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.

Short-term Detection of Fast Progressors in Glaucoma: The Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study.

PURPOSE: To evaluate the performance of an intensive, clustered testing approach in identifying eyes with rapid glaucoma progression over 6 months in the Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 125 eyes from 65 primary open-angle glaucoma (POAG) subjects. METHODS: Subjects underwent 2 sets of 5 weekly visits (clusters) separated by an average of 6 months and then were followed with single visits every 6 months for an overall mean follow-up of 25 months (mean of 17 tests). Each visit consisted of testing with standard automated perimetry (SAP) 24-2 and 10-2, and spectral-domain OCT (SD-OCT). Progression was assessed using trend analyses of SAP mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Generalized estimating equations were applied to adjust for correlations between eyes for confidence interval (CI) estimation and hypothesis testing. MAIN OUTCOME MEASURES: Diagnostic accuracy of the 6-month clustering period to identify progression detected during the overall follow-up. RESULTS: A total of 19 of 125 eyes (15%, CI, 9%-24%) progressed based on SAP 24-2 MD over the 6-month clustering period. A total of 14 eyes (11%, CI, 6%-20%) progressed on SAP 10-2 MD, and 16 eyes (13%, CI, 8%-21%) progressed by RNFL thickness, with 30 of 125 eyes (24%, CI, 16%-34%) progressing by function, structure, or both. Of the 35 eyes progressing during the overall follow-up, 25 had progressed during the 6-month clustering period, for a sensitivity of 71% (CI, 53%-85%). Of the 90 eyes that did not progress during the overall follow-up, 85 also did not progress during the 6-month period, for a specificity of 94% (CI, 88%-98%). Of the 14 eyes considered fast progressors by SAP 24-2, SAP 10-2, or SD-OCT during the overall follow-up, 13 were identified as progressing during the 6-month cluster period, for a sensitivity of 93% (CI, 66%-100%) for identifying fast progression with a specificity of 85% (CI, 77%-90%). CONCLUSIONS: Clustered testing in the Fast-PACE Study detected fast-progressing glaucoma eyes over 6 months. The methodology could be applied in clinical trials investigating interventions to slow glaucoma progression and may be of value for short-term assessment of high-risk subjects. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.

Interpretation of the Visual Field in Neuro-ophthalmic Disorders.

PURPOSE OF REVIEW: In this review, we will describe current methods for visual field testing in neuro-ophthalmic clinical practice and research, develop terminology that accurately describes patterns of field deficits, and discuss recent advances such as augmented or virtual reality-based perimetry and the use of artificial intelligence in visual field interpretation. RECENT FINDINGS: New testing strategies that reduce testing times, improve patient comfort, and increase sensitivity for detecting small central or paracentral scotomas have been developed for static automated perimetry. Various forms of machine learning-based tools such as archetypal analysis are being tested to quantitatively depict and monitor visual field abnormalities in optic neuropathies. Studies show that the combined use of optical coherence tomography and standard automated perimetry to determine the structure-function relationship improves clinical care in neuro-ophthalmic disorders. Visual field assessment must be performed in all patients with neuro-ophthalmic disorders affecting the afferent visual pathway. Quantitative visual field analysis using standard automated perimetry is critical in initial diagnosis, monitoring disease progression, and guidance of therapeutic plans. Visual field defects can adversely impact activities of daily living such as reading, navigation, and driving and thus impact quality of life. Visual field testing can direct appropriate occupational low vision rehabilitation in affected individuals.

ISCEV and IPS guideline for the full-field stimulus test (FST).

The full-field stimulus test (FST) is a psychophysical technique designed for the measurement of visual function in low vision. The method involves the use of a ganzfeld stimulator, as used in routine full-field electroretinography, to deliver full-field flashes of light. This guideline was developed jointly by the International Society for Clinical Electrophysiology of Vision (ISCEV) and Imaging and Perimetry Society (IPS) in order to provide technical information, promote consistency of testing and reporting, and encourage convergence of methods for FST. It is intended to aid practitioners and guide the formulation of FST protocols, with a view to future standardisation.

Pattern electroretinogram, blue-yellow visual evoked potentials and the risk of developing visual field defects in glaucoma suspects: a longitudinal "survival" analysis with a very long follow-up.

PURPOSE: Estimating glaucoma suspects' risk for visual field defects helps to avoid under- and over-treatment. In this retrospective, longitudinal cohort study with a very long follow-up, we studied whether pattern electroretinograms (PERG) amplitudes and blue-on-yellow visual evoked potential (BY-VEP) latencies can predict visual field defects. METHODS: Participants of the Erlangen Glaucoma Study were examined with PERG and BY-VEP between 9/1991 and 8/2001. Stimuli were created using an optical bench with Maxwellian view and consisted of vertical gratings (0,88 cpd) in a 32° field for both PERG and BY-VEP. Patients were treated according to clinical standards and performed standard automated perimetry (SAP) annually. Retrospectively, patients with normal SAP at baseline were selected. Primary endpoint was conversion to perimetric glaucoma. Predictive value was modeled using Kaplan-Meier analyses and a multivariate cox proportional hazards model with the continuous variables PERG amplitude, BY-VEP peak time and SAP square-root of loss variance (sLV) after stratification for Jonas classification of the optic discs. RESULTS: Of 412 patients (288: Jonas 0, 103: I, and 21: II; baseline age: 20-60 years), 65 converted to perimetric glaucoma during follow-up (0.5-23.3 years; median 5.5 years). Optic disc classification was a strong risk factor for conversion (log rank p < 0.0001), and patients with more advanced changes progressed earlier. In the multivariate analysis (log rank p = 0.005), only PERG amplitude remained an independent risk factor after stratification for optic disc morphology (p = 0.021), with a ~ 30% higher risk per µV amplitude decrease. CONCLUSIONS: PERG helps to estimate glaucoma suspects' risk for visual field defects.

Comparing 2-dimensional macular pigment optical density with objective and subjective perimetry and visual acuity in age-related macular degeneration.

PURPOSE: To compare diagnostic power for different severities of age-related macular degeneration (AMD) of two-dimensional macular pigment optical densities (2D-MPOD) and spatially matched objective perimetry, with standard perimetry and best-corrected visual acuity (BCVA). METHODS: The ObjectiveField Analyser (OFA) provided objective perimetry, and a Heidelberg Spectralis optical coherence tomography (OCT) measured 2D-MPOD in AMD patients, both completed twice over 0.99 ± 0.16 years. From each 2D-MPOD image, we extracted 20 regions/macula, matched to the 20 OFA stimuli/macula. For each region, we calculated 7 measures from the 2D-MPOD pixel values and correlated those with OFA sensitivities and delays. We quantified 2D-MPOD changes, the ability of 2D-MPOD and OFA to discriminate AMD stages, and the discriminatory power of Matrix perimetry and BCVA using percentage area under receiver operator characteristic plots (%AUROC). RESULTS: In 58 eyes of 29 subjects (71.6 ± 6.3 years, 22 females), we found significant correlations between 2D-MPOD and OFA sensitivities for Age-Related Eye Disease Studies (AREDS)-3 and AREDS-4 severities. Delays showed significant correlations with AREDS-2. For AREDS-4, correlations extended across all eccentricities. Regression associated with the Bland-Altman plots showed significant changes in 2D-MPOD over the study period, especially variability measures. MPOD per-region medians discriminated AREDS-1 from AREDS-3 eyes at a %AUROC of 80.0 ± 6.3%, outperforming OFA, Matrix perimetry, and BCVA. CONCLUSIONS: MPOD changes correlated with central functional changes and significant correlations extended peripherally in later-stage AMD. Good diagnostic power for earlier-stage AMD and significant change over the study suggest that 2D-MPOD and OFA may provide effective biomarkers.

The structure-function relationship between multifocal pupil perimetry and retinal nerve fibre layer in glaucoma.

BACKGROUND: Multifocal pupillographic objective perimetry (mfPOP) is a novel method for assessing functional change in diseases like glaucoma. Previous research has suggested that, in contrast to the pretectally-mediated melanopsin response of intrinsically photosensitive retinal ganglion cells, mfPOP responses to transient onset stimuli involve the extrastriate cortex, and thus the main visual pathway. We therefore investigate the correlation between peripapillary retinal nerve fibre layer (pRNFL) thickness and glaucomatous visual field changes detected using mfPOP. Parallel analyses are undertaken using white on white standard automated perimetry (SAP) for comparison. METHODS: Twenty-five glaucoma patients and 24 normal subjects were tested using SAP, 3 mfPOP variants, and optical coherence tomography (OCT). Arcuate clusters of the SAP and mfPOP deviations were weighted according to their contribution to published arcuate divisions of the retinal nerve fibre layer. Structure-function correlation coefficients (r) were computed between pRNFL clock-hour sector thickness measurements, and the local visual field sensitivities from both SAP and mfPOP. RESULTS: The strongest correlation was observed in the superior-superotemporal disc sector in patients with worst eye SAP MD < -12 dB: r = 0.93 for the mfPOP LumBal test (p < 0.001). Correlations across all disc-sectors were strongest in these same patients in both SAP and mfPOP: SAP r = 0.54, mfPOP LumBal r = 0.55 (p < 0.001). In patients with SAP MD ≥ -6 dB in both eyes, SAP correlations across all sectors were higher than mfPOP; mfPOP correlations however, were higher than SAP in more advanced disease, and in normal subjects. CONCLUSIONS: For both methods the largest correlations with pRNFL thickness corresponded to the inferior nasal field of more severely damaged eyes. Head-to-head comparison of mfPOP and SAP showed similar structure-function relationships. This agrees with our recent reports that mfPOP primarily stimulates the cortical drive to the pupils.

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.

Mechanisms of cone sensitivity loss in retinitis pigmentosa.

PURPOSE: To explore the mechanisms of cone sensitivity loss in retinitis pigmentosa by combining two-colour perimetry with threshold versus intensity (tvi) testing. METHODS: Seven subjects with autosomal recessive retinitis pigmentosa and 10 normal subjects were recruited and underwent perimetric testing of one eye using 480- and 640-nm Goldman size V targets presented under scotopic conditions (no background illumination) and against a white background ranging in luminance from -1.5 to 2 log cd m-2 in 0.5 log cd m-2 steps. Data were fitted with tvi functions of the form logT = logT0 + log ((A + A0)/A0)n, where T is the threshold, T0 is the absolute threshold, A is the background intensity, A0 is the 'dark-light' constant and n is a gain constant. RESULTS: Reliable tvi functions could not be obtained within the region of the visual field corresponding to loss of the ellipsoid zone on optical coherence tomography. At fixation, changes in both T0 and A0 were observed, consistent with a d1 mechanism loss, which resulted in an upwards and rightwards shift of the tvi function. Losses at [±3°, ±3°] demonstrated changes in T0, consistent with a d3 mechanism loss, resulting in an upwards translation of the tvi curve. CONCLUSIONS: Although the absolute cone threshold was elevated at each location, shifts in the tvi function (so-called d1 mechanism loss) at fixation minimise threshold elevation in the presence of white adapting backgrounds, such as those typically employed in standard two-colour perimetry. At more peripheral testing locations, changes in threshold occurred independent of background luminance (so-called d3 mechanism loss). These findings suggest that backgrounds which selectively adapt rods while maintaining cones at, or near, absolute threshold may be preferable to conventional two-colour perimetry for assessing loss of cone sensitivity, especially at the point of fixation.

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.

Development and evaluation of Order of Magnitude (OM): a virtual reality-based visual field analyzer for glaucoma detection.

PURPOSE: This study introduces the Order of Magnitude (OM), a cost-effective, indigenous, virtual reality-based visual field analyzer designed for detecting glaucomatous visual field loss. METHODS: The OM test employs a two-step supra-thresholding algorithm utilizing stimuli of 0.43°diameter (equivalent to Goldmann size III) at low and high thresholds. A comparative analysis was conducted against the Humphrey visual field (HVF) test, considered the gold standard in clinical practice. Participants, including those with glaucoma and normal individuals, underwent comprehensive eye examinations alongside the OM and HVF tests between April and October 2019. Diagnostic sensitivity and specificity of the OM test were assessed against clinical diagnoses made by specialists. RESULTS: We studied 157 eyes (74 glaucomatous, 83 control) of 152 participants. Results demonstrated a high level of reliability for both OM and HVF tests, with no significant difference observed (P = 0.19, Chi-square test). The sensitivity and specificity of the OM test were found to be 93% (95% CI 86-100%) and 83% (95% CI 72.4-93%), respectively, while the HVF test showed sensitivity and specificity of 98% (95% CI 93.9-100%) and 83% (95% CI 73.9-92.8%), respectively. CONCLUSION: These findings suggest that the OM test is non-inferior to the reference standard HVF test in identifying glaucomatous visual field loss.

[Role of point-by-point light sensitivity in the assessment of glaucoma progression]. / Rol' potochechnoi svetochuvstvitel'nosti v otsenke progressirovaniya glaukomy.

PURPOSE: This study analyzes changes in light sensitivity in each test point of the visual field in patients with different stages of glaucoma. MATERIAL AND METHODS: The data of a prospective analytical case-control study were analyzed. All patients underwent assessment of retinal light sensitivity and its variability in 54 points corresponding to the 24-2 program. Mean light sensitivity values were calculated in each point. Intergroup analysis was performed to evaluate changes in light sensitivity in each point. RESULTS: The range of light sensitivity decrease in the early glaucoma group compared to the control group was from 1.5 to 3.6 dB. The range of light sensitivity decrease in the moderate glaucoma group compared to the control group was from 2.1 to 11.5 dB, and compared to the early glaucoma group - from -0.9 to 7.9 dB. The most frequent decrease in light sensitivity was detected in the nasal sector and along the horizontal line in the upper half of the visual field. This trend persisted within the central 10 degrees of the visual field. The range of light sensitivity decrease in the advanced glaucoma group compared to the control group was from 14.1 to 28.0 dB, and compared to the early glaucoma group - from 11.35 to 26.08 dB, compared to the moderate glaucoma group - from 9.1 to 23.5 dB. The most frequent and severe decrease in light sensitivity was detected in the paracentral zone in the lower half of the visual field. CONCLUSION: The study analyzed the trends in the development of glaucoma from the early to the advanced stage. The most frequent and severe defect in light sensitivity in cases of verified advanced glaucoma was found in the lower half of the visual field. Points No. 32, 33 and 40 can be indicated as the area of interest in assessing the progression of glaucoma, as they were found to have the most profound changes in light sensitivity as glaucoma progressed.

[Thresholds and variability of retinal light sensitivity in each point of the examined visual field]. / Porogovye znacheniya i variabel'nost' svetochuvstvitel'nosti setchatki v kazhdoi tochke issleduemogo polya zreniya.

PURPOSE: This study assesses the light sensitivity and its variability in each point of the visual field in patients without glaucoma and with different stages of glaucoma. MATERIAL AND METHODS: The data of a prospective analytical case-control study involving 500 patients were analyzed. The initial examination of all patients was performed using basic ophthalmological methods, including static perimetry. Retinal light sensitivity and its variability were assessed in 54 points corresponding to the Humphrey 24-2 program. Mean deviation and pattern standard deviation of light sensitivity were calculated for each point. RESULTS: The lowest light sensitivity values in patients with moderate glaucoma were found in the periphery of the nasal sector, at point No. 27 - 14.4 dB, and at points No. 24-26 along the horizontal axis from the nasal side - from 17.7 to 22.7 dB. The maximum variability of light sensitivity was found in the nasal sector on both sides of the horizontal line - from 10.7 to 11.5 dB. The average light sensitivity above the horizontal axis in patients with advanced glaucoma was 10.8 dB, which is 2 dB higher than in the lower half of the visual field - 8.8 dB. The highest light sensitivity values were found at points No. 24 - 17.7 dB and No. 31 - 16.78 dB, the lowest - at point No. 32 - 4.5 dB. The average variability values of light sensitivity in the upper half of the visual field were 9.6 dB, which is 1 dB less than in the lower half of the visual field - 10.6 dB. CONCLUSION: According to our data, points No. 32 and No. 40 are of particular interest in the diagnostic plan. In these loci, the highest light sensitivity values were determined in early and moderate glaucoma. However, the values in these points decrease significantly in advanced glaucoma. It can be assumed that changes in light sensitivity in these loci at the early stages of glaucoma may be a predictor of glaucoma progression.

Identifying the severity of diabetic retinopathy by visual function measures using both traditional statistical methods and interpretable machine learning: a cross-sectional study.

AIMS/HYPOTHESIS: To determine the extent to which diabetic retinopathy severity stage may be classified using machine learning (ML) and commonly used clinical measures of visual function together with age and sex. METHODS: We measured the visual function of 1901 eyes from 1032 participants in the Northern Ireland Sensory Ageing Study, deriving 12 variables from nine visual function tests. Missing values were imputed using chained equations. Participants were divided into four groups using clinical measures and grading of ophthalmic images: no diabetes mellitus (no DM), diabetes but no diabetic retinopathy (DM no DR), diabetic retinopathy without diabetic macular oedema (DR no DMO) and diabetic retinopathy with DMO (DR with DMO). Ensemble ML models were fitted to classify group membership for three tasks, distinguishing (A) the DM no DR group from the no DM group; (B) the DR no DMO group from the DM no DR group; and (C) the DR with DMO group from the DR no DMO group. More conventional multiple logistic regression models were also fitted for comparison. An interpretable ML technique was used to rank the contribution of visual function variables to predictions and to disentangle associations between diabetic eye disease and visual function from artefacts of the data collection process. RESULTS: The performance of the ensemble ML models was good across all three classification tasks, with accuracies of 0.92, 1.00 and 0.84, respectively, for tasks A-C, substantially exceeding the accuracies for logistic regression (0.84, 0.61 and 0.80, respectively). Reading index was highly ranked for tasks A and B, whereas near visual acuity and Moorfields chart acuity were important for task C. Microperimetry variables ranked highly for all three tasks, but this was partly due to a data artefact (a large proportion of missing values). CONCLUSIONS/INTERPRETATION: Ensemble ML models predicted status of diabetic eye disease with high accuracy using just age, sex and measures of visual function. Interpretable ML methods enabled us to identify profiles of visual function associated with different stages of diabetic eye disease, and to disentangle associations from artefacts of the data collection process. Together, these two techniques have great potential for developing prediction models using untidy real-world clinical data.

Evaluation of the Consistency of Glaucomatous Visual Field Defects Using a Clustered SITA-Faster Protocol.

PURPOSE: Frontloading SITA-Faster (SFR) visual fields (2 tests per eye on the same visit) has been shown to provide repeatable perimetric data at minimal time cost. This study reports the outcomes of using frontloaded SFR in the evaluation of pointwise visual field (VF) defects in a cohort of patients with glaucoma when transitioned from SITA-Standard (SS). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: A total of 144 eyes of 91 patients with confirmed or suspected glaucoma who had an SS test on a previous visit. METHODS: Two SFR tests (T1, T2) per eye on the same visit. MAIN OUTCOME MEASURES: Global sensitivity, reliability indices, and pointwise deviation map probability scores from the pattern deviation grid of each patient were compared across the 3 sequential tests to evaluate the consistency of VF defects. RESULTS: The mean age was 68.6 years, and 79.2% of patients had a diagnosis of glaucoma. There was no significant difference in mean deviation (MD) across the 3 tests (-5.83 decibels [dB], -5.28 dB, and -5.71 dB in SS, SFR1, and SFR2, respectively, repeated-measures analysis of variance [ANOVA], P = 0.48). The frontloaded SFR tests provided repeatable VFs that confirmed existing pointwise data on the SS in 4661 (62.3%) locations, reversed an SS defect in 614 (8.2%) locations, and demonstrated a new repeatable defect in 406 (5.4%) locations of the pattern deviation grid. A new defect of at least 3 contiguous points was identified in 20.1% of eyes. The non-repeatable points on the 2 SFR tests displayed no significant difference in the distribution of defect/nondefect points based on test order or peripheral versus central locations. There was no significant difference in the rate of obtaining at least 1 reliable test result between SS and the frontloaded SFR T1 and T2 (P = 0.77). Test duration significantly decreased from SS to SFR1/2 (379 vs. 160 vs. 158 seconds, P < 0.0001). CONCLUSIONS: Frontloading SFR tests can provide repeatable data for the evaluation of the consistency of pattern deviation defects in glaucoma, with no observable decline in performance from test fatigue. This is achieved at equivalent duration and reliability as a single SS test. Frontloading SFR may be helpful in increasing testing frequency/quantity to meet recommended guidelines for progression analysis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Validation of Rates of Mean Deviation Change as Clinically Relevant End Points for Glaucoma Progression.

PURPOSE: To investigate whether rates of standard automated perimetry (SAP) mean deviation (MD) over an initial 2-year follow-up period were predictive of events of visual field progression over an extended follow-up. DESIGN: Longitudinal, prospective, observational study. PARTICIPANTS: Two hundred forty-six eyes of 168 patients with glaucoma followed up every 6 months for up to 5 years. METHODS: Patients were required to have a minimum of 5 reliable SAP tests during the first 2 years of follow-up. Events of progression were evaluated using 2 methods: Guided Progression Analysis (GPA; Carl Zeiss Meditec, Inc) and a United States Food and Drug Administration (FDA)-suggested end point. The date of the first test showing progression after the first 2 years was considered to be the event date. Rates of change in SAP MD were calculated for the first 2 years of follow-up, and joint longitudinal survival models were used to assess the risk of faster initial MD loss for subsequent progression based on each event analysis. MAIN OUTCOME MEASURE: Risk of having an event of progression based on initial rates of SAP MD change. RESULTS: Fifty-six eye (22.8%) showed an event of progression by the GPA and 51 eyes (20.7%) did so by the FDA end point. Each 0.1-dB/year faster rate of SAP MD loss in the first 2 years was associated with a 26% increase in risk of a GPA progression end point developing (R2 = 76%) and 32% risk of an FDA-based end point developing (R2 = 83%). A reduction of 30% in the rate of MD change in the first 2 years was associated with a 20% reduction in the cumulative probability of a progression event developing over 5 years of follow-up. CONCLUSIONS: Rates of SAP MD change for eyes with glaucoma calculated over the initial 2 years of follow-up were strongly predictive of events of progression over subsequent follow-up. Our findings give support for the use of slopes of MD change as suitable end points of progression in clinical trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Fundus imaging and perimetry in patients with idiopathic intracranial hypertension-an intermethod and interrater validity study.

BACKGROUND AND PURPOSE: There is a need to improve the diagnostic process of patients suspected of papilledema. In patients with known or suspected idiopathic intracranial hypertension a fundus imaging and perimetric visual field assessment system (COMPASS) performed at a headache center was validated in comparison to an assessment (Topcon plus OCTOPUS) at a neuroophthalmological clinic. METHODS: For intermethod assessment, blinded fundus images and perimetry from COMPASS versus Topcon plus OCTOPUS were assessed by a neuroophthalmologist. For interrater assessment, fundus images and perimetry obtained by the COMPASS system were assessed by an untrained medical doctor, a trained neurologist and a trained medical student and compared to the neuroophthalmologist's assessments. RESULTS: For the intermethod variation of the presence of papilledema on fundus images, a kappa value of 0.60, sensitivity of 87% and specificity of 73% were found. The interrater variation of the presence of papilledema on fundus images showed kappa values ranging from 0.43 to 0.74, sensitivity values ranging from 70% to 96% and specificity values ranging from 46% to 93% when comparing the assessments made by the headache center staff with neuroophthalmologist's assessments. The COMPASS showed a 59% sensitivity and moderate agreement in detecting visual field defects compared with OCTOPUS. The visual field assessment showed only slight to fair agreement from 0.19 to 0.31 between assessments made by the headache center staff and the neuroophthalmologist. CONCLUSION: The COMPASS system can be used with reasonable sensitivity in the assessment of papilledema in patients suspected of idiopathic intracranial hypertension at a tertiary headache center.

Temporal summation in myopia and its implications for the investigation of glaucoma.

PURPOSE: We have previously demonstrated the upper limit of complete spatial summation (Ricco's area) to increase in non-pathological axial myopia compared to non-myopic controls. This study sought to investigate whether temporal summation is also altered in axial myopia to determine if this aspect of visual function, like in glaucoma, is influenced by reductions in retinal ganglion cell (RGC) density. METHODS: Achromatic contrast thresholds were measured for a GIII-equivalent stimulus (0.43° diameter) of six different stimulus durations (1-24 frames, 1.1-187.8 ms) in 24 participants with axial myopia (mean spherical refractive error: -4.65D, range: -1.00D to -11.25D, mean age: 34.1, range: 21-57 years) and 21 age-similar non-myopic controls (mean spherical refractive error: +0.87D, range: -0.25D to +2.00D, mean age: 31.0, range: 18-55 years). Measurements were performed at 10° eccentricity along the 90°, 180°, 270° and 360° meridians on an achromatic 10 cd/m2 background. The upper limit of complete temporal summation (critical duration, CD) was estimated from the data with iterative two-phase regression analysis. RESULTS: There was no significant difference (p = 0.90, Mann-Whitney U-test) in median CD between myopes (median: 44.3 ms; IQR: 26.5, 51.2) and non-myopes (median: 41.6 ms; IQR: 27.3, 48.5). Despite RGC numbers underlying the stimulus being significantly lower in the myopic group (p < 0.001), no relationship was observed between the CD estimate and co-localised RGC number (Pearson's r = -0.13, p = 0.43) or ocular length (Pearson's r = -0.08, p = 0.61). CONCLUSIONS: Unlike spatial summation, temporal summation is unchanged in myopia. This contrasts with glaucoma where both temporal and spatial summation are altered. As such, perimetric methods optimised to test for anomalies of temporal summation may provide a means to differentiate between conditions causing only a reduced RGC density (e.g., myopia), and pathological processes causing both a reduced RGC density and RGC dysfunction (e.g., glaucoma).

Investigating the linkage between mesopic spatial summation and variations in retinal ganglion cell density across the central visual field.

PURPOSE: The relationship between perimetric stimulus area and Ricco's area (RA) determines measured thresholds and the sensitivity of perimetry to retinal disease. The nature of this relationship, in addition to effect of retinal ganglion cell (RGC) number on this, is currently unknown for the adaptation conditions of mesopic microperimetry. In this study, achromatic mesopic spatial summation was measured across the central visual field to estimate RA with the number of RGCs underlying RA also being established. METHODS: Achromatic luminance thresholds were measured for six incremental spot stimuli (0.009-2.07 deg2 ) and 190.4 ms duration, at four locations, each at 2.5°, 5° and 10° eccentricity in five healthy observers (mean age 61.4 years) under mesopic conditions (background 1.58 cd/m2 ). RA was estimated using two-phase regression analysis with the number of RGCs underlying RA being calculated using normative histological RGC counts. RESULTS: Ricco's area exhibited a small but statistically insignificant increase between 2.5° and 10° eccentricity. Compared with photopic conditions, RA was larger, with the difference between RA and the Goldmann III stimulus (0.43°) being minimised. RGC number underlying RA was also higher than reported for photopic conditions (median 70 cells, IQR 36-93), with no significant difference being observed across test locations. CONCLUSIONS: Ricco's area and the number of RGCs underlying RA do not vary significantly across the central visual field in mesopic conditions. However, RA is larger and more similar to the standard perimetric Goldmann III stimulus under mesopic compared with photopic adaptation conditions. Further work is required to determine if compensatory enlargements in RA occur in age-related macular degeneration, to establish the optimal stimulus parameters for AMD-specific microperimetry.

Visualising structural and functional characteristics distinguishing between newly diagnosed high-tension and low-tension glaucoma patients.

PURPOSE: To determine whether there are quantifiable structural or functional differences that can distinguish between high-tension glaucoma (HTG; intraocular pressure [IOP] > 21 mm Hg) and low-tension glaucoma (LTG; IOP ≤ 21 mm Hg) at diagnosis. METHOD: This was a retrospective, cross-sectional study. Clinical results of one eye from 90 newly diagnosed HTG and 319 newly diagnosed LTG patients (117 with very-low-tension glaucoma [vLTG; ≤15 mm Hg] and 202 with middling LTG [mLTG; >15 mm Hg, ≤21 mm Hg]) were extracted, which included relevant demographic covariates of glaucoma, quantitative optical coherence tomography (including the optic nerve head, retinal nerve fibre layer and ganglion cell-inner plexiform layer) measurements and standard automated perimetry global metrics. We used binary logistic regression analysis to identify statistically significant clinical parameters distinguishing between phenotypic groups for inclusion in principal component (PC) (factor) analysis (PCA). The separability between each centroid for each cohort was calculated using the Euclidean distance (d(x,y)). RESULTS: The binary logistic regression comparing HTG and all LTG identified eight statistically significant clinical parameters. Subsequent PCA results included three PCs with an eigenvalue >1. PCs 1 and 2 accounted for 21.2% and 20.2% of the model, respectively, with a d(x,y) = 0.468, indicating low separability between HTG and LTG. The analysis comparing vLTG, mLTG and HTG identified 15 significant clinical parameters, which were subsequently grouped into five PCs. PCs 1 and 2 accounted for 24.1% and 17.8%, respectively. The largest separation was observed between vLTG and HTG (d(x,y) = 0.581), followed by vLTG and mLTG (d(x,y) = 0.435) and lastly mLTG and HTG (d(x,y) = 0.210). CONCLUSION: Conventional quantitative structural or functional parameters could not distinguish between pressure-defined glaucoma phenotypes at the point of diagnosis and are therefore not contributory to separating cohorts. The overlap in findings highlights the heterogeneity of the primary open-angle glaucoma clinical presentations among pressure-defined groups at the cohort level.