Constant luminance (cd·s/m2) versus constant retinal illuminance (Td·s) stimulation in flicker ERGs

Abstract

Purpose: To compare the effect of variable pupil size on the flicker electroretinogram (ERG) between a stimulus having constant luminance and a stimulus having constant retinal illuminance (constant Troland) that compensates for pupil size.

Methods: Subjects (n = 18) were tested with 12 pairs of the stimuli. The stimulus pair consisted of the ISCEV standard constant luminance stimulus (3 cd·s/m2 with a 30 cd/m2 background) and a constant retinal illuminance stimulus (32 Td·s with a 320 Td background) selected to provide the same stimulus and background when the pupil diameter is 3.7 mm. Half the subjects were artificially dilated, and their response was measured before and during the dilation. The natural pupil group was used to assess intra- and inter-subject variability. The artificially dilated group was used to measure the flicker ERG's dependence on pupil size.

Results: With natural pupils, intra-subject variability was lower with the constant Troland stimulus, while inter-subject variability was similar between stimuli. During pupil dilation, the constant Troland stimulus did not have a dependence on pupil size up to 6.3 mm and had slightly larger amplitudes with longer implicit times for fully dilated pupils. For the constant luminance stimulus, waveform amplitudes varied by 22% per mm change in pupil diameter, or by 48% over the 2.2 mm diameter range measured in dilated pupil size. There was no difference in inter-subject variability between constant Troland natural pupils and the same subjects with a constant luminance stimulus when dilated (i.e., the ISCEV standard condition).

Conclusions: These results suggest that a constant Troland flicker ERG test with natural pupils may be advantageous in clinical testing. Because of its insensitivity to pupil size, constant Troland stimuli should produce smaller reference ranges, which in turn should improve the sensitivity for detection of abnormalities and for monitoring changes. In addition, the test can be administered more efficiently as it does not require artificial dilation.

Clinical trial registration number: This trial is registered at ClinicalTrials.gov (NCT02466607).

Keywords: Dilation; Flicker electroretinogram (ERG); Mydriasis; Pupil; Reference range; Troland.

Conflict of interest statement

Conflict of interest

These conflicts of interest are relevant to this research: employment (Q. Davis and O. Kraszewska), stock ownership (Q. Davis), and study sponsorship by LKC Technologies, Inc. C. Manning has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from each subject after explanation of the nature and possible consequences of the study. The study was approved by an institutional review board (SAIRB-15-0017) and is registered at ClinicalTrials.gov (NCT02466607).

Figures

Fig. 1

Definitions of implicit time and amplitude for the waveform (left) and fundamental (right). The fundamental of the waveform (purple curve) is overlaid on the original waveform (green curve). Time 0 is the center of the light flash; other light flashes occur at ±35.3 ms, ±70.6 ms, etc. The voltage measured is the difference between the potential at an electrode below the lower eyelid (positive) and the temple (negative) in the sensor strip electrode array

Fig. 2

Effective retinal illuminance with a 3 cd·s/m2 with a 30 cd/m2 background, computed using the pupil measurements taken in all trials in 1 subject with natural pupils. In some trials (2, 8, 10, 11, 12), the retinal illumination was relatively constant, while in other trials (1, 3, 4, 6, 9) the retinal illumination dropped by ~1.5× in the first second, while in the remaining trails (5, 7) the retinal illumination changed slowly throughout the 5 s trial. Curves are smoothed with a 2.4 Hz low-pass filter for clarity

Fig. 3

Pupil diameter (ϕ) distribution for the two stimuli for natural (orange bars) and dilated (blue bars) pupils. There are 18 subjects with natural pupils and only 9 subjects with dilated pupils because all subjects started with natural pupils and only half were dilated. For each group, the mean, standard deviation (SD), minimum, maximum, and number of subjects (n) are shown

Fig. 4

Representative ERG responses from 3 subjects (one subject per row) that received dilation drops after the first two stimulus pairs. The left panels show the electrical response versus time for 12 time points for the two stimuli, with the color of each curve corresponding to the measured pupil diameter (ϕ) as indicated by the bar chart key. The photographs on the right side are infrared photographs of the eye taken automatically by the RETeval device immediately prior to the first and last set of stimulus pairs

Fig. 5

Dependence of implicit times (top plots) and amplitudes (bottom plots) on pupil size. Red curves are data from the constant luminance (candela) stimulus; blue curves are data from the Troland stimulus. Each subject tested has one red and one blue curve. Black points are the measured values, with straight lines connecting them

Fig. 6

Relative dependence of implicit times (top plots) and amplitudes (middle and bottom plots) on pupil size. Red curves are data from the constant luminance (candela) stimulus; blue curves are data from the Troland stimulus. Each subject tested has one red and one blue curve. Black points are the measured values, with straight lines connecting them. Δ implicit times and Δ amplitudes are the difference between the measurement and the predicted measurement at a pupil size of 2.6 mm for that subject. Amplitude ratios are the ratio of the amplitude to the predicted measurement at a pupil size 2.6 mm for that subject and are plotted on a logarithmic scale. The predicted measurements are calculated using a linear least squares fit to the measurements for pupil sizes less than 5 mm. The value of 2.6 mm is the average natural pupil size found in this study

Fig. 7

Comparison between pupil size dependence of the flicker ERG between a constant luminance (cd) and constant Troland (Td) stimulus. The ratio of the linear slope between the two stimulus conditions is shown as a filled circle for each subject and each waveform metric on a logarithmic scale. Positive/negative ratios are shown in blue/gold colors. Shown is the median line, whose value and p value are labeled after taking the absolute value of the points. Ratio magnitudes greater than 1 indicate that the constant retinal illuminance stimulus (Td) had less dependence on pupil size, while ratio magnitudes less than 1 indicate that the constant luminance stimulus (cd) had less dependence on pupil size