Pupil light reflex in normal and diseased eyes: Diagnosis of visual dysfunction using waveform partitioning

Abstract

Objective To evaluate changes in pupil size (corresponding to neuronal firing) within different time windows of the pupil light reflex in patients and normal subjects to understand which segments of the pupil waveform are best able to differentiate normal from abnormal subjects. Design Comparative, observational case series. Participants Forty-nine normal subjects and 25 patients with known unilateral or asymmetric visual field damage were tested. Methods A dual-channel infrared pupillograph was used to simultaneously record the right and left pupil diameters at a rate of 60 Hz. Each eye was stimulated alternately (30° full-field, 200 milliseconds duration every 3 seconds) over 10 different stimulus intensities. The recorded waveform of the pupil light reflex was subdivided into six time windows based on landmarks corresponding to contraction onset, maximum contraction velocity, peak contraction, and maximum dilation velocity to assess which portion was most affected by disease. Main outcome measures The linear correlation between pupil contractions elicited by right versus left full-field stimulation at different light intensities provided diagnostic parameters (slope, intercept, and correlation coefficient R 2) that were useful for differentiating normal subjects from patients and for categorizing disease. Sensitivity and specificity of the time windows were evaluated with receiver-operator curve analysis. Results The diagnosis of asymmetric disease was greatest at time windows that included pupil contraction but not dilation. When the contraction phase was subdivided into an early phase and into a late phase, the late phase was the most diagnostic compared with the entire phase of contraction amplitude (onset to peak contraction). Conclusions By use of a range of light intensity, the change in pupil size measured between the time at which maximum contraction velocity occurs and the time to peak contraction provided the best response parameter for objective diagnosis of asymmetric disease of the anterior visual pathway. The waveform of the pupil light reflex may be an expression of the firing of retinal ganglion cells. Therefore, understanding which segment of the pupil light reflex provides maximal diagnostic power may give insight into how disease affects the pattern of neuronal firing rate.