Karen Holopigian

A comparison of the components of the multifocal and full-field ERGs

The multi-input technique of Sutter and Tran (1992) yields multiple focal ERGs. The purpose here was to compare the components of this multifocal ERG to the components of the standard, full-field ERG. To record multifocal ERGs, an array of 103 hexagons was displayed on a monitor. Full-field (Ganzfeld) ERGs were elicited by flashes presented upon steady background fields. The latencies of two prominent subcomponents of the full-field ERG were altered by varying the intensity of the incremental flash or the intensity of the background field. By showing that similar manipulations of the multi-input parameters produce similar changes in latency, we were able to relate the components of the multifocal ERG to the components of the full-field ERG. The biphasic responses of the multifocal ERG appear to be generated by the same cells generating the a-wave and positive peaks of the full-field cone ERG.

Assessment of local retinal function in patients with retinitis pigmentosa using the multi-focal ERG technique

To assess local retinal function in patients with retinitis pigmentosa (RP), multi-focal ERGs and local thresholds (static visual fields) were obtained on eight RP patients with visual acuities of 20/25 or better. All eight patients showed multi-focal responses with normal timing within the central 5 deg. However, there were few responses with normal timing in the areas outside the central 7.5 deg, except in the case of the only patient with a 30 Hz full-field response with normal timing. Since full-field ERGs are dominated by responses from the periphery, this finding supplies a foundation for the commonly observed delays in the full-field cone ERGs of patients with RP. With respect to amplitude, only two patients showed multi-focal responses with near normal amplitudes anywhere in the field. The loss of amplitude at any point was not a good predictor of visual sensitivity in the Humphrey visual field. On the other hand, all areas with normal timing had near normal sensitivity. Timing changes appear to be an early indication of local retinal damage to the cone system. Nearly all areas with sensitivity losses greater than 0.5 log unit, and some areas with near normal sensitivity, showed significantly delayed multi-focal ERGs. Finally areas with extreme sensitivity loss show multi-focal responses with a wide range of amplitudes and implicit times across patients, suggesting different mechanisms of disease action in different patients.

Identifying Inner Retinal Contributions to the Human Multifocal ERG

Contributions to the multifocal electroretinogram (ERG) from the inner retina (i.e. ganglion and amacrine cells) were identified by recording from monkeys before and after intravitreal injections of n-methyl DL aspartate (NMDLA) and/or tetrodotoxin (TTX). Components similar in waveform to those removed by the drugs were identified in the human multifocal ERG if the stimulus contrast was set at 50% rather than the typically employed 100% contrast. These components were found to be missing or diminished in the records from some patients with glaucoma and diabetes, diseases which affect the inner retina.

Rates of Change Differ among Measures of Visual Function in Patients with Retinitis Pigmentosa

PURPOSE To assess changes in measures of visual function in patients with retinitis pigmentosa (RP) over time. METHODS Patients with RP and visual acuity of 20/40 or better and central visual fields of 10 degrees or larger were enrolled in a 9-year prospective study. The following measures of visual function were obtained annually over the follow-up period: visual acuity, Goldmann visual fields (V4e target), focal electroretinograms, and hue discrimination. RESULTS Over the follow-up period, the averaged group data showed changes in all measures of visual function. The smallest amount of change occurred for visual acuity and hue discrimination, and the greatest amount of change occurred for visual field area. Examination of individual patient data over the follow-up period indicated that the rates of change varied among patients and that losses in function for one measure did not correlate well with losses on other measures. CONCLUSIONS These results stress that although visual function deteriorated over time for this group of patients with RP, there were differences among our measures of visual function. Measures that primarily assess central retinal function change relatively slowly compared with measures that assess more peripheral retinal function.

Method for deriving visual field boundaries from OCT scans of patients with retinitis pigmentosa.

The location of the loss of the inner segment (IS)/outer segment (OS) border, as seen with frequency domain optical coherence tomography (fdOCT), was determined on fdOCT scans from patients with retinitis pigmentosa. A comparison to visual field loss supported the hypothesis, based upon previous work, that the point at which the IS/OS border disappears provides a structural marker for the edge of the visual field. Repeat fdOCT measures showed good within day reproducibility, while data obtained on average 22.5 months later showed signs of progression. The IS/OS contour shows promise as a measure for following changes in patients undergoing treatment.

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 highintensity 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 highintensity 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.

Scotopic sensitivity and color vision with a blue-light-absorbing intraocular lens

PURPOSE: To investigate possible adverse effects of a yellow‐tinted intraocular lens (IOL) on scotopic sensitivity and hue discrimination. SETTING: Departments of Ophthalmology, Columbia University and New York University School of Medicine, New York, New York, USA. METHODS: Nine patients with a yellow‐tinted IOL in 1 eye and a colorless ultraviolet IOL in the fellow eye and 9 young phakic subjects with and without a yellow‐tinted clip‐on lens were tested. Hue discrimination was measured with the Farnsworth‐Munsell (FM) 100‐hue test. Dark‐adapted thresholds to 440 nm, 500 nm, and 650 nm lights were measured at 23 locations using a modified Humphrey perimeter, and dark‐adapted thresholds to white light were measured at 15 degrees temporal retina. RESULTS: In the 9 patients, there were no significant differences in dark‐adapted sensitivities to 440, 500, 650 nm, or white‐light stimuli and no differences in FM 100‐hue error scores between eyes with yellow‐tinted IOLs and those with colorless IOLs. Similarly, in young phakic subjects, there were no significant differences in FM 100‐hue error scores or dark‐adapted sensitivity to the white light with and without the yellow‐tinted clip‐on lens. However, with the clip‐on lens, mean sensitivities to the 440 nm, 500 nm, and 650 nm stimuli were significantly decreased by 2.7 to 2.8 dB, 0.7 to 1.0 dB, and 0 to 1.2 dB, respectively. CONCLUSION: Results suggest that implantation of a yellow‐tinted IOL has non‐significant effect on scotopic sensitivity and hue discrimination.

Temporal frequency dependent adaptation at the level of the outer retina in humans

The focal electroretinogram (FERG) was used to examine temporal frequency tuning at the outer retinal level in humans by measuring temporal modulation thresholds. Changes in FERG thresholds as a function of ambient light level were compared to temporal modulation thresholds obtained psychophysically using the same stimuli. At lower temporal frequencies, both FERG and psychophysical thresholds changed sensitivity proportional to the mean illuminance level. At higher illuminance levels, both threshold measures were relatively independent of illuminance. The comparison of the FERG to the behavioral data suggest that most of the adaptation-dependent changes in temporal sensitivity in humans occur at the level of the photoreceptor complex.

Variability of the pattern electroretinogram

Conflicting results have been obtained concerning the parametric properties of the pattern electroretinogram. These discrepancies may be due to the large amount of variability inherent in recording amplitudes. We have found the variability within a single stimulus condition to be so large (ranging from 30% to 67% of the mean value) that it could mask any underlying spatial frequency tuning. Changing the stimulus conditions failed to significantly reduce the observed variability, although changing recording conditions produced some reduction. The use of a narrower rejection band, a greater number of sweeps, and placement of the reference electrode on the ipsilateral ear (as opposed to the ipsilateral temple) combined to decrease variability of the pattern electroretinogram within a single recording session; however, intersession variability remained high. Therefore one must be careful in evaluating data from this technique, and caution is advised in its clinical use.

The effects of dopamine blockade on the human flash electroretinogram

Single-cell electrophysiologic studies have shown that dopamine modulates retinal activity, but its role in human retinal processing is unclear. We investigated the effects of short-term oral administration of dopaminergic receptor blocking agents on the flash electroretinogram in humans. Both chlorpromazine (25 and 50 mg) and fluphenazine (1 and 2 mg) significantly reduced electroretinogram b-wave amplitudes and also selectively reduced the amplitude of the first oscillatory potential. Implicit times were not altered. Metoclopramide (10 and 20 mg) had no effect on any electroretinographic variable. Our study indicates that dopamine receptor blocking agents with both D-1 and D-2 receptor affinities reduce the amplitude of the electroretinogram in humans.