Reference ranges for clinical electrophysiology of vision

INTRODUCTION: Establishing robust reference intervals for clinical procedures has received much attention from international clinical laboratories, with approved guidelines. Physiological measurement laboratories have given this topic less attention; however, most of the principles are transferable. METHODS: Herein, we summarise those principles and expand them to cover bilateral measurements and one-tailed reference intervals, which are common issues for those interpreting clinical visual electrophysiology tests such as electroretinograms (ERGs), visual evoked potentials (VEPs) and electrooculograms (EOGs). RESULTS: The gold standard process of establishing and defining reference intervals, which are adequately reliable, entails collecting data from a minimum of 120 suitable reference individuals for each partition (e.g. sex, age) and defining limits with nonparametric methods. Parametric techniques may be used under some conditions. A brief outline of methods for defining reference limits from patient data (indirect sampling) is given. Reference intervals established elsewhere, or with older protocols, can be transferred or verified with as few as 40 and 20 suitable reference individuals, respectively. Consideration is given to small numbers of reference subjects, interpretation of serial measurements using subject-based reference values, multidimensional reference regions and age-dependent reference values. Bilateral measurements, despite their correlation, can be used to improve reference intervals although additional care is required in computing the confidence in the reference interval or the reference interval itself when bilateral measurements are only available from some of subjects. DISCUSSION: Good quality reference limits minimise false-positive and false-negative results, thereby maximising the clinical utility and patient benefit. Quality indicators include using appropriately sized reference datasets with appropriate numerical handling for reporting; using subject-based reference limits where appropriate; and limiting tests for each patient to only those which are clinically indicated, independent and highly discriminating. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10633-021-09831-1.