Full-field Flicker Research Articles

Spatiotemporal resonance in mouse primary visual cortex

Human primary visual cortex (V1) responds more strongly, or resonates, when exposed to ∼10, ∼15-20, and ∼40-50Hz rhythmic flickering light. Full-field flicker also evokes the perception of hallucinatory geometric patterns, which mathematical models explain as standing-wave formations emerging from periodic forcing at resonant frequencies of the simulated neural network. However, empirical evidence for such flicker-induced standing waves in the visual cortex was missing. We recorded cortical responses to flicker in awake mice using high-spatial-resolution widefield imaging in combination with high-temporal-resolution glutamate-sensing fluorescent reporter (iGluSnFR). The temporal frequency tuningcurves in the mouse V1 were similar to those observed in humans, showing a banded structure with multiple resonance peaks (8, 15, and 33Hz). Spatially, all flicker frequencies evoked responses inV1 corresponding to retinotopic stimulus location, but some evoked additional peaks. These flicker-induced cortical patterns displayed standing-wave characteristics and matched linear wave equationsolutions in an area restricted to the visual cortex. Taken together, the interaction of periodic traveling waves with cortical area boundaries leads to spatiotemporal activity patterns that may affect perception.

Retinal Dystrophy Associated With RLBP1 Retinitis Pigmentosa: A Five-Year Prospective Natural History Study.

To assess the progression in functional and structural measures over a five-year period in patients with retinal dystrophy caused by RLBP1 gene mutation. This prospective, noninterventional study included patients with biallelic RLBP1 mutations from two clinical sites in Sweden and Canada. Key assessments included ocular examinations, visual functional measures (best-corrected visual acuity [BCVA], contrast sensitivity [CS], dark-adaptation [DA] kinetics up to six hours for two wavelengths [450 and 632 nm], Humphrey visual fields [HVF], full-field flicker electroretinograms), and structural ocular assessments. Of the 45 patients enrolled, 38 completed the full five years of follow-up. At baseline, patients had BCVA ranging from -0.2 to 1.3 logMAR, poor CS, HVF defects, and prominent thinning in central foveal thickness. All patients had extremely prolonged DA rod recovery of approximately six hours at both wavelengths. The test-retest repeatability was high across all anatomic and functional endpoints. Cross-sectionally, poorer VA was associated with older age (right eye, correlation coefficient [CC]: 0.606; left eye, CC: -0.578; P < 0.001) and HVF MD values decreased with age (right eye, CC: -0.672, left eye, CC: -0.654; P < 0.001). However, no major changes in functional or structural measures were noted longitudinally over the five-year period. This natural history study, which is the first study to monitor patients with RLBP1 RD for five years, showed that severely delayed DA sensitivity recovery, a characteristic feature of this disease, was observed in all patients across all age groups (17-69 years), making it a potentially suitable efficacy assessment for gene therapy treatment in this patient population.

Gain Changes in Response to Full Field Flicker

Gain Changes in Response to Full Field Flicker

Measuring Temporal and Spatial Variability of Red Blood Cell Velocity in Human Retinal Vessels.

PurposeThe retinal circulation regulates blood flow through various internal and external factors; however, it is unclear how locally these factors act within the retinal microcirculation. We measured the temporal and spatial variability of blood velocity in small retinal vessels using a dual-beam adaptive optics scanning laser ophthalmoscope.MethodsIn young healthy subjects (n = 3), temporal blood velocity variability was measured in a local vascular region consisting of an arteriole, capillary, and venule repeatedly over 2 days. Data consisted of 10 imaging periods separated into two sessions: (1) five 6-minute image acquisition periods with 30-minute breaks, and (2) five 6-minute image acquisition periods with 10-minute breaks. In another group of young healthy subjects (n = 5), spatial distribution of velocity variability was measured by imaging three capillary segments during three 2-minute conditions: (1) baseline imaging condition (no flicker), (2) full-field flicker, and (3) no flicker condition again.ResultsBlood velocities were measurable in all subjects with a reliability of about 2%. The coefficient of variation (CV) was used as an estimate of the physiological variability of each vessel. Over 2 days, the average CV in arterioles was 7% (±2%); in capillaries, it was 19% (±6%); and, in venules, it was 8% (±2%). During flicker stimulation, the average capillary CV was 16% during baseline, 15% during flicker stimulation, and 18% after flicker stimulation.ConclusionsCapillaries in the human retina exhibit spatial and temporal variations in blood velocity. This inherent variation in blood velocity places limits on studying the vascular regulation of individual capillaries, and the study presented here serves as a foundation for future endeavors.

Mydriasis-Free Flicker Electroretinograms in 204 Healthy Children Aged 0-18 Years: Reference Data From Two Cohorts.

PurposeThe purpose of this study was to summarize the flicker electroretinogram responses (ERGs) in healthy children using RETeval, a small handheld mydriasis-free full-field flicker ERG system.MethodsFlicker ERGs were recorded with the use of the RETeval system in 204 healthy children (aged 18 years and below) from 2 countries, China and the United States. The effects on ERG measurements of the subject's demographics and location were analyzed.ResultsThe implicit times have no correlation with the population (China cohort and US cohort), sex, and refractive error. In contrast, the amplitudes were dependent on demographics. The amplitude differences were small compared to the 95% reference interval; therefore, a single (age-corrected) reference interval can be used in both locations and both sexes. The implicit times and amplitudes mature over the first decade of life with exponential time constants of 2.5 years and 4.1 years, respectively, whereas most of the trend is within the first 6 years (implicit times) and 9 years (amplitudes).ConclusionsThe age dependence and percentiles obtained in this study could serve as reference data against which the ERG responses from pediatric patients can be compared.Translational RelevanceThe flicker ERG is one of the standard methods for the assessment and diagnosis of vision-related disorders. This study provides reference data in pediatric subjects, which can then be used to aid in the interpretation of flicker ERG results.

Impact of Temporal Visual Flicker on Spatial Contrast Sensitivity in Myopia.

PurposeTo investigate whether short-term exposure to high temporal frequency full-field flicker has an impact on spatial visual acuity in individuals with varying degrees of myopia.MethodsThirty subjects (evenly divided between control and experimental groups) underwent a 5-min exposure to full-field flicker. The flicker rate was lower than critical flicker frequency (CFF) for the experimental group (12.5 Hz) and significantly higher than CFF for the controls (60 Hz). Spatial contrast sensitivity function (CSF) was measured before and immediately after flicker exposure. We examined whether the post flicker CSF parameters were different from the pre-exposure CSF values in either of the subject groups. Additionally, we examined the relationship between the amount of CSF change from pre to post timepoints and the degree of subjects’ myopia. The CSF parameters included peak frequency, peak sensitivity, bandwidth, truncation, and area under log CSF (AULCSF).ResultsThere was no significant difference of all five pre-exposure CSF parameters between the two groups at baseline (P = 0.333 ∼ 0.424). Experimental group subjects exhibited significant (P < 0.005) increases in peak sensitivity and AULCSF, when comparing post-exposure results to pre-exposure ones. Controls showed no such enhancements. Furthermore, the extent of these changes in the experimental group was correlated significantly with the participants’ refractive error (P = 0.005 and 0.018, respectively).ConclusionOur data suggest that exposure to perceivable high-frequency flicker (but, not to supra-CFF frequencies) enhances important aspects of spatial contrast sensitivity, and these enhancements are correlated to the degree of myopia. This finding has implications for potential interventions for cases of modest myopia.

Full-field flicker evoked changes in parafoveal retinal blood flow

When retinal activity is increased by exposure to dynamic visual stimuli, blood vessels dilate and the flow of blood within vessels increases to meet the oxygen and glucose demands of the neurons. This relationship is termed ‘neurovascular coupling’ and it is critical for regulating control of the human retinal vasculature. In this study, we used a recently developed technique based on a dual-beam adaptive optics scanning laser ophthalmoscope to measure changes in red blood cell velocities, vessel diameter, and flow in interconnected small parafoveal retinal vessels (< 50 µm) of nine healthy participants. A full-field flicker stimulus was presented onto the retina to induce a vascular response to neural activity. Flicker stimulation increased blood velocity, vessel diameter, and therefore flow in arterioles, capillaries, and venules in all nine subjects. ANOVA and post hoc t-test showed significant increases in velocity and flow in arterioles and venules. These measurements indicate that the mechanism of neurovascular coupling systematically affects the vascular response in small retinal vessels in order to maintain hemodynamic regulation in the retina when exposed to visual stimulation, in our case flicker. Our findings may provide insight into future investigations on the impairments of neurovascular coupling from vascular diseases such as diabetic mellitus.

Management of retinitis pigmentosa by Wharton\u2019s jelly-derived mesenchymal stem cells: prospective analysis of 1-year results

PurposeThe aim of the study was to investigate annual structural and functional results, and their correlation with inheritance pattern of retinitis pigmentosa (RP) patients who were treated with Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs).Material and methodsThis prospective, sequential, open-label phase-3 clinical study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology, between April 2019 and May 2020. The study included 34 eyes from 32 retinitis pigmentosa patients of various genotypes who were enrolled in the stem cells clinical trial. The patients were followed for 12 months after the WJ-MSCs transplantation into subtenon space and evaluated with consecutive examinations. Genetic mutations were investigated using a retinitis pigmentosa panel sequencing method consisting of 90 genes. All patients underwent a complete routine ophthalmic examination with best corrected visual acuity, optical coherence tomography angiography, visual field, and full-field electroretinography. Quantitative data obtained from baseline (T0), 6th month (T1), and 12th month (T2) examinations were compared.ResultsAccording to timepoints at T0, T1, and T2: The mean outer retinal thickness was 100.3 μm, 119.1 μm, and 118.0 μm, respectively (p = 0.01; T0 < T1, T2). The mean horizontal ellipsoid zone width were 2.65 mm, 2.70 mm, and 2.69 mm respectively (p = 0.01; T0 < T1, T2). The mean best corrected visual acuity (BCVA) were 70.5 letters, 80.6 letters, and 79.9 letters, respectively (p = 0.01; T0 < T1, T2). The mean fundus perimetry deviation index (FPDI) was 8.0%, 11.4%, and 11.6%, respectively (p = 0.01; T0 < T1, T2). The mean full-field flicker ERG parameters at T0, T1, and T2: amplitudes were 2.4 mV, 5.0 mV, and 4.6 mV, respectively (p = 0.01; T0 < T1, T2). Implicit time were 43.3 ms, 37.9 ms, and 38.6 ms, respectively (p = 0.01; T0 > T1, T2). According to inheritance pattern, BCVA, FPDI, ERG amplitude, and implicit time data improved significantly in autosomal dominant (AD) and in autosomal recessive (AR) RP at 1 year follow-up (pAD = 0.01, pAR = 0.01; pAD = pAR > pX-linked). No ocular or systemic adverse events related to the surgical methods and/or WJ-MSCs were observed during the 1 year follow-up period.ConclusionSubtenon transplantation of WJ-MSCs was found to be effective and safe in the treatment of RP during the first year, similar to the sixth month’s results. In autosomal dominant and autosomal recessive inheritance of RP, regardless of the genetic mutations, subtenon administration of WJ-MSCs can be considered an effective and safe option without any adverse effect for slowing or stopping the disease progression.Trial registrationClinicalTrials.gov, NCT04224207. Registered 8 January 2020

Management of retinitis pigmentosa by Wharton\u2019s jelly derived mesenchymal stem cells: preliminary clinical results

PurposeThe aim of this study is to determine if umbilical cord Wharton’s jelly derived mesenchymal stem cells implanted in sub-tenon space have beneficial effects on visual functions in retinitis pigmentosa patients by reactivating the degenerated photoreceptors in dormant phase.Material and methodsThis prospective, open-label, phase-3 clinical trial was conducted between April of 2019 and October of 2019 at Ankara University Faculty of Medicine, Department of Ophthalmology. 32 RP patients (34 eyes) were included in the study. The patients were followed for 6 months after the Wharton’s jelly derived mesenchymal stem cell administration, and evaluated with consecutive examinations. All patients underwent a complete routine ophthalmic examination, and best corrected visual acuity, optical coherens tomography angiography, visual field, multifocal and full-field electroretinography were performed. The quantitative results were obtained from a comparison of the pre-injection and final examination (6th month) values.ResultsThe mean best corrected visual acuity was 70.5 letters prior to Wharton’s jelly derived mesenchymal stem cell application and 80.6 letters at the 6th month (p = 0.01). The mean visual field median deviation value was 27.3 dB before the treatment and 24.7 dB at the 6th month (p = 0.01). The mean outer retinal thickness was 100.3 μm before the treatment and 119.1 μm at 6th month (p = 0.01). In the multifocal electroretinography results, P1 amplitudes improved in ring1 from 24.8 to 39.8 nv/deg2 (p = 0.01), in ring2 from 6.8 to 13.6 nv/deg2 (p = 0.01), and in ring3 from 3.1 to 5.7 nv/deg2 (p = 0.02). P1 implicit times improved in ring1 from 44.2 to 32.4 ms (p = 0.01), in ring2 from 45.2 to 33.2 ms (p = 0.02), and in ring3 from 41.9 to 32.4 ms (p = 0.01). The mean amplitude improved in 16 Tds from 2.4 to 5.0 nv/deg2 (p = 0.01) and in 32 Tds from 2.4 to 4.8 nv/deg2 (p = 0.01) in the full-field flicker electroretinography results. Full field flicker electroretinography mean implicit time also improved in 16 Tds from 43.3 to 37.9 ms (p = 0.01). No ocular or systemic adverse events related to the two types of surgical methods and/or Wharton’s jelly derived mesenchymal stem cells itself were observed during the follow-up period.ConclusionRP is a genetic disorder that can result in blindness with outer retinal degeneration. Regardless of the type of genetic mutation, sub-tenon Wharton’s jelly derived mesenchymal stem cell administration appears to be an effective and safe option. There are no serious adverse events or ophthalmic / systemic side effects for 6 months follow-up. Although the long-term adverse effects are still unknown, as an extraocular approach, subtenon implantation of the stem cells seems to be a reasonable way to avoid the devastating side effects of intravitreal/submacular injection. Further studies that include long-term follow-up are needed to determine the duration of efficacy and the frequency of application.Trial registrationSHGM56733164. Redistered 28 January 2019 https://shgm.saglik.gov.tr/organ-ve-doku-nakli-koordinatorlugu/56733164/203 E.507.

Screening for diabetic retinopathy in diabetic patients with a mydriasis-free, full-field flicker electroretinogram recording device.

To investigate the accuracy of the RETeval full-field flicker ERG in the screening of diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) and to determine a suitable range of DR diagnostic reference for patients with type 2 diabetes mellitus (T2DM). This was a cross-sectional study involving 172 subjects with T2DM, including 71 subjects without clinically detectable DR (NDR), 25 subjects with mild non-proliferative diabetic retinopathy (NPDR), 24 subjects with moderate NPDR, 27 subjects with severe NPDR and 25 subjects with proliferative diabetic retinopathy (PDR). All the subjects underwent a full-field flicker ERG using the RETeval device (DR assessment protocol), which is a mydriasis-free, full-field electroretinogram (ERG) recording system. The performance of the DR assessment protocol in detecting the DR (including mild NPDR, moderate NPDR, severe NPDR and PDR) and VTDR was analyzed with the receiver operating characteristic (ROC) curve. For the detection of DR (mild NPDR, moderate NPDR, severe NPDR, PDR), the area under the ROC curve was 0.867 (p < 0.001, 95% CI 0.814-0.920), and the best cutoff value for DR was determined to be 20.75, with a sensitivity of 80.2% and specificity of 81.7%. Meanwhile, for the detection of VTDR, the area under the ROC curve was 0.965 (p < 0.001, 95% CI 0.941-0.989), and the best cutoff value was set to 23.05, with a sensitivity of 94.6% and a specificity of 88.8%. The DR assessment protocol in RETeval device was effective in screening for DR (mild NPDR, moderate NPDR, severe NPDR, PDR) and VTDR in patients with diabetes. It could be helpful in referring and managing patients with T2DM in primary healthcare setting. However, caution should be taken that optimal cutoff value of DR assessment protocol may vary in different ethnic populations.

AMPLITUDE LOSS OF THE HIGH-FREQUENCY FLICKER ELECTRORETINOGRAM IN EARLY DIABETIC RETINOPATHY.

To evaluate retinal dysfunction in diabetic patients who have mild or no nonproliferative diabetic retinopathy (DR) using the high-frequency flicker electroretinogram. Light-adapted flicker electroretinograms were recorded from 15 diabetic patients who have no clinically apparent retinopathy, 15 diabetic patients who have mild nonproliferative DR, and 15 nondiabetic, age-equivalent controls. Electroretinograms were elicited by full-field flicker at 2 temporal frequencies, 31.25 and 62.5 Hz, and were recorded using conventional techniques. Amplitude and timing of the flicker responses were compared among the groups and correlated with clinical characteristics including age, acuity, disease duration, and HbA1c. The 31.25-Hz flicker amplitude was slightly, but nonsignificantly, smaller for subjects with no DR and mild nonproliferative DR , compared with the control group (both t < 1.38, P > 0.31); small, nonsignificant response delays for both patient groups were also observed (both t < 1.57, P > 0.12). By contrast, there were significant amplitude reductions for the 62.5-Hz flicker stimulus: mean amplitude was reduced by 32% for subjects with no DR and by 41% for subjects with mild nonproliferative DR (both t > 2.92 and P < 0.01). Response timing at 62.5 Hz did not differ significantly from control for either group (both t < 1.2 and P > 0.39). Electroretinogram amplitude and timing were not correlated significantly with clinical characteristics. The 62.5-Hz flicker electroretinogram is useful for evaluating retinal dysfunction in diabetic patients who have mild or no DR because this response can be significantly reduced. Attenuation of the high-frequency flicker electroretinogram, which is primarily generated by bipolar cells, suggests a relatively early retinal site of neural dysfunction.

Test-retest repeatability of the pattern electroretinogram and flicker electroretinogram.

To evaluate the repeatability of the steady-state pattern electroretinogram (PERG) and full-field flicker electroretinogram (Flicker ERG) protocols, delivered by the office-based Neuro Optic Vision Assessment (NOVA)™ testing platform, in healthy subjects. Healthy individuals underwent PERG (16° and 24°) and Flicker ERG [fixed luminance (FL) and multi-luminance (ML)] testing protocols. Test-retest repeatability of protocols was calculated using intra-class correlation coefficients (ICC). Reference values of the parameters of the aforementioned tests were also calculated. The ICCs for the PERG parameters ranged from 0.793 to 0.911 (p < 0.001). The ICCs for the Flicker ERG parameters ranged from 0.968 to 0.994 (p < 0.001). A linear regression analysis was applied to assess the impact of age on ERG responses. Age had a significant impact on all PERG parameters (16° or 24°). The phase response of the FL Flicker ERG significantly decreased with age (β = - 0.837, p ≤ 0.001). The FL Flicker ERG Magnitude was also impacted with a significant quadratic effect of age (β = - 0.0047, p = 0.0004). Similarly, the Phase Area Under the Curve (Phase AUC) of the ML Flicker ERG significantly declined with age (β = - 0.007, p = 0.009), and the impact on the Magnitude AUC was significant as well, with a negative quadratic age effect. The PERG and Flicker ERG protocols, delivered by an office-based testing platform, were shown to have good-to-excellent test-retest repeatability when tests were performed in the same order and in immediate succession.

Early retinal neurovascular impairment in patients with diabetes without clinically detectable retinopathy

AimsTo investigate the function and the corresponding neurovascular structures in patients with diabetes without clinically detectable retinopathy.Methods Sixty-six patients with type 2 diabetes without retinopathy (NDR) and 62 healthy controls...

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

To determine if the RETeval system can be used for the screening of diabetic retinopathy (DR) to provide early diagnosis. 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. 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. 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.

Factors Affecting Mydriasis-Free Flicker ERGs Recorded With Real-Time Correction for Retinal Illuminance: Study of 150 Young Healthy Subjects.

A small, full-field flicker electroretinogram (ERG) recording system was recently developed to record flicker ERGs without mydriasis (RETeval). The device delivers a stimulus with constant retinal illuminance by adjusting the retinal luminance to compensate for changes in the pupillary area. The purpose of this study was to determine what factors affect the fundamental components of the flicker ERGs recorded by RETeval in young healthy subjects. Flicker ERGs were recorded with the RETeval system from 150 eyes of 150 young healthy subjects (age, 20-29 years). Univariate and multivariate linear regression analyses were performed to identify the factors that affected the implicit times and amplitudes of the fundamental component of the flicker ERGs. The independent variables included age, sex, refractive error, axial length, and pupillary area. Multivariate regression analyses indicated that a longer axial length (P = 0.03) and larger pupillary area (P = 0.008) were independent factors that were significantly associated with longer implicit times of the fundamental component of the flicker ERGs. Multivariate regression analyses also showed that the female sex (P = 0.03) was an independent factor, which was significantly associated with larger amplitude fundamental component of the flicker ERGs. These results indicate that the fundamental components of the RETeval flicker ERGs are significantly affected by the axial length, pupillary area, and sex of young healthy subjects. The results also suggest that it would be better to compensate for the Stiles-Crawford effect when flicker ERGs are recorded with natural pupils.

Diet enriched with the Amazon fruit açaí (Euterpe oleracea) prevents electrophysiological deficits and oxidative stress induced by methyl-mercury in the rat retina

Background: The protective effect of a diet supplemented by the Amazonian fruit Euterpe oleracea (EO) against methylmercury (MeHg) toxicity in rat retina was studied using electroretinography (ERG) and biochemical evaluation of oxidative stress.Method: Wistar rats were submitted to conventional diet or EO-enriched diet for 28 days. After that, each group received saline solution or 5 mg/kg/day of MeHg for 7 days. Full-field single flash, flash and flicker ERGs were evaluated in the following groups: control, EO, MeHg, and EO+MeHg. The amplitudes of the a-wave, b-wave, photopic negative response from rod and/or cone were measured by ERGs as well as the amplitudes and phases of the fundamental component of the sine-wave flicker ERG. Lipid peroxidation was determined by thiobarbituric acid reactive species.Results: All ERG components had decreased amplitudes in the MeHg group when compared with controls. EO-enriched food had no effect on the non-intoxicated animals. The intoxicated animals and those that received the supplemented diet presented significant amplitude reductions of the cone b-wave and of the fundamental flicker component when compared with non-intoxicated control. The protective effect of the diet on scotopic conditions was only observed for bright flashes eliciting a mixed rod and cone response. There was a significant increase of lipid peroxidation in the retina from animals exposed to MeHg and EO-supplemented diet was able to prevent MeHg-induced oxidative stress in retinal tissue.Conclusion: These findings open up perspectives for the use of diets supplemented with EO as a protective strategy against visual damage induced by MeHg.

Cone implicit time as a predictor of visual outcome in macular hole surgery.

To investigate whether preoperative retinal function measured by full-field ERG and multifocal ERG is correlated to postoperative visual acuity after macular hole surgery. Standard pars plana vitrectomy with removal of the internal limiting membrane (ILM) was performed on 19 consecutive patients undergoing macular hole surgery. Intraocular gas tamponade with a C2F6 gas-air mixture was employed, followed by a face-down position for at least 5 days. The patients were examined with the ETDRS chart, full-field ERG (Espion), multifocal ERG (Veris 6), and optical coherence tomography (OCT) preoperatively, and 6 weeks, 6 months, and 18 months after surgery. The cone 30-Hz flicker implicit time in the full-field ERG reflecting retinal function was prolonged (p = 0.016) before surgery compared to aged-matched controls. After macula hole surgery, longstanding alteration of cone function reflected by mfERG and full-field ERG was verified 18 months after surgery. The prolonged cone 30-Hz flicker implicit time in the full-field ERG before surgery was significantly correlated to the ETDRS visual acuity 6 months postoperatively (p = 0.03). Preoperative evaluation of retinal function with multifocal ERG and full-field ERG improves the understanding of the retinal recovery process after macular hole surgery. The cone implicit time in full-field 30-Hz flicker ERG could be a valid predictor of long-term visual outcome, which may be useful for selecting patients suitable for surgery.

Electroretinographic Responses in Epileptic Children Treated With Vigabatrin

Vigabatrin is an antiepileptic drug that results in higher gamma-aminobutyrate levels in the brain and retina. Vigabatrin-induced visual field defects are usually asymptomatic and only detectable by perimetry. Further, perimetry requires good cooperation, and children aged under 10 years cannot do it. Electroretinogram response amplitude to full-field 30-Hz flicker shine has been offered to be more specific in predicting visual field defects. This study is scheduled to investigate the vigabatrin-associated visual complications in 67 epileptic children taking vigabatrin using full-field electroretinogram. Electroretinographic surveys showed normal range parameters despite 3 months of vigabatrin treatment, and just 3 (4.47%) children had been visually impaired at the end of 6-month treatment. Among these 3 cases, 1 patient had persistent electroretinogram abnormality despite vigabatrin discontinuation. Our study suggests that vigabatrin is secure for short-term pediatric antiepileptic treatment, with few cases of visual impairments and that are often reversible.

Population receptive fields in human visual cortex measured with subdural electrodes

PURPOSE. Electrophysiological methods in animal models have been used to identify receptive field properties of neurons within retinotopic maps. More recently functional magnetic resonance imaging (fMRI) methods in human have been used to estimate population receptive fields (pRF) (Dumoulin and Wandell, 2008; Kay et al., 2008). Following Yoshor et al. (2007), we developed an efficient method of electrocorticography (ECoG) using subdural electrodes in pre-surgical clinical subjects to estimate pRFs in human visual cortex. These measures bridge human fMRI and animal electrophysiological studies. METHODS. Two patients with implanted intracranial electrodes (2-mm surface diameter) viewed a flickering contrast pattern through a bar aperture that swept across the visual field 8 times (4 cardinal, 4 diagonal directions; 96 seconds total). The contrast pattern flickered at 7.5 Hz, creating a steady-state ECoG response with power concentrated at twice the stimulus frequency (15 Hz). For each electrode a time-series of the time-varying 15-Hz amplitude was extracted, and modeled using an isotropic 2D-Gaussian pRF. RESULTS. The pRF model fit occipital electrodes' time-series well, explaining up to 83% of the variance. The pRF parameters were similar to those obtained from fMRI; for example, the pRF size increased with eccentricity and was larger in extrastriate regions than in electrodes near the occipital pole. The signal response latencies were estimated from the phase of the response to full-field flicker (separate runs). We observed robust position-dependent latency effects, ranging from 10–40 ms delay relative to responses near the occipital pole. CONCLUSION. Population receptive fields can be estimated using ECoG. There is good agreement between fMRI and ECoG measures despite significant differences in their physiological bases. The ECoG data provide latency information that is unavailable in the fMRI responses. This is a valuable method for probing population-level spatiotemporal properties of receptive fields in human visual cortex.

Monocular and binocular steady-state flicker VEPs: frequency–response functions to sinusoidal and square-wave luminance modulation

Steady-state VEPs to full-field flicker (FFF) using sinusoidally modulated light were compared with those elicited by square-wave modulated light across a wide range of stimulus frequencies with monocular and binocular FFF stimulation. Binocular and monocular VEPs were elicited in 12 adult volunteers to FFF with two modes of temporal modulation: sinusoidal or square-wave (abrupt onset and offset, 50% duty cycle) at ten temporal frequencies ranging from 2.83 to 58.8 Hz. All stimuli had a mean luminance of 100 cd/m(2) with an 80% modulation depth (20-180 cd/m(2)). Response magnitudes at the stimulus frequency (F1) and at the double and triple harmonics (F2 and F3) were compared. For both sinusoidal and square-wave flicker, the FFF-VEP magnitudes at F1 were maximal for 7.52 Hz flicker. F2 was maximal for 5.29 Hz flicker, and F3 magnitudes are largest for flicker stimulation from 3.75 to 7.52 Hz. Square-wave flicker produced significantly larger F1 and F2 magnitudes for slow flicker rates (up to 5.29 Hz for F1; at 2.83 and 3.75 Hz for F2). The F3 magnitudes were larger overall for square-wave flicker. Binocular FFF-VEP magnitudes are larger than those of monocular FFF-VEPs, and the amount of this binocular enhancement is not dependant on the mode of flicker stimulation (mean binocular: monocular ratio 1.41, 95% CI: 1.2-1.6). Binocular enhancement of F1 for 21.3 Hz flicker was increased to a factor of 2.5 (95% CI: 1.8-3.5). In the healthy adult visual system, FFF-VEP magnitudes can be characterized by the frequency-response functions of F1, F2 and F3. Low-frequency roll-off in the FFF-VEP magnitudes is greater for sinusoidal flicker than for square-wave flicker for rates ≤ 5.29 Hz; magnitudes for higher-frequency flicker are similar for the two types of flicker. Binocular FFF-VEPs are larger overall than those recorded monocularly, and this binocular summation is enhanced at 21.3 Hz in the mid-frequency range.