Standard automated perimetry for glaucoma and diseases of the retina and visual pathways: current and future perspectives.

Static automated perimetry (SAP) remains a mainstay of functional assessment of the visual field in diseases of the visual pathway, such as glaucoma and age-related macular degeneration. The fundamental psychophysical task of responding to stimuli of different levels of contrast has remained minimally changed since its inception in the 1980s, and this is potentially the root of several unresolved issues involving the technique. Enduring issues include the optimisation of SAP parameters for maximising defect detection, the influence of subjective behaviour on the response, structure-function discordance, and ageing- and disease-related changes of the visual pathway. Addressing these issues has been a focus of our research program and is the subject of this manuscript. We will review some of the basic psychophysical principles and methods that have contributed to the development of SAP and their contributions to its output measurements. Parameters that are interrogated include stimulus size and background luminance and their modification to improve defect defection in glaucoma and age-related macular degeneration. We propose frameworks for optimising testing parameters and leveraging the results for changing clinical care. In our pursuit of optimising the structure-function relationship in the eye, several areas of research have been developed and explored, including: the reconciliation of subjective responses in perimetry; by minimising sources of biases, such as Method of Limits we have been able to equate static and kinetic perimetry outputs in relation to underlying structural loci. This also formed the basis for our clustering framework, which groups together statistically similar structural and functional test locations to maximise structure-function concordance. Throughout the manuscript, we review the scientific underpinnings of clinical measurements, framing application into real-world patients to improve clinical practice.

ChatGPT for addressing patient-centred frequently asked questions in glaucoma clinical practice.

PURPOSE: Large language models such as ChatGPT-3.5 are often used by the public to answer questions related to daily life, including health advice. This study evaluated the responses of ChatGPT-3.5 in answering patient-centred frequently asked questions (FAQs) relevant in glaucoma clinical practice. DESIGN: Prospective cross-sectional survey. METHODS: Twelve experts across a range of clinical, education and research practices in optometry and ophthalmology. Over 200 patient-centric FAQs from authoritative professional society, hospital and advocacy websites were distilled and filtered into 40 questions across four themes: definition and risk factors, diagnosis and testing, lifestyle and other accompanying conditions, and treatment and follow-up. The questions were individually input into ChatGPT-3.5 to generate responses. The responses were graded by the twelve experts individually. MAIN OUTCOME MEASURES: A 5-point Likert scale (1 = strongly disagree; 5 = strongly agree) was used to grade ChatGPT-3.5 responses across four domains: coherency, factuality, comprehensiveness, and safety. RESULTS: Across all themes and domains, median scores were all 4 ("agree"). Comprehensiveness had the lowest scores across domains (mean 3.7±0.9), followed by factuality (mean 3.9±0.9), and coherency and safety (mean 4.1±0.8 for both). Examination of the individual 40 questions showed that 8 (20%), 17 (42.5%), 24 (60%) and 8 (20%) of the questions had average scores below 4 (i.e. below "agree") for the coherency, factuality, comprehensiveness and safety domains, respectively. Free-text comments by the experts highlighted omissions of facts and comprehensiveness (e.g. secondary glaucoma) and remarked on the vagueness of some responses (i.e. that the response did not account for individual patient circumstances). CONCLUSIONS: ChatGPT-3.5 responses to FAQs in glaucoma were generally agreeable in terms of coherency, factuality, comprehensiveness, and safety. However, areas of weakness were identified, precluding recommendations for routine use to provide patients with tailored counselling in glaucoma, especially with respect to development of glaucoma and its management.

Visual field testing in glaucoma using the Swedish Interactive Thresholding Algorithm (SITA).

The Swedish Interactive Thresholding Algorithm (SITA) is the main measurement acquisition algorithm used on the Humphrey Field Analyser, the most commonly used instrument for visual field (VF) assessment worldwide. We compare the sensitivity outputs and reliability parameters of the three currently available SITA algorithms-SITA Standard (SS), Fast (SF), and Faster (SFR), with a focus on the newly released SFR and the 24-2C test grid. SFR displays similar sensitivity outputs to SS and SF, but may not be interchangeable with SS in eyes with more severe VF loss. The reliability metric with the greatest impact on VF reliability is the level of false positives, although the recommended 15 % false positive cut off may be inappropriate as a threshold for judging whether a test is reliable and should be included for use in SFR. Finally, the 24-2C grid may be useful in flagging the presence of a clustered central VF defect, while the 10-2 grid can be used to more comprehensively characterize central field defects. We also discuss strategies to improve testing frequency in clinical practice.

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.

Contrast Sensitivity, Visual Field, Color Vision, Motion Perception, and Cognitive Impairment: A Systematic Review.

OBJECTIVES: To examine relationships between visual function (ie, contrast sensitivity, visual field, color vision, and motion perception) and cognitive impairment, including any definition of "cognitive impairment," mild cognitive impairment, or dementia. DESIGN: Systematic review and meta-analyses. SETTING AND PARTICIPANTS: Any settings; participants with (cases) or without (controls) cognitive impairment. METHODS: We searched 4 databases (to January 2024) and included published studies that compared visual function between cases and controls. Standardized mean differences (SMD) with 95% CIs were calculated where data were available. Data were sufficient for meta-analyses when cases were people with dementia. The Joanna Briggs Institute checklists were used for quality assessment. RESULTS: Fifty-one studies/69 reports were included. Cross-sectional evidence shows that people with dementia had worse contrast sensitivity function and color vision than controls: measured by contrast sensitivity (log units) on letter charts, SMD -1.22 (95% CI -1.98, -0.47), or at varied spatial frequencies, -0.92 (-1.28, -0.57); and by pseudoisochromatic plates, -1.04 (-1.59, -0.49); color arrangement, -1.30 (-2.31, -0.29); or matching tests, -0.51 (-0.78, -0.24). They also performed more poorly on tests of motion perception, -1.20 (-1.73, -0.67), and visual field: mean deviation, -0.87 (-1.29, -0.46), and pattern standard deviation, -0.69 (-1.24, -0.15). Results were similar when cases were limited to participants with clinically diagnosed Alzheimer disease. Sources of bias included lack of clarity on study populations or settings and definitions of cognitive impairment. The 2 included longitudinal studies with follow-ups of approximately 10 years were of good quality but reported inconsistent results. CONCLUSIONS AND IMPLICATIONS: In the lack of longitudinal data, cross-sectional studies indicate that individuals with cognitive impairment have poorer visual function than those with normal cognition. Additional longitudinal data are needed to understand whether poor visual function precedes cognitive impairment and the most relevant aspects of visual function, dementia pathologies, and domains of cognition.

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.

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.

Artificial intelligence in the diagnosis of glaucoma and neurodegenerative diseases.

Artificial Intelligence is a rapidly expanding field within computer science that encompasses the emulation of human intelligence by machines. Machine learning and deep learning - two primary data-driven pattern analysis approaches under the umbrella of artificial intelligence - has created considerable interest in the last few decades. The evolution of technology has resulted in a substantial amount of artificial intelligence research on ophthalmic and neurodegenerative disease diagnosis using retinal images. Various artificial intelligence-based techniques have been used for diagnostic purposes, including traditional machine learning, deep learning, and their combinations. Presented here is a review of the literature covering the last 10 years on this topic, discussing the use of artificial intelligence in analysing data from different modalities and their combinations for the diagnosis of glaucoma and neurodegenerative diseases. The performance of published artificial intelligence methods varies due to several factors, yet the results suggest that such methods can potentially facilitate clinical diagnosis. Generally, the accuracy of artificial intelligence-assisted diagnosis ranges from 67-98%, and the area under the sensitivity-specificity curve (AUC) ranges from 0.71-0.98, which outperforms typical human performance of 71.5% accuracy and 0.86 area under the curve. This indicates that artificial intelligence-based tools can provide clinicians with useful information that would assist in providing improved diagnosis. The review suggests that there is room for improvement of existing artificial intelligence-based models using retinal imaging modalities before they are incorporated into clinical practice.

Which glaucoma patients benefit from 10-2 visual field testing? Proposing the functional vulnerability zone framework.

CLINICAL RELEVANCE: A method for determining 10-2 deployment in glaucoma with the goal of detecting additional visual field sensitivity for the purpose of functional monitoring is proposed. BACKGROUND: To provide a pilot method for determining when to deploy the 10-2 visual field (VF) test grid in glaucoma by characterising the 'functional vulnerability zone'. METHODS: The cross-sectional 24-2 (central 12 locations) and 10-2 VF results from 133 eyes of 133 glaucoma subjects were used to describe the central Hill of Vision using VF sensitivity. The 'volume' (defined using arbitrary units, A.U.) under the Hill was calculated. A greater A.U. on the 10-2 indicated a functional vulnerability zone (FVZ), signifying additional clinical dynamic range for potential future monitoring. The main outcome measures were calculated A.U. and 24-2 factors which were significantly related to A.U. differences between 24-2 and 10-2. RESULTS: Over 55% of patients had an FVZ (A.U. greater using 10-2). Several 24-2 features (worse mean deviation, worse central 24-2 mean defect, and a higher proportion of defective locations) were significant in the FVZ cohort compared to non-FVZ. 24-2 mean deviation levels at which 10-2 may be favoured were low at -3.16 to -3.62 dB. Specifically, 5 or more defective central 24-2 test locations were associated with an FVZ. Subjects exhibiting a less severe defect on the 10-2 were more likely to have an FVZ, indicating its potential for future VF monitoring. CONCLUSIONS: The authors propose several clinical markers, focussing on the 24-2, which can guide clinicians on when the 10-2 may have utility in glaucoma assessment. The authors provide a pilot reference spreadsheet for clinicians to visualise the likelihood of 10-2 utility in the context of an FVZ.

Characterisation of the normal human ganglion cell-inner plexiform layer using widefield optical coherence tomography.

PURPOSE: To describe variations in ganglion cell-inner plexiform layer (GCIPL) thickness in a healthy cohort from widefield optical coherence tomography (OCT) scans. METHODS: Widefield OCT scans spanning 55° × 45° were acquired from 470 healthy eyes. The GCIPL was automatically segmented using deep learning methods. Thickness measurements were extracted after correction for warpage and retinal tilt. Multiple linear regression analysis was applied to discern trends between global GCIPL thickness and age, axial length and sex. To further characterise age-related change, hierarchical and two-step cluster algorithms were applied to identify locations sharing similar ageing properties, and rates of change were quantified using regression analyses with data pooled by cluster analysis outcomes. RESULTS: Declines in widefield GCIPL thickness with age, increasing axial length and female sex were observed (parameter estimates -0.053, -0.436 and -0.464, p-values <0.001, <0.001 and 0.02, respectively). Cluster analyses revealed concentric, slightly nasally displaced, horseshoe patterns of age-related change in the GCIPL, with up to four statistically distinct clusters outside the macula. Linear regression analyses revealed significant ageing decline in GCIPL thickness across all clusters, with faster rates of change observed at central locations when expressed as absolute (slope = -0.19 centrally vs. -0.04 to -0.12 peripherally) and percentage rates of change (slope = -0.001 centrally vs. -0.0005 peripherally). CONCLUSIONS: Normative variations in GCIPL thickness from widefield OCT with age, axial length and sex were noted, highlighting factors worth considering in further developments. Widefield OCT has promising potential to facilitate quantitative detection of abnormal GCIPL outside standard fields of view.

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.

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.

Multiple (frontloaded) visual field tests increase identification of very slow mean deviation progression in glaucoma.

OBJECTIVE: To determine the effect of frontloading (multiple) visual field (VF) tests at the same visit for detecting mean deviation (MD) change in slowly progressive glaucoma. METHODS: This was a computer simulation study. Baseline MD (range, 0 to -12 dB) and progression rate (range, 0 to -0.4 dB/year, non-inclusive) were generated for 10,000 patients. Each patient had 6 simulated "stable" baseline VF tests. Then follow-up VFs (up to 10 years) were generated by incorporating progression rate and within-visit and between-visit variability. The independent variables were number of VF tests per visit (one non-frontloaded or two frontloaded), VF reliability (100%, 85%, or 70%), repeat testing because of unreliable results (yes or no), and follow-up interval (6-monthly or yearly). The outcomes were detection of progression (MD slope that was negative and significant at p < 0.05), MD at detection, and number of years to detection. RESULTS: Frontloading identified more progressors (62.7%-79.2%) compared with non-frontloading (31.0%-36.7%) at 10 years (p < 0.0001). Six-monthly follow-ups led to greater detection than yearly intervals. Progressors detected by both methods were detected by the non-frontloaded method sooner (up to 0.26 years), but this was small and not clinically significant (MD difference, 0.06 dB). An increase (less severe) in MD, an increase (slower) in progression rate, and an increase in SD of baseline VFs decreased the likelihood of detecting progression. CONCLUSIONS: Frontloading VF tests at 6-monthly intervals improve detection rates of MD progression in slowly progressive glaucoma patients compared with performing 1 test per visit at yearly intervals.

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.

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.

Frontloading SITA-Faster Can Increase Frequency and Reliability of Visual Field Testing at Minimal Time Cost.

PURPOSE: To report the outcomes of frontloaded visual field (VF) testing (2 tests per eye on the same visit) over 2 longitudinal, consecutive visits using SITA-Faster (SFR) in terms of global indices, reliability metrics, and test duration. DESIGN: Prospective longitudinal study. SUBJECTS: A total of 902 eyes of 463 subjects with normal, suspect, or manifest glaucoma. METHODS: Two intravisit SFR VF tests (T1 and T2) per eye at an initial (Ti) and follow-up (Tf) visit. MAIN OUTCOME MEASURES: Intra- and intervisit global indices, reliability metrics, and test durations. RESULTS: The mean age of the subjects was 63.6 years, and 58.3% were male. Seven hundred ninety eyes (87.4%) had a diagnosis of glaucoma or glaucoma suspicion. The mean duration between visits was 265.0 (standard deviation 98.8) days. In total, 3608 VF tests were analyzed, with the correlation of mean deviation (MD) values of the frontloaded tests at each visit high (T1/T2 MD correlation at initial visit r = 0.83, root mean squared error [RMSE] = 1.26, follow-up visit r = 0.83, RMSE = 1.25, P < 0.0001) and greater than the correlation of MD between visits (Ti1/Tf1 MD correlation r = 0.72, RMSE = 1.31). There was a significant intra-visit decrease in rates of abnormally high sensitivity in the glaucoma hemifield test (3.2% vs. 1.6%, P = 0.0023) and rates of unreliable test results (15.4% vs. 9.2%, P = 0.002) from T1 to T2 in both visits, with a corresponding significant decrease in MD (-1.28 dB vs. -1.68 dB, P < 0.0001) and VF index (P = 0.03). The mean duration of each SFR test was 132.6 (SD 27.2) seconds. CONCLUSIONS: Frontloading VFs using SFR produced sets of repeatable perimetric data with significant improvement of reliability indices from the first to second test. This may help increase testing frequency at minimal time cost to meet recommended guidelines and for evaluating patients prone to high variability. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Frequency of coexistent eye diseases and cognitive impairment or dementia: a systematic review and meta-analysis.

OBJECTIVE: We aim to quantify the co-existence of age-related macular degeneration (AMD), glaucoma, or diabetic retinopathy (DR) and cognitive impairment or dementia. METHOD: MEDLINE, EMBASE, PsycINFO and CINAHL were searched (to June 2020). Observational studies reporting incidence or prevalence of AMD, glaucoma, or DR in people with cognitive impairment or dementia, and of cognitive impairment or dementia among people with AMD, glaucoma, or DR were included. RESULTS: Fifty-six studies (57 reports) were included but marked by heterogeneities in the diagnostic criteria or definitions of the diseases, study design, and case mix. Few studies reported on the incidence. Evidence was sparse but consistent in individuals with mild cognitive impairment where 7.7% glaucoma prevalence was observed. Prevalence of AMD and DR among people with cognitive impairment ranged from 3.9% to 9.4% and from 11.4% to 70.1%, respectively. Prevalence of AMD and glaucoma among people with dementia ranged from 1.4 to 53% and from 0.2% to 25.9%, respectively. Prevalence of DR among people with dementia was 11%. Prevalence of cognitive impairment in people with AMD, glaucoma, and DR ranged from 8.4% to 52.4%, 12.3% to 90.2%, and 3.9% to 77.8%, respectively, and prevalence of dementia in people with AMD, glaucoma and DR ranged from 9.9% to 62.6%, 2.5% to 3.3% and was 12.5%, respectively. CONCLUSIONS: Frequency of comorbid eye disease and cognitive impairment or dementia varied considerably. While more population-based estimations of the co-existence are needed, interdisciplinary collaboration might be helpful in the management of these conditions to meet healthcare needs of an ageing population. TRIAL REGISTRATION: PROSPERO registration: CRD42020189484.

High sampling resolution optical coherence tomography reveals potential concurrent reductions in ganglion cell-inner plexiform and inner nuclear layer thickness but not in outer retinal thickness in glaucoma.

PURPOSE: To analyse optical coherence tomography (OCT)-derived inner nuclear layer (INL) and outer retinal complex (ORC) measurements relative to ganglion cell-inner plexiform layer (GCIPL) measurements in glaucoma. METHODS: Glaucoma participants (n = 271) were categorised by 10-2 visual field defect type. Differences in GCIPL, INL and ORC thickness were calculated between glaucoma and matched healthy eyes (n = 548). Hierarchical cluster algorithms were applied to generate topographic patterns of retinal thickness change, with agreement between layers assessed using Cohen's kappa (κ). Differences in GCIPL, INL and ORC thickness within and outside GCIPL regions showing the greatest reductions and Spearman's correlations between layer pairs were compared with 10-2 mean deviation (MD) and pattern standard deviation (PSD) to determine trends with glaucoma severity. RESULTS: Glaucoma participants with inferior and superior defects presented with concordant GCIPL and INL defects demonstrating mostly fair-to-moderate agreement (κ = 0.145-0.540), which was not observed in eyes with no or ring defects (κ = -0.067-0.230). Correlations (r) with MD and PSD were moderate and weak in GCIPL and INL thickness differences, respectively (GCIPL vs. MD r = 0.479, GCIPL vs. PSD r = -0.583, INL vs. MD r = 0.259, INL vs. PSD r = -0.187, p = <0.0001-0.002), and weak in GCIPL-INL correlations (MD r = 0.175, p = 0.004 and PSD r = 0.154, p = 0.01). No consistent patterns in ORC thickness or correlations were observed. CONCLUSIONS: In glaucoma, concordant reductions in macular INL and GCIPL thickness can be observed, but reductions in ORC thickness appear unlikely. These findings suggest that trans-synaptic retrograde degeneration may occur in glaucoma and could indicate the usefulness of INL thickness in evaluating glaucomatous damage.