Intensity response function of the photopic negative response (PhNR): effect of age and test–retest reliability

Joshi, Nabin; Ly, Emma; Viswanáthan, Suresh

doi:10.1007/s10633-017-9591-0

Cited by 20 publications

(11 citation statements)

References 60 publications

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“…While this may not be a problem if a single flash strength is used as in this study, it would lengthen the time of recording if several flash strengths are recorded as in a stimulus response function. 33,34…”

Section: Resultsmentioning

confidence: 99%

A Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response

Tang

Hui

Hadoux

et al. 2018

Trans. Vis. Sci. Tech.

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PurposeTo 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.MethodsTwenty-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.ResultsThe 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.ConclusionsSensor 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 RelevanceSensor strip electrodes can simplify PhNR recordings in the clinic, potentially eliminating the need for an experienced operator.

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Section: Resultsmentioning

confidence: 99%

A Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response

Tang

Hui

Hadoux

et al. 2018

Trans. Vis. Sci. Tech.

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“…The b-wave amplitudes were measured at their peak from the b-wave trough. OPs in the range of 70-300 Hz were extracted by digital filtering and quantified by summing the peak-to-trough amplitudes of the individual OPs within the first 100 ms. A generalized Naka Ruston equation (59) was fit to the data, and the maximum response amplitude (V max ), the slope (n), and the semisaturation constant (K) were estimated.…”

Section: Methodsmentioning

confidence: 99%

Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy

Slavi

Toychiev

Kosmidis

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Degeneration of retinal astrocytes precedes hypoxia-driven pathologic neovascularization and vascular leakage in ischemic retinopathies. However, the molecular events that underlie astrocyte loss remain unclear. Astrocytes abundantly express connexin 43 (Cx43), a transmembrane protein that forms gap junction (GJ) channels and hemichannels. Cx channels can transfer toxic signals from dying cells to healthy neighbors under pathologic conditions. Here we show that Cx43 plays a critical role in astrocyte apoptosis and the resulting preretinal neovascularization in a mouse model of oxygen-induced retinopathy. Opening of Cx43 hemichannels was not observed following hypoxia. In contrast, GJ coupling between astrocytes increased, which could lead to amplification of injury. Accordingly, conditional deletion of Cx43 maintained a higher density of astrocytes in the hypoxic retina. We also identify a role for Cx43 phosphorylation in mediating these processes. Increased coupling in response to hypoxia is due to phosphorylation of Cx43 by casein kinase 1δ (CK1δ). Suppression of this phosphorylation using an inhibitor of CK1δ or in site-specific phosphorylation-deficient mice similarly protected astrocytes from hypoxic damage. Rescue of astrocytes led to restoration of a functional retinal vasculature and lowered the hypoxic burden, thereby curtailing neovascularization and neuroretinal dysfunction. We also find that absence of astrocytic Cx43 does not affect developmental angiogenesis or neuronal function in normoxic retinas. Our in vivo work directly links phosphorylation of Cx43 to astrocytic coupling and apoptosis and ultimately to vascular regeneration in retinal ischemia. This study reveals that targeting Cx43 phosphorylation in astrocytes is a potential direction for the treatment of proliferative retinopathies.

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“…For the PhNR, n was fixed at 1.2 (consistent with our pilot data, and similar to others). 44,45 Further, the PhNR Vmax was analyzed as a ratio to the b-wave Vmax (Vmax ratio) to account for any changes to the b-wave between sessions.…”

Section: Discussionmentioning

confidence: 99%

Improvement in Inner Retinal Function in Glaucoma with Nicotinamide (Vitamin B₃) Supplementation: A Crossover Randomised Clinical Trial

Hui

Tang

Williams

et al. 2020

Preprint

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Importance: Retinal ganglion cells endure significant metabolic stress with ageing and glaucoma-related stressors. Injured cells require increased energy for repair but maintain capacity to recover function despite periods of functional loss. Nicotinamide, a precursor of redox co-factor and metabolite, NAD+, is low in serum of patients with primary open-angle glaucoma and its supplementation provides robust protection of retinal ganglion cells by targeting mitochondrial health in glaucoma models. However, the potential of nicotinamide to improve retinal ganglion cell function in humans with glaucoma is yet unknown. Objective: To determine whether nicotinamide supplementation taken in conjunction with conventional IOP-lowering therapy leads to early improvement in retinal ganglion cell function in people with glaucoma. Design: Crossover, double-masked, randomized clinical trial conducted between October 2017 to January 2019. Setting: Study participants recruited from two tertiary care centers in Melbourne, Australia. Participants: Adults diagnosed and treated for primary glaucoma. Ninety-four participants assessed for study eligibility. Intervention: Participants randomized to first receive oral placebo or nicotinamide and reviewed six-weekly. Accelerated dosing method utilized; participants commenced 6-week course of 1.5 grams/day followed by 6 weeks of 3.0 grams/day. After 12 weeks, participants crossed over to other intervention for 12 weeks without washout. At each visit, visual function measured using full-field flash electroretinography and white-on-white perimetry. Main outcome measures: Primary endpoint was change in inner retinal function determined a-priori as change in photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). Results: Fifty-seven participants (65.5±10.0 years, 39% female) enrolled. PhNR Vmax improved beyond 95% coefficient of repeatability (COR) in 23% of participants following 12 weeks of nicotinamide versus 9% on placebo. Conversely, PhNR Vmax deteriorated in 9% on placebo and 7% on nicotinamide. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (p=0.02) on nicotinamide and 5.2% [-4.2%, 14.6%], (p=0.27) on placebo. Vmax ratio improved on average by 12.6% [5.0%, 20.2%], (p=0.002) following nicotinamide and 3.6% [-3.4%, 10.5%], (p=0.30) on placebo. A concomitant trend for improved visual field mean deviation was observed with 27% improving ≥1dB on nicotinamide and fewer deteriorating ≥1dB (4%) compared to placebo (p=0.02). Moderate correlation was observed between PhNR and visual field change with treatment. Participants demonstrated excellent treatment adherence rates (>94%) and nicotinamide was well tolerated with minimal side effects. Conclusions and Relevance: Nicotinamide supplementation can improve inner retinal function in patients receiving concurrent IOP-lowering glaucoma therapy. Further studies are underway to elucidate the effects of long-term nicotinamide supplementation on glaucoma progression.

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Intensity response function of the photopic negative response (PhNR): effect of age and test–retest reliability

Cited by 20 publications

References 60 publications

A Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response

A Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response

Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy

Improvement in Inner Retinal Function in Glaucoma with Nicotinamide (Vitamin B₃) Supplementation: A Crossover Randomised Clinical Trial

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Intensity response function of the photopic negative response (PhNR): effect of age and test–retest reliability

Cited by 20 publications

References 60 publications

A Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response

A Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response

Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy

Improvement in Inner Retinal Function in Glaucoma with Nicotinamide (Vitamin B3) Supplementation: A Crossover Randomised Clinical Trial

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Product

Resources

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Improvement in Inner Retinal Function in Glaucoma with Nicotinamide (Vitamin B₃) Supplementation: A Crossover Randomised Clinical Trial