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ies on (Na+ + K+)-activated ATPase. Biochem Biophys Acta
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11. Kinoshita JH: Annual review. Selected topics in ophthalmic
biochemistry. Arch Ophthalmol 72:554, 1964.
Investigative Ophthalmology & Visual Science, Vol. 32, No. 10, September 1991
Copyright © Association for Research in Vision and Ophthalmology
Normal Change in the Foveal Cone ERG with
Increasing Duration of Light Exposure
Asher Weiner*f and Michael A. Sandberg*
Foveal cone electroretinograms (ERG) were elicited with a stimulator-ophthalmoscope from 24 normal subjects with a 4° stimulus flickering at 42 Hz and centered within a 12° steady surround. The
stimulus and surround were presented at retinal illuminances of 4.8 log td and 5.5 log td, respectively, to
facilitate visualization of the fundus. Several consecutive averaged responses were evaluated to determine whether increasing duration of light exposure causes an increase in amplitude, as previously found
for the full-field cone ERG. On average, amplitude increased by 27% over time, and the linear regression of amplitude on recording number accounted, on average, for 42% of the amplitude variability
between consecutive responses. Two subjects had amplitudes that were initially subnormal, based on
previously published norms, but that value increased to within the normal range in subsequent recordings. These findings show that a significant change in the cone ERG occurs in the fovea with increasing
duration of light exposure at these retinal illuminances, and suggest that, when the stimulator-ophthalmoscope is used, consecutive foveal cone ERGs should be obtained from patients with suspected
macular disease to avoid a false diagnosis of retinal malfunction. Invest Ophthalmol Vis Sci 32:28422845,1991
Foveal cone electroretinography has been used by
various centers over the last 25 yr to detect macular
malfunction and to supplement information obtained from funduscopy and fluorescein angiography.1"8 Since 1977, this approach has been combined
in some centers with ophthalmoscopic viewing of the
fundus, using visible light, as a way to ensure that the
stimulus is centered on the fovea throughout testing, even in patients with variable or eccentric fixation.3"5-8 While using such instrumentation, ie, a stimulator-ophthalmoscope, we have observed a tendency for foveal response amplitude to increase during continued testing in some subjects. This increase
is reminiscent of increases in amplitude in the fullfield cone electroretinogram (ERG)910 which reflects
primarily extrafoveal cone function.11 This study was
done to determine whether foveal cone ERGs elicited
with a stimulator-ophthalmoscope change systematically with increasing duration of light exposure in
normal subjects and, if so, to quantify the magnitude
of this effect as it may bear upon response variability
and the clinical assessment of foveal function.
Subjects and Methods. Foveal cone ERG responses
were evaluated retrospectively from 24 consecutive
normal subjects (range: 8-60 yr) who participated as
volunteers (15 subjects) or were patients referred with
a question of reduced vision but had visual acuities of
20/25 or better and no abnormalities detected by visual field, color vision, dark adaptation, full-field or
focal electroretinography, or ophthalmoscopy (9 subjects). All subjects gave informed consent before they
were tested. They were maintained in ambient room
illumination with dilated pupils before testing in accord with our routine diagnostic protocol. Testing
was done by one or the other authors. Both were experienced in focal cone electroretinography with the
methods described below. Recordings were obtained
in a dimly lit room with a hand-held, dual-beam stim-
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2843
.5
.45
>
.4
mpli tud
.35
<
.3
.25
.2
.15
Lower Normal Limit
.1
Recording
Recording
Fig. 1. Foveal cone ERG amplitude vs recording number in three representative normal subjects (left) and in two normal subjects who
showed subnormal amplitudes at baseline (right). Responses were elicited with a stimulator-ophthalmoscope. Recording periods lasted 15-60
sec and were separated by 30-sec intervals in the dark.
ulator-ophthalmoscope (Maculoscope, Doran Instruments, Littleton, MA),8 similar to instrumentation described previously.45 Responses were elicited
with a 4° white stimulusflickering(50% duty cycle) at
42 Hz at a retinal illuminance of 4.8 log td (mean
retinal illuminance: 4.5 log td). The stimulus was positioned on the fovea and centered within a 12° white,
steady surround of 5.5 log td.
Responses were monitored with a bipolar BurianAllen contact lens electrode on the topically anesthetized cornea. Signals were differentially amplified,
smoothed by a narrow bandpassfiltertuned to 42 Hz,
and summed by a signal-averaging computer containing an artifact reject buffer that eliminated voltage
deflections of >5 ^V due to eye or lid movements.
Testing involved consecutive recording periods that
lasted from 15-60 sec each (depending on response
phase reliability) and were separated by 30 sec in the
dark for data transfer, display and storage on disk by a
personal computer (Macintosh SE, Apple Computer,
Cupertino, CA). Responses, which appeared sinusoidal, were quantified by Fourier analysis with respect
to amplitude and implicit time, ie, interval from stimulus onset to the corresponding cornea-positive response peak, and these values were printed to the
screen. In all cases, at least three recordings were
made, usually until responses had stabilized. Stabilization occurred if the last recording showed a change
in amplitude opposite in direction to the prior trend
and an amplitude and implicit time that were not different from those of the previous response by more
than 10% and 1 msec, respectively.
In addition to the above protocol, five normal subjects were tested prospectively in a dark room, after 45
min of dark adaptation and 5 min of adjustment to
the contact lens electrode. Subjects were tested for at
least 9 min and until response stabilization was evident. One of the authors positioned the stimulus and
surround on the macula, centered on the fovea,
within 10-15 sec of illuminating the retina, and maintained its location during both recording and data
analysis periods. The data were transferred, displayed,
and stored by the other author. Four of the five subjects had prior experience as subjects for focal ERG
testing.
Results. Foveal cone ERG amplitude increased in
21 subjects (Figure 1), remained unchanged in 1 subject, and decreased slightly in 2 subjects over consecutive recordings under the conditions of our routine
diagnostic protocol. Based on finding from all 24 subjects, mean change in amplitude between thefirstand
third recordings was +27% (t = 3.64 based on log
data, P = 0.001). Linear regression of amplitude vs
recording number accounted, on average, for 42% of
the amplitude variability between consecutive responses. Two of the subjects had amplitudes that were
subnormal at baseline (< 0.18 IJ,V) based on a previously published lower limit of normal,4 but that value
increased to within the normal range by the second
recording (Fig. 1, right). The amplitude change between the first and third recordings was inversely related to baseline amplitude (P = 0.006); subjects with
smaller baseline amplitudes tended to show larger relative increases (Fig. 2). Foveal cone ERG implicit time
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INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / Seprember 1991
Vol. 32
0.2
300%
Fig. 2. Change in foveal cone ERG amplitude with increasing duration of light exposure vs baseline amplitude.
Scatter plot (O) andfittedthird-order polynomial regression
for A log amplitude (ie, log amplitude of third response
minus log amplitude offirstresponse) vs baseline log amplitude (ie, log amplitude of first response) of the foveal cone
100% ERG in 24 normal subjects. Responses were elicited with a
stimulator-ophthalmoscope. Solid line is: y = -0.009
- O.lOlx - 0.547x2 - 1.095x3 (r2 = 0.37).
200%
-.9
Baseline Log Amplitude
increased over sequential recordings in 21 subjects,
remained unchanged in 2 subjects, and decreased in 1
subject. Based on all 24 subjects, the mean change
between the first and third recordings was +0.7 msec
(t = 3.27, P = 0.003). Change in implicit time was not
significantly related to baseline implicit time for this
sample size.
For the five subjects who were tested prospectively,
amplitude data were each fitted to a second-order
polynomial as a function of time of light exposure.
Initial and final amplitudes were derived from the fitted curves for time points that represented 30 and 460
sec, respectively. Mean change in amplitude was
+34%, not significantly different from the +27% seen
in the retrospective analysis on 24 subjects. Two of
the five subjects tested prospectively were also among
those whose ERG findings were evaluated retrospectively, and their increases in amplitude were remarkably similar retrospectively vs prospectively (32% vs
30% and 3% vs 3%, respectively).
Discussion. This study shows that, on average, a
substantial increase in amplitude (27%) and a small
increase in implicit time (<1 msec) occurred in the
foveal cone ERG recorded from 24 normal subjects,
using a stimulator-ophthalmoscope, with increasing
duration of light exposure. Response amplitude typically increased over several recordings before it stabilized. This amplitude change in the foveal ERG with
increasing duration of light exposure cannot be attributed to such factors as stimulus localization on the
fovea or adjustment of the subjects to the contact lens
electrode; both examiners were well trained in foveal
ERG testing and stimulus localization, and normal
subjects have no difficulties fixating at the center of
the stimulus throughout testing. Furthermore, in the
prospective study, subjects were given 5 min to adjust
to the contact lens electrode before recording and still
showed the increase in amplitude over time.
The amplitude increase at the fovea is reminiscent
of that which occurs in the full-field cone ERG with
increasing exposure to lower retinal illumination.910
The physiologic basis for either of these effects is not
known. Interactions between cones and rods or
within the cone system itself have been suggested as
mediatingflickerdetection in the fovea depending on
background brightness; the retinal illuminances used
in this work (>2 log td) appear to favor an effect that
involves only cones.12 The foveal ERG amplitude increase was smaller, on average, than the 60-75% increase seen in the full-field cone ERG,910 which could
reflect a regional variation. However, several differences exist between our routine diagnostic method of
focal testing and that used in full-field studies, these
differences may account for the smaller effect seen in
the foveal ERG. One difference is the higher cone pigment bleach caused by the retinal illuminance of our
focal stimulus (ie, ~75%13) compared with that produced by the lower retinal illuminances of conventional full-field stimulation (ie, < 10% bleach13). The
bleach from the focal stimulus, which would take 1-3
min to reach steady state with continuous stimulation, may partially negate the mechanism underlying
the increase in amplitude by progressively reducing
quantum catch. Another difference is the 15-60 sec
averaging that is necessary to determine amplitudes of
less than 1 ^V, and that which may have artificially
limited the range of change seen in the foveal response. Two other differences in methodology—the
fact that subjects were maintained in ambient room
illumination before they were tested and the use of
30-sec dark intervals between successive recordings
for data analysis, display, and storage—do not appear
to have been factors, because subjects tested prospectively after full dark adaptation and with continuous
light exposure showed an average increase in amplitude comparable to that seen with our routine diagnostic protocol.
Our practice in quantifying foveal function in pa-
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No. 10
tients with known or suspected macular disease is to
record consecutive responses to show waveform reproducibility.4 These findings suggest that repeated recordings should be performed to allow for any
changes that may be related to increasing duration of
light exposure. Because the increase in amplitude was
greatest for subjects with the smallest initial amplitudes and because two of our normal subjects had
amplitudes that fell below the normal range initially,
we suggest obtaining several consecutive recordings in
patients who show a subnormal amplitude to determine whether foveal function is subnormal.
Key words: cone, electroretinogram, fovea, light exposure,
macular malfunction
From the *Berman-Gund Laboratory for the Study of Retinal
Degenerations, Harvard Medical School, Massachusetts Eye and
Ear Infirmary, Boston, Massachusetts. Supported by grant
EY08398 from the National Eye Institute, National Institutes of
Health, Bethesda, Maryland, the National Retinitis Pigmentosa
Foundation Fighting Blindness, Baltimore, Maryland, and the
Massachusetts Lions Eye Research Fund, Inc. f Recipient of a fellowship from the American Physicians Fellowship, Inc., for Medicine in Israel. Submitted for publication: January 8,1991; accepted
April 25, 1991. Reprint requests: Michael A. Sandberg, PhD, Berman-Gund Laboratory, Massachusetts Eye and Ear Infirmary, 243
Charles Street, Boston, MA 02114.
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