An electrooculogram (EOG) is an electrophysiological test that records the standing potential present in the eye using skin electrodes placed at the outer canthus. This standing potential is positive at the cornea and negative at the posterior pole (Bruch’s membrane side), with a potential difference of about 6 mV in a healthy eye. The signal amplitude recorded during an actual test is typically around 250 to 1,000 μV.
The standing potential of the EOG indirectly reflects the transepithelial potential (TEP) of the RPE. This potential difference, which changes in response to light stimulation, is recorded over time, and the ratio of the dark trough to the light peak is calculated to evaluate RPE function.
The EOG was described and named by Erwin Marg in 1951. In 1962, Geoffrey Arden reported the clinical usefulness of the Arden ratio, leading to its widespread use as a diagnostic test for fundus diseases. Currently, the International Society for Clinical Electrophysiology of Vision (ISCEV) sets the standard, with the latest version published in 2017.
Unlike the electroretinogram (ERG), which evaluates the function of photoreceptors and bipolar cells, the EOG primarily reflects the functional integrity of the RPE. Therefore, it is useful for diagnosing diseases where the ERG is normal but the EOG is selectively abnormal. The test takes about one hour, so its frequency in general clinical practice is limited.
The ERG mainly evaluates the function of the neural retina, including photoreceptors (cones and rods) and bipolar cells. The EOG reflects the functional integrity of the RPE (retinal pigment epithelium). In Best vitelliform macular dystrophy, the ERG is normal but the EOG is abnormal, making the combination of these two tests useful for diagnosis.
The EOG itself has no subjective symptoms. The following symptoms are observed in retinal and RPE diseases that show abnormal EOG.
The Arden ratio (L/D ratio: light peak ÷ dark trough) obtained from the EOG test is the main evaluation index.
The criteria for the Arden ratio are shown below.
| Judgment | Arden ratio | Clinical significance |
|---|---|---|
| Normal | ≥1.80 | Normal RPE function |
| Borderline | 1.65–1.80 | Further examination required |
| Abnormal | <1.65 | Widespread RPE dysfunction |
A value less than 1.5 strongly suggests widespread outer retinal damage. The 2017 ISCEV recommends the term “light peak to dark trough ratio” over Arden ratio.
Characteristic findings of the EOG waveform are as follows:
In MEWDS, a “supernormal response” has been reported in which the Arden ratio of the affected eye exceeds that of the fellow eye.
Wang F et al. (2024) evaluated a case of MEWDS by combining EOG with en-face IS/OS-ellipsoid zone (EZ) complex imaging. The Arden ratio of the affected eye (right eye) was 2.5, showing a supernormal response exceeding the fellow eye (left eye) ratio of 1.7. The dark trough was 5.0 min/422.0 μV in the right eye and 7.0 min/351.5 μV in the left eye, and the light peak was 19.0 min/1,051.1 μV in the right eye and 21.0 min/611.7 μV in the left eye1).
The mechanism of this supernormal response is unknown, but it is speculated to involve RPE hyperactivation during the acute inflammatory phase1).
Best vitelliform macular dystrophy is the most representative condition, where the EOG is selectively reduced even when the electroretinogram is normal. Other conditions such as fundus albipunctatus, choroideremia, chloroquine/hydroxychloroquine toxicity, and diabetic retinopathy (advanced cases) also show low values. For details, see the section “Diseases and conditions with abnormal EOG”.
Abnormalities in the EOG (decreased or normal Arden ratio) reflect the functional state of the RPE. Understanding the EOG findings for each disease is useful for diagnosis.
The EOG findings for major diseases are summarized below.
| Disease name | EOG findings | Notes |
|---|---|---|
| Best disease | Markedly reduced | Electroretinogram normal |
| Retinitis punctata albescens | Reduced to normal | No light rise after brief dark adaptation |
| Stargardt disease (advanced stage) | Decreased | May be normal in early stages |
| Choroideremia | Decreased | Worsens with disease stage |
| Retinitis pigmentosa | Decreased | Rod-cone dystrophy similarly |
| Chloroquine toxicity | Decreased | Persists after drug discontinuation |
In the following diseases, RPE function is preserved, so EOG is within the normal range.
The following drugs are known to alter the EOG resting potential.
The standard EOG testing procedure follows ISCEV (2017 edition).
The main steps of the test are shown below.
| Step | Time | Content |
|---|---|---|
| Pre-adaptation | At least 15 minutes | Under 35-70 lux room lighting |
| Dark adaptation recording | 15-20 minutes | Dark room, red LED tracking |
| Light adaptation recording | 15–20 minutes | Ganzfeld illumination / LED tracking |
While providing uniform light stimulation with a Ganzfeld dome, have the patient alternately track a red LED every minute (10 times per round trip).
ISCEV Reporting Items
Light peak: dark trough ratio: Equivalent to Arden ratio. Normal is 1.80 or higher.
Dark trough amplitude: Absolute value of dark minimum (mV). Reflects RPE structural integrity.
Light peak time: Time elapsed from light onset (minutes). Usually 7–12 minutes.
Precautions during examination
Thorough pre-adaptation: 35–70 lux for at least 15 minutes. Avoid strong light stimuli.
Accuracy of pursuit: 5 round trips per minute. Difficult to perform if there is an eye movement disorder.
Beware of false normalization: If the baseline potential is extremely low, the L/D ratio may become falsely normalized.
ISCEV offers an optional test called “Fast Oscillations (FO).” It alternates dark and light phases every minute and reflects the function of the CFTR (cystic fibrosis transmembrane conductance regulator) chloride ion channel in the RPE basal membrane. It has been suggested that FO may be reduced in cystic fibrosis (CF).
In addition to pre-adaptation (at least 15 minutes at 35–70 lux), dark adaptation recording takes 15–20 minutes and light adaptation recording takes 15–20 minutes, so the entire procedure takes about 1 hour. It may be difficult to perform in infants, elderly individuals, and patients with eye movement disorders because accurate tracking is challenging.
The resting potential recorded by EOG reflects the transepithelial potential (TEP) of the RPE. TEP is generated by the difference in membrane potential between the apical membrane and the basolateral membrane of RPE cells.
During dark adaptation, ion transport from photoreceptors changes, reducing ion influx into the RPE. As a result, the transepithelial potential of the RPE decreases, forming the dark trough. The dark trough is a non-photosensitive component and depends on the structural integrity of the RPE itself (cell density and cell membrane integrity).
During light adaptation, the following sequence of mechanisms causes RPE depolarization, increasing the potential and forming the light peak.
The central role of bestrophin in this cascade explains why EOG is selectively abnormal in Best disease. In Best disease, BEST1 gene mutations impair bestrophin function, making it difficult to generate a light peak, thus reducing the Arden ratio.
Light stimulation induces Ca²⁺ release from the endoplasmic reticulum, opening calcium-dependent Cl⁻ channels mediated by bestrophin (the BEST1 gene product). Chloride ions are expelled from the RPE, causing RPE depolarization, which increases the transepithelial potential and forms the light peak. The selective reduction of EOG in Best disease is due to this bestrophin dysfunction.
Research on BCI/HCI technology that reads intentions from eye movements using EOG electrical signals has increased rapidly since the 2000s.
Belkhiria et al. (2022) reviewed the literature on EOG-based HCI from 2000 to 2020 and reported that applications for communication support for people with disabilities, wheelchair control via eye movements, and eye tracking are rapidly expanding 3).
EOG sensors have been integrated into eyeglass-type wearable devices such as J!NS MEME, enabling applications for monitoring eye movements, drowsiness, and concentration in daily life 3). Methods using infrared CCD cameras for direct recording of eye movements are also becoming widespread, gradually replacing conventional ENG (electronystagmography).
Electronystagmography (ENG), which applies the principle of EOG, is used for quantitative recording of eye movements. EOG is also standardly used as an eye movement channel in polysomnography (PSG).
Shoukat et al. (2022) reported PSG findings in a case of convergence-retraction nystagmus after midbrain hemorrhage. During wakefulness, nystagmus with a frequency of 2.8 Hz and amplitude of 60 μV was recorded on EOG 2). Nystagmus due to central nervous system (CNS) disorders usually disappears during sleep, but in this case, nystagmus persisted during both non-REM and REM sleep, which was considered characteristic of midbrain hemorrhage 2).
The mechanism by which a supernormal response, where the Arden ratio in the affected eye exceeds that in the healthy eye, occurs during the acute phase of MEWDS remains unknown. Acute inflammatory hyperactivation of the RPE may be involved, but elucidating the molecular mechanism is a future challenge 1).
