• An Anatomically Customizable Computational Model Relating the Visual Field to the Optic Nerve Head in Individual Eyes

      Denniss, Jonathan; McKendrick, A.M.; Turpin, A. (2012-10)
      To present a computational model mapping visual field (VF) locations to optic nerve head (ONH) sectors accounting for individual ocular anatomy, and to describe the effects of anatomical variability on maps produced. A previous model that related retinal locations to ONH sectors was adapted to model eyes with varying axial length, ONH position and ONH dimensions. Maps (n = 11,550) relating VF locations (24-2 pattern, n = 52 non–blind-spot locations) to 1° ONH sectors were generated for a range of clinically plausible anatomical parameters. Infrequently mapped ONH sectors (5%) were discarded for all locations. The influence of anatomical variables on the maps was explored by multiple linear regression. Across all anatomical variants, for individual VF locations (24-2), total number of mapped 1° ONH sectors ranged from 12 to 90. Forty-one locations varied more than 30°. In five nasal-step locations, mapped ONH sectors were bimodally distributed, mapping to vertically opposite ONH sectors depending on vertical ONH position. Mapped ONH sectors were significantly influenced (P < 0.0002) by axial length, ONH position, and ONH dimensions for 39, 52, and 30 VF locations, respectively. On average across all VF locations, vertical ONH position explained the most variance in mapped ONH sector, followed by horizontal ONH position, axial length, and ONH dimensions. Relations between ONH sectors and many VF locations are strongly anatomy-dependent. Our model may be used to produce customized maps from VF locations to the ONH in individual eyes where some simple biometric parameters are known.
    • Effects of criterion bias on perimetric sensitivity and response variability in glaucoma

      Rubinstein, N.J.; Turpin, A.; Denniss, Jonathan; McKendrick, A.M. (2021-01)
      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. 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. 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). 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. The effect of response criterion on perimetric response variability varies widely and unpredictably, even within a single test.
    • Enhanced structure-function relationship in glaucoma with an anatomically and geometrically accurate neuroretinal rim measurement

      Danthurebandara, V.M.; Sharpe, G.P.; Hutchison, D.M.; Denniss, Jonathan; Nicolela, M.T.; McKendrick, A.M.; Turpin, A.; Chauhan, B.C. (2015)
      Purpose: To evaluate the structure–function relationship between disc margin–based rim area (DM-RA) obtained with confocal scanning laser tomography (CSLT), Bruch's membrane opening–based horizontal rim width (BMO-HRW), minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer thickness (RNFLT) obtained with spectral-domain optical coherence tomography (SD-OCT), and visual field sensitivity. Methods: We examined 151 glaucoma patients with CSLT, SD-OCT, and standard automated perimetry on the same day. Optic nerve head (ONH) and RNFL with SD-OCT were acquired relative to a fixed coordinate system (acquired image frame [AIF]) and to the eye-specific fovea-BMO center (FoBMO) axis. Visual field locations were mapped to ONH and RNFL sectors with fixed Garway-Heath (VFGH) and patient-specific (VFPS) maps customized for various biometric parameters. Results: Globally and sectorally, the structure–function relationships between DM-RA and VFGH, BMO-HRWAIF and VFGH, and BMO-HRWFoBMO and VFPS were equally weak. The R2 for the relationship between DM-RA and VFGH ranged from 0.1% (inferonasal) to 11% (superotemporal) whereas that between BMO-HRWAIF and VFGH ranged from 0.1% (nasal) to 10% (superotemporal). Relatively stronger global and sectoral structure–function relationships with BMO-MRWAIF and with BMO-MRWFoBMO were obtained. The R2 between BMO-MRWAIF and VFGH ranged from 5% (nasal) to 30% (superotemporal), whereas that between BMO-MRWFoBMO and VFPS ranged from 5% (nasal) to 25% (inferotemporal). The structure–function relationship with RNFLT was not significantly different from that with BMO-MRW, regardless of image acquisition method. Conclusions: The structure–function relationship was enhanced with BMO-MRW compared with the other neuroretinal rim measurements, due mainly to its geometrically accurate properties.
    • Enhancing Structure-Function Correlations in Glaucoma with Customised Spatial Mapping

      Ganeshrao, S.B.; Turpin, A.; Denniss, Jonathan; McKendrick, A.M. (2015-08)
      Purpose To determine whether the structure–function relationship in glaucoma can be strengthened by using more precise structural and functional measurements combined with individualized structure–function maps and custom sector selection on the optic nerve head (ONH). Design Cross-sectional study. Participants One eye of each of 23 participants with glaucoma. Methods Participants were tested twice. Visual fields were collected on a high-resolution 3° × 3° grid (164 locations) using a Zippy Estimation by Sequential Testing test procedure with uniform prior probability to improve the accuracy and precision of scotoma characterization relative to standard methods. Retinal nerve fiber layer (RNFL) thickness was measured using spectral-domain optical coherence tomography (OCT; 4 scans, 2 per visit) with manual removal of blood vessels. Individualized maps, based on biometric data, were used. To customize the areas of the ONH and visual field to correlate, we chose a 30° sector centered on the largest defect shown by OCT and chose visual field locations using the individualized maps. Baseline structure–function correlations were calculated between 24-2 locations (n = 52) of the first tested visual field and RNFL thickness from 1 OCT scan, using the sectors of the Garway-Heath map. We added additional data (averaged visual field and OCT, additional 106 visual field locations and OCT without blood vessels, individualized map, and customized sector) and recomputed the correlations. Main Outcome Measures Spearman correlation between structure and function. Results The highest baseline correlation was 0.52 (95% confidence interval [CI], 0.13–0.78) in the superior temporal ONH sector. Improved measurements increased the correlation marginally to 0.58 (95% CI, 0.21–0.81). Applying the individualized map to the large, predefined ONH sectors did not improve the correlation; however, using the individualized map with the single 30° ONH sector resulted in a large increase in correlation to 0.77 (95% CI, 0.47–0.92). Conclusions Using more precise visual field and OCT measurements did not improve structure–function correlation in our cohort, but customizing the ONH sector and its associated visual field points substantially improved correlation. We suggest using customized ONH sectors mapped to individually relevant visual field locations to unmask localized structural and functional loss.
    • Individualized Structure–Function Mapping for Glaucoma: Practical Constraints on Map Resolution for Clinical and Research Applications

      Denniss, Jonathan; Turpin, A.; McKendrick, A.M. (2014)
      Purpose: We have developed customized maps that relate visual field and optic nerve head (ONH) regions according to individual anatomy. In this study, we aimed to determine feasible map resolution for research use, and to make a principled recommendation of sector size for clinical applications. Methods: Measurement variability in fovea–ONH distance and angle was estimated from 10 repeat OCT scans of 10 healthy people. Errors in estimating axial length from refractive error were determined from published data. Structure–function maps were generated, and customized to varied clinically-plausible anatomical parameters. For each parameter set (n = 210), 200 maps were generated by sampling from measurement/estimation error distributions. Mapped 1° sectors at each visual field location from each parameter set were normalized to difference from their mean. Variation (90% ranges) in normalized mapped sectors represents the precision of individualized maps. Results: Standard deviations of repeated measures of fovea–ONH distance and angle were 61 μm and 0.97° (coefficients of variation 1.3% and 12.0%, respectively). Neither measure varied systematically with mean (Spearmans's ρ = 0.26, P = 0.47 for distance, ρ = −0.31, P = 0.39 for angle). Variation (90% ranges) in normalized mapped sectors varied across the visual field and ranged from 3° to 18° when axial length was measured accurately, and from 6° to 32° when axial length was estimated from refractive error. Conclusions: The 90% ranges represent the minimum feasible ONH sector size at each visual field location. For clinical use an easily interpretable scheme of 30° sectors is suggested.
    • Patients' views of visual field testing and priorities for research development and translation into practice

      Muthusamy, V.; Turpin, A.; Nguyen, B.N.; Denniss, Jonathan; McKendrick, A.M. (2021-10)
      There is limited information regarding the views of patients, as healthcare consumers, on visual field testing, and no information regarding their preferences for future test developments. This study aimed to increase knowledge of patients' subjective experience of visual field assessment and to explore their opinions and priorities regarding current active areas of research and development. Online questionnaire with purposive sampling design. Adults who regularly perform visual field tests in Australia who report having glaucoma or being at risk of glaucoma. 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. The survey assessed three domains: 1) opinions regarding visual field test duration and visit frequency; 2) subjective experience; and 3) perspectives on future developments for perimetry. 152 complete survey responses were obtained. The median (IQR) age of participants was 66 (60-72) years. Most participants (70%) had experience of performing 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, 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, IQR: 2-4 visits per year), in order 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." Our study confirms, in a different population and healthcare system, previous research reporting patient perspectives on visual field assessment. We further reveal that healthcare 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.
    • A Perimetric Test Procedure That Uses Structural Information

      Ganeshrao, S.B.; McKendrick, A.M.; Denniss, Jonathan; Turpin, A. (2015-01)
      Purpose: To develop a perimetric test strategy, Structure Estimation of Minimum Uncertainty (SEMU), that uses structural information to drive stimulus choices. Methods: Structure Estimation of Minimum Uncertainty uses retinal nerve fiber layer (RNFL) thickness data as measured by optical coherence tomography to predict perimetric sensitivity. This prediction is used to set suprathreshold levels that then alter a prior probability distribution of the final test output. Using computer simulation, we studied SEMU’s performance under three different patient error response conditions: No Error, Typical False Positive errors, and Extremely Unreliable patients. In experiment 1, SEMU was compared with an existing suprathreshold cum thresholding combination test procedure, Estimation of Minimum Uncertainty (EMU), on single visual field locations. We used these results to finalize SEMU parameters. In experiment 2, SEMU was compared with full threshold (FT) on 163 glaucomatous visual fields. Results: On individual locations, SEMU has similar accuracy to EMU, but is, on average, one presentation faster than EMU. For the typical false-positive error condition, SEMU has significantly lower error compared with FT (SEMU average 0.33 dB lower; p < 0.001) and the 90% measured sensitivity range for SEMU is also smaller than that for FT. For unreliable patients, however, FT has lower mean and SD of error. Structure Estimation of Minimum Uncertainty makes significantly fewer presentations than FT (1.08 presentation on average fewer in a typical false-positive condition; p < 0.001). Assuming that a location in the field is marked abnormal if it falls below the 5th percentile of normal, SEMU has a false-positive rate of less than 10% for all error conditions compared with FT’s rate of 20% or more. Conclusions: On average, simulations show that using RNFL information to guide stimulus placement in a perimetric test procedure maintains accuracy, improves precision, and decreases test duration for patients with less than 15% false-positive rates.
    • The proportion of individuals likely to benefit from customized optic nerve head structure-function mapping

      McKendrick, A.M.; Denniss, Jonathan; Wang, Y.X.; Jonas, J.B.; Turpin, A. (2017)
      Purpose: Inter-individual variance in optic nerve head (ONH) position, axial length and location of the temporal raphe suggest that customizing mapping between visual field locations and optic nerve head sectors for individuals may be clinically useful. Here 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; single case report of an individual with primary open angle glaucoma Methods: Using the morphometric fundus data of the Beijing Eye Study on 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 visual field the proportion of eyes for which, in the customized approach as compared to 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 15°, 30° or 60°. Main outcome measures: Mapping correspondence between locations in visual field space to localized sectors on the optic nerve head Results: The largest inter-individual 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 anatomical features. For these visual field locations, approximately 12% of eyes showed a mapping opposite to conventional expectations. Conclusions: Anatomically customised 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.
    • Relating optical coherence tomography to visual fields in glaucoma: structure–function mapping, limitations and future applications

      Denniss, Jonathan; Turpin, A.; McKendrick, A.M. (2019-05)
      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.
    • Response times across the visual field: Empirical observations and application to threshold determination

      McKendrick, A.M.; Denniss, Jonathan; Turpin, A. (2014-08)
      This study aimed to determine if response times gathered during perimetry can be exploited within a thresholding algorithm to improve the speed and accuracy of the test. Frequency of seeing (FoS) curves were measured at 24 locations across the central 30° of the visual field of 10 subjects using a Method of Constant Stimuli, with response times recorded for each presentation. Spatial locations were interleaved, and built up over multiple 5-min blocks, in order to mimic the attentional conditions of clinical perimetry. FoS curves were fitted to each participant’s data for each location, and response times derived as a function of distance-from-threshold normalised to the slope of each FoS curve. This data was then used to derive a function for the probability of observing response times given the distance-from-threshold, and to seed simulations of a new test procedure (BURTO) that exploited the probability function for stimulus placement. Test time and error were then simulated for patients with various false response rates. When compared with a ZEST algorithm, simulations revealed that BURTO was about one presentation per location faster than ZEST, on average, while sacrificing less precision and bias in threshold estimates than simply terminating the ZEST earlier. Despite response times varying considerably for a given individual and their thresholds, response times can be exploited to reduce the number of presentations required in a visual field test without loss of accuracy.
    • Structure–Function Mapping: Variability and Conviction in Tracing Retinal Nerve Fiber Bundles and Comparison to a Computational Model

      Denniss, Jonathan; Turpin, A.; Tanabe, F.; Matsumoto, C.; McKendrick, A.M. (2014)
      Purpose: We evaluated variability and conviction in tracing paths of retinal nerve fiber bundles (RNFBs) in retinal images, and compared traced paths to a computational model that produces anatomically-customized structure–function maps. Methods: Ten retinal images were overlaid with 24-2 visual field locations. Eight clinicians and 6 naïve observers traced RNFBs from each location to the optic nerve head (ONH), recording their best estimate and certain range of insertion. Three clinicians and 2 naïve observers traced RNFBs in 3 images, 3 times, 7 to 19 days apart. The model predicted 10° ONH sectors relating to each location. Variability and repeatability in best estimates, certain range width, and differences between best estimates and model-predictions were evaluated. Results: Median between-observer variability in best estimates was 27° (interquartile range [IQR] 20°–38°) for clinicians and 33° (IQR 22°–50°) for naïve observers. Median certain range width was 30° (IQR 14°–45°) for clinicians and 75° (IQR 45°–180°) for naïve observers. Median repeatability was 10° (IQR 5°–20°) for clinicians and 15° (IQR 10°–29°) for naïve observers. All measures were worse further from the ONH. Systematic differences between model predictions and best estimates were negligible; median absolute differences were 17° (IQR 9°–30°) for clinicians and 20° (IQR 10°–36°) for naïve observers. Larger departures from the model coincided with greater variability in tracing. Conclusions: Concordance between the model and RNFB tracing was good, and greatest where tracing variability was lowest. When RNFB tracing is used for structure–function mapping, variability should be considered.
    • Towards patient-tailored perimetry: automated perimetry can be improved by seeding procedures with patient-specific structural information

      Denniss, Jonathan; McKendrick, A.M.; Turpin, A. (2013-04)
      To explore the performance of patient-specific prior information, for example, from structural imaging, in improving perimetric procedures. Computer simulation was used to determine the error distribution and presentation count for Structure–Zippy Estimation by Sequential Testing (ZEST), a Bayesian procedure with prior distribution centered on a threshold prediction from structure. Structure-ZEST (SZEST) was trialled for single locations with combinations of true and predicted thresholds between 1 to 35 dB, and compared with a standard procedure with variability similar to Swedish Interactive Thresholding Algorithm (SITA) (Full-Threshold, FT). Clinical tests of glaucomatous visual fields (n = 163, median mean deviation −1.8 dB, 90% range +2.1 to −22.6 dB) were also compared between techniques. For single locations, SZEST typically outperformed FT when structural predictions were within ± 9 dB of true sensitivity, depending on response errors. In damaged locations, mean absolute error was 0.5 to 1.8 dB lower, SD of threshold estimates was 1.2 to 1.5 dB lower, and 2 to 4 (29%–41%) fewer presentations were made for SZEST. Gains were smaller across whole visual fields (SZEST, mean absolute error: 0.5 to 1.2 dB lower, threshold estimate SD: 0.3 to 0.8 dB lower, 1 [17%] fewer presentation). The 90% retest limits of SZEST were median 1 to 3 dB narrower and more consistent (interquartile range 2–8 dB narrower) across the dynamic range than those for FT. Seeding Bayesian perimetric procedures with structural measurements can reduce test variability of perimetry in glaucoma, despite imprecise structural predictions of threshold. Structural data can reduce the variability of current perimetric techniques. A strong structure–function relationship is not necessary, however, structure must predict function within ±9 dB for gains to be realized.
    • Visual Contrast Detection Cannot Be Predicted From Surrogate Measures of Retinal Ganglion Cell Number and Sampling Density in Healthy Young Adults

      Denniss, Jonathan; Turpin, A.; McKendrick, A.M. (2014-12)
      Purpose.: To establish whether a clinically exploitable relationship exists between surrogate measures of retinal ganglion cell number and functional sampling density and visual contrast sensitivity in healthy young eyes. Methods.: Psychometric functions for contrast detection were measured at 9° eccentricity in superior and inferior visual field from 20 healthy adults (age 23–43, median 26 years). Functions were compared with corresponding localized regions of retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography, a surrogate of retinal ganglion cell number, and to grating resolution acuity, a psychophysical surrogate of retinal ganglion cell sampling density. Correlations between psychometric function parameters and retinal ganglion cell surrogates were measured by Spearman's rank correlation. Results.: All measures exhibited a 2- to 4-fold variation in our sample. Despite this, correlations between measures were weak. Correlations between psychometric function parameters (threshold, spread) and RNFL thickness ranged in magnitude from 0.05 to 0.19 (P = 0.43–0.85). Grating resolution was sampling limited for 16 of 20 participants in superior visual field, and for 12 of 20 participants in inferior visual field. Correlations between psychometric function parameters and grating resolution acuities ranged in magnitude from 0.05 to 0.36 (P = 0.12–0.85) when all data were considered, and from 0.06 to 0.36 (P = 0.26–0.87) when only sampling-limited data were considered. Conclusions.: Despite considerable variation in both psychometric functions for contrast detection and surrogate measures of retinal ganglion cell number and sampling density among healthy eyes, relationships between these measures are weak. These relationships are unlikely to be exploitable for improving clinical tests in healthy populations.