A Review of Silent Substitution Devices for Melanopsin Stimulation in Humans

One way to study the specific response of the non-visual melanopsin photoreceptors of the human eye is to silence the response of cones and rods. Melanopsin photoreceptors (ipRGC), highlighted in the early 2000s, are intimately linked to the circadian rhythm and therefore to our sleep and wakefulness. Rest and sleep regulation, health and cognitive functions are all linked to ipRGC and play an important role in work and human relationships. Thus, we believe that the study of ipRGC responses is important.We searched and reviewed scientific articles describing instrumentation dedicated to these studies. PubMed lists more than 90,000 articles created since the year 2000 that contain the word circadian but only 252 with silent substitution. In relation to melanopsin, we found 39 relevant articles from which only 11 give a device description for humans, which is incomplete in most cases. We did not find any consensus for light intensity description, melanopsin contrast, sequences of melanopsin light stimulation and optical setup to expose the retina to the light.

Pupil responses to hidden photoreceptor–specific modulations in movies

Under typical daytime light levels, the human pupillary light response (PLR) is driven by the activity of the L, M, and S cones, and melanopsin expressed in the so-called intrinsically photosensitive retinal ganglion cells (ipRGCs). However, the importance of each of these photoreceptive mechanisms in defining pupil size under real-world viewing conditions remains to be established. To address this question, we embedded photoreceptor-specific modulations in a movie displayed using a novel projector-based five-primary spatial stimulation system, which allowed for the precise control of photoreceptor activations in time and space. We measured the pupillary light response in eleven observers, who viewed short cartoon movies which contained hidden low-frequency (0.25 Hz) silent-substitution modulations of the L, M and S cones (no stimulation of melanopsin), melanopsin (no stimulation of L, M and S cones), both L, M, and S cones and melanopsin or no modulation at all. We find that all photoreceptors active at photopic light levels regulate pupil size under this condition. Our data imply that embedding modulations in photoreceptor contrast could provide a method to manipulate key adaptive aspects of the human visual system in everyday, real-world activities such as watching a movie.

Pulses of melanopsin-directed contrast produce highly reproducible pupilresponses that are insensitive to a change in background radiance

PurposeTo measure the pupil response to pulses of melanopsin-directed contrast, and compare this response to those evoked by cone-directed contrast and spectrally-narrowband stimuli.Methods3-second unipolar pulses were used to elicit pupil responses in human subjects across 3 sessions. Thirty subjects were studied in Session 1, and most returned for Sessions 2 and 3. The stimuli of primary interest were “silent substitution” cone‐ and melanopsin-directed modulations. Red and blue narrowband pulses delivered using the post-illumination pupil response (PIPR) paradigm were also studied. Sessions 1 and 2 were identical, while Session 3 involved modulations around higher radiance backgrounds. The pupil responses were fit by a model whose parameters described response amplitude and temporal shape.ResultsGroup average pupil responses for all stimuli overlapped extensively across Sessions 1 and 2, indicating high reproducibility. Model fits indicate that the response to melanopsin-directed contrast is prolonged relative to that elicited by cone-directed contrast. The group average cone‐ and melanopsin-directed pupil responses from Session 3 were highly similar to those from Sessions 1 and 2, suggesting that these responses are insensitive to background radiance over the range studied. The increase in radiance enhanced persistent pupil constriction to blue light.ConclusionsThe group average pupil response to stimuli designed through silent substitution provides a reliable probe of the function of a melanopsin-mediated system in humans. As disruption of the melanopsin system may relate to clinical pathology, the reproducibility of response suggests that silent substitution pupillometry can test if melanopsin signals differ between clinical groups.