Jonathan Denniss

Enhanced Structure–Function Relationship in Glaucoma With an Anatomically and Geometrically Accurate Neuroretinal Rim Measurement

PURPOSE To evaluate the structure-function relationship between disc margin-based rim area (DM-RA) obtained with confocal scanning laser tomography (CSLT), Bruchs 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 (VF(GH)) and patient-specific (VF(PS)) maps customized for various biometric parameters. RESULTS Globally and sectorally, the structure-function relationships between DM-RA and VF(GH), BMO-HRW(AIF) and VF(GH), and BMO-HRW(FoBMO) and VF(PS) were equally weak. The R(2) for the relationship between DM-RA and VF(GH) ranged from 0.1% (inferonasal) to 11% (superotemporal) whereas that between BMO-HRW(AIF) and VF(GH) ranged from 0.1% (nasal) to 10% (superotemporal). Relatively stronger global and sectoral structure-function relationships with BMO-MRW(AIF) and with BMO-MRW(FoBMO) were obtained. The R(2) between BMO-MRW(AIF) and VF(GH) ranged from 5% (nasal) to 30% (superotemporal), whereas that between BMO-MRW(FoBMO) and VF(PS) 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.

An anatomically customizable computational model relating the visual field to the optic nerve head in individual eyes.

PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Spatial and Spectral Imaging of Retinal Laser Photocoagulation Burns

PURPOSE To correlate in vivo spatial and spectral morphologic changes of short- to long-pulse 532 nm Nd:YAG retinal laser lesions using Fourier-domain optical coherence tomography (FD OCT), autofluorescence (AF), fluorescein angiography (FA), and multispectral imaging. METHODS Ten eyes with treatment-naive preproliferative or proliferative diabetic retinopathy were studied. A titration grid of laser burns at 20, 100, and 200 milliseconds was applied to the nasal retina and laser fluence titrated to produce four grades of laser lesion visibility: subvisible (SV), barely visible (BV, light-gray), threshold (TH, gray-white), and suprathreshold (ST, white). The AF, FA, FD-OCT, and multispectral imaging were performed 1 week before laser, and 1 hour, 4 weeks, and 3 and 6 months post-laser. Multispectral imaging measured relative tissue oxygen concentration. RESULTS Laser burn visibility and lesion size increased in a linear relationship according to fixed fluence levels. At fixed pulse durations, there was a semilogarithmic increase in lesion size over 6 months. At 20 milliseconds, all grades of laser lesion were reduced significantly in size after 6 months: SV, 51%; BV, 54%; TH, 49%; and ST, 50% (P < 0.001), with retinal pigment epithelial proliferation and photoreceptor infilling. At 20 milliseconds, there was healing of photoreceptor inner segment/outer segment junction layers compared with 100- and 200-millisecond lesions. Significant increases in mean tissue oxygenation (range, four to six units) within the laser titration area and in oxygen concentration across the laser lesions (P < 0.01) were detected at 6 months. CONCLUSIONS For patients undergoing therapeutic laser, there may be improved tissue oxygenation, higher predictability of burn morphology, and more spatial localization of healing responses of burns at 20 milliseconds compared with longer pulse durations over time.

Structure-Function Mapping: Variability and Conviction in Tracing Retinal Nerve Fiber Bundles and Comparison to a Computational Model

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.

High-resolution hyperspectral imaging of the retina with a modified fundus camera

PURPOSE to examine the practical feasibility of developing a hyperspectral camera from a Zeiss fundus camera and to illustrate its use in imaging diabetic retinopathy and glaucoma patients. METHODS the original light source of the camera was replaced with an external lamp filtered by a fast tunable liquid-crystal filter. The filtered light was then brought into the camera through an optical fiber. The original film camera was replaced by a digital camera. Images were obtained in normals and patients (primary open angle glaucoma, diabetic retinopathy) recruited at the Manchester Royal Eye Hospital. RESULTS a series of eight images were captured across 495- to 720-nm wavelengths, and recording time was less than 1.6s. The light level at the cornea was below the ANSI limits, and patients judged the measurement to be very comfortable. Images were of high quality and were used to generate a pixel-to-pixel oxygenation map of the optic nerve head. Frame alignment is necessary for frame-to-frame comparison but can be achieved through simple methods. CONCLUSIONS we have developed a hyperspectral camera with high spatial and spectral resolution across the whole visible spectrum that can be adapted from a standard fundus camera. The hyperspectral technique allows wavelength-specific visualization of retinal lesions that may be subvisible using a white light source camera. This hyperspectral technique may facilitate localization of retinal and disc pathology and consequently facilitate the diagnosis and management of retinal disease.

Individualized Structure–Function Mapping for Glaucoma: Practical Constraints on Map Resolution for Clinical and Research Applications

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 (Spearmanss 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.

Relationships between visual field sensitivity and spectral absorption properties of the neuroretinal rim in glaucoma by multispectral imaging.

PURPOSE To investigate the relationship between neuroretinal rim (NRR) differential light absorption (DLA, a measure of spectral absorption properties) and visual field (VF) sensitivity in primary open-angle glaucoma (POAG). METHODS Patients diagnosed with (n = 22) or suspected of having (n = 7) POAG were imaged with a multispectral system incorporating a modified digital fundus camera, 250-W tungsten-halogen lamp, and fast-tuneable liquid crystal filter. Five images were captured sequentially within 1.0 second at wavelengths selected according to absorption properties of hemoglobin (range, 570-610 nm), and a Beer-Lambert law model was used to produce DLA maps of residual NRR from the images. Patients also underwent VF testing. Differences in NRR DLA in vertically opposing 180° and 45° sectors either side of the horizontal midline were compared with corresponding differences in VF sensitivity on both decibel and linear scales by Spearmans rank correlation. RESULTS The decibel VF sensitivity scale showed significant relationships between superior-inferior NRR DLA difference and sensitivity differences between corresponding VF areas in 180° NRR sectors (Spearman ρ = 0.68; P < 0.0001), superior-/inferior-temporal 45° NRR sectors (ρ = 0.57; P < 0.002), and superior-/inferior-nasal 45° NRR sectors (ρ = 0.59; P < 0.001). Using the linear VF sensitivity scale significant relationships were found for 180° NRR sectors (ρ = 0.62; P < 0.0002) and superior-inferior-nasal 45° NRR sectors (ρ = 0.53; P < 0.002). No significant difference was found between correlations using the linear or decibel VF sensitivity scales. CONCLUSIONS Residual NRR DLA is related to VF sensitivity in POAG. Multispectral imaging may provide clinically important information for the assessment and management of POAG.

Enhancing Structure–Function Correlations in Glaucoma with Customized Spatial Mapping

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.

Response times across the visual field: Empirical observations and application to threshold determination

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 participants 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.

Central Perimetric Sensitivity Estimates are Directly Influenced by the Fixation Target

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.