Tony Redmond

Visual crowding is the disruptive effect of nearby details on the perception of a target. This influence is dependent on both spatial separation and perceived similarity between target and flanker elements. However, it is not clear how these simultaneous influences combine to produce the final "crowded" percept as flankers traverse the limits of the crowding zone. We investigated the reported appearance of a peripherally presented Landolt-C target flanked by a pair of simultaneously presented Landolt-Cs across different levels of target-flanker similarity (relative orientation), spatial separation, and target eccentricity. The distributions of errors in reported target orientation were fitted with a pooling model that simulated errors using a weighted combination of target and flanker orientation signals. The change in error distribution with target-flanker spacing (the "spatial profile") was fitted with a logistic function, estimating both the rate at which target- and flanker-signal weighting varies as target-flanker spatial separation decreases (slope) and the spatial separation at which signals were balanced (midpoint). We found that the slope of the spatial profile increases as target-flanker similarity decreases, with similar modulation patterns across target eccentricities. In contrast, spatial profile midpoints increased linearly with eccentricity, in line with Bouma's law, but were invariant of target-flanker similarity. This suggests similarity-related modulation may operate within a fixed spatial extent at each eccentricity. Investigating the spatial profile of crowding disentangles effects related to the appearance of targets and flankers (i.e., similarity) from appearance-independent influences, which can be confounded when using other common measures to define crowding zone extent.

Standard automated perimetry, a psychophysical task performed routinely in eyecare clinics, requires observers to maintain fixation for several minutes at a time in order to measure visual field sensitivity. Detection of visual field damage is confounded by eye movements, making the technique unreliable in poorly attentive individuals and those with pathologically unstable fixation, such as nystagmus. Microperimetry, which utilizes ‘partial gaze-contingency’ (PGC), aims to counteract eye movements but only corrects for gaze position errors prior to each stimulus onset. Here, we present a novel method of visual field examination in which stimulus position is updated during presentation, which we refer to as ‘continuous gaze-contingency’ (CGC). In the first part of this study, we present three case examples that demonstrate the ability of CGC to measure the edges of the physiological blind spot in infantile nystagmus with greater accuracy than PGC and standard ‘no gaze-contingency’ (NoGC), as initial proof-of-concept for the utility of the paradigm in measurements of absolute scotomas in these individuals. The second part of this study focused on healthy observers, in which we demonstrate that CGC has the lowest stimulus positional error (gaze-contingent precision: CGC = ± 0.29°, PGC = ± 0.54°, NoGC = ± 0.81°). CGC test–retest variability was shown to be at least as good as both PGC and NoGC. Overall, CGC is supported as a reliable method of visual field examination in healthy observers. Preliminary findings demonstrate the spatially accurate estimation of visual field thresholds related to retinal structure using CGC in individuals with infantile nystagmus.

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 deg ² ) 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/m ² ). 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.

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/m ² 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).

Purpose: To investigate age-related changes of the outer nuclear layer (ONL) thickness and cone density, and their associations in healthy participants using a modified, narrow scan-angle Heidelberg Retina Angiograph (HRA2). Methods: Retinal cones were imaged outside the fovea at 8.8° eccentricity and cone density was compared to ONL thickness measurements obtained by Spectral-Domain Optical Coherence Tomography (SD-OCT) at the same locations. Fifty-six eyes of 56 healthy participants with a median age (interquartile range, IQR) of 37 years (29–55) were included. Results: Median (IQR) cone count was 7,472 (7,188, 7,746) cones/mm² and median (IQR) ONL thickness was 56 (52, 60) µm for healthy participants. Both cone density and ONL thickness were negatively associated with age: cone density, R² = 0.16 (F(1,54) = 10.41, P = 0.002); ONL thickness, R² = 0.12 (F(1,54) = 7.41, P = 0.009). No significant association was seen between cone density and ONL thickness (R² = 0.03; F(1,54) = 1.66, P = 0.20). Conclusion: Cone density was lower, and ONL thinner, in older compared to younger participants, therefore, image-based structural measures should be compared to age-related data. However, cone density and ONL thickness were not strongly associated, indicating that determinants of ONL thickness measurements other than cone density measurements, and including measurement error, have a major influence.

Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells. However, the earliest degenerative events that occur in human glaucoma are relatively unknown. Work in animal models has demonstrated that retinal ganglion cell dendrites remodel and atrophy prior to the loss of the cell soma. Whether this occurs in human glaucoma has yet to be elucidated. Serial block face scanning electron microscopy is well established as a method to determine neuronal connectivity at high resolution but so far has only been performed in normal retina from animal models. To assess the structure–function relationship of early human glaucomatous neurodegeneration, regions of inner retina assessed to have none-to-moderate loss of retinal ganglion cell number were processed using serial block face scanning electron microscopy (n = 4 normal retinas, n = 4 glaucoma retinas). This allowed detailed 3D reconstruction of retinal ganglion cells and their intracellular components at a nanometre scale. In our datasets, retinal ganglion cell dendrites degenerate early in human glaucoma, with remodelling and redistribution of the mitochondria. We assessed the relationship between visual sensitivity and retinal ganglion cell density and discovered that this only partially conformed to predicted models of structure–function relationships, which may be affected by these early neurodegenerative changes. In this study, human glaucomatous retinal ganglion cells demonstrate compartmentalized degenerative changes as observed in animal models. Importantly, in these models, many of these changes have been demonstrated to be reversible, increasing the likelihood of translation to viable therapies for human glaucoma.

Ricco’s area (the largest area of visual space in which stimulus area and intensity are inversely proportional at threshold) has previously been hypothesised to be a result of centre/surround antagonism in retinal ganglion cell receptive fields, but recent evidence suggests a sizeable cortical contribution. Here, Ricco’s area was measured in amblyopia, a condition in which retinal receptive fields are normal, to better understand its physiological basis. Spatial summation functions were determined at 12 visual field locations in both eyes of 14 amblyopic adults and 15 normal-sighted controls. Ricco’s area was significantly larger in amblyopic eyes than in fellow non-amblyopic eyes. Compared to the size of Ricco’s area in control eyes, Ricco’s area measured significantly larger in amblyopic eyes. Additionally, Ricco’s area in the fellow, non-amblyopic eye of amblyopic participants measured significantly smaller than in control eyes. Compared to controls, Ricco’s area was larger in amblyopic eyes and smaller in fellow non-amblyopic eyes. Amblyopia type, binocularity, and inter-ocular difference in visual acuity were significantly associated with inter-ocular differences in Ricco’s area in amblyopes. The physiological basis for Ricco’s area is unlikely to be confined to the retina, but more likely representative of spatial summation at multiple sites along the visual pathway.

Identification of glaucomatous damage and progression by perimetry are limited by measurement and response variability. This study tested the hypothesis that the glaucoma damage signal/noise ratio is greater with stimuli varying in area, either solely, or simultaneously with contrast, than with conventional stimuli varying in contrast only (Goldmann III, GIII). Thirty glaucoma patients and 20 age-similar healthy controls were tested with the Method of Constant Stimuli (MOCS). One stimulus modulated in area (A), one modulated in contrast within Ricco’s area (C_R), one modulated in both area and contrast simultaneously (AC), and the reference stimulus was a GIII, modulating in contrast. Stimuli were presented on a common platform with a common scale (energy). A three-stage protocol minimised artefactual MOCS slope bias that can occur due to differences in psychometric function sampling between conditions. Threshold difference from age-matched normal (total deviation), response variability, and signal/noise ratio were compared between stimuli. Total deviation was greater with, and response variability less dependent on defect depth with A, AC, and C_R stimuli, compared with GIII. Both A and AC stimuli showed a significantly greater signal/noise ratio than the GIII, indicating that area-modulated stimuli offer benefits over the GIII for identifying early glaucoma and measuring progression.

Purpose: To examine the temporal summation of a Goldmann III–sized stimulus under the conditions of standard automated perimetry in healthy participants of varying age. Methods: Twenty-seven healthy individuals of varying age (24–80 years) were tested. Achromatic contrast thresholds were measured for seven 0.48° diameter (near Goldmann III) spot stimuli of varying presentation duration (1–24 frames, 1.8–191.9 ms) at 8.8° eccentricity in the visual field along the 45°, 135°, 225°, and 315° meridians. All stimuli were displayed on a CRT display with a background set to 10 cd/m². Iterative two-phase regression analysis was used to estimate the critical duration from each localized temporal summation function. Results: A significant decrease in contrast sensitivity for all stimulus durations examined in this study was observed with increasing age in both the superior and inferior hemifield (P < 0.001). Despite this, no significant change in the critical duration was observed as a function of age in either the superior (r² = 9.1 × 10⁻⁹, P = 0.99) or inferior hemifield (r² = 2.4 × 10⁻⁵, P = 0.98). Conclusions: Age-related changes in the visual system, although leading to a reduction in contrast sensitivity, are not accompanied by a change in temporal summation for a detection task with an achromatic 0.48° diameter spot stimulus. This is important to know when proceeding to examine temporal summation changes in diseases like glaucoma.