Electro-physiology

1. Electro-physiology

2. Electro-oculogram (EOG) • Conventional electro-oculography (the EOG slow oscillation) records the light induced rise in ocular standing potential following a period of dark adaptation. This reflects the rise in the potential across the retinal pigment epithelium (RPE) resulting from the progressive depolarisation of the basal membrane of the RPE which occurs in response to light adaptation. The clinical value of the EOG, and a reliable method for its measurement, were developed in the early 1960s by Arden's group

3. Recording methods • To record the EOG, surface electrodes are positioned at the medial and outer canthi of each eye. After a short period of pre-adaptation, the patient, usually seated at a Ganzfeld bowl with two light emitting diodes (LEDs) to provide fixation lights, performs fixed excursion lateral eye movements of approximately 30 degrees for 15-20 minutes during dark adaptation. During this time the standing potential, reflected in the amplitude of the signal measured between the lateral and outer canthus electrodes in relation to the eye movements, will usually reach a minimum value, the Dark Trough. The background light of the Ganzfeld is then switched on to create a full-field photopic environment, and the patient continues to make the same lateral movements during light adaptation until the gradual increase in standing potential which occurs has reached a maximum, usually at 7-10 minutes - the Light Peak.

4. Normal results • The value of the amplitude of the Light Peak divided by the Dark Trough expressed as a percentage is known as the Arden index, and will be >170% in a normal subject. A normal EOG requires a normally functioning RPE and a normally functioning rod population with the retina in contact with the RPE.

5. Clinical uses • In most diseases an abnormality of the EOG light rise reflects demise or dysfunction of the (rod) photoreceptors, but can also indicate primary RPE disease. The EOG is of principal value in Best disease (vitelliform macular dystrophy), where loss of the EOG light rise is accompanied by a normal ERG; in most other diseases, loss of the EOG light rise is usually accompanied by an abnormal rod ERG.

6. Full field electroretinogram (ERG • The ERG measures the mass response of the whole retina, reflects photoreceptor and inner nuclear layer retinal function, and allows separate functional assessment of the photopic and scotopic systems

7. Full field electroretinogram (ERG) • The leading edge of the a-wave of the scotopic ERG arises from hyperpolarisation of the (rod) photoreceptors. The b-wave is probably generated by Muller cells in response to changes in extracellular potassium consequent upon depolarisation of the ON-bipolar cells. There is recent evidence that the hyperpolarising bipolar cells may have a role in "shaping" the photopic cone b-wave.

8. Recording methods • The ERG protocols now commonly adopted in most respectable laboratories include the recommendations by ISCEV, the ISCEV Standard ERG. This specifies the brightness of a "standard flash", and requires that the response to this flash (the mixed rod-cone maximal response), and to the same flash attenuated by 2.5 log units of neutral density filter (the scotopic rod response) be recorded under full dark adaptation, and that following light adaptation photopic transient and flicker ERGs be recorded. 30 Hz is usually used for the flicker ERG. In addition to the presence of a rod-saturating background in the Ganzfeld, the rods have poor temporal resolution and cannot respond to a 30 Hz flicker.

9. Clinical Uses • In general, diseases that affect photoreceptor function will cause a-wave reduction accompanied by reduction in the amplitude of the b-wave, whereas diseases that have a maximal effect post-phototransductionally will give a "negative" ERG, so called because the overall waveform is dominated by the negative a-wave and where there is relative loss of the post-receptorally derived b-wave. Generalised retinal degenerations, the retinitis pigmentosa (RP) type conditions, will tend to give overall reduction of the ERG usually accompanied by changes in implicit time. The ERG may be extinguished in severe disease. Restricted disease, such as sector RP or retinal detachment, will tend to give amplitude reduction but no change in implicit time. Causes of a "negative" ERG include: central retinal artery occlusion, where the a-wave sparing reflects the preservation of photoreceptor function due to intact choroidal circulation, X-linked retinoschisis, X-linked congenital stationary night blindness, quinine toxicity, melanoma associated retinopathy and others.

10. Pattern electroretinogram (PERG) • The pattern electroretinogram (PERG) assesses the retinal response to a structured non-luminance stimulus such as a reversing black and white checkerboard. It provides useful information in the distinction between optic nerve disease and macular disease in patients with poor central visual acuity. This recording has a much lower amplitude than the full-field ERG, and signal extraction using computer averaging is necessary.

11. Normal tracings • The PERG consists of two main components, P50 and N95, with N95 and much, but not all, of P50 probably arising in relation to central inner retina (ganglion cell). Analysis of the PERG concentrates on the latency and amplitude of P50, measured from the N35 trough, and the amplitude of N95 measured from the peak of P50.

12. Clinical uses • A normal P50 component suggests a normally functioning macula, and macular dysfunction will reduce or extinguish this component, usually with concomitant reduction or extinction of N95. Disease of the ganglion cells, either primary such as dominant optic atrophy (DOA), or secondary due to retrograde degeneration from an optic nerve insult, may result in specific loss of the N95 component with sparing of P50. This allows a distinction between optic nerve disease and macular disease. In severe optic nerve/ganglion cell disease, there will probably be involvement of the P50 component, but this will not be extinguished even if the pattern VEP is abolished.

13. Clinical uses • Furthermore, when taken in conjunction with the full-field ERG, the PERG permits a distinction between macular dystrophy and cone or cone-rod dystrophy in the patient with an abnormal macula on ophthalmoscopy; in disease confined to the macula the PERG is abnormal but the ERG is unaffected. It should be remembered that a normal retinal or macular appearance does not necessarily imply normal function. Although there has been only limited application of the PERG to date, it is possible that changes in the PERG may assist in the early detection of central dysfunction in patients with retinal dystrophy and normal visual acuity. This may have prognostic implications.

14. Visual evoked cortical potential (VEP or VECP) • Introduction • The VEP can be elicited by various stimuli, usually pattern reversal, pattern appearance or diffuse flash. Pattern appearance, also known as onset/offset is where a contrast pattern appears from a uniform background of identical mean luminance, is present for a short period, and then disappears. In clinical practice the reversing checkerboard is perhaps the most common and useful stimulus, but pattern appearance and diffuse flash both have their uses.

15. Clinical uses • The pioneering work of Halliday's group in the 1970s demonstrated not only that the pattern reversal VEP was delayed in patients with demyelinating optic neuritis, and that delay remained following resolution of the clinical symptoms, but also that patients with multiple sclerosis could show delayed VEP from eyes with no signs or symptoms of optic nerve disease, i.e. the VEP was able to detect sub-clinical demyelination. It soon became apparent that the VEP was a sensitive indicator of optic nerve dysfunction, but that the delay found in association with optic nerve demyelination was not pathognomonic, and that delays could also occur in compression, vitamin B12 deficiency etc.

16. Clinical uses • Ischaemic optic neuropathy may produce amplitude reduction without latency delay. The abnormal distribution of the VEP across the scalp in chiasmal dysfunction was also first described by Halliday's group; single channel mid-line recording may fail to detect chiasmal involvement. It should be noted that delayed VEPs are commonplace in relation to macular dysfunction and a delayed VEP cannot in itself be regarded as an indicator of optic nerve dysfunction. The additional information provided by PERG may be crucial to the accurate interpretation of an abnormal pattern VEP. There is also an abnormal distribution of the pattern appearance VEP in association with the intra-cranial misrouting of ocular albinism where the majority of fibres from each eye decussate to the contralateral hemisphere. VEPs, together with the other electrophysiological tests, are of crucial importance in the diagnosis of non-organic or "functional" visual loss, which may reflect psychological disturbance or malingering. In such cases there are normal electrophysiological findings in association with symptoms which should suggest otherwise.