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A 33-year-old white man developed premature presbyopia and anisocoria as initial manifestations of acute pandysautonomia. Nine months later signs and symptoms of generalized, severe autonomic dysfunction developed, and six years later only paralysis of pupillary reactions, presbyopia, and orthostatic hypotension were unresolved. Pharmacologic testing of the pupils demonstrated no mydriasis to cocaine 4% or hydroxyamphetamine 1% and hypersensitivity to epinephrine 0.1%, methacholine 2.5%, and pilocarpine 0.0625%, suggesting the presence of sympathetic and parasympathetic, postganglionic blockage of autonomic innervation of the iris.

A thin slit-lamp beam illuminating the pupil margin produced clearly visible pupil oscillations. These oscillations were timed with a stopwatch, thus producing a measurement of the "pupil cycle time". The pupil cycle time was remarkably stable in various testing situations and repeatable within +/- 3% over extended periods of time. When the iris muscles were normally innervated and responsive, the pupil cycle time was dependent on the speed of conduction and the number and strength of optic nerve impulses. Pupil cycle time can be measured in most persons with active or inactive optic neuritis. In the few patients whose light reflex is so poor that the pupil cycle time cannot be measured, the inability to induce cycling can itself be taken as a definite abnormality of the light reflex arc. Only 5% of normal persons 12 to 50 years of age are expected to have a pupil cycle time in either eye longer than 954 msec, or a difference in pupil cycle time between the two eyes longer than 70 msec. Pupil cycle time was significantly longer in patients with optic neuritis, with a P-value less than .001. The pupil cycle time is similar to visual evoked response latency time in that it can detect and quantitate subclinical defects in optic nerve conduction time. Pupil cycle time is objective and quantitative for each eye individually. It is a fast, simple, and reliable clinic test of optic nerve function.

We recorded pupillary responses to alternating half-field visual stimuli in 13 normal subjects (eight men and five women ranging in age from 23 to 28 years). We found that stimulation of the temporal visual field caused more pupillary constriction than did equivalent stimulation of the nasal field. Temporal stimuli also produced a direct pupillary response that was larger than the consensual response. Nasal stimulation, however, elicited a larger consensual pupillary response than a direct response. Our findings imply an asymmetric decussation of pupillomotor pathways in the midbrain in humans, as well as greater sensitivity of the nasal retina.