Suprathreshold Approaches to Mapping the Visual Field in Advanced Glaucoma.

Purpose: Measuring the spatial extent of defects may be advantageous in advanced glaucoma where conventional perimetric sensitivity measurements are unreliable. We test whether suprathreshold tests on a higher density grid can more efficiently map advanced visual field loss. Methods: Data from 97 patients with mean deviation < -10 dB were used in simulations comparing two suprathreshold procedures (on a high-density 1.5° grid) to interpolated Full Threshold 24-2. Spatial binary search (SpaBS) presented 20-dB stimuli at locations bisecting seen/unseen points until the seen status of all neighbors matched or until tested points were adjacent. The SupraThreshold Adaptive Mapping Procedure (STAMP) presented 20-dB stimuli where entropy was maximal and modified the status of all points after each presentation, stopping after a fixed number of presentations (estimated as 50%-100% of the presentation number of a current procedure). Results: With typical response errors, SpaBS had worse mean accuracy and repeatability than Full Threshold (both P < 0.0001). Compared to Full Threshold, mean accuracy (Full Threshold: median, 91%; interquartile range [IQR], 87%-94%) was slightly better with STAMP for all stopping criteria, although this was not statistically significant until 100% of conventional test presentations were used. Mean repeatability for STAMP was similar for all stopping criteria (P ≥ 0.02) compared to Full Threshold (Full Threshold: median, 89%; IQR, 82%-93%). Conclusions: STAMP accurately and repeatably maps the spatial extent of advanced visual field defects in as few as 50% of conventional perimetric test presentations. Further work is needed to test STAMP in human observers and in progressive loss. Translational Relevance: New perimetric approaches may improve information available for advanced glaucoma management and may potentially be more acceptable to patients.

Concordance of Objectively Detected Retinal Nerve Fiber Bundle Defects in En Face OCT Images with Conventional Structural and Functional Changes in Glaucoma.

PURPOSE: To assess how objectively detected defects in retinal nerve fiber bundle (RNFB) reflectance on en face OCT images relate to circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and visual field defects. DESIGN: Cross-sectional study. PARTICIPANTS: Sixteen participants with early glaucoma and 29 age-matched healthy controls, of whom 22 had usable en face images for the establishment of normative levels of RNFB reflectance. METHODS: All the participants underwent cpRNFLT scans, visual field examination, and wide-field OCT. En face reflectivity was assessed objectively using the Summary of Multiple Anatomically Adjusted Slabs method. En face defects were deemed concordant with cpRNFLT when they had at least 1 cpRNFLT point with P < 0.01, within ± 15° of the predicted insertion on the optic disc. Visual fields were examined using custom suprathreshold perimetry and SITA Standard 24-2. For each visual field location, the corresponding reflectance was deemed abnormal if any en face superpixel within ± 1° was abnormal. The overall, positive, and negative agreements were measured in each participant. MAIN OUTCOME MEASURES: Proportion of concordant defects between en face reflectance analysis and cpRNFLT (%) as well as overall, positive, and negative agreements between en face reflectance analysis and visual field results. RESULTS: Most en face abnormalities had concordant cpRNFLT defects in the mapped sector (median proportion concordant, 0.85; interquartile range, 0.74-0.95). In eyes with glaucoma, a median of 8.1% (range, 2.4%-23.7%) and 14.9% (range, 3.5%-29.1%) locations showed corresponding en face and visual field defects using 24-2 and custom perimetry, respectively. Both the perimetric strategies had moderate-to-good raw agreement with en face analysis (0.66-0.68), with stronger agreement on normal findings than on defects (0.77-0.78 and 0.4-0.44). CONCLUSIONS: Objectively extracted reflectance defects showed strong concordance with conventional cpRNFLT damage and good agreement with perimetry, which could be enhanced by further minimization of image artifacts.

Effects of glaucoma on detection and discrimination of image blur.

PURPOSE: Blur is one of the most commonly reported visual symptoms of glaucoma, but it is not directly measured by current clinical tests. We aimed to investigate the effects of glaucoma on detection and discrimination of image blur. METHODS: Participants were people with glaucoma, separated into two groups with (n = 15) or without (n = 17) central visual field defects measured by 10-2 perimetry, and an age-similar control group (n = 18). First, we measured contrast detection thresholds centrally using a 2-interval forced choice procedure. We then measured blur detection and discrimination thresholds for the same stimuli (reference blurs 0, 1 arcmin) using a 2-alternative forced choice procedure under two contrast conditions: 4× individual detection threshold for the low contrast condition; 95% contrast for the high contrast condition. The stimulus was a horizontal edge bisecting a hard-edged circle of 4.5° diameter. Data were analysed by linear mixed modelling. RESULTS: Contrast detection thresholds for the glaucoma group with central visual field defects were raised by 0.01 ± 0.004 (mean ± SE, Michelson units) (p = 0.002) and by 0.01 ± 0.004 (p = 0.03) relative to control and glaucoma without central visual field defect groups, respectively. Blur detection and discrimination thresholds were similar between groups, with small elevations in blur detection thresholds in the glaucoma groups not reaching statistical significance (detection p = 0.29, discrimination p = 0.91). The lower contrast level increased thresholds from the higher contrast level by 1.30 ± 0.10 arcmin (p < 0.001) and 1.05 ± 0.10 arcmin (p < 0.001) for blur detection and discrimination thresholds, respectively. CONCLUSIONS: Early-moderate glaucoma resulted in only minimal elevations of blur detection thresholds that did not reach statistical significance in this study. Despite the prevalence of blur as a visual symptom of glaucoma, psychophysical measurements of blur detection or discrimination may not be good candidates for development as clinical tests for glaucoma.

Patients' Views of Visual Field Testing and Priorities for Research Development and Translation into Practice.

PURPOSE: Information regarding the views of patients, on visual field testing is limited, and no information exists regarding their preferences for test developments. This study aimed to increase knowledge of patients' experiences of visual field assessment and to explore their opinions and priorities regarding current areas of research and development. DESIGN: Online questionnaire with purposive sampling design. PARTICIPANTS: Adults who regularly undergo visual field tests in Australia who report having glaucoma or being at glaucomatous risk. METHODS: An anonymous survey, implemented using the Qualtrics webtool, with both closed- and-open ended questions designed to explore opinions regarding visual field testing, visit attendance for perimetry, as well as priorities for developments. MAIN OUTCOME MEASURES: The survey assessed 3 domains: (1) opinions regarding test duration and visit frequency, (2) subjective experience, and (3) perspectives on future developments. RESULTS: One hundred fifty-two complete survey responses were obtained. The median age of participants was 66 years (interquartile range [IQR], 60-72 years). Most participants (70%) had experience of undergoing more than 11 visual field tests. Participants recalled that they completed visual field tests in median of 6 minutes (IQR, 5-8 minutes) and were willing to accept additional time (median, 5 minutes; IQR, 3-6 minutes) to obtain more information. Participants were prepared to increase both the number of visual field tests per eye and the frequency of visual field tests (median, 3 visits per year; IQR, 2-4 visits per year) to gain more information about their visual status. Regarding future developments, the most preferred option was "similar test times but an increase in the level of information about my visual field," which ranked significantly higher than all other options, including "shorter test times that maintain the currently available level of information about my visual field." CONCLUSIONS: Our study confirms, in a different population and health care system, previous research reporting patient perspectives on visual field assessment. We further revealed that health care consumers show a strong preference for accurate information about their vision and report being prepared to undergo longer visual field tests or more visual field tests to achieve that outcome.

Enhanced Objective Detection of Retinal Nerve Fiber Bundle Defects in Glaucoma With a Novel Method for En Face OCT Slab Image Construction and Analysis.

Purpose: To introduce and evaluate the performance in detecting glaucomatous abnormalities of a novel method for extracting en face slab images (SMAS), which considers varying individual anatomy and configuration of retinal nerve fiber bundles. Methods: Dense central retinal spectral domain optical coherence tomography scans were acquired in 16 participants with glaucoma and 19 age-similar controls. Slab images were generated by averaging reflectivity over different depths below the inner limiting membrane according to several methods. SMAS considered multiple 16 µm thick slabs from 8 to 116 µm below the inner limiting membrane, whereas 5 alternative methods considered single summary slabs of various thicknesses and depths. Superpixels in eyes with glaucoma were considered abnormal if below the first percentile of distributions fitted to control data for each method. The ability to detect glaucoma defects was measured by the proportion of abnormal superpixels. Proportion of superpixels below the fitted first percentile in controls was used as a surrogate false-positive rate. The effects of slab methods on performance measures were evaluated with linear mixed models. Results: The ability to detect glaucoma defects varied between slab methods, χ2(5) = 120.9, P < 0.0001, with SMAS showing proportion of abnormal superpixels 0.05 to 0.09 greater than alternatives (all P < 0.0001). No slab method found abnormal superpixels in controls. Conclusions: SMAS outperformed alternatives in detecting abnormalities in eyes with glaucoma. SMAS evaluates all depths with potential retinal nerve fiber bundle presence by combining multiple slabs, resulting in greater detection of reflectance abnormalities with no increase in surrogate false positives. Translational Relevance: SMAS may be used to objectively detect glaucoma defects in en face optical coherence tomography images.

A Simple Subjective Evaluation of Enface OCT Reflectance Images Distinguishes Glaucoma From Healthy Eyes.

Purpose: We present a subjective approach to detecting glaucomatous defects in enface images and assess its diagnostic performance. We also test the hypothesis that if reflectivity changes precede thickness changes in glaucoma there should be reduced correlation between the modalities in glaucoma compared to controls. Methods: Twenty glaucoma participants and 20 age-matched controls underwent high-resolution OCT scans of one eye. 4 µm-thick enface slabs were constructed through the retina. Enface indices were depths of first gap in visible retinal nerve fiber bundles (RNFBs) and last visible bundle, subjectively evaluated in six sectors of a 3.5 mm circle around the optic disc. Retinal nerve fiber layer thickness (RNFLT) along the same circle was extracted at angles corresponding to enface indices. Between-group differences were tested by linear mixed models. Diagnostic performance was measured by partial receiver operating characteristic area (pAUC). Results: First gap and last visible bundle were closer to the inner limiting membrane in glaucoma eyes (both P < 0.0001). Enface indices showed excellent diagnostic performance (pAUCs 0.63-1.00), similar to RNFLT (pAUCs 0.63-0.95). Correlation between enface and RNFLT parameters was strong in healthy (r = 0.81-0.92) and glaucoma eyes (r = 0.73-0.80). Conclusions: This simple subjective method reliably identifies glaucomatous defects in enface images with diagnostic performance at least as good as existing thickness indices. Thickness and reflectivity were similarly related in healthy and glaucoma eyes, providing no strong evidence of reflectivity loss preceding thinning. Objective analyses may realize further potential of enface OCT images in glaucoma. Translational Relevance: Novel enface OCT indices may aid glaucoma diagnosis.

Effects of Criterion Bias on Perimetric Sensitivity and Response Variability in Glaucoma.

Purpose: The purpose of this study was to isolate and quantify the effects of observer response criterion on perimetric sensitivity, response variability, and maximum response probability. Methods: Twelve people with glaucoma were tested at three locations in the visual field (age = 47-77 years, mean deviation = -0.61 to -14.54 dB, test location Humphrey field analyzer [HFA] sensitivities = 1 to 30 dB). Frequency of seeing (FoS) curves were measured using a method of constant stimuli with two response paradigms: a "yes-no" paradigm similar to static automated perimetry and a criterion-free two interval forced choice (2IFC) paradigm. Comparison measures of sensitivity, maximum response probability, and response variability were derived from the fitted FoS curves. Results: Sensitivity differences between the tasks varied widely (range = -11.3 dB to 21.6 dB) and did not correlate with visual field sensitivity nor whether the visual field location was in an area of steep sensitivity gradient within the visual field. Due to the wide variation in differences between the methods, there was no significant difference in mean sensitivity between the 2IFC task relative to the yes-no task, but a trend for higher sensitivity (mean = 1.9 dB, SD = 6.0 dB, P = 0.11). Response variability and maximum response probability did not differ between the tasks (P > 0.99 and 0.95, respectively). Conclusions: Perimetric sensitivity estimates are demonstrably altered by observer response criterion but the effect varies widely and unpredictably, even within a single test. Response bias should be considered a factor in perimetric test variability and when comparing sensitivities to nonperimetric data. Translational Relevance: The effect of response criterion on perimetric response variability varies widely and unpredictably, even within a single test.

Fundus-controlled perimetry (microperimetry): Application as outcome measure in clinical trials.

Fundus-controlled perimetry (FCP, also called 'microperimetry') allows for spatially-resolved mapping of visual sensitivity and measurement of fixation stability, both in clinical practice as well as research. The accurate spatial characterization of visual function enabled by FCP can provide insightful information about disease severity and progression not reflected by best-corrected visual acuity in a large range of disorders. This is especially important for monitoring of retinal diseases that initially spare the central retina in earlier disease stages. Improved intra- and inter-session retest-variability through fundus-tracking and precise point-wise follow-up examinations even in patients with unstable fixation represent key advantages of these technique. The design of disease-specific test patterns and protocols reduces the burden of extensive and time-consuming FCP testing, permitting a more meaningful and focused application. Recent developments also allow for photoreceptor-specific testing through implementation of dark-adapted chromatic and photopic testing. A detailed understanding of the variety of available devices and test settings is a key prerequisite for the design and optimization of FCP protocols in future natural history studies and clinical trials. Accordingly, this review describes the theoretical and technical background of FCP, its prior application in clinical and research settings, data that qualify the application of FCP as an outcome measure in clinical trials as well as ongoing and future developments.

Depth-resolved variations in visibility of retinal nerve fibre bundles across the retina in enface OCT images of healthy eyes.

PURPOSE: Recent developments in optical coherence tomography (OCT) technology enable direct enface visualisation of retinal nerve fibre bundle (RNFB) loss in glaucoma. However, the optimum depth at which to visualise RNFBs across the retina is unknown. We aimed to evaluate the range of depths and optimum depth at which RNFBs can be visualised across the retina in healthy eyes. METHODS: The central ± 25° retina of 10 healthy eyes from 10 people aged 57-75 years (median 68.5 years) were imaged with spectral domain OCT. Slab images of maximum axial resolution (4 µm) containing depth-resolved attenuation coefficients were extracted from 0 to 193.5 µm below the inner limiting membrane (ILM). Bundle visibility within 10 regions of a superimposed grid was assessed subjectively by trained optometrists (n = 8), according to written instructions. Anterior and posterior limits of RNFB visibility and depth of best visibility were identified for each grid sector. Effects of retinal location and individual eye on RNFB visibility were explored using linear mixed modelling with likelihood ratio tests. Intraclass correlation coefficient (ICC) was used to measure overall agreement and repeatability of grading. Spearman's correlation was used to measure correlation between depth range of visible RNFBs and retinal nerve fibre layer thickness (RNFLT). RESULTS: Retinal location and individual eye affected anterior limit of visibility (χ2(9)  = 58.6 and 60.5, both p < 0.0001), but none of the differences exceeded instrument resolution, making anterior limit consistent across the retina and different eyes. Greater differences were observed in the posterior limit of visibility across retinal areas (χ2(9)  = 1671.1, p < 0.0001) and different eyes (χ2(9)  = 88.7, p < 0.0001). Optimal depth for visualisation of RNFBs was around 20 µm below the ILM in most regions. It varied slightly with retinal location (χ2(9)  = 58.8, p < 0.0001), but it was not affected by individual eye (χ2(9)  = 10.7, p = 0.29). RNFB visibility showed good agreement between graders (ICC 0.89, 95%CI 0.87-0.91), and excellent repeatability (ICC 0.96-0.99). Depth range of visible RNFBs was highly correlated with RNFLT (ρ = 0.9, 95%CI: 0.86-0.95). CONCLUSIONS: The range of depths with visible RNFBs varies markedly across the healthy retina, consistently with RNFLT. To extract all RNFB information consistently across the retina, slab properties should account for differences across retinal locations and between individual eyes.

Unaltered Perception of Suprathreshold Contrast in Early Glaucoma Despite Sensitivity Loss.

Purpose: Glaucoma raises contrast detection thresholds, but our natural visual environment is dominated by high contrast that may remain suprathreshold in early to moderate glaucoma. This study investigates the effect of glaucoma on the apparent contrast of visible stimuli. Methods: Twenty participants with glaucoma with partial visual field defects (mean age, 72 ± 7 years) and 20 age-similar healthy controls (mean age, 70 ± 7 years) took part. Contrast detection thresholds for Gabor stimuli (SD, 0.75°) of four spatial frequencies (0.5, 1.0, 2.0, and 4.0 c/deg) were first measured at 10° eccentricity, both within and outside of visual field defects for participants with glaucoma. Subsequently, the contrast of a central Gabor was matched to that of a peripheral Gabor with contrast fixed at two times or four times the detection threshold. Data were analyzed by linear mixed modelling. Results: Compared with controls, detection thresholds for participants with glaucoma were raised by 0.05 ± 0.025 (Michelson units, ± SE; P = 0.12) and by 0.141 ± 0.026 (P < 0.001) outside and within visual field defects, respectively. For reference stimuli at two times the detection contrast, matched contrast ratios (matched/reference contrast) were 0.16 ± 0.039 (P < 0.001) higher outside compared with within visual field defects in participants with glaucoma. Matched contrast ratios within visual field defects were similar to controls (mean 0.033 ± 0.066 lower; P = 0.87). For reference stimuli at four times the detection contrast, matched contrast ratios were similar across all three groups (P = 0.58). Spatial frequency had a minimal effect on matched contrast ratios. Conclusions: Despite decreased contrast sensitivity, people with glaucoma perceive the contrast of visible suprathreshold stimuli similarly to healthy controls. These results suggest possible compensation for sensitivity loss in the visual system.

Relating optical coherence tomography to visual fields in glaucoma: structure-function mapping, limitations and future applications.

Combining information from optical coherence tomography (OCT) imaging and visual field testing is useful in the clinical assessment and monitoring of patients with glaucoma. Measurements of retinal nerve fibre layer thickness or neuroretinal rim width taken around the optic nerve head may be related to the visual field using a structure-function map. In this review, the structure-function mapping methods in clinical use are discussed. Typical clinical maps provide a population average, 'one size fits all' representation, but in recent years methods for customising structure-function maps to individual eyes have been developed and these are reviewed here. In the macula, visual field stimuli stimulate photoreceptors for which associated retinal ganglion cells are peripherally displaced. Recently developed methods that relate OCT measurements to visual field test locations in the macula are therefore also reviewed. The use of structure-function maps to relate OCT measurements to localised visual field sensitivity in new applications is also explored. These new applications include the selection of visual field test locations and stimulus intensities based on OCT data, and the formal post-test combination of results across modalities. Such applications promise to exploit the structure-function relationship in glaucoma to improve disease diagnosis and monitoring of progression. Limitations in the validation and use of current structure-function mapping techniques are discussed.

Estimation of Contrast Sensitivity From Fixational Eye Movements.

Purpose: Even during steady fixation, people make small eye movements such as microsaccades, whose rate is altered by presentation of salient stimuli. Our goal was to develop a practical method for objectively and robustly estimating contrast sensitivity from microsaccade rates in a diverse population. Methods: Participants, recruited to cover a range of contrast sensitivities, were visually normal (n = 19), amblyopic (n = 10), or had cataract (n = 9). Monocular contrast sensitivity was estimated behaviorally while binocular eye movements were recorded during interleaved passive trials. A probabilistic inference approach was used to establish the likelihood of observed microsaccade rates given the presence or absence of a salient stimulus. Contrast sensitivity was estimated from a function fitted to the scaled log-likelihood ratio of the observed microsaccades in the presence or absence of a salient stimulus across a range of contrasts. Results: Microsaccade rate signature shapes were heterogeneous; nevertheless, estimates of contrast sensitivity could be obtained in all participants. Microsaccade-estimated contrast sensitivity was unbiased compared to behavioral estimates (1.2% mean), with which they were strongly correlated (Spearman's ρ 0.74, P < 0.001, median absolute difference 7.6%). Measurement precision of microsaccade-based contrast sensitivity estimates was worse than that of behavioral estimates, requiring more than 20 times as many presentations to equate precision. Conclusions: Microsaccade rate signatures are heterogeneous in shape when measured across populations with a broad range of contrast sensitivities. Contrast sensitivity can be robustly estimated from rate signatures by probabilistic inference, but more stimulus presentations are currently required to achieve similarly precise estimates to behavioral techniques.

Predicting Visual Acuity From Visual Field Sensitivity in Age-Related Macular Degeneration.

Purpose: To investigate how well visual field sensitivity predicts visual acuity at the same locations in macular disease, and to assess whether such predictions may be useful for selecting an optimum area for fixation training. Methods: Visual field sensitivity and acuity were measured at nine locations in the central 10° in 20 people with AMD and stable foveal fixation. A linear mixed model was constructed to predict acuity from sensitivity, taking into account within-subject effects and eccentricity. Cross validation was used to test the ability to predict acuity from sensitivity in a new patient. Simulations tested whether sensitivity can predict nonfoveal regions with greatest acuity in individual patients. Results: Visual field sensitivity (P < 0.0001), eccentricity (P = 0.007), and random effects of subject on eccentricity (P = 0.043) improved the model. For known subjects, 95% of acuity prediction errors (predicted - measured acuity) fell within -0.21 logMAR to +0.18 logMAR (median +0.00 logMAR). For unknown subjects, cross validation gave 95% of acuity prediction errors within -0.35 logMAR to +0.31 logMAR (median -0.01 logMAR). In simulations, the nonfoveal location with greatest predicted acuity had greatest "true" acuity on median 26% of occasions, and median difference in acuity between the location with greatest predicted acuity and the best possible location was +0.14 logMAR (range +0.04 to +0.17). Conclusions: The relationship between sensitivity and acuity in macular disease is not strongly predictive. The location with greatest sensitivity on microperimetry is unlikely to represent the location with the best visual acuity, even if eccentricity is taken into account.

Modified images reflecting effects of age-related macular degeneration on perception of everyday scenes.

BACKGROUND: Depictions of vision with age-related macular degeneration (AMD) in public information material typically show a central region of absolute vision loss. Patients with early and moderate disease frequently do not report this. We aimed to measure how a group of people with AMD perceive everyday scenes in order to produce accurate depictions. METHODS: We report on six people aged 65-82 years with monocular AMD (visual acuity +0.04 to +1.64 logMAR) and normal vision in the fellow eye. Participants viewed four images monocularly, alternating between eyes. The image was digitally altered to approximate participants' descriptions of their perception with the affected eye. The altered image was viewed with the unaffected eye, and compared with the original image viewed with the affected eye. This was repeated iteratively until a perceptual match was achieved between the modified image/unaffected eye and the original image/affected eye. RESULTS: For five AMD participants with visual acuity +0.04 to +0.50 logMAR the modified images did not resemble those in current public information material. Image modifications required to achieve perceptual similarity with the affected eyes included localised distortion, contrast reduction and blur. Widespread colour desaturation was also required in some cases. One participant with advanced geographic atrophy reported an absolute positive scotoma, similar to existing depictions. CONCLUSIONS: Vision in people with AMD may not conform to the common depiction of a central region of absolute vision loss. The accurate representations of AMD patients' vision produced in this study will enable better understanding of the visual consequences of AMD.

Properties of Visual Field Defects Around the Monocular Preferred Retinal Locus in Age-Related Macular Degeneration.

Purpose: To compare microperimetric sensitivity around the monocular preferred retinal locus (mPRL) in age-related macular degeneration (AMD) to normative data, and to describe the characteristics of visual field defects around the mPRL in AMD. Methods: Participants with AMD (total n = 185) were either prospectively recruited (n = 135) or retrospectively reviewed from an existing database (n = 50). Participants underwent microperimetry using a test pattern (37 point, 5° radius) centered on their mPRL. Sensitivities were compared to normative data by spatial interpolation, and conventional perimetric indices were calculated. The location of the mPRL relative to the fovea and to visual field defects was also investigated. Results: Location of mPRL varied approximately 15° horizontally and vertically. Visual field loss within 5° of the mPRL was considerable in the majority of participants (median mean deviation -14.7 dB, interquartile range [IQR] -19.6 to -9.6 dB, median pattern standard deviation 7.1 dB [IQR 4.8-9.0 dB]). Over 95% of participants had mean total deviation worse than -2 dB across all tested locations and similarly within 1° of their mPRL. A common pattern of placing the mPRL just foveal to a region of normal pattern deviation was found in 78% of participants. Total deviation was outside normal limits in this region in 68%. Conclusions: Despite altering fixation to improve vision, people with AMD exhibit considerable visual field loss at and around their mPRL. The location of the mPRL was typically just foveal to, but not within, a region of relatively normal sensitivity for the individual, suggesting that a combination of factors drives mPRL selection.

The Proportion of Individuals Likely to Benefit from Customized Optic Nerve Head Structure-Function Mapping.

PURPOSE: Interindividual variance in optic nerve head (ONH) position, axial length, and location of the temporal raphe suggest that customizing mapping between visual field locations and ONH sectors for individuals may be clinically useful. Herein we quantify the proportion of the population predicted to have structure-function mappings that markedly deviate from "average," and thus would benefit from customized mapping. DESIGN: Database study and case report. PARTICIPANTS: Population database of 2836 eyes from the Beijing Eye Study and a single case report of an individual with primary open-angle glaucoma. METHODS: Using the morphometric fundus data of the Beijing Eye Study for 2836 eyes and applying a recently developed model based on axial length and ONH position relative to the fovea, we determined for each measurement location in the 24-2 Humphrey (Carl Zeiss Meditec, Dublin, CA) visual field the proportion of eyes for which, in the customized approach as compared with the generalized approach, the mapped ONH sector was shifted into a different sector. We determined the proportion of eyes for which the mapped ONH location was shifted by more than 15°, 30°, or 60°. MAIN OUTCOME MEASURES: Mapping correspondence between locations in visual field space to localized sectors on the ONH. RESULTS: The largest interindividual differences in mapping are in the nasal step region, where the same visual field location can map to either the superior or inferior ONH, depending on other anatomic features. For these visual field locations, approximately 12% of eyes showed a mapping opposite to conventional expectations. CONCLUSIONS: Anatomically customized mapping shifts the map markedly in approximately 12% of the general population in the nasal step region, where visual field locations can map to the opposite pole of the ONH than conventionally considered. Early glaucomatous damage commonly affects this region; hence, individually matching structure to function may prove clinically useful for the diagnosis and monitoring of progression within individuals.

Spatial Interpolation Enables Normative Data Comparison in Gaze-Contingent Microperimetry.

PURPOSE: To demonstrate methods that enable visual field sensitivities to be compared with normative data without restriction to a fixed test pattern. METHODS: Healthy participants (n = 60, age 19-50) undertook microperimetry (MAIA-2) using 237 spatially dense locations up to 13° eccentricity. Surfaces were fit to the mean, variance, and 5th percentile sensitivities. Goodness-of-fit was assessed by refitting the surfaces 1000 times to the dataset and comparing estimated and measured sensitivities at 50 randomly excluded locations. A leave-one-out method was used to compare individual data with the 5th percentile surface. We also considered cases with unknown fovea location by adding error sampled from the distribution of relative fovea-optic disc positions to the test locations and comparing shifted data to the fixed surface. RESULTS: Root mean square (RMS) difference between estimated and measured sensitivities were less than 0.5 dB and less than 1.0 dB for the mean and 5th percentile surfaces, respectively. Root mean square differences were greater for the variance surface, median 1.4 dB, range 0.8 to 2.7 dB. Across all participants 3.9% (interquartile range, 1.8-8.9%) of sensitivities fell beneath the 5th percentile surface, close to the expected 5%. Positional error added to the test grid altered the number of locations falling beneath the 5th percentile surface by less than 1.3% in 95% of participants. CONCLUSIONS: Spatial interpolation of normative data enables comparison of sensitivity measurements from varied visual field locations. Conventional indices and probability maps familiar from standard automated perimetry can be produced. These methods may enhance the clinical use of microperimetry, especially in cases of nonfoveal fixation.

Central visual field sensitivity data from microperimetry with spatially dense sampling.

Microperimetry, also referred to as fundus perimetry or fundus-driven perimetry, enables simultaneous acquisition of visual sensitivity and eye movement data. We present sensitivity data collected from 60 participants with normal vision using gaze-contingent perimetry. A custom designed spatially dense test grid was used to collect data across the visual field within 13° of fixation. These data are supplemental to a study in which we demonstrated a spatial interpolation method that facilitates comparison of acquired data from any set of spatial locations to normative data and thus screening of individuals with both normal and non-foveal fixation (Denniss and Astle, 2016) [1].

Central perimetric sensitivity estimates are directly influenced by the fixation target.

PURPOSE: Perimetry is increasingly being used to measure sensitivity at central visual field locations. For many tasks, the central (0°, 0°) location is functionally the most important, however threshold estimates at this location may be affected by masking by the nearby spatial structure of the fixation target. We investigated this effect. METHODS: First we retrospectively analysed microperimetry (MAIA-2; CenterVue, Padova, Italy) data from 60 healthy subjects, tested on a custom grid with 1° central spacing. We compared sensitivity at (0°, 0°) to the mean sensitivity at the eight adjacent locations. We then prospectively tested 15 further healthy subjects on the same instrument using a cross-shaped test pattern with 1° spacing. Testing was carried out with and without the central fixation target, and sensitivity estimates at (0°, 0°) were compared. We also compared sensitivity at (0°, 0°) to the mean of the adjacent four locations in each condition. Three subjects undertook 10 repeated tests with the fixation target in place to assess within-subject variability of the effect. RESULTS: In the retrospective analysis, central sensitivity was median 2.8 dB lower (95% range 0.1-8.8 dB lower, p < 0.0001) than the mean of the adjacent locations. In the prospective study, central sensitivity was median 2.0 dB lower with the fixation target vs without (95% range 0.4-4.7 dB lower, p = 0.0011). With the fixation target in place central sensitivity was median 2.5 dB lower than mean sensitivity of adjacent locations (95% range 0.8-4.2 dB lower, p = 0.0007), whilst without the fixation target there was no difference (mean 0.4 dB lower, S.D. 0.9 dB, p = 0.15). These differences could not be explained by reduced fixation stability. Mean within subject standard deviation in the difference between central and adjacent locations' sensitivity was 1.84 dB for the repeated tests. CONCLUSIONS: Perimetric sensitivity estimates from the central (0°, 0°) location are, on-average, reduced by 2 to 3 dB, corresponding to a 60-100% increase in stimulus luminance at threshold. This effect can be explained by masking by the nearby fixation target. The considerable within- and between-subject variability in magnitude, and the unknown effects of disease may hamper attempts to compensate threshold estimates for this effect. Clinicians should interpret central perimetric sensitivity estimates with caution, especially in patients with reduced sensitivity due to disease.

Flicker-defined form stimuli are minimally affected by centre-surround lateral contrast interactions.

PURPOSE: Flicker-defined form (FDF) stimuli have recently been adopted for visual field testing. A key difference between FDF and traditional perimetric stimuli is that the entire display background contains flickering dots. The purpose of this study was to determine whether the perception of FDF stimuli is influenced by lateral interactions involving regions beyond the stimulus border in young healthy observers. METHODS: Experiment 1 measured the effect of surround size and retinal eccentricity on the detection of the FDF contour. Psychometric functions were collected for surround diameters of 20°, 30° and 40°, and with stimuli centred at eccentricities of 0°, 10° and 20°. Experiment 2 measured the effect of target-surround temporal phase difference on apparent temporal contrast (flicker strength) of the target for both the FDF stimulus and a solid-field stimulus. Psychometric functions were collected for target-surround phase differences of 0°, 45°, 90°, 135° and 180°. RESULTS: Our results show a mild surround-suppression effect for FDF stimuli that is independent of surround size. Magnitudes of FDF surround suppression were consistent with the reduced temporal contrast energy of the stimulus compared to solid-field stimuli. CONCLUSION: FDF stimuli necessarily have both flickering target and background. Our results suggest that visual field defects outside the target are unlikely to markedly influence the detection and perception of the FDF stimulus. Nevertheless, mild surround suppression of contrast arises for FDF stimuli, hence interactions between the background and the target area may influence FDF results in conditions that alter centre-surround perceptual effects.