Electrophysiology (ERG and EOG) Simplified........

Simplifying ERG and EOG....... A topic seldom touched by ophthalmologists due to its apparent complexity !!

1. ELECTRORETINOGRAPHY (ERG) & ELECTROOCULOGRAPHY (EOG) Dr Sumeet Agrawal Vitreo-Retina Fellow Narayana Nethralaya Bangalor e

2. OVERVIEW INTRODUCTION HISTORY RELEVANT ANATOMY AND PHYSIOLOGY INDICATIONS PERFORMING THE TESTS INTERPRETATION EXAMPLES CLINICAL SCENARIOS PEARLS AND PITFALLS

3. ELECTRORETINOGRAPHY

4. INTRODUCTION Electrophysiological test Functional status of retina Potential change that is related to light-induced electrical activity within the retina Full field ERG is a mass response of the retina to light stimulus

5. HISTORY 1865 : First known recording of an ERG (amphibian retina) Swedish physiologist Alarik Frithiof 1877 : Holmgren, James Dewar of Scotland (humans) 1908 : Einthoven and Jolly separated the ERG response into three components: a-wave, b-wave and c-wave 1941 : American psychologist Lorin Riggs introduced the contact-lens electrode (clinical use) 1967 : Ragnar Granit Nobel Prize for Physiology and Medicine (demonstrated the physiology of the receptor potential of each component of the ERG) 1989 : ISCEV standards 1992 : Erich Sutter mfERG

6. ANATOMY AND PHYSIOLOGY Cones maximally concentrated at the fovea But 90% cones located outside the fovea Rods maximum at 15 degrees from fixation

7. EYEBALL ACTS AS A DIPOLE

8. STEP 1 OPSIN ACTIVATION STEP 2 OPSIN ACTIVATES TRANSDUCIN WHICH ACTIVATES PDE STEP 3 CYCLIC GMP DECLINES ; GATED Na+ Channels CLOSE STEP 4 RATE OF NEUROTRANSMITTER DECLINES

9. a wave from photoreceptors

10. b wave Bipolar cells and the Muller cells. Muller cells response extracellular K+ concentration K+ released from photorecptors Muller cell respond by changing its membrane potential From either cone or rod receptors c wave Positive wave Reflects function of pigment epithelium in response to rod signals only

11. PHOTOPIC NEGATIVE RESPONSE (PhNR) In flash erg Phnr is the negative wave following the “b” wave Amplitude of phnr is measured from the baseline to the trough of the negative wave This wave is believed to originate from the ganglion cell layer of the retina and is earliest affected in glaucoma and appears before visual field defects

12. TYPES OF ERG FULL FIELD ERG FOCAL ERG MULTIFOCAL ERG PATTERN ERG

13. ISCEV International Society for Clinical Electrophysiology of Vision Standardised the protocols for performing electrophysiological tests (1989) Ensures uniformity and thus comparability between labs

14. 1 Dark-adapted 0.01 ERG A rod-driven response of bipolar cells 2 Dark-adapted 3 ERG Combined responses arising from photoreceptors and bipolar cells of both the rod and cone systems ; rod dominated 3 Dark-adapted 3 oscillatory potentials Responses primarily from amacrine cells 4 Dark- adapted 10 ERG Combined response with enhanced a-waves reflecting photoreceptor function 5 Light-adapted 3 ERG A cone-driven response of bipolar cells 6 Light- adapted 30 Hz flicker ERG A sensitive cone-pathway -driven response McCulloch, Daphne L., et al. "ISCEV Standard for full-field clinical electroretinography (2015 update)." Documenta Ophthalmologica 130.1 (2015): 1-12.

15. McCulloch, Daphne L., et al. "ISCEV Standard for full-field clinical electroretinography (2015 update)." Documenta Ophthalmologica 130.1 (2015): 1-12.

16. Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section 2, Chapter 8. Page 202-25.

17. McCulloch, Daphne L., et al. "ISCEV Standard for full-field clinical electroretinography (2015 update)." Documenta Ophthalmologica 130.1 (2015): 1-12.

18. PERFORMING THE TESTS Dark room with non-reflecting walls Preparation of the patient Pupillary dilatation Pre-adaptation to light or dark 20 min dark adaptation 10 min light adaptation Pre-exposure to light FFA, Fundus photography should be avoided Fixation Should not disturb dark adaptation Visible in light adapted state

19. ELECTRODES GROUND ELECTRODE – FOREHEAD REFERENCE ELECTRODE – OUTER CANTHUS ACTIVE ELECTRODE - Cornea (contact lens electrode) in flash ERG Conjunctival sac – used in pattern ERG

20. ELECTRODES

21. LIGHT STIMULUS FOR ERG stimulus and background light should be homogeneous and cover the entire retina Strobe lamp and LEDs - mobile and can be easily placed in front of a person whether sitting or reclining.

22. GANZFELD STIMULATION GLOBE The Ganzfeld allows the best control of background illumination and stimulus flash intensity. Large ­diameter (40­cm) hemispheric dome with a xenon stroboscopic light bulb placed at the top of the dome.

23. DARK ADAPTED 0.01 ERG Minimum 20 min dark adaptation 0.010 photopic cd.s.m -2 ; 0.025 scotopic cd.s.m -2 Minimum 2 s interval between flashes Rod system response

24. DARK ADAPTED 3 ERG Directly following 0.01 ERG 3.0 photopic cd.s.m -2 and 7.5 scotopic cd.s.m -2 Minimum interval 10s

25. DARK ADAPTED 10 ERG 10 photopic cd.s.m -2 and 25 scotopic cd.s.m -2 Interval 20s Better defined a wave Enhanced oscillatory potentials Opaque media / immature retina

26. DARK ADAPTED 3 OSCILLATORY POTENTIALS Filtering out 75 Hz or less from the ERG waveform from dark adapted 3 ERG Taken from 2nd stimulus onwards

27. LIGHT ADAPTED 3 ERG 10 min light adaptation Back ground luminance : 30 photopic cd.s.m -2 and 75 scotopic cd.s.m -2 3.0 cd.s.m -2 stimuli with 0.5 s interval

28. LIGHT ADAPTED 30 Hz FLICKER ERG Same parameters as light adapted 3 ERG 28 to 33 Hz Diascard initial few responses

29. INTERPRETATION AMPLITUDE a-wave amplitude : baseline to the a-wave trough; b-wave amplitude : a-wave trough to the b-wave peak. TIME DELAY Implicit time (peak time) : onset of the stimulus to the trough of the a-wave or the peak of the b-wave Effect of stimulus duration

30. INTERPRETATION Each lab should have its own normal values Adjust for age

31. Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section 2, Chapter 8. Page 202-25.

32. a-wave; b-wave and Oscillatory potentials (OP) (b-wave usually larger than the a-wave)

33. Oscillatory Potentials Reduced amplitude time delay Both implies early diabetic retinopathy, retinal circulatory disturbances Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section 2, Chapter 8. Page 202-25.

34. SUBNORMAL ERG Reduced amplitude (proportional to area of functional retina) maintained ratio of a and b waves eg media opacities, following PRP Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section 2, Chapter 8. Page 202-25.

35. NEGATIVE ERG b-wave smaller than a-wave (b/a ratio < 1) Diagnostic value Prognostic value Central Retinal Vein Occlusion Proliferative diabetic retinopathy Endophthalmitis

36. NEGATIVE ERG b/a <1 Normal a-wave amplitude Subnormal a-wave amplitude Second order neuron abnormality Combined dysfunction of photorecep­tor and middle retinal layer Photopic hill phenomenon

37. NEGATIVE ERG Congenital Complete­ type congenital stationary night blindness (CSNB) Incomplete­ type CSNB X-­linked juvenile retinoschisis (XLRS), Juvenile­onset neu­ronal ceroid lipofuscinosis Infantile Refsum disease

38. CONGENITAL STATIONARY NIGHT BLINDNESS Complete and incomplete forms On and On-Off bipolar cell dysfunction

39. NEGATIVE ERG Acquired causes Autoimmune retinopathy Birdshot choroidopathy Ocular siderosis Quinine retinopathy

40. PROGNOSTIC VALUE OF NEGATIVE ERG Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section 2, Chapter 8. Page 202-25.

41. Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section 2, Chapter 8. Page 202-25.

42. IRON INTRAOCULAR FOREIGN BODY In general if b-wave amplitudes are reduced 50% or greater compared to the fellow eye, it is unlikely that the retinal physiology will recover unless the foreign body is removed.

43. The effects of toxic medications can be detected and quantified using ERGs. Chloroquine retinopathy appears as a characteristic “bullseye” maculopathy

44. EXTINCT ERG Advanced stage of rod– cone dystrophy, Retinitis pigmentosa G yrate atrophy Choroideremia Leber’s congenital amauorosis Autoimmune retinopathy Total retinal detachment Central retinal artery occlusion

45. ISOLATED CONE DYSFUNCTIONS Rod monochromacy Complete form Incomplete form Selectively decreased photopic responses

46. Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section 2, Chapter 8. Page 202-25.

47. ROD RECEPTOR DYSFUNCTION Oguchi disease Fundus albipunctatus

48. OGUCHI DISEASE Absent rod ERG Normal cone ERG Negative configuration of combined response; normal OP Photopic hill phenomenon Improvement after prolonged dark adaptation

49. FUNDUS ALBIPUNCTATUS Rod ERG absent after 30 min dark adaptation Normal after 3 hour dark adaptation Combined response : negative after 30 min, normal after 3 hours

50. Clinical Electrophysiology. M Yoka, S Kei. Retina (5th edition) Stephen J Ryan. Section 2, Chapter 8. Page 202-25.

51. ROD-CONE and CONE-ROD DYSTROPHIES

52. FACTORS AFFECTING 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.

53. MULTIFOCAL ERG Limitation of Full Field ERG - Unless 20% or more of the retina is affected with a diseased state the ERGs are usually normal Erich Sutter used binary m-sequences to extract hundreds of focal ERGs from a single electrical signal ERG activity in small areas of retina.

54. Small scotomas can be mapped and quantified. 61 or 103 focal ERG responses can be recorded from the cone-driven retina. 20-30 degrees to each side of the fovea

55. PATTERN ERG Measure of macular function and generalized bipolar cell function. Checkerboard stimulus composed of white and black squares Reduction of PERG amplitude reflect the reduced activity of dysfunctional RGCs Inner retinal activity under light-adaptation.

56. P rinciple : N et retinal illumination remains constant. Only a redistribution of the pattern of light and dark areas is made

57. 17” monitor from a distance of 1 meter and stimulus field is 15 °. 150 stimuli for signal averaging at a frequency of 1 pulse per second are used. Central fixation is necessary.

58. Should be used in combination with a traditional light-adapted luminance ERG to have an index of outer retina function Glaucoma, optic neuritis, ischemic optic neuropathy, and mitochondrial optic neuropathy Can help differentiate Macular from Optic nerve related pathologies

59. The normal pattern electroretinogram :   N35 - a small negative component with a peak time occurring around 35 ms; P50 - a prominent positive wave emerging around 50 ms N95 - a wide negative wave around 95 ms

60. Macular diseases:- The P50 component was shown to be altered in all patients with retinal and macular diseases. Optic nerve disease:- N95 component was abnormal in 81% of patients with diseases of the optic nerve. The P50 component remain normal.

61. ELECTRO-OCULOGRAPHY

62. ELECTRO-OCULOGRAPHY Outer retina and retinal pigment epithelium Change in the electrical potential between the cornea and the fundus successive periods of dark and light adaptation. Standing electrical potential between front and back, sometimes called the corneo-fundal potential

63. Mainly derived from the retinal pigment epithelium (RPE), response to retinal illumination The potential decreases for 8–10 min in darkness. Subsequent retinal illumination causes an initial fall in the standing potential, followed by a slow rise for 7–14 min (the light response). These phenomena arise from ion permeability changes across the basal RPE membrane.

64. Indirect measurement of the minimum amplitude of the standing potential in the dark and then again at its peak after the light rise. This is usually expressed as a ratio of ‘light peak to dark trough’ and referred to as the Arden ratio .

65. Calibration of the signal Gazing at consecutively at two different fixation points located at known angle apart and recording the concomitant EOGs . Skin electrodes on both sides of an eye the potential can measure the potential by having the subject move his or her eyes horizontally a set distance .

66. After training the patient in the eye movements, the lights are turned off. About every minute a sample of eye movement is taken as the patient is asked to look back and forth between the two lights . After 15 minutes the lights are turned on and the patient is again asked about once a minute to move his or her eyes back and forth for about 10 seconds.

67. Light switched off

68. Typically the voltage becomes a little smaller in the dark reaching its lowest potential after about 8-12 minutes, the so-called “dark trough”. When the lights are turned on the potential rises, the light rise, reaching its peak in about 10 minutes. When the size of the "light peak" is compared to the "dark trough" the relative size should be about 2:1 or greater . A light/dark ratio of less than about 1.7 is considered abnormal.

69. Most common use : to confirm Best’s vitelliform disease Clinical utility : Carriers ; end stage disease

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