USING RETeval SYSTEM FLICKER ELECTRORETINOGRAPHY FOR EVALUATION OF DENSE VITREOUS HEMORRHAGE.

PURPOSE: To determine whether the RETeval electroretinography (ERG) system can be used to evaluate eyes with dense vitreous hemorrhage (VH). METHODS: This retrospective case series study included 69 eyes of 69 patients with acute dense VH. Flicker ERGs were recorded by the RETeval system, an ERG device with adhesive skin electrodes. We evaluated the flicker ERG amplitudes in eyes with VH and the ratio of the VH eye amplitudes compared with the fellow eye amplitudes for each VH cause. RESULTS: In patients with rhegmatogenous retinal detachment, the amplitude ratios were extremely low (0.08 ± 0.03). To detect rhegmatogenous retinal detachment, the area under the receiver operating characteristic curve was 0.977 (95% confidence interval, 0.943-1.000) (best rhegmatogenous retinal detachment cutoff value, 0.14; sensitivity, 100.0%; and specificity, 95.4%). The flicker ERG amplitude was not significantly correlated with the initial visual acuity (ρ = -0.189, P = 0.120) but was positively correlated with the postoperative visual acuity in eyes with VH (ρ = -0.328, P = 0.006). CONCLUSION: The RETeval ERG system was found to be a useful diagnostic option in situations where dense VH precluded fundus examination or posterior vitreous detachment was indistinguishable from rhegmatogenous retinal detachment.

A Diagnostic Model for Screening Diabetic Retinopathy Using the Hand-Held Electroretinogram Device RETeval.

Purpose: To construct a proper model to screen for diabetic retinopathy (DR) with the RETeval. Method: This was a cross-sectional study. Two hundred thirty-two diabetic patients and seventy controls were recruited. The DR risk assessment protocol was performed to obtain subjects' DR risk score using the RETeval. Afterwards, the receiver operating characteristic (ROC) curve was used to determine the best cutoff for diagnosing DR. Random forest and decision tree models were constructed. Results: With increasing DR severity, the DR score gradually increased. When the DR score was used to diagnose DR, the ROC curve had an area under the curve of 0.881 (95% confidence interval: 0.836-0.927, P < 0.001), with a best cutoff value of 22.95, a sensitivity of 74.3% (95 CI: 66.0%~82.6%), and a specificity of 90.6% (95 CI: 83.7% ~94.8%). The top four risk factors selected by the random forest were used to construct the decision tree for diagnosing DR, which had a sensitivity of 93.3% (95% CI: 86.3%~97.0%) and a specificity of 80.3% (95% CI: 72.1% ~86.6%). Conclusions: The DR risk assessment protocol combined with the decision tree model was innovatively used to evaluate the risk of DR, improving the sensitivity of diagnosis, which makes this method more suitable than the current protocol for DR screening.

All-printed stretchable corneal sensor on soft contact lenses for noninvasive and painless ocular electrodiagnosis.

Electroretinogram examinations serve as routine clinical procedures in ophthalmology for the diagnosis and management of many ocular diseases. However, the rigid form factor of current corneal sensors produces a mismatch with the soft, curvilinear, and exceptionally sensitive human cornea, which typically requires the use of topical anesthesia and a speculum for pain management and safety. Here we report a design of an all-printed stretchable corneal sensor built on commercially-available disposable soft contact lenses that can intimately and non-invasively interface with the corneal surface of human eyes. The corneal sensor is integrated with soft contact lenses via an electrochemical anchoring mechanism in a seamless manner that ensures its mechanical and chemical reliability. Thus, the resulting device enables the high-fidelity recording of full-field electroretinogram signals in human eyes without the need of topical anesthesia or a speculum. The device, superior to clinical standards in terms of signal quality and comfortability, is expected to address unmet clinical needs in the field of ocular electrodiagnosis.

Electroretinography (ERG) in the wild giant panda (Ailuropoda melanoleuca).

PURPOSE: Using a quick electroretinography (ERG) protocol for rapid assessment of the retinal function of wild giant pandas (Ailuropoda melanoleuca) performed in field conditions to demonstrate the range of ERG recordings in giant pandas of unknown retinal status. ANIMALS STUDIED: Nine free range giant pandas. PROCEDURE: All the giant pandas were anesthetized using an intramuscular dexMTZ injection, which is a combination of dexmedetomidine and tiletamine-zolazepam. After 20 mins of dark adaptation, scotopic ERGs were obtained by using three flash intensities: -25 dB (0.0087 cd·s/m2 ), 0 dB (2.75 cd·s/m2 ), and +5 dB (8.7 cd·s/m2 ). Next, photopic ERGs were acquired using a single flash protocol with a flash intensity of 3.0 cd·s/m2 after 10 minutes of light adaptation. RESULTS: In scotopic ERG at 0.0087 cd·s/m2 , mean b-wave amplitude and peak time were 82.26 µV (SD ± 16.65 and 95% CI 68.33-96.18) and 66.97 ms (SD ± 10.86 and 95% CI 57.90-76.05), respectively. This flash intensity was below a-wave threshold and resulted in b waves with greater peak times compared to those with higher intensities. At 2.75 cd·s/m2 , the mean a-wave amplitude and peak time were 53.95 µV (SD ± 11.63 and 95% CI 44.23-63.67) and 16.13 ms (SD ± 2.62 and 95% CI 13.94-18.31), and mean b-wave amplitude and peak time were 119.57 µV (SD ± 15.54 and 95% CI 106.57-132.56) and 32.00 ms (SD ± 6.47 and 95% CI 26.59-37.41). At 8.7 cd·s/m2 , the mean a-wave amplitude and peak time were 58.85 µV (SD ± 14.90 and 95% CI 46.39-71.31) and 15.59 ms (SD ± 2.63 and 95% CI 13.40-17.79), and the mean b-wave amplitude and peak time were 132.97 µV (SD ± 22.11 and 95% CI 114.48-151.46) and 32.66 ms (SD ± 6.87 and 95% CI 26.91-38.40). In photopic ERG at 2.75 cd·s/m2 , the mean a-wave amplitude and peak time were 62.08 µV (SD ± 16.61 and 95% CI 48.19-75.97) and 16.28 ms (SD ± 0.90 and 95% CI 15.53-17.03), and the mean b-wave amplitude and peak time were 214.93 µV (SD ± 70.41 and 95% CI 156.07-273.80) and 33.09 ms (SD ± 1.27 and 95% CI 32.03-34.15). CONCLUSION: Using a portable ERG system with a brief ERG protocol to perform electroretinographies in wild giant pandas is a practical, useful, and reliable method for the rapid assessment of their retinal function.

Neuroretinal dysfunction revealed by a flicker electroretinogram correlated with peripheral nerve dysfunction and parameters of atherosclerosis in patients with diabetes.

AIMS/INTRODUCTION: Diabetic polyneuropathy (DPN) develops in the early stage of diabetes. However, no common diagnostic protocol has yet been established. Here, to verify that the flicker electroretinogram using a hand-held device can detect the early dysfunction of the peripheral nervous system in patients with diabetes, we investigated the correlation between the progression of DPN and neuroretinal dysfunction. MATERIALS AND METHODS: In total, 184 participants with type 1 or 2 diabetes underwent a flicker electroretinogram (ERG) using a hand-held device RETeval™ and nerve conduction study. Participants were also evaluated for intima-media thickness, ankle-brachial index, toe brachial index and brachial-ankle pulse wave velocity. Parameters of the nerve conduction study were used to diagnose the severity according to Baba's classification. A multiple regression analysis was used to examine the associations of ERG parameters with the severity of DPN categorized by Baba's classification. Diagnostic properties of the device in DPN were evaluated using a receiver operating characteristic curve. RESULTS: A multiple regression model to predict the severity of DPN was generated using ERG. In the model, moderate-to-severe DPN was effectively diagnosed (area under the receiver operating characteristic curve 0.692, sensitivity 56.5%, specificity 78.3%, positive predictive value 70.6%, negative predictive value 66.1%, positive likelihood ratio 2.60, negative likelihood ratio 0.56). In the patients without diabetic retinopathy, the implicit time and amplitude in ERG significantly correlated with the parameters of the nerve conduction study, brachial-ankle pulse wave velocity and intima-media thickness. CONCLUSIONS: Electroretinogram parameters obtained by the hand-held device successfully predict the severity of DPN. The device might be useful to evaluate DPN.

Diagnosis of night blindness through standardized interview and electroretinography / Diagnóstico de la ceguera nocturna mediante entrevista normalizada y electrorretinografía

Objective: To compare the diagnosis of NB through the use of the standardized interview of the World Health Organization/Pan American Health Organization (WHO/PAHO) with electroretinography, and also to evaluate the association of these diagnoses with serum concentrations of retinol in class III obesity individuals. Methods: Adult patients of both genders, in the 20-60 age group, with BMI = 40 kg/m² were studied. NB was diagnosed through electroretinography and the standardized interview validated by the WHO/PAHO. Serum level of retinol was quantified by the HPLC-UV method, and VAD was diagnosed when levels were <1.05 µmol /L, and severity was also evaluated. Statistical analysis was carried out through the Statistical Package for the Social Sciences, version 21.0 (p < 0.05). Results: Mean BMI was 44.9 ? 11.8 kg/m², and a negative correlation was found in serum levels of retinol (p= 0.01). The prevalence of VAD, according to the serum concentrations of retinol, was 14%, and of this percentage 23.3% had NB according to the standardized interview, and 22.0% according to electroretinography. NB diagnosed by both methods showed an association with VAD according to the serum concentrations of retinol. Of these individuals with NB, according to the standardized interview, 6.9% showed severe VAD, 10.3% moderate VAD and 82.8% marginal VAD. Conclusion: The standardized interview for the diagnosis of NB can be a good strategy to evaluate the nutritional status of vitamin A, and it is a simple, non-invasive and low-cost method

Introducción: la deficiencia de vitamina A (DVA) es uno de los mayores problemas de salud pública a escala mundial, y la ceguera nocturna (CN) es el primer cambio funcional causado por la falta de esta vitamina. En este contexto, la electrorretinografía se destaca como el método de diagnóstico de referencia; sin embargo, es un método de coste elevado y su aplicabilidad en la práctica clínica presenta algunas dificultades. Objetivo: comparar el diagnóstico de CN mediante el uso de la entrevista estandarizada de la Organización Mundial de la Salud/Organización Panamericana de la Salud (OMS/OPS) con la electrorretinografía, y también evaluar la asociación de estos diagnósticos con las concentraciones séricas de retinol en las personas con obesidad de clase III. Métodos: se estudiaron pacientes adultos de ambos sexos, en el grupo de 20 a 60 años de edad y con IMC = 40 kg/m². La NB se diagnosticó mediante electrorretinografía y la entrevista estandarizada validada por la OMS/OPS. El nivel sérico de retinol se cuantificó mediante el método HPLC-UV, y el DVA se diagnosticó cuando los niveles eran < 1.05 µmol/l; también se evaluó la gravedad. El análisis estadístico se realizó a través del Paquete Estadístico para las Ciencias Sociales, versión 21.0 (p < 0,05). Resultados: el IMC promedio fue de 44,9 ± 11,8 kg/m² y se encontró una correlación negativa en los niveles séricos de retinol (p = 0,01). La prevalencia de DVA, según las concentraciones séricas de retinol, fue del 14 %; de este porcentaje, el 23,3 % tenían NB de acuerdo con la entrevista estandarizada y el 22,0 % según la electrorretinografía. La NB diagnosticada por ambos métodos mostró asociación con el DVA según las concentraciones séricas de retinol. De estos individuos con NB, según la entrevista estandarizada, el 6,9 % tenían VAD grave, el 10,3 % VAD moderado y el 82,8 % VAD marginal. Conclusión: la entrevista estandarizada para el diagnóstico de NB puede ser una buena estrategia para evaluar el estado nutricional de la vitamina A y es un método simple, no invasivo y de bajo coste

Effects of DTL electrode position on the amplitude and implicit time of the electroretinogram.

PURPOSE: This study sought to investigate whether there is an optimal position of the Dawson, Trick, and Litzkow (DTL) electrodes when measuring the full-field electroretinogram (ERG) for monitoring purposes. METHODS: In 200 uveitis patients, an extended light-adapted (LA) ERG protocol was measured twice, incorporating the International Society for Clinical Electrophysiology of Vision standards. First, a LA ERG was measured with the DTL in the lower lid position (LLP) and thereafter in the fornix position. Differences in amplitudes and implicit times of a-waves, b-waves, and the 30 Hz peak were investigated. Intraclass correlation coefficients (ICCs) as well as coefficients of variation (CoV) were calculated, to assess both reliability and relative variability between the two DTL positions. RESULTS: Implicit times showed no statistically significant differences between the two DTL positions. As expected, amplitudes at the different stimulus strengths were 1.12-1.19 higher in the LLP, but there were no significant differences in the CoV between the two DTL positions. The ICC was high for the b-wave and 30 Hz flicker response (0.842-0.979), but lower for the a-wave, especially for amplitudes (0.584-0.716). CONCLUSIONS: For monitoring purposes in patients, we conclude that based on relative variability, no position is preferable above the other. However, because in most diseases amplitudes are decreased, the LLP may be chosen because it yields higher amplitudes. Whatever the choice, it is important to ensure that the DTL position remains stable during an ERG recording.

Electroretinograms.

The electroretinogram (ERG) is an electrical response of the retina to photic stimulation. A flash of light or bright appearance of a pattern elicits a biphasic negative/positive waveform. The a-wave originating in the receptor level of rods and cones is the initial large negative wave. The b-wave originating in the midretina is the following large positive component. Protocols include full-field and multifocal ERGs. Full-field ERGs are recorded if one is most interested in the global health of the retina, such as in retinitis pigmentosa. A limitation of the full-field ERG is that the recording is a massed potential from the whole retina. Multifocal ERGs can map small scotomas in the central 40+ degrees of visual field. Abbreviated methods are used with infants and in the operating room as part of an exam under anesthesia. The effects of toxic medications can be detected and quantified using ERGs. The ERG is useful to assess cases of retinal foreign bodies and trauma to estimate the extent of retinal dysfunction. Foreign bodies affect retinal function depending on the extent of trauma to the retina and the location and composition of the object. Systemic metabolic disorders usually reduce ERG b-wave amplitudes, particularly the scotopic dim flash ERGs.

Flicker electroretinogram recorded with portable ERG device in prematurely born schoolchildren with and without ROP.

PURPOSE: The purpose of this study was to compare electroretinographic (ERG) responses of preterm schoolchildren, with and without a history of retinopathy of prematurity (ROP) with those of full-term schoolchildren by using a portable ERG device (RETeval system). METHODS: Twenty five prematurely born schoolchildren with a mean gestational age of 27 + 1/7w (range 23-30w) and a mean birth weight of 1030 g (range 580-1700 g) who were 6.9 ± 2.2 years old participated in the study (premature group). A further subdivision according to a history of ROP (ROP+ group) or its absence (ROP- group) was introduced. Twenty eight healthy full-term schoolchildren with an average age of 8.6 ± 1.9 years participated as the control group. 30-Hz flicker ERG responses were obtained, and implicit times and amplitudes were compared between the groups. RESULTS: 30-Hz flicker ERG implicit times showed a significant difference between all three groups of children. The mean value of the implicit time in the term group was 25.76 ± 0.9 ms, whereas in the preterm ROP + group it was 28.96 ± 1.0 ms and in the preterm ROP- group it was 26.87 ± 1.5 ms. 30-Hz flicker ERG amplitudes did not show significant difference between term children and children born prematurely with or without ROP. CONCLUSIONS: Prematurely born schoolchildren exhibit longer implicit time of the 30-Hz flicker ERG response compared to controls, suggesting a possible abnormality of the retinal cone system function. Under such circumstances, portable ERG device might be used clinically as a screening tool for retinal function evaluation in prematurely born children.

Hand-held, dilation-free, electroretinography in children under 3 years of age treated with vigabatrin.

PURPOSE: The anti-epileptic drug vigabatrin is associated with reduction in light-adapted 30-Hz flicker electroretinogram (ERG) amplitude. Ophthalmological assessments, including ERGs, monitor retinal health during vigabatrin treatment. RETeval™ is a hand-held ERG device adapted for dilation-free ERG assessment. To evaluate the usefulness of RETeval™ for vigabatrin ERG assessment, we evaluated intra-visit reliability and clinical feasibility of RETeval™ ERG assessment in children under 3 years of age undergoing vigabatrin treatment. METHODS: In this prospective study, children underwent 30-Hz flicker ERG assessment with RETeval™ before routine vigabatrin monitoring including sedated-ERG using the Espion E2 Colour Dome. Intraclass correlation coefficient (ICC) statistics identified the degree of intra-visit reliability from two repeated measurements of the same participant within one testing session. The omega squared (ω2) statistic identified the level of association between RETeval™ and Espion light-adapted 30-Hz flicker responses. RESULTS: Nine children completed RETeval™ ERG testing. The intra-visit ICCs for the RETeval™ 30-Hz flicker amplitude (µV) were high: 0.81 (right eye) and 0.86 (left eye), while the implicit times (ms) were 0.79 (right eye) and 0.42 (left eye). The RETeval™ 30-Hz flicker amplitude was positively associated with the Espion 30-Hz flicker response (ω2 = 0.71). The Bland-Altman plot showed no bias in the mean difference of amplitudes between the two systems. CONCLUSION: This is the first study to assess the utility of RETeval™ device in children under 3 years of age undergoing vigabatrin treatment. RETeval™ demonstrated high intra-visit reliability with responses consistent with the standard Espion ERG. RETeval™ may be beneficial for assessment of retinal toxicity in young children treated with vigabatrin.

Comparison of electroretinographic measurements between tabletop and handheld stimulators in healthy subjects.

PURPOSE: To compare full-field electroretinography (ffERG) parameters obtained from handheld and tabletop electroretinography (ERG) devices in normal subjects. METHODS: Twenty volunteers underwent ffERG using a tabletop and handheld stimulator. The responses obtained from the right eyes were compared. The coefficient of variation and intraclass correlation coefficient (ICC) were derived to assess inter- and intra-individual reliability. RESULTS: The b-wave in the rod response, a- and b-waves in the maximal combined response, a-wave in the cone response, and the 30-Hz flicker response showed significantly greater amplitudes when recorded with the tabletop stimulator than with the handheld stimulator. The implicit time of response (ITR) in the 30-Hz flicker response was longer when recorded with the handheld stimulator than when recorded with the tabletop stimulator. With regard to amplitude, the ICC indicated moderate-to-high reliability in the measurement of the b-wave in the rod response, and a- and b-waves in the maximal combined response. With regard to ITR, measurement of the b-wave in the rod response and a-wave in the maximal combined response showed moderate-to-high reliability. CONCLUSION: Despite the significantly lower ERG amplitude measurements recorded by the handheld stimulator, there were no significant differences in variability between the two stimulators.

Modified ERG-Jet™ contact lens electrodes for use in infants and toddlers-update.

PURPOSE: To describe recent changes in the dimensions of the ERG-jet contact lens electrode, and to suggest corresponding changes in the dimensions of cylindrical stents to facilitate the use of ERG-jet contact lens electrodes in infants and small children. METHODS: Upon the observation that existing cylindrical stents no longer fit newly purchased ERG-jet contact lenses, the spacings between the "bumps" on the front surface of old and new electrodes were measured with calipers, and prototype stents were newly machined from acrylic plastic. RESULTS: Cylindrical stents with an outside diameter of 0.277 inches (about 7.04 mm) were found to fit snugly between the front surface "bumps" of new ERG-jet contact lens electrodes. CONCLUSIONS: Recent modifications in the injection molds for ERG-jet contact lens electrodes have resulted in an increase in the space between the "bumps" on the front surface of the electrodes, necessitating a corresponding increase in the outside diameter of cylindrical stents intended to fit snugly between the "bumps" for ease of insertion and prevention of lid closure.

Evaluation of light- and dark-adapted ERGs using a mydriasis-free, portable system: clinical classifications and normative data.

PURPOSE: The full-field electroretinogram (ff-ERG) is a widely used clinical tool to evaluate generalized retinal function by recording electrical potentials generated by the cells in the retina in response to flash stimuli and requires mydriasis. The purpose of this study was to determine the intra-visit reliability and diagnostic capability of a handheld, mydriasis-free ERG, RETeval (LKC Technologies, Gaithersburg, MD, USA), in comparison with the standard clinical ff-ERG by measuring responses recommended by the International Society for Clinical Electrophysiology of Vision (ISCEV). METHODS: This prospective, cross-sectional study included 35 patients recruited at the Hospital for Sick Children (median age = 17, range 11 months-69 years) who had undergone a clinical ff-ERG according to ISCEV standards. For RETeval (n = 35), pupils were undilated in most (n = 29) and sensor strip electrodes were placed under the inferior orbital rim. Stimulus settings on RETeval were equivalent to those used in the clinical ERG. Fifty-seven control participants (median age = 22, range 8-65 years) underwent undilated RETeval ERG to establish standard values for comparison. Patient waveform components with amplitudes < 5th percentile, or implicit times > 95th percentile of normal relative to control data were classified as abnormal for the RETeval system. RESULTS: The RETeval system demonstrated a high degree of within-visit reliability for amplitudes (ICC = 0.82) and moderate reliability for implicit times (ICC = 0.53). Cohen's Kappa analysis revealed a substantial level of agreement between the diagnostic capability of RETeval in comparison with clinical ff-ERG (k = 0.82), with a sensitivity and specificity of 1.00 and 0.82, respectively. Pearson's correlations for clinical ERG versus RETeval demonstrated a positive correlation for amplitudes across the rod (r = 0.65) and cone (r = 0.74) ERG waveforms. Bland-Altman plots showed no bias between the mean differences across all amplitude and implicit time parameters of the two systems. CONCLUSIONS: The present study demonstrated that RETeval is a reliable tool with reasonable accuracy in comparison with the clinical ERG. The portable nature of RETeval system enables its incorporation at resource-limited centers where the ff-ERG is not readily available. The avoidance of sedation and pupillary dilation are added advantages of RETeval ERG.

Role of a mydriasis-free, full-field flicker ERG device in the detection of diabetic retinopathy.

PURPOSE: To determine if the RETeval system can be used for the screening of diabetic retinopathy (DR) to provide early diagnosis. METHODS: The subjects were 42 diabetic patients selectively recruited by examination of their medical records to have varying severities of DR. The severity of DR was classified into four groups according to the International Clinical Diabetic Retinopathy Disease Severity Scale. Full-field electroretinograms (ERG) without mydriasis were obtained by the DR assessment protocol of the RETeval system. Macular retinal nerve fiber layer (RNFL) thickness was measured by optical coherence tomography. We compared the DR assessment protocol results and the macular RNFL thickness among four groups. Moreover, an analysis was conducted on whether there was any correlation among the DR assessment protocol results, duration of diabetes mellitus, and RNFL thickness individually for each group of patients. RESULTS: The mean ages and mean duration of diabetes mellitus of the four groups were similar. The DR assessment protocol results in the moderate-severe nonproliferative DR, and proliferative DR groups were significantly higher than those in the other groups (p < 0.001). The mean macular RNFL thickness was similar in all groups. No significant correlation was found between the DR assessment protocol results and duration of DM and the RNFL thickness. CONCLUSIONS: Our results suggest that the RETeval full-field ERG system can be used as an adjunctive tool for the mass screening of DR, while macular RNFL thickness would not be useful.

Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system.

PURPOSE: A handheld device (the RETeval system, LKC Technologies) aims to increase the ease of electroretinogram (ERG) recording by using specially designed skin electrodes, rather than corneal electrodes. We explored effects of electrode position on response parameters recorded using this device. METHODS: Healthy adult twins were recruited from the TwinsUK cohort and underwent recording of light-adapted flicker ERGs (corresponding to international standard stimuli). In Group 1, skin electrodes were placed in a "comfortable" position, which was up to 20 mm below the lid margin. For subsequent participants (Group 2), the electrode was positioned 2 mm from the lid margin as recommended by the manufacturer. Amplitudes and peak times (averaged from both eyes) were compared between groups after age-matching and inclusion of only one twin per pair. Light-adapted flicker and flash ERGs were recorded for an additional 10 healthy subjects in two consecutive recording sessions: in the test eye, electrode position was varied from 2 to 10-20 mm below the lid margin between sessions; in the fellow (control) eye, the electrode was 2 mm below the lid margin throughout. Amplitudes and peak times (test eye normalised to control eye) were compared for the two sessions. RESULTS: Including one twin per pair, and age-matching yielded 28 individuals per group. Flicker ERG amplitudes were significantly lower for Group 1 than Group 2 participants (p = 0.0024). However, mean peak times did not differ between groups (p = 0.54). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly lower when positioned further from the lid margin (p < 0.005), but peak times were similar (p > 0.5). CONCLUSIONS: Moving the skin electrodes further from the lid margin significantly reduces response amplitudes, highlighting the importance of consistent electrode positioning. However, this does not significantly affect peak times. Thus, it may be feasible to adopt a more comfortable position in participants who cannot tolerate the recommended position if analysis is restricted to peak time parameters.

Three-Dimensional Model of Electroretinogram Field Potentials in the Rat Eye.

OBJECTIVE: The information derived from the electroretinogram (ERG), especially with regard to local areas of retinal dysfunction or therapeutic rescue, can be enhanced by an increased understanding of the relationship between local retinal current sources and local ERG potentials measured at the cornea. A critical step in this direction is the development of a robust bioelectric field model of the ERG. METHODS: A finite-element model was created to simulate ERG potentials at the cornea resulting from physiologically relevant transretinal currents. A magnetic resonance image of a rat eye was segmented to define all major ocular structures, tissues were assigned conductivity values from the literature. The model was optimized to multi-electrode ERG (meERG) data recorded in healthy rat eyes, and validated with meERG data from eyes with experimental lesions in peripheral retina. RESULTS: Following optimization, the simulated distribution of corneal potentials was in good agreement with measured values; residual error was comparable to the average difference of individual eyes from the measured mean. The model predicted the corneal potential distribution for eight eyes with experimental lesions with similar accuracy, and a measure of pre- to post-lesion changes in corneal potential distribution was well correlated with the location of the lesion. CONCLUSION: An eye model with high anatomical accuracy was successfully validated against a robust dataset. SIGNIFICANCE: This model can now be used for optimization of ERG electrode design, and to support functional mapping of the retina from meERG data via solving the inverse bioelectric source problem.

Soft transparent graphene contact lens electrodes for conformal full-cornea recording of electroretinogram.

Visual electrophysiology measurements are important for ophthalmic diagnostic testing. Electrodes with combined optical transparency and softness are highly desirable, and sometimes indispensable for many ocular electrophysiology measurements. Here we report the fabrication of soft graphene contact lens electrodes (GRACEs) with broad-spectrum optical transparency, and their application in conformal, full-cornea recording of electroretinography (ERG) from cynomolgus monkeys. The GRACEs give higher signal amplitude than conventional ERG electrodes in recordings of various full-field ERG responses. High-quality topographic mapping of multifocal ERG under simultaneous fundus monitoring is realized. A conformal and tight interface between the GRACEs and cornea is revealed. Neither corneal irritation nor abnormal behavior of the animals is observed after ERG measurements with GRACEs. Furthermore, spatially resolved ERG recordings on rabbits with graphene multi-electrode array reveal a stronger signal at the central cornea than the periphery. These results demonstrate the unique capabilities of the graphene-based electrodes for in vivo visual electrophysiology studies.

Measuring Retinal Function in the Mouse.

Electroretinography is a crucial assay for studying the function and the functional integrity of the retina. The mouse is an important animal model for studying the retinal neurons and circuitries. In addition, it is often used as animal model for human retinal disorders. Therefore, a good understanding of the procedures in animal handling, of the methods for data analysis and of the requirements for stimulators and for the data acquisition equipment is of importance. Here, the currently most common methods and materials for in vivo electroretinography in the mouse are discussed.

RPE Visual Cycle and Biochemical Phenotypes of Mutant Mouse Models.

The retinal pigmented epithelium (RPE) is a single layer of polarized epithelial cells which plays many important roles for visual function. One of such roles is production of visual chromophore, 11-cis-retinal through the visual cycle. The visual cycle consists of biochemical processes for regenerating chromophore by a collective action of the RPE and photoreceptor. Photoreceptors harbor the G protein-coupled receptors, opsin which enables to receive light when it bounds to 11-cis-retinal. With absorption of a photon of light, 11-cis-retinal photoisomerizes to all-trans-retinal. All-trans-retinal reduces to all-trans-retinol in the photoreceptor and further recycles back to 11-cis-retinal in the RPE. Acyltransferases and isomerohydrolase(s) along with retinol dehydrogenases sequentially convert all-trans-retinol to 11-cis-retinal in the RPE. Dysfunctions of any retinoid cycle enzymes in the RPE can cause retinal diseases. Phenotyping RPE functions by the use of mutant mouse models will provide great detailed biochemical insights of the visual cycle and further manipulative strategies to protect against retinal degeneration. Here, we describe biochemical analyses of the visual cycle in mouse models using RPE cells.

Use of Direct Current Electroretinography for Analysis of Retinal Pigment Epithelium Function in Mouse Models.

A monolayer of pigmented epithelial cells, the retinal pigment epithelium (RPE), supports photoreceptor function in many ways. Consistent with these roles, RPE dysfunction underlies a number of hereditary retinal disorders. To monitor RPE function in vivo models for these conditions, we adapted an electroretinographic (ERG) technique based on direct current amplification (DC-ERG). This chapter describes the main features of this approach and its application to mouse models involving the RPE.