Yonago Acta medica 2004;47:37–44

Fast and Slow Oscillation Electrooculography in Harada
DiseaseAkihiko Tamai*, Junji Hamamoto†, Jiro Hasegawa, Takashi Baba, Shiro Hatta andYuji Sasaki
Division of Ophthalmology and Visual Science, Department of Medicine of Sensory and Motor
Organs, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, *Clinicof Ophthalmology, Hino Hospital Association Hino Hospital, Hino 689-4504 and †Clinic of
Ophthalmology, Matsue Municipal Hospital, Matsue 690-8509 Japan
We assessed clinical utility of fast and slow oscillations (FO and SO) of the electrooculogram (EOG) in Harada disease. In 12 eyes of 4 female and 2 male subject patients
aged 18 to 77 years (average: 41.8 years), FO and SO were recorded using an automatedelectrooculograph, the Nidek EOG-2, in the acute period before treatment and in theremission period under corticosteroid therapy. FO parameters, namely the RfFO [theaverage ratio in percentage of the maximum amplitude in the dark period (AD)/theminimum amplitude in the light period (AL) during FO measurement] and the dfFO
(the average difference in µV between AD and AL) were evaluated. The L/DSO (the light
peak/dark trough ratio of the SO) was calculated as an SO parameter. The RfFO, dfFO
and L/DSO showed low values in 7 (58.3%), 10 (83.3%) and 8 (66.7%) out of all 12 eyesin the acute period, respectively. In the remission period, values in the normal range
were obtained in 12 (100%), 11 (91.7%) and 8 (66.7%) out of 12 eyes in the RfFO, dfFO
and L/DSO, respectively. In mutual relation to each RfFO, dfFO and L/DSO in the acuteand remission periods, all 12 eyes showed recovery values both in the RfFO and dfFO
in the remission stage after systemic administration of corticosteroids, but 4 out of 12eyes (33.3%) showed no recovery in the L/DSO. The FO may therefore well reflect theaffected or ameliorated conditions in the outer layers of the retina and the choroid inHarada disease, in contrast to the SO. However, further observations are requested in
more Harada disease patients.
Key words: acute and remission periods; electrooculogram; fast oscillation; Harada disease; slow
oscillation

Harada disease is a posterior uveitic disease
manifesting exudative retinal detachment that isclassified as the posterior uveitis type of VogtKoyanagi-Harada (VKH) syndrome. Indocyanine

green (ICG) fluorescence angiography has revealed
severe disturbance of choroidal circulation derived from compression due to the high-grade infiltration of inflammatory cells into the choroid in

Abbreviations: AD, maximum amplitude in the dark period; AL, minimum amplitude in the light period during FO
measurement; CRVO, Central retinal vein occlusion; dfFO, average difference in µV between AD and AL during
the FO measurement; EOG, electrooculogram; FO, fast oscillation; ICG, indocynine green; L/DSO, light/dark troughratio of the SO; RfFO, average ratio in percentage of AD/AL; SO, slow oscillation; VKH, Vogt-Koyanagi-Harada

37

A. Tamai et al.

Harada disease; in the early to late stage, leakage
from the choroid into the subretinal space is seen
in ICG angiography at the same leak points seenin fluorescein fundus angiography, and in the latephase, filling delay of the choroidal circulationand indistinct choroidal vessels correlate with theseverity of the disease (Matsunaga et al., 1994).
VKH syndrome is considered to be an autoimmune syndrome against melanocytes (Moorthy
et al., 1995). The mechanism and immunologicalreactions against melanocytes are not well understood (Hayakawa et al., 2004), but clinically VKH
syndrome can be treated relatively easily by systemic corticosteroids, although the inflammation may
be prolonged and result in reduced visual acuity insome cases.
Choroidal circulation supplies the outer portion of the retina, including the photoreceptor cells
and retinal pigment epithelium. Thus, it is naturalthat choroidal circulation disturbance should influence fast and slow oscillations (FO and SO) of theelectrooculogram (EOG) originating from the outerportion of the retina, mainly the retinal pigment
epithelium under the influence of choroidal circulation (Nakao et al., 1995; Tamai et al., 1997; Inoueet al., 2003), but little attention has been paid tothe behavior of both potentials, especially the FO
in various types of choroidal diseases including
Harada disease (Tamai et al., 1997; Tamai, 2003).
In the present study, we assessed clinical utility of
the FO and SO of the EOG in Harada disease.

Patients and Methods
Patient selection
Six patients (2 males, 4 females; age range 18–77
years, average 41.8 years) with Harada disease in
the acute period before treatment were randomly
chosen for EOG recording over the past 4 years(August 1996 to September 2000) at the Department of Ophthalmology, Tottori University Hospital (Table 1). Both eyes showed typicallyaffected diffuse or focal chorioretinal lesions,
ophthalmoscopically and fluorescein fundus
angiographically at the initial clinical examinationin each patient. All patients were treated bysystemic corticosteroids with intravenous injectionof methylpredonisolone 1,000 mg for 3 days

Table 1. Clinical data of 12 eyes of 6 patients with Harada disease
Patient
numberAge (year)

Sex

Affected eye

147

Female2

77

Female321Female418

Female

5

33

Male

6

55

Male

Right
Left
Right
Left
Right
Left
Right
Left
Right
Left
Right
Left

Average

41.8

RD, exudative retinal detachment in the acute period.
† Limited in the arcade.

38

Corrected visual acuity
Acute period Remission period
0.03
0.04
0.5
0.2
0.03
0.02
0.7
0.7
0.5
0.05
0.8
0.7

1.2
0.8
0.9
0.9
1.2
1.2
1.0
0.8
1.2
1.2
1.0
0.9

0.23

0.87

Type of RD
Diffuse
Diffuse
Diffuse
Diffuse
Diffuse
Diffuse
Focal†
Focal
Diffuse
Diffuse
Focal
Focal

EOG FO and SO in Harada disease

Table 2. Results of the RfFO of the EOG in 12 eyes of 6 patients with Harada disease
Patient
numberAffectedeye

Acute period
RfFO (%)<114.7%*

Remission period
RfFO (%)≥114.7%†

1

Right
Left
Right
Left
Right
Left
Right
Left
Right
Left
Right
Left

108
109
124
110
138
127
114
113
108
108
130
128

119
121
139
124
147
133
155
150
135
142
135
138

2
3
4
5
6
Ratio

7/12 (58.3%)

12/12 (100%)

Recovery value§

12/12 (100%)* Data under 114.7% indicate low values of the RfFO in the present study.
† Data over 114.7% indicate values in the normal range.
§ Increased RfFO obtained in the remission period, compared with the RfFO in the acute period.
Pertinent data in each column are marked by a solid circle ( ).

followed by gradually decreased administrationof predonisolone from 60 mg to 5 mg every week
until the remission stage.
Their corrected visual acuities from 0.02 to 0.7
averaging 0.23 in the acute period showed remarkably
recovered visions from 0.8 to 1.2 averaging 0.87 in
the remission period under corticosteroid therapy(Table 1).
Patients were excluded from this study if they
had an opaque media and a bilateral refraction error
difference of more than 3 diopters.

W) produce a background luminance of 1,270 lx,
when measured at the location of the patient’s eyes.
For every patient, cup-shaped silver-silver
chloride conductive electrodes, 8 mm in diameter,
were placed beside both canthi of each eye on theorbital margin, and a grounding electrode, with thesame cup shape, was placed on the left earlobe, asroutinely used. Before setting these electrodes,
the skin was cleaned with 90% alcohol, and thenelectrodes were applied with a conductive paste.
Electrode resistance was below 10 kΩ.
Before FO recording, a 10-min adaptation
period at a background luminance level of 1,270 lx
was given to the patients. Then the patients were
instructed to fixate alternately on a pair of targets on
the screen inside the dome. The 2 targets subtended
40° to the eye, and were presented alternately witha frequency of 0.5 Hz.
On the FO recording, the dome was periodically illuminated for 1 min followed by 1 min of
darkness. The measurements were started 40 s
after each dark or light period began. There were
10 measurements in each dark or light period. Six
out of 10 EOG amplitudes were automaticallyFO and SO recordings
By a newly devised automated electrooculograph,
the Nidek EOG-2 (Nidek, Gamagori, Japan) (Nakaoet al., 1995; Inoue et al., 2003), the FO and SO
were recorded in the acute period before treatment
and in the remission period under corticosteroid
therapy in each patient. The EOG-2 consists of adome, a personal computer, an index controller,
an amplifier, a printer and an EOG pen recorder.
Inside the dome is a hemispheric screen with aradius of 300 nm. Four tungsten lamps (115 V, 50

39

A. Tamai et al.

Table 3. Results of the dfFO of the EOG in 12 eyes of 6 patients with Harada disease
Patient
numberAffectedeye

Acute period
dfFO (µV)<108.4 µV*

1

Right
Left
Right
Left
Right
Left
Right
Left
Right
Left
Right
Left

55
45
83
47
80
78
124
114
23
18
92
101

2
3
4
5
6
Ratio

Remission period
dfFO (µV)≥108.4 µV†

Recovery value§

109
124
181
125
113
104
191
144
210
110
138
127
10/12 (83.3%)

11/12 (91.7%)

12/12 (100%)* Data under 108.4 µV indicate low values of the dfFO in the present study.
† Data over 108.4 µV indicate values in the normal range.
§ Increased dfFO obtained in the remission period, compared with the dfFO in the acute period.
Pertinent data in each column are marked by a solid circle ( ).

averaged and recorded at the end of each dark or
light period through the EOG artifact rejection
system on the Nidek EOG-2 (Inoue et al., 2003).
In 10 pairs of FO measurements (dark-lightperiod of 1 min each), FO parameters, namely
the RfFO [the average ratio in percentage of the

maximum amplitude in the dark period (AD)/theminimum amplitude in the light period (AL)] andthe df FO (the average difference in µV between
AD and AL during the FO measurement) were calculated, referring to the report by De Rouck andKayembe (1981), only if at least 3 successive steps

Table 4. Results of the L/DSO of the EOG in 12 eyes of 6 patients with Harada disease
Patient
numberAffected
eye

1

Right
Left
Right
Left
Right
Left
Right
Left
Right
Left
Right
Left

2
3
4
5
6
Ratio

Acute period
L/DSO
<1.6*

Remission period
L/DSO
≥1.6†

1.37
1.29
2.45
1.76
1.40
1.34
1.43
1.44
1.00
1.30
2.37
2.27

2.14
2.14
1.96
1.47
3.37
3.59
1.85
1.91
1.06
1.48
1.51
1.68
8/12 (66.7%)

8/12 (66.7%)* Data under 1.6 indicate low values of the L/DSO in the present study.
† Data over 1.6 indicate values in the normal range.
§ Increased L/DSO obtained in the remission period, compared with the L/DSO in the acute period.
Pertinent data in each column are marked by a solid circle ( ).

40

Recovery value§

8/12 (66.7%)

EOG FO and SO in Harada disease

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Fig. 1. EOG fast oscillation (FO) and slow oscillation (SO) patterns in the acute and remission periods in both eyes ofPatient 1 with Harada disease (47-year-old female). R, right eye; L, left eye. D, dark period; L, light period (horizontalaxis).

showed some identical amplitude change. Dated
and occasional large amplitude changes were nottaken into account (Inoue et al., 2003).
Then the SO was recorded in all patients. Before the SO recording, the patients were subjected
to a 10-min pre-light adaptation in the same manner as in the FO recording. On the recording,where 20 min of darkness was followed by 20 minof illumination, EOG measurements were started
40 s before the end of each 1-min period during
the dark and light adaptations. Six out of 10 EOG
amplitudes were automatically averaged and recorded every 1 min during the SO measurement as
in the FO recording.
The SO shows a trough in the dark adaptation(dark trough) and a peak in the light adaptation(light peak) in response to dark and light periodsof approximately 12.5 min each. The L/DSO (thelight peak/dark trough ratio of the SO) developed
by Arden and others (1962) was automaticallycalculated as an SO parameter in the present
survey.
In this study, the calibration sensitivity for the
pen recorder was 200 µV/division on the printer.
The time constant of the amplifier was set at 3 s,
and a high frequency cutoff of -3 dB was set at 20
Hz for both FO and SO recordings.
Pupillary dilation provides better controlof retinal illumination levels, but prolongs thetime for the EOG examination and may makethe examination somewhat more uncomfortable
for some patients. Therefore, the FO and SO recordings were performed with pupils undilated.

41

A. Tamai et al.

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Fig. 2. Mutual relation to the RfFO of the EOG in theacute and remission periods in 12 eyes of 6 patients with
Harada disease.

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Fig. 3. Mutual relation to the dfFO of the EOG in theacute and remission periods in 12 eyes of 6 patients with
Harada disease.

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Marks indicating each eye of each patient in Figs. 2 to 4:
�Patient 1right eye
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left eye
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right eye
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Fig. 4. Mutual relation to the L/DSO of the EOG in theacute and remission periods in 12 eyes of 6 patients with
Harada disease.

Patient 4right eye
Patient 4
left eye
Patient 5
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Patient 5
left eye
Patient 6
right eye
Patient 6
left eyetentatively regarded as those in the normal range inthe present analysis.

Normal control eyes
Twenty-one fellow intact eyes of 21 patients withunilateral, ischemic central retinal vein occlusion(CRVO) previously reported by Inoue and others(2003) served as normal control eyes in the present
survey. Mean ± SD of the RfFO, dfFO and L/DSO
were 125.9 ± 11.2% [n = 21], 168.9 ± 60.5 µV [n =21] and 1.93 ± 0.33 [n = 20], respectively in their
FO and SO measurements (Inoue et al., 2003).
Therefore, values over 114.7%, 108.4 µV and 1.6
in the Rf FO, df FO and L/D SO, respectively were

Results
The FO and SO results obtained in the present
study are summarized in Tables 2 to 4.
Practical EOG FO and SO patterns in both eyesof Patient 1 (47-year-old female) are demonstrated
in Fig. 1. In this patient, reduced or deteriorated
FO and SO patterns were observed in both eyes in

42

EOG FO and SO in Harada disease

the acute period manifesting diffuse chorioretinal
lesions before treatment. Normal FO and SO
patterns, however, were detected in both eyes in theremission period after systemic administration ofcorticosteroids reflecting ameliorated conditions in
her fundi.
Compared with normal control eyes, the RfFO,
dfFO and L/DSO showed low values in 7 (58.3%), 10(83.3%) and 8 (66.7%) out of all 12 examined eyesof the 6 patients in the acute period, respectively(Tables 2 to 4). In the remission period, values
in the normal range were obtained in 12 (100%),
11 (91.7%) and 8 (66.7%) out of 12 eyes of thepatients in the RfFO, dfFO and L/DSO, respectively(Tables 2 to 4).
In mutual relation to the RfFO in the acute andremission periods in the 6 patients (12 eyes), all 12eyes showed recovery values in the remission stage
under corticosteroid therapy (Table 2, Fig. 2).
In mutual relation to the dfFO in the acute andremission periods in the 6 patients (12 eyes), all 12eyes also showed recovery values in the remission
period (Table 3, Fig. 3).
However, in mutual relation to the L/DSO in
the acute and remission periods in the 6 patients (12eyes), 4 out of 12 eyes (33.3%) showed no recovery
in their values in the remission stage under thetherapy (Table 4, Fig. 4).

systemic administration of corticosteroids withamelioration of their ocular findings, although
their highly fluctuated, irregular SO patterns
before treatment showed no remarkable recovery
in their patterns after the treatment by systemic
corticosteroids (Tamai et al., 1997; Tamai, 2003).
The FO may therefore be well reflected evenin Harada disease, in contrast to the SO, althoughfurther observation is required using more Haradadisease patients.
Some physiological factors, such as age andsex, may influence the FO potential (Nakao et al.,
1995; Tamai et al., 1997). Thus we need more
prudent, long-term observations on the FO patterns
in these chorioretinal diseases including Haradadisease, considering these factors.
In the present study, the visual outcome after
the treatment by systemic corticosteroids was all
well in the 12 eyes of the 6 patients. This time,
statistical analysis was not undertaken on thecorrelation between each parameter in the FO andSO recordings and corrected visual acuity in eachpatient’s eye both in the acute and remission period
due to a small number of samples. As for the visual
prognosis, utility of a cone-dominated activity on
the FO was pointed out in patients with unilateral,
ischemic CRVO (Inoue et al., 2003). Accordingly,
although the background of macular functional
disturbance in Harada disease is different from thatin CRVO in etiology, such FO-dominated patternchanges in the present survey might be helpful
for detecting the severity of macular functional
disturbance and predicting the visual outcome forthis entity. Further work is required to investigate
these aspects in more Harada disease patients.
Anyway, the results obtained in the present
study may indicate that the FO is an effective examination method to detect the affected or ameliorated
conditions in the outer layers of the retina and thechoroid in Harada disease, in contrast to the SO.
However, further observations are requested in
more Harada disease patients, as described above.

Discussion
Concerning the origin and occurrence of the FO
and SO potentials in which the outer layers of theretina, mainly the retinal pigment epithelium in its
basal membrane are almost equally involved under
the influence of choroidal disorders (Arden et al.,
1962; Steinberg et al., 1983; Joseph and Miller,
1991), our FO-dominated pattern changes in thepresent study are not necessarily explainable, but
it is of note that in 2 patients (2 eyes) with acuteposterior multifocal placoid pigment epitheliopathy,
one of the other chorioretinal diseases, almost
the same tendency of recovery of their reduced
FO patterns before treatment was observed after43

A. Tamai et al.

Acknowledgments: We express our sincere thanks toProfessor Yoshitsugu Inoue, Division of Ophthalmology
and Visual Science, Department of Medicine of Sensory
and Motor Organs, School of Medicine, Tottori University
Faculty of Medicine, for his generous help.

6 Matsunaga H, Matsubara T, Fukushima I, Uyama
M. Indocyanine green fluorescence angiography
in Harada disease. Nippon Ganka Gakkai Zasshi
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7 Moorthy RS, Inomata H, Rao NA. Vogt-KoyanagiHarada syndrome. Surv Ophthalmol 1995;39:265–
292.
8 Nakao H, Miki N, Nagata M, Sasaki Y, Yamasaki
A, Endo M, et al. Fast oscillations of the electrooculogram in a series of normal subjects. Jpn J
Ophthalmol 1995;39:113–119.
9 Steinberg RH, Linsenmeier RA, Griff ER. Threelight-evoked responses of the retinal pigment
epithelium. Vision Res 1983;23:1315–1323.
10 Tamai A. Fast oscillation electrooculography invarious types of occlusive retinal vascular and chorioretinal diseases. Advances in Ophthalmology. New
York: Science Press; 2003. p. 88–93.
11 Tamai A, Sasaki Y, Inoue M, Hamamoto J, Kumagami
T, Setogawa A, et al. Clinical application of fast
oscillation electro-oculogram. Ganka Rinsho Iho
1997;91:535–538 (in Japanese with English abstract).

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Received June 23, 2004; accepted July 13, 2004
Corresponding author : Akihiko Tamai, MD

44