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Ocular Resting Potential in Myotonic Dystrophy
OCULAR RESTING P O T E N T I A L IN MYOTONIC DYSTROPHY RODNEY A. ANDERSON, M.D.,
AND HERMANN M.
BURIAN,
M.D.
Iowa City, Iowa
In addition to the myotonic cataract which has long been recognized as characteristic of myotonic dystrophy, there is wide-spread involvement of the ocular tissues1"3 which can no longer be considered coincidental. Studies from this laboratory have been directed to functional and morphologic abnormalities of the retina in patients with myotonic dystro phy. One of the outstanding findings was the functional deficit frequently evidenced by electroretinography (ERG) and by dark ad aptation studies, even in the absence of sig nificant ophthalmoscopically visible retinal changes.2"4 The ERG gives information about the functional state of the retinal layers from the sensory epithelium to the bipolar cells. The electro-oculogram (EOG) is said to originate primarily in the pigment epithe lium.5 The combined information from the ERG and the EOG enables one, therefore, to achieve further refinement in the localization of retinal lesions. The EOG, as used in this study, consists of a determination of the influence of light and dark adaptation on the standing poten tial of the eye. It is not possible to determine this potential directly in the human eye, but relative determinations can be made by em ploying potential changes induced by eye movements between fixed electrodes placed on the skin to the sides of the eyes. Using this method, it has been found6'7 that the standing potential of the eye de creases during dark adaptation and increases From the ERG laboratory of the Department of Ophthalmology and the Neurosensory Center (Paper No. 136), College of Medicine, University of Iowa. The Neurosensory Center is supported by Program Project Grant NB-33S4. Presented at the Annual Meeting of the Midwestern Section of the Association for Research in Ophthalmology, Den ver, Colorado, March 13, 1969. Reprint requests to Hermann M. Burian, M.D., University Hospitals, Iowa City, Iowa 52240.
during subsequent light adaptation. The ab solute values of these potentials depend on many factors and are not as useful as the ratio between the dark trough (the lowest potential during the dark adaptation) and the light peak (the highest value reached during subsequent light adaptation). The light/dark ratio of the EOG ( L / D ratio) gives a useful index for clinical evaluation of the normalcy of the standing potential of the eye. The results of a typical normal re sponse in terms of amplitude changes with dark adaptation and subsequent light adapta tion are shown in Figure 1. MATERIAL AND METHODS
The light/dark ratio of the EOG in 44 normal eyes was compared to the light/dark ratio in 38 eyes of patients with myotonic dystrophy. The normal population was rep resented by individuals between the ages of 20 and SO years; the younger group con sisted of volunteers and the older group was made up of patients with minor refractive errors who had otherwise normal eyes and who had come to the clinic for a refraction. EEG silver-silver chloride electrodes (Grass Company) were fastened and taped 1.0 cm from the outer and inner canthus of each eye. The electrodes were carefully and accurately placed, since we found that the positioning of the electrodes markedly in fluenced the amplitudes of the EOG; al though this was of minor significance for the light/dark ratio, it was considered wise to make the test as repeatable as possible. The patient was placed in a recumbent po sition and his head was centered in relation to a light box one meter above his head. The light box contained the adaptation light and two fixation lights, placed so that the eyes had to make total excursions of 60 degrees when shifting fixation from one light to the other. The adaptation light was turned on
863
864
AMERICAN JOURNAL OF OPHTHALMOLOGY
NOVEMBER, 1969
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Light
=-:
Dark TIME IN MINUTES
1—
Light
Fig. 1 (Anderson and Burian). Typical normal results of EOG test in terms of amplitude of resting current. Note reduction in the dark and increase with subsequent light adaptation. and the patient made a few fixation sweeps from one fixation light to the other every minute. After 12 minutes of light adaptation, the adapting light was turned off and, except for the fixation lights, the patient remained in complete darkness for 24 minutes. From the fifth to the 15th minute in the dark the patient made a few sweeps between the fixation lights every minute. He then rested and at the end of the 24th minute he again made a few sweeps. The adapting light was turned on and the test continued in a lightadapted state for another 12 minutes. The patient and the lights were in a shielded room. The signals were fed through a direct-current differential amplifier with a gain of 1,000 and recorded on a strip chart.
RESULTS
Normal subjects. In accordance with the findings of other workers, the influence of dark adaptation and subsequent light adapta tion showed the typical dark trough and light peak of the standing potential of the eye (fig. 1). The mean of the light/dark ratio was found to be 2.38 with a standard devia tion of 0.337. The distribution of the light/dark ratio in this population of 31 eyes of normal subjects is shown in Figure 2. There appeared to be no significant age-re lated difference in these subjects. Myotonic patients. The light/dark ratio of the patients with myotonic dystrophy had a mean of 2.36, that is, it was identical with that of the normal subjects, but there was a
865
EOG IN MYOTONIC DYSTROPHY
VOL. 68, NO. 5
wider spread of the values as indicated by a standard deviation of 0.507. This distribu tion is also shown in Figure 2. The graph in dicates that 25 eyes of the patients with myotonic dystrophy had a light/dark ratio which ranged from 1.5 to 2.5 ; the ratio for the 31 eyes of the normal subjects lay be tween the same limits. In contrast, 13 eyes of the patients with myotonic dystrophy and 13 eyes of the normal subjects had a light/dark ratio between 2.5 and 3.5 ; only one normal eye had a ratio higher than 3.0, while in six eyes of the patients with myo tonic dystrophy, the ratio was above 3.0. DISCUSSION
3.0 25 :
.
-
C: 2.0 •
·
·
·
0.5-
These findings appear to indicate that the standing potential of the eyes of patients with myotonic dystrophy is not seriously af fected by their disease. None of the eyes of these patients had lower light/dark ratios than those found in some normal subjects, although the number of eyes of myotonic subjects with a light/dark ratio lower than 2.5 was greater than in the normal subjects. However, this is balanced by the greater number of myotonic eyes with light/dark ra tios between 3.01 and 3.50. The relatively normal EOG which we found markedly contrasts with the ERG regjj Normal Subjects _ ■
1.50-2.00 2.01-2.50
3.5
Myotonic Subjects
2.51-3.00
3.01-3.50
L/D RATIO
Fig. 2 (Anderson and Burian). Histogram show ing distribution of light/dark (L/D) ratios of EOG in normal subjects and in patients with myotonic dystrophy.
0.0
50
_L 100
J_ 150
JL 200
250
AMPLITUDE OF ERG o-WAVE IN MICROVOLTS
Fig. 3 (Anderson and Burian). Scatter diagram relating the light/dark (L/D) ratio and the ampli tude of the a-wave of the ERG in patients with myotonic dystrophy. sponses of myotonic patients, which are gen erally low and sometimes very low. These results would indicate that the process af fecting the eyes of these patients is largely intraretinal. It appeared worthwhile to compare sep arately the light/dark ratios with the a- and b-wave amplitudes of the ERGs in the pa tients with myotonic dystrophy. These com parisons are shown in the form of scattergrams in Figures 3 and 4. Figure 3 seems to indicate a trend correlating the a-wave am plitudes and the light/dark ratio. The figures published by Junge 3 also point in the same direction. However, the correlation coefficient was r=0.184, implying that there was no sta tistically significant correlation. Figure 4 clearly demonstrates that there was no corre lation between the amplitude of the b-wave and the light/dark ratio. SUMMARY
Electro-oculographic studies of 44 normal eyes and 38 eyes of patients with myotonic
866
AMERICAN JOURNAL OF OPHTHALMOLOGY
NOVEMBER, 1969
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AMPLITUDE OF ERG b-WAVE IN MICROVOLTS Fig. 4 (Anderson and Burian). Scatter diagram relating the light/dark (L/D) ratio and the b-wave of the ERG in patients with myotonic dystrophy. dystrophy showed that the mean light/dark ratio of the normal eyes was 2.38 with a standard deviation of 0.337. The light/dark ratio of the patients with myotonic dystro phy was 2.36 with a standard deviation of 0.507. The relative normalcy shown by the light/dark ratio of the electro-oculogram of these patients strongly contrasts to their generally low electroretinogram amplitudes. This would appear to indicate an intraretinal site for the lesions in myotonic dystrophy. REFERENCES
1. Pendefunda, G., Cernea, P. and Dobrescu, G. : Manifestärile oculare în miotonia distrofica Steinert. Oftalmologia (Bucarest) 7:219, 1964.
2. Burian, H. M. and Burns, C. A. : Ocular changes in myotonic dystrophy. Tr. Am. Ophth. Soc. 46:250, 1966; Am. J. Ophth. 63:22, 1967. 3. Junge, J. : Ocular changes in dystrophia myotonica, paramyotonia and myotonia congenita. Docum. Ophthal. 21:1, 1966. 4. Burian, H. M. and Burns, C. A. : Electroretinography and dark adaptation in patients with myo tonic dystrophy. Am. J. Ophth. 61:1044 (May, Pt. I I ) , 1966. 5. Noell, W. K. : Azide-sensitive potential differ ence across the eye-bulb. Am. J. Physiol. 170:217, 1952. 6. François, J., Verriest, G. and DeRouck, A. : Modification of the amplitude of the human electrooculogram by light and dark adaptation. Brit. J. Ophth. 39:398, 1955. 7. Arden, G. B. and Kelsey, J. H. : Changes pro duced by light in the standing potential of the human eye. J. Physiol. 161:189, 1962.
AND HERMANN M.
BURIAN,
M.D.
Iowa City, Iowa
In addition to the myotonic cataract which has long been recognized as characteristic of myotonic dystrophy, there is wide-spread involvement of the ocular tissues1"3 which can no longer be considered coincidental. Studies from this laboratory have been directed to functional and morphologic abnormalities of the retina in patients with myotonic dystro phy. One of the outstanding findings was the functional deficit frequently evidenced by electroretinography (ERG) and by dark ad aptation studies, even in the absence of sig nificant ophthalmoscopically visible retinal changes.2"4 The ERG gives information about the functional state of the retinal layers from the sensory epithelium to the bipolar cells. The electro-oculogram (EOG) is said to originate primarily in the pigment epithe lium.5 The combined information from the ERG and the EOG enables one, therefore, to achieve further refinement in the localization of retinal lesions. The EOG, as used in this study, consists of a determination of the influence of light and dark adaptation on the standing poten tial of the eye. It is not possible to determine this potential directly in the human eye, but relative determinations can be made by em ploying potential changes induced by eye movements between fixed electrodes placed on the skin to the sides of the eyes. Using this method, it has been found6'7 that the standing potential of the eye de creases during dark adaptation and increases From the ERG laboratory of the Department of Ophthalmology and the Neurosensory Center (Paper No. 136), College of Medicine, University of Iowa. The Neurosensory Center is supported by Program Project Grant NB-33S4. Presented at the Annual Meeting of the Midwestern Section of the Association for Research in Ophthalmology, Den ver, Colorado, March 13, 1969. Reprint requests to Hermann M. Burian, M.D., University Hospitals, Iowa City, Iowa 52240.
during subsequent light adaptation. The ab solute values of these potentials depend on many factors and are not as useful as the ratio between the dark trough (the lowest potential during the dark adaptation) and the light peak (the highest value reached during subsequent light adaptation). The light/dark ratio of the EOG ( L / D ratio) gives a useful index for clinical evaluation of the normalcy of the standing potential of the eye. The results of a typical normal re sponse in terms of amplitude changes with dark adaptation and subsequent light adapta tion are shown in Figure 1. MATERIAL AND METHODS
The light/dark ratio of the EOG in 44 normal eyes was compared to the light/dark ratio in 38 eyes of patients with myotonic dystrophy. The normal population was rep resented by individuals between the ages of 20 and SO years; the younger group con sisted of volunteers and the older group was made up of patients with minor refractive errors who had otherwise normal eyes and who had come to the clinic for a refraction. EEG silver-silver chloride electrodes (Grass Company) were fastened and taped 1.0 cm from the outer and inner canthus of each eye. The electrodes were carefully and accurately placed, since we found that the positioning of the electrodes markedly in fluenced the amplitudes of the EOG; al though this was of minor significance for the light/dark ratio, it was considered wise to make the test as repeatable as possible. The patient was placed in a recumbent po sition and his head was centered in relation to a light box one meter above his head. The light box contained the adaptation light and two fixation lights, placed so that the eyes had to make total excursions of 60 degrees when shifting fixation from one light to the other. The adaptation light was turned on
863
864
AMERICAN JOURNAL OF OPHTHALMOLOGY
NOVEMBER, 1969
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' ' ■ «
IO 12 2 4 6 8 IO 12 14 16 18 20 22 24 2 4 6 8 IO 12 I-TTH
Light
=-:
Dark TIME IN MINUTES
1—
Light
Fig. 1 (Anderson and Burian). Typical normal results of EOG test in terms of amplitude of resting current. Note reduction in the dark and increase with subsequent light adaptation. and the patient made a few fixation sweeps from one fixation light to the other every minute. After 12 minutes of light adaptation, the adapting light was turned off and, except for the fixation lights, the patient remained in complete darkness for 24 minutes. From the fifth to the 15th minute in the dark the patient made a few sweeps between the fixation lights every minute. He then rested and at the end of the 24th minute he again made a few sweeps. The adapting light was turned on and the test continued in a lightadapted state for another 12 minutes. The patient and the lights were in a shielded room. The signals were fed through a direct-current differential amplifier with a gain of 1,000 and recorded on a strip chart.
RESULTS
Normal subjects. In accordance with the findings of other workers, the influence of dark adaptation and subsequent light adapta tion showed the typical dark trough and light peak of the standing potential of the eye (fig. 1). The mean of the light/dark ratio was found to be 2.38 with a standard devia tion of 0.337. The distribution of the light/dark ratio in this population of 31 eyes of normal subjects is shown in Figure 2. There appeared to be no significant age-re lated difference in these subjects. Myotonic patients. The light/dark ratio of the patients with myotonic dystrophy had a mean of 2.36, that is, it was identical with that of the normal subjects, but there was a
865
EOG IN MYOTONIC DYSTROPHY
VOL. 68, NO. 5
wider spread of the values as indicated by a standard deviation of 0.507. This distribu tion is also shown in Figure 2. The graph in dicates that 25 eyes of the patients with myotonic dystrophy had a light/dark ratio which ranged from 1.5 to 2.5 ; the ratio for the 31 eyes of the normal subjects lay be tween the same limits. In contrast, 13 eyes of the patients with myotonic dystrophy and 13 eyes of the normal subjects had a light/dark ratio between 2.5 and 3.5 ; only one normal eye had a ratio higher than 3.0, while in six eyes of the patients with myo tonic dystrophy, the ratio was above 3.0. DISCUSSION
3.0 25 :
.
-
C: 2.0 •
·
·
·
0.5-
These findings appear to indicate that the standing potential of the eyes of patients with myotonic dystrophy is not seriously af fected by their disease. None of the eyes of these patients had lower light/dark ratios than those found in some normal subjects, although the number of eyes of myotonic subjects with a light/dark ratio lower than 2.5 was greater than in the normal subjects. However, this is balanced by the greater number of myotonic eyes with light/dark ra tios between 3.01 and 3.50. The relatively normal EOG which we found markedly contrasts with the ERG regjj Normal Subjects _ ■
1.50-2.00 2.01-2.50
3.5
Myotonic Subjects
2.51-3.00
3.01-3.50
L/D RATIO
Fig. 2 (Anderson and Burian). Histogram show ing distribution of light/dark (L/D) ratios of EOG in normal subjects and in patients with myotonic dystrophy.
0.0
50
_L 100
J_ 150
JL 200
250
AMPLITUDE OF ERG o-WAVE IN MICROVOLTS
Fig. 3 (Anderson and Burian). Scatter diagram relating the light/dark (L/D) ratio and the ampli tude of the a-wave of the ERG in patients with myotonic dystrophy. sponses of myotonic patients, which are gen erally low and sometimes very low. These results would indicate that the process af fecting the eyes of these patients is largely intraretinal. It appeared worthwhile to compare sep arately the light/dark ratios with the a- and b-wave amplitudes of the ERGs in the pa tients with myotonic dystrophy. These com parisons are shown in the form of scattergrams in Figures 3 and 4. Figure 3 seems to indicate a trend correlating the a-wave am plitudes and the light/dark ratio. The figures published by Junge 3 also point in the same direction. However, the correlation coefficient was r=0.184, implying that there was no sta tistically significant correlation. Figure 4 clearly demonstrates that there was no corre lation between the amplitude of the b-wave and the light/dark ratio. SUMMARY
Electro-oculographic studies of 44 normal eyes and 38 eyes of patients with myotonic
866
AMERICAN JOURNAL OF OPHTHALMOLOGY
NOVEMBER, 1969
3.5 • •
3.0
•
•
•
•
•
•
•
2.5
• •
•
2.0 -
· ·
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•
· ·
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•
•
•
•
1.5
•
0.0 0.5
•
50
100
·
150
200
250
1
1
300
350
1 400
1 450
AMPLITUDE OF ERG b-WAVE IN MICROVOLTS Fig. 4 (Anderson and Burian). Scatter diagram relating the light/dark (L/D) ratio and the b-wave of the ERG in patients with myotonic dystrophy. dystrophy showed that the mean light/dark ratio of the normal eyes was 2.38 with a standard deviation of 0.337. The light/dark ratio of the patients with myotonic dystro phy was 2.36 with a standard deviation of 0.507. The relative normalcy shown by the light/dark ratio of the electro-oculogram of these patients strongly contrasts to their generally low electroretinogram amplitudes. This would appear to indicate an intraretinal site for the lesions in myotonic dystrophy. REFERENCES
1. Pendefunda, G., Cernea, P. and Dobrescu, G. : Manifestärile oculare în miotonia distrofica Steinert. Oftalmologia (Bucarest) 7:219, 1964.
2. Burian, H. M. and Burns, C. A. : Ocular changes in myotonic dystrophy. Tr. Am. Ophth. Soc. 46:250, 1966; Am. J. Ophth. 63:22, 1967. 3. Junge, J. : Ocular changes in dystrophia myotonica, paramyotonia and myotonia congenita. Docum. Ophthal. 21:1, 1966. 4. Burian, H. M. and Burns, C. A. : Electroretinography and dark adaptation in patients with myo tonic dystrophy. Am. J. Ophth. 61:1044 (May, Pt. I I ) , 1966. 5. Noell, W. K. : Azide-sensitive potential differ ence across the eye-bulb. Am. J. Physiol. 170:217, 1952. 6. François, J., Verriest, G. and DeRouck, A. : Modification of the amplitude of the human electrooculogram by light and dark adaptation. Brit. J. Ophth. 39:398, 1955. 7. Arden, G. B. and Kelsey, J. H. : Changes pro duced by light in the standing potential of the human eye. J. Physiol. 161:189, 1962.