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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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Presentation on theme: "Functional Testing of the Eye: Clinical Electrophysiology of Vision Matthew L. Severns, Ph.D. LKC Technologies, Inc. USA."— Presentation transcript:

1 Functional Testing of the Eye: Clinical Electrophysiology of Vision Matthew L. Severns, Ph.D. LKC Technologies, Inc. USA

2 Electrophysiology and Psychophysics Electrophysiology tests record the electrical responses generated by the eyes or visual cortex Psychophysical tests measure the patient’s responses through mental process and behavior Both are functional tests, but electrophysiology is objective and psychophysics is subjective We will focus on electrophysiology tests

3 Common Visual Electrodiagnostic Tests ERG (Electroretinogram) –Ganzfeld –Pattern –Multifocal EOG (Electro-oculogram) VEP/VER (Visual Evoked Potential/Response) –Pattern –Flash

4 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

5 Recording Electrode Amp. Reference Electrode Computer Ear Ground Electrode ERG Recording Setup Ganzfeld Dome ERG Response

6 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) B-Wave A-Wave

7 Anatomy of the Retina

8 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

9 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 13:1, scotopic B-wave is a measure of the response from the Rod system, especially for dim flash

10 Dilate the pupil with mydriatic to maximize the light entering the eye and minimize the interference from pupil contraction Dark adapt > 25 minutes to maximize the rod responsiveness Connect the electrodes: –Corneal electrodes on eyes –Reference electrode on forehead –Ground on ear ERG: Test Procedure

11 ERG: Recording Electrodes ERG-Jet Burian-Allen DTL Commonly used corneal electrodes:

12 ISCEV ERG Protocol: Step #1 “Rod 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

13 ISCEV ERG Protocol: Step #2 “Maximal 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

14 Filtered ERG Unfiltered ERG ICSEV ERG Protocol: Step #3 “Oscillatory 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 LKC software provides automatic analysis of Oscillatory Potentials

15 ICSEV ERG Protocol: Step #4 “Cone Response” The patient is exposed to background light (30 cd/m 2 ) 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

16 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 ICSEV ERG Protocol: Step #5 “Flicker Response” LKC software provides automatic analysis of Flicker ERG

17 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 ERG: Clinical Applications

18 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

19 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

20 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

21 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

22 EOG Testing: First Steps Connect electrodes to inner and outer canthii: Patient looks side to side at alternating lights LKC system automatically measures the potentials, and analyzes EOG data Pupil dilation and dark adaptation are not required for EOG test EOG electrodes

23 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

24 EOG: A Normal Recording Arden Ratio: Light / Dark > 2.0 is OK

25 EOG: Clinical Applications Most commonly used in Best’s Disease (Best’s 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)

26 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

27 VEP: Electrode Placement Recording Electrode Ground Electrode Reference Electrode Computer Amp.

28 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

29 Pattern VEP: A Normal Recording P100 (  100 ms)

30 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

31 Flash VEP: Applications Assessing visual function behind media opacities Surgical monitoring –Intraorbital surgery with risk for optic nerve damage –Endoscopic sinus surgery

32 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

33 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 amplitudes are automatically meas- ured, and the estimated acuity is determined by the user selection of valid data points VEP Amplitude Phase Small GratingLarge Grating Amplitude = 0 : No response = visual acuity! VEP Amplitude vs. Grating Width

34 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 baby’s attention Average several sweeps for best results. –5 to 10 sweeps may be needed for a good result Select proper points for analysis

35 Sweep VEP: A Typical Recording Larger StripesSmaller Stripes

36 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.

37 MFERG: The Concept Recording Electrode Amp. Reference Electrode Computer Ear Ground Electrode Stimulus on high- quality video monitor

38 MFERG: The Individual Response and 3-Dimensional Display Blind spot Foveal peak 3D display of ERG response densityFocal ERG from each retina area

39 MFERG: Map And Focal Analyze summarized ERG responses from different regions Analyze the overall response from the central retina area of 50 - 60 0 view angle

40 MFERG: Recording Procedure Dilate patient’s 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

41 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

42 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.

43 Thank You! LKC Technologies, Inc. 2 Professional Drive Gaithersburg, MD 20879 USA Tel.: +1-301-840-1992 Website:

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