ERG & CLINICAL PRESENTATION

[Link] PARTANI
L V Prasad Eye Institute India

Clinical Electrophysiology
Electroretinogram (ERG): Flash, pattern, multifocal, bright flash Electro-oculogram (EOG)
Visually Evoked Cortical Potentials (VECP): pattern, flash, multifocal, multichannel

History
1877-Year of birth of Human ERG (First record by Dewar)

1908 -Einthoven and Jolly designated parts of ERG by letters

1941 -Riggs introduced Contact lens electrode

1945 -Karpe reported 64 normal and 87 abnormal ERG results and introduced routine ERG in his clinic

Electroretinogram (ERG)

Recording of the bioelectric potential and the summed activity of the retinal cells, when stimulated by light

Physiology of ERG
Light induced changes in the trans membrane movements of ions in retinal cells, mainly sodium and potassium, making the cells hyperpolarized i.e. more negative to the extracellular space than in the dark

Origin of ERG waveform

a-wave -Corneal negative, -light induced hyper polarization of photoreceptor cells

b-wave -Corneal positive - Muller cells due to lightinduced changes of extra cellular potassium

Origin of ERG waveform

c-wave is positive but slower & generated by the retinal pigment epithelium (RPE) as a consequence of interaction with the rods. Oscillatory potentials - small amplitude waves, generated from amacrine cells in the inner plexiform layer and require a bright stimulus, Decrease in ischemia & congenital stationary night blindness, early indicators of DR

Components of the ERG Measurements

b i.t. b-wave

Implicit time (i.t.)= time from stimulus until peak of activity Amplitude (amp)= voltage magnitude at peak of activity

b amp a amp

a i.t.
a-wave

ERG values with Maximum-Intensity Stimuli

Photopic
A-implicit time 14-20 m sec

Scotopic
20-26 m sec

A-wave amplitude

20-50 micro volt

190-300 micro volt

40-56 m sec

B-wave implicit time 26-34 m sec

B-wave amplitude

90-180 micro volt

400-700 micro volt

Recording the ERG

Ganzfeld stimulator Electrodes Signal Averager

Ganzfeld stimulator

Background light intensity -1734 cds.m-2 (7-10 foot-lamberts)

Standard flash -1.53.0 cdsm-2

(candela-seconds per meter squared)

Light Adjustment and calibration

Attenuation of stimulus strength over range of 3 log units in 0.3 log unit step. Stimulus and background calibration*

*Brigell M et al. Guidelines for calibration - -Doc. Ophthalmol 1998; 95: 1-4

Mini-Ganzfeld LED Stimulator

4.5 inch diameter
Espion Colorburst

blue (470 nm) green (525 nm) red (640 nm) 7 log unit luminance range Optoelectronic stimulation can be more precisely controlled and calibrated than xenon discharge tubes

EPSILON PORTABLE LED STIMULATOR

ELECTRODES
Active Electrodes are placed in contact with the cornea or nearby bulbar conjunctiva. Corneal electrodes give higher amplitude than noncorneal electrodes Corneal Burian -Allen Electrode, Jet Electrodes

Non corneal- DTL, Gold foil, Conjunctival loop and LVP Electrode

Corneal Electrodes

Jet

Burian-Allen

ERG-Jet Electrodes
Disposable mono-polar contact lens electrode. Reduced possibility of nosocomial eye infections. Gold foil on polymethylmethacrylate with lead wire. Ease of insertion Disadvantage -movement of lens during recording and absence of lid speculum contribute to variability of recordings

Burian-Allen Electrodes
Bipolar, reusable contact lens electrode with built-in lid speculum and Reference electrodes

Ideal for testing infants.

Disadvantage - PMMA shows variable degree of blurring so not suitable for recording pattern ERG where image clarity is vital

DTL-Plus MicroconductiveThread Electrode (Dawson-Trick-Litzkow)

Conductive thread (50 microns) floats on the corneal film surface Neglible mass Convenient to use, disposable, low cost , clear image No interference with pupil or optics Reliable ERG recordings Well tolerated by children

LVP-Zari electrodes
DTL (Dawson-Trick-Litzkow) LVP-Zari electrodes

* Ram LSM, Jalali S, et al. Doc Ophthalmol 2003; 107:179-83

Gold Foil Electrodes

Useful when 1. you can't use a contact lens electrode 2. when you don't want to anesthetize the cornea. ERG amplitudes will be substantially affected by this electrode. Requires an adaptor

Additional Electrode
Ear-clip electrode

Reference gold cup electrode

Reference electrode is unipolar electrodes-in outer canthus Ground electrode-- Ear clip electrode

Patient preparation for ERG

Full dilatation 30 minutes Dark adaptation for scotopic 10 minutes light adaptation for photopic response Avoid FFA or fundus photography before ERG If done, dark adaptation must be 1 hour

Factors influencing normal ERG

Physiological : Pupil, Age, Sex, Ref. Error, Diurnal
Variation, Dark adaptation, anesthesia.

Instrumental: amplification, gain, stimulus, electrodes. Artifacts: Blinking, tearing, eye movements, air bubbles
under electrode.

Types of ERG
Single flash ERG

Flicker fusion ERG 25-30 Hz (cone response)

Pattern evoked ERG Focal ERG (foveal / parafoveal) Multifocal ERG

ISCEV Recommendation for Single flash ERG 2004

ERG to a weak flash (arising from the rods) in the dark-adapted eye (Rod response) ERG to a strong flash in the dark-adapted eye (standard combined

response)
Oscillatory potentials
ERG to a strong flash (arising from the cones) in the light-adapted eye (Single flash cone response) ERGs to a rapidly repeated stimulus (30 Hz flicker)
1989 a Basic protocol 1999 updated

Isolated Rod Response

After 30 Minutes of dark adaptation White dim flash-strength 2.5 log units (24 dB) below the standard flash (dim blue also can be used)

2 second interval between the flashes to allow the rods to return

to dark-adapted state

no a-wave slowly rising, broad-b-wave

Maximal Combined Responses

Scotopic White standard flash (0 dB) 10 seconds interval

A sharp a wave and a much larger, rapidly rising peaked b-wave which comes to baseline very slowly

Oscillatory potentials
Originate in middle/inner retina Higher frequency oscillations (100-160Hz) Scotopic condition , Standard Flash (0 dB-white) Higher frequency filter (75 to 300 Hz) 15 seconds interval Flashes

3 major peaks followed by a smaller peak

Single flash cone response

10 minutes light adaptation (by background light in the dome, 17 to 34 cd.m.2 luminance)
Standard Flash (0dB) Interval between stimulus> 0.5 secs.

30 Hz flicker responses
Standard Flash 30 stimuli per second suppress the rod system The normal responses -the peak falls just before the stimulus onset for the next response

ROD RESPONSE

RODS

STANDARD COMBINED RESPONSE

RODS + CONES

OSCILLATORY POTENTIALS

SINGLE FLASH CONE RESPONSE

CONES

30 Hz FLICKER

CONES

ROD RESPONSE

CONE RESPONSE Light adaptation Brighter stimulus 30 Hz flicker

Dark adaptation
Dim stimulus Blue stimulus

ERG normal report

a wave
Implicit time ms ROD RESPONSE

b wave
amplitude microvoltage

Implicit time amplitude microvoltage ms

53.7371.77 14.6421.06 161.70315.54 34.1845.54

176.47281.87 310.04545.28

COMBINED REPSONSE

SINGLE FLASH CONE RESPONSE

30 HZ FLICKER RESPONSE

12.3315.87

29.36-62.36

27.2332.09
28.8330.00

121.40224.08
93.16-170.12

Pattern ERG (PERG)

Elicited by pattern stimulation (usually checkerboard or bar gratings) much lower amplitude than flash ERGs fixation is critical for PERG, not flash ERG Cells with center surround receptive fields (ganglion cells) are strongly stimulated Photoreceptors which respond to

Pattern ERG
N35 photoreceptors P50 muller + bipolar cells N95 ganglion cells Loss of N95 in optic nerve disorders Ratio of P50 /N95 Normal < 2 Abnormal > 2

PERG - Application

1. Glaucoma

2. Ocular hypertension
3. Optic nerve disease

Focal ERG (FERG)

ERG evoked by small (<100) focal stimulus

Fovea / macula tested by this technique

Very difficult to record
stimulate of exact location scattered light effect

Stimulation of exact location

Scattered light effect

Central flickering stimulus surrounded by a white annular surround light

FERG - Applications
Unexplained visual loss Idiopathic macular hole - fellow eye Idiopathic central serous chorioretinopathy

Multifocal ERG- The Principle

Mf-ERG developed by Sutter and Tran Mf-ERG is an investigation that can simultaneously measure multiple ERG responses at different retinal locations by cross-correlation techniques.

Allows topographic mapping of retinal function in the central of the retina. Sensitive test for quantifying the visual function of maculopathies.

Standard V/s Multifocal ERG

Standard ERG - uses fairly large stimuli to test large retinal areas at a time, focal damages cannot be detected this way

Early retinal disease affect small areas on the retina.

 Instead of a single stimulus and a single response, retina divide into several areas each which are stimulated with a pseudo random probability seq ( M SEQUENCE) Cover up to +/- 25 degrees of the visual field Underlying mathematical system derives the true signal from each location and form retinal map of ERG

M sequence

Multifocal ERG
N1 - contributions from the same components as the awave of full field cone ERG
P1 - contribution from the components of the cone bwave and OPs
P1

N1

N2

20

arteries veins

Some depressions are due to shadows cast by blood vessels

APPLICATIONS OF MFERG
MACULOPATHIESCentral responses are lost or reduced ,surrounded by normal [Link]. ARMD, macular dystrophy ,CSR - crater or volcano like appearance in 3-D plot of response density VASCULAR DISORDERSoverall decreases in amplitude and delay in implicit time DISORDERS OF GANGLION CELLS AND VISUAL PATHWAY

Clinical Uses of ERG

To assess retinal function in case of media opacity and infant Inherited Retinal Dystrophies & degenerations Acquired Retinal Disorders Unexplained visual loss/ hysteria / malingering Disorders of dark adaptation ,colour vision &VA

Retinitis Pigmentosa

Diagnostic Prognostic

Detection of carriers

Abnormal even in early stages Reduced scotopic & photopic b-wave Delayed implicit time Av 16 18% loss of ERG amplitudes per year

Congenital Stationary Night Blindness

CSNB with normal fundus: diminished b wave in amplitude, producing a negative ERG Reduced / non recordable scotopic response CSNB with abnormal fundus : Oguchis disease

Fundus albipunctatus

Normal Fundus CSNB

OGUCHIS DISEASE
Early H/o defective night vision Vision and peripheral fields are generaly normal in daylight and manifest defect is seen in dim illumination.

OGUCHIS DISEASE
FUNDUS Light adapted - a yellow gray sheen from optic disc to equator. Dark adapted after 2 to 3 hours, fundus appears normal (MIZUO PHENOMENON)

Oguchis disease
Scotopic b wave is diminished in amplitude, producing a negative ERG pattern. OPS normal or reduced. Photopic functions are normal

Fundus Albipunctatus

ERG-delay in rod and cone response

Prolonged dark adaptation ERG recovers to normal

CONE DYSTROPHY

photopic response subnormal or non recordable

Normal scotopic response

Cone Rod Dystrophy

AD-Bulls- eye pattern, AR-more diffuse central atrophy Photoaversion Central scotoma Defective colour vision

The rod specific ERG and the cone derived 30 Hz flicker and single flash photopic ERGs are undetectable.

ERG results in Diab. Retinopathy

Before onset of clinically visible retinopathy (?metabolic effect on neurosensory retina) OP amplitude reduction can predict progression from NPDR to PDR and is esp. seen in NVD
Depicts inner retinal ischemia even though the capillary non-perfusion on FFA is not as marked

Central retinal vein occlusion

Reduced b-wave amplitude and increased 30Hz flicker latency indicate ischemia

Non- ischemic CRVO

Ischemic CRVO

Hayreh SS etal Graefes Arch Clin Exptl Ophthalmol 1990; 228:201

TOXIC STATES
SIDEROSIS :supranormal in early stage and subnormal in advanced stage
CHALCOSIS CHLOROQUINE / QUININE TOXICITY LEAD PHENOTHIAZINES

GLAUCOMA
PERG is the test of choice Reflects ganglion cell dysfunction not detected by perimetry Can help in decision regarding treatment of ocular hypertension Outer retinal damage to rods and blue cones detected by dark adapted flash/light adapted flicker ERG

NEGATIVE ERG
a-wave is larger than the b-wave in scotopic maximal response

Diseases sparing the photoreceptors and involving the middle retinal layers

Congenital stationary blindness X linked retinoshisis Central retinal artery obstruction Quinine toxicity Melanoma associated retinopathy Batten disease Cone Rod dystrophy

Completely extinguished ERG

Leber's congenital amaurosis Severe retinitis pigmentosa Retinal aplasia Total detachment of retina Ophthalmic artery occlusion

Thank you!

L V Prasad Eye Institute

[Link]

Excellenc

Equity

Efficiency

 The Electroretinogram in Diabetic Retinopathy

R. Tzekov, MD, PhD, Surv Ophthalmol 44:5360, 1999.

Electroretinography (ERG) is an objective method of evaluating retinal function. Since its introduction to clinical practice in the 1940s, it has become a useful and routine diagnostic clinical tool in ophthalmology. This review summarizes the role of ERG as a clinical technique for evaluating the progression of diabetic retinopathy and as a research tool for increasing our understanding of the pathophysiology of diabetic retinopathy

 . Most studies show unequivocally that the different types of ERG tests detect local abnormalities or widespread pathology, even in very early stages of the disease. It seems plausible that measurements from ERG recordings, particularly the oscillatory potentials, may be useful for predicting progression from nonproliferative to the more sight-threatening stagespreproliferative or proliferativeof diabetic retinopathy. Some recent work implies that the ERG can also be a useful diagnostic method for discriminating between eyes with diabetic retinopathy and those without the condition. (

NO CLINICALLY APPARRENT RETINOPATHY

most consistent alteration is a significant increase in the OP1 implicit time. Increase in implicit time of OP1 occurs in almost all the stage 0 cases (i.e., not only before ophthalmoscopic changes are apparent, but also before fluorescein angiography and vitreous fluorophotometry changes can be seen). Significant reduction of scotopic b-wave amplitude has also been found in children with insulindependent diabetes mellitus who have no diabetic retinopathy detectable on fluorescein angiography.

MILD AND MODERATE NONPROLIFERATIVE DIABETIC RETINOPATHY Virtually all studies using OPs report distinctive
changes in cases with mild NPRD (Table 1). Recently, more detailed studies have revealed that several ERG parameters can be affected in cases of mild NPDR: scotopic b-wave implicit times, 30-Hz flicker amplitude and implicit times, OP amplitudes to both blue and white flashes (including selective reduction of OP3 and OP2), OP implicit times, and photopic ERG implicit times.

 Oscillatory potential amplitudes correlate well with the severity of diabetic retinopathy. The few studies published to date that include patients with severe NPDR showed significantly reduced and sometimes absent Ops.

SEVERE AND VERY SEVERE NONPROLIFERATIVE DIABETIC RETINOPATHY

 in all ERG parameters, including decrease of the OP amplitude (up to complete disappearance of the OPs) or delay of the implicit time of the OPs (Table 1), decrease of photopic and scotopic a- and b-waves, and 30-Hz flicker delay.

EARLY AND HIGH-RISK PROLIFERATIVE DIABETIC RETINOPATHY Significant abnormalities have been reported

Other changes
The amplitudes of N1 and P1 in 1 2 rings were decreased dramatically in patients with CSME.

The dramatic decrease of visual function was shown by the reduced visual acuity, subjectively, and the decreased average amplitudes of mfERG, objectively. It is suggested that the slight damage of outer retina may cause the decreased amplitude and that the more severe damage of the full-thickness retina could lead to further decrease in the amplitude.

 The Multi focal-ERG reveals local retinal dysfunction in diabetic eyes even before retinopathy. The magnitude of delay of local ERG implicit time reflects the degree of local clinical abnormality in eyes with retinopathy. Local response delays found in some eyes without retinopathy suggest that the Multifocal-ERG detects subclinical local retinal dysfunction in diabetes. Analysis of Multifocal-ERG implicit time, independent of amplitude, improves the sensitivity of detection of local retinal dysfunction in diabetes.
Brad Fortune et al Investigative Ophthalmology and Visual Science. 1999

 Palmowski et al. demonstrated that in some patients with diabetes, M-ERG responses (averaged across relatively large areas of retina) were smaller in amplitude and delayed in comparison with those in normal subjects. However, they did not determine the extent to which local abnormalities were detected (versus abnormalities present throughout the retina).

RPC Thesis Dr. Thirumalesah

As a cross sectional ,Multifocal electro retinogram shall be used to study the macular changes in diabetics so as to establish pattern to predict early changes of retinopathy Compare the predictability of Multifocal ERG with the already existing standard OCT, so as to standardize the patterns

Review of literature
The implicit times of P1 and OPs were significantly delayed in the diabetics in the peripheral tested regions (2040) but not in the central area. After PRP, the amplitudes of P1 were markedly reduced in all areas tested; however, the changes of the P1 implicit time were not significant. The amplitudes of the OPs were significantly reduced in the peripheral regions after PRP; however, the changes in the implicit times were not significant. Retinal function in the posterior pole is markedly impaired in eyes with pre-PDR. PRP altered the mfERGs significantly, however, the reductions were limited to the amplitude.
Onozu H. et al Documenta Ohthalmologica , Volume 106, Number 3, May 2003

Full-field ERG,multifocal ERG and multifocal VEP in patients with retinitis pigmentosa and residual central visual fields Purpose: To evaluate (with three different electrophysiological methods) the residual retinal function in a selected group of patients with retinitis pigmentosa and remaining small central visual fields . Methods: Fourteen patients from several different genetic subgroups, who had been followed with visual acuity and visual field testing for periods up to 32 years,

were examined. Ophthalmological examination included full-field electroretinography (ERG), multifocal electroretinography (mfERG) and multifocal visual evoked potential (mfVEP). Results: The ERGs were severely reduced in all patients. The mfERGs demonstrated the residual central retinal function in five of the patients. The mfVEPs showed measurable amplitudes centrally in most of the patients. The follow-up

examinations demonstrated the slowly progressive course of the disease with preservation or only slight further loss of visual fields over a period of 732 years. Conclusion: Patients with retinitis pigmentosa may not always follow the typical natural course with progressive loss of visual fields, which may in some patients remain unaffected over several decades Multifocal ERG and mfVEP may be clinically useful for evaluating remaining visual function in these patients
Acta Ophthalmol. Scand. 2004: 82: 701706

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