electrophysiology (erg and eog) simplified

ELECTRORETINOGRAPHY (ERG)

&ELECTROOCULOGRAPHY

(EOG)

Dr Sumeet AgrawalVitreo-Retina Fellow

Narayana NethralayaBangalore

OVER

VIEW

INTRODUCTION HISTORY RELEVANT ANATOMY AND PHYSIOLOGY INDICATIONS PERFORMING THE TESTS INTERPRETATION EXAMPLES CLINICAL SCENARIOS PEARLS AND PITFALLS

ELECTRORETINOGRAPHY

INTRODUCTION Electrophysiological test Functional status of retina Potential change that is related to light-

induced electrical activity within the retina

Full field ERG is a mass response of the retina to light stimulus

HISTORY1865 : First known recording of an ERG (amphibian retina) Swedish physiologist Alarik Frithiof

1877 : Holmgren, James Dewar of Scotland (humans)

1908 : Einthoven and Jolly separated the ERG response into three components: a-wave, b-wave and c-wave

1941 : American psychologist Lorin Riggs introduced the contact-lens electrode (clinical use)

1967 : Ragnar Granit Nobel Prize for Physiology and Medicine (demonstrated the physiology of the receptor potential of each component of the ERG)

1989 : ISCEV standards

1992 : Erich Sutter mfERG

ANATOMY AND PHYSIOLOGY Cones maximally

concentrated at the fovea

But 90% cones located outside the fovea

Rods maximum at 15 degrees from fixation

• EYEBALL ACTS AS A DIPOLE

STEP 1OPSIN ACTIVATION

STEP 2OPSIN ACTIVATES TRANSDUCIN

WHICH ACTIVATES PDE

STEP 3CYCLIC GMP DECLINES ;

GATED Na+ Channels CLOSE

STEP 4RATE OF NEUROTRANSMITTER DECLINES

a wave

from photoreceptors

b wave Bipolar cells and the Muller cells. Muller cells response extracellular K+

concentration K+ released from photorecptors Muller cell respond by changing its

membrane potential From either cone or rod receptors

c wave Positive wave Reflects function of pigment epithelium in

response to rod signals only

PHOTOPIC NEGATIVE RESPONSE (PhNR)

• In flash erg Phnr is the negative wave following the “b” wave

• Amplitude of phnr is measured from the baseline to the trough of the negative wave

• This wave is believed to originate from the ganglion cell layer of the retina and is earliest affected in glaucoma and appears before visual field defects

TYPES OF ERG

FULL FIELD ERG

FOCAL ERG

MULTIFOCAL ERG

PATTERN ERG

ISCEVInternational Society for Clinical Electrophysiology of Vision

Standardised the protocols for performing electrophysiological tests (1989)

Ensures uniformity and thus comparability between labs

1 Dark-adapted 0.01 ERG A rod-driven response of bipolar cells

2 Dark-adapted 3 ERGCombined responses arising from photoreceptors

and bipolar cells of both the rod and cone systems; rod dominated

3 Dark-adapted 3 oscillatory potentials Responses primarily from amacrine cells

4 Dark- adapted 10 ERG Combined response with enhanced a-waves reflecting photoreceptor function

5 Light-adapted 3 ERG A cone-driven response of bipolar cells

6 Light- adapted 30 Hz flicker ERG A sensitive cone-pathway-driven response

McCulloch, Daphne L., et al. "ISCEV Standard for full-field clinical electroretinography (2015 update)." Documenta Ophthalmologica 130.1 (2015): 1-12.

McCulloch, Daphne L., et al. "ISCEV

Standard for full-field clinical

electroretinography (2015 update)."

Documenta Ophthalmologica

130.1 (2015): 1-12.

Clinical Electrophysiology. M Yoka, S

Kei. Retina (5th edition)

Stephen J Ryan. Section 2, Chapter 8.

2-25.

McCulloch, Daphne L., et al. "ISCEV Standard for full-field clinical electroretinography (2015 update)." Documenta Ophthalmologica 130.1 (2015): 1-12.

PERFORMING THE TESTS Dark room with non-reflecting walls Preparation of the patient Pupillary dilatation Pre-adaptation to light or dark 20 min dark adaptation 10 min light adaptation

Pre-exposure to light FFA, Fundus photography should be

avoided Fixation Should not disturb dark adaptation Visible in light adapted state

ELECTRODESGROUND ELECTRODE – FOREHEAD

REFERENCE ELECTRODE – OUTER CANTHUS

ACTIVE ELECTRODE - Cornea (contact lens electrode) in flash ERG Conjunctival sac – used in pattern ERG

ELECTRODES

LIGHT STIMULUS FOR ERGstimulus and background light should be homogeneous and cover the entire retina

Strobe lamp and LEDs - mobile and can be easily placed in front of a person whether sitting or reclining.

GANZFELD STIMULATION GLOBE

The Ganzfeld allows the best control of background illumination and stimulus flash intensity.

Large diameter (40 cm) hemispheric dome with a xenon stroboscopic light bulb placed at the top of the dome.

DARK ADAPTED 0.01 ERG

Minimum 20 min dark adaptation 0.010 photopic cd.s.m-2 ; 0.025

scotopic cd.s.m-2

Minimum 2 s interval between flashes

Rod system response

DARK ADAPTED 3 ERG

Directly following 0.01 ERG 3.0 photopic cd.s.m-2 and

7.5 scotopic cd.s.m-2

Minimum interval 10s

DARK ADAPTED 10 ERG

10 photopic cd.s.m-2 and 25 scotopic cd.s.m-2

Interval 20s

Better defined a wave Enhanced oscillatory

potentials Opaque media / immature

retina

DARK ADAPTED 3 OSCILLATORY POTENTIALS

Filtering out 75 Hz or less from the ERG waveform from dark adapted 3 ERG

Taken from 2nd stimulus onwards

LIGHT ADAPTED 3 ERG

10 min light adaptation Back ground luminance : 30

photopic cd.s.m-2 and 75 scotopic

cd.s.m-2

3.0 cd.s.m-2 stimuli with 0.5 s interval

LIGHT ADAPTED 30 Hz FLICKER ERG

Same parameters as light adapted 3 ERG

28 to 33 Hz Diascard initial few

responses

INTERPRETATION AMPLITUDE

• a-wave amplitude : baseline to the a-wave trough;

• b-wave amplitude : a-wave trough to the b-wave peak.

TIME DELAY• Implicit time (peak time) : onset of the

stimulus to the trough of the a-wave or the peak of the b-wave

Effect of stimulus duration

INTERPRETATION Each lab should have its own normal

values

Adjust for age

Clinical Electrophysiology. M Yoka, S

Kei. Retina (5th edition)

Stephen J Ryan. Section 2,

Chapter 8. Page 202-25.

a-wave;

b-wave and

Oscillatory potentials (OP)

(b-wave usually larger than the a-wave)

Oscillatory Potentials

Reduced amplitude

time delay

Both

implies early diabetic retinopathy, retinal circulatory disturbances

Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section 2, Chapter 8. Page 202-25.

SUBNORMAL ERG

Reduced amplitude (proportional to area of functional retina)

maintained ratio of a and b waves

eg media opacities, following PRP

Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section

2, Chapter 8. Page 202-25.

NEGATIVE ERG b-wave smaller than a-wave

(b/a ratio < 1) Diagnostic value

Prognostic value Central Retinal Vein

Occlusion Proliferative diabetic

retinopathy Endophthalmitis

NEGATIVE ERG

b/a <1

Normal a-wave amplitude

Subnormal a-wave amplitude

Second order neuron abnormality

Combined dysfunction of photorecep tor and middle retinal layer Photopic hill phenomenon

NEGATIVE ERG• Congenital

Complete type congenital stationary night blindness (CSNB)

Incomplete type CSNB X- linked juvenile retinoschisis

(XLRS), Juvenile onset neu ronal ceroid

lipofuscinosis Infantile Refsum disease

CONGENITAL STATIONARY NIGHT BLINDNESS

Complete and incomplete forms

On and On-Off bipolar cell dysfunction

NEGATIVE ERG

Acquired causes

Autoimmune retinopathy

Birdshot choroidopathy

Ocular siderosis

Quinine retinopathy

PROGNOSTIC VALUE OF NEGATIVE ERG


IRON INTRAOCULAR FOREIGN BODY

In general if b-wave amplitudes are reduced 50% or greater compared to the fellow eye, it is unlikely that the retinal physiology will recover unless the foreign body is removed.

The effects of toxic medications can be detected and quantified using ERGs.

Chloroquine retinopathy appears as a characteristic “bullseye” maculopathy

EXTINCT ERG• Advanced stage of rod– cone

dystrophy, • Retinitis pigmentosa • Gyrate atrophy • Choroideremia• Leber’s congenital amauorosis• Autoimmune retinopathy• Total retinal detachment • Central retinal artery occlusion

ISOLATED CONE DYSFUNCTIONS

Rod monochromacy

Complete form

Incomplete form

Selectively decreased photopic responses

ROD RECEPTOR DYSFUNCTION

Oguchi disease

Fundus albipunctatus

OGUCHI DISEASE Absent rod ERG

Normal cone ERG

Negative configuration of combined response; normal OP

Photopic hill phenomenon

Improvement after prolonged dark adaptation

FUNDUS ALBIPUNCTATUS

Rod ERG absent after 30 min dark adaptation

Normal after 3 hour dark adaptation

Combined response : negative after 30 min, normal after 3 hours

ROD-CONE and CONE-ROD DYSTROPHIES

FACTORS AFFECTING ERG Physiological : Pupil, Age, Sex,

Ref. Error, Diurnal Variation, Dark adaptation, anesthesia

Instrumental : amplification, gain, stimulus, electrodes

Artifacts : Blinking, tearing, eye movements, air bubbles under electrode.

MULTIFOCAL ERG Limitation of Full Field ERG -

Unless 20% or more of the retina is affected with a diseased state the ERGs are usually normal

Erich Sutter used binary m-sequences to extract hundreds of focal ERGs from a single electrical signal

ERG activity in small areas of retina.

Small scotomas can be mapped and quantified.

61 or 103 focal ERG responses can be recorded from the cone-driven retina.

20-30 degrees to each side of the fovea

PATTERN ERG Measure of macular function and generalized

bipolar cell function.

Checkerboard stimulus composed of white and black squares

Reduction of PERG amplitude reflect the reduced activity of dysfunctional RGCs

Inner retinal activity under light-adaptation.

• Principle : • Net retinal illumination

remains constant. Only a redistribution of the pattern of light and dark areas is made

• 17” monitor from a distance of 1 meter and stimulus field is 15 °. 150 stimuli for signal

averaging at a frequency of 1 pulse per second are used.

• Central fixation is necessary.

Should be used in combination with a traditional light-adapted luminance ERG to have an index of outer retina function

Glaucoma, optic neuritis, ischemic optic neuropathy, and mitochondrial optic neuropathy

Can help differentiate Macular from Optic nerve related pathologies

The normal pattern electroretinogram :

N35- a small negative component with a peak time occurring around 35 ms;

• P50- a prominent positive wave emerging around 50 ms

• N95- a wide negative wave around 95 ms

Macular diseases:-

The P50 component was shown to be altered in all patients with retinal and macular diseases.

Optic nerve disease:-

N95 component was abnormal in 81% of patients with diseases of the optic nerve. The P50 component remain normal.

ELECTRO-OCULOGRAPHY

ELECTRO-OCULOGRAPHY

Outer retina and retinal pigment epithelium

Change in the electrical potential between the cornea and the fundus

successive periods of dark and light adaptation.

Standing electrical potential between front and back, sometimes called the corneo-fundal potential

Mainly derived from the retinal pigment epithelium (RPE), response to retinal illumination

The potential decreases for 8–10 min in darkness.

Subsequent retinal illumination causes an initial fall in the standing potential, followed by a slow rise for 7–14 min (the light response).

These phenomena arise from ion permeability changes across the basal RPE membrane.

Indirect measurement of the minimum amplitude of the standing potential in the dark and then again at its peak after the light rise.

This is usually expressed as a ratio of ‘light peak to dark trough’ and referred to as the Arden ratio.

Calibration of the signal

Gazing at consecutively at two different fixation points located at known angle apart and recording the concomitant EOGs .

Skin electrodes on both sides of an eye the potential can measure the potential by having the subject move his or her eyes horizontally a set distance .

After training the patient in the eye movements, the lights are turned off.

About every minute a sample of eye movement is taken as the patient is asked to look back and forth between the two lights .

After 15 minutes the lights are turned on and the patient is again asked about once a minute to move his or her eyes back and forth for about 10 seconds.

Light switched

off

Typically the voltage becomes a little smaller in the dark reaching its lowest potential after about 8-12 minutes, the so-called “dark trough”.

When the lights are turned on the potential rises, the light rise, reaching its peak in about 10 minutes.

When the size of the "light peak" is compared to the "dark trough" the relative size should be about 2:1 or greater .

A light/dark ratio of less than about 1.7 is considered abnormal.

Most common use : to confirm Best’s vitelliform disease

Clinical utility : Carriers ; end stage disease

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electrophysiology (erg and eog) simplified

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