Robert Whytt correctly argued with the influential physician Albrecht von Haller 250 years ago that the PLR required a pathway through the brain. Whytt could not have appreciated why his idea would be so important to physicians in the 21st century, who no longer define life in terms of cardiac function. Light on the retina is a benign non-noxious stimulus and the reflex it produces can be rapidly non-invasively recorded and time-stamped. It is not depressed by paralyzing agents that can confound the assessment of brain stem function by other methods (breathing, eye movements, corneal reflexes). An intact PLR reveals that the observed patient was alive at that time because it confirms the absence of brainstem death. This fact alone justifies special attention to this important reflex.

There is a need for consensus by physicians on what features of the PLR are clinically useful. Some authors rely on the percent reflex [1] while others use constriction velocity [2] or latency of constriction [5]. In judging the quality of the PLR, it may be unwise to place emphasis on a single parameter of the PLR waveform [6]. A proprietary algorithm designed to gauge the strength of the PLR, the Neurological Pupil Index (NPi), is scaled from 0 to 5, with 0 being an absent reflex [7]. The rarely observed “tonic light reflex” [8, 9] has a delayed constriction velocity and low reflex amplitude, and would require either several measurements or a longer light stimulus to determine the presence or absence of a PLR.

If the PRL is absent or severely depressed, then clinicians are required to draw upon their knowledge of the physiology and pharmacology of the pupil. A host of syndromes and drugs can depress or obliterate the PLR [9, 10]. The crossed afferent PLR pathway passes through the optic nerve, into the pretectal area, and then into the preganglionic pupilloctonstrictor (Edinger-Westphal) nucleus. This nucleus is embedded within the mesencephalic reticular formation, the integrity of which is necessary for the state of awareness. The efferent pathway of the PLR is important because of its tortuous pathway through the base of the pons, next to the tentorium, into the cavernous sinus, and then into the orbit. Each portion of the efferent pathway is vulnerable to compression by aneurysms, tumors, blood clots, and swollen brain tissue.

The clinician thus has several pathological processes to think about when evaluating the depressed PLR. Asymmetric efferent lesions produce anisocoria that can be detected more precisely with infrared pupillometry [1]. Asymmetric afferent lesions produce a relative afferent pupillary defect (RAPD). Most clinicians can perform the swinging flashlight test to evaluate this defect [9], but it is likely that within a few years the portable infrared method will be able to quantify the extent of RAPD.

In addition to pupil size, PLR, and anisocoria, there are other pupillary measures that have been considered for use in critical care units. Pupillary Reflex Dilation (PRD) is the dilation of the pupil that follows an alerting stimulus such as a tetanic electrical stimulus [10]. PRD during propofol administration is depressed in a dose-related manner by opioids [10] and has been used to predict pain-related behaviors in unconscious patients during subsequent noxious procedures [11, 12]. In awake subjects the PLR has been used for the same purpose [13]. Another pupillary measure is derived from the spontaneous fluctuations in pupil size during exposure to ambient light (termed pupillary unrest in ambient light (PUAL)). These fluctuations are depressed by opioids and can serve as a measure of opioid effect in awake subjects [14], but PUAL has not been evaluated in the critical care setting. Neither PRD nor PUAL can be measured with the pen-light examination, and thus require the use of portable infrared pupillometers in order to obtain accurate measurements.

PLR, pupillary light reflex; PUAL, pupillary unrest in ambient light; RAPD, relative afferent pupillary defect.