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
http://www.diagnosysllc.com/home/
Pattern stimulator Ganzfeld (flash stimuli)
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-adaptedReflects gross outer retina/RPE function
http://webvision.med.utah.edu/ClinicalERG.html
http://brainconnection.positscience.com/med/medart/l/eye-xsection-side.gif
+ -
Visually Evoked Potential (VEP)Assess macular-cortical pathway’s gross integrity
http://www.aph.org/cvi/brain.html
http://www.metrovision.fr
Record
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 6/12 OS: -2.00/-3.50 x 180 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
NyctalopiaCauses:
Retinitis pigmentosa (RP)
Choroideremia Congenital stationary night
blindness (CSNB)
Pan-retinal laser surgery Vitamin A deficiency Non-retinal
Night myopia Optical defects (e.g., cataract)
Problem Specific Testing: DFE Visual fields
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 SyndromeAR inheritance1/179 carry geneProgressive vision loss
Nyctalopia Constricted Fields Acuity loss
Optometrist duties: Low vision care Referral for genetic work-up Referral to nephrologist
Cardinal Features (4 of 6) Retinal dystrophy (RP) Polydactyly Obesity Cognitive impairment Hypogonadism Nephropathy
Retinal-based Function TestsERG
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
fERGsStandardized 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 fERGsa-wave: Amplitude & implicit timeb-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 ElectrodesGold 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 ElectrodesOther 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)
Response Component 100th 50th 5th 0thRod b-wave 347.27 235.16 184.77 181.64
Maximal b-wave 686.33 437.50 312.89 277.89a-wave 367.97 244.14 162.11 140.24
OPs OP2 141.41 72.66 33.59 22.66Cone b-wave 286.33 203.91 152.74 143.73
a-wave 159.38 112.11 79.69 76.96Flicker W1 254.30 123.44 98.83 87.11
Supernormal = > 100th percentile
WNL = ≥ 5th percentileDiminished = < 5th percentile
S
P
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 retinopathyPre-surgical evaluation
obstructed retina due to cataract, hemorrhage or penetrating injury
Retinal toxicity hydroxychloroquine
Unexplained vision loss
fERG: RPE-Photoreceptor Disease
http://webvision.med.utah.edu/ClinicalERG.html
rod
maximal
cone
flicker
fERG: Photoreceptor Disease
http://webvision.med.utah.edu/ClinicalERG.html
rod
maximal
cone
flicker
fERG: Photoreceptor Disease
http://webvision.med.utah.edu/ClinicalERG.html
rod
maximal
cone
flicker
pERG (seldom done)Reflects central retinal response (incl. ganglion cell)
Macular disease Toxic/nutritional disease Unexplained central vision loss
2012 ISCEV standard
http://www.iscev.org/standards/perg.html
http://www.diagnosysllc.com/home/
mfERG2011 ISCEV standardTopographical 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 mfERGMacular disease
e.g., Stargardt Disease, ARMDUnexplained central vision loss
mfERG
Normal mfERG
ARMD mfERG
Electro-oculogram (EOG)Seldom done2010 ISCEV standardReflects global outer retina/RPE functionClinical diagnostic use:
Best vitelliform macular dystrophy (rare, AD inheritance)
http://img.medscape.com/pi/emed/ckb/ophthalmology/1189694-1227128-71.jpg
EOG
EOGEyes have a ‘standing potential’
Cornea positive; RPE negativeDerived from RPE; changes with retinal illumination
Potential decreases in dark; increases in lightTest involves:
Making lateral saccades through a dark & light phases
http://brainconnection.positscience.com/med/medart/l/eye-xsection-side.gif
+ -
http://www.iscev.org/standards/pdfs/eog-standard-2006.pdf
EOG Arden RatioLight 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 6/24 OS: +2.50/-0.50 x 020 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 hypopigmented skin macules
Optometrist duties: Strabismus Dx/Mx Low vision care Referral for genetic work-up
Main Features Sl. lighter hair & skin
complexion (not necessary) Nystagmus (most horizontal &
pendular) Iris tranillumination Macular hypoplasia Fundus hypopigmentation Visual pathway
decussation abnormality
Albinism: Problem Specific Testing
http://journals1.scholarsportal.info/tmp/1186526813808035824.pdf
Ocular Motility Iris tranillumination DFE VEP OCT (nystagmus preclude?)
Visually Evoked Potential (VEP)Assess macular-cortical pathway’s gross integrity
http://www.aph.org/cvi/brain.html
http://www.metrovision.fr
Record
NOTE: VEP = VER = VECP (latter 2: older terms)
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 ElectrodesScalp 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
z
ISCEV Active
ISCEV Ref
http://www.brainmaster.com
VEP Electrode PlacementMulti-channel placement
Pre-chiasmal: Better Post-chiasmal: Required
OZ
http://www.brainmaster.comhttp://www.opt.indiana.edu
Measuring pVEPsP100:Cortical response (Amplitude in μv) to checkerboard reversal (IT: Implicit time ~100ms)
Amp
IT
Transient VEP (<4Hz)
http://www.iscev.org/standards/pdfs/vep-standard-2004.pdf
Simulated pVEP Normative Database(Implicit Time [ms]: 20-39 yrs)
WNL = ≤ 5th percentile Delayed = > 5th percentile
Check Size Component 100th 50th 5th 0th4' P-100 120.28 125.00 136.72 142.198' P-100 113.28 122.66 128.91 128.91
16' P-100 101.56 112.50 117.97 121.8832' P-100 102.34 106.25 117.19 128.0064' P-100 103.91 107.81 110.94 118.75
128' P-100 101.56 109.38 114.06 121.88256' P-100 101.56 110.94 118.75 120.12
Measuring fVEPsP2: 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 pVEPOptic 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
AmblyopiaPsychogenic vision lossUnexplained vision loss
Optic Neuritis
http://opt.pacificu.edu/test/index.html
Visual Pathway Asymmetry
http://www.nature.com/eye/journal/v21/n10/images/6702839f3.jpg
Albinism
~55% decussate ~80% decussate++ ++ ++ + ++ +++
Visual Electrophysiology in CanadaSpecific 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 CanadaOther 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