The Pupillary Light Reflex as a Biomarker of Concussion

The pupillary light reflex (PLR) is not a simple reflex — its function is modulated by cognitive brain function, and any long-term changes in brain function secondary to injury should cause measurable changes in PLR parameters. This retrospective clinical review of the PLR in patients using the Brightlamp Reflex iPhone app examined over 20,000 subjects, making it the largest qPLR study to date.

Background

Pupil size changes continuously in response to ambient light levels, but it is also modulated by output from the cerebral cortex, the locus coeruleus, and other brain structures independent of light stimulation. This means the PLR reflects cognitive brain function — not just a simple peripheral reflex. PLR function is correlated with heart rate variability, attention, and autonomic tone. There are also significant gender differences in autonomic function that manifest in PLR responses.

Methodology

A retrospective clinical review was performed of PLR recordings from patients in a neurological clinic network over the calendar year January 2019 to January 2020, using the Brightlamp Reflex iPhone app. All subjects were classified as having suffered a concussion if their history documented a concussion diagnosis by a health care professional. The PLR variables measured were latency, maximum pupil diameter (MaxPD), minimum pupil diameter (MinPD), maximum constriction velocity (MCV), and the 75% recovery time (75% PRT).

Key Findings

Maximum pupil diameter

Both males and females with a history of concussion had a significantly smaller maximum pupil diameter compared to non-concussion subjects, regardless of whether they had current symptoms. This relationship was stable over ten years following a concussion, with only a minor non-significant trend to decrease over time.

Minimum pupil diameter

Concussion subjects had a significantly larger minimum pupil diameter — meaning their pupils did not constrict as much in response to light. The spread between concussion and non-concussion subjects was more pronounced for minimum diameter than maximum diameter.

75% pupillary recovery time

Both eyes in the concussion group had a 75% PRT that was significantly faster than the non-concussion group. Symptomatic concussion subjects showed a slower 75% PRT than asymptomatic concussion subjects. Notably, males with concussion had a significantly faster 75% PRT than females — a gender bias that did not exist in the non-concussion group.

Maximum constriction velocity

The non-concussion group demonstrated slower MCV than the concussion group overall. However, there was a paradoxical increase in MCV in concussion subjects over the lifespan — the opposite of the non-concussion pattern, where MCV decreased significantly with age.

Latency

Subjects with a history of concussion, with or without symptoms, showed slower latency than subjects without concussion history. Females without a concussion history had the fastest latencies.

Clinical Significance

These observations suggest that the PLR might be used as a diagnostic biomarker for the success or failure of treatment strategies — and that changes in PLR metrics persist over the lifespan following a concussion. The PLR differences between concussion and non-concussion groups were observed in non-laboratory, ambient lighting conditions, confirming the practical utility of mobile pupillometry outside controlled settings.

Conclusion

The PLR is more than a simple reflexogenic change in pupil size when exposed to light. Subjects who have suffered a concussion will have different latencies to constriction, different maximum and minimum pupillary diameters, and differences in the speed of contraction and dilation. The differences in PLR metrics are modulated not only by concussion history but also by gender and symptom status. A concussive injury to the brain is associated with changes in the PLR that persist over the lifespan, representing biomarkers that might be used in clinical diagnosis, treatment, and decision making.