Flash Visual Evoked Potentials Research Articles

Study on the variation of visual evoked potential and its diagnostic value in children with optic neuritis

Objective To investigate the characteristics and clinical value of visual evoked potentials(VEP) in children with optic neuritis. Methods The VEP of 33 children with optic neuritis were tested by NICOLET evoked potential instrument.The results were compared with those of cranial and/or orbital MRI and fundus examination, and the consistency with visual performance was analyzed.The correlation between visual sensitivity and VEP results was analyzed. Results Among 33 children with optic neuritis, the abnormal rate of VEP in 52 abnormal eyes was 88.5%; the abnormal rate of cranial and/or orbital MRI was 38.5%; the abnormal rate of fundus examination was 62.2%; the abnormal rate of VEP examination was significantly higher than that of cranial and/or orbital MRI and fundus examination (P<0.05); the consistency rate between VEP examination and visual acuity was 84.8%.The consistency rate between pattern reversal visual evoked potential (P-VEP) and visual acuity was 86.8%, and that between flash visual evoked potential (F-VEP) and visual acuity was 82.1%.With the increase of visual impairment, the percentage of P100 wave loss increased gradually.There was no correlation between visual acuity and the prolongation of P100 wave latency. Conclusion There are significant differences between VEP and fundus examination and MRI, the sensitivity of VEP is superior to both.P-VEP is more consistent with visual acuity than F-VEP.VEP has certain value in evaluating the degree of visual impairment in children with optic neuritis.It can not be used to evaluate the level of optic sensitivity when the latency of P100 wave is prolonging. Key words: Optic neuritis; Visual evoked potentials; Visual; Children

Deep Learning for Automatically Visual Evoked Potential Classification During Surgical Decompression of Sellar Region Tumors.

PurposeDetection of the huge amount of data generated in real-time visual evoked potential (VEP) requires labor-intensive work and experienced electrophysiologists. This study aims to build an automatic VEP classification system by using a deep learning algorithm.MethodsPatients with sellar region tumor and optic chiasm compression were enrolled. Flash VEP monitoring was applied during surgical decompression. Sequential VEP images were fed into three neural network algorithms to train VEP classification models.ResultsWe included 76 patients. During surgical decompression, we observed 68 eyes with increased VEP amplitude, 47 eyes with a transient decrease, and 37 eyes without change. We generated 2,843 sequences (39,802 images) in total (887 sequences with increasing VEP, 276 sequences with decreasing VEP, and 1680 sequences without change). The model combining convolutional and recurrent neural network had the highest accuracy (87.4%; 95% confidence interval, 84.2%–90.1%). The sensitivity of predicting no change VEP, increasing VEP, and decreasing VEP was 92.6%, 78.9%, and 83.7%, respectively. The specificity of predicting no change VEP, increasing VEP, and decreasing VEP was 80.5%, 93.3%, and 100.0%, respectively. The class activation map visualization technique showed that the P2-N3-P3 complex was important in determining the output.ConclusionsWe identified three VEP responses (no change, increase, and decrease) during transsphenoidal surgical decompression of sellar region tumors. We developed a deep learning model to classify the sequential changes of intraoperative VEP.Translational RelevanceOur model may have the potential to be applied in real-time monitoring during surgical resection of sellar region tumors.

Sema3A inhibits axonal regeneration of retinal ganglion cells via ROCK2

Successful regeneration of injured axons in the adult mammalian central nervous system (CNS) is mainly limited by lesion-induced neuronal apoptosis and the inhibitory environment consisting of numerous extrinsic and intrinsic factors. Semaphorin 3A (Sema3A), a classic axonal guidance cue, contributes to the failure of axonal regeneration and can be neutralized to enhance axonal regeneration. Previous studies have suggested that blockage of rho-associated protein kinase 2 (ROCK2) also exerts a protective effect on the survival and axonal regeneration of retinal ganglion cells (RGC, RGCs) after injury. Yet unresolved question is the interaction between the two factors. We thus evaluated the role of Sema3A and ROCK2 in RGC axonal regeneration. In this study, we first examined the expression of Sema3A and ROCK2 against optic nerve crush in vivo and oxygen-glucose deprivation insult to RGCs in vitro at different time points. Then Sema3A, ROCK2 inhibitor Y-27632, combination of both and phosphate-buffered saline (PBS) only were injected into the vitreous cavity after optic nerve crush at various times in different experiments. In order to assess axonal regeneration, we detected the mRNA levels of small proline-rich protein 1A (Sprr1A) and growth-associated protein 43 (GAP43) by quantitative real time-polymerase chain reaction (RT-qPCR), evaluated visual function by Flash Visual Evoked Potentials (F-VEPs), and checked the protein level of GAP43 by immunofluorescent staining. Our results demonstrated that Sema3A significantly suppressed optic nerve regeneration and this effect can be attenuated via blocking ROCK2. Moreover, Sema3A promoted the phosphorylation of myosin light chain 2 (MLC2) (specific downstream effector of ROCK2 concerning neurite growth). Collectively, Sema3A may negatively regulate axonal regeneration through ROCK2 in RGCs.

The Detection Of Misrouting In Albinism: Evaluation of Different VEP Procedures in a Heterogeneous Cohort.

To investigate the optimal procedures for multichannel visually evoked potentials (VEPs) to detect misrouting in albinism subjects. Investigations were done in a phenotypically heterogeneous group of 180 albinism subjects and 187 controls with and without ocular pathology. We retrospectively compared standard flash VEP (fVEP), high-frequency fVEP with a handheld device (hh fVEP), pattern-onset VEP (poVEP), and short-onset acuity sweep VEP. The diagnostic power of these stimuli were estimated by calculating the area under the curve (AUC). Subjects were divided in three age groups (<3, 3-6 [toddler], and ≥6 years). Subjects ≥6 years of age were further divided in two visual acuity groups (≤0.3 logMAR and >0.3 logMAR). The optimal stimulus was hh fVEP, standard fVEP, and poVEP 60' for subjects <3, 3-6, and ≥6 years of age, respectively. In subjects ≥6 years old with poor visual acuity, the area under the curve of fVEP was almost equal to that of poVEP 60'. For the optimal detection of misrouting with multichannel VEP recordings, we recommend using a high-frequency hh fVEP in children <3 years of age, standard fVEP in toddlers, and poVEP 60' in subjects ≥6 years of age. fVEP can also be used in the oldest age group for subjects with visual acuity of >0.3 logMAR. Remarkably, some albinism subjects showed misrouting on full-field stimulation but normal routing of the central retina, suggesting that not the whole line of decussation is shifted temporally.

Therapeutic Effects of Puerarin Against Anterior Ischemic Optic Neuropathy Through Antiapoptotic and Anti-Inflammatory Actions.

This study investigated the therapeutic effects of puerarin (PR) on a rat model of anterior ischemic optic neuropathy (rAION). The neuroprotective effects of PR on rAION were evaluated using flash visual-evoked potentials (FVEP), retrograde labeling of retinal ganglion cells (RGCs), TUNEL assay of the retina, optical coherence tomography (OCT) images of optic nerve width, and ED1 staining of the optic nerve (ON). The inflammatory response of ON and Akt signaling pathways were analyzed through Western blot. M2 polarization was determined by immunostaining and immunoblotting in ONs. In FVEP analysis, the amplitude of P1-N2 and the RGC density in the PR-treated group were 2.3- and 1.6-fold higher than those in the PBS-treated group, respectively (P < 0.05). The number of apoptotic RGC in the PR-treated group was 2.8-fold lower than that in the PBS-treated group. OCT images demonstrated that PR treatment-reduced ON edema in the acute phase compared to PBS treatment (P < 0.05). Macrophage infiltration was reduced by 5.2-fold by PR treatment compared with the PBS treatment (P < 0.05). PR treatment inhibited the levels of iNOS, IL-1β, and TNF-α, induced the levels of IL-10, Arg1, and Fizz1 in the rAION model. The levels of p-Akt1 and C/EBPβ in the PR-treated group increased by 3.4-fold and 5.89-fold compared with those in the PBS-treated group (P < 0.05). Inhibition of Akt activation reduced the number of M2 macrophage in the PR-treated group (P < 0.05). PR treatment provided the neuroprotective effects in the rAION model, which may lead to new clinical applications.

Effect of simulated microgravity on the photopic negative response of flash electroretinogram in adult mice

Objective To observe the effect of simulated microgravity on the photopic negative response (PhNR) of full-field flash ERG in adult mice. Methods In an experimental study, forty-eight adult male C57BL/6J mice (48 eyes) were randomly divided into model and control groups. Model mice were further divided into three subgroups of 8 each: tail-suspended for 15 days (subgroup A), tail-suspended for 30 days (subgroup B), and tail-suspended for 30 days followed by returning to normal position for 30 days (subgroup C). The three control subgroups were similarly fixed with a harness but kept in the normal position for corresponding periods of 15, 30, and 60 days. The mice were immediately examined using ERG-PhNR, flash VEP, OCT and visually-guided behavior in vivo, and subsequently sacrificed to analyze the retinal histology in vitro. PhNR amplitude was measured from baseline to PhNR trough. N1 peak-time and N1-P1 amplitude of VEP was analyzed. The escape duration was used to quantitatively evaluate the visual function of mice. In addition, inner retinal thickness was analyzed by OCT imaging. Data were compared by the independent sample t-test. Results PhNR amplitude in the model subgroup A was obviously lower than the corresponding control subgroup, the difference was statistically significant (t=−3.196, P 0.05). There was no significant difference in FVEP N1 peak-time or N1-P1 amplitude between any of the three model subgroups and the corresponding control subgroup (P>0.05). There was no significant difference in OCT-measured inner retinal thickness between any of the three model subgroups and the corresponding control subgroup (t=−0.461, 2.073, −0.402; P>0.05). The three model subgroups showed almost normal retinal structure, including the retinal ganglion cell, inner pexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, ellipsoid zone and RPE. There was no significant difference in visually-guided escape time between any of the three model subgroups and the corresponding control subgroup (t=−0.637, −0.955, 1.297; P>0.05). Conclusion Via tail-suspension, short-term simulated microgravity can affect the PhNR of flash ERG; however, the change is reversible and does not affect visual function of mice. Key words: Weightlessness simulation; Electroretinography; Animal experimentation

Influence of enriched environment on visual function and synaptic plasticity in adult amblyopic mice

Objective To examine role and possible mechanism of enriched environment (EE) on regulating recovery of visual function in adult monocular deprivation amblyopia mice. Methods A total of 72 healthy Kunming mice were divided into normal control group, monocular deprivation (MD) group, MD+ EE group and MD+ fluoxetine group by random number table.Except for the normal control group, the mice in the other groups were sutured on the right eyelid 21 days after birth to establish MD amblyopia model.the mice were fed in standard environment or EE for 4 weeks according to the group.Visual acuity and flash visual evoked potential (F-VEP) of mice in each group were detected.The distribution of microtubule associated protein 2 (MAP2) in visual cortex of adult amblyopic mice were detected by immunohistochemistry.The expression of MAP2, synaptophysin (SYP) and postsynaptic density protein-95 (PSD-95) protein in visual cortex of adult amblyopic mice were detected by western blot.The experimental protocol was approved by the Animal Care and Use Committee of Hunan Children's Hospital and conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Results There was a significant difference in the visual acuity of deprived eye among each group (F=114.632, P<0.001). The visual acuity in MD group is lower than that in normal control group, with a significant difference (t=15.480, P<0.001). Compared with MD group, visual acuity was restored in MD+ EE group and MD+ fluoxetine group, with significant differences (t=15.071, P<0.001; t=14.841, P<0.001). There was a significant difference in the P2 latency and amplitude of F-VEP in deprived eye among each group (F=36.510, P=0.000; F=34.140, P=0.000). Compare with normal control group, P2 latency was prolonged and P2 amplitude of F-VEP was decreased in deprived eye in MD group, with significant differences (t=10.220, P=0.000; t=10.09, P=0.000). Western blot assay showed that there was a significant difference in the expression of MAP2 in visual cortex contralateral deprived eye among each group (F=18.142, P=0.000). The expression of MAP2 in MD group was significantly lower than that in normal contral group (t=3.056, P<0.01); Compared with MD group, MAP2 expression was increased in MD+ EE group and MD+ fluoxetine group (t=2.541, P=0.031; t=2.157, P=0.017). There were significant differences in the expression of SYP and PSD-95 in visual cortex contralateral to deprived eye among each group (F=12.871, P=0.000; F=25.060, P=0.000). Compared with normal contral group, SYP and PSD-95 expression in visual cortex were down-regulated in MD group, with significant differences (t=6.054, P=0.000; t=8.631, P=0.000). The expression of SYP and PSD-95 protein in MD+ EE group and MD+ fluoxetine group were significantly higher than those in MD group (all at P<0.05). Conclusions EE can recover visual function through up-regulating the expression of MAP2, which can modulate the dendritic branch trim and neural plasticity of visual cortex in adult MD mice. Key words: Enriched environment; Monocular deprivation; Amblyopia; Visual cortex; Plasticity

Analysis of clinical characteristics of optic nerve metastases

Objective To explore the clinical features, primary lesions and prognosis of optic nerve metastases. Methods Seven patients (11 eyes) with optic nerve metastatic tumor diagnosed by the examinations of ophthalmology, laboratory and pathology in Chinese PLA General Hospital from April 2015 to September 2017 were included in this study. All patients underwent BCVA, flash VEP, OCT, orbital MRI, serum tumor marker, cerebral spinal fluid detection and PET-CT. Histopathological examination of primary or near superficial metastases was performed. The follow-up period was ranged from 16 to 44 months, with the mean of 23.0±10.9 months. The clinical characteristics, primary tumor, imaging features, treatment and clinical prognosis in the patients were analyzed. Results Among 7 patients, there were 5 males and 2 females, with the mean age of 53.90±14.99 years; 3 patients with unilateral optic nerve involvement, 4 patients with bilateral optic nerve involvement; 5 patients (71.4%) first diagnosed in ophthalmology. Five patients (45.5%) were misdiagnosed as optic neuritis, optic disc edema in 6 eyes (54.5%). All of them appear loss of visual acuity, including 8 eyes (72.7%) with BCVA 0.5. MRI results show that 1 patient with intraorbital segment, 1 patient with internal segment of optic canal, 4 patients with intracranial segment, 1 patient with intracranial segment and optic chiasma involved simultaneously, 4 patients involving surrounding tissue. There were 4 patients (57.1 %) with lung cancer, 2 patients (28.6%) with kidney cancer, 1 patient (14.3%) with gastric cance; 6 patients (85.7%) with metastasis from other sites, 2 patients with brain metastasis (1 patient with meningitis carcinomatosa). There were 2 patients(28.6%) with previous primary cancer surgery. After diagnosis, 1 patient received chemotherapy, 1 patient received radiotherapy, 5 patients gave up treatment. At the end of follow-up, 1 patient (1 eye) of chemotherapy with BCVA increased by 2 line; 1 patient (2 eyes) of radiotherapy with no change in BCVA; of the 5 patients who gave up treatment, 1 patient died of disease, 1 patient lost follow-up, and 3 patients (4 eyes) had no change in BCVA. Conclusions With atypically clinical manifestations, the optic nerve metastases easily misdiagnosed as optic neuritis, and with poor therapeutic effect. Primary lesions are mostly found in lung cancer. Key words: Optic nerve neoplasms; Neoplasm metastasis; Lung neoplasms; Disease attributes

Intraoperative Flash Visual Evoked Potential Recording and Relationship to Visual Outcome.

To determine the relationship between intraoperative flash visual evoked potential (FVEP) monitoring and visual function. Intraoperative FVEPs were recorded from electrodes placed in the scalp overlying the visual cortex (Oz) after flashing red light stimulation delivered by Cadwell LED stimulating goggles in 89 patients. Restrictive filtering (typically 10-100 Hz), optimal reject window settings, mastoid reference site, total intravenous anesthetic (TIVA), and stable retinal stimulation (ensured by concomitant electroretinogram [ERG] recording) were used to enhance FVEP reproducibility. The relationship between FVEP amplitude change and visual outcome was determined from 179 eyes. One eye had a permanent intraoperative FVEP loss despite stable ERG, and this eye had new, severe postoperative visual dysfunction. Seven eyes had transient significant FVEP change (&gt;50% amplitude decrease that recovered by the end of surgery), but only one of those had a decrease in postoperative visual acuity. FVEP changes in all eight eyes (one permanent FVEP loss plus seven transient FVEP changes) were related to surgical manipulation. In each case the surgeon was promptly informed of the FVEP deterioration and took remedial action. The other eyes did not have FVEP changes, and none of those eyes had new postoperative visual deficits. Our FVEP findings relate to visual outcome with a sensitivity and specificity of 1.0. New methods for rapidly acquiring reproducible FVEP waveforms allowed for timely reporting of significant FVEP change resulting in prompt surgical action. This may have accounted for the low postoperative visual deficit rate (1%) in this series.

Semi-invasive and non-invasive recording of visual evoked potentials in mice.

Visual evoked potentials (VEPs) are used to assess visual function in preclinical models of neurodegenerative diseases. VEP recording with epidural screw electrodes is a common method to study visual function in rodents, despite being an invasive procedure that can damage the tissue under the skull. The present study was performed to test a semi-invasive (epicranial) and a non-invasive (epidermal) VEP recording technique, comparing them with the classic epidural acquisition method. Flash VEPs were recorded from C57BL/6 mice on three separate days within 2weeks. Waveforms, latencies and amplitudes of the components were compared between the three different methods, utilizing coefficient of repeatability, coefficient of variation and intersession standard deviation to evaluate reproducibility. While epidural electrodes succeeded in recording two negative peaks (N1 and N2), epicranial and epidermal electrodes recorded a single peak (N1). Statistical indexes showed a comparable reproducibility between the three techniques, with a greater stability of N1 latency recorded through epicranial electrodes. Moreover, N1 amplitudes recorded with the new less-invasive methods were more reproducible compared to the invasive gold-standard technique. These results demonstrate the reliability of semi- and non-invasive VEP recordings, which can be useful to evaluate murine models of neurological diseases.

Visual Outcome of Carotid Endarterectomy in Patients with Carotid Artery Stenosis

Carotid endarterectomy (CEA) is deemed to restore the blood flow of the carotid and ophthalmic arteries in patients with carotid artery stenosis. However, specific changes in visual function before and after CEA are not well understood; hence, this observational study aimed to investigate the functional and structural changes in vision after CEA in those patients. Patients with severe carotid artery stenosis (>70% with standard carotid duplex scanning or arteriography) scheduled to undergo CEA were consecutively recruited for the study between September 2015 and July 2016. All patients underwent a standardized ophthalmic examination, including intraocular pressure (IOP) measurement, slit-lamp examination, and fundus examination. Visual acuity, best corrected visual acuity (BCVA), and kinetic and static visual fields (VFs) were tested to evaluate subjective visual function. Flash and pattern visual evoked potentials (VEPs) and an electroretinogram (ERG) were measured for objective visual function. Retinal nerve fiber layer (RNFL) thickness was scanned using optical coherence tomography for structural evaluation. The study involved 15 patients (11 male and 4 female, corresponding to 30 eyes; mean age 62.8±5.0years). After CEA, both uncorrected visual acuity and BCVA improved, and IOP significantly decreased from 17.41±2.59 to 15.95±2.50mm Hg (P=0.0022). Kinetic VF range increased significantly (P=0.0126) as did mean sensitivity from 18.8±5.5 to 20.6±4.3dB(P=0.0208), whereas mean defect decreased from 8.2±5.3 to 6.5±4.2dB(P=0.025). RNFL thickness was not significantly altered. Latency of the P2 wave on flash VEP reduced significantly after CEA (P=0.0151), whereas the oscillatory potential amplitude of waveform 3 in the ERG significantly increased after CEA. Our results demonstrate that an improvement in carotid artery and ophthalmic artery blood flow after CEA does indeed enhance subjective and objective assessments of visual function in patients with carotid artery stenosis, including visual acuity, kinetic and static VF, P2 latency, and ocular pressure amplitude; however, it did not affect RNFL thickness.

Mitochondria-targeted antioxidant peptide SS-31 mediates neuroprotection in a rat experimental glaucoma model.

To investigate the neuroprotective effects of the mitochondria-targeted antioxidant Szeto-Schiller peptide 31 (SS-31) in a rat experimental glaucoma model, SS-31 was intraperitoneally (IP) injected into Sprague-Dawley rats, followed by intracameral injection of polystyrene microspheres to induce elevated intraocular pressure (IOP). After 6 weeks, electroretinography (ERG) and flash visual-evoked potentials (F-VEPs) were recorded to assess retinal function. Hematoxylin-eosin staining was performed on retinal cross-sections to measure ganglion cell complex (GCC) thickness. Apoptotic retinal cells were assessed by TUNEL staining. Brn3a-positive retinal ganglion cells (RGCs) were counted in retinal flat mounts via immunofluorescence. The retinal total SOD, SOD2, and MDA expression levels were assessed in retinal tissue homogenates. The cyt c, Bax, and Bcl-2 protein levels in rat retinas were detected by western blot analysis. Bax and Bcl-2 expressions were also evaluated using immunohistochemistry in paraffinized sections. Our results showed that the rats that received microsphere injection developed elevated IOP. SS-31 ameliorated the reductions in the a- and b-wave amplitudes on ERG and the F-VEP amplitude in glaucomatous eyes. GCC thickness was preserved, TUNEL-positive cells were decreased in the retina, and Brn3a-positive RGCs were increased in the SS-31-treated glaucoma group compared with those in the non-treated glaucoma group. SS-31 significantly reduced MDA levels and increased SOD2 levels after glaucoma induction. Significant suppression of cyt c release, upregulation of Bcl-2, and downregulation of Bax were observed following SS-31 administration. In summary, SS-31 exerts neuroprotective effects in this experimental glaucoma model by inhibiting mitochondrial dysfunction and therefore represents a promising therapeutic agent for glaucoma.

Age Related Decline in Cortical Multifocal Flash VEP: Latency Increases Shown to Be Predominately Magnocellular.

As the visual system ages, flicker sensitivity decreases and the latencies of cortical visual evoked potentials (VEP) increase. However, the extent to which these effects reflect age-related changes in the magnocellular (M) and or parvocellular (P) pathways remain unclear. Here, we investigated the relation between flicker fusion frequencies and VEP non-linearities induced by rapid stimulation, as a function of age over 6 decades. The approach, using Wiener kernel analysis of multifocal flash (mf)VEP, allows the extraction of signatures of both M and P processing and hence establishing a neural basis of the known decline in flicker fusion threshold. We predicted that, in a sample of 86 participants, age would be associated with a latency increase in early mfVEP response components and that flicker fusion thresholds, for both low and high contrast stimuli, would relate to the temporal efficiency of the M-generated VEP component amplitudes. As expected, flicker fusion frequency reduced with age, while latencies of early second order peaks of the mfVEP increased with age, but M temporal efficiency (amplitude ratio of first to second order peaks) was not strongly age-related. The steepest increases in latency were associated with the M dominated K2.1 (second order first slice) N70 components recorded at low and high contrast (6.7 and 5.9 ms/decade, respectively). Interestingly, significant age-related latency shifts were not observed in the first order responses. Significant decreases in amplitude were found in multiple first and second order components up to 30 years of age, after which they remained relatively constant. Thus, aging and decline in visual function appears to be most closely related to the response latencies of non-linearities generated by the M pathway.

Electroretinogram (ERGs) and visual evoked potentials (VEPs) study in prion disease (CJD)

Literature reported on ERGs and VEPs changes in patients with prion disease (CJD). To characterize the extent of ERG and VEPs involvement in confirmed CJD; to assess ERGs and VEPs diagnostic usefulness in the workout of suspected CJD. White flash ERG (a/b-wave, 30-Hz flicker, oscillatory potentials) and VEP (P1, N1 and P2 components) were recorded in 122 consecutive unselected CJD patients (57 females, 65 males, mean age: 61.98 years) and compared with: (a) normal and control non-CJD (sensitivity and specificity), and (b) EEG, MRI and laboratory tests. ERG changes were correlated with pathology of the retina performed in several cases. ERG/VEPs were abnormal in just over 60% of CJD, compared with 76% MRI and 66% EEG abnormal rate; ERG changes revealed definite correlation with the codon129, VEPs did not; giant VEPs was recorded in the MM subtype; the VV patients had the most severe retinal changes. Twenty-two patients recorded over a period of six months showed ERG deteriorative pattern, VEPs did not, for it remained stable. ERGs/VEPs revealed abnormalities in CJD patients whose EEG and/or MRI did not show typical changes; although nonspecific they contribute to propose a diagnostic workout of patients suspected of CJD.

Steady-state flash VEPs in children with optic nerve atrophy: preliminary data

Flash steady state visual evoked potentials (fSSVEPs) were introduced over 80 years ago. In infancy, fSSVEPs may be useful because of their rapid acquisition time and small variability. Few studies proved their utility in clinical setting.1,2. The aim of this study was to evaluate 33 Hz fSSVEPs in children with optic atrophy using standardized visual inspection analysis. Twenty-seven children (mean age 3.9 ± 3.2 years) diagnosed with optic nerve atrophy underwent transient and fSSVEPs in Robert Hollman Foundation. Stimuli consisted of white light flash at 1–33 Hz. Analysis: N1 and P2 waves of TVEP and visual inspection of fSSVEPs for presence/absence of the fundamental response or other harmonics. 3 subjects were excluded because of artifacts. 16/24 patients with abnormal TPEV had absence of fundamental frequency but presence of a subharmonic; 5 patients had an absent or markedly reduced response. All subjects with normal TPEV had absent or markedly reduced fundamental harmonic and presence of a subharmonic. According to Shpak2 fSSVEPs can be useful in differential diagnosis of optic atrophy in children. These preliminary results suggest that the implementation of flash TVEPs methodology with fSSVEPs can provide further diagnostic information and encourage further studies in optic nerve and visual pathways disorders.

Optic nerve head width and retinal nerve fiber layer changes are proper indexes for validating the successful induction of experimental anterior ischemic optic neuropathy

Reproducible skills are essential for successful induction of a rat model of anterior ischemic optic neuropathy (rAION). We established an in vivo validation index by measuring the natural course of optic nerve head (ONH) width and retinal nerve fiber layer (RNFL) thickness in the rAION model using optical coherence tomography (OCT). The rAION model was induced by photodynamic operations. We measured the ONH width, RNFL, Inner Plexiform layer (IPL) and Ganglion cell complex (GCC) thickness in the acute stage (<3 days), subacute stage (day-7 to day-14) and later stage (day-14 to day-28) post-infarct by OCT. Retinal layers were measured by hematoxylin and eosin stain (HE) to confirm the OCT findings. The RGCs survival rate was determined by retrograde Fluoro-gold labeling, and the visual function was assessed with flash visual-evoked potentials (FVEPs) 4 weeks post-infarct. We observed significant thinning in GCC, IPL, and RNFL at day-14 and day-28 but only RNFL showed significant thinning between day-14 and day-28. The ONH showed significant swelling in the acute stage which correlated at a greater extent with RNFL than GCC and IPL. Further RNFL correlated at a greater extent at with GCC than IPL. HE-stained retina cross sections also showed IPL and RNFL thinning, which further confirmed our OCT findings. The RGC density and P1-N2 amplitude were significantly reduced in rAION. Our data suggest that Swelling, reduction of swelling, and atrophy of RNFL in acute, sub-acute, and later stage, respectively and ONH swelling in the acute stage are essential events for confirming the successful induction of rAION.

Flash visual evoked potentials (FVEP) in various stimulation conditions

AimTo compare flash visual evoked potentials (FVEP) elicited using a Ganzfeld bowl (G), Mini Ganzfeld (MG) and Flash Goggles (GG) with eyes open and closed.Patients and methodThe study group comprised 17 volunteers with mean age of 30 years; all of them were examined with the Roland Consult electrophysiological diagnostic system. Active electrodes were placed at O1 and O2. With the G and MG stimulators, the flash generated by white-light-emitting diodes (LEDs) presented standard flash of 3 cd s m−2. The GG used red LED flash of 3 cd s m−2. Stimulus frequency of 1.0 Hz, low-pass filter of 1.0 Hz and high-pass filters of 100 Hz (G); 50 Hz (MG); 30 Hz (GG) were used. P2 amplitude and latency were compared by the means of the Wilcoxon matched-pairs signed-rank test.ResultsAfter right eye stimulation (from O1; n = 17), the mean amplitudes of P2, elicited with the G, MG and GG, were 13, 7 and 10 µV, respectively. The respective latencies were 129, 114 and 110 ms. Hence, the difference between the results obtained with these stimulators was statistically significant (p < 0.05). The mean P2 amplitudes, acquired by the means of the G, MG and GG, were 13 µV, 7 µV and 10 µV for open eyes, and 11 µV, 8 µV and 8 µV for closed eyes. The respective latencies were 129, 114 and 110 ms for eyes open, and 127, 125 and 121 ms for eyes closed. These results of the MG (latency only) and GG (latency and amplitude) stimulation differed significantly (p < 0.05).ConclusionThe amplitudes and latencies of the FVEP P2 elicited with different stimulators are not suitable for comparison. Closing the eye during the examination had a significant effect on the components of FVEP waveform elicited with the Flash Goggle and on the latency of P2 elicited with the MG.

A rodent model of anterior ischemic optic neuropathy (AION) based on laser photoactivation of verteporfin

BackgroundA rodent model of photodynamic AION resulting from intravenous verteporfin is presented. The analysis of the morphological function, the pathological changes and the potential mechanism of action were further investigated.MethodsPhotodynamic treatment was conducted on the optic nerve head (ONH) following administration of the photosensitizer. The fellow eye was considered as sham control. Fundus Fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT) and Flash-visual evoked potential (F-VEP) recordings were conducted at different time points. Immunohistochemistry was used to observe apoptotic cell death (TUNEL) and macrophage infiltration (ED-1/Iba-1). Retrograde labeling of retinal ganglion cells (RGCs) was used to evaluate the loss of RGCs.ResultsAfter laser treatment, SD-OCT indicated optic nerve edema, while FFA indicated late leakage of the ONH. F-VEPs were distinctly reduced compared to control eyes. The number of apoptotic RGCs peaked on day 14 (5.71 ± 0.76, p < 0.01). The infiltration of ED-1 and Iba-1 increased on the 3rd day following PDT, while it peaked on day 14 (67.5 ± 9.57 and 77.5 ± 12.58 respectively, p < 0.01). Following 3 weeks of AION, the densities of RGCs in the central retinas of the normal and AION eyes were 3075 ± 298/mm2 and 2078 ± 141/mm2 (p < 0.01), respectively.ConclusionsVerteporfin photodynamic treatment on rodents ONH can lead to functional, histological, and pathological changes. This type of animal model of AION is easy to establish and stable. It can be used for studying the mechanism and neuroprotective medicine of AION injury.

Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis

ObjectiveTo evaluate the ophthalmic phenotypes associated with T-cell immune regulator 1 (TCIRG1) mutations in Chinese patients with infantile malignant osteopetrosis (IMO).Methods and analysis27 Chinese TCIRG1-related osteoporosis infants were enrolled using...

Cases of visual impairment caused by cerebral venous sinus occlusion-induced intracranial hypertension in the absence of headache

BackgroundCerebral venous sinus thrombosis or stenosis (here collectively referred to as cerebral venous sinus occlusion, CVSO) can cause chronically-elevated intracranial pressure (ICP). Patients may have no neurological symptoms other than visual impairment, secondary to bilateral papilledema. Correctly recognizing these conditions, through proper ophthalmological examination and brain imaging, is very important to avoid delayed diagnosis and treatment.Case presentationWe report a case series of 3 patients with chronic CVSO, who were admitted to an ophthalmological department in Chongqing, China, from 2015 March to 2017 February. All patients presented with decreased vision and bilateral papilledema, but had no headache or other neurological symptoms. The visual fields of all patients were impaired. Flash visual evoked potentials (VEPs) in two patients showed essentially normal peak time of P2 wave, and pattern VEPs in one patient displayed decreased P100 amplitude in one eye, while a normal P100 wave in the other eye. In all patients, lumbar puncture (LP) revealed significantly elevated ICP. And magnetic resonance venography (MRV) demonstrated cerebral venous sinus abnormalities in every patient: one right sigmoid sinus thrombosis, one superior sagittal sinus thrombosis, and one right transverse sinus stenosis.ConclusionsCVSO can cause chronically-elevated ICP, leading to bilateral papilledema and visual impairment. A considerable amount of patients have no apparent neurological symptoms other than visual loss. Unlike other optic nerve lesions, such as neuritis or ischemic optic neuropathy, the optic disc edema in CVSO is usually bilateral, the flash or pattern VEP is often normal or only mildly affected, and patients are often not sensitive to steroid therapy. CVSO should be suspected in such patients when unenhanced brain imaging is normal. Further investigations, such as LP and contrast-enhanced imaging (MRV and digital subtraction angiography), should be performed to diagnose or exclude CVSO.