Rods, cones and melanopsin containing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) operate in concert to regulate pupil diameter. The temporal properties of intrinsic ipRGC signalling are distinct to those of rods and cones, including longer latencies and sustained signalling after light offset. We examined whether the melanopsin mediated post-illumination pupil response (PIPR) and pupil constriction were dependent upon the inter-stimulus interval (ISI) between successive light pulses and the temporal frequency of sinusoidal light stimuli. Melanopsin excitation was altered by variation of stimulus wavelength (464 nm and 638 nm lights) and irradiance (11.4 and 15.2 log photons.cm−2.s−1). We found that 6s PIPR amplitude was independent of ISI and temporal frequency for all melanopsin excitation levels, indicating complete summation. In contrast to the PIPR, the maximum pupil constriction increased with increasing ISI with high and low melanopsin excitation, but time to minimum diameter was slower with high melanopsin excitation only. This melanopsin response to briefly presented pulses (16 and 100 ms) slows the temporal response of the maximum pupil constriction. We also demonstrate that high melanopsin excitation attenuates the phasic peak-trough pupil amplitude compared to conditions with low melanopsin excitation, indicating an interaction between inner and outer retinal inputs to the pupil light reflex. We infer that outer retina summation is important for rapidly controlling pupil diameter in response to short timescale fluctuations in illumination and may occur at two potential sites, one that is presynaptic to extrinsic photoreceptor input to ipRGCs, or another within the pupil control pathway if ipRGCs have differential temporal tuning to extrinsic and intrinsic signalling.

Parkinson’s disease (PD) is characterised by non-motor symptoms including sleep and circadian disruption. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals to brain areas controlling circadian rhythms and the pupil light reflex. To determine if non-motor symptoms observed in PD are linked to ipRGC dysfunction, we evaluated melanopsin and rod/cone contributions to the pupil response in medicated participants with PD (n = 17) and controls (n = 12). Autonomic tone was evaluated by measuring pupillary unrest in darkness. In the PD group, there is evidence for an attenuated post-illumination pupil response (PIPR) amplitude and reduced pupil constriction amplitude, and PIPR amplitudes did not correlate with measures of sleep quality, retinal nerve fibre layer thickness, disease severity, or medication dosage. Both groups exhibited similar pupillary unrest. We show that melanopsin- and the rod/cone-photoreceptor contributions to the pupil control pathway are impaired in people with early-stage PD who have no clinically observable ophthalmic abnormalities. Given that ipRGCs project to brain targets involved in arousal, sleep and circadian rhythms, ipRGC dysfunction may underpin some of the non-motor symptoms observed in PD.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) regulate pupil size by integrating extrinsic rod and cone signals with intrinsic melanopsin-mediated phototransduction. Light adapted pupil diameter is determined by the corneal flux density (CFD), and for central visual field stimulation the melanopsin-mediated post-illumination pupil response (PIPR) follows this same CFD relationship. Rods, cones, and ipRGCs vary in size, density, and distribution across the retina, but how these differences affect the amplitude and timing of the extrinsic and intrinsic pupil light reflex in the central and peripheral retina is unknown. We determined the relationship between stimulus area and photon flux with stimuli constant for CFD, irradiance, or area at central (0°) and peripheral (20°) eccentricities with high and low melanopsin excitation. We show that the pupil constriction amplitude was similar at both eccentricities and the time to minimum diameter increased as melanopsin excitation increased. In contrast, the peripheral PIPR follows a CFD relationship but with lower amplitude compared with that at the fovea. This indicates differences in the spatial and temporal characteristics of extrinsic and intrinsic ipRGC inputs to the pupil control pathway for the central and peripheral retina. The eccentricity-dependent change in PIPR amplitude may be analogous to the hill of vision observed in visual perimetry; such knowledge is an important precursor to the development of pupil perimetry paradigms to measure the PIPR in select regions of the visual field.

The findings have implications for standardizing light adaptation paradigms and the choice of pupil metrics in both laboratory and clinical settings. Light and dark adaptation have opposite effects on the pupil metrics, which should be normalized to baseline to minimize significant correlations between constriction and PIPR amplitudes.

Actigraphs are the reference standard for measuring light exposure in human non‐laboratory experiments due to their portability and long battery lives. However, actigraphs typically have a limited illuminance operating range not representative of real‐world conditions, and for many actigraphs, the accuracy of their light measurement has not been verified independently. We assessed the illuminances recorded by Activinsights GENEActiv Original and Philips Actiwatch 2 actigraphs in comparison to a calibrated, laboratory‐standard photometer, under both artificial light‐emitting diode (LED) and natural sunlight illuminations that might be encountered by a person under real‐world conditions. We show that in response to ~20,000 lux white LED light, the GENEActiv and Actiwatch 2 underestimate illuminance by recording 50% and 25% of the true value, respectively. Under ~30,000 lux sunlight, the GENEActiv readily saturates whereas the Actiwatch 2 reports ~46% of the true illuminance. These underestimations are highly linear and we provide correction factors to estimate the illuminance levels of the ambient environment measured by the actigraphs. We also evaluate the application of neutral density filters for extending the operating range of both devices in natural sunlight illuminations (as high as 30,000 lux during our measurements) and demonstrate that this may be a viable approach for increasing the operating range of the Actiwatch 2 but not the GENEActiv. We conclude that both actigraphs provide good performance in monitoring the temporal patterning of light, whereas the absolute illuminance values require correction to accurately evaluate the effects of light intensity on human health and behaviours.

We studied the effect of rod–cone interactions on mesopic visual reaction time (RT). Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. It was observed that (1) lateral rod–cone interactions increase the cone-mediated RTs; (2) the rod–cone interactions are strongest when rod sensitivity is maximal in a dark surround, but weaker with increased rod activity in a light surround; and (3) the presence of a dark surround nonselectively increased the mean and variability of chromatic (+L−M, S-cone) and luminance (L + M + S) RTs independent of the level of rod activity. The results demonstrate that lateral rod–cone interactions must be considered when deriving mesopic luminous efficiency using RT.

No abstract

No abstract