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

## TL;DR

This paper reviews non-invasive imaging tools to better assess treatment success in actinic keratosis, aiming to reduce recurrences and unnecessary biopsies.

## Contribution

The paper introduces a multimodal framework integrating advanced imaging techniques for more accurate non-invasive monitoring of actinic keratosis treatment response.

## Key findings

- Reflectance confocal microscopy and line-field optical coherence tomography detect residual disease not visible clinically.
- High-frequency ultrasound tracks superficial dermal remodeling after field-directed therapies.
- Dermoscopy alone may miss subclinical persistence, highlighting the need for multimodal strategies.

## Abstract

Actinic keratoses are common skin lesions caused by long-term sun damage and may progress to skin cancer. After field-directed treatments, such as photodynamic therapy or topical drugs, lesions often appear clinically healed, but microscopic disease may persist and lead to recurrence. This review explains why clinical examination and dermoscopy alone may not be sufficient to assess treatment success, and discusses how non-invasive imaging techniques can improve follow-up. We summarize how advanced tools, including reflectance confocal microscopy, line-field optical coherence tomography, and high-frequency ultrasound can detect subtle residual disease and tissue recovery that are not visible to the naked eye. We also describe emerging optical approaches that analyze tissue chemistry. By integrating these methods in a multimodal strategy, clinicians may better evaluate treatment response, reduce unnecessary biopsies, and improve long-term management of sun-damaged skin.

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.