Wavefront Shaping for Deep‐Tissue Therapeutic Light Delivery: From Optical Focusing to Precision Photomedicine

Objectives To systematically evaluate wavefront shaping (WFS) as a strategy for deep‐tissue phototherapy, assessing progress and translational readiness across four clinically relevant dimensions. Methods Narrative review of three mainstream WFS strategies—feedback iterative optimization, transmission matrix (TM) measurement, and optical phase conjugation (OPC)—evaluated against the core requirements of phototherapy: penetration depth, energy deposition accuracy, dynamic stability, and clinical translation. Results Time‐reversal of ultrasound‐encoded (TRUE)‐based WFS has achieved TRUE‐based WFS has demonstrated focusing through approximately 2 mm of living brain tissue, substantially exceeding the approximately 1 mm limit of conventional optics. Peak‐to‐background ratios (PBR) exceeding 400 have been demonstrated with natural gradient optimization algorithms, and millisecond‐scale system response times have been achieved with digital optical phase conjugation. However, no study has simultaneously demonstrated millisecond‐scale correction and sustained, therapeutically effective, and safe light‐dose delivery in a living model, and only one study has established a quantitative relationship between WFS optical optimization and a biophysical therapeutic endpoint. Conclusions WFS demonstrates compelling optical capabilities that directly address the physical barriers limiting conventional phototherapy. Clinical translation requires a shift from optical demonstration to therapeutic validation, incorporating standardized preclinical protocols, absolute light‐dose measurement at the target, and multidimensional biological endpoint assessment.