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.

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.

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.

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.

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.

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.

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.

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.

Evaluating the clinical relevance and reliability of outer retinal band length on optical coherence tomography in retinal disease: a cross-sectional study.

OBJECTIVES: Hyper-reflective outer retinal band (HORB) disruptions are reported across a range of retinal disease, yet a reliable, easily implemented assessment method and thorough evaluation of their association to retinal disease is lacking. The purpose of the study was to assess the reliability of using magnitude estimation to evaluate HORB length and determine its association to visual acuity and retinal disease. DESIGN: Cross-sectional, retrospective study. SETTING: Patients attending a secondary eye care clinic in Sydney, Australia. PARTICIPANTS: 2039 unique consecutive patients were screened for inclusion between 2 November and 18 January 2021, and 600 were included in the study population. Patients were included if they were referred from primary care, presented for an initial, comprehensive eye examination during the study period, imaged with optical coherence tomography during their visit and over 18 years of age. PRIMARY OUTCOME: Reliability of HORB length estimations and associations to clinical outcomes. RESULTS: Intragrader (intraclass correlation coefficient, ICCfovea=0.81; ICCworst=0.91) and intergrader (ICCfovea=0.78-0.79; ICCworst=0.75-0.88) agreement of HORB length was good to excellent. HORB length was significantly associated with age (p<0.001, ß=-0.22 to -0.24) and refractive error (p<0.001, ß=0.12-0.16) at all B-scan locations. Visual acuity (p=0.001, ß=-0.13) was associated with the primary outcome for foveal B-scans and eccentricity (p=0.002, ß=-0.13) and device type (p=0.002, ß=0.13) for non-foveal B-scans. Glaucoma was associated with HORB length on univariate analysis (p=0.05-0.06, ß=-0.08); however, multivariate analysis revealed no significant association between HORB length and retinal disease. CONCLUSION: HORB length is reliably assessed using magnitude estimation and may be useful as a surrogate biomarker of visual acuity. Several factors affect HORB length estimations, which may contribute to the lack of association to retinal disease and highlights the need for covariable adjustment when examining HORB disruptions.

Development of a rabbit model of Adenosine triphosphate-induced monocular retinal degeneration for optimization of retinal prostheses.

Optimization of retinal prostheses requires preclinical animal models that mimic features of human retinal disease, have appropriate eye sizes to accommodate implantable arrays, and provide options for unilateral degeneration so as to enable a contralateral, within-animal control eye. In absence of a suitable non-human primate model and shortcomings of our previous feline model generated through intravitreal injections of Adenosine Triphosphate (ATP), we aimed in the present study to develop an ATP induced degeneration model in the rabbit. Six normally sighted Dutch rabbits were monocularly blinded with this technique. Subsequent retinal degeneration was assessed with optical coherence tomography, electroretinography, and histological assays. Overall, there was a 42% and 26% reduction in a-wave and oscillatory potential amplitudes in the electroretinograms respectively, along with a global decrease in retinal thickness, with increased variability. Qualitative inspection also revealed that there were variable levels of retinal degeneration and remodeling both within and between treated eyes, mimicking the disease heterogeneity observed in retinitis pigmentosa. These findings confirm that ATP can be utilized to unilaterally induce blinding in rabbits and, potentially present an ideal model for future cortical recording experiments aimed at optimizing vision restoration strategies.Clinical Relevance- A rapid, unilaterally induced model of retinal degeneration in an animal with low binocular overlap and large eyes will allow for clinically valid recordings of downstream cortical activity following retinal stimulation. Such a model would be highly beneficial for the optimization of clinically appropriate vision restoration approaches.

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.

Spatial Cluster Patterns of Retinal Sensitivity Loss in Intermediate Age-Related Macular Degeneration Features.

Purpose: To examine spatial patterns of retinal sensitivity loss in the three key features of intermediate age-related macular degeneration (iAMD). Methods: One-hundred individuals (53 iAMD, 47 normal) underwent 10-2 mesopic microperimetry testing in one eye. Pointwise sensitivities (dB) were corrected for age, sex, iAMD status, and co-presence of co-localized key iAMD features: drusen load, pigmentary abnormalities, and reticular pseudodrusen (RPD). Clusters (labeled by ranks of magnitude C-2, C-1, C0) were derived from pointwise sensitivities and then assessed by quadrants and eccentricity/rings. Results: Two clusters of decreased sensitivities were evident in iAMD versus normal: C-2, -1.67 dB (95% CI (confidence intervals), -2.36 to -0.98; P < 0.0001); C-1, -0.93 dB (95% CI, -1.5 to -0.36; P < 0.01). One cluster of decreased sensitivity was independently associated each with increased drusen load (13.57 µm increase per -1 dB; P < 0.0001), pigmentary abnormalities (C-1: -2.23 dB; 95% CI, -3.36 to -1.1; P < 0.01), and RPD (C-1: -1.07 dB; 95% CI, -2 to -0.14; P < 0.01). Sensitivity loss in iAMD was biased toward the superior and central macula (P = 0.16 to <0.0001), aligning with structural distributions of features. However, sensitivity loss associated with drusen load also extended to the peripheral macula (P < 0.0001) with paracentral sparing, which was discordant with the central distribution of drusen. Conclusions: Drusen load, pigmentary abnormalities, and RPD are associated with patterns of retinal sensitivity loss commonly demonstrating superior and central bias. Results highlighted that a clinical focus on these three key iAMD features using structural measures alone does not capture the complex, spatial extent of vision-related functional impairment in iAMD. Translational Relevance: Defining the spatial patterns of retinal sensitivity loss in iAMD can facilitate a targeted visual field protocol for iAMD assessment.

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.

Effective health communication for age-related macular degeneration: An exploratory qualitative study.

PURPOSE: Age-related macular degeneration (AMD) is a major cause of vision loss globally. Patients with AMD may not always understand or retain the information about AMD communicated by their eyecare practitioner. This study aims to explore the characteristics of effective health communication for AMD, from both patients' and eyecare practitioners' perspectives. The purpose is to provide a foundation for understanding how health communication for AMD could potentially be improved in the future. METHODS: A total of 10 focus groups involving 17 patients with AMD and 17 optometrists were conducted via web conferencing. Each session was audio-recorded, transcribed and analysed using the Grounded Theory Methodology. RESULTS: The five themes identified are as follows: (1) materials' quality, (2) materials' relevance, (3) contextualising for the individual, (4) contextualising for the disease and (5) support network. Participants expressed concern about the unrealistic yet common depiction of vision loss in AMD as a black patch overlying common visual scenes. They also preferred education materials tailored to a specific disease stage and the regular opportunity to ask or answer questions. Longer appointment durations and peer support (from family, friends or others with AMD) were also valued. CONCLUSION: Optometrists are encouraged to focus on three over-arching dimensions when counselling patients with AMD in routine clinical practice: (1) curating and using disease and stage-specific, impactful education materials, (2) their chairside verbal communication techniques and (3) AMD-specific opportunities for care coordination among patient family and friends, peers and other multidisciplinary members of the care support team.

Derivation of human retinal cell densities using high-density, spatially localized optical coherence tomography data from the human retina.

This study sought to identify demographic variations in retinal thickness measurements from optical coherence tomography (OCT), to enable the calculation of cell density parameters across the neural layers of the healthy human macula. From macular OCTs (n = 247), ganglion cell (GCL), inner nuclear (INL), and inner segment-outer segment (ISOS) layer measurements were extracted using a customized high-density grid. Variations with age, sex, ethnicity, and refractive error were assessed with multiple linear regression analyses, with age-related distributions further assessed using hierarchical cluster analysis and regression models. Models were tested on a naïve healthy cohort (n = 40) with Mann-Whitney tests to determine generalizability. Quantitative cell density data were calculated from histological data from previous human studies. Eccentricity-dependent variations in OCT retinal thickness closely resemble topographic cell density maps from human histological studies. Age was consistently identified as significantly impacting retinal thickness (p = .0006, .0007, and .003 for GCL, INL and ISOS), with gender affecting ISOS only (p < .0001). Regression models demonstrated that age-related changes in the GCL and INL begin in the 30th decade and were linear for the ISOS. Model testing revealed significant differences in INL and ISOS thickness (p = .0008 and .0001; however, differences fell within the OCT's axial resolution. Qualitative comparisons show close alignment between OCT and histological cell densities when using unique, high-resolution OCT data, and correction for demographics-related variability. Overall, this study describes a process to calculate in vivo cell density from OCT for all neural layers of the human retina, providing a framework for basic science and clinical investigations.

Loss of Müller cell glutamine synthetase immunoreactivity is associated with neuronal changes in late-stage retinal degeneration.

Introduction: A hallmark of photoreceptor degenerations is progressive, aberrant remodeling of the surviving retinal neurons and glia following photoreceptor loss. The exact relationship between neurons and glia remodeling in this late stage of retinal degeneration, however, is unclear. This study assessed this by examining Müller cell dysfunction via glutamine synthetase immunoreactivity and its spatial association with retinal neuron subpopulations through various cell markers. Methods: Aged Rd1 mice retinae (P150 - P536, n = minimum 5 per age) and control heterozygous rd1 mice retinae (P536, n = 5) were isolated, fixed and cryosectioned. Fluorescent immunolabeling of glutamine synthetase was performed and retinal areas quantified as having low glutamine synthetase immunoreactivity if proportion of labeled pixels in an area was less than two standard deviations of the mean of the total retina. Other Müller cell markers such as Sox9 and Glial fibrillary acidic protein along with neuronal cell markers Calbindin, Calretinin, recoverin, Protein kinase C-α, Glutamic acid decarboxylase 67, and Islet-1 were then quantified within areas of low and normal synthetase immunoreactivity. Results: Glutamine synthetase immunoreactivity was lost as a function of age in the rd1 mouse retina (P150 - P536). Immunoreactivity of other Müller cell markers, however, were unaffected suggesting Müller cells were still present in these low glutamine synthetase immunoreactive regions. Glutamine synthetase immunoreactivity loss affected specific neuronal populations: Type 2, Type 8 cone, and rod bipolar cells, as well as AII amacrine cells based on reduced recoverin, protein kinase Ca and parvalbumin immunoreactivity, respectively. The number of cell nuclei within regions of low glutamine synthetase immunoreactivity was also reduced suggesting possible neuronal loss rather than reduced cell marker immunoreactivity. Conclusion: These findings further support a strong interplay between glia-neuronal alterations in late-stage degeneration and highlight a need for future studies and consideration in intervention development.

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.