Submicrovolt full-field cone electroretinograms: artifacts and reproducibility

The clinical utility of submicrovolt full-field 30-Hz (cone) electroretinograms was assessed by quantifying their contamination by electrical and photoelectric artifacts from xenon-flash stimulators and their test-retest variation in patients with retinitis pigmentosa. Artifacts obtained in saline with four commonly used electrodes varied with electrode type and consisted of an early, brief electrical component and a superimposed, extended photoelectric component. Techniques for minimizing these artifacts are described. Electroretinogram recordings from patients with advanced retinitis pigmentosa or congenital rod monochromatism indicate that these artifacts can be virtually eliminated with bipolar lenses. To assess test-retest variation, narrow-band-filtered responses were obtained twice during 6 weeks from patients with amplitudes less than 1 μV; threshold criteria for signficant (p<0.05) change in amplitude with this technique were approximately 0.25 log unit for each of two different systems.     

Photoreceptor synapses degenerate early in experimental choroidal neovascularization

Severe visual loss in patients with age-related macular degeneration is associated with the development of choroidal neovascularization (CNV). The pathogenic mechanisms for CNV formation have been extensively investigated, but remarkably little research has addressed the mechanisms for dysfunction of the retina in CNV. Using laser-induced CNV in mice, we evaluated the mechanisms of retinal dysfunction. At 3 days, 1 week, 2 weeks, and 4 weeks after laser application, retinas under experimental CNV were characterized physiologically (ERG recordings, synaptic uptake of the exocytotic marker FM1-43, and light-induced translocation of transducin), histologically, and immunohistochemically. ERG amplitudes were reduced by 20% at 1 week after CNV. Depolarization-induced FM1-43 uptake in photoreceptor synapses was selectively reduced by 45% at 1 week after CNV. Although photoreceptor outer segments were shortened by 36%, light adaptation as measured by transducin translocation was mostly preserved. Early in CNV (3 days to 1 week), Muller cells demonstrated induction of c-fos and pERK expression. Also, the density of macrophage-like, F4/80 immunoreactive cells increased approximately 3-fold. Minimal photoreceptor death occurred during the first week, and was variable thereafter. At later times in CNV formation (> or =2 weeks), expression of photoreceptor synaptic markers was reduced in the outer plexiform layer, indicating loss of photoreceptor synaptic terminals. ERG amplitudes, synaptic uptake of FM1-43, and the induction of c-fos and pERK in Muller cells were altered within 1 week of experimental CNV, suggesting that during CNV formation, deficits in retinal function, in particular photoreceptor synaptic function, precede degeneration of photoreceptor terminals and photoreceptor cell death.     

Optimal discrimination of an Abyssinian cat recessive retinal degeneration: a short electroretinogram protocol is more efficient than a long one

AIM: To determine the diagnostic efficiency of scores in a long protocol ectroretinogram (ERG) for Abyssinian cat slow recessive rod/cone dystrophy. METHODS: Kittens (n = 22) were bred from homozygous,affected and heterozygous normals. Ophthalmoscopy was regularly performed and disease signs noted. Cats (age > or = 8 months, 40 sessions, 1-3 repeats) were dark-adapted overnight, anaesthetized and simultaneous binocular ERG recorded using a long protocol. Conventional a- and b-amplitudes and peak implicit times were measured and b/a ratios calculated, initially only for ERG to the maximum photopic and scotopic stimulus. Principal components factor analysis was applied to various subsets of these scores plus age at testing. RESULTS: Six cats with ophthalmoscopic change were classed as affected. Three cats, one tested three times, were suspect. The rest were considered normal. The first analysis, of 80 eyes and 37 parameters, showed that the first factor was the only effective one. Using it, the groups overlapped 5%, scotopic amplitudes and b/a ratios loaded higher than peak times, the eyes were very similar, and age and photopic b/a ratios loaded poorly. The groups were discriminable with all the data. A second analysis, with eyes averaged and the 20 measures loading over 0.5 on the first factor, showed better group separation on factor I alone. An iterative search with varying data sets found that factor I was optimal, with eight ERG measures to the three brightest scotopic and one brightest photopic response. It produced a large absolute separation and classified the suspects consistently. With b/a ratios on these four ERG also included, 12 parameters gave better separation. CONCLUSION: Twelve scores on four ERG separate affected from normal cats with a wide gap and consistently classify suspects. It may work for earlier ages. Additional data probably adds noise. This combination of optimal scores needs confirmation in new data.     

Alterations in electroretinograms and retinal morphology in rabbits treated with vigabatrin

PURPOSE: To determine whether long-term treatment with the anti-epileptic drug vigabatrin causes damage to rabbit retina. METHODS: Five rabbits were treated continuously with a daily dose of vigabatrin solution per orally during a period of 1-8 months. Two rabbits receiving water were used as controls. Repeated full-field electroretinograms (every two weeks) were assessed during this period. Vigabatrin serum concentration was repeatedly measured for securing successful drug administration. After termination of treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied. RESULTS: In all rabbits treated with vigabatrin the serum analyses repeatedly demonstrated elevated drug concentration. Full-field electroretinograms demonstrated normal rod function in all treated rabbits, but reduced cone function in two of the five treated rabbits verified by 30Hz flicker stimulation. Morphologic studies of the sectioned retina demonstrated GFAP immunoactivity of the glial cells localized in the retinal periphery in all five treated rabbits, one of which had staining also in the centrally localized glial cells. The treated rabbits also demonstrated a weaker GAD staining in the IPL and less positive amacrine cells, compared to the controls. Only two treated rabbits had normal GABA staining while three had an enhanced GABA immunoreactivity and undistinguishable fibers in the IPL. In three out of five treated rabbits the Müller cells were short, stubby and fragmented, with swollen endfeet. CONCLUSION: This study demonstrates changes in histopathology caused by vigabatrin in an animal model, which has not been reported previously. We have found that vigabatrin orally administrated to rabbits does not affect rod function but may reduce cone function in the full-field electroretinogram, which is similar to the previously reported vigabatrin effect on the human ERG. The results indicate that vigabatrin may damage or influence, at least one cell type in the rabbit retina.     

Changes in the s-Wave of Multifocal Electroretinograms in Eyes with Primary Open-Angle Glaucoma

Purpose To determine whether the s-wave is present in the multifocal electroretinogram (mfERG) and whether it is altered in eyes with primary open-angle glaucoma (POAG).Methods A Visual Evoked Response Imaging System was used to record mfERGs from 15 eyes of 15 normal adults, as control eyes, and from 15 eyes of 15 patients with POAG. The stimulus consisted of 37 hexagonal stimulating elements with luminances of 200cd/m² (white), 66.6cd/m² (gray), and 4cd/m² (black). The white or black element was presented at five different base periods (bpds) from 13.3 to 213.3ms according to a binary m-sequence. In the intervals between the white and black (or white) elements, gray elements were inserted at 75Hz. The changes in the amplitude and implicit time of the s-wave of the all-trace waveform of the first-order kernel of the mfERG were compared with the mean deviation (MD) of retinal sensitivity in the whole visual field measured with a Humphrey Field Analyzer.Results The s-wave was present as a positive wavelet on the descending limb of the first-order kernel response of the mfERGs of all eyes with POAG. The s-wave amplitude increased with prolongation of the bpd, as occurs in normal eyes. The mean amplitudes of the s-waves at bpds of 53.3 and 106.7ms were significantly smaller in the eyes with POAG than in the control eyes. The correlation between the s-wave amplitude and the severity of disturbance in the entire visual field indicated by the MD was not significant in eyes with POAG.Conclusions The characteristics of the s-wave in glaucomatous eyes were the same as those in the control eyes, but the amplitude of the s-waves in POAG eyes was significantly lower than that in the control eyes. This suggests that ganglion cells may be involved in the development of the s-wave. When comparing the s-wave with static perimetry, more local responses of the s-wave and more local retinal sensitivity in the static perimetry will be appropriate. Jpn J Ophthalmol 2004;48:208–214 © Japanese Ophthalmological Society 2004     

3D flash lag illusion

Objective of this research is to study the presence of 3D flash lag illusion created by a moving object that has a motion-in-depth and a flash object. An object consisting of two thin sticks was simulated to approach the subject who observed it with a stereoscope. In the process of approaching, another stick was briefly presented in the middle of the moving sticks. Five human subjects took part in our experiments and all perceived 3D flash lag illusion. The perceived depth created by 3D flash lag illusion was measured by two different psychophysical experiments, by use of a vernier caliper and by a method of nulling with another depth cue. We studied relation between the perceived depth and the presentation distance. The experimental results indicate that the perceived gap by 3D flash lag illusion is independent from the presentation distance.     

Electroretinography of short-wavelength-sensitive cones with a LED built-in electrode and its normal values

To record electroretinograms (ERG) produced by short-wavelength-sensitive cone mechanisms (SWS-cone ERG), the authors used three kinds (blue, green, and red) of light-emitting diode (LED) which were built into a contact lens electrode assembly. The LEDs were used as both stimulus and background light sources. ERG was recorded using blue LED after 10 min of yellow light adaptation produced by green and red LEDs. Duration of photo-stimulation was either 2 or 100 ms. ERG recorded in normal human subjects showed two positive waves with 2 ms photo-stimulation. Amplitude of the former positive wave (b1-wave) was attenuated when the luminance of yellow background increased, and the latter positive wave (b2-wave) was attenuated when the color of photo-stimulation was green or red. These findings suggest that middle-wavelength-sensitive and long-wavelength-sensitive cone mechanisms generated the former positive wave (b1-wave) and SWS-cone mechanisms generated the latter positive wave (b2-wave). Ratio of b2-wave-amplitude to b1-wave-amplitude with 2 ms photo-stimulation measured on 39 normal subjects ranged from 0.5 to 2.0. It was concluded that this three-colored LED built-in electrode was useful for recording SWS-cone ERG.     

S-cone electroretinograms in multiple evanescent white dot syndrome

Cone electroretinograms (ERGs), elicited by different color flashes under Ganzfeld conditions, were recorded from 6 patients with multiple evanescent white dot syndrome (MEWDS). All of the patients had normal color vision as determined by the Farnsworth Panel D-15 except for one who showed non-specific errors. The b-waves elicited from short wavelength sensitive (S-) cones were reduced more than the mixed long (L-) and middle (M-) wavelength sensitive cones in the affected eyes. The ratio of the S-cone b-wave amplitude of the affected eyes to that of the normal fellow eyes was significantly lower than the comparable ratio for the L- and M-cone ERG b-waves (p= 0.012). The S-cone ERGs recorded from 2 patients recovered to normal levels after their symptoms abated. These ERG results indicate that the S-cone system is more impaired than the L- and M-cone systems in the acute stage of MEWDS, and the changes in the S-cones may be reversible.     

慢性甲醇中毒性视神经病变晚期视觉电生理改变

目的：观察慢性甲醇中毒笥视神经病变晚期视觉电生理改变。方法：对２１例（４２只眼）患者随访２年并进行视觉电重量检测。结果：图形视觉诱发电位表现为Ｐ１００潜伏期延长和Ｐ１００波幅值降低,与正常对照组之间的差异非常显著（Ｐ〈０．０１）,闪光多膜电图的ａ、ｂ波潜伏期和波幅值与正常对照组比较差异无显著性（Ｐ〉０．０５）。结论：甲醇中毒的眼部损害部位主要在视神经,中毒早晚期的视觉电生理改变基本一致。     

Development of receptoral responses in pigmented and albino guinea-pigs (Cavia porcellus)

We describe the postnatal development of the electroretinogram (ERG) receptoral response in the guinea pig. In addition, the time course and nature of maturation was compared between albino and pigmented strains to consider the role that melanogenesis might have in this process. Electroretinograms were collected on groups of albino and pigmented animals from postnatal day (PD) PD1 to PD60. A-wave amplitudes and implicit times were extracted from filtered data (0–75 Hz). Receptoral components were modelled using the delayed gaussian model of Hood and Birch [1] fitted as an ensemble to the raw data. Guinea pigs show saturated amplitudes (Rm_P3) that are 50% of adult values at birth, these mature by PD12. Receptoral delay (t_d) also undergoes some postnatal maturation, while phototransduction gain (log S) is adult-like at birth. Albino animals had significantly (p<0.05) larger Rm_P3 and log S across all ages. Guinea pigs have significant postnatal development in their receptoral response. Maturation of Rm_P3 implies a postnatal increase in rod outer segment length. Whereas the adult values of log S implies a mature phototransduction process at birth. We argue that the likely cause for the larger log S of albino eyes is compatible with theories of increased levels of internal light. Whereas the larger Rm_P3, even after allowing for increased light effectiveness, may reflect a lower ocular resistance in albino eyes due to their lower levels of melanin. Furthermore, decreased Rm_P3 and log S with age is observed in the pigmented group only and is consistent with increased ocular resistance due to melanin development in this strain. This revised version was published online in July 2006 with corrections to the Cover Date.