Contact lens bioelectronic platform for non-invasive depression treatment with machine-learning-based evaluation

Abstract

Here, we present a wearable, non-invasive contact lens bioelectronic platform designed to enable a more fundamental treatment of depression. Through the implementation of temporal-interference-based transcorneal electrical stimulation (TI-TES), the contact lens platform enables effective delivery of stimulation from the corneal surface to the retina and ultimately to the brain. The TI-TES platform features ultrathin gallium oxide and platinum layers as transparent, flexible electrodes, enabling seamless integration into soft contact lenses. This approach preserves vision and ensures conformal ocular coupling. In a preclinical stress-induced mouse model that recapitulates key behavioral and biological features associated with depression, TI-TES enhanced behavioral resilience, restored prefrontal-hippocampal oscillatory synchrony, and normalized depression-related biomarkers. Machine-learning integration of behavioral, electrophysiological, and biological data consistently distinguished treated from control groups. These preclinical findings establish TI-TES as a non-invasive bioelectronic strategy that overcomes current limitations, enabling selective eye-brain pathway modulation for depression and potentially other brain disorders.