Download Normal pattern electroretinograms in amblyopia.

Reports
No. 1
mit one to see only the occasional extreme case of an
alteration that can be detected more readily when lucifer yellow is employed as an extracellular probe.
In conclusion, our results show that mechanical disruption of the intact relationship between the ROSs
and the RPE and/or interphotoreceptor matrix prevents the abscission of the terminal disks under conditions in which they would normally be shed. Particularly in view of the above discussion, this finding does
not necessarily mean that the RPE actively bites off
the ends of ROSs by "piecemeal phagocytosis" without
any participation by the rods, but it does indicate that
the neural retina does not have autonomous control
over the shedding of its ROS disks.
Key words: photoreceptor outer segments, rod disk, retinal
pigment epithelium, membrane turnover, retinal detachment
Acknowledgments. We gratefully acknowledge Dean Bok's
critical comments on a draft of the manuscript and Steve
Bernstein's preparation of Figure 2.
From the *Neuroscience Research Program and Department of
Biological Sciences, University of California, Santa Barbara, the t Jules
Stein Eye Institute, UCLA School of Medicine, Los Angeles, and the
tDepartment of Visual Science, Indiana University, Bloomington.
Supported by NSF Grant BNS-8420242 and NIH Grant EY-00888.
Submitted for publication: June 27, 1985. Reprint requests: David
S. Williams, Department of Visual Sciences, School of Optometry,
Indiana University, Bloomington, IN 47405.
References
1. White RH: The effect of light and light deprivation upon the
structure of the larval mosquito eye. Ill Multivesicular bodies
and protein uptake. J Exp Zool 169:261, 1968.
187
2. Williams DS and Blest AD: Extracellular shedding of photoreceptor membrane in the open rhabdom of a tipulid fly. Cell
Tissue Res 205:423, 1980.
3. Young RW and Bok D: Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol
42:392, 1969.
4. O'Day WT and Young RW: Rhythmic daily shedding of outer
segment membranes by visual cells in the goldfish. J Cell Biol
76:593, 1978.
5. Young RW: Shedding of discs from rod outer segments in the
Rhesus monkey. J Ultrastruct Res 34:190, 1971.
6. Spitznas M and Hogan MJ: Outer segments of photoreceptors
and the retinal pigment epithelium. Arch Ophthalmol 84:810,
1970.
7. Bok D and Young RW: Phagocytic properties of the retinal pigment epithelium. In The Retinal Pigment Epithelium, Zinn KM
and Marmor MF, editors. Cambridge, MA, Harvard University
Press, 1979, pp. 148-174.
8. Besharse JC: The daily light-dark cycle and rhythmic metabolism
in the photoreceptor-pigment epithelial complex. Prog Retina
Res 1:81, 1982.
9. Hollyfield JG and Rayborn ME: Membrane assembly in photoreceptor outer segments: progressive increase in 'open' basal
discs with increased temperature. Exp Eye Res 34:115, 1982.
10. Besharse JC, Terrill RO, and Dunis DA: Light-evoked disc shedding by rod photoreceptors in vitro: relationship to medium bicarbonate concentration. Invest Ophthalmol Vis Sci 19:1512,
1980.
11. Currie JR, Hollyfield JG, and Rayborn ME: Rod outer segments
elongate in constant light: darkness is required for normal shedding. Vision Res 18:995, 1978.
12. Heath AR and Basinger SF: Simple sugars inhibit rod outer segment disc shedding by the frog retina. Vision Res 23:1371, 1983.
13. Williams DS, Wilson C, Linberg K, and Fisher S: Effects of low
sodium, ouabain, and strophanthidin on the shedding of rod
outer segment discs. J Comp Physiol A 154:763, 1984.
14. Matsumoto B and Besharse JC: Light and temperature modulated
staining of the rod outer segment distal tips with lucifer yellow.
Invest Ophthalmol Vis Sci 26:628, 1985.
Normal Pattern Electroretinograms in Amblyopia
Irene Gortlob* and Lufz Welge-Lussenf
Checkerboard reversal stimuli were used to evoke transient
pattern electroretinograms (P-ERGs) from the eyes of 14 patients with amblyopia and 14 normal subjects. In the control
group, and in normal eyes of patients, pattern electroretinograms were obtained with monocular central fixation. Amblyopic eyes were examined by monocular and binocular fixation, and the fixation point was shifted horizontally and/or
vertically until the P-ERG reached its maximal amplitude.
After adjusting visual fixation, there were no significant differences in amplitude between the normal and the amblyopic
eyes. In addition, the differences between both eyes were
compared with the right-left eye variability of the 14 normal
subjects. In the amblyopic eyes, no P-ERG abnormality was
observed. These results do not support previous reports of
reduced P-ERG amplitudes and are in agreement with recent
findings obtained under steady-state conditions. Invest
Ophthalmol Vis Sci 28:187-191, 1987
The question as to what extent the retina is affected
in amblyopia has remained unanswered. In amblyopic
eyes, several authors1"3 have described a reduction of
the first positive component of the transient pattern
electroretinogram (P-ERG). Recently, Arden et al4
found in a large population of amblyopic children that
the transient P-ERG amplitude was reduced in most
amblyopic eyes at 2 Hz modulation. Occlusion at an
earlier age reduces the P-ERG amplitude and orthoptic
treatment increases it. Hess et al5'6 showed that with
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188
INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / January 1987
optimized optical focus, fixation alignment, and fixation stability for each amblyopic eye, no P-ERG abnormality was observed under steady-state conditions
(8-Hz modulation). The purpose of the present investigation is to resolve the conflicting results by using
stimulus conditions (checkerboard stimulus with transient conditions at 2-Hz modulation) comparable to
those of Arden et al4 with optimal fixation for each
individual eye.
Materials and Methods. Stimulation and recording
technique: An alternating checkerboard pattern was
produced on a TV monitor by a Medelec pattern generator (Medelec, Ltd., Surrey, UK) and presented at a
distance of 1 m. Each check subtended 41 min arc, the
test field was 26° X 21°, the contrast was 97%, the
mean luminance was 30 candela/m 2 , and a temporal
frequency of 4 reversals per second (2 Hz) was used.
The P-ERG was recorded with gold foil electrodes.7
The reference electrode was placed on the ipsilateral
temple, while the ground electrode was on the contralateral temple. Signals were measured every 0.8 ms over
a period of 200 ms, filtered between 1 Hz and 30 Hz
and averaged 256 times by a Medelec ER94a/Sensor
with artifact rejection. The amplitude between the first
negative and positive peak was evaluated.
Normal group and patients: 14 adults (from 18 to
34 yr; mean age, 26 yr) with normal visual acuity and
14 patients (from 9 to 60 yr; mean age, 24 yr) with
amblyopia of varying severity were examined after informed consent was obtained. A full ophthalmologic
examination was given to each subject to verify that
there was no additional sign of ocular pathology. In
Table 1, clinical details of the patients are given. Natural pupils were used and found to be of equal diameter
in all subjects. Refractive errors were determined
skiascopically and, in some patients, were verified by
adding plus or minus lenses and noting changes of the
P-ERG amplitude.
In the control group, monocular P-ERGs with central fixation were recorded from both eyes. In addition,
for two normal subjects the fixation point was shifted
horizontally and vertically. For all patients, P-ERGs
of the normal eye were obtained with monocular central fixation. Depending on the type of amblyopia (ie,
strabismic or anisometropic) fixation was better with
either monocular or binocular fixation. All patients
were examined with both methods and the fixation
point was then shifted horizontally and/or vertically
until the P-ERG reached its maximal amplitude. In
order to control the influence of visual evoked responses or of other distant potentials from the unoccluded normal eye during binocular fixation,8 we also
recorded the P-ERG with the gold foil electrode placed
on the amblyopic occluded eye, while the normal eye
fixed the monitor. In this case, no measurable response
Vol. 28
was obtained. Amplitudes of the P-ERG were compared by t-tests.
Results. In the normal subjects, the means and standard deviations of the absolute P-ERG amplitudes were
5.14 ± 1.34 /iV for the right eyes and 5.29 ± 1.16 ixV
for the left eyes. In order to compare both eyes of the
normal individuals, the difference was calculated by
subtracting the amplitude of the left eye response from
that of the right eye. The mean and standard deviation
of the differences between the two eyes were -0.15
± 0.88 ^V.
In the patients, the mean and standard deviations
of the responses of normal eyes were 4.61 ± 0.92 /xV;
these values were not significantly different from the
responses of normal subjects. While the normal eye
fixated the monitor, when recording from the occluded
amblyopic eye we never obtained reproducible potentials at the peak time of the first positive component
of P-ERG. Thus, during binocular fixation, potentials
from the normal eye (eg, a contralateral ERG) or from
the cortex (eg, VEP) which have been reported for
steady-state stimulation8 were avoided. Figure 1 shows
the P-ERG amplitudes of two normal individuals when
the fixation point was shifted horizontally and vertically. As reported previously,9 our results confirm that
under these stimulus conditions, the P-ERG has largest
amplitude at the fovea and reduces as the stimulus is
imaged eccentrically.
The results of the P-ERG amplitudes are listed in
Table 1. Depending on the clinical details, the amplitudes were larger with either monocular or binocular
fixation.
In Figure 2, the raw data of patient 4 are shown.
With monocular fixation (curves a and b), there was a
large amplitude difference between the normal right
eye (4.7 /iV) and the amblyopic left eye (0.7 jiV). Because of the low visual acuity of 0.03 of this patient,
his monocular fixation was accompanied by large eye
movements. With binocular fixation of the center of
the test field, the P-ERG increased to 1.4 jiV (curve c).
In view of the large squint angle of 17.5°, we shifted
the fixation point temporally up to 24° (curves d-h).
The amplitudes increased up to 4.1 /iV at a fixation of
20° eccentricity (curve g) and decreased with further
eccentric fixation (curve h). The temporal fixation point
at 20° fixation was then shifted up or down (curves ik). A maximal amplitude of 4.4 /*V was reached with
a fixation at 20° temporal and 2° above (curve j). The
amplitude difference of - 0 . 3 nV between the amblyopic and the normal eye is in the normal range. It
is remarkable that latenties of the P-ERG do not change
with fixation eccentricity (Fig. 2). The results are shown
schematically in Figures 3a and 3b.
Figures 3c and 3d show other examples of patients
in which the amplitude was larger than with binocular
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189
Reporrs
No. 1
Table 1. Clinical findings
P-ERG amplitude faV)
Patient
Sex
Visual
Fixation
Age
(yr)
acuity
(RE/LE)
eccentricity
(nasal)
1
F
23
1.0/0.4
2
F
35
0.1/1.0
3
F
22
4
M
23
1.0/0.03
5
M
40
0.5/1.0
6
F
28
1.2/0.03
7
8
M
M
11
19
1.0/0.3
1.2/0.1
9
M
12
1.0/0.03
10
F
24
0.63/1.0
11
F
60
0.2/1.0
12
F
18
0.07/1.2
13
M
9
0.8/0.15
14
M
14
1.0/0.6
'
1.0/0.03
Class
Strabismic, esotropia
at 4 yr, no therapy
Strabismic, surgery
at 35 yr
Strabismic, surgery
at 22 yr
Strabismic, esotropia
at 3 yr, patching
therapy
Anisometropic and
strabismic, first
refractive
correction at 7 yr
Anisometropic and
strabismic, first
refractive
correction at
11 yr, surgery at
22 yr
Strabismic, 0 therapy
Deprivation,
congenital ptosis,
surgery and
patching therapy
at 6yr
Strabismic, patching
therapy at 6 yr
Strabismic, patching
therapy at 6 yr
Strabismic, surgery
at 3 and 17 yr,
diplopia
Anisometropic, first
refractive
correction at 8 yr,
patching therapy
Anisometropic, first
refractive
correction at 8 yr
Anisometropic, first
refractive
correction at 10 yr
Amblyopic eye
Squint
angle
Normal eye
monocular
Monocular
Binocular
0°-4°
+0°-+5°
4.1
4.9
4.9
12°-15°
0
4.7
2.8
4.8
14°
0
4.2
1.1
4.2
Optic disc
+ 17.5°
4.7
0.7
4.4
Central
-2°
4.7
4.9
4.9
12°-14°
0
5.7
3.9
5.6
Central
8°
-0.3°
-6°
5.2
4.6
5.8
3.7
4.7
4.0
4°
+7°
3.6
3.0
3.6
Central
+0°-2°
5.8
6.3
6.6
+2°-3°
+20°
5.1
4.3
3.2
3°
0
6.0
5.8
5.8
2°
0
3.0
1.9
3.3
Central
0
3.2
3.2
3.7
fixation with monocular fixation. Patient 6 had a
straight eye position after surgery and the maximum
of P-ERG amplitude was found with binocular fixation
of the middle of the monitor. Patient 10 had a squint
angle of +0°-+2°, which fits well with her amplitude
maximum of P-ERG at +2°.
Figures 3e and 3f give examples of patients in which
the P-ERG amplitude was equal or larger with monocular fixation than with binocular fixation. Patient 5
(Fig. 3e) had a visual acuity of 0.5 in his amblyopic
eye and a very unsteady binocular fixation. With monocular central fixation, his P-ERG amplitude was reproducible and reached its maximum. In all horizontal
positions, patient 7 (Fig. 3f) had larger P-ERG ampli-
tudes with monocular fixation. Patient 11 experienced
diplopia and unsteady fixation; even with eccentric fixation corresponding to the clinical squint angle binocularly, her P-ERG amplitudes were only 3.2 nV.
Monocular fixation was better, although accompanied
by eye movements, and the P-ERG amplitude was 4.3
jiV. The difference in the P-ERG between the normal
and amblyopic eye was -0.8 nV and was in normal
range in spite of unsteady fixation.
The mean and standard deviation of the absolute PERG amplitude of amblyopic eyes was 4.70 ± 0.96
nV. The mean and standard deviation of the differences between normal and amblyopic eyes was 0.09
± 0.48 MV.
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INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / January 1987
190
Discussion. Conflicting results have been reported
as to whether the P-ERG is reduced in amblyopia. Several authors1"4 used transient checkerboard stimuli at
2 Hz and described a large reduction of the P-ERG
amplitude. Recently, Hess et al5'6 did not find a difference between normal eyes and amblyopic eyes with
square-wave gratings that were sinusoidally reversed at
8 Hz. We used stimulus conditions similar in contrast,
stimulus form, frequency, and size of checks and test
field to those used by Arden et al2'4, Sokol et al1, and
Wanger et al.3
Nevertheless, we did not find any significant difference between normal eyes and amblyopic eyes when
the eyes were optimally focused and aligned (ie, eccentricfixationtaken into account). With normal fixation,
the P-ERG amplitude of most of the amblyopes was
reduced; but when optimizing the fixation condition
for each individual eye, the amplitude of the P-ERG
increased. It was important to use fixation conditions
corresponding to the clinical findings of the patients.
For eyes with very low visual acuity and eccentric
monocular fixation, binocular fixation generally was
best (Table 1); but, in some patients with diplopia or
central fixation, the P-ERG amplitude was greater or
equal with monocularfixationthan with binocular fixation. It is indeed difficult to ensure correct fixation
alignment in patients with both poor visual acuity and
a large squint angle. In spite of this, we found that by
careful assessment of fixation alignment, the P-ERG
was normal in all types of amblyopia. Our patients
covered a wide age range (from 9 to 60 yr) and our
results do not support the notion that there are changes
6
go
3°
30
temporal
6°
top
0c
Vol. 28
6°
nasal
3°
6°
bottom
Fig. 1. Effect of eccentric fixation on P-ERG amplitude of two
normal individuals, a, Horizontal shifting, b, Vertical shifting.
There were no significant differences in either the
absolute amplitudes or in the relative differences of
amblyopic eyes and normal eyes. Latencies of amblyopic eyes were in normal range.
AE
Binocular fixation
Mpnocular
fixation
top
3
0c
.d
bottom r0°
6C
nasal
• e .f .g .h
.k
14° 17° 20° 24°
temporal
AE
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Fig. 2. P-ERG recordings
from the normal (NE) and
amblyopic eye (AE) of patient 1. Left, Monocular fixation of the normal eye
(curve a) and the amblyopic
eye (curve b). Middle, Horizontal fixation shift of the
binocularly fixating amblyopic eye (curves c-h).
Right, Vertical fixation shift
of the binocularly fixating
amblyopic eye at 20° temporal (curves g-j). (Inset)
Points of fixation.
Hv
T3
3 4
limit of
testf ield
4
Acknowledgments. The authors acknowledge Professor E.
Dodt for continous support and encouragement and Dr. W.
Skrandies for helpful discussion.
4
•
.
< o
191
Reports
No. 1
4° 0 4
nasal
Hv
8
•
^ <
V
4° 2 0
bottom
12 16 20 24
temp
2
4
top
.10
6
From the *Max Planck Institute for Clinical and Physiological
Research, Bad Nauheim, F.R.G., and 1st University Eye Clinic,
Vienna, Austria; and fSt. Marienkrankenhaus, Frankfurt, F.R.G.
Submitted for publication: October 17, 1985. Reprint requests: Dr.
Irene Gottlob, 1st University Eye Clinic, Spitalg-2, A-1090, Vienna,
Austria.
6
References
4
tude
o rv>
V ^^
Q.
E 6
4
2
n
V
7 .
5
A(
6°
0
nasal
•
6°
temp
0
6°
nasal
•
6°
temp
Fig. 3. P-ERG amplitudes (ordinates) of amblyopic eyes of patients
(4, 6, 10, 5, 7) plotted against horizontal or vertical eccentricity. •:
normal eye; • : amblyopic eye, monocular fixation; 0: amblyopic
eye, binocular fixation.
at the retinal level caused by long-term disuse (see Arden and Wooding4) in functional amblyopia.
Thus, we are in agreement with thefindingsof Hess
et al5'6 of a normal P-ERG response in amblyopic eyes.
Key words: amblyopia, pattern electroretinogram, electrophysiology
1. Sokol S and Nadler D: Simultaneous electroretinograms and
visual evoked potentials from adult amblyopes in response to
pattern stimuli. Invest Ophthalmol Vis Sci 18:848, 1979.
2. Arden GB, Vaegan, Hogg CG, Powell DJ, and Carter RM: Pattern
ERGs are abnormal in many amblyopes. Trans Ophthalmol Soc
UK 308:82, 1980.
3. Wanger P and Person HE: Oscillatory potentials, flash and pattern-reversal electroretinograms in amblyopia. Acta Ophthalmol
62:643, 1984.
4. Arden GB and Wooding SL: Pattern ERGs in amblyopia. Invest
Ophthalmol Vis Sci 26:88, 1985.
5. Hess RF and Baker CL: Assessment of retinal function in severely
amblyopic individuals. Vision Res 24:1367, 1984.
6. Hess RF, Baker CL, Verhoeve JN, Tulunay Keesey U, and France
TD: The pattern evoked electroretinogram: its variability in normals and its relationship to amblyopia. Invest Ophthalmol Vis
Sci 26:1610, 1985.
7. Arden GB, Carger RM, Hogg C, Siegel IM, and Margolis S: A
gold foil electrode: extending the horizons for clinical electroretinography. Invest Ophthalmol Vis Sci 18:421 1979.
8. Seipel WH and Siegel IM: Recording the pattern electroretinogram: a cautionary note. Invest Ophthalmol Vis Sci 24:796, 1983.
9. Hess RF and Baker CL: Human pattern-evoked electroretinogram. J Neurophysiol 51:939, 1984.
Orthogonal Astigmatic Axes in Chinese and Caucasian Infants
Frank Thorn,* Richard Held.f and Li-Luo
Caucasian infants are known to have a high incidence of
astigmatism. The axis of greatest power is usually in the orientation orthogonal to the most common type found in Caucasian adults, with-the-rule astigmatism. We now find that
Chinese infants also have a high incidence of astigmatism
relative to adults, but its orientation is orthogonal to that of
Caucasian infants. The source of this racial difference is not
clear. It is unlikely to be due to the most obvious difference,
the structure of the eyelids. Invest Ophthalmol Vis Sci 28:
191-194,1987
The high incidence of astigmatism in human infants
has been rediscovered in recent years.1"4 Three different
techniques, near retinoscopy,2 cycloplegic retinoscopy,3
and photo-refraction,4 all demonstrate it. They agree
that the predominant axis of negative cylindrical power
is vertical, that is, against-the-rule astigmatism. These
studies were all performed in the United States and
the subjects were all Caucasians. Recently a visiting
investigator from the People's Republic of China (LiLuo Fang) joined the M.I.T. Infant Vision Laboratory.
Herfluencyin Chinese allowed us to work with Chinese
parents and their Chinese infants. To our surprise, we
discovered that these infants had an incidence of astigmatism equal to that of Caucasians, but with the predominant axis in the orthogonal orientation, that is,
with-the-rule astigmatism.
Materials and Methods. Near retinoscopy was used
by FT to refract 45 Caucasian infants (both parents
were Caucasian), 22 Chinese infants (both parents were
Chinese), 47 Caucasian adults, and 40 Chinese adults.
The Chinese subjects were recruited by Dr. Fang, pri-
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