Chancellery Research - Research Publications

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    Optic nerve tissue displacement during mild intraocular pressure elevation: its relationship to central corneal thickness and corneal hysteresis
    Bedggood, P ; Tanabe, F ; McKendrick, AM ; Turpin, A ; Anderson, AJ ; Bui, BV (WILEY, 2018-07-01)
    PURPOSE: To determine the extent to which (1) optic nerve tissue is displaced following mild acute elevation of intraocular pressure, and (2) clinically accessible measures at the anterior eye can be used as a surrogate for such displacements. METHODS: We imaged the optic disc of 21 healthy subjects before and after intraocular pressure (IOP) elevation of ~10 mmHg delivered by ophthalmodynamometry. Steady-state tissue displacement during IOP elevation was assessed axially from OCT data, and laterally from SLO data. Recovery from IOP elevation was assessed by tracking a single vertical B-scan through the cup centre. Anatomical structures were demarcated by three masked clinicians to determine lateral shifts for temporal cup edge and central disc vessels, and axial shifts of disc surface and anterior lamina cribrosa. Spatial maps of deformation were constructed within the demarcated cup and disc to assess within-tissue displacement. Measured displacements were correlated with corneal hysteresis, corneal thickness, and IOP. RESULTS: The temporal cup edge moved more temporally with higher baseline IOP (R2  = 0.33, p = 0.006) and with lesser elevation of IOP (R2  = 0.43, p = 0.001); it moved more superiorly for thinner corneas (R2  = 0.35, p = 0.007). Thinner corneas also produced less within-cup deformation, relative to that of the disc (R2  = 0.39, p = 0.004). Axial displacement of the lamina and lateral displacement of vessels were often substantial (lamina 20 ± 15 μm, range 1-60 μm; vessels 37 ± 25 μm, range 2-102 μm) but did not correlate with measured parameters. Recovery from IOP elevation did not take more than 300-400 ms in any subject. CONCLUSIONS: Mild acute elevation of IOP produces large and rapidly reversible shifts in optic nerve tissue in young, healthy eyes. The resulting degree, direction and spatial distribution of cup movement are associated with IOP status and corneal thickness, but not corneal hysteresis.
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    The association between retinal vein pulsation pressure and optic disc haemorrhages in glaucoma
    An, D ; House, P ; Barry, C ; Turpin, A ; McKendrick, AM ; Chauhan, BC ; Manners, S ; Graham, SL ; Yu, D-Y ; Morgan, WH ; Bhattacharya, S (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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    Improving Spatial Resolution and Test Times of Visual Field Testing Using ARREST
    Turpin, A ; Morgan, WH ; Mckendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-09-01)
    PURPOSE: Correctly classifying progression in moderate to advanced glaucoma is difficult. Pointwise visual field test-retest variability is high for sensitivities below approximately 20 dB; hence, reliably detecting progression requires many test repeats. We developed a testing approach that does not attempt to threshold accurately in areas with high variability, but instead expends presentations increasing spatial fidelity. METHODS: Our visual field procedure Australian Reduced Range Extended Spatial Test (ARREST; a variant of the Bayesian procedure Zippy Estimation by Sequential Testing [ZEST]) applies the following approach: once a location has an estimated sensitivity of <17 dB (a "defect"), it is checked that it is not an absolute defect (<0 dB, "blind"). Saved presentations are used to test extra locations that are located near the defect. Visual field deterioration events are either: (1) decreasing in the range of 40 to 17 dB, (2) decreasing from >17 dB to "defect", or (3) "defect" to blind. To test this approach we used an empirical database of progressing moderate-advanced 24-2 visual fields (121 eyes) that we "reverse engineered" to create visual field series that progressed from normal to the end observed field. ARREST and ZEST were run on these fields with test accuracy, presentation time, and ability to detect progression compared. RESULTS: With specificity for detecting progression matched at 95%, ZEST and ARREST showed similar sensitivity for detecting progression. However, ARREST used approximately 25% to 40% fewer test presentations to achieve this result in advanced visual field damage. ARREST spatially defined the visual field deficit with greater precision than ZEST due to the addition of non-24-2 locations. CONCLUSIONS: Spending time trying to accurately measure visual field locations that have high variability is not productive. Our simulations indicate that giving up attempting to quantify size III white-on-white sensitivities below 17 dB and using the presentations saved to test extra locations should better describe progression in moderate-to-advanced glaucoma in shorter time. TRANSLATIONAL RELEVANCE: ARREST is a new visual field test algorithm that provides better spatial definition of visual field defects in faster test time than current procedures. This outcome is achieved by substituting inaccurate quantification of sensitivities <17 dB with new spatial locations.
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    Data obtained with an open-source static automated perimetry test of the full visual field in healthy adults
    Marin-Franch, I ; Artes, PH ; Chong, LX ; Turpin, A ; Wall, M (ELSEVIER SCIENCE BV, 2018-12-01)
    The data were gathered from 98 eyes of 98 ocular healthy subjects. The subject ages ranged from 18 to 79 years with a mean (and standard deviation) of 47 (17) years. Each subject underwent two visual field tests, one of the central visual field (64 locations within 26° of fixation) and one of the peripheral visual field (64 locations with eccentricity from 26° to up to 81°). Luminance thresholds for the Goldmann size V stimulus (with a diameter of 1.72° of visual angle) were obtained with the ZEST Bayesian test procedure. Each test was conducted twice within 90 days.
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    Robot Assistants for Perimetry: A Study of Patient Experience and Performance
    McKendrick, AM ; Zeman, A ; Liu, P ; Aktepe, D ; Aden, I ; Bhagat, D ; Do, K ; Nguyen, HD ; Turpin, A (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019-06-01)
    PURPOSE: People enjoy supervision during visual field assessment, although resource demands often make this difficult. We evaluated outcomes and subjective experience of methods of receiving feedback during perimetry, with specific goals to compare a humanoid robot to a computerized voice in participants with minimal prior perimetric experience. Human feedback and no feedback also were compared. METHODS: Twenty-two younger (aged 21-31 years) and 18 older (aged 52-76 years) adults participated. Visual field tests were conducted using an Octopus 900, controlled with the Open Perimetry Interface. Participants underwent four tests with the following feedback conditions: (1) human, (2) humanoid robot, (3) computer speaker, and (4) no feedback, in random order. Feedback rules for the speaker and robot were identical, with the difference being a social interaction with the robot before the test. Quantitative perimetric performance compared mean sensitivity (dB), fixation losses, and false-positives. Subjective experience was collected via survey. RESULTS: There was no significant effect of feedback type on the quantitative measures. For younger adults, the human and robot were preferred to the computer speaker (P < 0.01). For older adults, the experience rating was similar for the speaker and robot. No feedback was the least preferred option of 77% younger and 50% older adults. CONCLUSIONS: During perimetry, a social robot was preferred to a computer speaker providing the same feedback, despite the robot not being visible during the test. Making visual field testing more enjoyable for patients and operators may improve compliance and attitude to perimetry, leading to improved clinical outcomes. TRANSLATIONAL RELEVANCE: Our data suggest that humanoid robots can replace some aspects of human interaction during perimetry and are preferable to receiving no human feedback.
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    Home Monitoring of Retinal Sensitivity on a Tablet Device in Intermediate Age-Related Macular Degeneration
    Adams, M ; Ho, CYD ; Baglin, E ; Sharangan, P ; Wu, Z ; Lawson, DJ ; Luu, CD ; Turpin, A ; McKendrick, AM ; Guymer, RH (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-09-01)
    PURPOSE: We determine the feasibility of using a home-based tablet device to monitor retinal sensitivity (RS) in intermediate age-related macular degeneration (iAMD), the benefits of weekly reminders, and the comparison with clinic-based results. METHODS: A customized test for tablets was designed to measure RS (within central 2°) in individuals with iAMD at weekly intervals in their home, with remote data collection. Half of the participants were randomized to receive weekly test reminders. Clinic-based microperimetric macular sensitivity results were compared to tablet results. Participation rates were analyzed at 2 months. RESULTS: Of 38 participants (mean age, 70.3 years) with iAMD enrolled in the study, 21 (55%) were using the tablet-based test at 2 months. Common reasons for inactivity were noncompatible devices (41.1%) or other technology access issues (35.3%). Participants with weekly reminders completed tests more regularly (6.6 ± 3.9 vs. 8.7 ± 4.1 days, P = 0.01), but weekly reminders showed no effect on participation rates (P = 0.69). Mean RS from the tablet device (25.03 ± 2.41 dB) was not significantly different from the clinic-based microperimetry performance (25.21 ± 2.20 dB; P = 0.58). CONCLUSIONS: Regular monitoring of retinal function on a tablet device in a home setting in individuals with iAMD is feasible with results comparable to those of clinic-based microperimetry. Weekly reminders resulted in more frequent testing. Seamless ability to access technology will be important for higher participation rates. TRANSLATIONAL RELEVANCE: The use of home-monitoring on a tablet-device is promising, but adequate support for an older cohort to take up technology is required if such a tool is to be useful for long-term home monitoring.
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    Orientation of the Temporal Nerve Fiber Raphe in Healthy and in Glaucomatous Eyes
    Bedggood, P ; Nguyen, B ; Lakkis, G ; Turpin, A ; McKendrick, AM (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017-08-01)
    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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    Daily vision testing can expose the prodromal phase of migraine
    McKendrick, AM ; Chan, YM ; Vingrys, AJ ; Turpin, A ; Badcock, DR (SAGE PUBLICATIONS LTD, 2018-08-01)
    Background Several visual tasks have been proposed as indirect assays of the balance between cortical inhibition and excitation in migraine. This study aimed to determine whether daily measurement of performance on such tasks can reveal perceptual changes in the build up to migraine events. Methods Visual performance was measured daily at home in 16 non-headache controls and 18 individuals with migraine using a testing protocol on a portable tablet device. Observers performed two tasks: luminance increment detection in spatial luminance noise and centre surround contrast suppression. Results Luminance thresholds were reduced in migraine compared to control groups ( p < 0.05), but thresholds did not alter across the migraine cycle; while headache-free, centre-surround contrast suppression was stronger for the migraine group relative to controls ( p < 0.05). Surround suppression weakened at around 48 hours prior to a migraine attack and strengthened to approach their headache-free levels by 24 hours post-migraine (main effect of timing, p < 0.05). Conclusions Daily portable testing of vision enabled insight into perceptual performance in the lead up to migraine events, a time point that is typically difficult to capture experimentally. Perceptual surround suppression of contrast fluctuates during the migraine cycle, supporting the utility of this measure as an indirect, non-invasive assay of the balance between cortical inhibition and excitation.
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    A Tablet-Based Retinal Function Test in Neovascular Age-Related Macular Degeneration Eyes and At-Risk Fellow Eye
    Ho, CYD ; Wu, Z ; Turpin, A ; Lawson, DJ ; Luu, CD ; McKendrick, AM ; Guymer, RH (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-03-01)
    PURPOSE: To determine the feasibility of a tablet-based application to detect changes in retinal sensitivity and correlations with underlying pathology in neovascular age-related macular degeneration (nAMD) eyes undergoing treatment and in at-risk fellow eyes. METHOD: Participants with nAMD in at least one eye were recruited, examined, and imaged using spectral-domain optical coherence tomography (SD-OCT). Retinal sensitivity was measured within the central 5° at 12 locations using a customized test delivered on an iPad. Test points were superimposed on SD-OCT locations to investigate structure/function relationships. RESULTS: Included in the study were 53 nAMD eyes and 21 at-risk fellow eyes. In nAMD eyes, the mean retinal sensitivity was 24.1 ± 1.8 dB with reduced retinal sensitivity associated with the presence of atrophy (P < 0.01), retinal pigment epithelium (RPE) disruption (P < 0.01), and absent ellipsoid zone (EZ) (P < 0.01), but not with the presence of subretinal fluid (P = 0.94) nor intraretinal fluid (P = 0.52). In at-risk eyes, the average retinal sensitivity was 28.8 ± 0.6 dB, with reduced sensitivity significantly associated with the presence of drusen, atrophy, RPE disruption, and absent EZ (P < 0.01). CONCLUSION: The tablet-based test of retinal sensitivity was able to be performed by an elderly cohort with nAMD. The ability to correlate differences in sensitivity with pathology is encouraging when considering using the tablet devices as a home monitoring tool with remote surveillance. Dual pathology often present with retinal fluid confounded our ability to correlate fluid with sensitivity. TRANSLATIONAL RELEVANCE: These findings highlight the potential of tablet-based devices in performing visual function measures as a home monitoring tool with remote surveillance for the earlier detection of nAMD.
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    The Proportion of Individuals Likely to Benefit from Customized Optic Nerve Head Structure-Function Mapping
    McKendrick, AM ; Denniss, J ; Wang, YX ; Jonas, JB ; Turpin, A (ELSEVIER SCIENCE INC, 2017-04-01)
    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.