Non-Invasive Assessment of Treatment Response in Actinic Keratosis: A Clinically Oriented Multimodal Review

BACKGROUND: In actinic keratosis (AK), clinical clearance after field-directed therapies does not necessarily correspond to histological resolution, resulting in subclinical persistence and risk of recurrence. OBJECTIVE: To provide a practical, up-to-date framework for non-invasive monitoring of treatment response in AK, integrating clinical assessment and dermoscopy with high-resolution imaging techniques, reflectance confocal microscopy (RCM), line-field confocal optical coherence tomography (LC-OCT), and high-frequency ultrasound (HFUS), and to discuss emerging optical biomarkers based on Raman spectroscopy. RESULTS: For each modality, we summarize pre- and post-treatment imaging patterns, proposed response criteria, recommended follow-up timing, and correlations with clinical outcomes (including clearance and AKASI) and, when available, histological findings. The available evidence is derived from a limited number of observational studies, predominantly involving RCM and LC-OCT, whereas data on HFUS and Raman spectroscopy remain comparatively scarce. RCM and LC-OCT allow in vivo assessment of epidermal architectural normalization and reduction of intraepidermal keratinocyte atypia. HFUS captures quantitative trajectories of superficial dermal remodeling, including changes in the subepidermal low-echogenic band (SLEB) and dermal echogenicity after photodynamic therapy and other field treatments. Dermoscopy remains the first-line tool for routine follow-up but may fail to detect minimal subclinical persistence. Finally, we discuss the potential role of in vivo Raman spectroscopy for dynamic molecular endpoints and its possible integration with artificial intelligence-based analytical approaches. CONCLUSIONS: A standardized multimodal follow-up strategy improves the accuracy of treatment-response assessment compared with clinical evaluation alone. We propose a technique-specific checklist of minimal response criteria and a pragmatic temporal assessment scheme, and outline a research roadmap to support validation and clinical implementation of non-invasive imaging-guided monitoring in actinic keratosis.