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.

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.

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.

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.

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.

Effect of varying CRT refresh rate on the measurement of temporal summation.

PURPOSE: To quantify the effect of cathode-tube-ray (CRT) monitor refresh rate on the measurement of the upper limit of complete temporal summation (critical duration) in the peripheral visual field of healthy observers. METHODS: Contrast thresholds were measured for seven achromatic spot stimuli (diameter 0.48°) of varying duration (nominal values: 10-200 ms) at an eccentricity of 8.8° along the 45°, 135°, 225° and 315° meridians of the visual field in three healthy, psychophysically experienced observers. Stimuli were presented on a CRT display with a refresh rate of 60 and 160 Hz. Contrast thresholds were expressed as contrast energy with stimulus durations being estimated using (1) the sum-of-frames (SOF) method and (2) Bridgeman's method incorporating measurements of phosphor persistence. Estimates of the critical duration were produced using iterative two-phase regression analysis. RESULTS: With stimulus duration expressed as SOF equivalent the critical duration was, on average, 10.6 ms longer with a refresh rate of 60 Hz (mean 45.7 ms, S.D. 10.1 ms) relative to 160 Hz (35.1 ms, S.D. 7.6 ms). When the Bridgeman method was used, minimal differences (1.8 ms) in critical duration values between the two refresh rates (60 Hz: 33.0 ms, S.D. 9.4 ms; 160 Hz: 31.2 ms, S.D. 7.0 ms) were observed. Identical trends were observed in all three subjects. CONCLUSIONS: Psychophysical measurements of temporal summation are independent of variations in CRT refresh rate when the Bridgeman method, incorporating measured values of phosphor persistence, is used to estimate stimulus duration. This has significant implications for the specification of stimulus duration in psychophysical studies of vision employing conventional display monitors.

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.

Changes in Ricco's area with background luminance in the S-cone pathway.

PURPOSE: The area of complete spatial summation (Ricco's area) for achromatic stimuli has previously been shown to decrease with increased background luminance. A popular hypothesis is that such a phenomenon reflects increased center-surround antagonism within the receptive field of the retinal ganglion cell. We wished to investigate if similar changes in Ricco's area occur with blue background luminance for the S-cone pathway, guided by the knowledge that the retinal ganglion cells with S-cone input do not display S-cone-mediated center-surround antagonism (S+/S-). METHODS: Spatial summation functions were measured for four young healthy observers under S-cone pathway isolation by presenting blue test stimuli on a background consisting of intense fixed yellow (600 cd/m) component in combination with a variable blue component (background range, 1.78 to 2.82 log S-Td). Ricco's area was estimated by two-phase regression analysis. RESULTS: All subjects demonstrated a notable decrease in Ricco's area with increasing blue background luminance. On average, Ricco's area decreased in size by 0.39 log units per log unit increase in blue background luminance. CONCLUSIONS: The change in Ricco's area with the blue background component is not what one would initially expect given the known organization of S-cone-driven cells at the retinal level. Spatial reorganization by the suppressive surround of the receptive fields at a cortical level and a reduction in the contribution from S-cones with the lowest weights in the retinal receptive field periphery are among the possible mechanisms of the summation changes observed. These findings have implications for the design of clinical tests of the S-cone pathway.

Assessment of optic disc photographs for glaucoma by UK optometrists: the Moorfields Optic Disc Assessment Study (MODAS).

PURPOSE: To assess the ability of UK optometrists to accurately discriminate between stereoscopic photographs of healthy and glaucomatous optic discs. METHODS: An online survey, including questions relating to qualification, practice environment, and diagnostic methods was completed by 1256 optometrists. Based on their responses, 208 (17%) were selected to undertake an online disc assessment exercise. Optometrists evaluated the same disc images previously assessed by European ophthalmologists as part of the European Optic Disc Assessment Trial (EODAT); the task was to state if the disc appeared healthy or glaucomatous. There were 110 stereoscopic disc images, of which 40 were healthy, 48 glaucomatous, and six ocular hypertensive, with 16 duplicates images. Sensitivity, specificity and overall accuracy were calculated and compared between optometrist groups and with the EODAT ophthalmologists using permutation analysis. RESULTS: Median sensitivity was 0.92 (95% CI: 0.70, 1.00) and median specificity was 0.74 (95% CI: 0.62, 0.88). Median overall accuracy was 80% (95% CI: 67%, 88%). Agreement between optometrists was moderate (Fleiss' κ: 0.57). Optometrists with higher qualifications did not have overall higher sensitivity than those without (p = 0.23), but had higher specificity (p = 0.001) and higher overall accuracy (p < 0.001). Optometrists displayed higher sensitivity but lower specificity than the EODAT ophthalmologists. CONCLUSION: UK optometrists displayed a high sensitivity and moderate specificity when assessing optic discs for the presence of glaucoma, in the context of this study.

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.

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.

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.

Vanishing Optotype acuity: repeatability and effect of the number of alternatives.

PURPOSE: Vanishing Optotype letters have a pseudo high-pass design so that the mean luminance of the target is the same as the background and the letters thus 'vanish' soon after the resolution threshold is reached. We wished to determine the variability of acuity measurements using these letters compared to conventional letters, and in particular how acuity is affected by the number of alternatives available to the subject. METHODS: Acuity was measured using high contrast letters of both conventional and Vanishing Optotype design for three experienced normal subjects. Thresholds were determined for central vision in a forced choice paradigm for two alternatives (2AFC; AU and OQ), 4AFC (AQUO), 6AFC (QUANGO) and 26AFC (whole alphabet) using a QUEST procedure. Three measurements were made for each condition. RESULTS: Threshold letter size was always larger for the Vanishing Optotypes than conventional letters, although the size of this difference (0.11-0.34 logMAR) depended on the number of alternatives and what they were. The effect of the number of AFC, and the individual letters employed, was smaller for the Vanishing Optotypes, implying that they are more equally legible than conventional optotypes. Variability was also lower for the Vanishing Optotype sets (0.01-0.03 logMAR) than the conventional letter sets (0.03-0.06). CONCLUSIONS: The smaller effect of the number of letter alternatives, combined with more equal discriminability and lower threshold variability, implies that Vanishing Optotypes may be appropriate targets from which to design letter charts to measure small clinical changes in acuity.

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.

Investigation of changes in the myopic retina using multifocal electroretinograms, optical coherence tomography and peripheral resolution acuity.

We investigated relationships between retinal structure using optical coherence tomography (OCT) and retinal function using peripheral resolution acuity and multifocal electroretinograms (mfERG) in 56 subjects with a range of refractive errors (+0.50 to -15.00 D). Retinal thinning occurred in moderate and high myopia which appeared to be primarily due to reduced thickness of the middle to inner retina (MIR) (outer plexiform layer to the nerve fiber layer). MIR thickness was correlated with reduced spatial resolution and delayed mfERG timing in the peripheral retina. The findings suggest the structure and function of the post-receptor retina is susceptible to disruption in moderately and highly myopic eyes.