Purpose. The area of complete spatial summation (Ricco's area) is the largest stimulus size for which area × intensity is constant at threshold. The authors sought to investigate whether Ricco's area changes in early glaucoma to account for the decreased visual signal/noise ratio that may accompany retinal ganglion cell loss. Methods. Spatial summation functions were measured, and Ricco's area was determined at four 10° retinal locations in 24 patients with early glaucoma (total deviation at test locations, mean, −1.3 dB; range, +2 dB to −8 dB) and 26 age-similar healthy subjects under achromatic and S-cone isolation conditions. Achromatic grating resolution acuity was measured at the same locations to estimate functional ganglion cell density. Results. Ricco's area was enlarged in patients compared with controls for both achromatic (enlarged by: superior field, 0.57 log units, P < 0.01; inferior field, 0.72 log units, P < 0.01) and chromatic (enlarged by: superior field, 0.26 log units, P < 0.01; inferior field, 0.25 log units, P = 0.065) stimuli, with negligible vertical summation curve shifts along the intensity axis. Resolution acuity was significantly reduced in glaucoma patients in both hemifields (P < 0.001). There was a weak, but significant, relationship between Ricco's area and resolution acuity. Conclusions. Enlargement of Ricco's area completely compensates for reduced perimetric sensitivity in early glaucoma to maintain constant threshold at Ricco's area, suggesting an increase in signal pooling in response to ganglion cell loss. The rightward displacement of the spatial summation curve indicates that perimetric stimuli should be capable of modulating in size as well as/instead of contrast, which may boost the glaucoma signal within measurement noise.

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.

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.

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.