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Functional Testing of the Eye: Clinical Electrophysiology of Vision

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Title: Functional Testing of the Eye: Clinical Electrophysiology of Vision


1
Functional Testing of the Eye Clinical
Electrophysiology of Vision
  • Matthew L. Severns, Ph.D.
  • LKC Technologies, Inc. USA

2
Electrophysiology and Psychophysics
  • Electrophysiology tests record the electrical
    responses generated by the eyes or visual cortex
  • Psychophysical tests measure the patients
    responses through mental process and behavior
  • Both are functional tests, but electrophysiology
    is objective and psychophysics is subjective
  • We will focus on electrophysiology tests

3
Common Visual Electrodiagnostic Tests
  • ERG (Electroretinogram)
  • Ganzfeld
  • Pattern
  • Multifocal
  • EOG (Electro-oculogram)
  • VEP/VER (Visual Evoked Potential/Response)
  • Pattern
  • Flash

4
ERG Functional Testing of Retina
  • A flash of light will elicit an electrical
    response from the retina
  • The response can be recorded by placing
    electrodes on the surface of eye
  • The recorded response is weak and needs to be
    amplified
  • Recorded data can be stored and analyzed on a
    computer

5
ERG Recording Setup
6
Typical ERG Response
  • A-Wave Mostly due to Photoreceptor activity
    (outer retina)
  • B-wave Mostly due to On- and Off- Bipolar and
    Müller cell activity (inner retina)

7
Anatomy of the Retina
8
The Origin of A-Wave
  • The photoreceptor cells are hyper-polarized in
    response to a flash stimulus, causing the
    negative A-wave
  • Dim flash does not elicit an A-wave early enough
    to be recorded
  • The early part of the A-wave is a direct measure
    of function of the photoreceptor cells including
    the Transducin (G-protein) cascade

9
The Origin of B-Wave
  • Photoreceptors trigger the On- and Off- Bipolar
    cells
  • Bipolar cell depolarization causes extracellular
    K changes, which trigger Müller cell membrane
    potential changes
  • Most of the B-wave is caused Bipolar and Müller
    cells
  • Because the ratio of Rods vs Cones is about 131,
    scotopic B-wave is a measure of the response from
    the Rod system, especially for dim flash

10
ERG Test Procedure
  • Dilate the pupil with mydriatic to maximize the
    light entering the eye and minimize the
    interference from pupil contraction
  • Dark adapt gt 25 minutes to maximize the rod
    responsiveness
  • Connect the electrodes
  • Corneal electrodes on eyes
  • Reference electrode on forehead
  • Ground on ear

11
ERG Recording Electrodes
Commonly used corneal electrodes
12
ISCEV ERG Protocol Step 1Rod Response
  • Patient is dark adapted, and there is no
    background light when ERG is recorded. The
    response is Scotopic
  • A dim flash stimulus (-24 dB) activates Rod
    photoreceptor cells but not Cones. Only B-wave
    response is recorded
  • Useful for the evaluation of Rod function

13
ISCEV ERG Protocol Step 2Maximal Response
  • Patient remains dark adapted, and so the response
    is also Scotopic
  • Standard flash stimulus (0 dB) activates both
    Rods and Cones
  • The response contains both A-wave and B-waves
  • In normal retina, this stimulus intensity elicits
    the maximal response

14
ICSEV ERG Protocol Step 3Oscillatory
Potentials
  • Same stimulus as Step 2 also elicits Oscillatory
    Potentials (OPs), which ride on the ascending
    B-wave
  • OPs have frequency range of 100-160 Hz
  • Affected by retinal ischemia
  • Diabetics, CRVO have reduced OP Amplitude
  • OP Amplitude predicts high-risk diabetic patients

15
ICSEV ERG Protocol Step 4Cone Response
  • The patient is exposed to background light (30
    cd/m2) and then stimulated with a standard flash
    (0 dB), Photopic
  • The Rod photoreceptors are bleached by the
    background light, so response from Rods is
    suppressed
  • The response is mainly from Cone photoreceptors

16
ICSEV ERG Protocol Step 5Flicker Response
  • Flicker stimulation (15-60 Hz) at the standard
    intensity (0 dB) with background on elicits
    photopic response
  • The B-wave from Cones is recorded, primarily
    inner retinal response
  • Applications Retinal Ischemia cone and rod-cone
    disorders

LKC software provides automatic analysis of
Flicker ERG
17
ERG Clinical Applications
  • Helps Diagnose
  • Retinitis Pigmentosa and other inherited retinal
    degenerations
  • Congenital and acquired night blindness
  • Inflammatory conditions (AZOOR, MEWDS)
  • Vitamin A deficiency
  • Helps Manage
  • Diabetic Retinopathy
  • Central and Branch Vein or Artery Occlusion
  • Monitor retinal toxicity of drugs such as
    Plaquenil, Quinine, Cisplatin, Vigabatrin
  • Helps Prognosis
  • Ocular trauma
  • Detached Retina

18
ERG Additional Tests
  • Pattern ERG
  • Important point Patient need to be refracted
    using tri-lenses. Use temporal fossa for
    reference electrode, and forehead for ground
    electrode.
  • Recording electrode DTL or Gold Foil Electrode
    (no lens electrode)
  • Generated by retinal ganglion cells
  • Glaucoma evaluation
  • Macular dysfunction
  • Very bright flash (25dB) test for pre-operative
    evaluation
  • Dense cataract
  • Vitreous hemorrhage

19
ERG Additional Tests
  • Photopic Negative Response ERG
  • Test condition Dilated, photopic test
  • Stimulus Red Flash on Blue Background
  • Generated by retinal ganglion cells
  • Early glaucoma evaluation
  • On/Off Response ERG
  • Test condition Dilated, photopic test
  • Stimulus Red Flash on Blue Background
  • Looking at On and Off Bipolar Cells responses
  • Inner retina dysfunction
  • S-Cone ERG
  • Test condition Dilated, photopic test
  • Stimulus Blue Flash on Amber background
  • Generated by S-Cone Photoreceptors
  • Enhanced S-Cone Syndrome

20
ERG Additional Tests - Research
  • Scotopic Threshold response ERG
  • Test condition Dilated, scotopic test
  • Stimulus Series of flash of increasing intensity
    starting from below threshold (starting intensity
    is species dependent)
  • Double Flash ERG
  • Stimulus Bright Flash followed by medium flash

21
EOG The Electro-Oculogram
  • Records the standing potential between the front
    and back of eye
  • Also called Corneo-Fundal Potential
  • Measures function of Retinal Pigment Epithelium
    (RPE)
  • Amplitude of potential changes with retinal
    illumination over a period of minutes
  • Dark smaller potential
  • Light larger potential

22
EOG Testing First Steps
  • Pupil dilation and dark adaptation are not
    required for EOG test
  • Connect electrodes to inner and outer canthii

EOG electrodes
  • Patient looks side to side at alternating lights
  • LKC system automatically measures the potentials,
    and analyzes EOG data

23
EOG Recording Phases
  • Three phases are typically recorded in EOG
  • The pre-adapt light phase is to standardize the
    standing potential, taking 1-5 min.
  • The dark-adapt phase is to discharge the
    standing potential, taking 10 - 20 min.
  • The light phase is to recharge the standing
    potential, taking 4 - 10 min.
  • The test takes about 30 - 40 min in total.
    Recording of both eyes are recommended to save
    time

24
EOG A Normal Recording
Arden Ratio Light / Dark gt 2.0 is OK
25
EOG Clinical Applications
  • Most commonly used in Bests Disease (Bests
    Vitelliform Macular Dystrophy)
  • ERG Normal, EOG Abnormal is CONFIRMING diagnosis
  • Abnormal EOG even in patients with no symptoms of
    the disorder
  • Abnormal EOG also found in
  • Retinal pigmentary degenerations
  • Chorioretinal dystrophies (e.g. choroideremia)

26
VEP Visual Evoked Potential
  • Measures function of visual pathway fovea, optic
    nerve, primary visual cortex
  • Pattern or Flash Stimulus
  • Normally use pattern stimulus (less variability)
  • Alternating grating, sinusoid, or checkerboard
    pattern
  • Stimulus may be full field or hemi-field
  • Record signals at visual cortex

27
VEP Electrode Placement
28
VEP Recording Procedure
  • VEP response is very small, about 20?V or less,
    and spontaneous brain activity and EMG may
    dominate the individual responses
  • Need to average 50-100 responses to remove noise
    and reveal the underlying response
  • Artifacts caused by head movements may distort
    the recording, and so the sweeps contaminated
    with artifact should be rejected. LKC software
    automatically does this.
  • For Pattern VEP
  • Patient should be properly refracted (near
    correction)
  • For Flash VEP
  • Must patch contralateral eye to avoid artifacts

29
Pattern VEP A Normal Recording
30
Pattern VEP Applications
  • Optic Nerve Disorders
  • Optic neuropathy (compressive, ischemic)
  • Optic nerve atrophy
  • Compressive tumors
  • Demyelinating disease (e.g., Multiple Sclerosis)
  • Toxic optic neuropathies (ethambutol, cisplatin)
  • Malingering, hysterical blindness
  • Can use hemifield stimulation to distinguish
    pre-chiasmal from post-chiasmal effects

31
Flash VEP Applications
  • Assessing visual function behind media opacities
  • Surgical monitoring
  • Intraorbital surgery with risk for optic nerve
    damage
  • Endoscopic sinus surgery

32
Sweep VEP Objective Measurement of Visual Acuity
  • Useful for patients who are unable to respond
  • Pre-verbal infants (assessment of amblyopia)
  • Traumatic brain injury
  • Mental retardation
  • Detection of malingering

33
Sweep VEP Recording and Analysis Procedure
  • The electrode placement is same as for regular
    VEP
  • There are several steps of recording, each of
    which is made with a different grating width
  • The response amplitudesare automatically
    meas-ured, and the estimatedacuity is
    determined by
  • the user selection of valid
  • data points

34
Sweep VEP Technique
  • The subject must be looking at the screen for the
    entire sweep (approx 10 seconds). This can be
    difficult with babies
  • Remove other stimuli (especially faces)
  • Use movies on screen to attract attention before
    sweep
  • Laser pointer or other device to direct babys
    attention
  • Average several sweeps for best results.
  • 5 to 10 sweeps may be needed for a good result
  • Select proper points for analysis

35
Sweep VEP A Typical Recording
Larger Stripes
Smaller Stripes
36
Multifocal ERG (MFERG) Mapping of Retinal
Function
  • MFERG tests individual retinal areas in central
    30 area
  • Stimulation is provided by video display
  • Sophisticated algorithms extract the response of
    each retinal area from the overall recording
  • Photopic test (cone function)
  • Response amplitude related to cone density.
    Typically, stimulus areas are scaled to provide
    equal response.

37
MFERG The Concept
Stimulus on high-quality video monitor
38
MFERG The Individual Response and 3-Dimensional
Display
Blind spot Foveal peak
3D display of ERG response density
Focal ERG from each retina area
39
MFERG Map And Focal
  • Analyze summarized ERG responses from different
    regions
  • Analyze the overall response from the central
    retina area of 50 - 600 view angle

40
MFERG Recording Procedure
  • Dilate patients pupil with a mydratic. No dark
    adaptation is necessary.
  • Refractive correction is recommended but not
    required.
  • Recording using Burian-Allen or DTL electrode on
    the eye, a reference electrode (only for DTL),
    and a ground electrode
  • The test is composed of several segments, 10 - 30
    seconds each, and total recording time is 5 - 10
    minutes per eye
  • It is critical that patient is staring at the
    fixation during recording the eye can be
    monitored using a fixation camera
  • Eye or body movement will distort the recording,
    and the segments should be repeated if there is
    too much noise

41
MFERG Applications
  • Diagnosing macular disease
  • ARMD, others
  • Retinal toxicity (Plaquenil and other drugs)
  • AZOOR (Acute Zonal Occult Outer Retinopathy)
  • Macula vs optic nerve in unexplained visual loss
  • Early diagnosis of retinal disease Many retinal
    disorders affect small areas in early stages
  • Diabetic retinopathy
  • Retinitis pigmentosa

42
Conclusions
  • Visual Electrodiagnostic testing provides a way
    to measure the function of the retina and the
    visual pathway.
  • The functional examination is at the cellular
    level, and the recordings can be further studied
    with morphological data.
  • Clinical applications of visual electrophysiology
    are broad, and researches are being carried out
    for more applications.
  • LKC Technologies, the leader in diagnostic
    electrophysiology of vision, has been providing
    high quality techniques and products for nearly
    30 years.

43
Thank You!
LKC Technologies, Inc. 2 Professional
Drive Gaithersburg, MD 20879 USA Tel.
1-301-840-1992 Website www.lkc.com
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