Selective reduction of oscillatory potentials and pattern electroretinograms after retinal ganglion cell damage by disease in humans or by kainic acid toxicity in cats

We recorded pattern electroretinograms, scotopic threshold responses, oscillatory potentials and ganzfeld flash electroretinograms in patients with glaucoma or other optic nerve diseases and in cats with inner retinal damage caused by intravitreal injections of kainic acid. In both studies, the scotopic b-wave and the scotopic threshold responses were normal but the oscillatory potentials and pattern electroretinograms were not. The photopic b-wave was also often reduced in patients with scotopic oscillatory potential reduction, and the reduction was proportionate to the oscillatory potential change. Oscillatory potentials were as frequently reduced as pattern electroretinograms in both patient groups, and in the few cases where only one response was reduced, there was no bias toward either measure. In cats, the effects of intravitreal injection of various doses of kainic acid on the retina were evaluated electrophysiologically, and structural damage was assessed histologically. After 25 nmol of kainic acid, the pattern electroretinograms and oscillatory potentials were reduced but neither the b-waves nor the scotopic threshold responses, were affected. Histologic studies of retinas after this dose showed swollen dendrites that were restricted to the outer part (off-sublamina) of the inner plexiform layer. Serial semithin sections indicated that most, if not all, of the swelling was confined to dendrites of large ganglion cells. Our results indicate that the size and sensitivity of the oscillatory potential response may have a role in the diagnosis and management of early glaucoma and optic nerve disease, and that the photopic electroretinogram may give similar information.     

Effect of levodopa on the human luminance electroretinogram

Scotopic and photopic electroretinograms (ERGs) were recorded in 12 healthy volunteers before and 90 and 180 min after administration of levodopa. After 90 min the drug significantly increased the scotopic ERG b-wave amplitude and implicit time. The dark-adapted oscillatory potentials (OPs) were selectively affected, while no changes were observed in the photopic ERG. Levodopa had no effect on the ERG after 180 min drug applications. As a control, the experimental procedure was repeated without drug administration, and no changes were observed.     

Neuroretinal function during systemic hyperoxia and hypercapnia in humans.

PURPOSE: Breathing pure oxygen (O2) or carbogen is known to have differential effects on the retinal and choroidal blood flow. Our objective was to evaluate the effects these hemodynamic changes have on various retinal neurons receiving their vital nutrients from these two vascular beds. To that effect, we recorded the photopic flash electroretinogram (fERG) and oscillatory potentials (OP's) in man. METHODS: Eighteen adults participated in two test sessions to examine the effects of breathing pure O2 or carbogen on the fERG's and OP's. The retinal potentials were recorded at the end of each of the following breathing phases: (1) room air for 5 min, (2) pure O2 or carbogen for 5 min, (3) immediately after the flow of gas was stopped, and (4) 10 min after the flow of gas was stopped. The heart rate, respiratory rate, oxygen saturation (Sao2), and end-tidal carbon dioxide (Etco2) were monitored. The blood pressure and intraocular pressure were measured to derive the ocular perfusion pressure. RESULTS: Breathing pure O2 increased Sao2, decreased heart rate and Etco2, but did not alter respiratory rate and ocular perfusion pressure. Breathing carbogen increased Sao2, Etco2, and ocular perfusion pressure, decreased respiratory rate but did not alter heart rate. The fERG's and OP's were not detrimentally affected by breathing either pure oxygen or carbogen. Only OP4 was delayed at the end of testing in the O2 session. CONCLUSION: Our results show that the neural generators of the photopic fERG's and OP's in man are largely unaltered by the degree of systemic hyperoxia and hypercapnia induced and their reported effects on retinal and choroidal hemodynamics. These results, combined with earlier studies showing that some components of the scotopic fERG's and OP's were altered during similar testing conditions, suggest that the photopic system is more resistant than the scotopic system to altered ocular hemodynamics.     

Light adaptation of the human photopic oscillatory potentials: Influence of the length of the dark adaptation period

Photopic electroretinograms recorded immediately after a period of dark adaptation show a regular increase in amplitude with time spent in light. The retinal mechanisms at the origin of this light adaptation effect remain obscure. The purpose of this study was to investigate the duration of the dark adaptation period needed to produce an optimal light adaptation effect as demonstrated by photopic oscillatory potential recordings. Our results indicate that the light adaptation effect can be separated into two distinct processes. The first one, activated early in the dark adaptation process, reduces the amplitude of the fourth oscillatory potential to 32% of control after less than 5 min of dark adaptation, while the second process, activated after more than 10 min of dark adaptation, appears to impact solely the amplitude of the earlier oscillatory potentials 2 and 3. Our results suggest that the light adaptation effect is mediated by two distinct retinal pathways or mechanisms.Abbreviations DA dark adaptation - LAE light adaptation effect     

A comparison of photopic and scotopic electroretinographic changes in early diabetic retinopathy.

Previous studies of early diabetic retinopathy have shown that oscillatory potential (OP) amplitudes are reduced in many diabetic patients. OP amplitude is believed to be a more sensitive indicator of the development of future retinopathy than b-wave amplitude of the scotopic electroretinogram (ERG). Because OPs measured to a bright white flash reflect both rod and cone system activity, it is important to compare OP amplitudes to photopic ERG measures as well as scotopic measures in early diabetic retinopathy. In this study, OPs and ERG responses were measured under photopic and scotopic conditions in a group of diabetic patients. Although OPs were reduced in amplitude in the diabetic group, several other parameters of the scotopic and photopic b-waves were impaired. The results indicate that b-wave activity may indicate retinal changes in early diabetic retinopathy in the same manner as the OPs.     

The postnatal development of the oscillatory potentials of the electroretinogram. IV. Mesopic characteristics.

The postnatal development of the oscillatory potentials (OP) of the rat's electroretinogram (ERG) was studied during relatively mesopic adaptational conditions. The behaviour of the OPs induced at an interstimulus interval (ISI) of 30 sec entailed photopic qualities at an individual level, but when summated conformed to a scotopic course of postnatal maturation. An ISI of 1 min elicited OPs with individual scotopic characteristics. The total oscillatory activity culminated at 17 days of age at both ISIs, similar to more scotopically induced oscillations. These results show that relatively mesopic states of adaptation do not promote any earlier appearance of the OPs, and that the immature mesopically induced OPs seem to contain both scotopic and photopic qualities reflecting a postnatal change of balance between these components. Furthermore, photopic mechanisms seem to govern the oscillatory activity in the mature rat retina. We suggest that the differences in relation to adaptational conditions between the immature and mature OPs may reflect the postnatal status of the dopamine and its synthetizing enzyme, tyrosine-hydroxylase.     

Changes in Electroretinogram Oscillatory Potentials During Dark Adaptation

Purpose

To investigate changes in the oscillatory potentials (OPs) of electroretinograms (ERGs) during dark adaptation (DA).

Methods

ERGs were recorded from ten normal subjects. Following 15?min of light adaptation, ERGs were recorded every 30?s for 20?min to follow the changes in the OPs during the course of DA. A 20-ms, 560-nm rectangular pulse of light was presented at 3.3?Hz to elicit the ERGs.

Results

The latencies of OP1 and OP2 did not change significantly, but the amplitudes decreased slightly during DA. OP3 was not observed at 30?s, but appeared after 1?min of DA between OP2 and OP4. Similar results were obtained with stimulus durations of 10 to 100?ms in 10-ms steps. The amplitude of OP3 increased to 10?min of DA and then plateaued.

Conclusion

The characteristics of OP3, which increases during DA, indicate that it is probably related to rod activity. Jpn J Ophthalmol 2005;49:420–422 © Japanese Ophthalmological Society 2005     

Electroretinographic assessment of early changes in ocular siderosis

We examined a patient with an iron intraocular foreign body and recorded electroretinograms (ERGs) before and after the removal of the foreign body by vitrectomy. The amplitudes of the rod and cone ERGs and the oscillatory potentials (OPs) in the injured eye were reduced before the operation. In addition, the photopic on-responses (b wave) were more reduced than off-responses (d wave). One year after surgery, the amplitudes of the rod, cone and photopic on- and off-responses were markedly improved to within the low normal limit. However, the OP amplitudes remained unchanged with lower values. These findings suggest that iron retinotoxicity leads to a dysfunction of all layers but the changes may be reversible in the early period of the disease. The late period iron toxicity produces more severe damage to the inner retina than the outer retina.     

Hypobaric hypoxia reduces the amplitude of oscillatory potentials in the human ERG

PURPOSE: To explore the retinal functions in healthy volunteers during acute hypoxic exposure, applying a set of electrophysiological tests. METHODS: Standard electroretinograms (ERGs) of the retina (rod-(scotopic) ERGs, cone-(photopic) ERGs, maximal responses and oscillatory potentials (OPs)) and 30-Hz flicker ERGs were recorded according to ISCEV (International Society of Clinical Electrophysiology of Vision) recommendations in 14 healthy volunteers during a 15-min exposure to a simulated altitude of 5500 m. RESULTS: The mean arterial oxygen saturation level was significantly reduced (P < 0.001) during the hypobaric challenge. It returned to the normal level very shortly after the end of the hypoxic exposure. No significant change in the latency or amplitude of the slow components of the ERG was found in any recording. The OPs of the ERG, however, revealed a significant decrease in amplitude during hypoxic exposure. Both OP1 and OP2 amplitudes were significantly different (P < 0.05) from the baseline values during hypoxia. Partial recovery of these waves occurred after termination of the hypoxia. CONCLUSIONS: These results appear to support the notion that the inner layers of the retina presumed to be the main source of the OPs, display the highest sensitivity towards circulatory and/or hypoxic challenges.     

Electroretinographic oscillatory potentials are reduced in adenylyl cyclase type I deficient mice

Electroretinography (ERG) of adult Adcy1(brl) mutant mice, which are deficient in adenylyl cyclase type 1 (AC1) activity, revealed decreased amplitude of the oscillatory potentials (OP) and of the primary rising phase of the b-wave intensity-response function in scotopic conditions. These abnormalities were less discernable in 3-6 week old mutants. No abnormalities were detected in the ERG signal obtained in photopic conditions or in the dark adaptation dynamics. The mutants displayed no histologic evidence of retinal degeneration. Retinal output, as measured by visual evoked potentials, was not different from heterozygous control mice. AC1-dependent pathways contribute to the generation of the retinal response to light. They may be necessary for the maintenance of the neural generators of the ERG OP.     

Origin of electroretinogram amplitude growth during light adaptation in pigmented rats

We assessed the growth of the rat photopic electroretinogram (ERG) during light adaptation and the mechanisms underlying this process. Full field ERG responses were recorded from anesthetized adult Brown-Norway rats at each minute for 20 min of light adaptation (backgrounds: 1.8, 2.1, 2.4 log scotopic cd m(-2)). The rat photopic b-wave amplitude increased with duration of light adaptation and its width at 33% maximal amplitude narrowed (by approximately 40 ms). These effects peaked 12-15 min after background onset. The narrowing of the b-wave reflected steepening of the b-wave recovery phase, with little change in the rising phase. OP amplitudes grew in proportion to the b-wave. Inhibition of inner retinal responses using TTX resulted in a greater relative growth of b-wave and OP amplitude compared with fellow control eyes, and delayed the change in recovery phase by approximately 5 min. Inhibition of all ionotropic glutamate receptors with CNQX/D-AP7 delayed both rising and recovery phases equally (approximately 12 ms) without altering b-wave width or the time course of adaptation changes. These outcomes suggest that inner retinal light responses are not directly responsible for b-wave amplitude growth, but may contribute to the change in its recovery phase during adaptation. A TTX-sensitive mechanism may help to hasten this process. The cone a-wave was isolated using PDA/L-AP4 or CNQX/L-AP4. A-wave amplitude (35 ms after stimulus onset) also increased with time during light adaptation and reached a maximum (130 +/- 29% above baseline) 12-15 min after background onset. B-wave amplitude growth in fellow control eyes closely followed the course and relative magnitude of cone a-wave amplitude growth. Hence, the increase of the cone response during light adaptation is sufficient to explain b-wave amplitude growth.     

Oscillatory potential changes related to stimulus intensity and light adaptation

The oscillatory potentials (OPs) are a series of subcomponents of the flash ERG which probably originate in the inner plexiform layer of the retina. Abnormal OPs in various forms of retinopathy include central retinal vein occlusion, congenital stationary night blindness, and diabetic retinopathy. We investigated the effects of stimulus intensity and light adaptation on the OP components identified in our laboratory. OPs were recorded from 20 adult eyes to full-field ganzfeld stimulation at four stimulus intensities from 12 to 62cd/m². Stimulus flashes were superimposed over a steady background luminance in the ganzfeld. Four background luminances were used over a 3-log unit range from mesopic to photopic levels. Peak-to-peak amplitude and peak implicit time measures of the OPs were obtained. Latency-intensity functions were derived for each of the four OP components at each light-adaptation level. These latency-intensity functions revealed similar curve fitting slopes for all OP subcomponents at lower light-adaptation levels. At higher levels of light adaptation the later subcomponents (OP3 and OP4) showed a flattening of the slope of the latency-intensity function. The investigator concludes that this saturation effect is related to an interaction of rod and cone contribution to the OP waveform.     

ERG Oscillatory Potentials in Infants

Purpose: Study the scotopic and photopic oscillatory potentials (OPs) of the electroretinogram (ERG) in 10-week old infants. Methods: Term-born 10-week old infants (n = 15) and adults (n = 12) were tested. Full-field ERGs were recorded under scotopic and photopic conditions. The records were filtered (75–300 Hz) to demonstrate the oscillatory wavelets. The amplitudes and implicit times of the infants’ OPs were compared to those in adults and also to amplitudes of the saturated photoreceptor responses. Results: In infants, the mean OP amplitudes are similar in scotopic and photopic conditions and do not vary significantly with OP number. Infants’ OPs are significantly smaller than in adults, with scotopic OPs averaging 19% of that in adults and photopic OPs averaging 47%, whereas the amplitudes of the saturated photoreceptor responses are 43% and 66% of those in adults. Mean interpeak intervals are similar in infants and adults, indicating oscillatory behavior at a frequency of 155 Hz in scotopic conditions and 135 Hz in photopic conditions. Conclusions: In young infants, the OPs are relatively immature compared to the photoreceptor responses, with the immaturity of the scotopic responses being more marked than that of the photopic responses.     

Three-dimensional analysis of averaged electro-retinograms: normal appearance and bioelectric artifacts

In 10 normal subjects, three-dimensional analysis (X-Y plane and time) was carried out of the dominantly photopic and scotopic components of the electroretinograms (ERG) for the purpose of functional imaging of the retina, after having evaluated bioelectric artifacts. The study of the artifacts had revealed that the major causes of distorting the topographical distribution were blinking, myogenic activities, eye movement, eye position and background activities of the electroencephalograms. In normal subjects, the maximal amplitude of the dominantly scotopic components was located around the lower eyelid, while that of the dominantly photopic components was situated around the upper eyelid. The mechanisms of the equivalent dipole axis of the dominantly photopic and scotopic components were different. However, similar changes in the equivalent dipole axes were found during the periods of eccentric eye positions. Similar topographical characteristics were noted in the latency mapping. The isopotential line of the dominantly scotopic components had a steep gradient and were suggestive of a superficial (peripheral retinal) origin, while that of the dominantly photopic components had a gradual gradient and seemed to be of deep (central retinal) origin. ERG topography would make functional imaging of the retina possible and would be of great diagnostic value.     

Electroretinographic abnormalities in a rat glaucoma model with chronic elevated intraocular pressure

The purpose of this study was to determine the ability of electroretinographic (ERG) measurements to document progression of the retinopathy in a rat glaucoma model. Thirty four rats with a chronic intraocular pressure (IOP) elevation induced in one eye by cautery of three episcleral/extra-orbital veins were studied in four separate groups. ERGs were recorded sequentially in Group A rats (n = 12) at baseline, and after approximately 20, 40 and 60 days of high IOP, and in three additional groups of rats (n = 6 or 10 per group) after approximately 58, 30 and 175 days of high IOP, respectively. Scotopic ERG parameters recorded simultaneously from both eyes in Group A rats were: a- and b-wave amplitudes, implicit times, oscillatory potential amplitudes (OPs) determined at three different light-flash intensities, and the light-adapted (photopic) ERG b-wave amplitude. In the other groups of rats, only scotopic ERG a-wave, b-wave and OP amplitudes were measured.In Group A rats that were followed sequentially, all the ERG parameters recorded with attenuated stimuli showed significant time-dependent changes in glaucomatous eyes relative to their contralateral normal eyes, with OPs showing the earliest significant difference after only 3 weeks of high IOP. When different groups of unilateral glaucomatous rats were compared beyond 8 weeks of elevated IOP only the OPs showed a continued decrease with time and good discrimination between glaucoma and normal eyes. Over a 25 week period of high IOP the scotopic OPs measured with attenuated light stimuli declined at the rate of approximately 1.5% per week and provided the best ERG measure to monitor progression of retinal pathophysiology in the vein-occlusion rat glaucoma model.     

The negative response of the flash electroretinogram in glaucoma

The existence of a negative ERG component following the b-wave has been known for a long time. Recently, in unilateral macaque experimental glaucoma, a negative response in flash electroretinograms under scotopic as well as photopic conditions has been shown to be greatly reduced or absent compared to the healthy fellow eye. The aim of this pilot study was to test whether a late negative electroretinogram component is reduced also in human glaucoma patients under different stimulus conditions. Dark-adapted ganzfeld flash electroretinograms were recorded after 30 min of dark using two test conditions, obtained as optimal in pilot studies on controls. Under the scotopic condition I white Xenon-flashes of intensity 0.53 Log photopic Td s were presented on a low white background of 1.38 Log scotopic Td. Under the more photopic condition II orange flashes of intensity –0.37 Log photopic Td s were presented on a blue-adapting background of 2.5 Log scotopic Td. Nine controls and 18 patients with advanced glaucoma were analyzed. The amplitude of the negative response was not significantly reduced in glaucoma patients (condition I: –28.5±23.7 V; condition II: –25.2±19.7 V) compared to controls (condition I: –41.4±36.6 V; condition II: –31.3±26.2 V). The peak latency of the responses under condition I and II did not differ significantly between patients and controls. Thus, the late negative electroretinogram component in ganzfeld flash electroretinograms obtained under scotopic and more photopic conditions does not seem to distinguish as easy between human controls and glaucoma patients as animal experiments suggest.     

Local macular electroretinographic responses in idiopathic central serous chorioretinopathy

Using focal stimuli to human macular regions, we recorded electroretinograms in 24 patients with central serous chorioretinopathy of recent onset (mean visual acuity, 20/20). The stimulus spot was 10 degrees in diameter. Intact fellow eyes served as controls. The local macular electroretinograms of the affected eyes were significantly reduced and the implicit time in each component was significantly prolonged. The mean (+/- S.D.) amplitudes, expressed as percentages of mean amplitudes recorded in fellow eyes, were 64.6% +/- 22.7% (a-wave), 49.6% +/- 21.0% (b-wave), and 15.0% +/- 21.6% (oscillatory potentials). Two to five months after the macular detachment resolved, recordings in 18 patients showed remarkable recovery of a- and b-waves and shortened implicit times. However, the oscillatory potentials showed significantly small recovery in amplitude. Since oscillatory potentials and b-waves were significantly more deteriorated than a-waves in the presence of macular detachment, and oscillatory potentials showed selective delay of recovery in the convalescent stage, central serous chorioretinopathy may involve functional disturbances in the inner retinal layer as well as the photoreceptors.     

Evidence supportive of a functional discrimination between photopic oscillatory potentials as revealed with cone and rod mediated retinopathies

We report on a family where four of the eleven children presented with reduced visual acuities, a red-green deficit at the Farnsworth-Munsel FM 100-hue test, normal appearing fundi and unexpected electroretinographic findings. Light- (photopic) and dark- (scotopic) adapted electroretinograms (ERG) and oscillatory potentials (OPs) were obtained following an accepted standard protocol. The b-wave of their photopic ERG was significantly more attenuated than the a-wave due to the specific abolition of OP4, while the amplitudes of OP2 and OP3 were within the normal range, giving to the b-wave a truncated appearance reminiscent of that seen in congenital stationary night blindness (CSNB) with myopia. Interestingly in the latter condition, which is believed to result from an ON-retinal pathway anomaly, it is OP2 and OP3 which are specifically abolished while OP4 is of normal amplitude thus resulting in an OP response pattern which complements that seen with our patients. Also of interest is the fact that, in our patients, the amplitude of the dark-adapted OP2 was, on average, 240% larger than that measured in light-adaptation while, in normal, a non-significant 14% increase is noted; a finding which is in keeping with other studies reporting supernormal scotopic ERGs in some forms of cone dystrophies. Based on the photopic OP response pattern, our patients represent the electrophysiological complement of patients affected with CSNB. Interestingly their symptoms are also complementary, a finding which could support a functional discrimination between the photopic OPs. This revised version was published online in July 2006 with corrections to the Cover Date.     

Experimentally reduced perfusion of one eye impairs retinal function in both eyes.

PURPOSE: The oscillatory potential index of scotopic white flash electroretinograms is reversibly enhanced in the contralateral eye when the ocular perfusion pressure (OPP) to the test eye is transiently reduced. A transient increase in the intraocular pressure (IOP) and decrease in the OPP in the test eye induced quantifiable vascular changes in the optic nerve head of the contralateral eye. We explored this contralateral phenomenon looking at ganglion cell function in both eyes during elevated IOP and decreased OPP in the test eye only. Our specific objective was to characterize the effects that transient hypoperfusion had on the neural generators of the pattern-reversal electroretinograms (pERGs), the ganglion cells, and preganglion neurons. METHODS: A transient elevation in the IOP was sustained in 10 healthy subjects by scleral suction to reduce the baseline OPP by 15, 30, 45, and 60% for 2-min intervals. For each level of OPP, pERGs were evoked by a checkerboard with 75 minarc high-contrast black-white checks reversing at 5 Hz and recorded bilaterally using DTL fiber electrodes. The pERGs were also recorded immediately after removal of scleral suction and at 2-min intervals thereafter for an 8-min recovery interval. RESULTS: The unilateral decrease in OPP differentially reduced the pERG in the test and contralateral eyes. The pERG for the test eye returned to baseline amplitude within 2 min of removing the suction cup. In contrast, the pERG in the contralateral eye remained below baseline throughout the entire 8-min recovery interval. CONCLUSIONS: The observation of a bilateral decrease in the pERGs while the OPP was decreased in the test eye only suggested that these neuronal changes were modified at more central visual centers for retinal function to be compromised bilaterally. This latter effect may have been mediated by the transiently altered OPP or yet unknown neurohormonal mechanisms.     

Influence of transiently altered retinal vascular perfusion pressure on rod/cone contributions to scotopic oscillatory potentials

The oscillatory potentials (OPs) are sensitive to vascular disturbances in the retina. Rods in man are more susceptible than cones to ischaemia. The findings in a recent study showed that the white flash OP-5 had a heightened sensitivity to altered retinal vascular perfusion pressure (RVPP), compared with earlier OPs and the b-wave. In the present study, a comparison was made of the sensitivity of scotopically matched blue and red flash OPs to dim white flash OPs, to transient stepwise changes in the RVPP, in 10 healthy young adults. After 30 minutes of dark adaptation, two consecutive 0.3 Hz flash groups (n = 20) were filtered and averaged to obtain 100 ms flash ERGs and OPs simultaneously via DTL fibre electrodes for white, blue, and red flashes. To minimize any carry-over effects across flash colour, or repeated testing, the retinal responses to each of these stimuli were measured in separate test sessions several hours to days apart. The RVPP was increased or decreased by 20% and 40% non-invasively by body inversion and scleral suction respectively. For the flash intensities used, blue and red flash OPs appeared more variable than white flash OPs. The OP index increased or decreased across all flash colours when the RVPP was increased, with blue OPs showing the greatest spread of data. Retesting in five subjects using white and red flashes against a blue background disclosed the input of both rods and cones to the white flash scotopic OPs. The provocative test conditions described here offer a potentially profitable approach for studies attempting to differentiate the effects of vascular disorders on rod versus cone function.