The pupillary dark reflex in acute disorders of consciousness

Abstract

Background. In intensive care patients with disorders of consciousness (DoC), the pupillary light reflex is a measure of pupillary parasympathetic function. By contrast, the pupillary dark reflex leads to pupil dilation in response to darkness and primarily reflects the sympathetic function of the pupil. To our knowledge, this reflex has not been systematically investigated in DoC patients. We hypothesized that the pupillary dark reflex correlates with consciousness levels after acute brain injury, and that this correlation is not necessarily the same as that of the pupillary light reflex. Methods. From November 2022 to March 2023, we enrolled 100 study participants: 25 clinically unresponsive (coma or unresponsive wakefulness syndrome) and 25 clinically low-responsive (minimally conscious state or better) patients from the intensive care units of a tertiary referral center, and 50 age- and sex-matched healthy controls. Exclusion criteria were active or chronic eye disease. We used automated pupillometry to assess the pupillary dark reflex and the pupillary light reflex of both eyes under scotopic conditions in all study participants. Results. The pupillary dark reflex was strongly correlated with consciousness levels (r = 0.62, p < 0.001), the increase in pupillary diameters being smallest in unresponsive patients (mean ± SD: 20% ± 21%), followed by low-responsive patients (47% ± 26%) and healthy controls (67 % ± 17%; p < 0.001). Similar, yet less pronounced patterns were observed for the pupillary light reflex. Twenty-one of 25 unresponsive patients had preserved pupillary light reflexes, but only seven had preserved pupillary dark reflexes (p < 0.0001). Of these seven patients, five regained awareness. Conclusion. The pupillary dark reflex is more sensitive to consciousness levels after brain injury than the pupillary light reflex. The clinical implications of this finding seem worthy of further investigation, particularly regarding possible benefits for neuromonitoring and prognostication after brain injury.