Examining the concordance of retinal ganglion cell counts generated using measures of structure and function

PURPOSE: There are several indirect methods used to estimate retinal ganglion cell (RGC) count in an individual eye, but there is limited information as to the agreement between these methods. In this work, RGC receptive field (RGC‐RF) count underlying a spot stimulus (0.43°, Goldmann III) was calculated and compared using three different methods. METHODS: RGC‐RF count was calculated at a retinal eccentricity of 2.32 mm for 44 healthy adult participants (aged 18–58 years, refractive error −9.75 DS to +1.75 DS) using: (i) functional measures of achromatic peripheral grating resolution acuity (PGRA), (ii) structural measures of RGC‐layer thickness (OCT‐model, based on the method outlined by Raza and Hood) and (iii) scaling published histology density data to simulate a global expansion in myopia (Histology‐Balloon). RESULTS: Whilst average RGC‐RF counts from the OCT‐model (median 105.3, IQR 99.6–111.0) and the Histology‐Balloon model (median 107.5, IQR 97.7–114.6) were similar, PGRA estimates were approximately 65% lower (median 37.7, IQR 33.8–46.0). However, there was poor agreement between all three methods (Bland–Altman 95% limits of agreement; PGRA/OCT: 55.4; PGRA/Histology‐Balloon 59.3; OCT/Histology‐Balloon: 52.4). High intersubject variability in RGC‐RF count was evident using all three methods. CONCLUSIONS: The lower PGRA RGC‐RF counts may be the result of targeting only a specific subset of functional RGCs, as opposed to the coarser approach of the OCT‐model and Histology‐Balloon, which include all RGCs, and also likely displaced amacrine cells. In the absence of a ‘ground truth’, direct measure of RGC‐RF count, it is not possible to determine which method is most accurate, and each has limitations. However, what is clear is the poor agreement found between the methods prevents direct comparison of RGC‐RF counts between studies utilising different methodologies and highlights the need to utilise the same method in longitudinal work

The Effect of Age on the Temporal Summation of Achromatic Perimetric Stimuli

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

Spatiotemporal Summation of Perimetric Stimuli in Early Glaucoma

PURPOSE: To investigate achromatic temporal summation under the conditions of standard automated perimetry (SAP), using a Goldmann III (GIII) stimulus and a stimulus scaled to the local area of complete spatial summation (Ricco's area) in open-angle glaucoma (OAG) patients and healthy age-similar control participants. METHODS: Twenty patients with OAG (mean age, 63 years; mean MD, -3.3 dB) and 15 healthy controls (mean age, 64 years) were recruited. Contrast thresholds were measured for seven stimulus durations (1-24 frames, 1.8-191.9 ms) using a near-GIII stimulus (0.48° diameter) and stimuli scaled to the local Ricco's area, in four oblique meridians at 8.8° eccentricity in the visual field. The upper limit of complete temporal summation (critical duration) was estimated using iterative two-phase regression analysis. RESULTS: Median critical duration values were significantly longer (P < 0.05) in the OAG group for the near-GIII (107.2 ms; interquartile range [IQR], 38.0-190.5) and Ricco's area-scaled (83.2 ms, 41.7-151.4) stimuli, compared to those in healthy subjects (near-GIII, 34.7 ms; 18.2-47.9; Ricco's area-scaled, 49.0 ms; 25.1-64.6). The greatest difference in contrast thresholds between healthy and OAG subjects (i.e., disease signal) was found when stimuli were scaled to Ricco's area and shorter than or equal to the critical duration in healthy observers. CONCLUSIONS: Temporal summation is altered in glaucoma. The stimulus duration and area of conventional SAP may be suboptimal for identifying early functional damage. Simultaneously modulating stimulus duration, area, and luminance during the examination may improve the diagnostic capability of SAP and expand the dynamic range of current instruments

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

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

Investigating the Linkage Between Mesopic Spatial Summation and Variations in Retinal Ganglion Cell Density Across the Central Visual Field:Mesopic Spatial Summation with Eccentricity

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

Human Factor and Usability Testing of a Binocular Optical Coherence Tomography System

PURPOSE: To perform usability testing of a binocular optical coherence tomography (OCT) prototype to predict its function in a clinical setting, and to identify any potential user errors, especially in an elderly and visually impaired population. METHODS: Forty-five participants with chronic eye disease (mean age 62.7 years) and 15 healthy controls (mean age 53 years) underwent automated eye examination using the prototype. Examination included 'whole-eye' OCT, ocular motility, visual acuity measurement, perimetry, and pupillometry. Interviews were conducted to assess the subjective appeal and ease of use for this cohort of first-time users. RESULTS: All participants completed the full suite of tests. Eighty-one percent of the chronic eye disease group, and 79% of healthy controls, found the prototype easier to use than common technologies, such as smartphones. Overall, 86% described the device to be appealing for use in a clinical setting. There was no statistically significant difference in the total time taken to complete the examination between participants with chronic eye disease (median 702 seconds) and healthy volunteers (median 637 seconds) (P = 0.81). CONCLUSION: On their first use, elderly and visually impaired users completed the automated examination without assistance. Binocular OCT has the potential to perform a comprehensive eye examination in an automated manner, and thus improve the efficiency and quality of eye care. TRANSLATIONAL RELEVANCE: A usable binocular OCT system has been developed that can be administered in an automated manner. We have identified areas that would benefit from further development to guide the translation of this technology into clinical practice

Estimating the Critical Duration for Temporal Summation of Standard Achromatic Perimetric Stimuli

Purpose: To estimate the critical duration of temporal summation for achromatic Goldmann III stimuli under the conditions of standard automated perimetry (SAP) and quantify response variability for short duration stimuli. Methods: Contrast thresholds were gathered using the method of constant stimuli for seven circular (0.48° diameter) incremental stimuli of varying duration (sum-of-frames equivalent: 8.3-198.3 msec), at an eccentricity of 8.8° along the four principal meridians of the visual field in two healthy, psychophysically experienced observers. Stimuli were presented on a high-resolution CRT display with a background luminance of 10 cd/m2. Psychometric functions were fitted using a probit model and non-parametric local linear analysis. The critical duration was estimated using iterative two-phase regression analysis, the results also being compared with values produced using previously published methods of analysis. Results: The median critical duration estimated using iterative two-phase regression analysis was 27.7 msec (IQR 22.5-29.8). A slight steepening of the psychometric function slope (lower variability) was observed for longer stimulus durations, using both probit and local-linear analysis techniques, but this was not statistically significant. Conclusions: Critical duration estimates in this study are substantially shorter than those previously reported for a Goldmann III stimulus under the conditions of SAP. Further work is required to firmly establish the relationship between measurement variability and the degree of local temporal and spatial summation