Commentary: Visual electrophysiology and laboratory-specific normative values - How important are they?

Electrophysiology tests are noninvasive methods that study the response of our nervous system to various sensory stimuli. The most commonly used tests in visual electrophysiology are the visual evoked potential (VEP), electroretinogram (ERG), and the electrooculogram (EOG). Despite the technology being around for long, there is lack of reproducibility in the readings of these tests between two laboratories. The International Society for Clinical Electrophysiology of Vision (ISCEV) has tried to address this grey area by giving out standards for recording each type of test since 1961.[1] However, there are a variety of approved electrophysiology equipment with individual calibration requirements which leads to significant inter-laboratory variability. Very few companies provide a normative database along with the equipment contrary to other diagnostic equipment in ophthalmology like visual field analyzer and optical coherence tomography. The ISCEV also acknowledges this variability and addresses this by stating “Each laboratory should establish or confirm typical reference values for its own equipment, recording protocols and patient population giving attention to appropriate sample sizes.”[2]

Multiple factors can affect electrophysiology results including technical factors, demographic factors, and patient-specific factors. The main technical factor for variability is the luminance of the light source used. The xenon flash tubes used in older equipment can have random fluctuation in the percentage of light output and also produce less light as they age. The light-emitting diode (LED) light source has better stability and luminance values for the same have been given by ISCEV in their latest standards update in 2015.[2] The type of electrode used is another source of variation. Each electrode type has its own impedance, signal-to-noise ratio, inherent artifacts, and recording characteristics. A survey of ISCEV members on preferred electrodes used showed over 80% of respondents used two or more types of electrodes in their electrophysiology laboratory.[3] Technical training of the technician performing the tests can also lead to variability with regard to the placement of electrodes and patient cooperation. Lack of regular calibration of equipment can lead to variation in contrast and luminance at which the tests are performed. ISCEV recommends calibration once every six months. Internal calibration reminders incorporated by some equipment makers certainly help in this regard. Most of the technical factors can be equalized amongst various laboratories by strict adherence to the ISCEV standards updated from time to time.

Demographic factors play an important role in determining the normative distribution for a population set. Rod and cone responses have been shown to progressively decline with age.[4] This can be multifactorial due to reduction in photopigment optical density and bipolar/Müller cell degeneration. Thus having an age-matched comparative normative dataset is very important. Ethnicity can have an impact on the electrophysiology values mainly due to variable pigmentation of the fundi and refractive error. Difference in gender while performing ERG has been well known with females having higher b-wave amplitudes.[4] Hence comparing a male patient to a normative dataset of females would not be correct.

Patient-specific factors are ones over which we can have the least control over. Pupil size can affect the amount of stimulus reaching the photoreceptors. Some patients with ocular conditions such as pseudoexfoliation or uveitis may have non-dilating pupils. Axial length and refractive error are important patient variables that can affect electrophysiology readings. Higher axial length and refractive error both lead to a reduction in electrophysiology amplitudes.[4] Level of alertness of the patient and concomitant use of drugs which can affect central nervous system functioning including anti-depressants, antipsychotics, opioids, or alcohol can delay the response of the subject to stimuli.[5]

These factors show the need for laboratory-specific normative values and also the importance of appropriately selecting subjects for the same. Databases of a single age group or refractive state may not represent the true normative values for that population. Furthermore, consistency in technique, recording conditions, recording time, and regular upkeep of equipment are also vital. The study by researchers from Indonesia is a step in this direction and will go a long way in providing a normative dataset in their region for future reference purposes.[6]