Scotopic Oscillatory Potentials Research Articles

Hilbert transform analysis of the mouse scotopic electroretinogram reveals two distinct bursts of oscillatory potentials with progressively dimmer flashes.

Study the scotopic oscillatory potentials (OPs) in mice over a wide range of flash luminance levels using the Hilbert transform (HT) to extract new features of the high frequency components of the electroretinogram (ERG). Scotopic ERGs [Intensity: - 6.3 to 0.9 log cd∙s∙m-2; 12h of dark-adaptation] were obtained from adult mice (C57BL/6; n = 7). The Hilbert transform (HT) was obtained within 3 consecutive frequency bands (65-90Hz, 90-115Hz and 115-140Hz), with OPs being denoised, automatically identified and analyzed. Measurements included: number of OPs, duration of the OP response, surface-under-the-curve (SUC) of the HT envelopes, implicit times, and instantaneous frequency at the HT envelope peak, mean peak time differences (PTD) between the envelopes of each frequency band (measuring their synchrony), correlation coefficient and lag between consecutive HT envelopes, as well as the number of peaks on the HT envelopes. The OP response duration, number of OPs and PTD all peaked for flashesbetween the level corresponding to the RodVmax (maximal b-wave amplitude of the rod ERG; i.e., the first asymptote of the scotopic luminance-response curve) and K (the flash luminance at which the amplitude of the b-wave is half of that of the RodVmax;), i.e., between -3.9 and -2.4 log cd∙s∙m-2. The correlation between consecutive envelopes is close to 1 at flashes > -1.2 log cd∙s∙m-2, with small lags (min. = 1.93 ± 0.45ms at - 1.2 log cd∙s∙m-2), then gradually drops to 0.81 ± 0.02 at the dimmest flash intensity (with a max. lag = 14.76 ± 8.92ms at - 5.1 log cd∙s∙m-2). Finally, we found that the single OP burst (i.e., a single HT envelope peak) seen at flash intensities > - 1.2 log cd∙s∙m-2 progressively divided in two (or more) OP bursts (i.e., multiple HT envelope peaks) with gradually dimmer flashes. Our HT method enabled the analysis of the OP response without the subjective interpretation of the experimenter. Analysis of the scotopic OPs at dim flashes with the HT revealed a novel feature of the OP response not yet reported elsewhere, namely: a split of the OP response into two (or more) distinct bursts. Furthermore, the synchrony peak (measured with the PTD) matched the peak in OP response duration between K and RodVmax, suggesting a disorganization (or dephasing) of the retinal signal in ERGs evoked for weaker flashes. The increased synchronization and correlation of the single burst observed for the strongest flashes could suggest an optimization or saturation of the retinal response. We believe that these novel features of the OP components of the ERG went unnoticed given that previous studies did not use weak enough flashes and failed to recognize the added value that time and frequency domain analysis of the ERG (such as what is achieved with the HT) brings to the interpretation (and our understanding) of the retinal response.

Trophoblast glycoprotein is required for efficient synaptic vesicle exocytosis from retinal rod bipolar cells.

Rod bipolar cells (RBCs) faithfully transmit light-driven signals from rod photoreceptors in the outer retina to third order neurons in the inner retina. Recently, significant work has focused on the role of leucine-rich repeat (LRR) proteins in synaptic development and signal transduction at RBC synapses. We previously identified trophoblast glycoprotein (TPBG) as a novel transmembrane LRR protein localized to the dendrites and axon terminals of RBCs. We examined the effects on RBC physiology and retinal processing of TPBG genetic knockout in mice using immunofluorescence and electron microscopy, electroretinogram recording, patch-clamp electrophysiology, and time-resolved membrane capacitance measurements. The scotopic electroretinogram showed a modest increase in the b-wave and a marked attenuation in oscillatory potentials in the TPBG knockout. No effect of TPBG knockout was observed on the RBC dendritic morphology, TRPM1 currents, or RBC excitability. Because scotopic oscillatory potentials primarily reflect RBC-driven rhythmic activity of the inner retina, we investigated the contribution of TPBG to downstream transmission from RBCs to third-order neurons. Using electron microscopy, we found shorter synaptic ribbons in TPBG knockout axon terminals in RBCs. Time-resolved capacitance measurements indicated that TPBG knockout reduces synaptic vesicle exocytosis and subsequent GABAergic reciprocal feedback without altering voltage-gated Ca2+ currents. TPBG is required for normal synaptic ribbon development and efficient neurotransmitter release from RBCs to downstream cells. Our results highlight a novel synaptic role for TPBG at RBC ribbon synapses and support further examination into the mechanisms by which TPBG regulates RBC physiology and circuit function.

Lack of a Retinal Phenotype in a Syne-2/Nesprin-2 Knockout Mouse Model.

Syne-2 (also known as Nesprin-2) is a member of a family of proteins that are found primarily in the outer nuclear membrane, as well as other subcellular compartments. Syne-2 contains a C-terminal KASH transmembrane domain and is part of a protein network that associates the nuclear envelope to the cytoskeleton via the binding to actin filaments. Syne-2 plays a role in nuclear migration, nuclear positioning during retinal development, and in ciliogenesis. In a previous study, we showed a connection between Syne-2 and the multifunctional scaffold protein Pericentrin (Pcnt). The elimination of the interaction of Syne-2 and Pcnt showed defects in nuclear migration and the formation of outer segments during retinal development, as well as disturbances in centrosomal migration at the beginning of ciliogenesis in general. In this study, the Syne-2 KO mouse model Nesprin-2△ABD (Syne-2tm1Ngl, MGI) with special attention to Pcnt and ciliogenesis was analyzed. We show reduced expression of Syne-2 in the retina of the Syne-2 KO mouse but found no significant structural—and only a minor functional—phenotype. For the first time, detailed expression analyses showed an expression of a Syne-2 protein larger than 400 kDa (~750 kDa) in the Syne-2/Nesprin-2 KO mouse. In conclusion, the lack of an overt phenotype in Syne-2/Nesprin-2 KO mice suggests the usage of alternative translational start sites, producing Syne-2 splice variants with an intact Pcnt interaction site. Nevertheless, deletion of the actin-binding site in the Syne-2/Nesprin-2 KO mouse revealed a high variability in scotopic oscillatory potentials assuming a novel function of Syne-2 in synchronizing inner retinal processes.

Alterations of Ocular Hemodynamics Impair Ophthalmic Vascular and Neuroretinal Function

Hypertension is associated with numerous diseases, but its direct impact on the ocular circulation and neuroretinal function remains unclear. Herein, mouse eyes were challenged with different levels of hemodynamic insult via transverse aortic coarctation, which increased blood pressure and flow velocity by 50% and 40%, respectively, in the right common carotid artery, and reduced those parameters by 30% and 40%, respectively, in the left common carotid artery. Blood velocity in the right central retinal artery gradually increased up to 40% at 4 weeks of transverse aortic coarctation, and the velocity in the left central retinal artery gradually decreased by 20%. The fundus and retinal architecture were unaltered by hemodynamic changes. Endothelium-dependent vasodilations to acetylcholine and adenosine were reduced only in right (hypertensive) ophthalmic arteries. Increased cellularity in the nerve fiber/ganglion cell layers, enhanced glial fibrillary acidic protein expression, and elevated superoxide level were found only in hypertensive retinas. The electroretinogram showed decreased scotopic b-waves in the hypertensive eyes and decreased scotopic oscillatory potentials in both hypertensive and hypotensive eyes. In conclusion, hypertension sustained for 4 weeks causes ophthalmic vascular dysfunction, retinal glial cell activation, oxidative stress, and neuroretinal impairment. Although ophthalmic vasoregulation is insensitive to hypotensive insult, the ocular hypoperfusion causes neuroretinal dysfunction.

Ocular safety assessment of sodium iodate in cynomolgus monkeys

Although sodium iodate (NaIO3)-induced retinal injury model has been widely used in rodents, its application in large animal species has encountered variation in retinal toxicity. NaIO3 induced retinal degeneration and functional changes in sheep, but not in swine. In monkeys, administration of NaIO3 via a carotid artery affected only the cell function of ipsilateral retinal pigment epithelium. The aim of the present study was to identify the dosage and route of NaIO3 administration resulting in morphologic and functional retinal changes in cynomolgus monkeys. Separate groups of animals received NaIO3 intravenously in three different dosing paradigms. Vehicle control animals received phosphate-buffered saline. At selected time points following dosing, flash electroretinograms (ERGs) were recorded followed by necropsy. The eyes were examined microscopically post-necropsy and the levels of circulating microRNA-183 cluster were evaluated in the blood samples collected on days 1, 4, and 5 postdose. A statistically significant reduction in both scotopic a-wave and scotopic and photopic b-wave signals ( p < 0.05) were observed between the ERG signals acquired from NaIO3-treated and vehicle control animals, coupled with time-dependent elevations in plasma miR-183 cluster. Mild to moderate retinal degeneration was observed in the outer layer of the retina, which correlated well with the functional and clinical observations. There were no statistically significant differences in scotopic oscillatory potentials. These findings suggest that intravenous injection of sublethal NaIO3 markedly damaged the cone and rod photoreceptors both functionally and morphologically, and plasma miR-183 reflected the retinal toxicity in those animals with moderate retinal damage.

Retinal A2A and A3 adenosine receptors modulate the components of the rat electroretinogram.

Adenosine is a neuromodulator present in various areas of the central nervous system, including the retina. Adenosine may serve a neuroprotective role in the retina, based on electroretinogram (ERG) recordings from the rat retina. Our purpose was to assess the role of A2A and A3 adenosine receptors in the generation and modulation of the rat ERG. The flash ERG was recorded with corneal electrodes from Sprague Dawley rats. Agonists and antagonists for A2A and A3 receptors, and adenosine were injected (5 µl) into the vitreous. The effects on the components of the single flash scotopic and photopic ERGs were examined, and ERG flicker. Adenosine (0.5 mM) increased the mean amplitudes of the scotopic ERG a-waves (68 ± 8 to 97 ± 14 µV, P = 0.042), and b-waves (236 ± 38 µV to 305 ± 42 µV). A2A agonist CGS21680 (2 mM) reduced the mean amplitude of the ERG b-wave, from 298 ± 21 µV in response to the brightest stimulus to 212 ± 19 µV (P = 0.005), and mean scotopic oscillatory potentials (OPs) from 100 ± 9 µV to 47 ± 11 µV (P = 0.023). ZM241385 [4 mM], an A2A antagonist, decreased the scotopic b-wave of the ERG. A3 agonist 2-CI-IB-MECA (0.5 mM) increased the a-wave, while decreasing the scotopic and photopic ERG b-waves, and the scotopic OPs. A3 antagonist VUF5574 (1 mM) increased the mean amplitude of the scotopic a-wave (66 ± 8 to 140 ± 29 µV, P = 0.046) and b-wave (224 ± 20 to 312 ± 39 µV, P = 0.0037). No significant effects on ERG flicker were found. We conclude that retinal neurons containing A2A and/or A3 adenosine receptors contribute to the generation of the ERG a- and b-waves and OPs.

Retinal function and morphology in Mitf mutant mice

PurposeThe Mitf (microphthalmia‐associated transcription factor) gene that is essential for the normal development of the retinal pigment epithelium (RPE). Mutations in this gene can cause hypopigmentation, microphthalmia and blindness. The purpose of this work was to analyze the retinal function and morphology in mice with specific Mitf mutations.MethodsThe following Mitf mutations were used: Mitfmi‐enu122 (398), Mitfmi‐wh/+, Mitfmi‐wh/Mitfmi and wild type (C5BL/6J) mice as a control. Mice were anesthetized by an intraperitoneal injection of 40 mg/kg−1 Ketamine and 4 mg/kg−1 Xylazine. Flash electroretinography (ERG), from mice with pupils dilated, with a corneal electrode and a reference electrode placed in the mouth, was used to determine the role of the MITF protein in retinal function. Histological retinal sections were stained with hematoxylin and eosin.ResultsERG recordings revealed that only one of the four mutants had any retinal function. The wild type mice had significantly higher mean amplitudes of the photopic a‐waves and scotopic oscillatory potentials than the Mitfmi‐enu122 (398) animals (α = 0.05). Furthermore, Mitfmi‐enu122 (398) had significantly shorter implicit times for the photopic b‐waves and c‐waves. Histology revealed that the RPE layer in the Mitfmi‐enu122 (398) and shows localized thinning of the RPE and their retinas look normal. However, the Mitfmi‐wh/+ showed a profound RPE degeneration and this layer is missing from the Mitfmi‐wh/Mitfmi animals. Furthermore, Mitfmi‐wh/+ and Mitfmi‐wh/Mitfmi have an immense retinal degeneration, lacking the photoreceptor and outer plexiform layers.ConclusionsThis study demonstrates that the Mitf gene has an impact on retinal function in mice, and the morphology of the neuroretina and the RPE.

Bioelectrical function and structural assessment of the retina in patients with early stages of Parkinson's disease (PD).

Purpose To determine bioelectrical function and structural changes of the retina in patients with early stages of Parkinson’s disease (PD).Materials and methodsThirty-eight eyes of 20 patients with early idiopathic PD and 38 eyes of 20 healthy age- and sex-matched controls were ophthalmologically examined, including assessment of distance best-corrected visual acuity (DBCVA), slit lamp examination of the anterior and posterior segment of the eye, evaluation of the eye structures: paramacular retinal thickness (RT) and retinal nerve fiber layer (RNFL) thickness with the aid of OCT, and the bioelectrical function by full-field electroretinogram (ERG). Additionally, PD patients were interviewed as to the presence of dopamine-dependent visual functions abnormalities.ResultsIn patients with early PD, statistically significant changes in comparison with the control group were observed in ERG. They contained a reduction in mean amplitudes of the scotopic a-wave (rod–cone response), the scotopic oscillatory potentials (OPs)—OP2 and OP3, the photopic b-wave, and a reduction in the overall index (OP1 + OP2 + OP3) and a prolongation of mean peak times of the scotopic OP1, OP2, OP3, OP4 (p < 0.05). A questionnaire concerning abnormalities of dopamine-dependent visual functions revealed that PD patients with abnormal peak times of OP1, OP2, and OP3 reported non-specific visual disturbances more frequently in comparison with PD patients with normal peak times of OPs. Other analyzed parameters of ERG, DBCVA, RT, and RNFL did not significantly differ between patients with PD and the control group.ConclusionIn patients with early PD, bioelectrical dysfunction of the retina was observed in the ERG test, probably as a result of dopamine deficiency in the retina. The results of our study indicate that ERG may also be a useful tool for understanding the reason for non-specific visual disturbances occurring in PD patients.

Monitoring retinal morphologic and functional changes in mice following optic nerve crush.

We characterized the morphologic and functional changes in optic nerve crushed mice and evaluated electroretinogram (ERG) responses as tools to monitor retinal ganglion cell (RGC) dysfunction. We performed optic nerve crush (ONC) unilaterally in adult BALB/cJ mice. The neuronal loss in the RGC layer (GCL) and superior colliculus (SC) was determined by Nissl staining. Retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT) imaging. Retinal function was determined by pattern ERG and full-field flash ERG. Responses of pattern ERG, positive scotopic threshold response (pSTR), scotopic oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed. The ONC induced progressive neuronal loss in GCL and contralateral SC starting from 7 and 28 days following ONC, respectively. A linear correlation was observed between combined thickness of nerve fiber layer (NFL), GCL, and inner plexiform layer (IPL) imaged by SD-OCT and cell numbers in GCL. Only half of the normal BALB/cJ mice exhibited pattern ERG response, which was smaller and later compared to C57BL/6J mice. The ONC reduced pattern ERG and pSTR, but the reduction of pattern ERG was earlier than pSTR, preceding the anatomical cell loss in the GCL. The PhNR and scotopic OPs were not affected by ONC. The SD-OCT and ERG can be used to monitor noninvasively retinal morphologic and functional changes induced by ONC. Pattern ERG and pSTR are able to detect early RGC dysfunction, but pattern ERG exhibits higher sensitivity. Our results support the use of these tools in studies using the mouse ONC model.

GlyT1 inhibitor reduces oscillatory potentials of the electroretinogram in rats

Context: Selective inhibitors of glycine transporter type 1 (GlyT1) increase synaptic glycine concentrations and are being developed to treat cognitive and negative symptoms of schizophrenia. However, increases in systemic glycine levels have been associated with visual disturbances and electroretinogram (ERG) alternations.Objective: To determine whether the selective GlyT1 inhibitor PF-03463275 causes changes in ERG responses in albino rats.Materials and methods: Male Sprague-Dawley rats were administered PF-03463275 subcutaneously at 1, 3 and 10 mg/kg 1 h prior to ERG acquisition. Scotopic and photopic luminance responses, photopic adaptometry and flicker responses were measured. Plasma and vitreous samples were obtained at necropsy for determination of PF-03463275 concentrations.Results: A dose-dependent reduction (up to ∼70%) in the amplitude of the scotopic ERG oscillatory potentials (OPs) was observed following PF-03463275 administration. The amplitude of the OPs was also negatively correlated to the concentration of PF-03463275 in the vitreous humor (r = −0.64, p < 0.0001). With the exception of a small increase in scotopic ERG a-wave amplitude and latency no effects were observed on other ERG parameters tested.Conclusions: We conclude that inhibition of the GlyT1 transporter in the retina causes ERG changes which may underlie recent reports of visual disturbance with GlyT1 inhibitors in clinical trials.

S.P.62 Ocular characteristics of Duchenne Muscular Dystrophy

<h2>Abstract</h2> Electroretinogram (ERG) abnormalities have been described in Duchenne Muscular Dystrophy (DMD). Short isoforms of dystrophin are highly expressed in retina. We sought to expand the retinal phenotypes associated with different DMD genotypes. We studied the ocular characteristics of 16 DMD boys, mean age 9.5years (range 4–15years), glucocorticosteroid (GC) treated, with a range of genotypes: six had mutations at the 5′ end of the gene involving exons 3–13, predicted to affect the full length dystrophin Dp427, seven patients exons 44–57, affecting Dp427 and Dp260, and three patients at the 3′ end, in exon 70, affecting expression of Dp427, Dp260 and Dp71. Visual acuity, colour vision, intra-ocular pressure measures (IOP) and full field ganzfeld flash ISCEV Electroretinograms (ERGs) were assessed. Patients had normal visual acuity, one boy had a red-green colour vision defect, and two had raised IOP due to steroid use. ‘Negative' scotopic ERGs with reduced a:b-wave amplitude ratios were recorded in all patients with mutations involving exons 44–57, one patient with a 8–13 deletion and two patients with the 3′ mutation involving exon 70. The scotopic oscillatory potential (OP2) was reduced in all boys with mutations of exons 44–57, and in one with 8–13. The photopic OP2 was reduced in patients with deletions upstream of exon 30, but preserved in those patients in whom scotopic OP2 was attenuated. Photopic ERG a:b-wave amplitude ratios were reduced across the cohort, including those with 5′ mutations in whom scotopic a:b ratios had been normal. These data show a strong association of mutations downstream of exon 30, the promoter region for Dp260, with abnormal scotopic ERGs. In contrast photopic ERG abnormalities were widespread across all genotypes which may relate to the greater proportion of Dp427, compared with other isoforms, at the synapse of cones to cone on-bipolar cells. Our clinical evaluation also reminds us to monitor IOP during GC treatment.

Retinal On-Pathway Deficit in Congenital Disorder of Glycosylation Due to Phosphomannomutase Deficiency

To describe novel electroretinographic (ERG) findings associated with congenital disorder of glycosylation due to phosphomannomutase deficiency (PMM2-CDG) (previously known as congenital disorder of glycosylation type 1a). Two male siblings with genetically confirmed PMM2-CDG underwent full-field ERG to a range of scotopic and photopic flash luminances that extended the International Society for Clinical Electrophysiology of Vision standard protocol and included scotopic 15-Hz flicker and photopic prolonged on-off stimulation. Photopic prolonged ERGs were profoundly electronegative with absent b-waves but preserved oscillatory potentials. Prolonged off-responses and off-oscillatory potentials were preserved. Transient full-field photopic ERGs revealed a broad a-wave and narrow b-wave, and the photopic 30-Hz flicker ERG had a sawtooth waveform. The scotopic b-waves of both cases were attenuated to the fifth percentile, whereas scotopic a-wave amplitudes were at the 50th to 75th percentile, giving a reduced a:b ratio. The scotopic a-wave waveform was well defined to bright flash luminance. The number of scotopic oscillatory potentials was preserved, although amplitudes were smaller than average. Scotopic 15-Hz flicker ERGs were evident to a range of flash luminances and showed an expected phase cancellation between -1.5 and -1.0 log scotopic td (troland) • s, but phase increased only for the fast rod pathway. We find, for the first time to our knowledge, an association of PMM2-CDG with a selective on-pathway dysfunction in the retina. This ERG phenotype localizes the site of retinal dysfunction to the on-bipolar synapse with photoreceptors. Modeling the unusual combination of ERG findings helps our understanding of the role of N -glycosylation at this synapse and provides a focus for future studies of potential intervention.

Electrophysiological Findings in a Porcine Model of Selective Retinal Capillary Closure

To determine the effects on the electroretinogram (ERG) of retinal capillary closure induced in the pig by embolization with microspheres. Fourteen Yorkshine Landrace pigs of 25- to 45-kg body weight were used. With a customized cannula introduced into the external carotid artery, 10-μm diameter microspheres were delivered to the origin of the vessel that supplies blood to the eye in the pig. Fundus fluorescein angiography and electroretinography were performed between days 7 and 28 post injection. The ERG responses of embolized eyes were compared with those of the contralateral nonembolized eyes. The amplitudes of the scotopic b-wave (P = 0.002), the maximal b-wave (P < 0.010), the photopic a-wave (P < 0.001) and b-wave (P < 0.001), and the scotopic oscillatory potentials (OPs) (P = 0.025) and photopic OPs (P = 0.036) were significantly reduced in embolized eyes. The reduction of these ERG amplitudes was significantly correlated with the number of microspheres in the retina. There was no significant difference in the combined rod-cone bright flash (maximal) ERG a-wave amplitude between eyes with and without microspheres. Implicit times, however, were similar in embolized and control eyes. In eyes embolized with microspheres, the amplitudes of most ERG components were significantly reduced without alteration of their implicit times. The magnitude of ERG amplitude reduction correlated with the number of microspheres in the retina.

Comparison of visual function in pigmented and albino rats by electroretinography and visual evoked potentials

To check differences in visual function between Wistar (albino) and Long-Evans (pigmented) rats. The animals were born in our facilities and reared under identical light conditions avoiding bright light. Visual electrophysiology was performed at the ages of 1.5, 4, 7 and 10 months (electroretinography, ERG) and at 1.5 and 7 months (visual evoked potentials, VEP). ERG measurements showed that: 1) The amplitudes of both scotopic and photopic b-waves were markedly larger in Long-Evans rats than in Wistar rats, and also the amplitudes of scotopic oscillatory potentials and photopic 30 Hz Flicker amplitudes, 2) scotopic a-wave amplitudes were larger in Wistar rats at low light intensities, whereas they were smaller in bright light, 3) both a-wave and b-wave latencies were shorter in Wistar rats, 4) the maximum response Rm(P3) was larger in Long-Evans rats, 5) the sensitivity parameter S was larger in Wistar rats, and 6) the post-receptoral response of cones was smaller in Wistar rats. In the VEP measurements, amplitudes of both photopic and scotopic visual evoked potentials of Long-Evans rats were only slightly larger than those of Wistar rats. ERG b-wave amplitudes are markedly decreased in Wistar rats, which requires further investigation. As the b/a and OP/a ratios were also decreased in Wistar rats, it can be suggested that post-receptoral processing, in particular, is impaired in albino animals.

Avaliação da retinopatia hipertensiva através do potencial oscilatório do eletrorretinograma

To evaluate the behavior of the scotopic Oscillatory Potentials (OP) of total field electroretinogram (ERG) in hypertensive retinopathy. Forty-four patients (n=44) were submitted to clinical evaluation and subdivided in to 2 groups: hypertensives (HT) and normotensives (NT). The hypertensives patients were maintained under placebo during the period of the study. Soon afterwards, they were submitted to ophthalmological evaluation and accomplishment of ERG. Total field electroretinogram (ERG), with recording of the answers: scotopic, maximum scotopic, OP scotopic, photopic and flicker.For analysis of the OP answer the latency of the first 2 peaks and the average value of the width of the first 3 peaks of the compound of 3 consecutive answers, denominated Oscillatory Index (OI) were considered. The sample was composed of 44 patients, with a mean age of 51.55 +/- 7.2 range (34 to 68) years, 24 being females. Arterial hypertension affected 26 (59.1%) of the patients, while 18 (40.9%) were normotensives. The average of the obtained IO was 257.41 microv in the NT group and of 217.81 microv in HT (p=0.006). The averages of latencies obtained for peaks 1 (NT-18.42 and HT-17.91) and 2 (NT-24.54 and HT - 24.29) were not different between the groups (p>0.05). The hypertensive patients presented significantly smaller oscillatory index than the normotensives, suggesting that arterial hypertension might cause dysfunction of the internal retina.

Changes in the electroretinogram resulting from discontinuation of vigabatrin in children.

Electroretinograms (ERGs) have been recorded longitudinally in children before and during treatment with the antiepileptic drug vigabatrin for the past 3.5 years. Vigabatrin induced changes in ERG responses occur in children; the most dramatic changes occur in the oscillatory potentials. The purpose of this study was to identify changes in ERG responses associated with discontinuation of vigabatrin treatment. If vigabatrin-induced changes reverse after discontinuation of the drug we infer that the original change is not an indicator of toxicity. ERG data were analyzed from 17 children who discontinued vigabatrin therapy. The duration of treatment ranged from 5 to 52 months, the age for the first ERG ranged from 6 to 38 months (median 10 months). ERGs were tested using the standard protocol established by the International Society for Clinical Electrophysiology of Vision, with Burian-Allen bipolar contact-lens electrodes. In addition to standard responses we recorded photopic oscillatory potentials (OPs). During vigabatrin treatment OPs show a greater change than other ERG responses, with the early occurring wavelets from the photopic OPs showing the greatest change. With discontinuation of vigabatrin the amplitude of the early wavelets of the photopic OPs increased dramatically compared with amplitudes while taking the drug (paired t-test, p = 0.000075). The scotopic oscillatory potentials also show some recovery. Although changes in oscillatory potentials may occur with vigabatrin toxicity, a large change likely occurs with a non-toxic pharmacological effect of vigabatrin on GABAergic amacrine cells in the inner plexiform layer. Reduction of OPs in children on vigabatrin may not be related to toxicity.

Modulation of the scotopic electroretinogram and oscillatory potentials with systemic hyperoxia and hypercapnia in humans

Purpose. Systemic hyperoxia reduces blood flow to the retina while systemic hypercapnia has the opposite effect. However, the effect this modification in blood flow has on neuroretinal function in humans has not been documented yet. The purpose of this study was to evaluate the effect of pure oxygen and carbogen breathing on scotopic electroretinograms (ERGs) and oscillatory potentials (OPs) in humans. Methods. Thirty-five healthy adults volunteered for this study. The ERGs and OPs were recorded: 1) during room air breathing, 2) after a period of pure oxygen (O 2) or carbogen breathing, 3) in room air just after the flow of gas was interrupted, and 4) 10 minutes after the end of the gas administration. Results. The amplitude and latency of the a- and b-waves were not altered during systemic hyperoxia. The amplitude of OP3 increased during hyperoxia while the amplitude of the other OPs was not altered. The latency of all OPs remained stable throughout the O 2 session. Ten minutes after the end of pure O 2 breathing, the a- and b-wave latencies were delayed. No change was found in the amplitude of the a-wave during the carbogen session that increased the end-tidal carbon dioxide by 7.1%, whereas the b-wave was reduced ten minutes after the end of carbogen breathing. The amplitude of OP5 was reduced during carbogen breathing, as well as 10 minutes later. The amplitude of all other OPs, as well as the latencies of all ERG and OP components remained stable throughout the carbogen session. Conclusions. Breathing pure O 2 or carbogen did not compromise retinal function in any major way, likely due to adequate retinal and choroidal regulatory mechanisms. Further investigations are required to better delineate the impact and temporal characteristics of such physiological challenges on retinal function.

Electroretinographic changes in the inner retinal layers of the retained eyes of patients with sporadic unilateral retinoblastoma

Purpose: Examination of retinal function as measured by flash electroretinogram (ERG) including oscillatory potentials (OPs) and pattern electroretinogram (PERG) in a series of patients with unilateral sporadic retinoblastoma. Patients: Studies were undertaken in the retained eye (without clinical evidence of retinoblastoma) of 13 patients with sporadic unilateral retinoblastoma and in 13 healthy controls. Methods: Standard flash ERG including scotopic OPs and PERG recordings were performed in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Results: Statistically significant differences between the studied and the control groups were observed with flash ERG (OP1 amplitude increase, p < 0.003; photopic flicker amplitude increase, p < 0.05) and PERG (P50 latency increase, p < 0.008). Conclusions: Inner retinal layer dysfunction may be a characteristic feature of individuals with unilateral sporadic retinoblastoma.

The electroretinogram recorded at the onset of dark-adaptation: understanding the origin of the scotopic oscillatory potentials.

The purpose of this study was to examine the origin of the oscillatory potentials (OPs) recorded at the onset of dark-adaptation. Our results show that following pre-exposure of the retina to progressively brighter photopic backgrounds there is a complete abolition of OP4 and approximately 50% of OP3, while OP2 is not affected in responses evoked to dim flashes of white light and recorded at the onset of dark-adaptation. These results bring further support to the claim that the short latency OP2 is cone-mediated while the OP3 and OP4 would have a significant rod contribution. However, a more complex picture of OP genesis arises when flicker and response to brighter white light flashes, also obtained within the first minute of dark-adaptation are considered. The latter would suggest that our understanding of the origin of the OPs cannot be exclusively based on which of the two class of photoreceptors is preferentially stimulated at the time the response is recorded.

Improving the diagnostic power of electroretinography by transient alteration of the ocular perfusion pressure.

In this report we present the results of a series of studies focusing on the effects of transient changes in the ocular perfusion pressure (OPP) on retinal function in normals as assessed by the flash electroretinogram (ERG). A transient increase or decrease in the OPP affected by body inversion and compression/suction ophthalmodynamometry (ODM), respectively, is shown to affect differentially the b-wave of scotopic and photopic ERG's. However, under dark-adapted conditions, the cone component of the red flash ERG b-wave exhibited a vulnerability to decreased OPP which approached that seen for the b-wave of the scotopic blue flash ERG b-wave. Similar test procedures used to investigate the functional response of the inner plexiform layer during altered OPP revealed component-specific changes in white flash scotopic oscillatory potentials (OP's). The results of these provocative tests of retinal function offer new insights into basic retinal physiology and encouraging prospects for practical clinical diagnostic procedures with enhanced sensitivity and specificity for subclinical retinal disorders.