Standards in Pupillography

Abstract

The number of research groups studying the pupil is increasing, as is the number of publications. Consequently, new standards in pupillography are needed to formalize the methodology including recording conditions, stimulus characteristics, as well as suitable parameters of evaluation. Since the description of intrinsically photosensitive retinal ganglion cells (ipRGCs) there has been an increased interest and broader application of pupillography in ophthalmology as well as other fields including psychology and chronobiology. Color pupillography plays an important role not only in research but also in clinical observational and therapy studies like gene therapy of hereditary retinal degenerations and psychopathology. Stimuli can vary in size, brightness, duration, and wavelength. Stimulus paradigms determine whether rhodopsin-driven rod responses, opsin-driven cone responses, or melanopsin-driven ipRGC responses are primarily elicited. Background illumination, adaptation state, and instruction for the participants will furthermore influence the results. This standard recommends a minimum set of variables to be used for pupillography and specified in the publication methodologies. Initiated at the 32nd International Pupil Colloquium 2017 in Morges, Switzerland, the aim of this manuscript is to outline standards in pupillography based on current knowledge and experience of pupil experts in order to achieve greater comparability of pupillographic studies. Such standards will particularly facilitate the proper application of pupillography by researchers new to the field. First we describe general standards, followed by specific suggestions concerning the demands of different targets of pupil research: the afferent and efferent reflex arc, pharmacology, psychology, sleepiness-related research and animal studies.

Keywords: analysis; application of pupillography; clinical standards; parameters of evaluation; pupillography; pupillometry; stimulus characteristics.

Figure 1

The pupillary pathway. The afferent pupillary pathway comprises the retinal photoreceptors, the bipolar cells and the retinal ganglion cells whose axons form the optic nerve. Temporal fibers run ipsilaterally while the nasal fibers cross to the contralateral side in the optic chiasm. Afterwards, they form the optic tract and synapse at the olivary pretectal nucleus therefrom connecting to both Edinger Westphal nuclei (blue continuous line). The efferent pathway from the Edinger Westphal nucleus to the pupillary sphincter via the ciliary ganglion is depicted in dashed lines.

Figure 2

Post-Illumination Pupil Response (PIPR) metrics. Consensual pupillary response to 1 s pulses (horizontal blue line at time 0; 465 nm blue, 637 nm red-the gray line represents the pre- and post-stimulus periods in the dark) measured in Maxwellian view (35.6° diameter stimulus; 15.1 log quanta.cm⁻².s⁻¹). Details of the pupil light response (PLR) and Post-Illumination Pupil Response (PIPR) metrics are described in the figure. Data are for a representative healthy observer (traces are the average of 3 repeats). Traces courtesy of Prakash Adhikari, Beatrix Feigl and Andrew J. Zele.

Figure 3

Pupil diameter (mm) measured in darkness after switching off a light stimulus over a time period of 20 s. The right eye (R) shows the typical quick redilation behavior of a healthy pupil while the left eye (L) reveals a dilation lag, typical for Horner syndrome. Data are taken from a patient with Horner syndrome in the left eye collected during standard care.

Figure 4

Targets of drugs in the neuronal network controlling the pupil. The pupil is an aperture in a diaphragm, the iris. The size of the pupil reflects the interaction between the circular sphincter muscle and the radial dilator muscle. The sphincter receives a parasympathetic and the dilator a sympathetic output. Both autonomic outputs consist of serially linked preganglionic and postganglionic neurones that are under the influence of premotor autonomic neurones. The premotor neurones channel the influence of other brain structures (e.g., cortex) and light to the preganglionic neurones. Premotor neurones: SCN: suprachiasmatic nucleus (hypothalamus); PVN: paraventricular nucleus (hypothalamus); LC: locus coeruleus (brainstem: pons); OPN: olivary pretectal nucleus (pretectum). Preganglionic neurones: IML: intermediate lateral column (spinal cord); EWN: Edinger-Westphal nucleus (brainstem: midbrain). Postganglionic neurones: SCG: superior cervical ganglion; GC: ciliary ganglion. Arrows are neuronal connections, red arrows are excitatory connections with identified neurotransmitters (Glu, glutamate; NA, noradrenaline; Ach, acetylcholine). Drugs can be applied topically to the surface of the cornea to affect the iris and the noradrenergic and cholinergic neuro-effector junctions, or systemically when they can affect any part of the central neuronal network. It should be noted that topically applied drugs may get into the systemic circulation leading to systemic effects, and systemically applied drugs may also affect the iris directly.