Purpose and use of this Standard 1 8 1 2 Clinical and research users of the clinical EOG are encouraged to use the current Standard Method where possible, to achieve consistency of results within and between test centres. Reports of EOG recordings performed to the Standard Method given here should cite this 2006 Standard. Where a method is used which deviates from the Standard Method, the deviations should be stated, together with any normative or reference data. Where the method used conforms to a previous EOG Standard, this may be cited instead. EOG origins, pathological effects, and principles of measurement Electrophysiology of the RPE in dark and light adaptation The eye has a standing electrical potential between front and back, sometimes called the corneo-fundal potential. The potential is mainly derived from the retinal pigment epithelium (RPE), and it changes in response to retinal illumination. The potential decreases for 8–10 min in darkness. Subsequent retinal illumination causes an initial fall in the standing potential over 60–75 s (the fast oscillation (FO)), followed by a slow rise for 7–14 min (the light response). These phenomena arise from ion permeability changes across the basal RPE membrane. The clinical electro-oculogram (EOG) makes an 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. The behaviour of the corneo-fundal potential in the normal eye is predictable in defined conditions, such as those described in this Standard, but changing from dark to light actually initiates a triggered response extending for about 2 h in the form of a diminishing sinusoidal oscillation. Diseases affecting the light response of the EOG The light response is affected in diffuse disorders of the RPE and the photoreceptor layer of the retina including some characterised by rod dysfunction, or chorio-retinal atrophic and inflammatory diseases. In most of these there is correlation with the electroretinogram (ERG), except notably in the case of Best’s vitelliform maculopathy, in which the clinical EOG is usually highly abnormal in the presence of a normal ERG. Measurement of the clinical EOG The potential across the RPE causes the front of the eye to be electrically positive compared to the back. As a result, potentials measured between two electrodes placed on the skin at each side of an eye will change as the eye turns from left to right. The EOG method is used widely to record eye movements, on the assumption of unchanging corneo-fundal potentials. In the clinical EOG described here, we use defined eye movements to monitor the changes in corneo-fundal potential. If the test subject looks alternately at targets a fixed angle apart, the potential recorded from the skin resembles a square wave whose amplitude will be a fixed proportion of the corneo-fundal potential. During a light/dark cycle, this indirectly measured potential will change in the same way as the source potentials, so that the Arden ratios (and timing of peaks etc.) will be a close approximation to the average changes occurring across the RPE. The Standard Method This section outlines the Standard Clinical EOG method, definitions, explanations, and instrument specifications. Further notes regarding testing strategies are given in later sections. Pupils Electrodes 1 Fig. 1 a b  Amplifier Full field (Ganzfeld) stimulator Pre-adaptation Preparing the test subject Dark phase Light phase 2 This completes the procedure for the test subject. Measure the amplitude of the EOG 2 Fig. 2 Idealised saccadic recording with d.c. amplifier (top) and example a.c. coupled amplifier with high pass filter at 0.5 Hz and 0.1 Hz. Overshoot is hard to recognise using 0.5 Hz  Plot the change in the responses 3 Fig. 3 Idealised (underlying) EOG response (top) and practical response with noise and trial/trial variability. Arrows show the dark trough (DT) and light peak (LP). The underlying curve must be estimated before recording the Arden ratio (LP/DT)  Calculate the Arden ratio underlying curve Report Deviation from the Standard This Standard represents a basic or core procedure. If a laboratory chooses a procedure which varies from the Standard Method above, it is critical to cite this Standard, but specify the deviations from the Standard Method, such as different luminance level for the adapting light. If a statistical report is given, then this must be supported by reference data obtained under the same conditions. Additional tests Some centres measure the ‘Fast Oscillation’ (FO), often in conjunction with the Clinical EOG. The fast oscillations: - - The FO is recorded using the same parameters as for the clinical EOG (amplification, electrode placement and stimulus light intensity). However, recordings should be made continuously as the subject executes regular horizontal saccades at 1/s. Alternating light and dark for 60 s each induces the FOs, which have a near sinusoidal appearance. During the light interval a light trough (LT) develops and begins to rise again after 30–40 s. The subsequent interval of darkness results in a dark rise (DR) at 30–40 s following the onset of darkness. The next interval of light induces another light trough. The total number of light-dark intervals should be at least 4 with 60 s periods of light and dark, making a total test time of 8 min. Pre-adaptation does not affect the FO, and so this test can be performed either independently or in conjunction with the clinical EOG, provided pre-adaptation conditions for the latter are consistent within the lab. 4 Fig. 4 Idealised representation of fast oscillations (FO). In the dark intervals (black bars) the standing potential increases to a dark rise maximum (DR). Following light onset the standing potential falls to a light trough (LT). The FO ratio of the DR:LT standing potentials should be recorded  Practical notes, instruments and definitions (alphabetical) Amplifiers 2 3 Amplifier saturation Arden ratio 3 Compliance of the patient The cost of unreliable performance is that the margins of error are widened. This does not mean that no information can be gleaned. If the suspected disorder is one with a clear test outcome, it may be possible to make the diagnosis on one or two reliable trials performed near the time of the trough and the peak, to ensure that there is indeed a light rise of some amplitude, or not. Diplopia Electrodes Fixation targets Full field (Ganzfeld) stimulator Interaction between eyes Light Luminance 2 3 Darkness Colour Normative data/reference range Photophobia Plotting 3 Pupil dilation Reporting Basic factual report Statistical report No fully authenticated normal reference data is available currently for the Standard Clinical EOG method given above. However, from a review of existing published data, Arden ratios <1.5 are reported as being abnormally low, and those >2.0 are reported as probably normal, and in between as borderline. This guidance may be useful in the absence of local normative data, but the values do not constitute validated diagnostic criteria. Saccade measurement If a computer algorithm is used there is a need to ensure that the values returned properly represent the true EOG amplitudes. Each algorithm is likely to make some mistakes. Fortunately, the final dark/light response curve will form an ‘average of averages’ in which the influence of a few errors should be swamped by the remaining data. 2 Standing potentials not Warning of start of each trial History and acknowledgements This Standard forms part of series of Standards, Recommendations and Guidelines prepared by the International Society for Clinical Electrophysiology of Vision (ISCEV): Participants in the review: ISCEV EOG Standard Revision Committee 2006; Malcolm Brown (Chairman), Royal Liverpool University Hospital, Liverpool UK Michael Marmor, Stanford University, California USA; Vaegan (ISCEV Board Member-at-Large) University of New South Wales, Australia, Eberhart Zrenner University Eye Hospital, Tuebingen, Germany EOG Standard Advisory Panel 2006 includes the members above plus: Michael Bach, (ISCEV President), Universität-Augenklinik, Freiburg, Germany: Mitchell Brigell, (ISCEV Director of Standard), Pfizer Global. R&D, Ann Arbor, Michigan USA: Graham Holder, (ISCEV Director of Education), Moorfields Eye Hospital, London UK Paul Constable, City University, London UK: Masao Yoshikawa, Mayo Corporation, Aichi, Japan; Carol Westall, Hospital for Sick Children, Toronto Canada; Geoffrey Arden, (Honorary ISCEV member) City University, London UK