Spectral responses of pupillary constriction during exposure to continuous light. (A) Pupillary light responses are shown in normally-sighted individuals (n = 5; gray traces) and in a blind participant without rod and cone function (black traces). Participants were exposed to 4 min of fixed-irradiance (13 log photons cm⁻² s⁻¹) narrow-bandwidth light at 8 different wavelengths. Error bars shown in light gray indicate SEM. (B) Spectral responses in sighted individuals and the blind individual are shown by gray and black circles, respectively. Percentage constriction was measured during the fourth minute of light exposure and plotted by corneal irradiance. The black trace shows the best-fit Gaussian function for spectral responses in the blind individual; peak spectral sensitivity is observed in the short-wavelength portion of the visual spectrum. (C) For each of the light exposures given, relative irradiance levels and spectral composition are shown.

Visual photoreceptors are required for pupillary responses to track intermittent light stimuli. (A) Pupillary constriction is shown in normally-sighted individuals (n = 4) and in a blind patient without rod and cone function in response to a single 6 s pulse of 480 nm light (13 log photons cm⁻² s⁻¹). (B) Participants were exposed to 4 min of continuous or intermittent 480 nm light at 13 log photons cm⁻² s⁻¹. During exposure to continuous light, sighted participants and the blind individual showed sustained pupillary constriction (top row). During an intermittent light stimulus with alternating periods of 5 s of light and 5 s of darkness, normally-sighted participants’ pupils were able to track each successive light pulse, whereas in the blind individual, responses were integrated over time until reaching a steady response about 1 minute after the onset of the stimulus (middle row). With alternating periods of 5 s of light and 15 s of darkness, the blind individual’s pupil was still able to integrate light information across longer episodes of darkness (bottom row). The pattern of light exposure is shown at the top of each plot, with upward deflections indicating times when participants were exposed to light. To highlight differences in pupillary constriction responses to intermittent light, pupil diameter in the blind individual is plotted on a different scale than for sighted participants. Gray traces in the left panels indicate SEM.

Pupillary responses to high frequency intermittent light. (A) Pupillary constriction responses are shown in a representative participant during the first 30 s of exposure to intermittent light. Intermittent green light (0.1 to 4 Hz) was given using an LCD screen (543 nm; 12 log photons cm⁻² s⁻¹). The frequency and pattern of light exposure are shown at the top of each trace. (B) Average pupillary constriction responses are shown in normally-sighted individuals (n = 6) during exposure to 30 min of intermittent light at different frequencies. Pupil diameter during ON and OFF pulses are shown by green and gray traces, respectively. Black traces show average pupil diameter in 30-s bins for both ON and OFF pulses.

Visual photoreceptors mediate pupillary constriction at low irradiances. (A) Pupillary constriction responses are shown in a normally-sighted participant (blue traces) and in a blind individual without rod and cone function (black traces) during exposure to 2 min of narrow-bandwidth 480 nm light. Irradiance levels are indicated at the top of each plot (photons cm⁻² s⁻¹). (B) Dose response curves for pupillary constriction to 480 nm light are shown for normally-sighted participants (n = 3; blue circles, left panel) and in the blind individual (black circles, center panel), assessed 90–120 s after the onset of light exposure. Best-fit dose-response functions are shown with confidence intervals indicated by dotted lines. Drop lines show the log ED₅₀ of each dose-response function. Dose-response curves are overlaid in the far right panel, demonstrating reduced sensitivity to 480 nm light at low irradiances in the blind participant. (C) The dose response curve for pupillary constriction is shown in normally-sighted participants exposed to 555 nm light. (D) The log ED₅₀ value is shown for dose-response curves to 480 nm versus 555 nm light in 30-s bins during exposure to 2 min of continuous light (left panel). Over time, there was a progressive decrease in sensitivity in sighted participants, with a greater reduction in sensitivity to 555 nm light. By comparison, in the blind individual the log ED₅₀ value for pupillary constriction in response to 480 nm (black circles) was stable over time. (E) In sighted individuals, the difference in log ED₅₀ values (480 nm versus 555 nm light) is shown during exposure to 2 min of continuous light. The dotted line shows the predicted difference in log relative sensitivity at these wavelengths for a vitamin A1-based photopigment with peak sensitivity to 480 nm light. (F) Dose-response curves are shown in 10-s bins for sighted individuals exposed to 480 nm versus 555 nm light, and in the blind patient exposed to 480 nm light. (G) Pupillary constriction is shown in normally sighted participants (n = 4) and in a blind individual exposed to 10 min of polychromatic white light (4100K). Black and gray traces show responses to 2,500 lux and 90 lux of light, respectively. Error bars indicate SEM. (H) The spectral composition of the fluorescent white light source is shown.

Kinetics of pupillary constriction following light exposure onset and offset. (A) Representative traces are shown for pupillary constriction in a sighted participant (gray) and in a blind individual without rod and cone function (black), matched for median response magnitude. Pupillary constriction was sluggish in the blind individual after light onset, and slow to re-dilate back to baseline after the offset of the light stimulus. (B) Pupillary constriction during the light stimulus is re-plotted from panel A on a logarithmic scale to demonstrate the difference in response latency with and without visual photoreceptors (gray and black traces, respectively). (C) Similarly, pupillary constriction after the offset of the light stimulus is shown to illustrate the relatively sluggish dilation of the blind participant’s pupil toward the dark-adapted state. (D) Response latency in the blind individual (black trace) was negatively correlated with the magnitude of sustained pupillary constriction, whereas response latency did not correlate with strength of pupillary constriction during exposure to continuous light in normally-sighted individuals (open circles). (E) The rate at which the pupils re-dilated after light exposure offset was about 5 times slower in the blind individual relative to responses measured in normally-sighted participants. (F) In sighted participants, the relationship was nonlinear between pupillary constriction near the beginning (0–30 s) and end (90–120 s) of exposure to 2 min of continuous 480 nm light. (G) Similarly, the decrease in strength of pupillary light responses was nonlinear during continuous exposure to 555 nm light. The dashed line shows the line of unity.

Pupillary escape occurs gradually in the presence of continuous low irradiance light. (A) Pupillary constriction is shown in normally-sighted individuals (n = 6) during exposure to 90 min of 480 nm light (blue traces) versus 555 nm light (green traces). Irradiance levels are indicated at the top of each plot (photons cm⁻² s⁻¹). Error bars indicate SEM. (B) In a blind individual without rod and cone function, pupillary constriction remained relatively stable during 40 min of exposure to 480 nm or 555 nm light.

Exposure to intermittent light enhances pupillary constriction responses. (A) The pupillary light reflex is shown in sighted participants (n = 6) during exposure to 30 min of continuous green light (gray trace) versus intermittent green light at 1 Hz (black trace) using an LCD monitor. Intermittent light (12 log photons cm⁻² s⁻¹) elicited pupillary constriction responses that were sustained and twice as great relative to exposure to continuous light at the same irradiance level. Error bars indicate SEM. (B) Data from panel A are re-binned and plotted on a logarithmic scale. Pupil diameter increased monotonically during exposure to 30 min of continuous green light (gray circles), whereas intermittent green light prevented pupillary escape (black circles). (C) Median pupillary constriction was about 25% during exposure to 30 min of continuous light, whereas intermittent light elicited pupillary constriction responses greater than 50% in the frequency range from 0.1–4 Hz. (D) Spectral characteristics are shown for the LCD green light stimulus.