Origins of Pupillary Hippus in the Autonomic Nervous System

The purpose of this study was to determine the relative roles of the sympathetic (SNS) and parasympathetic nervous system (PNS) in pupillary hippus.

We used a paired-eye control study design with three cohorts receiving either 1.0% tropicamide (PNS antagonist) in light (TL), 1.0% tropicamide in dark (TD), or 10% phenylephrine (SNS) in light (PL), n = 12 in each. Each subject received one drop to the randomly determined treatment eye, while the other eye served as control. Bilateral measures of pupil size and dynamics were made over 2.6 seconds using an infrared eye-tracker sampling at 500 Hz. Measures were taken at baseline, then every 5 minutes for 40 minutes. Hippus, analyzed in both time and frequency domains, was compared between eyes and cohorts.

Pupillary hippus with a distinct dominant frequency was present in all measures at baseline (mean: 0.62 Hz, SD: 0.213 Hz), and that frequency did not change in any group (P = 0.971). Hippus magnitude (treatment eye relative to control eye) decreased in the TL (-72.8 ± 4.7%, P < 0.0001) and TD (-71.3 ± 2.6%, P < 0.0001) groups, but did not change in the PL (+5.4 ± 13.7%, P = 0.173) group, despite PL pupils dilating to a proportion similar to TD.

Pupillary hippus can be extinguished by antagonizing the PNS, whereas agonizing the SNS dilates the pupil without affecting hippus. This suggests that hippus originates from central PNS activity, and not from SNS activity, or oscillations in the balance between PNS and SNS at the pupil.