A train of blue light pulses delivered through closed eyelids suppresses melatonin and phase shifts the human circadian system

Figures & data

Table 1 Light mask irradiance and illuminance

Quantity	Units	Blue flash (480 nm)	Green flash (527 nm)	Green continuous (527 nm)
Irradiance on eyelid	W/m^2	111	131	131
Illuminance on eyelid	lux	16,400	74,900	74,900

Table 2 Light mask stimulus quantities

Quantity	Units	Blue flash (480 nm)	Green flash (527 nm)	Green continuous (527 nm)
Mean eyelid optical density ± SD (transmittance)^Citation19	NA	2.56 ± 0.31 (0.0028)	2.27 ± 0.26 (0.0053)	2.27 ± 0.26 (0.0053)
Corneal irradiance	W/m^2	0.31	0.70	0.70
Corneal illuminance*	lux	59	380	380
CLA	NA	290	410	410
CS	NA	0.31	0.38	0.38
Integrated stimulus	W second/m^2	37	84	2,500
(1 hour) on cornea	lux second	7.1 × 10^3	4.5 × 10^4	1.4 × 10^6

Note:

* based upon luminous transmittance of eyelids.

Abbreviations: CS, circadian stimulus; NA, not applicable; SD, standard deviation; CL_A, Circadian illuminance.

Figure 1 Experimental protocol for each 30-hour session.

Notes: Each of four 30 hour sessions began at 6.30 pm. Subjects were given a sleep opportunity at 11.30 pm; otherwise they were awake in dim red light (<1 lx at cornea). Saliva samples for DLMO calculations were taken during both evenings (E1 and E2) of each session every 20 minutes, starting both evenings at 7 pm and ending at 11.20 pm during the first evening (E1) and midnight during the second evening (E2). Each session was associated with a single lighting condition: dark, continuous green light, flashing green light, and flashing blue light. All lighting conditions, including dark, were presented 90–120 minutes after the sleep opportunity period began (large arrow). One blood sample was collected immediately prior to light exposure and another blood sample was collected immediately after.
Abbreviation: DLMO, dim light melatonin onset.

Figure 2 Individual phase shifts in minutes (ordinate) for 16 subjects who completed the four 30-hour experimental sessions (filled diamonds).

Notes: A negative value means that dim light melatonin onset (DLMO) on the second evening occurred later than DLMO on the first evening. The mean ± standard error of the mean are also shown (filled circles). *Represents phase shifts significantly greater than zero (P < 0.05). When DLMO phase shift was adjusted to account for the natural drift that occurs in the dark (control) night, phase shift was significantly greater than zero (P < 0.05) only after exposure to flashing blue light.
Abbreviation: DLMO, dim light melatonin onset.

Table 3 Phase shift, adjusted phase shifts, and nocturnal melatonin suppression for the four 30-hour experimental sessions

	Dark	Flashing blue	Continuous green	Flashing Green
Phase shift (min)
Mean ± SEM	−12 ± 3	−32 ± 8*	−29 ± 10*	−20 ± 6*
Median	−3	−31	−24	−11
Adjusted phase shift (min)
Mean ± SEM		−20 ± 9*	−16 ± 13	−8 ± 11
Median		−22	−13	−4
Melatonin suppression
Mean ± SEM		14% ± 5*	56% ± 4**	7% ± 5
Median		14%	57%	11%

Notes: The mean ± standard error of the mean (SEM) and the median values are shown. The adjusted phase shifts (in minutes) accounted for the natural drift in circadian phase that occurred when subjects remained in the dark

* P < 0.05

** P < 0.01.

Figure 3 Mean ± standard error of the mean adjusted melatonin suppression for the three lighting conditions.

Note: Melatonin suppression significantly greater than zero (*P < 0.05 or **P < 0.01).

BiermanAFigueiroMGReaMSMeasuring and predicting eyelid spectral transmittanceJ Biomed Opt201116606701121721832

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