Visual evoked potentials

Overview

Visual evoked potentials record electrical responses to visual stimuli that are transmitted to scalp electrodes placed near the occipital visual cortex. The integrity of the visual pathway is evaluated from the retina to the primary visual cortex. The patient looks at a screen displaying various stimuli. The visual cortical responses are measured as each eye individually views the screen.

Pattern-reversal visual evoked potentials stimulated by contrast-reversing checkerboard patterns are commonly used for the evaluation of optic nerve function.

Historical note and terminology

In 1972, Halliday and colleagues first reported a delayed visual evoked potential response in optic neuritis. The delay persisted after visual acuity had returned to normal (07). In 1973, these investigators further demonstrated the value of delayed visual evoked potentials in revealing subclinical lesions in patients with multiple sclerosis who did not have a history of optic neuritis (08).

Technique

Pattern-reversal visual evoked potentials. In this test, the stimulus display consists of a high-contrast checkerboard pattern with uniform check sizes. The black and white checks reverse polarity. A single midline channel recording with an active electrode at the occiput (Oz), a reference electrode at Fz, and a ground electrode at the forehead or earlobe are usually used for assessing optic nerve function.

The typical pattern-reversal visual evoked potential waveform consists of an initial negative peak (N75) followed by a large positive peak (P100) and a second negative peak (N135). The most commonly used parameters are P100 implicit time (often called latency) measured from the stimulus onset to the positive peak and P100 amplitude (also called N75-P100 amplitude) measured from the N75 trough to the P100 peak.

Multifocal visual evoked potentials. Multifocal visual evoked potentials differ from pattern-reversal visual evoked potentials. The pattern-reversal visual evoked potential signal represents a summed response predominantly from the foveal and inferior visual field regions. Therefore, it does not provide topographic information and may miss local defects. The multifocal visual evoked potential technique permits simultaneous recording of visual evoked potentials from multiple locations (03; 12), a method that may be more sensitive than conventional pattern-reversal visual evoked potentials (01).

Indications

This test is useful when the diagnosis of optic neuropathy is unclear or may include concern for retinal disease. Although usually unnecessary in the diagnosis of optic neuritis, it serves as a supplement to the physical exam. This test can also be utilized in cases in which there is uncertainty regarding psychogenic vision loss or when the subjective tests are inconclusive or inconsistent with other clinical findings.

Results

Optic neuritis. The pattern-reversal visual evoked potential typically shows a delay in latency greater than 10 milliseconds with less marked amplitude change. However, a delayed latency is neither 100% sensitive nor specific to multiple sclerosis–related optic neuritis. Delayed latency in the same range as that of optic neuritis has been reported in other conditions, including neuromyelitis optica and neuromyelitis optica spectrum disorder, compressive optic neuropathy, neurosarcoidosis, Behcet disease, neurosyphilis, hereditary optic neuropathies, and retinal macular diseases (04; 02). It is important to rule out retinal macular disease in any patient with a delayed visual evoked potential (11).

The 2017 revision of the McDonald Criteria for multiple sclerosis diagnosis included a P100 latency prolongation in a patient reporting a previous episode of self-limited, painful, monocular visual impairment (21). When pattern-reversal visual evoked potentials findings are normal, the multifocal visual evoked potential test may reveal mild localized defects not shown by pattern-reversal visual evoked potentials (16).

Nonarteritic anterior ischemic optic neuropathy. Differentiating optic neuritis from other optic nerve disorders can be challenging in patients with nonclassical presentations (older age, male sex, lack of periocular pain, swollen optic disc, severe loss of vision, or binocular involvement). When optic nerve swelling is present without pain on eye movement, a delayed pattern-reversal visual evoked potential latency may favor the diagnosis of optic neuritis over non-arteritic ischemic optic neuropathy (NAION) (11; 13). In NAION, pattern-reversal visual evoked potentials usually show a reduced amplitude without a large delay in latency. For instance, Cox and colleagues showed a mean 21 ms delay in optic neuritis versus 3 ms for NAION (05). Pattern-reversal visual evoked potential amplitude and latency are normal in the unaffected fellow eye of patients with NAION. By contrast, delayed latency may be observed in the asymptomatic fellow eye of patients with optic neuritis, indicating subclinical demyelination.

Compressive optic neuropathy. A delayed pattern-reversal visual evoked potential latency is not pathognomonic for optic neuritis. Compressive optic neuropathy is another common pathology associated with increased latency (11; 10). A retrospective study reported an initial diagnostic error in 71.4% of the 35 patients with unilateral optic nerve sheath meningioma (14). Nearly half of the erroneous cases were diagnosed as optic neuritis. Accurate diagnosis depends on adequate imaging and interpretation of brain and orbit MRI with contrast.

Limitations

Pattern-reversal visual evoked potentials require an alert and cooperative patient. The testing administration also requires specially trained technicians. Caution should be taken in patients with seizure disorders triggered by flashing lights or patterns (avoid 10 to 13 Hz, which may induce seizures). Patients with poor fixation or those inattentive to the test may provide unreliable results, so a fixation laser pointer may be beneficial.

Scientific basis

Delayed pattern-reversal visual evoked potential latency has long been considered to reflect the extent of demyelination. In a rat model of lysolecithin-induced optic nerve demyelination, the magnitude of delay correlated with the length of demyelination (23). The time period during which latency shortening occurs after an acute optic neuritis corresponds to the period of remyelination observed in human postmortem tissues (19). Pattern-reversal visual evoked potential latency has been used in several clinical trials of potential remyelination agents as an outcome measure for remyelination (17; 02).

Amplitude reduction in the acute phase of optic nerve inflammation is believed to reflect temporal conduction block in optic nerve axons. Reversal of conduction block leads to amplitude recovery over the following weeks--the same period of time when resolution of MRI enhancement occurs (09). After resolution of acute optic neuritis, amplitude reduction reflects axonal loss or impaired conduction in surviving axons. The pattern-reversal visual evoked potential amplitude in eyes with optic neuritis occurring more than 6 months earlier correlated with axonal loss measured by optical coherence tomography (15; 18) and MRI (22).

Electroretinography

Overview

An electroretinogram measures the electrical activity of the retina. The patient wears a contact lens containing electrodes that record the potential in response to a stimulus. There are two kinds of electroretinography: full-field and multifocal. Both tests are used to identify retinal disease in patients with vision loss.

Historical note and terminology

In experimental work on cats, Granit established an understanding of the electroretinogram and its underlying components (06), for which he won the Nobel Prize in Physiology and Medicine in 1967.

Technique

The patient is dark adapted for at least 15 to 30 minutes (98% dark adaptation occurs in most subjects at 30 minutes). An active electrode (contact lens, thread) is placed on an anesthetized cornea or skin. A stimulus is then shown to the entire retina or the central retina, and response waveforms are produced.

Indications

Electroretinography is most applicable to patients with suspected rod-cone dystrophy, toxic retinopathies including hydroxychloroquine, and cancer retinopathies. This testing is also helpful in patients with abnormal visual evoked potentials to assist in quantifying the dysfunction.

Results

Full-field electroretinography. This electroretinography test measures the response of a stimulus presented to the entire retina. It produces a waveform that includes an A wave (negative), which stems from the photoreceptor layer in the outer retina, and a B wave (positive), which is derived from the Muller and bipolar cells of the inner retina. Rod and cone receptors can be distinguished by varying the stimuli and the completeness of adaptation.

When retinal function deteriorates, the light-induced electrical activity in the retina decreases. Amplitude is measured from the trough of the A wave to the peak of the B wave and is more variable than latency. Latency, or B-wave implicit time, is measured from onset of stimulus to peak of the B wave.

If 20% or more of the span of the retina is affected, the full-field electroretinogram will become abnormal. Thus, even a patient with severe macular degeneration or other retinal causes of central scotomas will have a normal full-field electroretinogram. The electroretinography is normal in optic neuropathies.

Multifocal electroretinography. Developed by Sutter in 1991 (20), the multifocal electroretinography is designed to detect local retinal abnormalities. Examples are early hydroxychloroquine retinal toxicity, retinal cone dystrophies, as well as diagnosing and distinguishing among the various punctate chorioretinopathies (“white dot syndromes”). It can also be used to monitor patients who have extinguished full-field electroretinography. These data can correlate electrophysiologic findings with visual field testing. Small scotomas in the retina can be mapped, the degree of retinal dysfunction can be quantified, and up to 103 separate locations (67 degrees) can be assessed in the central retina.

Rather than displaying a mass response that reflects a summation of retinal activity, the exam multifocal electroretinography records signals separately from up to 250 retinal locations in the central 30 degrees.

Hydroxychloroquine toxicity

Hydroxychloroquine, which is commonly used to treat discoid or systemic lupus erythematosus, rheumatoid arthritis, dermatological disorders, and Sjogren syndrome, can be toxic to the retina, producing ring scotomas as well as foveola damage. Multifocal electroretinography is superior to full-field electroretinography in identifying and quantifying retinal toxicity.

Retinal versus optic nerve lesions

In patients with visual acuity loss, a combination of the multifocal electroretinography and pattern-reversal visual evoked potentials can be used to discern whether visual loss is due to cone dystrophy or optic neuropathy.

Branch retinal artery occlusion

A localized decrease in multifocal electroretinography amplitude is seen in branch retinal artery occlusion corresponding to the segmental infarction. The amplitude remains decreased after the retina returns to its normal appearance on ophthalmoscopy.

Multifocal chorioretinal inflammations

There are many types of chorioretinal inflammations, which are distinguished, in part, on the basis of the appearance of the optic fundus on ophthalmoscopy. One example is multiple evanescent white dot syndrome. It can present with photopsia and an enlarged blind spot on visual field perimetry. The multifocal electroretinography can detect foci of reduced amplitude below the resolution of ophthalmoscopy.

Limitations

The pupils must be dilated for this test. The test requires specially trained technicians and equipment typically found at higher-level referral centers. Testing is time-consuming and requires patient cooperation and understanding to prevent wandering fixation, which will alter the response.

Table 1. Electrophysiological tests