Quantification and Predictors of Visual Field Variability in Healthy, Glaucoma Suspect, and Glaucomatous Eyes Using SITA-Faster.

PURPOSE: The newly released Swedish Interactive Thresholding Algorithm (SITA)-Faster (SFR) has significantly shorter testing durations compared with older SITA algorithms, but its variability is uncertain. This study quantified and established threshold limits of test-retest variability across the 24-2 test grid using SFR. DESIGN: Cross-sectional study with prospective longitudinal arm. PARTICIPANTS: 1426 eyes of 787 patients with healthy, suspected glaucoma, or manifest glaucoma eyes from hospital- and university- eye clinics. METHODS: Two SFR tests per eye at a baseline visit and at two follow-up visits. MAIN OUTCOME MEASURES: Pointwise variability measured by test-retest difference in pointwise sensitivity between tests one and two, mean global variability (test-retest variance) measured by average of pointwise variability for each participant, global sensitivity, and reliability indices of each eye. RESULTS: Of the 1426 eyes, 540 eyes (37.9%) had a diagnosis of glaucoma, 753 eyes (52.8%) were suspected of having glaucoma, and the remaining 133 eyes (9.3%) were healthy. Of 74 152 pointwise sensitivities obtained, the mean test-retest difference was 2.17 ± 2.9 dB, whereas the mean test-retest variance for each participant was 2.17 ± 1.2 dB. Pointwise and global variability increased with worsening threshold sensitivity and (MD), respectively, and was greater for peripheral compared with central test locations. In the longitudinal cohort, no significant difference in mean test-retest variance was found across the 3 visits (mean variability, 2.10 dB vs. 2.16 dB vs. 2.16 dB at visits F0 vs. F1 vs. F2; P = 0.53, repeated-measures analysis of variance). Baseline MD (-0.19 dB; 95% CI, -0.22 to 0.16 dB; P < 0.0001) and abnormally high sensitivity on glaucoma hemifield test (1.14 dB; 95% CI, 0.78-1.51 dB; P < 0.0001) were significantly associated with increased variability. Finally, test-retest MD showed minimal change around the recommended 15% false-positive cutoff threshold. CONCLUSIONS: The variability of SFR increases with worsening threshold sensitivity, is stable over time, and is greater for peripheral compared with central test locations. Worse baseline MD and abnormally high sensitivity are significant predictors of increased variability. A cutoff of 15% in false-positive results may be inappropriate as a threshold for judging test reliability in SFR. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparing a head-mounted virtual reality perimeter and the Humphrey Field Analyzer for visual field testing in healthy and glaucoma patients.

PURPOSE: To compare clinical visual field outputs in glaucoma and healthy patients returned by the Humphrey Field Analyzer (HFA) and virtual reality (Virtual Field, VF) perimetry. METHODS: One eye of 54 glaucoma patients and 41 healthy subjects was prospectively tested (three times each in random order) using the HFA and VF perimeters (24-2 test grids). We extracted and compared global indices (mean deviation [MD] and pattern standard deviation [PSD]), pointwise sensitivity (and calculated 'equivalent' sensitivity after accounting for differences in background luminance) and pointwise defects. Bland-Altman (mean difference [Mdiff ] and 95% limits of agreement [LoA]) and intraclass correlation analyses were performed. RESULTS: The VF test was shorter (by 76 s) and had lower fixation losses (by 0.08) and false-positive rate (by 0.01) compared to the HFA (all p < 0.0001). Intraclass correlations were 0.86, 0.82 and 0.47 for MD, PSD and pointwise sensitivity between devices, respectively. Test-retest variability was higher for VF (Mdiff 0.3 dB, LoA -7.6 to 8.2 dB) compared to the HFA (Mdiff -0.3 dB, LoA -6.4 to 5.9 dB), indicating greater test-retest variability. When using each device's underlying normative database, the HFA detected, on average, 7 more defects (at the p < 0.05 level) out of the 52 test locations compared to this iteration of VF in the glaucoma cohort. CONCLUSIONS: Virtual Field returns global results that are correlated with the HFA, but pointwise sensitivities were more variable. Differences in test-retest variability and defect detection by its current normative database raise questions about the widespread adoption of VF in lieu of the HFA.

Frontloading visual field tests detect earlier mean deviation progression when applied to real-world-derived early-stage glaucoma data.

PURPOSE: To examine the diagnostic accuracy of performing two (frontloaded) versus one (clinical standard) visual field (VF) test per visit for detecting the progression of early glaucoma in data derived from clinical populations. METHODS: A computer simulation model was used to follow the VFs of 10,000 glaucoma patients (derived from two cohorts: Heijl et al., Swedish cohort; and Chauhan et al., Canadian Glaucoma Study [CGS]) over a 10-year period to identify patients whose mean deviation (MD) progression was detected. Core data (baseline MD and progression rates) were extracted from two studies in clinical cohorts of glaucoma, which were modulated using SITA-Faster variability characteristics from previous work. Additional variables included follow-up intervals (six-monthly or yearly) and rates of perimetric data loss for any reason (0%, 15% and 30%). The main outcome measures were the proportions of progressors detected. RESULTS: When the Swedish cohort was reviewed six-monthly, the frontloaded strategy detected more progressors compared to the non-frontloaded method up to years 8, 9 and 10 of follow-up for 0%, 15% and 30% data loss conditions. The time required to detect 50% of cases was 1.0-1.5 years less for frontloading compared to non-frontloading. At 4 years, frontloading increased detection by 26.7%, 28.7% and 32.4% for 0%, 15% and 30% data loss conditions, respectively. Where both techniques detected progression, frontloading detected progressors earlier compared to the non-frontloaded strategy (78.5%-81.5% and by 1.0-1.3 years when reviewed six-monthly; 81%-82.9% and by 1.2-2.1 years when reviewed yearly). Accordingly, these patients had less severe MD scores (six-monthly review: 0.63-1.67 dB 'saved'; yearly review: 1.10-2.87 dB). The differences increased with higher rates of data loss. Similar tendencies were noted when applied to the CGS cohort. CONCLUSIONS: Frontloaded VFs applied to clinical distributions of MD and progression led to earlier detection of early glaucoma progression.

Exploring the relationship between 24-2 visual field and widefield optical coherence tomography data across healthy, glaucoma suspect and glaucoma eyes.

PURPOSE: To utilise ganglion cell-inner plexiform layer (GCIPL) measurements acquired using widefield optical coherence tomography (OCT) scans spanning 55° × 45° to explore the link between co-localised structural parameters and clinical visual field (VF) data. METHODS: Widefield OCT scans acquired from 311 healthy, 268 glaucoma suspect and 269 glaucoma eyes were segmented to generate GCIPL thickness measurements. Estimated ganglion cell (GC) counts, calculated from GCIPL measurements, were plotted against 24-2 SITA Faster visual field (VF) thresholds, and regression models were computed with data categorised by diagnosis and VF status. Classification of locations as VF defective or non-defective using GCIPL parameters computed across eccentricity- and hemifield-dependent clusters was assessed by analysing areas under receiver operating characteristic curves (AUROCCs). Sensitivities and specificities were calculated per diagnostic category. RESULTS: Segmented linear regression models between GC counts and VF thresholds demonstrated higher variability in VF defective locations relative to non-defective locations (mean absolute error 6.10-9.93 dB and 1.43-1.91 dB, respectively). AUROCCs from cluster-wide GCIPL parameters were similar across methods centrally (p = 0.06-0.84) but significantly greater peripherally, especially when considering classification of more central locations (p < 0.0001). Across diagnoses, cluster-wide GCIPL parameters demonstrated variable sensitivities and specificities (0.36-0.93 and 0.65-0.98, respectively), with the highest specificities observed across healthy eyes (0.73-0.98). CONCLUSIONS: Quantitative prediction of VF thresholds from widefield OCT is affected by high variability at VF defective locations. Prediction of VF status based on cluster-wide GCIPL parameters from widefield OCT could become useful to aid clinical decision-making in appropriately targeting VF assessments.

The effect of macular visual field test density on central structure-function concordance in glaucoma.

CLINICAL RELEVANCE: Central visual field (VF) testing often requires focussed high-density test grids. The critical number of test locations for maximising structure-function concordance in the macula is not known. PURPOSE: The aim of this work is to determine the impact of the number of test locations in the central VF on binarized structure-function concordance in glaucoma. METHODS: Humphrey Field Analyser (HFA) 10-2 test grid and Cirrus optical coherence tomography Ganglion Cell Analysis (GCA) results from one eye of 155 glaucoma patients were extracted. Following anatomical correction for retinal ganglion cell displacement, the pointwise results of the central 36 locations of the 10-2 pattern deviation map and their corresponding locations within the GCA deviation map were recorded. The number of test locations was systematically reduced from 36 (4 locations per step) and added from 1 (1 location per step) and binarized structure-function concordance (p < 0.05 for both) at each step was evaluated. Eleven test point subtraction and addition models were developed. Concordance rates (proportion) were plotted as a function of number of test locations, and were fitted using segmental nonlinear regression to identify the critical point of inflection at which concordance was maximised and discordance minimised. RESULTS: Subtractive and additive approaches returned two-way estimates of the critical number, with, on average 8-14 test locations being the range at which structure-function concordance was optimised in the present cohort across all models. A randomised approach to subtracting or adding test locations returned critical numbers that were similar to systematic and empirical models, suggesting that specific test location was not as critical in optimising structure-function concordance compared to the number of test locations. CONCLUSION: There is a potential critical number (8-14) in macular visual field testing where binarized structure-function concordance is optimised, providing a framework for guiding the development of integrated macular test locations in VF testing for glaucoma.

Optical coherence tomography angiography in the diagnosis of ocular disease.

Clinical imaging provided by optical coherence tomography (OCT) and its variant, OCT-angiography (OCT-A), has revolutionised eyecare practice. The imaging techniques allow for the identification and quantification of ocular structures, supporting the diagnosis and prognosis of eye disease. In this review, an overview of the usefulness of OCT-A imaging in the diagnosis and management of a range of ocular conditions is provided when used in isolation or in combination with other imaging modalities and measures of visual function (visual field results). OCT-A imaging has the capacity to identify and quantify ocular vasculature non-invasively, thereby assisting the clinician in the diagnosis or to determine the efficacy of intervention in ocular conditions impacting retinal vasculature. Thus, additional clinically useful information can be obtained in eye diseases involving conditions such as those impacting retinal vessel occlusion, in diabetic retinopathy, inherited retinal dystrophy, age-related macular degeneration, choroidal neovascularisation and optic nerve disorders. Through a clinical case series, various ocular conditions are reviewed, and the impact of OCT-A imaging is discussed. Although OCT-A imaging has great promise and is already used in clinical management, there is a lack of set standards to characterise altered vascular features in disease and consequently for prognostication, primarily due to a lack of large-scale clinical trials and variability in OCT-A algorithms when generating quantitative parameters.

Retinal sensitivity changes in early/intermediate AMD: a systematic review and meta-analysis of visual field testing under mesopic and scotopic lighting.

Visual fields under mesopic and scotopic lighting are increasingly being used for macular functional assessment. This review evaluates its statistical significance and clinical relevance, and the optimal testing protocol for early/intermediate age-related macular degeneration (AMD). PubMed and Embase were searched from inception to 14/05/2022. All quality assessments were performed according to GRADE guidelines. The primary outcome was global mean sensitivity (MS), further meta-analysed by: AMD classification scheme, device, test pattern, mesopic/scotopic lighting, stimuli size/chromaticity, pupil dilation, testing radius (area), background luminance, adaptation time, AMD severity, reticular pseudodrusen presence, and follow-up visit. From 1489 studies screened, 42 observational study results contributed to the primary meta-analysis. Supported by moderate GRADE certainty of the evidence, global MS was significantly reduced across all devices under mesopic and scotopic lighting with large effect size (-0.9 [-1.04, -0.75] Hedge's g, P < 0.0001). The device (P < 0.01) and lighting (P < 0.05) used were the only modifiable factors affecting global MS, whereby the mesopic MP-1 and MAIA produced the largest effect sizes and exceeded test-retest variabilities. Global MS was significantly affected by AMD severity (intermediate versus early AMD; -0.58 [-0.88, -0.29] Hedge's g or -2.55 [3.62, -1.47] MAIA-dB) and at follow-up visit (versus baseline; -0.62 [-0.84, -0.41] Hedge's g or -1.61[-2.69, -0.54] MAIA-dB). Magnitudes of retinal sensitivity changes in early/intermediate AMD are clinically relevant for the MP-1 and MAIA devices under mesopic lighting within the central 10° radius. Other factors including pupil dilation and dark adaptation did not significantly affect global MS in early/intermediate AMD.