Chancellery Research - Research Publications
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ItemThe association between retinal vein pulsation pressure and optic disc haemorrhages in glaucoma(PUBLIC LIBRARY SCIENCE, 2017-07-28)PURPOSE: To explore the potential relationship between optic disc haemorrhage, venous pulsation pressure (VPP), ocular perfusion pressures and visual field change in glaucomatous and glaucoma suspect eyes. MATERIALS AND METHODS: This prospective observational study examined 155 open angle glaucoma or glaucoma suspect eyes from 78 patients over 5 years. Patients were followed with 3 monthly non-mydriatic disc photographs, 6 monthly standard automated perimetry and annual ophthalmodynamometry. The number of disc haemorrhages in each hemidisc was counted across the study period. Visual field rate of change was calculated using linear regression on the sensitivity of each location over time, then averaged for the matching hemifield. VPP and central retinal artery diastolic pressure (CRADP) were calculated from the measured ophthalmodynanometric forces (ODF). The difference between brachial artery diastolic pressure (DiastBP) and CRADP was calculated as an index of possible flow pathology along the carotid and ophthalmic arteries. RESULTS: Mean age of the cohort was 71.9 ± 7.3 Years. 76 out of 155 eyes (49%) followed for a mean period of 64.2 months had at least 1 disc haemorrhage. 62 (81.6%) of these 76 eyes had recurrent haemorrhages, with a mean of 5.94 recurrences over 64.2 months. Using univariate analysis, rate of visual field change (P<0.0001), VPP (P = 0.0069), alternative ocular perfusion pressure (CRADP-VPP, P = 0.0036), carotid resistance index (DiastBP-CRADP, P = 0.0108) and mean brachial blood pressure (P = 0.0203) were significantly associated with the number of disc haemorrhages. Using multivariate analysis, increased baseline visual field sensitivity (P = 0.0243, coefficient = 0.0275) was significantly associated with disc haemorrhage, in conjunction with higher VPP (P = 0.0029, coefficient = 0.0631), higher mean blood pressure (P = 0.0113, coefficient = 0.0190), higher carotid resistance index (P = 0.0172, coefficient = 0.0566), and rate of visual field loss (P<0.0001, coefficient = -2.0695). CONCLUSIONS: Higher VPP was associated with disc haemorrhage and implicates the involvement of venous pathology, but the effect size is small. Additionally, a greater carotid resistance index suggests that flow pathology in the ophthalmic or carotid arteries may be associated with disc haemorrhage.
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ItemOrientation of the Temporal Nerve Fiber Raphe in Healthy and in Glaucomatous Eyes(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017-08)PURPOSE: To determine the normal variation in orientation of the temporal nerve fiber raphe, and the accuracy with which it may be predicted or approximated in lieu of direct measurement. METHODS: We previously described an algorithm for automatic measurement of raphe orientation from optical coherence tomography, using the intensity of vertically oriented macular cubes. Here this method was applied in 49 healthy participants (age 19-81 years) and 51 participants with primary open angle glaucoma (age 51-80 years). RESULTS: Mean fovea-disc-raphe angle was 173.5° ± 3.2° (range = 166°-182°) and 174.2° ± 3.4° (range = 166°-184°) in healthy and glaucoma patients, respectively. Differences between groups were not significant. Fovea-disc-raphe angle was not correlated with age or axial length (P > 0.4), showed some symmetry between eyes in glaucoma (R2 = 0.31, P < 0.001), and little symmetry in the healthy group (P = 0.06). Fovea-disc angle was correlated with fovea-raphe angle (R2 = 0.27, P = 0.0001), but was not a good predictor for raphe orientation (average error = 6.8°). The horizontal axis was a better predictor (average error = 3.2°; maximum error = 9.6°), but still gave approximately twice the error previously reported for direct measurement from macular cubes. CONCLUSIONS: There is substantial natural variation in temporal nerve fiber raphe orientation, which cannot be predicted from age, axial length, relative geometry of the disc and fovea, or the contralateral eye. For applications to which the orientation of the raphe is considered important, it should be measured directly.
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ItemThe Proportion of Individuals Likely to Benefit from Customized Optic Nerve Head Structure-Function Mapping(ELSEVIER SCIENCE INC, 2017-04)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.
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ItemDo Intense Perimetric Stimuli Saturate the Healthy Visual System?(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-11)PURPOSE: A recent proposal for why glaucomatous perimetric sensitivities of approximately 15 to 19 dB or less are unreliable involves the idea that the neural response of normal retinal ganglion cells saturates for intense perimetric stimuli. A predicted consequence of this saturation is that the neural response for two different high intensity stimuli will be the same, leading to an inability to discriminate between them. We test that prediction. METHODS: We used a two-interval forced-choice method of constant stimuli (7 steps, 40 presentations/step) to measure the ability of four healthy observers to discriminate between different intensity Size III perimetric stimuli at 0°, 9°, and 21° eccentricity. The lower intensity stimulus for each discrimination was either 27, 23, 19, 15, or 11 dB (Humphrey Field Analyzer equivalents). RESULTS: Foveally, discrimination performance exceeded 90% for all observers provided the more intense stimulus was made sufficiently intense, even if the lower intensity stimulus in the pair was itself already intense (≤19 dB). The shapes of the curves were similar across all lower intensity stimulus values investigated. At 21°, discrimination performance exceeded 90% in three of the four observers despite the lower intensity stimulus being 19 dB. CONCLUSIONS: Observers can reliably discriminate between two different, but both very intense, perimetric stimuli, indicating that responses of the human visual system are not saturated by such stimuli. Therefore, the cause of high perimetric test-retest variability is not readily predicted from our current knowledge of how normal ganglion cells respond to high intensity stimuli.
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ItemIndividual Differences in Foveal Shape: Feasibility of Individual Maps Between Structure and Function Within the Macular Region(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-09)PURPOSE: Recently in glaucoma, different mapping schemes to combine structural and functional information within the macula have been proposed. This paper aims to investigate whether the changes in foveal shape parameters are important in the mapping between structure and function within the macular region. METHODS: Twenty younger adults (aged 24- to 33-years old) and 10 older adults (aged 62- to 76-years old) participated. On each subject, four foveally-centered radial spectral-domain optical coherence tomography (SD-OCT) scans with 45° of separation between each scan were acquired. After scan acquisition, foveal shape was extracted by fitting a previously proposed model that has been used to customize structure-function mapping in the macular region. Three parameters were obtained from the scans and then compared: the central thickness, the maximum thickness, and the radius. RESULTS: There were significant differences in the foveal shape parameters between subjects. There was no main effect of the scan axis for the central thickness; however, there was an interaction between the scan axis and maximum thickness and between the scan axis and radius. With respect to the effect of age, we did not find a main effect for the central thickness, the maximum thickness or the radius, although this parameter approached statistical significance. CONCLUSIONS: In our study, we demonstrated that the foveal shape is different for different subjects, but predictable superiorly and inferiorly within an individual. Our study highlights features important for the development of individually customized structure-function maps for the investigation of glaucomatous damage in the macular region.
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ItemAutomatic identification of the temporal retinal nerve fiber raphe from macular cube data(OPTICAL SOC AMER, 2016-10-01)We evaluated several approaches for automatic location of the temporal nerve fiber raphe from standard macular cubes acquired on a Heidelberg Spectralis OCT. Macular cubes with B-scan separation of 96-122 µm were acquired from 15 healthy participants, and "high density" cubes with scan separation of 11 µm were acquired from the same eyes. These latter scans were assigned to experienced graders for subjective location of the raphe, providing the ground truth by which to compare methods operating on the lower density data. A variety of OCT scan parameters and image processing strategies were trialed. Vertically oriented scans, purposeful misalignment of the pupil to avoid reflective artifacts, and the use of intensity as opposed to thickness of the nerve fiber layer were all critical to minimize error. The best performing approach "cFan" involved projection of a fan of lines from each of several locations across the foveal pit; in each fan the line of least average intensity was identified. The centroid of the crossing points of these lines provided the raphe orientation with an average error of 1.5° (max = 4.1°) relative to the human graders. The disc-fovea-raphe angle was 172.4 ± 2.3° (range = 168.5-176.2°), which agrees well with other published estimates.
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ItemAssessing the GOANNA Visual Field Algorithm Using Artificial Scotoma Generation on Human Observers(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-09)PURPOSE: To validate the performance of a new perimetric algorithm (Gradient-Oriented Automated Natural Neighbor Approach; GOANNA) in humans using a novel combination of computer simulation and human testing, which we call Artificial Scotoma Generation (ASG). METHODS: Fifteen healthy observers were recruited. Baseline conventional automated perimetry was performed on the Octopus 900. Visual field sensitivity was measured using two different procedures: GOANNA and Zippy Estimation by Sequential Testing (ZEST). Four different scotoma types were induced in each observer by implementing a novel technique that inserts a step between the algorithm and the perimeter, which in turn alters presentation levels to simulate scotomata in human observers. Accuracy, precision, and unique number of locations tested were measured, with the maximum difference between a location and its neighbors (Max_d) used to stratify results. RESULTS: GOANNA sampled significantly more locations than ZEST (paired t-test, P < 0.001), while maintaining comparable test times. Difference plots showed that GOANNA displayed greater accuracy than ZEST when Max_d was in the 10 to 30 dB range (with the exception of Max_d = 20 dB; Wilcoxon, P < 0.001). Similarly, GOANNA demonstrated greater precision than ZEST when Max_d was in the 20 to 30 dB range (Wilcoxon, P < 0.001). CONCLUSIONS: We have introduced a novel method for assessing accuracy of perimetric algorithms in human observers. Results observed in the current study agreed with the results seen in earlier simulation studies, and thus provide support for performing larger scale clinical trials with GOANNA in the future. TRANSLATIONAL RELEVANCE: The GOANNA perimetric testing algorithm offers a new paradigm for visual field testing where locations for testing are chosen that target scotoma borders. Further, the ASG methodology used in this paper to assess GOANNA shows promise as a hybrid between computer simulation and patient testing, which may allow more rapid development of new perimetric approaches.
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ItemIncorporating Spatial Models in Visual Field Test Procedures(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-03)PURPOSE: To introduce a perimetric algorithm (Spatially Weighted Likelihoods in Zippy Estimation by Sequential Testing [ZEST] [SWeLZ]) that uses spatial information on every presentation to alter visual field (VF) estimates, to reduce test times without affecting output precision and accuracy. METHODS: SWeLZ is a maximum likelihood Bayesian procedure, which updates probability mass functions at VF locations using a spatial model. Spatial models were created from empirical data, computational models, nearest neighbor, random relationships, and interconnecting all locations. SWeLZ was compared to an implementation of the ZEST algorithm for perimetry using computer simulations on 163 glaucomatous and 233 normal VFs (Humphrey Field Analyzer 24-2). Output measures included number of presentations and visual sensitivity estimates. RESULTS: There was no significant difference in accuracy or precision of SWeLZ for the different spatial models relative to ZEST, either when collated across whole fields or when split by input sensitivity. Inspection of VF maps showed that SWeLZ was able to detect localized VF loss. SWeLZ was faster than ZEST for normal VFs: median number of presentations reduced by 20% to 38%. The number of presentations was equivalent for SWeLZ and ZEST when simulated on glaucomatous VFs. CONCLUSIONS: SWeLZ has the potential to reduce VF test times in people with normal VFs, without detriment to output precision and accuracy in glaucomatous VFs. TRANSLATIONAL RELEVANCE: SWeLZ is a novel perimetric algorithm. Simulations show that SWeLZ can reduce the number of test presentations for people with normal VFs. Since many patients have normal fields, this has the potential for significant time savings in clinical settings.
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ItemDevelopment of Visual Field Screening Procedures: A Case Study of the Octopus Perimeter(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-05)PURPOSE: We develop a methodology for designing perimetric screening procedures, using Octopus perimeters as a case study. METHODS: The process has three stages: analytically determining specificity and number of presentations required for different multisampling suprathreshold schemes at a single location of the visual field, ranking visual field locations by their positive predictive value (PPV) for glaucoma, and determining a pass/fail criteria for the test. For the case study the Octopus G-program visual field test pattern is used, and a dataset of 385 glaucoma and 86 normal patients. RESULTS: Using a 1-of-3 sampling strategy at a level equal to the 95 percentile of normal observers gave the most robust specificity under the influences of false-negative responses using an average of 1.5 presentations per location. The PPV analysis gave 19 locations that completely classified our glaucomatous data. A further 9 points were added to screen for nonglaucomatous loss. The final stage found that insisting that 3 locations are missed for the screening to fail gave a simulated specificity and sensitivity of approximately 95% for unreliable responders. CONCLUSIONS: Our method gives a principled approach to choosing between the many parameters of a visual field screening procedure. We have developed a procedure for the Octopus that should terminate in less than 1 minute for normal observers with high specificity and sensitivity to glaucoma. TRANSLATIONAL RELEVANCE: Visual field screening is used in community settings and eye care practice. This study provides a principled approach to the development of such screening procedures and details a new procedure.
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ItemEnhancing Structure-Function Correlations in Glaucoma with Customized Spatial Mapping(Elsevier Inc., 2015-01-20)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.