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Purpose: To characterize the s-wave of the multifocal electroretinogram (mfERG) in cats, and to determine the contribution of the inner retina to the s-wave by examining the effects of tetrodotoxin (TTX) and N-methyl D: -aspartate (NMDA) injected into the vitreous cavity., Methods: mfERGs were recorded from 15 eyes of 15 male cats under general anesthesia. The stimulus consisted of 37 elements, and the luminance of the bright and the black elements were 200 and 4 cd/m2, respectively. The stimuli were presented in a pseudorandom binary m-sequence at six different base periods (bpds) from 13.3 to 426.7 ms. Fifty microliters of 7.0 microM TTX followed by 50 microl of 4.0 mM NMDA were injected into the vitreous cavity., Results: The shape of the mfERGs in the cats resembled that in humans. The s-wave appeared on the descending limb of P1, as seen in human mfERGs, in 11 eyes, and the s-wave amplitude increased significantly as the bpd was increased. TTX and NMDA resulted in the disappearance of the s-wave at all bpds, while the amplitude of P1 remained unchanged., Conclusions: The s-wave is present in the mfERG in the cat, and its loss following injections of TTX and NMDA supports the view that the s-wave reflects the function of the ganglion cells and their axons., (Copyright Japanese Ophthalmological Society 2006.)

Purpose: To determine the functional changes in the rod and cone pathways after photoreceptor loss by continuous light exposure., Methods: Fifty-four male Sprague-Dawley rats were exposed to diffuse fluorescent light of 2000 lux for 24 or 48 hr. Two weeks after the light exposure, full-field scotopic and photopic electroretinograms (ERGs) were elicited by different stimulus intensities with a maximum luminance of 0.84 log cd-s/m2. The amplitudes of the a- and b-waves of the scotopic ERGs and the b-wave of the photopic ERGs were measured. The animals were sacrificed after the ERG recordings, and the number of surviving rod and cone nuclei in the outer nuclear layer was counted., Results: The logarithm (log) of the amplitudes of the maximum rod a-wave (rod Va(max)) and b-wave (rod Vb(max)) was reduced monotonically with a decrease in the rod nucleus counts (p < 0.0001). The regression line for the rod Va(max) decrease was significantly steeper than that for the rod Vb(max) (p < 0.005). The maximum b-wave amplitudes of the photopic ERGs (cone Vb(max)) were significantly correlated with the number of cone nuclei in a log-linear fashion. The slopes of the regression lines for the rod Vb(max) and cone Vb(max) were 0.0067 and 0.0140, respectively, which indicates that the amplitude of the cone b-wave was more severely affected than that of the rod b-waves by light-induced photoreceptor degeneration (p < 0.005)., Conclusions: The amplitudes of the rod and cone ERGs were correlated with rod and cone nuclei counts in a log-linear fashion in light-damaged rats. The functional loss from the photoreceptor death had a greater effect on the cone pathway than on the rod pathway when the retinal function was assessed by the b-wave.

Purpose: To determine possible mechanisms that shape the negative electroretinograms (ERGs) in rats with photoreceptor degeneration induced by destruction of the retinal pigment epithelium., Methods: Sprague-Dawley rats (n = 48) were injected intravenously with 60 mg/kg of sodium iodate (NaIO(3)). Full-field ERGs were elicited by different stimulus intensities with a maximum luminance of 1.23 log cd-s/m(2) and recorded at 6 hr and on days 7, 14, and 28 after the NaIO(3) injections. DL-2-amino-4-phosphonobutyric acid (APB, 1 mM) or N-methyl-L-aspartic acid (NMDA, 5 mM) was injected into the vitreous cavity to isolate photoreceptor (PIII), second-order, and third-order neuronal responses. After recording the ERGs, animals were sacrificed for histological analysis., Results: Negative ERGs were recorded under scotopic conditions on day 7 after the NaIO(3) injection. An intravitreal injection of NMDA eliminated most of the a-wave, resulting in the abolition of the negative ERG. On days 14 and 28, the a-wave amplitudes were reduced compared to those on day 7 with the loss of the negative ERGs. The mean amplitudes of the PIII and second-order neuronal responses were progressively reduced until day 7. In contrast, the mean amplitude of the third-order neuronal responses were relatively well-preserved until day 7 and then were decreased between days 7 and 14. As a result, the amplitude of the third-order neuronal response dominated over the second-order neuronal response on day 7. There was no significant difference in the middle and inner retinal morphology at each time point., Conclusions: NaIO(3) produced negative ERGs transiently, and the third-order neuronal responses were the main contributors to the negative ERG. The relative preservation of the third-order neuronal response plays a role in shaping the negative ERGs in this model.

Background: Birdshot chorioretinopathy, acute posterior multifocal placoid pigment epitheliopathy, and retinal pigment epithelial detachment have been reported as rare manifestations associated with sarcoidosis, suggesting that ocular sarcoidosis may affect the choroidal circulation. We report a case of ocular sarcoidosis representing a choroidal circulatory disturbance without the appearance of retinal lesions or loss of retinal function., Case: A 20-year-old woman was referred with blurred vision in the left eye. Inflammatory change in the anterior segment of the eye was noted with multiple nodules on the iris., Observations: Hematological examination revealed elevated lysozyme levels. Bilateral hilar lymphadenopathy was noted on chest X-ray. Specimens obtained by transbronchial lung biopsy revealed granuloma with Langhans giant cells, which led to the diagnosis of sarcoidosis. The eye was treated with topical steroid. The symptoms and the inflammatory change in the anterior segment disappeared within 10 days. However, despite the normal appearance of the ocular fundus, fluorescein angiography revealed multiple puncta of hyperfluorescence. In indocyanine green angiography, a filling delay was noted in the area corresponding to the punctate lesions. Static visual field testing and multifocal electroretinography showed no significant changes. At the last visit, 15 months after the left eye became asymptomatic, the choroidal lesions had disappeared with no residual alteration of the funduscopic appearance or visual function., Conclusions: This case indicates that choroidal circulatory disturbance can underlie ocular sarcoidosis even in the absence of funduscopically detectable lesions and loss of visual function., (Copyright Japanese Ophthalmological Society 2004)

Purpose: To investigate the relationship between retinal function and histopathology following retinal ischemia-reperfusion in rats., Methods: Retinal ischemia was induced in 27 Sprague-Dawley rats by raising the intraocular pressure for 60- or 90-minutes. Two weeks after the retinal ischemia-reperfusion, ganzfeld stimuli of different luminances (maximum 0.51 log cd-s/m2) were used to elicit full-field ERGs from the right (experimental) and left (control) eyes. The amplitudes of the scotopic b-waves were measured, and intensity-response curves were plotted. The b-wave amplitudes at the initial peak (VbIP), the dip (Vb(dip)), and the maximum stimulus intensity (Vb(max)) were measured. The animals were sacrificed after the ERG recordings to determine the surviving retinal cells in the inner nuclear layer (INL)., Results: The log values of the VbIP, Vb(dip) and Vb(max) were linearly correlated with the number of surviving cells in the INL (r = 0.928, 0.905, and 0.913 for VbIP, Vb(dip) and Vb(max), respectively; p < 0.0001 for each). The slope of the regression line for the Vb(dip) was significantly steeper than that for the VbIP and Vb(max) (p < 0.005). The regression line for the Vb(dip) reached undetectable level of the b-wave (<1 microV) even though approximately 25% of the cells still remained in the INL., Conclusions: The amplitude of the scotopic b-wave is a sensitive index of the surviving INL cells. However, if one selects the stimulus intensity at the dip, the functional loss would be exaggerated in spite of the presence of cells in the INL.

Purpose: To determine whether the amplitude of the s-wave on a multifocal electroretinogram (mfERG) is correlated with the degree of visual field depression in eyes with glaucoma., Methods: Twenty patients (20 eyes) with glaucoma,ages 46 to 69 years, were studied. Twenty healthy volunteers (20 eyes) with normal intraocular pressure and with no eye diseases served as controls. The retinal sensitivities of the upper and lower visual fields of the glaucomatous eyes were determined with a Humphrey Field Analyzer. The severity of retinal sensitivity depression was rated as mild (Group A), intermediate (Group B), or severe (Group C). To record the s-wave, mfERGs were elicited by pseudorandom stimulation, with the stimulus alternating according to a binary m-sequence for base periods (bpds) of 13.3, 26.7, 53.3, 106.7, and 213.3 ms. The mfERGwaves recorded from the upper and lower visual field were summed separately., Results: In the control group, the s-wave in the summed mfERG was observed in all visual field halves at all bpds 53.3 ms or longer. The s-wave amplitude at a bpd of 213.3 ms was significantly larger than that at a bpd of 53.3 ms ( P < 0.05). The s-wave was also present in the glaucoma patients' eyes, and the s-wave amplitude increased as the bpd increased. At bpds of 53.3, 106.7, and 213.3-ms, the mean s-wave amplitudes in Groups B and C were significantly smaller than those in the control group ( P < 0.05, 0.01, and 0.05, respectively). At bpds of 53.3 and 106.7 ms, the mean amplitude of the s-waves in Group C was significantly smaller than that in Group A ( P < 0.05). At a bpd of 106.7 ms, a significant correlation was observed between the retinal sensitivity and the s-wave amplitude ( P < 0.05)., Conclusions: The significant correlation between the retinal sensitivity and the amplitude of the swave at a bpd of 106.7 ms supports the suggestion that the s-wave originates from the retinal ganglion cells and their axons. The amplitude of the s-wave may serve as an objective indicator of the severity of retinal ganglion cell damage.

Purpose: To determine the effects of aging on the first and second-order kernels of the multifocal electroretinogram (ERG)., Methods: Multifocal ERGs were recorded from 52 healthy subjects (52 eyes) (0 >or= refractive error >or= -3.0 diopter). The ages of the subjects ranged from 12-76 years with a mean (+/-SD) of 44.0 +/- 20.2 years. The Visual Evoked Response Imaging System was used. The effects of aging on the response densities and on the implicit times of the first positive wave (P1) of the first-order kernel, and of the second and third positive waves (P2 and P3) of the second-order kernel were analyzed for the different age groups., Results: The response densities of the first-order kernel P1 and second-order kernel P2 waves decreased significantly, and the implicit times of the second-order kernel P2, and P3 were significantly prolonged (P <.05) in subjects over 50 years of age., Conclusion: The results suggest that the age of the subject should be considered when evaluating retinal function using multifocal ERGs in basic and clinical studies.

The influence of the duration of the retinal detachment on the function of detached retina was electrophysiologically investigated in the rabbit eye. Experimental retinal detachment with a diameter of 4 mm was made by injecting sodium hyaluronate into the subretinal space. The transretinal ERG (TR-ERG) was recorded from the detached retina between a pair of double-barreled microelectrodes of which the longer tip was positioned into the subretinal space, penetrating the detached retina and the shorter tip in the vitreous body. The vitreal ERG (VERG) from the undetached retina was simultaneously recorded between the shorter tip and a scleral electrode. The amplitude of the TR-ERG b-wave significantly decreased 2 hours after the onset of the detachment, and was gradually reduced to minimal value until 96 hours after the detachment. The amplitude of the VERG b-wave remained unchanged. The slow P III amplitude of the TR-ERG gradually decreased and extinguished 96 hours after the detachment, while the c-wave amplitude of the VERG showed no significant changes. The results suggested that the viability of the detached retina reduces rapidly and extinguishes within 96 hours in the rabbit eye.

To investigate the influence of the size of detachment to function of the detached retina, transretinal ERG (TR-ERG) was recorded from experimentally detached retina. Retinal detachment 4 or 8 mm in diameter was made by injecting sodium hyaluronate in the subretinal space. The TR-ERG was recorded for two hours from the detached retina by a double barreled microelectrode of which a longer tip entered into the subretinal space of the detached retina while a shorter one remained in the vitreous. Vitreal ERG (VERG) was simultaneously recorded between the shorter electrode and a scleral electrode. The b-wave amplitude of the TR-ERG recorded from the retina with 4 mm detachment decreased two hours after detachment, whereas the b-wave recorded from the retina with 8 mm detachment remarkably decreased 30 min after detachment and was stable up to two hours. There were no significant differences in amplitudes of VERG b-waves between 4 and 8 mm detachments during the experimental course. Less extensively detached retina maintained its function to a greater degree than the largely detached retina. The volume of the subretinal space may influence the viability of the detached retina by changing the concentration of nutrients.

The toxicity of beta-blocker, Befunolol HCl (BFE), to the retinal pigment epithelium was investigated electrophysiologically. Rabbit in vivo ERG b- and c-waves were recorded after intravitreal injections of 0.1 ml of 0.25, 1, 2, 4, 6 and 10% BFE solutions with osmolalities of 304, 340, 383, 432, 493 and 618 mOsm respectively. Phosphate solutions with osmotic pressure corresponding to the BFE solutions were injected as control. In eyes injected with 0.25% BFE, amplitude of either b- and c-waves were unchanged for 60 min, while in eyes injected with BFE with a higher concentration than 1%, the b-waves attenuated but the c-waves enhanced in proportion to the BFE concentrations. In the control group, the b-waves attenuated and the c-waves enhanced by the injection of the high osmotic phosphate solutions up to 500 mOsm, which corresponded to the osmotic pressure of 6% BFE, but attenuated by the phosphate solutions higher than 600 mOsm. Based on the above result, no acute toxicity of BFE to the retina was suggested in dose of its therapeutic use. The attenuation of b-waves by BFE was likely due to the influence of osmotic pressure since no significant difference in the b-waves amplitudes was found between BFE and equimolar phosphate solutions. However, high concentration of BFE itself was suggested to exhibit an effect to enhance the c-wave because a manifest difference was observed in the c-wave amplitudes between the group at higher BFE concentrations and the correspond control group.

The relation between osmotic gradient variation and change in the ERG c-wave was investigated. The vitreous side of the isolated chick retina was perfused with various solutions having osmotic pressures (pi v) ranging between 310 and 600 mOsm, while the choroidal side was maintained at 480 mOsm (pi c). When the osmotic difference (delta pi), (ie, pi v-pi c), was larger than -10 mOsm, normal c-waves with slow rise-times (cs-wave) were obtained; however, when the delta pi was smaller than -30 mOsm, c-waves with fast rise-times (cF-wave) were recorded. The peak time of the cS-waves ranged from 4-6 seconds, while that of the cF-waves was approximately 2 seconds. In addition, changes in the pigment granule distribution were also investigated histologically and photometrically. At delta pi of +10 mOsm, the distribution of pigment granules was similar to that in the dark-adapted chick retina. However, when the delta pi was -30 mOsm, the distribution of pigment granules was similar to that in the light-adapted chick retina. Under the control condition at delta pi of +10 mOsm, the pigment granules were distributed mainly within the cell body of the pigment epithelium, ie, in a direction opposite to the passive flow determined by the artificial osmotic gradient. However, after treatment by ouabain, the granules were spread toward the neural retina in the same direction as the passive flow, suggesting passive movement of these granules. These results suggest that a steep osmotic gradient is present within the normal retina and that the gradient is maintained by an ATPase-dependent mechanism. Moreover, the above results suggest that the cS-wave is scotopic and the cF-wave is photopic.