Characterization of the rod photoresponse isolated from the dark-adapted primate ERG

The a-wave of the human dark-adapted ERG is thought to derive from activity of rod photoreceptors. However, other sources within the retina could potentially perturb this simple equation. We investigated the extent to which the short-latency dark-adapted rod a-wave of the primate ERG is dominated by the rod photoresponse and the applicability of the phototransduction model to fit the rod a-wave. Dark-adapted Ganzfeld ERGs were elicited over a 5-log-unit intensity range using short bright xenon flashes, and the light-adapted cone responses were subtracted to isolate the rod ERG a-wave. Intravitreal 4-phosphono-butyric acid (APB) and cis-2,3-piperidine-dicarboxylic acid (PDA) were applied to isolate the photoreceptor response. The Hood and Birch version of the phototransduction model, Rmax[1 - e(-I x S x (t-t(eff)))2], was fitted to the a-wave data while allowing Rmax and S to vary. Three principle observations were made: (1) At flash intensities > or =0.77 log sc-td-s the leading edge of the normalized rod ERG a-wave tracks the isolated photoreceptor response across the first 20 ms or up to the point of b-wave intrusion. The rod ERG a-wave was essentially identical to the isolated receptor response for all intensities that produce peak responses within 14 ms after the flash. (2) The best fit of sensitivity (S) was not affected by APB and/or PDA, suggesting that the inner retina contributes very little to the dark-adapted a-wave. (3) APB always reduced the maximum dark-adapted a-wave amplitude (by 15-30%), and PDA always increased it (by 7-15%). Using the phototransduction model, both events can be interpreted as a scaling of the photoreceptor dark current. This suggests that activity of postreceptor cells somehow influences the rod dark current, possibly by feedback through horizontal cells (although currently not demonstrated for the rod system), or by altering the ionic concentrations near the photoreceptors, or by neuromodulator effects mediated by dopamine or melatonin.     

The a-wave of the dark adapted electroretinogram in glaucomas: are photoreceptors affected?

AIMS: To evaluate whether the a-wave of the dark adapted flash electroretinogram (ERG) is affected by glaucomatous damage. METHODS: ERGs were recorded in 20 patients (age 33-65 years) with advanced glaucomas (primary and secondary open angle and low tension glaucomas) and 20 normals using a ganzfeld stimulus. After 30 minutes of dark adaptation and pupil dilatation to at least 7.5 mm in diameter, luminance response functions were obtained presenting white flashes of increasing scotopic luminance (the highest flash intensity being 9.4 cd/s/m2, the lowest being 5.75 log units below it) with an interflash interval of 5 seconds. For each scotopic luminance, the responses of four flashes were averaged. The a-wave's amplitude was measured at 10, 11, and 12 ms. Within the glaucoma group, correlations between the interocular differences of the a-wave's amplitude and the mean deviation of a static perimetry (Octopus 500 perimeter, program G1) were computed for all flash intensities. Between normals and glaucomas, the a-wave's amplitude was compared for all flash intensities (paired t test). RESULTS: Within the glaucoma group, the interocular differences of the a-wave's amplitudes correlated significantly with the differences of the MD for flash intensities of 9.4, 5.3, 1.7, and 0.5 cd/s/m2. The a-wave's amplitude was significantly lower in the glaucoma compared with the normal group (p <0.005) for flash intensities of 9.4 and 5.3 cd/s/m2. CONCLUSION: These electrophysiological results imply that also the outer retinal structures, especially the photoreceptors, may be affected by glaucomatous damage.     

Empiric limits of rod photocurrent component underlying a-wave response in the electroretinogram

The corneally recorded rod photocurrent component (photoresponse) underlying the a-wave feature of the electroretinogram was analyzed. The results set empiric limits on critical photoresponse variables. Measurements were obtained from four normal adult subjects on a-wave amplitude, a-wave velocity, b-wave amplitude, b-wave implicit time and b-wave height above baseline. At high intensity, interference from the b-wave component was minimized and the amplitude of the saturated photoresponse component was approximated by the a-wave feature. At lower intensities, the a-wave feature represented progressively less of the underlying photoresponse amplitude. Photoresponse amplitude saturation was signaled by the abrupt slowing of the rate of decline of b-wave peak latency and occurred at an intensity about 2.5 log units above the first appearance of the b-wave. At the intensity of photoresponse saturation, the peak amplitude of the a-wave feature was only about 25% of the maximum amplitude of the underlying photoresponse component. A-wave leading edge velocity was found to increase up to 3 log units above the intensity of photoresponse amplitude saturation and to provide a good estimate of photoresponse velocity at higher intensities. A cascaded low-pass filter model with modifications to accommodate amplitude and timing nonlinearities was used to generate a set of probable underlying photoresponses from the analysis of a-wave amplitude and velocity. Movement of the a-wave leading edge to the left at higher intensities in algebraic combination with a static b-wave leading edge above the intensity of photoresponse amplitude saturation was found to explain the second rise of the b-wave amplitude function and the decline of b-wave amplitude above baseline at high intensities. This analysis provides a basis for modeling the underlying photoresponse on a biochemical level and for interpreting photoreceptor damage in disease states.Supported in part by a grant from the Ethel Brown Foerderer Foundation, Children's Hospital of Philadelphia, and by a grant from the Nina and Paul MacKall Trust.     

ERG rod a-wave in Oguchi disease

We analyzed the change in the ERG rod a-wave waveform during the course of dark adaptation in two patients with Oguchi disease. Two Japanese patients showed a homozygous arrestin 1147delA mutation. Scotopic flash ERGs were recorded after different periods of dark adaptation. ERG rod a-waves were obtained after subtraction of the cone ERG contribution. The rod a-waves were fitted with a model of the rod receptor signal. The parameters, Rm(p3) (maximum a-wave amplitude) and S (sensitivity) were calculated. Longer periods in the dark produced larger rod a-wave but only to the first flash presented. The amplitude of the response to subsequent flashes was essentially independent of the period of dark adaptation. Rm(p3) increased with advance of dark adaptation. However, S was nearly constant. Our results suggest that the cause of delayed dark adaptation is not to be sought in the activation of phototransduction process or the regeneration of rhodopsin per se but rather in the deactivation process of the phototransduction cascade.     

Rod multifocal electroretinograms in mice.

PURPOSE: To test the feasibility of recording rod multifocal electroretinograms (ERGs) from the mouse eye. METHODS: Multifocal ERGs were recorded from normal mice (C57BL/6J) using an array of equal-sized hexagons. Local stimuli were blue (W47A), and the number of blank frames between successive flashes at the same location was fixed at 14 (minimum 200 msec between flashes). Flash and surround intensity, and the number of hexagons, were varied to optimize the stimulus conditions for the mouse, and alterations in adaptation level were used to assess cone intrusion. Local response isolation was evaluated by comparing multifocal responses to full-field ERGs and by mapping local defects in laser-treated mice. RESULTS: Rod multifocal ERGs, although small, were clearly recordable and well formed under many conditions. Decreasing flash intensity or the size of stimulus elements, and/or increasing the surround intensity or adaptation level, decreased local response amplitudes. At the dimmest flash intensity (-0.70 log scotopic trolands [scot td]/s) and the smallest stimulus element (2.9 degrees x 3.5 degrees), local responses were nondetectable. Comparisons with full-field ERGs supported the hypothesis that the local responses were not contaminated by contributions from dark-adapted retinal areas surrounding the multifocal display. With sufficiently bright (0.30 log scot td-s) and relatively large (5.6 degrees x 6.9 degrees) stimulus elements, multifocal responses clearly revealed local retinal defects created with laser treatment. CONCLUSIONS: Rod multifocal ERGs can be recorded from the mouse eye to provide topographical maps of retinal function that have sufficient spatial resolution to be of practical use. The technique will be useful in characterizing the natural history of regional loss in mouse models of human retinal disease and in evaluating some forms of interventional therapy.     

From candelas to photoisomerizations in the mouse eye by rhodopsin bleaching in situ and the light-rearing dependence of the major components of the mouse ERG

To quantify the rate at which light in a ganzfeld produces photoisomerizations in mouse rods in situ, we measured the rate of rhodopsin bleaching in eyes of recently euthanized mice with fully dilated pupils. The amount of rhodopsin declined as a first-order (exponential) function of the duration of the exposure at the luminance of 920 scot cd m(-2): the rate constants of bleaching were 8.3 x 10(-6) and 2.8 x 10(-5) s(-1) (scot cd(-1)m2)(-1) for C57B1/6 and 129P3/J mice, respectively. When the approximately 3-fold difference in effective areas of the pupils of the mice are taken into consideration, the bleaching rates for both strains become essentially the same, 2.6 x 10(-6) fraction rhodopsin (scot Td s)(-1). Assuming 7 x 10(7) rhodopsin molecules per rod, this bleaching rate yields the result that a flash of 1 scot Td s produces 181 photoisomerizations per rod, a value close to that derived from analysis of the collecting area of the rod for axially propagating light. We measured the electroretinograms of mice of the two strains reared under controlled illumination conditions (2 and 100 lux), and compared their properties, using the calibrations to determine the absolute sensitivities of the b-wave and a-waves. The intensity that produces a half-saturating rod b-wave response is 0.3-0.6 photoisomerizations rod(-1), and the amplification constant of the rod a-wave is 5-6 s(-2) photoisomerization(-1), with little dependence on the strain.     

Electrophysiologic assessment of photoreceptor function in patients with primary open-angle glaucoma

PURPOSE: Electroretinograms to high-intensity flashes were obtained to determine the extent of rod and cone photoreceptor and postreceptor dysfunction in patients with primary open-angle glaucoma. METHODS: Full-field flash electroretinograms were obtained using brief high-intensity flashes. Dark-adapted (rod-dominated) and light-adapted (cone-dominated) electroretinogram responses were recorded to a "white" light as a function of flash intensity. The a-wave data were fitted with a model based on photopigment transduction to obtain values for the parameters of log Rmax (the maximum response) and log S (sensitivity). Oscillatory potentials were measured to the cone-dominated high-intensity flashes. Standard clinical 30 Hz flicker electroretinogram responses were recorded using a Grass photostimulator. RESULTS: Analysis of rod and cone a-wave data showed that log Rmax and log S values were within the normal range in nearly all of the patients. For some patients, oscillatory potentials were delayed beyond the normal range. CONCLUSION: Our results provide little evidence for widespread photoreceptor abnormalities in primary open-angle glaucoma.     

Recovery of the rod photoresponse in infants

PURPOSE: To study deactivation of the rod photoresponse in infants using a paired-flash procedure. Rhodopsin content increases and scales the parameters of the activation of rod phototransduction as rods develop. However, little is known about the kinetics of deactivation in the rods of young infants. METHODS: ERG responses to pairs of flashes were used to study the recovery of the rod response in 4- and 10-week-old infants and mature control subjects. The amplitudes of rod isolated a-wave responses to a probe flash (+3.3 log scot td . s) presented 2 to 120 seconds after an equal-intensity test flash were measured. The interstimulus interval (ISI) at which the amplitude was half that of the response to the probe flash alone (t(50)) was determined by linear interpolation. RESULTS: Recovery time (t(50)) was significantly longer in infants than in adults (F = 18.9, df 2, 32; P < 0.01). The shape of the recovery function did not vary with age. The t(50) values were inversely proportional to the parameters of activation of rod phototransduction. CONCLUSIONS: These results are evidence that the kinetics of deactivation in infants are slower and may be set by the proportion of rhodopsin isomerized.     

Third-order neuronal responses contribute to shaping the negative electroretinogram in sodium iodate-treated rats

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.     

Inter-ocular and inter-session reliability of the electroretinogram photopic negative response (PhNR) in non-human primates

PURPOSE: To assess the inter-ocular and inter-session reliability for a range of parameters derived from the photopic electroretinogram (ERG) in a group of normal non-human primates. METHODS: Inter-ocular differences for photopic ERGs were assessed in a group of normal anesthetized adult rhesus monkeys (Macaca mulatta, n=29); inter-session reliability was assessed for 23 eyes of 23 animals tested 3 months later. Signals were acquired using Burian-Allen contact lens electrodes, whereby the contralateral cornea served as a reference. Photopic ERGs were elicited using red Ganzfeld flashes (-0.5-0.67 log photopic cd.sm(-2)) on a rod suppressing blue-background (30 scotopic cdm(-2)). Measurement reliability was established for a-wave, b-wave, photopic negative response (PhNR) and oscillatory potential (OP) amplitudes, as well as for their implicit times, by calculation of the 95% limits-of-agreement (LOA) and the coefficient-of-variation (COV) for each parameter. RESULTS: OP and a-wave amplitudes increased with intensity up to 0.67 log photopic cd.sm(-2), following a typical saturating function, whereas b-wave and PhNR amplitudes both declined above 0.42 log photopic cd.sm(-2). Inter-session variability was greater than inter-ocular variability. The inter-session COVs for PhNR amplitude (10-20%) were similar to the other photopic ERG components (a-wave: 12-17%, b-wave: 12-17%, OPs: 13-19%). Inter-session LOAs were also similar across components, but on average, were smallest for responses to moderate intensities (0.0-0.42 log photopic cd.sm(-2)). CONCLUSION: In non-human primates, the 95% LOA for inter-session measurements of the photopic ERG a-wave, b-wave, OPs and PhNR are all similar. Inner-retinal damage may best be measured using the PhNR amplitude for moderately bright stimulus intensities. B-wave and PhNR amplitudes for brighter flashes are smaller and more variable. The ratio of PhNR:b-wave amplitudes manifests smaller variability and may therefore be useful for detection of selective PhNR loss.     

Slow and fast rod ERG pathways in patients with X-linked complete stationary night blindness carrying mutations in the NYX gene

PURPOSE: To study the slow and fast rod signals of the scotopic 15-Hz flicker ERG in patients carrying mutations in the NYX gene, which has been recently identified as the cause of the complete form of congenital stationary night blindness, CSNB1. METHODS: Twenty eyes of 11 patients with CSNB1 who had nondetectable standard ERG rod b-waves were involved in the study. Scotopic ERG response amplitudes and phases to flicker intensities ranging from -3.37 to -0.57 log scotopic trolands. sec (scot td. sec) were measured at a flicker frequency of 15 Hz. ERG signals to flicker intensities between -3.37 and -1.97 and between -1.17 and -0.57 log scot td. sec were considered to represent primarily the slow and fast rod ERG pathway, respectively. Additionally, standard ERGs were performed. Twenty-two normal volunteers served as control subjects. RESULTS: For the slow rod ERG pathway, all patients exhibited ERG signals that were indistinguishable from noise. Accordingly, there was no systematic phase behavior for the slow rod signals. For the fast rod ERG pathway, the signals were significantly above noise, but they were significantly reduced in amplitude and advanced in phase. CONCLUSIONS: There is evidence that the slow and the fast rod ERG signals can be attributed to the rod bipolar-AII cell pathway and the rod-cone-coupling pathway, respectively. The current study provides evidence to suggest that a defective NYX gene product (nyctalopin) prevents detectable signal transmission through ON rod bipolar cells, but there is a residual transmission through rod-cone gap junctions in CSNB1, possibly through the OFF cone pathway.     

Impact of aging and age-related maculopathy on activation of the a-wave of the rod-mediated electroretinogram

PURPOSE: To examine the impact of aging and age-related maculopathy (ARM) on the activation of phototransduction in rod photoreceptors by measuring the a-wave of the flash, full-field electroretinogram (ERG). METHODS: Enrollees consisted of older adults (> or = 60 years of age) in normal retinal health (n = 41) and those with early (n = 39) or late ARM (n = 7), in whom disease presence and severity were defined based on grading of stereoscopic color fundus photographs according to the Wisconsin Age-Related Maculopathy grading system. Young adults (ages 16-30 years; n = 27) were enrolled for comparison purposes. Previously established procedures were used to estimate the ERG response to two families of flash intensities. By computer subtraction of responses, the isolated rod response was identified. Each participant's ensemble rod responses were fit with the following equation to describe the response (R) as function of flash intensity (I), and time (t): R(I,t) = [1 - exp[-I x S x (t - td)2]] x RmP3, where S is sensitivity, td is the delay before onset of the a-wave, and Rm(P3) is the maximum amplitude. RESULTS: In analyses of older adults, there was no impact of early ARM presence or severity on log S, Rm(P3), or td after adjustment for age and intraocular lens presence. Differences between young and old normal subjects in log S, RmP3, and td disappeared when analyses were limited to older adults with intraocular lenses. CONCLUSIONS: When the light absorption of the aged lens is taken into account and reliable definitions of normal retinal aging and ARM are used, the activation of the a-wave as measured by the rod-mediated full-field ERG is not affected by early ARM, nor is it impacted by normal retinal aging.     

Cone and rod dysfunction in fundus albipunctatus with RDH5 mutation: an electrophysiological study

PURPOSE: A prior study showed that some patients with fundus albipunctatus (FA) have severely reduced full-field cone ERGs. The purpose of this study was to investigate the frequency of cone dysfunction and to determine the cause of the reduced full-field cone ERGs in patients with FA and whether the rod system is affected in patients with FA. METHODS: Sixteen consecutive patients with FA (from 1993 to 2003; eight males, eight females; mean age, 25.4 years) with an RDH5 gene mutation were studied. The amplitudes and implicit times of the standard cone ERGs in the patients with FA were compared to those obtained from normal subjects (n = 55). The a-waves of cone ERGs were also elicited by a bright flash and were fitted to a mathematical model of the a-wave. Rod ERG responses were elicited by dim blue flashes after 3 hours of dark adaptation. RESULTS: The amplitude of the b-wave of the cone ERG in the FA group varied considerably from within the normal limits to markedly decreased. Six of 16 patients with FA had b-wave amplitudes that were smaller than the lowest limit of the control subjects. The degree of cone dysfunction tended to be more severe in older patients. The analysis of the cone a-wave demonstrated that R(m) (maximal response amplitude) in the patients with FA with reduced standard cone ERGs was significantly smaller than that in control subjects. Rod ERGs were also reduced in the patients with FA who had reduced cone ERGs. CONCLUSIONS: In patients with FA, 38% had extensive cone dysfunction. The reduced full-field cone ERGs were mainly due to the loss of cone photoreceptors, and the rod system was also affected in some patients.     

A quantitative measure of the electrical activity of human rod photoreceptors using electroretinography

An electrical potential recorded from the cornea, the a-wave of the ERG, is evaluated as a measure of human photoreceptor activity by comparing its behavior to a model derived from in vitro recordings from rod photoreceptors. The leading edge of the ERG exhibits both the linear and nonlinear behavior predicted by this model. The capability for recording the electrical activity of human photoreceptors in vivo opens new avenues for assessing normal and abnormal receptor activity in humans. Furthermore, the quantitative model of the receptor response can be used to isolate the inner retinal contribution, Granit's PII, to the gross ERG. Based on this analysis, the practice of using the trough-to-peak amplitude of the b-wave as a proxy for the amplitude of the inner nuclear layer activity is evaluated.     

Functional changes in rod and cone pathways after photoreceptor loss in light-damaged rats

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.     

正常大鼠暗适应视网膜电图b波的光强-振幅曲线的观察

目的观察正常SD大鼠暗适应视网膜电图b波光强-振幅曲线的特点。方法取完全暗适应状态SD大鼠12只。利用中性滤光片降低全视野刺激器固有光强度,按0.5个对数单位的间隔衰减得到7档（分别为-5.0、-4.5、-4.0、-3.5、-3.0、-2.5和-2.0log cd·s·m^-2）,采用RETI-scan系统,自制的银环角膜电极和不锈钢针状电极,记录暗适应系列光视网膜电图。采用Naka-Rushton方法分析b波的强度-反应函数。结果b波阈强度为-4.5log cd·s·m-2,饱和强度为-2.5log cd·s·m-2。当刺激强度在-5.0～-2.0log cd·s·m-2范围时,b波光强-振幅曲线呈＂S＂型,符合Naka-Rushton等式;其中有两个重要参数（Rmax,I50）分别代表b波饱和幅值和产生1/2该幅值的刺激强度,本实验中Rmax为（721.2±89.5）μV,I50为（-3.30±0.36）log cd·s·m^-2。上述参数与人类正常值相比差异明显。结论大鼠视网膜反应特性与人类存在较大差异,应用视网膜电图b波光强-反应函数来评价其杆体系统功能时选择合适的刺激参数非常重要。     

CNGB3 mutations cause severe rod dysfunction

Purpose: Congenital achromatopsia or rod monochromatism is a rare autosomal recessive condition defined by a severe loss of cone photoreceptor function in which rods purportedly retain normal or near-to-normal function. This report describes the results of electroretinography in two siblings with CNGB3-associated achromatopsia.

Methods: Full field light- and dark-adapted electroretinograms (ERGs) were recorded using standard protocols detailed by the International Society for Clinical Electrophysiology of Vision (ISCEV). We also examined rod-mediated ERGs using series of stimuli that varied over a 6 log unit range of retinal illuminances (?1.9–3.5 log scotopic trolands).

Results: Dark-adapted ERGs in achromatopsia patients exhibited severely reduced b-wave amplitudes with abnormal b:a ratios (1.3 and 0.6). In comparison, the reduction in a-wave amplitude was less marked. The rod-mediated ERG took on an electronegative appearance at high-stimulus illuminances.

Conclusion: Although the defect that causes achromatopsia is primarily in the cone photoreceptors, our results reveal an accompanying disruption of rod function that is more severe than has previously been reported. The differential effects on the b-wave relative to the a-wave points to an inner-retinal locus for the disruption of rod function in these patients.     

Rod and Cone a-Waves in Central Retinal Vein Occlusion

Purpose

To evaluate rod and cone a-waves in cases with unilateral central retinal vein occlusion (CRVO).

Methods

Scotopic and photopic flash electroretinograms (ERGs) were recorded in seven patients aged 54–84 with unilateral hemorrhagic CRVO. Rod and cone a-waves were analyzed using photoreceptor models, and Rm _p3 (maximum a-wave amplitude) and S (sensitivity) were calculated.

Results

Decreased rod log?S was found in all seven cases, and decreased cone log?S was found in five cases. In only one case, rod log?S in the fellow eye was decreased. The alterations in rod and cone log Rm _p3 were smaller than those in rod and cone log?S. Of three cases in which ERGs could be recorded again after a certain follow-up period, rod log?S and cone logS became larger in two cases and smaller in one case.

Conclusions

The change in the phototransduction cascade was confirmed not only in rods but also in cones in five of our seven cases of CRVO. The ERG findings might reflect the functional change in the photoreceptor layer after the onset of CRVO. Jpn J Ophthalmol 2005;49:402–410 © Japanese Ophthalmological Society 2005     

A<Subscript>max</Subscript> to scotopic I<Subscript>max</Subscript> diagnoses feline hereditary rod cone degeneration more efficiently than any other combination of long protocol electroretinogram parameters

AIM: To evaluate two recent methods for detecting feline hereditary rod cone degeneration with maximum efficiency from a long full-field flash ERG protocol. One combines 12 of these measures in an equation that is derived from iterative principal components factor analysis. The other uses the amplitude of the a-wave to the brightest available flash alone. METHODS: We tested the original 12-parameter equation, by applying it to 50 new ERG series in 23 backcrossed cats. They were necessarily either heterozygous or homozygous for hereditary rod cone degeneration. A masked observer compared the ERG score and fundus examinations. We reanalyzed the old, new and combined data sets. Data sets with only one session per animal were analysed to avoid problems from non-random sampling. A two factor linear model of the a-wave was evaluated. RESULTS: The prior equation, applied to the new data, discriminated the groups as well as it had initially. In the reanalysis, group separation continued to increase with even fewer measures compared to the previously reported study. Eventually, one measure, the amplitude of the a-wave (amax) to the brightest scotopic flash (Imax) discriminated the groups better than any other measure or combination of measures in all analyses, including data sets using only one session for each animal and in a two factor linear model of the a-wave. CONCLUSION: Amax to Imax alone proved to be the best diagnostic criterion in all analyses. No linear model is likely to discriminate affected from unaffected animals more effectively because additional variables increased variance more rapidly than they increased discrimination. Amax to Imax may detect other rod and rod/cone dystrophies equally efficiently.     

Dark adaptation of rod photoreceptors in normal subjects, and in patients with Stargardt disease and an ABCA4 mutation

PURPOSE: Psychophysical and electroretinographic (ERG) studies indicate that patients with Stargardt disease exhibit abnormally slow rod dark adaptation after illumination that bleaches a substantial fraction of rhodopsin. However, relatively little information is available concerning rod recovery in this disease after weaker adapting (i.e., conditioning) light. With the use of a paired-flash ERG method, properties of the derived rod response to a low-bleach (<1%) but rod-saturating conditioning flash were investigated in seven normal subjects and in five Stargardt patients with identified sequence variations in the ABCA4 gene. METHODS: In the first of two experiments, the interval between a fixed conditioning flash (67 or 670 scotopic cd s m(-2)) and a bright probe flash of fixed strength was varied to determine the falling-phase kinetics of the derived rod response to the conditioning flash. In the second, the instantaneous amplitude-intensity function for the rod response at an intermediate stage of recovery from the conditioning flash was determined by presenting a test flash of various strengths at a fixed time after the conditioning flash, and a probe flash at 200 ms after the test flash. RESULTS: The maximum peak amplitude of the dark-adapted, rod-mediated a-wave determined in Stargardt patients (211 +/- 87 microV) was on average lower than that determined in normal subjects (325 +/- 91 microV; P = 0.06). The derived rod response to the 670 scotopic cd s m(-2) conditioning flash determined in normal subjects and Stargardt patients exhibited a biphasic recovery, and the kinetics of the early stage of this recovery were similar in the two subject groups. For both normal subjects and patients, normalized amplitude-intensity functions describing the dark-adapted derived rod response exhibited half-saturation at approximately 1.5 log scotopic troland second. In both groups, the normalized amplitude-intensity function determined at approximately 2 seconds after the 67 scotopic cd s m(-2) conditioning flash and at approximately 9 seconds after the 670 scotopic cd s m(-2) conditioning flash exhibited an average desensitization (i.e., an increase of test flash strength at half-saturation) of approximately 0.5 to 0.6 log unit relative to that determined under dark-adapted conditions. CONCLUSIONS: The results indicate that, despite a reduction in the average dark-adapted maximum a-wave amplitude in the Stargardt/ABCA4 patients, the early-stage recovery kinetics of the derived rod response to a low-bleaching conditioning flash as well as the lingering rod desensitization produced by such a flash are similar to those determined in normal subjects.