Hypothesis

Evening blue‑light blocking improves circadian alignment and sleep quality only in individuals whose chronotype subtype is characterized by a delayed melatonin onset and heightened ipRGC sensitivity to short‑wavelength light.

Rationale

Recent work shows five biologically distinct chronotype subtypes that explain heterogeneous health outcomes of late sleepers [1][2]. Morning and afternoon sunlight advances the sleep midpoint via retinal melanopsin (OPN4) signaling to the suprachiasmatic nucleus [3][4]. However, the effect of removing blue wavelengths after sunset has not been empirically tested [gap]. We propose that subtypes differ in the expression or polymorphisms of OPN4 and downstream signaling components (e.g., G‑protein β‑subunit, arrestin), leading to variable sensitivity to evening blue light. In the 'delayed‑melatonin' subtype, ipRGCs retain heightened responsiveness to short wavelengths, so blue‑light blocking should reduce melanopsin‑driven suppression of melatonin, thereby advancing dim‑light melatonin onset (DLMO). In contrast, subtypes with intrinsically lower ipRGC gain or altered PER3‑mediated feedback will show little change.

Predictions

1. Participants classified as delayed‑melatonin subtype (verified by melatonin assay and PER3 genotype) who wear blue‑light blocking glasses from sunset to bedtime will show a significant advance in DLMO (≥15 min) and reduced PSQI scores compared with a clear‑lens control.
2. No significant shift in DLMO or PSQI will be observed in advanced‑phase, intermediate, or two other subtypes under the same intervention.
3. The magnitude of DLMO advance will correlate with individual ipRGC sensitivity measured via pupil constriction response to 480 nm light before intervention.

Experimental Design

• Recruit 200 healthy adults, stratify into the five chronotype subtypes using hormonal (DLMO) and behavioral (MEQ) criteria plus PER3 genotyping.
• Within each subtype, randomize to blue‑light blocking (amber lenses, ≤500 nm transmission) or placebo (clear lenses) for 2 weeks.
• Collect salivary melatonin every 30 min in dim light to determine DLMO, actigraphy‑derived sleep midpoint, and PSQI at baseline and post‑intervention.
• Measure ipRGC function via infrared pupillometry to a 480 nm pulse at baseline.

Potential Outcomes

If the hypothesis holds, we will see a subtype‑specific benefit of evening blue‑light blocking, refining personalized circadian recommendations beyond broad 'avoid screens at night' advice. A null effect across all subtypes would challenge the presumed efficacy of blue‑light blockers and suggest that evening light mitigation requires alternative strategies (e.g., timing of light exposure rather than spectral filtering).