Expert CONsensus on Visual Evaluation in Retinal disease manaGEment: the CONVERGE study.

BACKGROUND/AIMS: Recent decades have seen significant advances in both structural and functional testing of retinal disease. However, the current clinical value of specific testing modalities, as well as future trends, need to be clearly identified in order to highlight areas for further development in routine care and clinical trials. METHODS: We designed a modified two-round Delphi study to obtain the opinion of a multidisciplinary group of 33 international experts involved in the field of retinal disease management/research to determine the level of agreement and consensus regarding the value and performance of specific structural and functional testing methods for retinal disease. On a Likert scale, a median of 1-2 indicated disagreement with the statement, and 5-6 indicated agreement with the statement. An IQR of ≤2 indicated consensus in the responses. Several questions also allowed comments on responses. RESULTS: There was overall agreement that structural testing currently predominates for detection and monitoring. There was moderate agreement that functional testing remains important and will continue to do so in the future because it provides complementary information. Certain respondents considered that properly designed and applied psychophysical tests are as reliable and repeatable as structural observations and that functional changes are the most important in the long run. Respondents considered future care and research to require a combination of structural and functional testing with strong consensus that the relative importance will depend on disease type and stage. CONCLUSION: The study obtained important insights from a group of international experts regarding current and future needs in the management of retinal disease using a mix of quantitative and qualitative approaches. Responses provide a rich range of opinions that will be of interest to researchers seeking to design tests for future patient care and clinical trials.

Investigating the Spatiotemporal Summation of Perimetric Stimuli in Dry Age-Related Macular Degeneration.

Purpose: To measure achromatic spatial, temporal, and spatiotemporal summation in dry age-related macular degeneration (AMD) compared to healthy controls under conditions of photopic gaze-contingent perimetry. Methods: Twenty participants with dry AMD (mean age, 74.6 years) and 20 healthy controls (mean age, 67.8 years) performed custom, gaze-contingent perimetry tests. An area-modulation test generated localized estimates of Ricco's area (RA) at 2.5° and 5° eccentricities along the 0°, 90°, 180°, and 270° meridians. Contrast thresholds were measured at the same test locations for stimuli of six durations (3.7-190.4 ms) with a Goldmann III stimulus (GIII, 0.43°) and RA-scaled stimuli. The upper limit (critical duration) of complete temporal summation (using the GIII stimulus) and spatiotemporal summation (using the RA stimuli) was estimated using iterative two-phase regression analysis. Results: Median (interquartile range [IQR]) RA estimates were significantly larger in AMD participants (2.5°: 0.21 [0.09-0.41] deg2; 5°: 0.32 [0.15-0.65 deg2]) compared to healthy controls (2.5°: 0.08 [0.05-0.13] deg2; 5°: 0.15 [0.08-0.22] deg2) at all test locations (all P < 0.05). No significant difference in median critical duration was found in AMD participants with the GIII stimulus (19.6 [9.9-30.4] ms) and RA-scaled stimuli (22.9 [13.9-40.3] ms) compared to healthy controls (GIII: 17.0 [11.3-24.0] ms; RA-scaled: 22.4 [14.3-33.1] ms) at all test locations (all P > 0.05). Conclusions: Spatial summation is altered in dry AMD, without commensurate changes in temporal summation. Translational Relevance: The sensitivity of perimetry to AMD may be improved by utilizing stimuli that probe alterations in spatial summation in the disease.

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.

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.

Ageing changes in retinal outer nuclear layer thickness and cone photoreceptor density using adaptive optics-free imaging.

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.

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.

Mesopic conditions optimise the detection of visual function loss in drivers with simulated media opacity.

Drivers have different visual demands across varying contrast and luminance conditions. However, vision assessments for driving are typically conducted under photopic conditions. This study investigated the sensitivity of photopic and mesopic conditions to detect contrast sensitivity (CS) loss in drivers with simulated media opacities. CS was measured in forty-seven healthy drivers aged 18-50 years (mean ± SD: 25.5 ± 6.5) under photopic and mesopic-adapted luminance levels with the Pelli-Robson chart and the Mesotest II (without glare). Media opacities were simulated using white-opacity containing Lee Fog filters (1-5) and CS measured in a randomised order. A significant (p < 0.001) reduction in photopic CS (logCS) was measured with the Pelli-Robson chart only when media opacity was simulated with Fog filter 5 (1.53 ± 0.15, 2.8 triplets reduction) compared to baseline (1.95 ± 0.03). Mean mesopic CS demonstrated a significant (all p < 0.001) reduction from baseline (1.67 ± 0.14) for Fog filters 3 (1.4 triplets, 1.45 ± 0.16), 4 (2.4 triplets, 1.31 ± 0.14) and 5 (4.3 triplets, 1.02 ± 0.15). For Mesotest II, only Fog filter 5 produced a significant reduction (0.10 ± 0.09; p < 0.001) in mean mesopic CS from baseline (0.30 ± 0.01). Mesopic CS is more vulnerable to different levels of simulated media opacity, hence should be considered clinically when assessing visual function in older drivers at risk of media opacity.

The Effect of Induced Intraocular Stray Light on Recognition Thresholds for Pseudo-High-Pass Filtered Letters.

Purpose: The Moorfields Acuity Chart (MAC)-comprising pseudo-high-pass filtered "vanishing optotype" (VO) letters-is more sensitive to functional visual loss in age-related macular degeneration (AMD) compared to conventional letter charts. It is currently unknown the degree to which MAC acuity is affected by optical factors such as cataract. This is important to know when determining whether an individual's vision loss owes more to neural or optical factors. Here we estimate recognition acuity for VOs and conventional letters with simulated lens aging, achieved using different levels of induced intraocular light scatter. Methods: Recognition thresholds were determined for two experienced and one naive participant with conventional and VO letters. Stimuli were presented either foveally or at 10 degrees in the horizontal temporal retina, under varying degrees of intraocular light scatter induced by white resin opacity-containing filters (WOFs grades 1 to 5). Results: Foveal acuity only became significantly different from baseline (no filter) for WOF grade 5 with conventional letters and WOF grades 4 and 5 with VOs. In the periphery, no statistical difference was found for any stray-light level for both conventional and VOs. Conclusions: Recognition acuity measured with conventional and VOs is robust to the effects of simulated lens opacification, and thus its higher sensitivity to neural damage should not simultaneously be confounded by such optical factors. Translational Relevance: The MAC may be better able to differentiate between neural and optical deficits of visual performance, making it more suitable for the assessment of patients with AMD, who may display both types of functional visual loss.

Resolution acuity and spatial summation of chromatic mechanisms in the peripheral retina.

Green stimuli are more difficult to detect than red stimuli in the retinal periphery, as reported previously. We examined the spatial characteristics of chromatic mechanisms using stimuli, modulated from an achromatic background to each pole of the "red-green" cardinal axis in DKL space at 20 deg eccentricity. The "blue-yellow" cardinal axis was also studied for comparison. By measuring both grating discrimination at the resolution limit (resolution acuity) and spatial summation, assessed by the Michaelis-Menten function, we demonstrated a marked "red-green" asymmetry. The resolution acuity was worse and spatial summation more extended for "green" compared to "red" stimuli, while showing significant individual variations. Ricco's area was also measured, but not determined for "green" spots because of the poor small stimuli detection. These results cannot be explained by differences in L- and M-cone numerosity and/or spatial arrangement, but rather have postreceptoral origin, probably at the cortical level.

Resolution acuity across the visual field for mesopic and scotopic illumination.

We investigated the classical question of why visual acuity decreases with decreasing retinal illuminance by holding retinal eccentricity fixed while illumination varied. Our results indicate that acuity is largely independent of illuminance at any given retinal location, which suggests that under classical free-viewing conditions acuity improves as illumination increases from rod threshold to rod saturation because the retinal location of the stimulus is permitted to migrate from a peripheral location of maximum sensitivity but poor acuity to the foveal location of maximum acuity but poor sensitivity. Comparison with anatomical sampling density of retinal neurons suggests that mesopic acuity at all eccentricities and scotopic acuity for eccentricities beyond about 20° is limited by the spacing of midget ganglion cells. In central retina, however, scotopic acuity is further limited by spatial filtering due to spatial summation within the large, overlapping receptive fields of the A-II class of amacrine cells interposed in the rod pathway between rod bipolars and midget ganglion cells. Our results offer a mechanistic interpretation of the clinical metrics for low-luminance visual dysfunction used to monitor progression of retinal disease.

Altered spatial summation optimizes visual function in axial myopia.

This study demonstrates significant differences between the area of complete spatial summation (Ricco's area, RA) in eyes with and without non-pathological, axial myopia. Contrast thresholds were measured for six stimuli (0.01-2.07 deg2) presented at 10º eccentricity in 24 myopic subjects and 20 age-similar non-myopic controls, with RA estimated using iterative two-phase regression analysis. To explore the effects of axial length-induced variations in retinal image size (RIS) on the measurement of RA, refractive error was separately corrected with (i) trial lenses at the anterior focal point (near constant inter-participant RIS in mm), and (ii) contact lenses (RIS changed with axial length). For spectacle corrected measurements, RA was significantly larger in the myopic group, with a significant positive correlation also being observed between RA and measures of co-localised peripheral ocular length. With contact lens correction, there was no significant difference in RA between the groups and no relationship with peripheral ocular length. The results suggest RA changes with axial elongation in myopia to compensate for reduced retinal ganglion cell density. Furthermore, as these changes are only observed when axial length induced variations in RIS are accounted for, they may reflect a functional adaptation of the axially-myopic visual system to an enlarged RIS.

Automated Pupillometry Using a Prototype Binocular Optical Coherence Tomography System.

PURPOSE: To determine the test-retest reliability and diagnostic accuracy of a binocular optical coherence tomography (OCT) prototype (Envision Diagnostics, El Segundo, California, USA) for pupillometry. DESIGN: Assessment of diagnostic reliability and accuracy. METHODS: Fifty participants with relative afferent pupillary defects (RAPDs) confirmed using the swinging flashlight method (mean age 49.6 years) and 50 healthy control subjects (mean age 31.3 years) were examined. Participants twice underwent an automated pupillometry examination using a binocular OCT system that presents a stimulus and simultaneously captures OCT images of the iris-pupil plane of both eyes. Participants underwent a single examination on the RAPDx (Konan Medical, Irvine, California, USA), an automated infrared pupillometer. Pupil parameters including maximum and minimum diameter, and anisocoria were measured. The magnitude of RAPD was calculated using the log of the ratio of the constriction amplitude between the eyes. A pathological RAPD was above ±0.5 log units on both devices. RESULTS: The intraclass correlation coefficient was >0.90 for OCT-derived maximum pupil diameter, minimum pupil diameter, and anisocoria. The RAPDx had a sensitivity of 82% and a specificity of 94% for detection of RAPD whereas the binocular OCT had a sensitivity of 74% and specificity of 86%. The diagnostic accuracy of the RAPDx and binocular OCT was 88% (95% confidence interval 80%-94%) and 80% (95% confidence interval 71%-87%) respectively. CONCLUSIONS: Binocular OCT-derived pupil parameters had excellent test-retest reliability. The diagnostic accuracy of RAPD was inferior to the RAPDx and is likely related to factors such as eye movement during OCT capture. As OCT becomes ubiquitous, OCT-derived measurements may provide an efficient method of objectively quantifying the pupil responses.

High-Resolution In Vivo Fundus Angiography using a Nonadaptive Optics Imaging System.

PURPOSE: We provide a proof of concept for the detailed characterization of retinal capillary features and surrounding photoreceptor mosaic using a customized nonadaptive optics angiography imaging system. METHODS: High-resolution fluorescein angiography (FFA) and/or indocyanine green angiography (ICGA) images were obtained using a modified Heidelberg retina angiograph (HRA2) device with a reduced scan angle enabling 3° field of view. Colocalized images of the photoreceptor mosaic also were captured in vivo using the same instrument. Visibility of vascular subbranches were compared between high-resolution images and conventional fundus angiography (FA) with a 30° field of view. RESULTS: High-resolution angiographic and infrared images (3° × 3° field of view, a 10-fold magnification) were obtained in 10 participants. These included seven patients with various retinal diseases, including myopic degeneration, diabetic retinopathy, macular telangiectasia, and central serous chorioretinopathy, as well as three healthy controls. Images of the retinal vasculature down to the capillary level were obtained on angiography with the ability to visualize a mean 1.2 levels more subbranches compared to conventional FA. In addition, imaging of the photoreceptor cone mosaic, to a sufficient resolution to calculate cone density, was possible. Movement of blood cells within the vasculature also was discernible on infrared videography. CONCLUSIONS: This exploratory study demonstrates that fast high-resolution angiography and cone visualization is feasible using a commercially available imaging system. TRANSLATIONAL RELEVANCE: This offers potential to better understand the relationship between the retinal neurovascular system in health and disease and the timing of therapeutic interventions in disease states.

Use of a Binocular Optical Coherence Tomography System to Evaluate Strabismus in Primary Position.

Importance: Current clinical methods for assessing strabismus can be prone to error. Binocular optical coherence tomography (OCT) has the potential to assess and quantify strabismus objectively and in an automated manner. Objective: To evaluate the use of a binocular OCT prototype to assess the presence and size of strabismus. Design, Setting, and Participants: Fifteen participants with strabismus were recruited in 2016 as part of the EASE study from Moorfields Eye Hospital National Health Service Foundation Trust, London, England, and 15 healthy volunteers underwent automated anterior segment imaging using the binocular OCT prototype. All participants had an orthoptic assessment, including alternating prism cover test (APCT), before undergoing imaging. Simultaneously acquired pairs of OCT images, captured with 1 eye fixating, were analyzed using ImageJ (National Institutes of Health) to assess the presence and angle of strabismus. Main Outcomes and Measures: The direction and size of strabismus measured using binocular OCT was compared with that found using APCT. Results: The median age for participants with strabismus was 55 years (interquartile range [IQR], 33-66.5 years) and for the healthy group, 50 years (IQR, 41-59 years); 15 participants (50%) were women, and 25 participants (83.3%) were white. The median magnitude of horizontal deviation was 20∆ (IQR, 13-35∆) and for vertical deviation, 3∆ (IQR, 0-5∆). Binocular OCT imaging correctly revealed the type and direction of the deviation in all 15 participants with strabismus, including horizontal and vertical deviations. The APCT and OCT measurements were strongly correlated for the horizontal (Pearson r = 0.85; 95% CI, 0.60-0.95; P < .001) and vertical (r = 0.89; 95% CI, 0.69-0.96; P < .001) deviations. In the healthy cohort, 9 of 15 participants (60%) had a latent horizontal deviation on APCT results (median magnitude 2∆, range 2-4∆). Six (40%) had orthophoria. Horizontal deviations were observed on OCT imaging results in 12 of the 15 participants (80%), and a vertical deviation was visible in 1 participant (6.7%). Conclusions and Relevance: These findings suggest that binocular anterior segment OCT imaging can provide clinicians with a precise measurement of strabismus. The prototype can potentially incorporate several binocular vision tests that will provide quantitative data for the assessment, diagnosis, and monitoring of ocular misalignments.

Optimising the glaucoma signal/noise ratio by mapping changes in spatial summation with area-modulated perimetric stimuli.

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 (CR), 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 CR 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.

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.

Relationship between Psychophysical Measures of Retinal Ganglion Cell Density and In Vivo Measures of Cone Density in Glaucoma.

PURPOSE: Considerable between-individual variation in retinal ganglion cell (RGC) density exists in healthy individuals, making identification of change from normal to glaucoma difficult. In ascertaining local cone-to-RGC density ratios in healthy individuals, we wished to investigate the usefulness of objective cone density estimates as a surrogate of baseline RGC density in glaucoma patients, and thus a more efficient way of identifying early changes. DESIGN: Exploratory cohort study. PARTICIPANTS: Twenty glaucoma patients (60% women) with a median age of 54 years and mean deviation (MD) in the visual field of -5 dB and 20 healthy controls (70% women) with a median age of 57 years and a mean MD of 0 dB were included. METHODS: Glaucoma patients and healthy participants underwent in vivo cone imaging at 4 locations of 8.8° eccentricity with a modified Heidelberg Retina Angiograph HRA2 (scan angle, 3°). Cones were counted using an automated program. Retinal ganglion cell density was estimated at the same test locations from peripheral grating resolution acuity thresholds. MAIN OUTCOME MEASURES: Retinal cone density, estimated RGC density, and cone-to-RGC ratios in glaucoma patients and healthy controls. RESULTS: Median cone-to-RGC density was 3.51:1 (interquartile range [IQR], 2.59:1-6.81:1) in glaucoma patients compared with 2.35:1 (IQR, 1.83:1-2.82:1) in healthy participants. Retinal ganglion cell density was 33% lower in glaucoma patients than in healthy participants; however, cone density was very similar in glaucoma patients (7248 cells/mm2) and healthy controls (7242 cells/mm2). The area under the receiver operator characteristic curve was 0.79 (95% confidence interval [CI], 0.71-0.86) for both RGC density and cone-to-RGC ratio and 0.49 (95% CI, 0.39-0.58) for cone density. CONCLUSIONS: Local measurements of cone density do not differ significantly from normal in glaucoma patients despite large differences in RGC density. There was no statistically significant association between RGC density and cone density in the normal participants, and the range of cone-to-RGC density ratios was relatively large in healthy controls. These findings suggest that estimates of baseline RGC density from cone density are unlikely to be precise and offer little advantage over determination of RGC alone in the identification of early glaucomatous change.

Visual acuity loss in patients with age-related macular degeneration measured using a novel high-pass letter chart.

BACKGROUND/AIMS: Conventional Logarithm of the Minimum Angle of Resolution (logMAR) acuity is the current gold standard for assessing visual function in age-related macular degeneration (AMD). However, visual acuity (VA) often remains 'normal' when measured with these charts, even with advanced retinal changes. We wished to investigate how VA measurements with the Moorfields Acuity Chart (MAC), which employs high-pass filtered letters, compares to conventional letter charts in subjects with AMD. METHODS: Monocular best-corrected VA measurements and test-retest variability (TRV) were compared for conventional and MAC charts in 38 normal observers (mean age 52.1 years) and 80 patients (mean age 80.6 years) with varying degrees of acuity loss owing to AMD. Methods of Bland-Altman and ordinary least-squares regression were employed for data analysis. RESULTS: A proportional bias was confirmed between conventional and MAC measurements (r(2)=0.133, p=0.001) such that MAC acuity was -0.45 logMAR 'worse' at the 0.00 logMAR acuity level, but only -0.26 logMAR 'worse' at the 1.00 logMAR level. The mean bias was much smaller in the normal subject group (-0.16 logMAR). Similar TRV (ranging from ±0.09 to ±0.12 logMAR) was found for both charts in both subject groups. CONCLUSIONS: VA measurements with the MAC chart appear to be more sensitive to functional loss in AMD compared with conventional letter charts, with similar TRV. Simulations indicate this may be because the high-pass filtered letters are more vulnerable to undersampling as a result of retinal cell loss in the disease process.

Neural bandwidth of veridical perception across the visual field.

Neural undersampling of the retinal image limits the range of spatial frequencies that can be represented veridically by the array of retinal ganglion cells conveying visual information from eye to brain. Our goal was to demarcate the neural bandwidth and local anisotropy of veridical perception, unencumbered by optical imperfections of the eye, and to test competing hypotheses that might account for the results. Using monochromatic interference fringes to stimulate the retina with high-contrast sinusoidal gratings, we measured sampling-limited visual resolution along eight meridians from 0° to 50° of eccentricity. The resulting isoacuity contour maps revealed all of the expected features of the human array of retinal ganglion cells. Contours in the radial fringe maps are elongated horizontally, revealing the functional equivalent of the anatomical visual streak, and are extended into nasal retina and superior retina, indicating higher resolution along those meridians. Contours are larger in diameter for radial gratings compared to tangential or oblique gratings, indicating local anisotropy with highest bandwidth for radially oriented gratings. Comparison of these results to anatomical predictions indicates acuity is proportional to the sampling density of retinal ganglion cells everywhere in the retina. These results support the long-standing hypothesis that "pixel density" of the discrete neural image carried by the human optic nerve limits the spatial bandwidth of veridical perception at all retinal locations.