Functional Testing of the Eye: Clinical Electrophysiology of Vision

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Functional Testing of the Eye Clinical
Electrophysiology of Vision

• Matthew L. Severns, Ph.D.
• LKC Technologies, Inc. USA

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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

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Common Visual Electrodiagnostic Tests

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

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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

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ERG Recording Setup
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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)

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Anatomy of the Retina
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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

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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

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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

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ERG Recording Electrodes
Commonly used corneal electrodes
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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

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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

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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

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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

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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
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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

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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

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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

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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

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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

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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

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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

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EOG A Normal Recording
Arden Ratio Light / Dark gt 2.0 is OK
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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)

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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

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VEP Electrode Placement
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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

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Pattern VEP A Normal Recording
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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

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Flash VEP Applications

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

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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

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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

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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

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Sweep VEP A Typical Recording
Larger Stripes
Smaller Stripes
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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.

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MFERG The Concept
Stimulus on high-quality video monitor
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MFERG The Individual Response and 3-Dimensional
Display
Blind spot Foveal peak
3D display of ERG response density
Focal ERG from each retina area
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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

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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

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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

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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.

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