Optometry and Vision Sciences - Research Publications
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ItemShort-Term Changes in the Photopic Negative Response Following Intraocular Pressure Lowering in Glaucoma(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2020-08)PURPOSE: To evaluate the short-term changes in inner retinal function using the photopic negative response (PhNR) after intraocular pressure (IOP) reduction in glaucoma. METHODS: Forty-seven participants with glaucoma who were commencing a new or additional IOP-lowering therapy (treatment group) and 39 participants with stable glaucoma (control group) were recruited. IOP, visual field, retinal nerve fiber layer thickness, and electroretinograms (ERGs) were recorded at baseline and at a follow-up visit (3 ± 2 months). An optimized protocol developed for a portable ERG device was used to record the PhNR. The PhNR saturated amplitude (Vmax), Vmax ratio, semi-saturation constant (K), and slope of the Naka-Rushton function were analyzed. RESULTS: A significant percentage reduction in IOP was observed in the treatment group (28 ± 3%) compared to the control group (2 ± 3%; P < 0.0001). For PhNR Vmax, there was no significant interaction (F1,83 = 2.099, P = 0.15), but there was a significant difference between the two time points (F1,83 = 5.689, P = 0.019). Post hoc analysis showed a significant difference between baseline and 3 months in the treatment group (mean difference, 1.23 µV; 95% confidence interval [CI], 0.24-2.22) but not in the control group (0.30 µV; 95% CI, 0.78-1.38). K and slope were not significantly different in either group. Improvement beyond test-retest variability was seen in 17% of participants in the treatment group compared to 3% in the control group (P = 0.007, χ2 test). CONCLUSIONS: The optimized protocol for measuring the PhNR detected short-term improvements in a proportion of participants following IOP reduction, although the majority showed no change.
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ItemImprovement in inner retinal function in glaucoma with nicotinamide (vitaminB3) supplementation: A crossover randomized clinical trial(WILEY, 2020-09)IMPORTANCE: Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+ , is low in serum of glaucoma patients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in human glaucoma is unknown. BACKGROUND: To examine the effects of nicotinamide on inner retinal function in glaucoma, in participants receiving concurrent glaucoma therapy. DESIGN: Crossover, double-masked, randomized clinical trial. Participants recruited from two tertiary care centres. PARTICIPANTS: Fifty-seven participants, diagnosed and treated for glaucoma. METHODS: Participants received oral placebo or nicotinamide and reviewed six-weekly. Participants commenced 6 weeks of 1.5 g/day then 6 weeks of 3.0 g/day followed by crossover without washout. Visual function measured using electroretinography and perimetry. MAIN OUTCOME MEASURES: Change in inner retinal function, determined by photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). RESULTS: PhNR Vmax improved beyond 95% coefficient of repeatability in 23% of participants following nicotinamide vs 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (P = .02) on nicotinamide and 5.2% [-4.2%, 14.6%], (P = .27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (P = .002) following nicotinamide, 3.6% [-3.4%, 10.5%], (P = .30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1 dB on nicotinamide and fewer deteriorating (4%) compared to placebo (P = .02). CONCLUSIONS: Nicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long-term nicotinamide supplementation.
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ItemBaseline Detrending for the Photopic Negative Response(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-09)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.
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ItemA Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-12)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.
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ItemOptimizing a Portable ERG Device for Glaucoma Clinic: The Effect of Interstimulus Frequency on the Photopic Negative Response(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-12)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.