VISUAL ELECTRO-DIAGNOSTIC CLINIC ELECTROPHYSIOLOGY TESTS OF THE VISUAL PATHWAY All tests  performed at the Visual Electro-Diagnostic Clinic are performed to the standards as recommended by the International Society of Electrophysiology of Vision. Dr Denis Stark is  the consultant ophthalmologist attached to this Clinic Extensive information regarding these tests is available below to assist practitioners understanding of the most appropriate tests to order and in their interpretation of the results.

VISUAL EVOKED POTENTIAL Definition

The visually evoked potential (V.E.P.) is the averaged encephalographic response, evoked by a repeated visual stimulus recorded with scalp electrodes.

It can be used as a measure of Retino-cortical conduction. Due to the large volume of macular fibres and the large area of the occipital cortex devoted to macular representation, the V.E.P. represents mainly the reception of the message from the central retina.

RECORDING TECHNIQUE

Equipment
Due to the minute amplitude of the visually evoked response and associated electroencephalographic noise, the potential is recorded after averaging the response to many stimuli.

The patient sits before a TV monitor, which displays a checkerboard and observes the screen. Recording a VEP                                                                                                                         .

The response is recorded with occipital electrodes. It is recommended that a minimum of 3 channels be used. Active electrodes are placed 2 cm above the inion and 4 cm to the left and right of this point. The electrodes are referenced to an electrode at the vertex.

The stimulus commonly used is a "pattern reversing checkerboard" with varying size checks. The checks can subtend a visual angle of 2.5’ – 80’ to the patient. A standard test uses 128 stimuli at 3Hz, but a steady state V.E.P. can be obtained using 12Hz.

A strobe flash is used if no response is obtained with the checkerboard stimulus.

The Normal V.E.P.
The V.E.P. has five waves occurring within 150 m.sec from the stimulus. The generators of the early waves is uncertain. In practice, the wave complex N1 P2 N2 occuring close to 100 milli-seconds after stimulation is the most constant wave. It is considered to be a cortical response.

Amplitude: The amplitude of this response is variable it is affected by the visual acuity of the patient, the integrity of the visual pathway and the type of stimulus. In a normal subject, interocular difference is minimal.

It can also be altered by skin resistance and other external factors.

Latency: The latency of P100 is constant and repeatable under constant test conditions. A Normal 3 channel VEP

THE CLINICAL USE OF THE V.E.P.


This test can assist in the diagnosis and clinical assessment in the following groups of conditions.

Optic Nerve Lesions
Assessment of Visual Acuity
Visual Field Abnormality
Macular Lesions

A. OPTIC NERVE DISORDERS

The V.E.P. gives the clinician a reliable, repeatable, objective measurement of optic nerve function. Abnormality of this response will be seen in even subclinical conditions.

It is of particular value in the following conditions.

Demyelinating Lesions
Compressive Lesion of the Anterior Visual Pathways
Toxic Lesions
Ischaemic Lesion
Optic Atrophy

Demyelination
In an acute episode of Retrobulbar Neuritis, the V.E.P. will be abnormal in waveform (with a reduced or abolished N1 P1 N2 complex). There will be a marked delay of P1. While the amplitude of the response will increase as visual acuity returns to normal levels, the delayed latency will be permanent.

The V.E.P. is therefore, a sensitive indicator of demyelination of the optic nerve. Halliday reports an abnormality of the V.E.P. in more than 90% of patients with Multiple Sclerosis, even where there is no history or clinical evidence of previous episodes of Retrobulbar Neuritis.

Thus, a normal V.E.P. makes the diagnosis of Multiple Sclerosis improbable, particularly if other evoked responses (the Auditory Brainstem response of Somatosensory Evoked response) are also normal. Conversely, the presence of more than one abnormal response is excellent evidence of a multifocal demyelinating condition.

Compressive Lesions of anterior visual pathway

Again, the V.E.P, can show evidence of abnormal optic nerve conduction prior to other clinical evidence of abnormality. Again, a delayed response will uaually be the initial abnormality. Abnormality of waveform reduction in amplitude will be seen as the condition deteriorates.
Examination of the visual field by combination of half field stimulation and multiple electrode recording will give further assistance in the detection of bi-temporal hemianopia or other hemianopic defect. This test can be performed in children too young for formal visual field testing.
Recent upgrading of recording facilities has resulted in a marked improvement in the ability to perform this examination.


3 & 4. Ischaemic and Toxic Lesions  Abnormal waveform with prolonged implicit time P100 (Posterior Ischaemic Optic Neuropathy following Meningitis)

The principle defect in these conditions will be disturbance of waveform. Delayed conduction may also occur. Progression of the defect can be monitored using the V.E.P.

Optic Atrophy
The V.E.P. provides a measurement of optic nerve function. It is therefore, able to be monitored If progressive visual deterioration is suspected. This will be of value in monitoring Hydrocephalus, Benign intracranial hypertension, etc.

B. ASSESSMENT OF VISUAL ACUITY (AVEP) AVEP traces. Subjective Acuity 6/60 Objective measurement 6/6

Again new facilities are now available in the VEDC which enable a rapid Fourier analysis of multiple test responses of a sweep VEP. This permits visual acuity to be measured with a much greater degree of accuracy and repeatability than formerly.

An estimation of minimum discriminable angle is given together with an estimation of a Snellen acuity range. This test is performed rapidly making it an excellent test for even very small or uncooperative children or adults.

It is to be recommended to assess a variety of conditions - Brain damaged patients, developmental delay, functional visual loss, Infancy, and uncooperative patients.

Serial AVEPs can be used to monitor improvement of vision in pre-verbal children. This technique is of use after surgery for congenital cataract.

C. ASSESSMENT OF VISUAL FIELDS
Evidence of delay and abnormality of response secondary to optic nerve lesions has been discussed.

Retro-chiasmal lesions can also be evaluated, by using hemi-field stimulation and response over the appropriate lateral electrode will confirm the field defect. 

ELECTROPHYSIOLOGY OF THE RETINA 

                     

It has been suggested that, the development of the Ophthalmoscope – and thus our ability to view the retina directly - resulted in a delayed appreciation of the clinical value of retinal electrophysiology.ut the retina can respond in only a limited number of ways to a pathological insult. Retinal tests -Ophthalmoscopy, OCT, Fluorescein Angiogaphy measure structure not function

The electrophysiological tests of retinal function include:

 erg01
These tests can give the clinician important additional information with regard to retinal function, diagnosis and visual prognosis.

HISTORY

Retinal electrophysiology is not a new science.

1848 – Dubois – Corneo Retinal Potential

1873 – Dewar and McKenrick – Human ERG

1943 – Rigg – Contact Lens Electrode

The increasing development in the sophistication of equipment, techniques and understanding of electrophysiology of vision, now make these tests a useful clinical adjunct, allowing a visual stimulus to be applied to the eye and subsequently, followed through the retinal layers to the optic nerve and thence to the visual cortex.

The retinal electrical activity is a complex function, but this function obeys the general rules of cell electro-physiology. As in all vertebrate eyes, the retina possesses an electrically charged membrane (the pigment epithelium positively charged internally and negatively charged externally). This results in a measurable ocular resting potential – the corneo retinal potential. The Corneo/Retinal Potential

This potential can be modified, by a change in light adaptation to a light stimulus.

THE ELECTRO RETINOGRAM

Definition: This is the retinal action potential produced by a stimulus, which varies the illumination of the retina anatomical duplicity of the retinal receptors – rods and cones provides a dual electrical response.

Similarly, the physiological ability of the retina to respond to differing standards of illumination results in a duplicity of responses from rods and cones, ie., a photopic and scotopic response, depending whether it is light adapted or dark adapted.

MORPHOLOGY OF THE ERG

The ERG has 2 major components:

Primary negative – downward deflection – A wave
A secondary positive deflection – B wave
Each wave is characterized by its

-form, latency, amplitude

The response of the light adapted retina will be dominated by the less sensitive faster cone system.

This reponse will be faster and smaller than the scotopic response – because of the smaller number of cones.

In the dark adapted state, particularly with a suitable stimulus (dim blue light), the cone response is virtually eliminated (the few blue cones are swamped numerically by the rods), giving a pure rod response. This response will be larger and slower than the cone response. The aciviity of the cones can be further tested, by increasing the stimulus rate beyond 10 c.p.s., at which speed, the cones alone will respond – a flicker fusion ERG results. Normal cones will respond at 30pps.

THE ORIGIN OF ERG COMPONENTS

A wave - arises from the inner segment of the photo receptors

B wave – appears to originate from the Muller cells

(Bipolar and horizontal cells do not appear to contribute to the ERG. Other ERG components can be found by using special techniques.)

- Early receptor potential arise from outer segment of the receptor cells

- Oscillatory potentials from the Amacrine cells, probably representing some form of feed-back mechanism.

The ERG represents a mass retinal response from the outer retinal layers, although a focal response can be obtained with special stimuli.

ERG3ERG4FIBRE ELECTRODEERG06

Recording Technique

The ERG is recorded by measuring the potential difference between electrodes one of which may be a contact lens electrode or other electrodes, conjunctical or skin, applied close to the eye. The reference electrode is applied to the forehead.

A strobe flash is used to stimulate the receptors. The test is repeated in a light adapted and dark adapted state.

By increasing the rapidity of the flash unto the response is lost the flicker ERG is obtained.

Recording the ERG

Dilating pupils ensures equal size pupil for all tests.

dilate (takes 15 mins to work fully) – dark adapt to ensure fully dilated before start testing

Anticholinergic drops – dilate but also effect the focusing muscles of the eyes

the effects last 3 – 5 hours depending on the patient

Surface Electrode ERG Can be the best method of testing infants if responses obtained are reliable. Very rarely need to go to GA. Difficult to interpret if low amplitude waves

Since ERG is a global response test in the dome to try and stimulate the whole retina

THE ELECTRO OCULOGRAM

Electrooculogram

The test records the slow, large change in the ocular resting potential which occurs as the retina passes from the light adapted to the dark adapted state.

The amplitude of the resting potential doubles in amplitude as the eye "light adapts". This is considered to be a function of the metabolism of the pigment epithelium influenced by light induced changes in the receptors.

The ratio of the light adapted potential to the dark adapted potential, expressed as a percentage, is the ARDEN INDEX. In a normal eye, this ratio is greater than 2.1. The Index is therefore greater than 200%.

Arden index = light peak x 100%

dark trough

Normal > 200%

Equivocal 1775 – 200%

Subnormal < 175%

Extinguished = 100%

It is reduced in disorders of the pigment epithelium or the receptors – particularly the rods.

Vitelliform Macular Dystrophy (Best's) causes AN ABNORMAL EOG BUT NORMAL ERG

Best's is dominantly inherited;

 

Pattern ERG – differentiate macular dysfunction from retinal problems

Differentiates macular from optic nerve abnormality

Beware that an abnormal VEP may be secondary to Macular dysfunction so always include a Pattern ERG With VEP.

Clinically Uses of the ERG and EOG:

1. establish the function of the rods and cones
2. determine the function of the outer retinal layers
3. determine the retinal level of a pathological insult.
      -pigment epithelium
      -receptor cell
      -inner nuclear layer
      -internal to nuclear layers

Retinal electrophysiology is of value

ERG10

The major components of the ERG response are:-

                A wave – is negative - origin-inner photo receptor segment

                B wave – is positive - origin-inner nuclear layer (?Muller cells)

                C wave – is late negative origin- outer nuclear layer defect

The minor components are:-

                early receptor potential- outer photo receptor segment

                oscillatory potential- inner nuclear layer

 ABNORMAL ERG’s

May be:-           Abolished or reduced

                       Reduced amplitude of A and B wave
                       Reduced scotopic and normal photopic
                       Reduced Photopic and normal scotopic
                       Normal A wave with reduced B wave 

Note: Cataract – acts as a diffuser and so enhances ERG

EXTINGUISHED ERG

EXAMPLE- ERG Right Normal Left Extinguished Photopic and Scotopic -Ophthalmic Artery occlusion 

Retinitis pigmentosa is the most common -lose the rods first therefore effects scotopic first. Patient experiences tunnel vision and night blindness.

Effect even from a very young age.

May be Recessive, X-linked, or autosomal dominant

Ophthalmic artery occlusion: Must lose both branches of ophthalmic artery to extinguish ERG fully

Metallosis (Siderosis): Causes a toxic effect - progresses from reduction to extinction;

Retinal detachment -

Drugs (Mellaril is the main one)

Leber’s amaurosis- A congentital condition causing blindness.  ERG is abolished. Causes nystagmus ++ and abolished ERG

REDUCED A WAVE AND REDUCED WAVE B


Retinitis Pigmentosa

Drugs

Retinal detachment

Media opacities- if it is vitreous haemorrhage, test with the bright flash

Test normal eye first and reduce filter levels until obtain a latency of 13 msec – then repeat this process with the damaged eye when the latencies are the same compare amplitudes. If the amplitude is reduced in the eye with haemorrhage- retinal damage-eg ischaemia or detachment may be present and poor retinal function predicted.

Stargardt’s disease -represents a spectrum of macular disorders: Normal ERG is usually present but pattern ERG is abnormal. Multifocal ERG is also abnormal in virtually ALL CASES.

Holder describes Types 1 Normal ERG; Type2 Abnormal Photopic ERG; Type 3 Abnormal Scotopic and Photopic ERG

NORMAL SCOTOPIC AND ABNORMAL PHOTOPIC

Rod monochromatism

Absence of cone cells. Causes nystagmus and reduced acuity. Day blindness and a preference for dim lights ERG confirms -Normal Scotopic, absent photopic.

Cone dystrophies    A recessive condition, prefer dim lights because causes day blindness (opposite of RP), onset at 10 –15 years and worsens with aging can only be diagnosed by ERG.

Cone /rod dystrophies    Variable reduction of scotopic together with loss of Photopic responses.

NORMAL PHOTOPIC AND ABNORMAL SCOTOPIC


Retinitis Pigmentosa patients may abolish the scotopic and retain photopic

Can progress so photopic also slightly affected but central vision is preserved

NORMAL A WAVES AND REDUCED B WAVES (ELECTRONEGATIVE ERG)

Congenital Stationary Night Blindness - never progresses. May be associated with myopia and nystagmus

Juvenile X-linked retinoschisis

Optic atrophy -Some forms of with trans-synaptic spread.

Central retinal artery occlusion -supplies the inner layer of the retina

Melanoma associated retinopathy

Auto Immune Retinopathy

Oguchi’s disease

Myotonic dystrophy

Lipo-pigment storage disorder

Coats disease

Quinine intoxication

Methanol intoxication

Cobalt toxic retinopathy

Fleck retina of Kandori