CLINICAL ELECTROPHYSIOLOGY:
Plugging into the visual system
Marlee M. Spafford, OD, MSc, PhD, FAAO
COPE Personal Disclosure
For this lecture, I have:
 developed the course material independently
 developed the course material without commercial interests
 no personal conflicts of interest
 no financial relationship with a commercial interest
Basic Electrodiagnostic Equipment
 Specialized computer hardware & software
 >$100,000 Cn
Pattern stimulator
Ganzfeld (flash stimuli)
http://www.diagnosysllc.com/home/
Visual Electrodiagnostic Tests
 Electroretinogram (ERG)
 Electro-oculogram (EOG)
 Visually Evoked Potential (VEP)
Electroretinogram (ERG)
 Reflects global changes in retinal electrical
potential in response to flash or pattern stimuli
http://webvision.med.utah.edu/ClinicalERG.html
Electro-oculogram (EOG)
 Records the ocular standing electrical potential
 Dark-adapted with light-adapted
 Reflects gross outer retina/RPE function
+
-
http://brainconnection.positscience.com/med/medart/l/eye-xsection-side.gif
http://webvision.med.utah.edu/ClinicalERG.html
Visually Evoked Potential (VEP)
 Assess macular-cortical pathway’s gross integrity
Record
http://www.metrovision.fr
http://www.aph.org/cvi/brain.html
Patient #1: 6-yr-old male
 VEP referral (family OD):
 Reduced VA, not corrected by spectacles: meridional amblyopia?
 OD: -1.00/-3.00 x 170
 OS: -2.00/-3.50 x 180
6/12
6/15
 Interview:
 Ocular Hx:
 1st Rx @ 4 yrs
 Nyctalopia: “always trips in the dark”
 Health Hx:
 Unremarkable
 Birth Hx:
 Polydactyl (surgery @ 1 yr)
 Negative family hx of eye disease
 1 step-brother (“normal” vision)
 No parental consanguinity
http://www.medes-salud.com.ar/causas.htm
Nyctalopia
 Causes:
 Problem Specific Testing:
 Retinitis pigmentosa (RP)
 DFE
 Choroideremia
 Visual fields
 Congenital stationary night
blindness (CSNB)
 Pan-retinal laser surgery
 Vitamin A deficiency
 Non-retinal
 Night myopia
 Optical defects (e.g., cataract)
 Automated > 30o; Goldmann
 ERG (full field ERG)
 Colour Vision
 adults; B-Y & R-G defects
DFE
http://www.scielo.br.proxy.lib.uwaterloo.ca/scielo.php?script=sci_arttext&pid=S0004-27492009000500019&lng=en&nrm=iso&tlng=en
Bardet-Biedl Syndrome
 AR inheritance
Cardinal Features (4 of 6)
 1/179 carry gene

 Progressive vision loss
 Nyctalopia
 Constricted Fields
 Acuity loss

 Optometrist duties:
 Low vision care
 Referral for genetic work-up
 Referral to nephrologist




Retinal dystrophy (RP)
Polydactyly
Obesity
Cognitive impairment
Hypogonadism
Nephropathy
Retinal-based Function Tests
 ERG
 Full-field ERG: fERG (typical referral)
 Pattern ERG: pERG
 Multi-focal ERG: mfERG
 EOG
Full-field ERGs
 Assess the gross integrity of the outer 2/3rds of the neural retina
 Good test for:
 widespread retinal diseases
 vision loss that changes with lighting conditions
fERG
http://webvision.med.utah.edu/ClinicalERG.html
fERGs
 Standardized fERG protocol exists:
 ISCEV standard: 2008
(International Society for Clinical Electrophysiology of Vision)
 Dark adapt (>20 min): scotopic ERGs (rod-isolated & rod-cone mixed)
 Light adapt (>3 min): photopic ERGs (cone-isolated)
http://webvision.med.utah.edu/ClinicalERG.html
Measuring fERGs
 a-wave: Amplitude & implicit time
 b-wave: Amplitude & implicit time
http://webvision.med.utah.edu/ClinicalERG.html
fERG Components
 a-wave: Photoreceptors
 b-wave: Müllers & On-Bipolars
 Oscillatory potentials (OPs): Amacrines
http://webvision.med.utah.edu/ClinicalERG.html
ISCEV Recording Electrodes
 Gold Standard
 Contact lens electrode
(e.g., Burian-Allen Speculum Contact Lens Electrode)
 Bipolar electrode design
 CL: active
 Speculum: reference
http://fn.bmjjournals.com/content/82/3/F233.abstract
ISCEV Recording Electrodes
 Other ISCEV Electrodes
 DTL Fiber
 Gold foil
 HK loop
http://www.diagnosysllc.com/products/product5.php
http://www.nature.com/eye/journal/v21/n6/fig_tab/6702309f2.html
DTL Fiber Electrode Insertion
Ganzfeld View
Chin Rest Prep
ERG Recording
ERG Recording
Simulated fERG Normative Database
(Amplitude [µV]: 20-39 yrs)
R esponse
S
C om ponent
Rod
M a x im a l
OPs
Cone
P
F lic k e r
1 0 0 th
5 0 th
5 th
0 th
b -w a ve
b -w a ve
3 4 7 .2 7
6 8 6 .3 3
2 3 5 .1 6
4 3 7 .5 0
1 8 4 .7 7
3 1 2 .8 9
1 8 1 .6 4
2 7 7 .8 9
a -w a ve
3 6 7 .9 7
2 4 4 .1 4
1 6 2 .1 1
1 4 0 .2 4
OP2
b -w a ve
1 4 1 .4 1
2 8 6 .3 3
7 2 .6 6
2 0 3 .9 1
3 3 .5 9
1 5 2 .7 4
2 2 .6 6
1 4 3 .7 3
a -w a ve
1 5 9 .3 8
1 1 2 .1 1
7 9 .6 9
7 6 .9 6
W1
2 5 4 .3 0
1 2 3 .4 4
9 8 .8 3
8 7 .1 1
Supernormal = > 100th percentile
WNL = ≥ 5th percentile
Diminished = < 5th percentile
Diagnostic Uses of fERG
 Inherited retinal disorders
 RPE photoreceptor disease, photoreceptor disease,
chorioretinal dystrophies, vitreoretinal dystrophies
 Retinal ischemic disease
 diabetic retinopathy, central retinal vein occlusion,
carotid artery stenosis, sickle cell retinopathy
 Pre-surgical evaluation
 obstructed retina due to cataract, hemorrhage or
penetrating injury
 Retinal toxicity
 hydroxychloroquine
 Unexplained vision loss
fERG: RPE-Photoreceptor Disease
rod
maximal
flicker
cone
http://webvision.med.utah.edu/ClinicalERG.html
fERG: Photoreceptor Disease
rod
maximal
flicker
cone
http://webvision.med.utah.edu/ClinicalERG.html
fERG: Photoreceptor Disease
rod
maximal
flicker
cone
http://webvision.med.utah.edu/ClinicalERG.html
pERG (seldom done)
 Reflects central retinal response (incl. ganglion cell)
 Macular disease
 Toxic/nutritional disease
 Unexplained central vision loss
 2012 ISCEV standard
http://www.diagnosysllc.com/home/
http://www.iscev.org/standards/perg.html
mfERG
 2011 ISCEV standard
 Topographical measure of outer 2/3rds of retina
 ~60-100 small retinal areas
 Local ERGs are mathematical extractions of the signal
 Dilated pupils; fiber electrode
www.Cephalon.dk
http://webvision.med.utah.edu/ClinicalERG.html
Diagnostic Uses of mfERG
 Macular disease
 e.g., Stargardt Disease, ARMD
 Unexplained central vision loss
mfERG
ARMD mfERG
Normal mfERG
Electro-oculogram (EOG)
 Seldom done
 2010 ISCEV standard
 Reflects global outer retina/RPE function
 Clinical diagnostic use:
 Best vitelliform macular dystrophy (rare, AD inheritance)
EOG
http://img.medscape.com/pi/emed/ckb/ophthalmology/1189694-1227128-71.jpg
EOG
Eyes have a ‘standing potential’
Cornea positive; RPE negative
Derived from RPE; changes with retinal illumination
Potential decreases in dark; increases in light
Test involves:
Making lateral saccades through a dark & light phases
+
http://www.iscev.org/standards/pdfs/eog-standard-2006.pdf
-
http://brainconnection.positscience.com/med/medart/l/eye-xsection-side.gif
EOG Arden Ratio
 Light peak (LP)/dark trough (DT)
 >2.0: normal
 1.5 to 2.0: borderline
 <1.5: abnormal
http://www.iscev.org/standards/pdfs/eog-standard-2006.pdf
Patient #2: 9-yr-old male
 VEP referral (family OD):
 Fine, mostly pendular, horizontal nystagmus, photodysphoria &
reduced VA: albinism?
 OD: +3.00/-1.00 x 150
 OS: +2.50/-0.50 x 020
6/24
6/21
 Interview:
 Ocular Hx:
 Congenital nystagmus
 Health Hx:
 Unremarkable
 Negative family hx of eye disease/low vision
 No parental consanguinity
http://www.kilgorevision.com/stories.htm
Ocular Albinism (OA)
 X-linked recessive
(GPR143 mutation at Xp22.3-22.2)
 Evidence of carrier status
 iris illumination
 ‘mud-spattered’ fundus
Main Features


pendular)
 hypopigmented skin macules

 Optometrist duties:

 Strabismus Dx/Mx

 Low vision care

 Referral for genetic work-up
Sl. lighter hair & skin
complexion (not necessary)
Nystagmus (most horizontal &
Iris tranillumination
Macular hypoplasia
Fundus hypopigmentation
Visual pathway
decussation abnormality
Albinism: Problem Specific Testing
 Ocular Motility
 Iris tranillumination
 DFE
 VEP
 OCT (nystagmus preclude?)
http://journals1.scholarsportal.info/tmp/1186526813808035824.pdf
Visually Evoked Potential (VEP)
 Assess macular-cortical pathway’s gross integrity
Record
http://www.metrovision.fr
NOTE:
VEP = VER = VECP
(latter 2: older terms)
http://www.aph.org/cvi/brain.html
Visually Evoked Potentials (VEPs)
 Types of clinical-based VEPs
 Pattern: pVEP
 2009 ISCEV standard
 Full-field: fVEP
 2009 ISCEV standard
 One example of research-based VEPs
 Sweep: sVEP
 No ISCEV standard yet
VEP Stimuli
pVEP
fVEP
NOTE:
pVEPs can be reversing checkerboards or gratings
http://www.metrovision.fr
http://webvision.med.utah.edu/ClinicalERG.html
ISCEV Recording Electrodes
 Scalp silver-silver chloride or gold disc surface
electrodes
 ISCEV standard:
 1 active (3 better) plus 1 reference electrode
www.lkc.com
VEP Electrode Placement
 International 10-20 system for electrode placement
ISCEV Ref
ISCEV Active
z
http://www.brainmaster.com
VEP Electrode Placement
 Multi-channel placement
 Pre-chiasmal: Better
 Post-chiasmal: Required
OZ
http://www.opt.indiana.edu
http://www.brainmaster.com
Measuring pVEPs
P100:
 Cortical response (Amplitude in μv) to
checkerboard reversal (IT: Implicit time ~100ms)
Transient VEP (<4Hz)
Amp
IT
http://www.iscev.org/standards/pdfs/vep-standard-2004.pdf
Simulated pVEP Normative Database
(Implicit Time [ms]: 20-39 yrs)
C h e c k S iz e
4'
8'
16'
32'
64'
128'
256'
C om ponent
P -1 0 0
P -1 0 0
P -1 0 0
P -1 0 0
P -1 0 0
P -1 0 0
P -1 0 0
1 0 0 th
1 2 0 .2 8
1 1 3 .2 8
1 0 1 .5 6
1 0 2 .3 4
1 0 3 .9 1
1 0 1 .5 6
1 0 1 .5 6
5 0 th
1 2 5 .0 0
1 2 2 .6 6
1 1 2 .5 0
1 0 6 .2 5
1 0 7 .8 1
1 0 9 .3 8
1 1 0 .9 4
WNL = ≤ 5th percentile
Delayed = > 5th percentile
5 th
1 3 6 .7 2
1 2 8 .9 1
1 1 7 .9 7
1 1 7 .1 9
1 1 0 .9 4
1 1 4 .0 6
1 1 8 .7 5
0 th
1 4 2 .1 9
1 2 8 .9 1
1 2 1 .8 8
1 2 8 .0 0
1 1 8 .7 5
1 2 1 .8 8
1 2 0 .1 2
Measuring fVEPs
P2:

Cortical response to 1 Hz flash stimulus (amplitude in μv;
IT: Implicit time ~100ms)

fVEP useful when pVEP fails
Amp
IT
http://www.iscev.org/standards/pdfs/vep-standard-2004.pdf
Diagnostic Uses of pVEP
 Optic nerve disease
 Optic neuritis (recovery more than dx); compressive optic
neuropathy; Leber’s hereditary optic neuropathy (LHON)
 Post-chiasmal disease (with multiple-channels)
 Demylinating disease; ocular albinism
 Amblyopia
 Psychogenic vision loss
 Unexplained vision loss
Optic Neuritis
http://opt.pacificu.edu/test/index.html
Visual Pathway Asymmetry
Albinism
~55% decussate
++
++
++
~80% decussate
+
++
+++
http://www.nature.com/eye/journal/v21/n10/images/6702839f3.jpg
Visual Electrophysiology in Canada
 Specific Locations:
 UW Electrodiagnostic Clinic (Waterloo)
 UM Clinique de la Vision (Montréal)
 University of Ottawa Eye Institute (Ottawa)
 Ivey Eye Institute (London)
 HSC Visual Electrophysiology Unit (Toronto)
 St. Michael’s Hospital (Toronto)
 Toronto Western Hospital (Toronto)
 VEP only
Visual Electrophysiology in Canada
 Other Locations? Good question!
 There is no Canadian registry for VE services
 Based on existing research activity, hospital-based,
university-based VE clinical services likely exist in:
 Vancouver (UBC)
 Calgary (UofC)
 Edmonton (UofA)
 Montreal (Laval & McGill)
 Halifax (Dalhousie)
 Other cities may also provide VE services
CLINICAL ELECTROPHYSIOLOGY:
Plugging into the visual system
Marlee M. Spafford, OD, MSc, PhD, FAAO