Full field electroretinogram

full field erg

1. full field Electroretinogram By Smriti Ranabhat M. Optom TIO

2. BACK IN TIME First described by Prof. E. D. Reymond who showed that cornea is electrically positive with respect to posterior pole of eye. In 1908 Einthoven & Jolly showed that a triphasic response could be produced by simple flash of light on retina .

3. ELECTRORETINOGRAM ERG is the corneal measure of an action potential produced by the retina when it is stimulated by light of adequate intensity. It is the composite of electrical activity from the photoreceptors, Muller cells & RPE

4. Anatomy and physioloigy The retina is organized into 10 layers comprising various cell types and synaptic connections important for visual processing . The primary role of the photoreceptors is to convert light energy into an electrical signal ( phototransduction ). The photoreceptors transmit visual information to second-order neurons known as bipolar cells in the middle retina . Rods synapse only with depolarizing bipolar cells, while cones synapse with both depolarizing and hyperpolarizing bipolar cells . The ganglion cells ultimately transmit this electrical information to the brain via the optic nerve. The ratio of rods to cones in the retina is 3:1. These photoreceptors also vary in spectral characteristics, including signal threshold, peak wavelength sensitivity, and rate of recovery.

5. Types of electroretinogram

6. FULL FIELD ELECTRORETINOGRAM ERG is the record of an action potential produced by the retina when it is stimulated by light of adequate intensity. A small part of the current escapes from the cornea, where it can be recorded as a voltage drop across the extracellular resistance, the ERG. The full-field electroretinogram ( ffERG ) is an test that provides non-invasive objective quantitative measures of the electrical activity in the retina. The ffERG represents an electrical response from the retina to a flash of light and measures global retinal function .

7. Recording signals from retina Full field electroretinogram measures ; Mass response of retinal cells to a light stimulation Electrical response in the retina occurs due to light induced changes Measured by placing electrodes These signals are very small µV( even after amplification)

8. Indications The ffERG is a specialized test beyond standard ophthalmologic examination. Electrophysiologic testing may be indicated in the following scenarios : Diagnose and follow optic nerve and retinal diseases Monitor retinal disease from toxic drug exposure Assess intraocular inflammation Evaluation of the construct of intraocular foreign bodies Evaluation of retinal vascular occlusions and associated ischemic damage Evaluation of malingering or hysteria

9. indications Aids in diagnosis of stationary or progressive inherited retinal disorders Asess patients with retinal toxicity due to metallosis ( Siderosis ) Asess retinal toxicity to medication Document therapeutic effect of surgery or medication ERG results are normal unless more than 20 % retina is affected

10. contraindications There are no specific contraindications for the ffERG .

11. Waveform components a-wave The a-wave is the initial negative deflection corresponding to the early hyperpolarization of the rod and cone photoreceptors. This wave-component reflects outer retinal function. b-wave The b-wave is the positive deflection following the a-wave that originates from the depolarization of inner retinal Muller and bipolar cells. This wave-component reflects phototransduction activity .

12. Oscillatory potentials Oscillatory potentials (OPs) are high-frequency rhythmic wavelets seen on the rising slope of the b-wave. OPs are visible at greater signal intensities and reflect the electrical activity of inner retinal feedback synaptic circuits, namely amacrine cells, as well as some vascular function. Photopic negative response The photopic negative response ( PhNR ) is the light-adapted, negative deflection that follows the b-wave. It originates from the retinal ganglion cells in response to a brief flash.

13. Waveform analysis Amplitude The amplitude is the maximal light-induced electrical response (voltage) generated by the various retinal cells. Implicit time Implicit time (time-to-peak) refers to the time needed for the electrical response to reach maximum amplitude. Latency Latency is the time from stimulus onset to response onset, as opposed to the peak of the response (i.e., implicit time). The b-wave to a-wave ratio The ratio of the b- to a-wave amplitudes provides an index of inner to outer retinal function .

14. We need ; Light stimulation Calibrated stimulus Electrodes Amplifier and signal averager Display monitor and printer

15. Light stimulation for ERG Several methods of stimulating the eye; Strobe lamp and LEDs that is mobile and can be easily placed in front of a person whether sitting or reclining Ganzfeld (globe) with a chin rest and fixation points ( german word –whole field) Grass xenon arc photostimulator Ganzfeld allows the best control of background illumination and stimulus flash intensity and fixation lights. Large diameter ( 40 cm ) hemispheric dome with xenon stroboscopic light bulb placed at the top of the dome.

16. stimuli Full field stimulators and light diffusion Ganz Feld provides dispersed light and uniform luminance over the maximal area of retina. A central fixation spot should be provided . Stimulators should allow observation of the patient to monitor fixation and other factors that may influence recordings e.g., electrode position, eye closure,eye , face and head movements . Ganzfeld stimulators may be large enough to stimulate both eyes simultaneously for two channel recordings, or a small (mini) ganzfeld can be used for sequential stimulation of each eye For sequential testing care is needed during stimulation to ensure that light is excluded from the opposite eye.

17. Stimulus duration shorter than integration time of photoreceptor < 5 ms Stimulus wavelength Flashes and background should be visibly white Historically, light stimuli specified by ISCEV were generated by xenon flashtube, superseded by light emitting diode ( LED)technology . Stimulus strength and unit Stimulators should be capable of flashes over a minimum range of 3 log units in strength, in steps of not more than 0.3 log units. Background luminance for light adaptation and LA ERG testing is specified in candelas per meter squared ( cd.m-2) Flash stimuli in units of candela-seconds per meter squared ( cd.s.m-2) Nomenclature Stimulus and background callibration

18. electrodes Important features of ERG recording electrodes include 1. Quality components with low intrinsic noise levels, which facilitate stability of responses 2. Patient tolerance, with limited irritation of the corneal surface 3. Availability at a reasonable cost Ground electrode – Forehead \ Earlobe\ Mastoid connected to ground input Reference electrode -Outer canthus or zygomatic fossae, connected to – input of recording system Active electrode- Cornea( contact lens electrode) in flash ERG - Conjunctival sac in pattern ERG or skin on lower eyelid, connected to + terminal

19. CORNEAL ELECTRODES Hard contact lenses that covers sclera such as- Burian allen electrode Doran gold contact lens Jet electrode (disposable ) FILAMENT TYPE DTL fibre electrode(Dawson-trick- Litzkow ) HK loop electrode Gold foil electrode

20. ELECTRODE CLEANING Recording ERGs involves the exposure of corneal electrodes to tears, and there is potential exposure of skin electrodes to blood if there is any break in the surface of the skin . Reusable electrodes must be cleaned and sterilized after each use to prevent transmission of infectious agents . The cleaning protocol should follow manufacturers’ recommendations and meet current local and national requirements for devices that contact skin and tears Impedance should be less than 5 kohm In the absence of light stimulation and eye movement, the baseline voltage should be stable

21. Recording and amplification The elicited response is then recorded from the anterior corneal surface by the contact lens electrode The signal is then channeled through consecutive devices for pre-amplification, amplification & finally display .

22. Real time display The ongoing recordings should be displayed during testing so that the operator can continuously monitor technical quality and stability, and make adjustments as necessary. Recording and storing ERG data Digital records of all ERGs should be stored. Ideally, these should be records of individual ERG waveforms rather than averages only, which may be distorted by artefact . Averaging Averaging may be essential to identify and measure pathologic ERGs of low amplitude or ERGs recorded from electrodes on the lower eyelid. Artefact rejection must be a part of any averaging system

23. Reading protocol

24. Pre exposure to light – FFA,Fundus photos avoided, OCT , imaging avoided 30 min recovery time if exposed DA -20 min LA- 10 min Fixation Looking at the fixation point Eye movements alters electrode position Straight ahead and steady eyes if cant see fixation point For non contact electrode gentle blinking before each flash may reduce artefacts Pupillary dilation and retinal illumination

25. Iscev standard erg protocol International society for clinical electrophysiology of vision Standardized the protocols for preforming electrophysiological tests (1989)

26. Dark adapted 0.01 ERG Rod driven response of bipolar cells ,a – rods b- bipolar Dark adapted 3 ERG Combined rod- cone response arising from bipolar cells and photoreceptors a –rod+ cone , b –bipolar Rod dominated Daark adapted Oscillatory potentials Responses primarily from amacrine cells Dark adapted 10 ERG Combined response with enhanced a wave reflecting photoreceptor function Light adapted 3 ERG Cone driven response of bipolar cells a- cone , b- bipolar cells Light adapted 30 Hz flicker ERG Sensitive cone pathway driven response a- cone

27. Dark adapted 0.01 erg (isolated rod response IRR) Minimum 20 minutes dark adaptation Phot 0.01cd.s.m2 or scot 0.025 cd.s.m2 Retina stimulated with dim flashlight of 2.5 log units\ 24 db Flash white or blue Resultant waveform has prominent b(positive) wave but no detectable a (negative)wave Minimum 2 secs interval between flashes

28. Dark adapted 3 ERG MAXIMAL COMBINED RESPONSE (MCR) Directly following 0.01 ERG Response produced by combination of rods and cones Large a wave and b wave amplitude OPs on b wave 10 secs interval between stimuli ( to remove effect of bleach) Phot 3cd.s. m2, scot 7.5cd.s.m2

29. Dark adapted 10 ERG Combined with enhanced a wave for photoreceptor function DA 10 a- wave is larger having shorter peak time consistent with greater rod photoreceptor contribution Interval of 20 secs between stimulus Enhanced OP compared to DA3 ERG b-wave to a-wave amplitude ratio smaller than for the DA 3 stimulus phot 10 cd.s.m2, scot 25cd.s.m2 DA10 ERG maybe more informative than ERGs to dim flashes in patients with opaque media, small pupils or immature retinae

30. DARK ADAPTED Op Generated by amacrine cells can be measured using both 3 or 10 cd.s.m2 flash stimuli On ascending limb of b wave of maximal combined response Other wavelets removed by resetting of filter to eliminate lower frequencies from dark adapted 3 ERG Band pass filter on amplifier set between 75 to 300 Hz to get these wavelets Sensitive to ischaemia in localized retinal areas.

31. Light adapted 3 ERG (Single flash erg) 10 min light adaptation Measure of cone system Phot. 3 cd.s . m2 stimuli 0.5 sec interval between successive flashes on light adapting background luminance 30 cd/m2 Has smaller a –wave and b –wave

32. Light adapted 3 flicker ERG Repetitive stimuli flickered at rate 30 Hz superimpose on light adapting background luminance 30 cd\m2 Rod theoretically respond to stimulus up to 20 HZ so screens out –gives Cone activity Interval of stimulus > 5 ms A flash presented close to 30Hz, superimposed on a light-adapting G enerated largely by cone On- and Off bipolar cells D ependent on the function of the long- and medium- wavelength sensitive cones (M- and L- cones)

33. Other factors affecting ERG Light stimulus Drugs Retinal development Media clarity Age , sex and refractive error Anesthesia Diurnal fluctuation

34. Analysis and reporting Amplitude a wave measured from the baseline to the trough of a-wave. b wave measured from the trough of a-wave to the peak of b-wave. Time sequences Latency : - Time interval b/w onset of stimulus & the beginning of the a-wave response. Normally it’s 2 ms. Implicit time:- time from the onset of light stimulus until the maximum a-wave or b-wave response. Considering only a-wave and b-wave response the duration of ERG is less than 1/4 s

35. I n single flash erg The peak times will depend on flash duration if measured from the beginning of the stimulus flash. S mall effect when the stimulus duration is less than a millisecond and can be ignored, for example , when stimuli are generated by a xenon flashtube. For longer flashes of up to 5 ms , such as those generated by LEDs, the time to peak should be measured from the midpoint of the flash, or half the flash duration subtracted from the peak time, to compensate. There are typically three main positive OP peaks , often followed by a fourth peak that is smaller. For routine applications, the presence and waveform of the OP peaks and their normality relative to appropriate reference data may be adequate for most clinical applications . Quantification is optional, but if used must specify the filter characteristics and measurement methods e.g. individual peak amplitudes measured from their preceding troughs or a sum of amplitudes of specified peaks .

36. The response to the initial onset of the flicker , which may resemble a single-flash ERG, should always be excluded. The peak time of the flicker ERG is measured from the midpoint of the stimulus flash to the following peak (avoiding the initial waveform). Abnormality of waveform shape should be described (e.g. a double-peak waveform), and the components that are measured clearly identified.

37. Analysis and reporting Each laboratory should have its own normative values for the equipment Rods more affected Cones more affected Both rods and cones affected Negative waveform

38. Normal ERG Localized macular dysfunction Optic nerve disease Central nervous system disease as amblyopia

39. Subnormal ERG Amplitude of all components are reduced approximately to same degree Early stages of rod cone dystrophy PRP for diabetic retinopathy (b/a ratio normal ) Vitreous hemorrhage (ERG+ USG) can be used in differentiation of TRD and dense vitreous SF6 and silicone oil Partial or sectoral retinal detachment

40. Negative ERG Amplitude of b wave smaller than that of a wave b\a ratio < 1 Normal a wave with reduced b wave – defect to post synaptic phototransduction process Negative erg is useful prognostic and diagnostic value in retinal disease CRAO , CRVO

41. EXTINCT ERG Advanced stage of rod cone dystrophy RP TRD Gyrate atrophy Choroidermia Ophthalmic artery occlusion Retinal aplasia Even when macular area is preserved ERG may become undetectable.

42. Diffuse photoreceptor dystrophy

43. retinitis pigmentosa ok

44. Associations to RP Lawerence -moon- biedl syndrome Usher syndrome Refsums syndrome Pigment in retina is prominent in many infectious disease . Early stages of rubella and syphilis can mimic fundus appearance of RP. ERG is normal or slightly subnormal in this infectious disease.

45. Early receptor potential in RP In a study small ERP amplitudes in the affected boy and the carrier women with sex-linked retinitis pigmentosa less than 20 % of normal reduction in affected , 50 % reduction in carrier defect exists in the outer segments of the photoreceptors Decreased amplitude may be due to decrease in visual pigment concerntration , no. of photoreceptor, disorientation of outer segment membranes . carrier females had rapid ERP recovery during dark adaptation suggesting that the cone visual pigments generate much of this response.

46. Cone-rod dystrophy Patients with cone-rod dystrophy typically show reduced visual acuity, color vision deficits, visual field impairment (including central or paracentral scotomas, midperipheral partial or complete ring scotomas, or peripheral restriction), and reduced ERG- cone and rod amplitudes Cone-rod dystrophy is a genetically heterogeneous condition, with autosomal dominant, autosomal recessive, and X- Iinked recessive modes of transmission occurring.

47. Stationary cone dysfunction disorders

48. Congenital achromatopsia

49. Stationary night blinding disorders

50. Congenital stationary night blindness csnb

51. Oguchis disease Rod receptor dysfunction AR Photopic normal , scotopic decrease in amplitude - ve ERG with high luminance Yellow phosphorescent discoloration in peripheral retina

52. Fundus albipunctatus Presence of numerous discrete dull-white spots scattered throughout the fundus , with the exception of the fovea C one and rod adaptations follow a prolonged time course of variable severity, ranging , for the rods, from approximately 45 min to several hours. Mutations in a gene encoding ll -cis retinol dehydrogenase Reduced activity of this enzyme would appear to account for the delay in regeneration of cone and rod visual pigments observed in this disease Rod ERG absent after 30 min dark adaptation Normal after 3 hours of dark adaptation Combined response – ve after 30 mins normal after 3 hours

53. Hereditary macular dystrophy

54. Stargardt macular dystrophy Full field ERG is normal except at very late stage where it becomes subnormal Macular multifocal is dramatically abnormal

55. BEST MACULAR DYSTROPHY ERG cone and rod a- and b-wave amplitudes are typically normal in patients with Best vitelliform macular dystrophy.

56. Cone dystrophy

57. Full field ERG is better for quantifying cone dystrophy Scotopic ERG is normal in appearance with slow implicit times .

58. Chorioretinal dystrophy

59. Choroidal atrophy AD, AR ERG is subnormal, becoming nondetectable with more advanced disease. Gyrate atrophy AR Patients are frequently myopic, and nearly all develop posterior subcapsular lens opacities ERG cone and rod amplitudes are usually either markedly reduced or non detectable Choroidermia R ecordings show a reduction of a- and bwave amplitudes under light- and dark adapted test conditions, with the prolongation of both rod and cone b-wave implicit times . X linked recessive

60. Hereditary vitreoretinal degeneration

61. X linked juvenile retinoschisis

62. Circulatory deficiency

63. Central retinal artery occlusion Decreased b-wave amplitude and diminished or nondetectable OPs accompany central retinal artery occlusion ( CRAO) A wave- choroidal blood supply to outer retina Inner retina supplied by CRA Negative wave can also be seen.

64. Central retinal venous occlusion Ischemic CRVO usually shows negative response than non ischemic For prognosis b/a ratio to be seen

65. In branch artery occlusion (BAO), there is generally either a slight b-wave reduction or a normal ERG response. Sickle cell retinopathy -ERG a-wave, b-wave, and OP amplitudes were found to be normal in the absence of peripheral retinal neovascularization and reduced in amplitude when peripheral retinal neovascularization was present. Carotid artery occlusion -ERG a- and b-wave amplitudes depends on the extent and severity of the occlusion, its location. -With occlusion of the internal carotid artery, a reduction in both a and b-wave amplitudes can be found. Ophthamic artery occlusion results in unrecorable ERG.

66. Toxic conditions

67. Chloroquine and hydroxy chloroquine If the changes are clinically apparent only in the macula, the ERG is usually normal or occasionally subnormal to a small degree. With more advanced and extensive disease, when peripheral pigmentary changes also become apparent, the ERG is usually moderately subnormal, while nondetectable or minimal responses are obtained in patients with advanced retinopathy . Multifocal ERG is best for drug toxicity.

68. The case of a 38-year-old man who, during the use of indomethacin, noted a deterioration of showed a reduced scotopic ERG b-wave amplitude . Quinine -Transient subnormal ERG response of both a and b-wave amplitudes is apparent if testing is done within the first 12 to 18 hours, -ERG is most frequently normal when recordings are obtained after 24 hours in acute quinine poisoning.

69. Vitamin a deficiency and retinoids S cotopic responses in patients with vitamin A deficiency. Subnormal-to-nondetectable responses were noted in patients with xerosis and night blindness. Reduction in ERG amplitudes most apparent under scotopic conditions with prolonged use of retinoids .

70. Optic nerve and ganglion cell disease Because the ganglion cells do not contribute to the flash-elicited full-field ERG response , an essentially normal ERG is obtained in most eyes blinded by glaucoma. ERG recordings have been reported in patients with optic nerve hypoplasia. The majority of these patients showed normal photopic and scotopic ERG amplitudes.

71. Opaque lens or vitreous Dense lens opacities can reduce the ERG a- and b-wave amplitudes. When present , the amplitude decrease is associated with a comparable increase in implicit time , relating to the resultant decrease in effective stimulus intensity. Lens opacities do not appear to modify the OPs . With longstanding vitreous hemorrhages, a marked reduction of ERG amplitudes is always possible because of the ever-present threat of siderotic changes occurring within the retina secondary to blood-breakdown products.

72. DIABETIC RETINOPATHY The most frequently reported ERG abnormalities in patients with diabetic retinopathy include a reduction in b-wave amplitude and a reduction or absence of Ops Reduced OP amplitudes have been noted at early stages of retinopathy, when ERG a- and b-wave amplitudes are normal, while delayed OP implicit times have been reported as an early functional abnormality in eyes with mild or even no retinopathy.

73. If PDR is present with vitreous hemorrhage, it is difficult to predict outcome after vitrectomy . Having undergone PRP ERG , amplitude decreases b/a ratio is normal b/a ratio provides useful prognosis after Vitrectomy.

74. The amplitudes of both a- and b-waves are related to the degree of retinal detachment . Karpe and Rendahl have reported subnormal ERG values in the normal eye when the contralateral eye has a retinal detachment. Extinguished ERG in TRD Retinal detachment

75. Silicone oil and sulfurhexafluride gas In the early postoperative period, a reduction of both a- and b-wave amplitudes which recovers later. Because resistance of vitreous increases by several folds causing reduction in current. Hyperthyroidism – thyrotoxic exopthalmus Supernormal ERG response due to increased bioelectrical activity Myxedema – subnormal response Parkinson disease - subnormal scotopic and photopic response Myopia- direct correlation between the amplitude of the b-wave and the degree myopia , with patients who have approximately 7 diopters or more of myopia already manifesting subnormal b-wave amplitudes In absence of degenerative myopic fundus normal ERG With degenerative myopic fundus -75% have subnormal ERG 25% have normal ERG pattern in patients with myopia is either negative or markedly reduced in amplitude , the myopia may be associated with an inherited retinal disorder like CSNB or RP.

76. Erg in myopia Several studies have shown that ERG amplitudes are inversely proportional to axial length. While all myopic eyes had a- to b-wave amplitude ratios that were within normal limits despite generalized amplitude reductions , hypermetropic eyes had a- to b-wave amplitude ratios that were either subnormal, normal, or hypernormal

77. ERG IN MULTIPLE SCLEROSIS AND DEMYELINATING OPTIC NEURITIS Decreased b wave amplitude in the affected eye. These results provide neurophysiological evidence that retinal damage is not due to loss of myelin but is an early feature of demyelinating optic neuritis. This damage preferentially affects the retinal elements associated with the generation of the 'b' wave of the ERG, probably the glial cells of Müller.

78. Intra ocular foreign body The time and rate of ERG changes associated with the retention of an intraocular foreign body depend on 1. The nature of the metal (its alloy content ) 2. The degree of encapsulation 3. The size and location of the particle 4. The duration within the eye Iron and copper affect rapidly whereas aluminum doesn’t When metal is in anterior segment or lens there is no significant change in ERG response. The ERG changes induced by the foreign body pass through the stages of a transient supernormal response, a negative positive response, a negative-negative response , and, finally, a no detectable response.

79. Photopic negative response The photopic negative response ( PhNR ) is a negative going wave seen after the b-wave in a brief-flash photopic (cone) ERG. PhNR , particularly when elicited by a red flash on a rod saturating blue background, is believed to originate primarily from retinal ganglion cells (RGCs ). When a long-duration flash is used the PhNR is seen once after the b-wave ( PhNR -ON) and again as a negative going wave after the d-wave ( PhNR -OFF). The PhNR -ON and PhNR -OFF are thought to reflect the activity of the ON- and OFF-RGC pathways respectively.

80. S tudies attempting to correlate PhNR amplitude loss with structural or functional losses in the RGC complex and/or nerve fiber layer show that central RGC losses produce significant amplitude losses in the focal PhNR , but not always in the full-field PhNR . On the other hand, diffuse or peripheral RGC losses show more prominent attenuation of the full-field PhNR amplitude. Despite the fact that the full field and focal PhNR are being used clinically in the diagnosis and monitoring of glaucoma and other diseases the assumption that a given reduction in PhNR amplitude corresponds with a similar reduction in RGC cell count is questionable.

81. Extinguishedd ERG Supranormal ERG Subnormal ERG Negative response Attenuated OP s TRD Siderosis bulbi Hypothyroidism CRAO CRVO CRAO , CRVO Retinal aplasia Hyperthyroidism Chloroquine Retinoschisis Diabetic retinopathy Severe RP Oguchi CSR Lebers congenital amaurosis Hypertensive retinopathy Ophthalmic artery occlusion

82. references Electrophysiological testing in disorders of retina, optic nerve , visual pathway , 2 nd edition ISCEV guides to visual electro diagnostic procedures Various internet sources