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-adapted

Reflects 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

Nyctalopia

Causes: 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 Syndrome

AR 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 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)

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 percentile

Diminished = < 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 light

Test 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 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

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 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

http://www.nature.com/eye/journal/v21/n10/images/6702839f3.jpg

Albinism

~55% decussate ~80% decussate++ ++ ++ + ++ +++

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