivity disparity between both eyes. PURPOSE: To investigate the influence of sensitivity disparity between both eyes on visual field results under binocular viewing in glaucoma. MATERIALS AND METHODS: Thirteen glaucoma patients tested by Humphrey Field Analyzer (HFA) and imo were reviewed retrospectively. On the basis of their HFA results, we defined the eye with a better HFA-MD as "the better eye" and the fellow eye with a worse HFA-MD as "the worse eye." Depending on the pointwise pattern deviation (PD) of both eyes, all evaluated test points were classified into 4 groups: normal PD in both eyes (N/N), normal PD in the better eye but abnormal in the worse eye (N/A), abnormal PD in the better eye but normal in the worse eye (A/N), and abnormal PD in both eyes (A/A). Using imo, which can measure sensitivity with and without occluding the nontested eye, the better eye's sensitivities with and without occlusion were compared in each group using weighted data. The weight was derived by applying the inverse probability weighting. RESULTS: Monocular sensitivity without occlusion was higher than that with occlusion in N/N (P<0.01) and the opposite was observed in A/A (P<0.05). No significant sensitivity difference between both conditions was seen in N/A or A/N. In N/A, the points showing a higher sensitivity without occlusion decreased as the sensitivity difference between both eyes increased. CONCLUSIONS: A difference between sensitivities measured with and without occlusion was observed in glaucoma. Owing to the sensitivity disparity between both eyes, monocular sensitivity without occlusion could have been affected differently by binocular interaction.

OCT Signal Enhancement with Deep Learning.

PURPOSE: To establish whether deep learning methods are able to improve the signal-to-noise ratio of time-domain (TD) OCT images to approach that of spectral-domain (SD) OCT images. DESIGN: Method agreement study and progression detection in a randomized, double-masked, placebo-controlled, multicenter trial for open-angle glaucoma (OAG), the United Kingdom Glaucoma Treatment Study (UKGTS). PARTICIPANTS: The training and validation cohort comprised 77 stable OAG participants with TD OCT and SD OCT imaging at up to 11 visits within 3 months. The testing cohort comprised 284 newly diagnosed OAG patients with TD OCT images from a cohort of 516 recruited at 10 United Kingdom centers between 2007 and 2010. METHODS: An ensemble of generative adversarial networks (GANs) was trained on TD OCT and SD OCT image pairs from the training dataset and applied to TD OCT images from the testing dataset. Time-domain OCT images were converted to synthesized SD OCT images and segmented via Bayesian fusion on the output of the GANs. MAIN OUTCOME MEASURES: Bland-Altman analysis assessed agreement between TD OCT and synthesized SD OCT average retinal nerve fiber layer thickness (RNFLT) measurements and the SD OCT RNFLT. Analysis of the distribution of the rates of RNFLT change in TD OCT and synthesized SD OCT in the two treatment arms of the UKGTS was compared. A Cox model for predictors of time-to-incident visual field (VF) progression was computed with the TD OCT and the synthesized SD OCT images. RESULTS: The 95% limits of agreement were between TD OCT and SD OCT were 26.64 to -22.95; between synthesized SD OCT and SD OCT were 8.11 to -6.73; and between SD OCT and SD OCT were 4.16 to -4.04. The mean difference in the rate of RNFLT change between UKGTS treatment and placebo arms with TD OCT was 0.24 (P = 0.11) and with synthesized SD OCT was 0.43 (P = 0.0017). The hazard ratio for RNFLT slope in Cox regression modeling for time to incident VF progression was 1.09 (95% confidence interval [CI], 1.02-1.21; P = 0.035) for TD OCT and 1.24 (95% CI, 1.08-1.39; P = 0.011) for synthesized SD OCT. CONCLUSIONS: Image enhancement significantly improved the agreement of TD OCT RNFLT measurements with SD OCT RNFLT measurements. The difference, and its significance, in rates of RNFLT change in the UKGTS treatment arms was enhanced and RNFLT change became a stronger predictor of VF progression.

Comparison of head-mounted perimeter (imo®) and Humphrey Field Analyzer.

PURPOSE: The head-mounted automated perimeter imo® is a new portable perimeter that does not require a dark room and can be used to examine patients in any setting. In this study, imo 24plus (1-2) AIZE examinations were compared with previous Humphrey Field Analyzer (HFA) 30-2 (SITA standard) examinations within the same patient. PATIENTS AND METHODS: imo examinations (either head-mounted [i-H] or fixed [i-F] type) were performed in patients with glaucoma or suspected glaucoma who had already experienced HFA five or more times. Measurement time and correlations of mean deviation (MD) and visual field index (VFI) values were compared between groups for HFA, i-H, i-F, and imo total (i-T). Fixation loss (FL), false-positive (FP), and false-negative (FN) detection rates were compared. The percentage of binocular random single-eye tests under possible non-occlusion conditions using imo was determined. Mann-Whitney U test was performed, and Spearman's rank-order correlation coefficient was calculated. RESULTS: The inclusion period was July to December 2016. Among 273 subjects (543 eyes), 147 (292 eyes) were tested with i-H type and 126 (251 eyes) with i-F type. Mean MD values for HFA and i-T were -6.1±7.8 and -6.2±7.1 dB, respectively. Mean measurement times for HFA, i-H, i-F, and i-T were 15.23±2.07, 10.47±2.11, 11.04±2.31, and 10.54±2.19 minutes, respectively (P<0.01 for HFA vs i-H/i-F). Total mean measurement time was shorter by 30.8% for i-T vs HFA. Correlation coefficients of MD and VFI were R 2>0.81 for HFA vs i-H and i-F. FP and FN detection rates were significantly higher with i-T than HFA; there was no significant difference in FL. Binocular random single-eye tests were possible in 85% of cases. CONCLUSION: imo reduced measurement time by 30.8%. imo VFI and MD values were highly correlated with HFA. As i-F and i-H types produced similar results, imo can be used in accordance with the patient's situation.

Utility of CLOCK CHART binocular edition for self-checking the binocular visual field in patients with glaucoma.

BACKGROUND/AIMS: Car accidents caused by drivers unaware of their visual field (VF) defects under binocular vision have become an issue. We developed a simple self-check chart (CLOCK CHART binocular edition (CCBE)) to help patients with glaucoma recognise their abnormalities in the binocular VF and evaluated its usefulness. METHODS: The chart has four targets displayed at 10°, 15°, 20° and 25° eccentricities. The examinee gradually rotates the chart 360° clockwise. At every 30°, the examinee confirms the fixation and indicates if all four targets can be seen. This study enrolled 88 eyes of 44 patients with glaucoma (mean age, 64.4±13.1 years) and 64 eyes of 32 visually normal individuals (mean age, 32.0±8.4 years). Except the CCBE test, static VF testing using the Humphrey field analyser (HFA) Swedish Interactive Threshold Algorithm-Standard 30-2 and binocular Esterman programmes was also performed for the subjects with glaucoma. RESULTS: VF abnormality was defined as two or more contiguous points with a sensitivity of <10 dB within the central 30°. The CCBE test had sensitivities of 85% and 82% with respect to the HFA and Esterman results, respectively. We also used the British VF standards for Group 1 (car/motorcycle) drivers, and a sensitivity of 88% was obtained for the CCBE. The chart had a specificity of 100% for the visually normal subjects. CONCLUSION: The CCBE test enables drivers with glaucoma to notice their VF abnormalities under binocular condition. The application of this simple self-check method appears promising for occasions such as driver licensing.

Noninvasive Fingerprinting-Based Tracking of Replicative Cellular Senescence Using a Colorimetric Polyion Complex Array.

A fingerprint-based sensing approach was used to characterize in vitro cellular senescence. Secretion profiles of cultured human fibroblasts in different senescent stages were transformed into colorimetric enzyme-activity fingerprints by applying cell culture media to a polyion complex array. Analysis of the obtained fingerprints using pattern recognition methods, such as linear discriminant analysis and hierarchical clustering analysis, revealed that the polyion complex array allows the noninvasive tracking of the replicative senescence progress even in those stages where a conventional marker such as senescence-associated ß-galactosidase is negative. This fingerprint-based approach should thus offer an effective way for the routine monitoring or screening of in vitro cell senescence studies.

Distribution and Progression of Visual Field Defects With Binocular Vision in Glaucoma.

PURPOSE: To evaluate the distribution and progression of glaucomatous visual field (VF) defects with binocular vision. PATIENTS AND METHODS: Subjects were 167 patients (average age, 67±10.7 y) with glaucoma who received the Humphrey 24-2 VF test (SITA-Standard) for the 2 eyes. Using the Best Location Algorithm, patient's binocular integrated VF (IVF) was calculated from their Humphrey 24-2 results. Of 167, 77 subjects (average age, 68±11.0 y) also underwent monocular/binocular Humphrey Esterman tests. Patient's stage of glaucomatous VF loss was classified by the Esterman Disability Score for each test, and the distribution and progression of the defects with binocular vision was evaluated for each stage. The frequencies of the defects in the upper and lower halves of the VF were also investigated. RESULTS: With the IVF, the glaucomatous VF defects were most frequently found around the Mariotte blind spots and the Bjerrum areas and extended to the periphery. With the binocular Humphrey Esterman VF, the defects were most frequently found around the bitemporal and Bjerrum areas. The IVF results showed 31%, 49%, and 20% of the patients with the earliest glaucoma having defects in the upper, lower, and both halves of the VF, respectively. CONCLUSIONS: Glaucomatous VF defects with binocular vision were frequently found at the Mariotte blind spots in the central VF and around the bitemporal areas in the periphery. They appeared to have distributions and progression different from those of the defects with monocular vision previously reported.

Exploring Test-Retest Variability Using High-Resolution Perimetry.

PURPOSE: Test-retest variability (TRV) of visual field (VF) data seriously degrades our capacity to recognize true VF progression. We conducted repeated high-resolution perimetry with a test interval of 0.5° to investigate the sources of TRV. In particular, we examined whether the spatial variance of the observed sensitivity changes or if their absolute magnitude was of more importance. METHODS: Sixteen eyes of 16 glaucoma patients were each tested three times at 61 VF locations along the superior-temporal 45° meridian using a modified protocol of the Octopus 900 perimeter. TRV was quantified as the standard deviation of the repeats at each point (retest-SD). We also computed the mean sensitivity at each point (retest-MS) and the running spatial-SD along the tested meridian. Multiple regression models investigated whether any of those variables (and also age, sex, and VF eccentricity) were significant independent determinants of TRV. RESULTS: The main independent determinants of TRV were the retest-MS at -0.04 dB TRV/dB loss (P < 0.0001, t-statistic 5.05), and the retest-SD at 0.47 dB spatial variance/dB loss (P < 0.0001, t-statistic 12.5). CONCLUSIONS: The larger effect for the spatial-SD suggested that it was perhaps a stronger determinant of TRV than scotoma depth per se. This might support the hypothesis that interactions between small perimetric stimuli, rapidly varying sensitivity across the field, and normal fixational jitter are strong determinants of TRV. TRANSLATIONAL RELEVANCE: Our study indicates that methods that might reduce the effects of jagged sensitivity changes, such as increasing stimulus size or better gaze tracking, could reduce TRV.

Test Conditions in Macular Visual Field Testing in Glaucoma.

PURPOSE: The purpose of this study is to evaluate the suitable visual field (VF) test conditions (target size, test type, and eccentricity) for the macular region, we investigated the correlations between the ganglion cell layer (GCL) thickness and 6 VF test results. METHODS: We tested 32 eyes of patients (61.1±9.2 y) with preperimetric (6), early-stage (16), and moderate-stage (10) glaucoma. The VF tests included 3 SAP (the 10-2 HFA using SITA with target size III [HFA SITA (III)], full threshold with size III [HFA FULL (III)] and size I [HFA FULL (I)]) and 3 visual function-specific perimetry tests (the 10-2 SWAP, 10-2 flicker, and 10-2 Humphrey Matrix). The GCL and inner plexiform layer (GCL+IPL) thickness was measured by Spectral Domain Optical Coherence Tomography (SD-OCT) with a macular 7×7 mm cube scan (3D OCT-2000, Topcon). The coefficient of determination (r) for the correlation between visual sensitivity and the GCL+IPL thickness was calculated for each test at eccentricities 0 to 5 degrees, 5 to 7 degrees, and 7 to 10 degrees using linear and quadratic regressions. RESULTS: All 6 tests showed the strongest correlation with the GCL+IPL thickness at 5 to 7 degrees. The respective r (linear) and R (quadratic) for HFA SITA (III), HFA FULL (III), HFA FULL (I), SWAP, Flicker, and Matrix were (0.40, 0.50), (0.43, 0.53), (0.44, 0.46), (0.51, 0.51), (0.33, 0.34), and (0.52, 0.52). CONCLUSIONS: As compared with the frequently-used SAP with a size III, SAP with size I and the function-specific perimetry tests (especially the Matrix) could be more suitable for testing the macular region.

Effects of head tilt on visual field testing with a head-mounted perimeter imo.

PURPOSE: A newly developed head-mounted perimeter termed "imo" enables visual field (VF) testing without a fixed head position. Because the positional relationship between the subject's head and the imo is fixed, the effects of head position changes on the test results are small compared with those obtained using a stationary perimeter. However, only ocular counter-roll (OCR) induced by head tilt might affect VF testing. To quantitatively reveal the effects of head tilt and OCR on the VF test results, we investigated the associations among the head-tilt angle, OCR amplitude and VF testing results. SUBJECTS AND METHODS: For 20 healthy subjects, we binocularly recorded static OCR (s-OCR) while tilting the subject's head at an arbitrary angle ranging from 0° to 60° rightward or leftward in 10° increments. By monitoring iris patterns, we evaluated the s-OCR amplitude. We also performed blind spot detection while tilting the subject's head by an arbitrary angle ranging from 0° to 50° rightward or leftward in 10° increments to calculate the angle by which the blind spot rotates because of head tilt. RESULTS: The association between s-OCR amplitude and head-tilt angle showed a sinusoidal relationship. In blind spot detection, the blind spot rotated to the opposite direction of the head tilt, and the association between the rotation angle of the blind spot and the head-tilt angle also showed a sinusoidal relationship. The rotation angle of the blind spot was strongly correlated with the s-OCR amplitude (R2≥0.94, p<0.0001). A head tilt greater than 20° with imo causes interference between adjacent test areas. CONCLUSIONS: Both the s-OCR amplitude and the rotation angle of the blind spot were correlated with the head-tilt angle by sinusoidal regression. The rotated VF was correlated with the s-OCR amplitude. During perimetry using imo, the change in the subject's head tilt should be limited to 20°.

Visual Field Testing with Head-Mounted Perimeter 'imo'.

PURPOSE: We developed a new portable head-mounted perimeter, "imo", which performs visual field (VF) testing under flexible conditions without a dark room. Besides the monocular eye test, imo can present a test target randomly to either eye without occlusion (a binocular random single eye test). The performance of imo was evaluated. METHODS: Using full HD transmissive LCD and high intensity LED backlights, imo can display a test target under the same test conditions as the Humphrey Field Analyzer (HFA). The monocular and binocular random single eye tests by imo and the HFA test were performed on 40 eyes of 20 subjects with glaucoma. VF sensitivity results by the monocular and binocular random single eye tests were compared, and these test results were further compared to those by the HFA. The subjects were asked whether they noticed which eye was being tested during the test. RESULTS: The mean sensitivity (MS) obtained with the HFA highly correlated with the MS by the imo monocular test (R: r = 0.96, L: r = 0.94, P < 0.001) and the binocular random single eye test (R: r = 0.97, L: r = 0.98, P < 0.001). The MS values by the monocular and binocular random single eye tests also highly correlated (R: r = 0.96, L: r = 0.95, P < 0.001). No subject could detect which eye was being tested during the examination. CONCLUSIONS: The perimeter imo can obtain VF sensitivity highly compatible to that by the standard automated perimeter. The binocular random single eye test provides a non-occlusion test condition without the examinee being aware of the tested eye.

Detectability of Visual Field Defects in Glaucoma With High-resolution Perimetry.

PURPOSE: To extrapolate the optimal test point resolution for assessment of glaucomatous visual field (VF) defects including subtle functional defects, we performed high-resolution perimetry with the 0.5 degrees test point resolution. SUBJECTS AND METHODS: Subjects were 11 eyes of 11 normal volunteers and 16 eyes of 16 glaucomatous patients. Octopus 900 custom test was used to measure 61 points with the test point resolution of 0.5 degrees on the temporal meridian of 45 degrees within the eccentricity of 30 degrees. In the glaucoma cases, VF profiles were extracted in 17 patterns of the test point resolutions that ranged from 0.5 to 8.5 degrees and the mean defect (MD), square root of loss variance (sLV), and maximum sensitivity loss (Max loss) were calculated. The influence of the test point resolution on MD, sLV, and Max loss was examined. In addition, the test range from the fixation point to the eccentricity of 30 degrees was divided into 3 zones. Similarly, each zone was investigated if the test point resolution exerted influence on the MD, sLV, and Max loss. RESULTS: Our glaucoma cases did not show any significant differences in MD and sLV regardless of the resolution. Max loss showed significant difference at resolution ≥1.0 degree. MD and sLV did not show significant differences by the change of resolution in each zone. Max loss showed significant differences at resolution ≥1.5 degrees within the central 10 degrees. CONCLUSIONS: To detect subtle VF defects within the eccentricity of 10 degrees, high-resolution perimetry with the test point resolution of <1.5 degrees is necessary.

Correlations between M-CHARTS and PHP findings and subjective perception of metamorphopsia in patients with macular diseases.

PURPOSE: To assess the correlations between a patient's subjective perception of metamorphopsia and the clinical measurements of metamorphopsia by M-CHARTS and PreView PHP (PHP). METHODS: The authors designed a 10-item questionnaire focusing on the symptoms of metamorphopsia and verified its validity with a Rasch analysis. M-CHARTS measured the minimum visual angle of a dotted line needed to detect metamorphopsia, and PHP used the hyperacuity function for detection. Subjects were 39 patients with idiopathic epiretinal membrane (ERM), 22 patients with idiopathic macular hole (M-hole), 19 patients with age-related macular degeneration (AMD), and 51 healthy controls. RESULTS: Rasch analysis suggested the elimination of one question. The nine-item questionnaire score significantly correlated to the M-CHARTS score in ERM (r = 0.59; P = 0.0004) but not in M-hole and to the PHP result in AMD (r = -0.29; P = 0.04) but not in ERM. Eighty percent of ERM patients with greater horizontal M-CHARTS score subjectively perceived horizontal metamorphopsia more often. M-CHARTS showed better sensitivities than PHP in both ERM (89% vs. 42%) and AMD (74% vs. 68%) and better specificity (100% vs. 71%) in healthy controls. Rasch analysis indicated that the present form of the questionnaire is better suited for moderate to severe cases of metamorphopsia than for mild cases. CONCLUSIONS: The questionnaire appears to be a valid assessment of patient subjective perception of metamorphopsia and can be used to supplement the clinical measurements of metamorphopsia by M-CHARTS and PHP in patients with macular diseases.

Detectability of glaucomatous changes using SAP, FDT, flicker perimetry, and OCT.

PURPOSE: To compare the detectability between glaucomatous visual field changes using standard automated perimetry (SAP), frequency doubling technology (FDT), short-wavelength automated perimetry (SWAP), and flicker perimetry and structural changes using optical coherence tomography (OCT). PARTICIPANTS: Fifty-nine eyes of fifty-nine patients with open-angle glaucoma, 24 eyes of 24 glaucoma suspects (GSs), and 40 eyes of 40 healthy age-matched subjects. METHODS: All subjects underwent Humphrey visual field analyzer II 24-2 full threshold (SAP), Swedish interactive threshold algorithm-SWAP, FDT (30-1, 30-5, 24-2-1, 24-2-5), flicker perimetry on Octopus 311 (4-zone probability 38S), and Stratus OCT [fast retinal nerve fiber layer thickness (NFLT) and fast optic disc]. To evaluate the visual field, FDT and flicker used the number of abnormal points, whereas SAP used mean deviation (MD) and SWAP used both the number of abnormal points and MD. The areas under the receiver operating characteristic curves [area under the curve (AUCs)] and sensitivities at fixed specificities were used to assess the detectability of glaucoma. RESULTS: The AUC for FDT 30-1, 30-5, 24-2-1, 24-2-5, flicker perimetry, SWAP (MD), and SWAP (number of abnormal points) were 0.95, 0.94, 0.88, 0.89, 0.99, 0.88, and 0.88 in the early glaucoma group and 0.67, 0.69, 0.65, 0.70, 0.80, 0.64, and 0.66 in the GS group, respectively. In the early glaucoma and GS groups, all OCT parameters had an AUC >0.81 except the disc area parameter. Especially, average NFLT had the highest AUC of 0.94 in the OCT parameters. CONCLUSIONS: FDT, SWAP, flicker perimetry, and OCT are all useful methods for discriminating between healthy eyes and eyes with early glaucoma. Among all 10 OCT parameters, NFLT has the highest sensitivity for detecting early glaucomatous changes in GS patients.