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Periorbital hyperpigmentation can be caused by shallow vascularization or thin skin in the infraorbital region, hyperpigmentation due to atopic or contact dermatitis, familial predisposition, symptomatic tear troughs, localized shadowing from skin laxity, excessive sun exposure, smoking, sleep deprivation, and fatigue (Citation2,Citation8)

doi: 10.1016/j.plantsci.2017.07.009 147 RoL

In endothelial cells, compensatory hyperinsulinemia can preferentially engage SHC/MAPK signaling, promoting expression of inflammatory mediators and adhesion molecules (ICAM-1, VCAM-1, E-selectin) while further suppressing PI3K/Akt activity [1012]