Ophthalmology (Eye & Ear Hospital) - Research Publications
Now showing items 1-12 of 167
Tablets at the bedside - iPad-based visual field test used in the diagnosis of Intrasellar Haemangiopericytoma: a case report
(BIOMED CENTRAL LTD, 2017-04-24)
BACKGROUND: In the assessment of a pituitary mass, objective visual field testing represents a valuable means of evaluating mass effect, and thus in deciding whether surgical management is warranted. CASE PRESENTATION: In this vignette, we describe a 73 year-old lady who presented with a three-week history of frontal headache, and 'blurriness' in the left side of her vision, due to a WHO grade III anaplastic haemangiopericytoma compressing the optic chiasm. We report how timely investigations, including an iPad-based visual field test (Melbourne Rapid Field, (MRF)) conducted at the bedside aided swift and appropriate management of the patient. CONCLUSIONS: We envisage such a test having a role in assessing bed-bound patients in hospital where access to formal visual field testing is difficult, or indeed in rapid testing of visual fields at the bedside to screen for post-operative complications, such as haematoma.
Visual Impairment as a Function of Visual Acuity in Both Eyes and Its Impact on Patient Reported Preferences
(PUBLIC LIBRARY SCIENCE, 2013-12-05)
PURPOSE: To assess the impact of VA loss on patient reported utilities taking both eyes into account compared to taking only the better or the worse eye into account. METHODS: In this cross-sectional study 1085 patients and 254 controls rated preferences with the generic health-related (EQ-5D; n = 868) and vision-specific (Vision and Quality of Life Index (VisQoL); n = 837) multi-attribute utility instruments (MAUIs). Utilities were calculated for three levels of VA in the better and worse eyes, as well as for 6 different vision states based on combinations of the better and worse eye VA. RESULTS: Using the VisQoL, utility scores decreased significantly with deteriorating vision in both the better and worse eyes when analysed separately. When stratified by the 6 vision states, VisQoL utilities decreased as VA declined in the worse eye despite stable VA in the better eye. Differences in VisQoL scores were statistically significant for cases where the better eye had no vision impairment and the worse seeing fellow eye had mild, moderate or severe vision impairment. In contrast, the EQ-5D failed to capture changes in better or worse eye VA, or any of the six vision states. CONCLUSIONS: Calculating utilities based only on better eye VA or using a generic MAUI is likely to underestimate the impact of vision impairment, particularly when the better eye has no or little VA loss and the worse eye is moderately to severely visually impaired. These findings have considerable implications for the assessment of overall visual impairment as well as economic evaluations within eye health.
Baseline Detrending for the Photopic Negative Response
(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-09-01)
Purpose: The photopic negative response (PhNR) of the light-adapted electroretinogram (ERG) holds promise as an objective marker of retinal ganglion cell function. We compared baseline detrending methods to improve PhNR repeatability without compromising its diagnostic ability in glaucoma. Methods: Photopic ERGs were recorded in 20 glaucoma and 18 age-matched control participants. A total of 50 brief, red-flashes (1.6 cd.s/m2) on a blue background (10 photopic cd/m2) were delivered using the RETeval device. Detrending methods compared were: (1) increasing the high-pass filter from 1 to 10 Hz and (2) estimating and removing the trend with an increasing polynomial (order from 1-10) applied to the prestimulus interval, prestimulus and postsignal interval, or the whole ERG signal. Coefficient of repeatability (COR%), unpaired Student's t-test, and area under the receiver operating characteristic curve (AUC) were used to compare the detrending methods. Results: Most detrending methods improved PhNR test-retest repeatability compared to the International Society for Clinical Electrophysiology of Vision (ISCEV) recommended 0.3 to 300 Hz band-pass filter (COR% ± 200%). In particular, detrending with a polynomial (order 3) applied to the whole signal performed the best (COR% ± 44%) while achieving similar diagnostic ability as ISCEV band-pass (AUC 0.74 vs. 0.75, respectively). However, over-correcting with higher orders of processing can cause waveform distortion and reduce diagnostic ability. Conclusions: Baseline detrending can improve the PhNR repeatability without compromising its clinical use in glaucoma. Further studies exploring more complex processing methods are encouraged. Translational Relevance: Baseline detrending can significantly improve the quality of the PhNR.
A Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response
(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-12-01)
Purpose: To compare the RETeval sensor strip and Dawson-Trick-Litzkow (DTL) electrodes for recording the photopic negative response (PhNR) using a portable electroretinogram (ERG) device in eyes with and without glaucoma. Methods: Twenty-six control and 31 glaucoma or glaucoma-suspect participants were recruited. Photopic ERGs were recorded with sensor strip and DTL electrodes in random order using the LKC RETeval device. Stimuli consisted of brief, red flashes (1.7 cd.s/m2) on a blue background (photopic 10 cd/m2). The PhNR amplitude was measured from baseline to trough and also expressed as a ratio over the b-wave amplitude. Results: The sensor strip-recorded PhNR amplitude was significantly attenuated (mean ± standard deviation [SD], 4.8 ± 2.1 vs. 12.7 ± 4.8 μV, P < 0.0001), with lower signal-to-noise ratio (SNR; 5.5 ± 2.1 vs. 8.1 ± 3.9, P < 0.0001), and a trend toward a larger PhNR/b-wave ratio compared with DTL electrodes. The PhNR amplitude, implicit time and PhNR/b-wave ratio correlated with visual field mean light sensitivity, although this fell short of significance for the sensor strip recorded PhNR amplitude. The electrodes demonstrated similar intersession repeatability with a coefficient of repeatability of ±27% and ±28% for the DTL and sensor strip, respectively. Conclusions: Sensor strip electrodes are a viable alternative for recording reproducible PhNRs, especially when values are normalized to the b-wave. However, DTL electrodes should be considered in cases of attenuated PhNR, or in elevated noise levels, due to its better signal-to-noise quality. Translational Relevance: Sensor strip electrodes can simplify PhNR recordings in the clinic, potentially eliminating the need for an experienced operator.
Optimizing a Portable ERG Device for Glaucoma Clinic: The Effect of Interstimulus Frequency on the Photopic Negative Response
(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-12-01)
Purpose: The purpose of this study was to investigate the effect of interstimulus frequency on the photopic negative response (PhNR) in the clinical electroretinogram (ERG) in glaucoma and healthy eyes. Methods: Participants with open angle glaucoma (n = 15) and age-matched controls (n = 20) were recruited. Photopic ERGs were recorded in one eye using five frequencies (1-5 Hz) delivered in random order. ERGs were analyzed for changes to amplitude and timing between groups and interstimulus frequency. Coefficient of variation (CoV) was used to examine variability within recordings for each frequency. Results: While the a-wave and b-wave showed minimal alteration, the PhNR was highly sensitive to changes in interstimulus frequency. The PhNR signal was largest at 1 Hz and steadily diminished with higher frequencies in both control and glaucoma groups. Significant differences in PhNR amplitude were found between controls and glaucoma groups at 2 and 3 Hz. While 1 Hz delivered the largest PhNR, it also showed a significantly greater CoV compared to other frequencies. Conclusions: An interstimulus frequency of 2 Hz was optimal for recording the PhNR, creating a good balance between testing time and signal quality. A higher frequency could be used to further shorten clinical testing times; however, this may compromise its clinical utility by dampening the PhNR. Translational Relevance: Here we show the importance of considering flash interstimulus frequency when designing ERG protocols for recording the PhNR as while higher frequencies can shorten test times, they also have considerable effects on the PhNR.
Photopic Negative Response Obtained Using a Handheld Electroretinogram Device: Determining the Optimal Measure and Repeatability
(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016-07-01)
PURPOSE: To determine the measure of the photopic negative response (PhNR) of the full-field electroretinogram (ERG) that exhibits the optimal level of test-retest repeatability, and examine its repeatability under different conditions using a handheld, nonmydriatic ERG system and self-adhering skin electrodes. METHODS: Multiple ERG recordings (using 200 sweeps each) were performed in both eyes of 20 normal participants at two different sessions to compare its coefficient of repeatability (CoR; where 95% of the test-retest difference is expected to lie) between different PhNR measures and under different testing conditions (within and between examiners, and between sessions). RESULTS: The ratio between the PhNR trough to b-wave peak and b-wave peak to a-wave trough amplitude (PhNR/B ratio) exhibited the lowest CoR relative to its effective dynamic range (30 ± 4%) when including three recordings. There were no significant changes in the PhNR/B ratio over seven measurements (4 right and 3 left eyes) at either session (P ≥ 0.100), or significant difference in its CoR between different testing conditions (P = 0.314). CONCLUSION: The PhNR/B ratio was the measure that minimized variability, and its measurements using a novel handheld ERG system with self-adhering skin electrodes and the protocols described in this study were comparable under different testing conditions and over multiple recordings. TRANSLATIONAL RELEVANCE: The PhNR can be measured for clinical and research purposes using a simple-to-implement technique that is consistent within and between visits, and also between examiners.
Non-invasive in vivo hyperspectral imaging of the retina for potential biomarker use in Alzheimer's disease
(NATURE PUBLISHING GROUP, 2019-09-17)
Studies of rodent models of Alzheimer's disease (AD) and of human tissues suggest that the retinal changes that occur in AD, including the accumulation of amyloid beta (Aβ), may serve as surrogate markers of brain Aβ levels. As Aβ has a wavelength-dependent effect on light scatter, we investigate the potential for in vivo retinal hyperspectral imaging to serve as a biomarker of brain Aβ. Significant differences in the retinal reflectance spectra are found between individuals with high Aβ burden on brain PET imaging and mild cognitive impairment (n = 15), and age-matched PET-negative controls (n = 20). Retinal imaging scores are correlated with brain Aβ loads. The findings are validated in an independent cohort, using a second hyperspectral camera. A similar spectral difference is found between control and 5xFAD transgenic mice that accumulate Aβ in the brain and retina. These findings indicate that retinal hyperspectral imaging may predict brain Aβ load.
Protecting retinal ganglion cells
(NATURE PUBLISHING GROUP, 2017-02-01)
Retinal ganglion cell degeneration underlies several conditions which give rise to significant visual compromise, including glaucoma, hereditary optic neuropathies, ischaemic optic neuropathies, and demyelinating disease. In this review, we discuss the emerging strategies for neuroprotection specifically in the context of glaucoma, including pharmacological neuroprotection, mesenchymal stem cells, and gene therapy approaches. We highlight potential pitfalls that need to be considered when developing these strategies and outline future directions, including the prospects for clinical trials.
Amyloid Precursor Protein Mediates Neuronal Protection from Rotenone Toxicity
Mitochondrial complex I dysfunction is the most common respiratory chain defect in human disorders and a hotspot for neurodegenerative diseases. Amyloid precursor protein (APP) and its non-amyloidogenic processing products, in particular soluble APP α (sAPPα), have been shown to provide neuroprotection in models of neuronal injury; however, APP-mediated protection from acute mitochondrial injury has not been previously reported. Here, we use the plant-derived pesticide rotenone, a potent complex I-specific mitochondrial inhibitor, to discover neuroprotective effects of APP and sAPPα in vitro, in neuronal cell lines over-expressing APP, and in vivo, in a retinal neuronal rotenone toxicity mouse model. Our results show that APP over-expression is protective against rotenone toxicity in neurons via sAPPα through an autocrine/paracrine mechanism that involves the Pi3K/Akt pro-survival pathway. APP-/- mice exhibit greater susceptibility to retinal rotenone toxicity, while intravitreal delivery of sAPPα reduces inner retinal neuronal death in wild-type mice following rotenone challenge. We also show a significant decrease in human retinal expression of APP with age. These findings provide insights into the therapeutic potential of non-amyloidogenic processing of APP in complex I-related neurodegeneration.
Home Monitoring of Retinal Sensitivity on a Tablet Device in Intermediate Age-Related Macular Degeneration
(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.
Progress in the clinical development and utilization of vision prostheses: an update
(DOVE MEDICAL PRESS LTD, 2016-01-01)
Vision prostheses, or "bionic eyes", are implantable medical bionic devices with the potential to restore rudimentary sight to people with profound vision loss or blindness. In the past two decades, this field has rapidly progressed, and there are now two commercially available retinal prostheses in the US and Europe, and a number of next-generation devices in development. This review provides an update on the development of these devices and a discussion on the future directions for the field.