Ocular Social Jetlag: A Driver of Immune-Metabolic Dysfunction in Dry Eye Disease

Yating ZhouJian YinYuliang GuTuo Jin^*

• Kunshan Traditional Chinese Medicine Hospital, Kunshan, China

Dry eye disease (DED) is increasingly prevalent among young individuals and often exhibits severe symptoms despite minimal structural damage, challenging the traditional structure–inflammation paradigm. We propose the concept of ocular "social jetlag," defined as chronic circadian misalignment imposed by modern lifestyles, as a key upstream driver of meibomian gland dysfunction and contemporary DED. We integrate emerging evidence to suggest that social jetlag disrupts peripheral ocular clocks, triggering immune–metabolic circadian reprogramming characterized by metabolic stress, loss of temporal immune gating, oxidative amplification, and inflammasome activation. This cascade precedes overt tissue damage and explains the mismatch between symptoms and structural findings. Viewing the ocular surface as a dynamic biosensor of systemic clock–immune–metabolism networks, we further highlight digital immune phenotyping and chronotherapeutic interventions as promising strategies for precision management. This framework reframes DED from a purely local disorder to a rhythm-driven systemic condition, opening new avenues for mechanism-based prevention and treatment.