‫بسم هللا الرحمن الرحيم‬

Physiology of The Eye

‫ممدوح الكفراوى‬
Electrophysiology
 Electrical phenomena of
the eye
• The eye is a sensory organ of
vision transforms the
information received by light
falling on it ( spatial , temporal ,
spectral and luminosity
characteristics of light stimulus)
into electrical signals which are
transmitted to the brain.
Electrical phenomena of
the eye
• The study of these electrical
signals is important to :
Understand the mechanism
of vision.
Diagnose retinal disease.
 Resting Potential
The resting potential of a cell is
the membrane potential that
would be maintained if there
were no action potentials,
synaptic potentials, or other
active changes in the membrane
potential.
 Resting Potential
• -70mv voltage difference between
inside and outside of cell
• How / why?
-Different ionic concentrations
-Ion = charged atom
-Higher concentration of sodium ions
outside cell (10:1)
-Higher concentration of potassium
ions inside cell (40:1)
 mV 70-

Intracellular Extracellular

Na
K
Cell
membrane
70+

70-
 Action Potential
• 'Nerve impulse'
• Produced when 'threshold
potential' (-55mV) reached .
• Sodium channels open
-Sodium ions enter
-Potential rises to +30mV
• Potassium channels open
-Potassium ions exit
-Potential sinks to -80mV
Action Potential
The Action Potential
 Electrophysiology Laboratory

• Electrooculography (EOG).
(resting membrane potential).
• Electroretinography (ERG) .
(Action potential)
• Visually Evoked Potential (VEP) .
(Sharp pulses of potential changes)
Electrophysiological tests are objective
methods of ophthalmological
examination.
VEP
Pattern ERG

ERG

EOG
 Retinal receptors
• Cones provide central
reading vision , and are
responsible for color vision.
• There are 6 to 7 million cones
in the retina of which about
650,000 are concentrated in
the foveola for central vision.
Outer Rhodopsin molecules
segment
Discs
Plasma membrane
Cone pigments
Connecting
cilium

Inner
segment

Cell
body
Synaptic
terminals Spherule Pedicle
 Retina

Ganglion cell
Fovea layer

Bipolar cell
layer

Photoreceptor
layer

Rods located in Cones located in the

periphery of retina Center of retina
 Retinal receptors

• Rods provide night vision and

detect motion.
• There are about 120 million
rods in the retina of which none
are located in the foveola.
 ELECTROPHYSIOLOGY OF
THE RETINA
• The retina is formed of millions of
neurons, the algebraic sum of
potential changes in the retina can be
recorded by extra-retinal electrodes:
 When the retina is at rest: electro-
oculogram (EOG) is recorded.
 When the retina is stimulated:
electro-retinogram (ERG) is recorded.
EOG
Retinal Resting Potential
• It is the resting membrane
potential of the retina .
• Generated at the junction
between the photoreceptors
and the pigment epithelium.
• It is recorded by electro-
oculography.
VEP
Pattern ERG

ERG

EOG
 Electro-oculography
(EOG)
• An indirect measure of the
standing potential of the eye.
• Inner retina is +ve as compared
with outer retina
• The amplitude of response changes
with the luminance conditions.
 Electro-oculogram (EOG)

• The eye globe is considered to

be electrically a dipole:

Positively charged anteriorly.

Negatively charged posteriorly.

 Positive

Negative

Inner retina is +ve as compared with outer retina

 Electro-oculogram (EOG)

•A pair of skin electrodes

(temple and nose) are

used to record the EOG.

A pair of skin electrodes (temple and nose)
.are used to record the EOG
Electro-oculogram (EOG)

• The subject is asked to look

from side to side over a
constant angle during 3
phases:
Phase for light /10 minutes.
Phase for dark/10 minutes.
Phase for light/10 minutes.
The subject is asked to look from side to side
over a constant angle during 3 phases:
Phase for light /10 minutes
Phase for dark/10 minutes.
Phase for light/10 minutes.
Electro-oculography (EOG)
Standard protocol:
• Electrodes are placed on either side
of the eye.
• The patient moves the eyes to the
right and to the left over a specific
distance.
• One electrode will become more +ve
than the other.
• Pre-adaptation period of several
minutes.
Electro-oculography (EOG)
Standard protocol:
– Recordings are made in dark at 1
minute interval.
– The lowest potential (dark trough)
is reached in 8-12 minutes.
– A bright light is then turned on.
– Recordings are made again at 1
minute interval.
– The highest potential (light peak) is
reached in 7-10 minutes.
 Electro-oculogram (EOG)
• The amplitude of the electrical correlate
of the saccades is measured: the light
maximum and dark minimum are
determined:
• The light rise ratio = light maximum x 100
Arden index dark minimum

Greater than 180% is considered normal

ratio, less than 180% is abnormal
 Electro-oculography
(EOG)
Parameters:

–The ratio of the light peak to

the dark trough (Arden

index).

–The normal ratio is > 180 %.

 .Current flow around the orbit
Basis of eye movement potential

Standing Potential
°/µV

Change in trace

Time (minutes)
 Electro-oculogram
(EOG)
• Unlike the ERG, which is
recorded with stimuli similar to
those experienced in daily living,
the EOG requires a bright , long-
duration stimulus not
experienced in daily living.
 Electro-oculogram
(EOG)
• The EOG requires
 Intact photoreceptors ( rods and
cons )
 Intact inner retinal layers.
 Normal retinal pigment epithelium.
 Good contact between neuro and
RPE.
 Adequate blood supply specially of
the choroid.
 Electro-oculogram
(EOG)
• If the ERG is normal; a normal EOG
indicates good function of RPE.
• Usually, abnormalities in EOG occur
earlier than in ERG especially in
macular lesions especially, due to RPE
diseases as :
 By intoxication with synthetic anti-
malarial drugs ( chloroquine ) .
 Vitelli-form macular degeneration.
 Electro-oculogram (EOG)

• The EOG must not be interpreted

except with ERG and other
functional tests.

• It is not painful to the patient.

• It is more sensitive than ERG.

 Electro-oculography
(EOG)
• The EOG had advantages over the ERG
in that electrodes did not touch the
surface of the eye.
• The changes in the standing potential
across the eyeball were recorded by
skin electrodes during simple eye
movements and after exposure to
periods of light and dark.
 Electro-oculography
(EOG)
Clinical uses:
– In general , EOG parallels the ERG
findings .

– The Only exception is Best`s disease

(vitelliform macular dystrophy) =
abnormal EOG , but normal ERG .
Best’s disease
ERG
The Global Or Full-field
Electroretinogram (ERG)
• Is a mass electrical response of
the retina to photic stimulation.

• The ERG is a test used worldwide

to assess the status of the retina
in eye diseases in human
patients
 Electroretinography
(E.R.G)
• The standard ERG is a recording of
electrical signals from the retina
elicited by a flash (produced by a
Strobe lamp ) of light.
• The response is believed to be
caused by a transient movement of
the ions in the extra cellular space
induced by the light.
Portable Strobe
Light Source
 ERG
ERG recording in human is
done along the B path

Pathway B shows the currents

leaving the retina through the
vitreous and the cornea and
returning to the retina through
the choroid and pigment
B .epithelium

A A represents local currents

Eyeball .within the retina

A schematic representation of
The extracellular currents that
are formed following light stimulation
 ELECTRO-
RETINOGRAPHY
• The ERG is the composite of
extracellular activity (action
potentials) from :
Photoreceptor
Muller cells
Retinal pigment epithelium.
 Methods
• Light stimulus is delivered via a full
field bowl (ganzfeld).
• ERG is recorded directly from the
eye via a corneal contact lens or
more recently by the Arden gold
leaf electrodes sitting on the lower
lids.
• The reference electrode on the
forehead.
• Signal is amplified and visualized.
 Ganzfeld
stimulator
 Arden gold
leaf electrodes
 ELECTRO-
RETINOGRAPHY
It must be realised that:
• In man, the electrodes are
put one on the cornea and
the other on the forehead i.e.
away from the retina itself.
 ELECTRO-
RETINOGRAPHY
It must be realised that:
• The record is algebraic sum of
millions of retinal cells.
• The response varies according to
retina tested (cone, rod or
mixed-retina), characteristics of
stimulus, type of machine used.
Electroretinography
• When light enters the eye
as a brief pulse a series of
rapid and will defined
electric responses defined
as action potential .
Electroretinography
• This action potential is recorded
by electroretinography (ERG)
which measure the action
potential in outer retinal layers.
• Pattern ERG measures the action
potential in all the retinal layers
including the ganglion cells.
 Standard flash ERG
• Measures the initial 200 ms
• 2 predominant response: A-wave
and B-Wave.
• A-wave is the initial downgoing
deflection: photoreceptor
response.
• B-wave is the upgoing deflection :
Műller and bipolar cell response.
 Standard flash ERG

• Oscillatory potential is seen

mainly on b-wave : amacrine
cell response.
 A - Wave
Negative
amplitude 100µV
preceded by a latent period of
20 milliseconds.
Origin:
photoreceptors (rods and cone).
 B - Wave
 Positive
 Amplitude 300 µV
 This amplitude is increased by:
- Stimulus : increased intensity, white
light (stimulates all cones and rods),
less frequency.
- Patient : not infant nor old above 60;
full dark adaptation.
 B - Wave
• Origin: Müller cells in inner
nuclear layer . ( and bipolars )

• When light strikes a

photoreceptor, it releases
potassium in amounts related to
the light intensity.
 B - Wave
• The Müller cells (although have
no synaptic connection) respond
to this potassium by changing its
membrane potential, since there
is a linear relationship between
the log of stimulus intensity and
the b –wave amplitude.
 B - Wave
• It responds to both rod and

cone signals.

• It was believed before to be

only related to bipolars.

 C- Wave
• Is positive like the b-wave, but

otherwise is considerably slower.

• It is generated by the retinal pigment

epithelium (RPE) as a consequence of

interaction with the rods. .

 The Oscillatory
Potentials
• The oscillatory potentials are
small wavelets on the light-
adapted b-wave
• Origin : inner retinal layers,
( amacrine cell response )

• disappear in cone dysfunction.

 Standard flash ERG
• Ganglion cells play no role at all.
Hence , inner layer and optic nerve
damaged : normal flash ERG.
• ERG is a mass response of the whole
retina
Hence , localized lesion in retina will
have normal flash ERG.
 Parameters
•Amplitude(µV):
– A-wave is measured from baseline to its
trough.
– B-wave is measured from the trough of
A-wave to the peak of B-wave.

•Latency(msec):
– Defined as the time from the stimulus
onset to the peak of the response.
Amplitude (µV)
Latency (msec)
Electroretinography (E.R.G)
Table shows the normal values in flash ERG:-

Oscillatory potentials B-wave A-wave Normal values

> 300µV >200µV

> 4 in number Scotopic

(-8-10µV)
> 60µV > 30µV
> 3 in number Photopic
30 Hz flicker
(4-5µV) (cone response)
 Early Receptor Potential
• A small deflection that appears
before the a-wave when intense
light stimulus is used in dark
adapted eye.
• It has a latency less than 0.2 sec.
• It consists of R1 (+ve) and R2
(-ve).
Early Receptor Potential

• Arises from the distal segments

of the photoreceptors.
• Caused by the movements of
charges on surface of visual
pigments molecules during the
bleaching of photopigments
before electric activity.
Early Receptor Potential
 Factors Influencing The
Response
Stimulus intensity:
• Increases brightness ,increases the
amplitude of both A-waves and B-
waves but the latter could
reach a plateau.
• The latency of peaks are
reduced.
• Oscillatory potentials change
positions.
 Factors Influencing The
Response

Frequency of stimulus:

• The critical flicker frequency (CFF) of

rods is lower than that of cones.

• To isolate cone response , a 30 Hz

flicker can be used.

 Factors Influencing The
Response

Frequency of stimulus:

• The critical flicker frequency (CFF) of

rods is lower than that of cones.

• Rods can not respond to flashes with

greater than 15 Hz frequencies.

 Factors Influencing The
Response
Colour of stimulus:

• Red is for photopic conditions.

• Blue is for scotopic conditions.

• To isolate rod response , a weak

(subcone threshold) blue light can
be used in a dark-adapted eye.
 Factors Influencing The
Response
Adaptation:

• Dark adaptation increases

amplitude of both A-waves and B-
waves , but also increases latency .

Age:

• Adult values reached at 2 years

(smaller before then).
 Clinical Uses Of ERG
ERG is used to:
– Confirm the diagnosis of generalized
degeneration of the retina , e.g. :
retinitis pigmentosa.
– Assess family members of known
hereditary retinal degeneration.
– Asses poor vision and nystagmus at
birth.
 Clinical Uses Of ERG
ERG is used to:
– Asses retinal function with opaque
media.

– Asses retinal function in vascular

occlusion.

– Investigate unexplained poor vision.

– Monitor drug toxicity , e.g. :quinine.

 Common Patterns Of ERG
.In Pathological Conditions
Retinitis pegmentosa (RP):
–Marked reduction in
amplitude of both A-waves
and B-waves.
–Female carriers in recessive
X-linked RP _ 50% with
abnormal ERG.
 Common Patterns Of ERG
.In Pathological Conditions
Achromatopsia (absence of cones):

–Normal rod ERG , but flat cones

ERG.
 Common Patterns Of ERG
.In Pathological Conditions
Leber`s congenital amaurosis:

–Extinguished ERG
 Common Patterns Of ERG
.In Pathological Conditions

Congenital stationary night blindness:

–Near normal A-wave , but

absent B-wave (except AD).
 Common Patterns Of ERG
.In Pathological Conditions
Diabetic retinopathy and central
retinal vein occlusion:
–Selective abolition of
oscillatory potentials related
to the degree of ischaemia.
–Doubtful value in assessing
risks for neovascularization.
 Common Patterns Of ERG
.In Pathological Conditions

Central retinal artery

occlusion:
–A-wave increases in
amplitude while B-wave
reduces and oscillatory
potentials disappear.
 Common Patterns Of ERG
.In Pathological Conditions

Quinine toxicity:
–Reduced ERG especially to
scotopic stimulation.
–ERG changes are usually
permanent.
 Common Patterns Of ERG
.In Pathological Conditions

Retinal detachment:

– B-wave reduction proportional to

area of detachment.

– Doubtful clinical prognostic value.

 Other ERG Tests
Focal ERG(FERG):
–Light directed to a small area of
the retina.
–Small signal : need signal
averaging machine to reduce
background noise.
–Need a background light to
desensitize other part of retina.
 Other ERG Tests
Focal ERG(FERG):
–Clinically , only used for macular
assessment.
–Might be useful in early stage of
Stargradts`s disease (hereditary
maculopathy).
 Other ERG Tests
Pattern ERG (PERG):
–Use dark and light squares
(checkerboard) in a TV screen.

–Can have variable size and rate of

pattern reversal.

–Alternating pattern stimulates

ganglion cells.
 Other ERG Tests
Pattern ERG (PERG):
 Other ERG Tests
Pattern ERG (PERG):
–It is more commonly used
than FERG for macular
assessment.

–Alternating pattern
stimulates ganglion cells.
 Pattern ERG (PERG)

The pattern reversal is 1-2 Hz

Alternating pattern stimulates ganglion cells

 Pattern ERG (PERG)

The pattern reversal is 1-2 Hz

Alternating pattern stimulates ganglion cells
 Other ERG Tests
Pattern ERG (PERG):

–The signals are so small that an

averaging technique is required.

–Produced by averaging the

responses to several hundred
stimuli presented in an
alternating checker board pattern
 Pattern ERG (PERG)
P50 = macular function

N35

N95 = Ganglion cell function

Normal pattern ERG recording
 Other ERG Tests
Pattern ERG (PERG):

It has 3 deflections:

–N35

–P50

–N95.

–N indicates a –ve deflection while

P indicates a +ve deflection.
 Other ERG Tests
Pattern ERG (PERG):

–Correlates with the integrity

of the optic nerve and gives

information about the

ganglion cells and their

interaction with the retina.

 Other ERG Tests
Pattern ERG (PERG):

–Only P50 and N95 have

clinical values: N95 indicates

ganglion cells while P50

indicates macular function.

 Pattern ERG (PERG)
P50 = macular function

N35

N95 = Ganglion cell function

Normal pattern ERG recording
 Other ERG Tests
Pattern ERG (PERG):
Might be useful in :
–Ocular hypertension
–Early glaucoma
–Optic neuritis
–Optic atrophy
–Disc drusen
–Diabetic retinopathy
–Amblyopia.
VEP
 Visual evoked cortical
.potentials (VECP)
•A gross electrical signal
generated by the brain in
response to visual stimuli.

• Commonly called visual evoked

response (VER) or visual
evoked potential (VEP) .
 Visual evoked cortical
.potentials (VECP)
• As ERG is also visual evoked
response or potential , hence
VECP is the best name.

• Mainly derived from the central

few degrees of visual field.
 Visual evoked cortical
.potentials (VECP)
• Stimulus:
Flash.
Pattern (reversal or on-off) –
checkerboard.

Pattern response give more info

and is better formed.
 Visual evoked cortical
potentials (VECP)
• Electrodes:
– Measuring – over occipital lobe.
– Reference – ear or forehead.
– Ground – jaw or nose .
• Parameters:
– Latency .
– Amplitude.
 Visual evoked cortical
potentials (VECP)
• Transient VECP:
– Discrete –ve and +ve deflections.
– Most commonly used clinically.
• Steady state VECP:
– Elecited by increasing the temporal
frequency to above 5 reversal/s or
5 Hz.
– Better in calculating latency.
– Might be useful in early glaucoma
detection-debatable.
 The form of VECP
P100
Voltage

Amplitude
Stimulus onset Of P100

Time

N75

Latency of P100
N135
 Visual evoked cortical
potentials (VECP)
Latency :
• VECP produces responses in
normal subjects with a
latency of 100 msec.
• VECP may give falsely
delayed latency if the patient
is  not concentrating
 Main indicatons in
.ophthalmology

• Optic nerve diseases:

–Optic neuritis increase

latency and decrease
amplitude , often persist
after resolution.
 Main indicatons in
.ophthalmology
• Investigation of unexplained
visual loss:

–Pattern VECP is usually very

variable with malingering
patient defocusing or refuse
to fixate.
Example of a VEP waveform done in the
case of suspected optic nerve disease
 Main indicatons in
.ophthalmology
• Assessment of vision in infant:
–Acuity estimation using
extrapolation of amplitude
changes in response to check
or grate size.
–Amblyopia increase latency for
pattern reversal VECP.
 Main indicatons in
.ophthalmology
• It is important to note that
pattern VECP can be abnormal in
both retinal and macular diseases .
• It is , therefore, useful to exclude
these other causes before an optic
nerve disease is diagnosed.
 Main indicatons in
.ophthalmology

•A suggested test strategy

for abnormal pattern VECP

is summarized in
 Abnormal
PVECP

Normal Abnormal
PERG PERG

Optic nerve Normal P50

Abnormal P50
disease .Abnormal N95

Normal ERG Abnormal ERG

A suggested test
strategy for
abnormal pattern VECP
Generalized
Macular
retinal
dysfunction
disease
 Main indicatons in
ophthalmology
• Summary of the main clinical indications
of electrodiagnostic tests:

– EOG =Best`s disease.

– ERG =Generalized retinal function.

– PERG=Primary assessment of macular

function.

– VECP=Optic nerve diseases.

Thank You
 Multifocal VEP and ERG
• The most recent advance in ERG
technology is the multifocal
pattern ERG, analysed and
mapped by computer averaging
techniques.
• It allows a detailed assessment
of the state of the macular area.
Multifocal (mf) ERG & VEP
 Multifocal VEP and ERG
• Multifocal exams provide an

objective perimetry based on

electroretinographic or visual

evoked potentials.
 Multifocal VEP and ERG
• Multifocal exams provide an

objective Field testing by

quantitative measurement of

ganglion cell layer and optic nerve

functions .
 Multifocal VEP and ERG
• The stimulation display includes a

large number of stimulating areas

(up to 250) that are activated in

an independent manner by the use

of maximum- length- sequences.

Multifocal VEP and ERG
 Multifocal VEP and ERG
• It can produce a topographic map of
the retina so , can detect localized
lesion in the retina.
• It is cone-generated.
• The normal MFERG has a high central
peak (25°) demonstrating maximum
light sensitivity in the fovea.
• There is gradual decline from fovea to
the periphery .
 Tridimensional representation of multifocal
electroretinographic ( mfERG ) responses
recorded from the right eye of a healthy human being.
Multifocal Pattern Reversal VEP
Thank You