Line-field confocal optical coherence tomography in dermato-oncology: A literature review towards harmonized histopathology-integrated terminology.

Non-invasive diagnostics like line-field confocal optical coherence tomography (LC-OCT) are being implemented in dermato-oncology. However, unification of terminology in LC-OCT is lacking. By reviewing the LC-OCT literature in the field of dermato-oncology, this study aimed to develop a unified terminological glossary integrated with traditional histopathology. A PRISMA-guided literature-search was conducted for English-language publications on LC-OCT of actinic keratosis (AK), keratinocyte carcinoma (KC), and malignant melanoma (MM). Study characteristics and terminology were compiled. To harmonize LC-OCT terminology and integrate with histopathology, synonymous terms for image features of AK, KC, and MM were merged by two authors, organized by skin layer and lesion-type. A subset of key LC-OCT image-markers with histopathological correlates that in combination were typical of AK, squamous cell carcinoma in situ (SCCis), invasive squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and MM in traditional histopathology, were selected from the glossary by an experienced dermatopathologist. Seventeen observational studies of AK (7 studies), KC (13 studies), MM (7 studies) utilizing LC-OCT were included, with 117 terms describing either AK, KC, or MM. These were merged to produce 45 merged-terms (61.5% reduction); 5 assigned to the stratum corneum (SC), 23 to the viable epidermis, 2 to dermo-epidermal junction (DEJ) and 15 to the dermis. For each lesion, mandatory key image-markers were a well-defined DEJ and presence of mild/moderate but not severe epidermal dysplasia for AK, severe epidermal dysplasia and well-defined DEJ for SCCis, interrupted DEJ and/or dermal broad infiltrative strands for invasive SCC, dermal lobules connected and/or unconnected to the epidermis for BCC, as well as single atypical melanocytes and/or nest of atypical melanocytes in the epidermis or dermis for MM. This review compiles evidence on LC-OCT in dermato-oncology, providing a harmonized histopathology-integrated terminology and key image-markers for each lesion. Further evaluation is required to determine the clinical value of these findings.

Mobile health technologies in an interventional hybrid study on actinic keratosis: Results from an early phase randomized controlled trial investigating the safety and efficacy of a cytosolic phospholipase A2 inhibitor gel in photodamaged skin.

Hybrid trials are a new trend in dermatological research that leverage mobile health technologies to decentralize a subset of clinical trial elements and thereby reduce the number of in-clinic visits. In a Phase I/IIa randomized controlled hybrid trial, the safety and efficacy of an anti-proliferative and anti-inflammatory drug inhibiting cytosolic phospholipase A2 (AVX001) was tested using 1%, 3% or vehicle gel in 60 patients with actinic keratosis (AK) and assessed in-clinic as well as remotely. Over the course of 12 weeks, patients were assessed in-clinic at baseline, end of treatment (EOT) and end of study (EOS), as well as 9 times remotely on a weekly to biweekly basis. Safety outcomes comprising local skin reactions (LSR; 0-5), adverse events (AE) and cosmesis, were graded in-clinic and remotely using patient-obtained smartphone photographs (PSPs) and questionnaires; efficacy was assessed in-clinic based on clinically visible clearance of AK target area of >50%. A total of 55 participants (91.7%) completed the treatment course. The average submission rate of PSPs was high (≥85%), of which 93% were of sufficient quality. No serious AE were reported and only two experienced temporary LSR >2 (scale 0-4) and cosmesis remained stable throughout the study. Based on the mild AE and LSR profile, daily application of AVX001 gel for 1 month appears safe, tolerable, and cosmetically acceptable for use in patients with AK. At EOT, AVX001 achieved a subtle treatment response with clearance of AK target area of >50% in 18% of patients. Remote and in-clinic assessments of LSRs were in high agreement, suggesting that the use of mobile health technologies in early-phase hybrid studies of AK does not compromise patient safety.

Accelerating patient recruitment using social media: Early adopter experience from a good clinical practice-monitored randomized controlled phase I/IIa clinical trial on actinic keratosis.

Background: Patient recruitment is a major cause of delays in randomized controlled trials (RCT). Online recruitment is evolving into an alternative to conventional in-clinic recruitment for RCT. The objective of this study was to test the effectiveness of online patient recruitment for an RCT on actinic keratosis (AK). Methods: In this proof-of-concept study, adults with AK were recruited for a Phase I/IIa RCT (NCT05164393) via social media using targeted advertising Interested users were directed to a landing page to learn about the study, respond to questionnaires, and upload self-obtained smartphone pictures of potential AK. Facebook Analytics was used to track the number of advertisement views, individual users exposed to the advertisement, and advertisement clicks. Following eligibility-review by remote dermatologists, candidates were contacted for an in-clinic visit. A review of pertinent RCTs on AK (2012-2022) was conducted to compare recruitment metrics. Results: The online campaign served 886,670 views, reached 309,000 users, and generated 27,814 clicks. A total of 556 users underwent eligibility review, leading to 140 pre-evaluated potential study subjects. The RCT's enrollment target of 60 patients (68.8 ± 7.1 years, 43.3 % female) was reached in 53 days after screening 90 participants in-clinic, corresponding to a screen failure rate of 33.3 %. The total cost of this online recruitment campaign was 14,285 USD i.e. 238 USD per randomized patient. Compared to the existing literature (44 RCTs), our online approach resulted in 9 times more time-efficient recruitment per site. Conclusion: Using targeted advertisements, 60 patients with AK were recruited for a single-center Phase I/IIa RCT in 53 days. Social media appears to be an efficient platform for online recruitment of patients with low-grade AK for RCT.

Melanin-dependent tissue interactions induced by a 755-nm picosecond-domain laser: complementary visualization by optical imaging and histology.

Fractional picosecond-domain lasers (PSL) induce optical breakdown, which correlates histologically to vacuolization in the epidermis and dermis. In this ex vivo porcine study, we sought to establish a framework for the investigation of laser-tissue interactions and their dependence on melanin density. Light- (melanin index: 24.5 [0-100]), medium- (58.7), and dark-pigmented (> 98) porcine skin samples were exposed to a 755-nm fractional PSL and examined with dermoscopy, line-field confocal optical coherence tomography (LC-OCT), conventional OCT, and subsequently biopsied for digitally stained ex vivo confocal microscopy (EVCM) and histology, using hematoxylin and eosin (HE) and Warthin-Starry (WS) melanin staining. Dermoscopy showed focal whitening in medium- and dark-pigmented skin. Similarly, LC-OCT and OCT visualized melanin-dependent differences in PSL-induced tissue alterations. Vacuoles were located superficially in the epidermis in dark-pigmented skin but at or below the dermal-epidermal junction in medium-pigmented skin; in light-pigmented skin, no vacuoles were observed. Histology confirmed the presence of vacuoles surrounded by areas void of WS staining and disrupted stratum corneum in darker skin. The combined use of optical imaging for multiplanar visualization and histological techniques for examination of all skin layers may mitigate the effect of common artifacts and attain a nuanced understanding of melanin-dependent laser-tissue interactions.

Investigating the efficacy and safety of calcipotriol/betamethasone dipropionate foam and laser microporation for psoriatic nail disease-A hybrid trial using a smartphone application, optical coherence tomography, and patient-reported outcome measures.

There is a lack of efficacious topical treatments for patients suffering from psoriatic nail disease (PND). We investigated the efficacy of Calcipotriol-Betamethasone Dipropionate (Cal/BD) foam with and without ablative fractional laser (AFL) in patients with PND. A total of 144 nails from 11 patients were treated in a 24-week long, open-label, randomized, intra-patient controlled proof-of-concept hybrid trial. In addition to daily Cal/BD foam application, half of each patient's psoriatic nails were randomized to receive optical coherence tomography (OCT)-guided AFL treatment at baseline, 6-, and 12-week follow-ups. In-clinic assessment (N-NAIL), patient-reported outcomes (PROMs), and drug consumption were supplemented by remote evaluation of 15 subclinical OCT features, smartphone app-based safety monitoring, and photo-based assessment (NAPSI). After 24 weeks of Cal/BD foam treatment, patients achieved a significant improvement (p < 0.001) in both clinical (N-NAIL -76%, NAPSI -68%) and subclinical (OCT -43%) PND severity as well as a 71% reduction in PROMs. AFL-assisted Cal/BD treatment led to higher clinical (N-NAIL -85%, NAPSI -78%) and OCT-assessed (-46%) reduction of PND signs than Cal/BD alone (N-NAIL -66%, NAPSI -58%, OCT -37%), but did not reach statistical significance. Smartphone app images documented adverse events and mild local skin reactions, particularly erythema (75%), laser-induced swelling (28%), and crusting (27%). This hybrid trial demonstrated a reduction in clinical NAPSI and N-NAIL scores, subclinical OCT features, and PROMs, suggesting that Cal/BD foam is a safe and efficacious treatment for PND. Larger trials are warranted to prove the clinical benefit of AFL pretreatment as a Cal/BD delivery enhancer.

The Copenhagen Actinic Keratosis Study (COAKS). A decentralised clinical trial to evaluate tolerability, safety and efficacy of daily field-directed topical treatment with cytosolic phospholipase A2 inhibitor, AVX001, in participants with actinic keratosis: protocol for a randomised controlled phase I/IIa trial.

INTRODUCTION: Actinic keratosis (AK) is the most common precancerous skin condition caused by long-term UV exposure. Given the high recurrence rate of 15%-53%, identifying safe and effective treatment options is warranted. AVX001, a cytosolic phospholipase A2α (cPLA2α) enzyme inhibitor, is a novel anti-inflammatory drug for field-directed, self-administered, topical therapy of AK. METHODS AND ANALYSIS: This study is a single-centre, randomised, vehicle-controlled, double-blind, parallel-group hybrid clinical trial in adults with multiple AK lesions Olsen grade 1 or 2. The hybrid design combines decentralised participant tasks and assessments with conventional in-clinic visits. Recruitment using targeted advertising on social media and eligibility prescreening are conducted via the Studies&Me online recruitment platform. Participants (n=60) are randomly assigned to 1 of 3 treatment arms: AVX001 gel 1%, AVX001 gel 3% or vehicle gel. The trial consists of a 4-week treatment period with daily field-directed topical application of the gel and an 8-week follow-up period. Participants attend in-clinic visits at baseline, week 4 and week 12. The remote participant trial tasks include questionnaires and upload of smartphone-obtained photos of the treated skin area using a study-specific web-based app. Both remote and in-clinic assessments of safety and efficacy will be performed. The primary objective is to evaluate the local tolerability of daily application of AVX001 gel (1% or 3%) compared with vehicle gel. Secondary objectives include safety, efficacy, dose-response efficacy relationship, treatment satisfaction and cosmetic outcome. Exploratory objectives include evaluations of tolerability and efficacy assessed by dermatologists using smartphone photos uploaded by participants, comparisons of in-clinic and remote assessments and assessment of AK-related skin changes by non-invasive optical imaging. ETHICS AND DISSEMINATION: Approved by the Ethics Committee of the Capital Region of Denmark (H-21018064) and the Danish Medicines Agency (2021032485). Results will be submitted for publication in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBERS: 2021-000934-32; NCT05164393.

Optical Imaging Visualizes a Homogeneous and Horizontal Band-Like Biodistribution of Large- and Small-Size Hydrophilic Compounds Delivered by Ablative Fractional Laser.

The skin barrier generally limits the topical delivery of hydrophilic molecules. Ablative fractional laser (AFL) facilitates cutaneous drug uptake of smaller hydrophilic compounds in several studies. In this imaging-based study, we aim to investigate the cutaneous biodistribution of two different-sized hydrophilic compounds delivered by an ablative fractional CO2 laser at minimally invasive settings. Intact or CO2 AFL-pretreated (2.5 mJ/mb and 5% density) ex vivo porcine skin was topically applied with a large or small hydrophilic compound (fluorescence labeled antibody nivolumab (150,000 g/mol, n = 4) or ATTO 647N (746 g/mol, n = 3)). Samples were incubated for 20 h in a Franz cell setup, whereafter optical coherence tomography (OCT) was used to assess laser channel depth, and ex vivo confocal microscopy (EVCM) was used to assess epidermal thickness and cutaneous biodistribution of nivolumab and ATTO 647N. With an EVCM-assessed median epidermal thickness of 70.3 µm and OCT-assessed ablation depth of 31.9 µm, minimally invasive settings enabled shallow penetration into the mid-epidermis. The AFL-assisted uptake of the antibody nivolumab and the smaller compound ATTO 647N showed a similar homogenous and horizontal band-like biodistribution pattern that reached mid-dermis. No uptake of nivolumab or ATTO 647N was observed in intact skin. In conclusion, AFL-induced mid-epidermal laser channels facilitates the cutaneous delivery of two hydrophilic compounds that are distributed in a similar homogeneous and horizontal band-like pattern, irrespective of their molecular size.

Fractional CO2 laser ablation leads to enhanced permeation of a fluorescent dye in healthy and mycotic nails-An imaging investigation of laser-tissue effects and their impact on ungual drug delivery.

PURPOSE: Conventional oral antifungal therapies for onychomycosis (OM) often do not achieve complete cure and may be associated with adverse effects, medical interactions, and compliance issues restricting their use in a large group of patients. Topical treatment can bypass the systemic side effects but is limited by the physical barrier of the nail plate. Ablative fractional laser (AFL) treatment can be used to improve the penetration of topical drugs into the nail. This study visualized the effects of laser ablation of nail tissue and assessed their impact on the biodistribution of a fluorescent dye in healthy and fungal nail tissue. METHODS: For the qualitative assessment of CO2 AFL effects on healthy nail tissue, scanning electron microscopy (SEM), coherent anti-Stokes Raman scattering microscopy (CARS-M), and widefield fluorescence microscopy (WFM) were used. To quantitate the effect of laser-pretreatment on the delivery of a fluorescent dye, ATTO-647N, into healthy and fungal nail tissue, ablation depth, nail plate thickness, and ATTO-647N fluorescence intensity in three nail plate layers were measured using WFM. A total of 30 nail clippings (healthy n = 18, fungal n = 12) were collected. An aqueous ATTO-647N solution was directly applied to the dorsal surface of 24 nail samples (healthy n = 12, fungal n = 12) and incubated for 4 hours, of which half (healthy n = 6, fungal n = 6) had been pretreated with AFL (30 mJ/mb, 15% density, 300 Hz, pulse duration <1 ms). RESULTS: Imaging revealed a three-layered nail structure, an AFL-induced porous ablation crater, and changes in autofluorescence. While intact fungal samples showed a 106% higher ATTO-647N signal intensity than healthy controls, microporation led to a significantly increased fluorophore permeation in all samples (p < 0.0001). AFL processing of nail tissue enhanced topical delivery of ATTO-647N in all layers, (average increase: healthy +108%, fungal +33%), most pronounced in the top nail layer (healthy +122%, fungal +68%). While proportionally deeper ablation craters correlated moderately with higher fluorescence intensities in healthy nail tissue, fungal samples showed no significant relationship. CONCLUSION: Fractional CO2 laser microporation is a simple way of enhancing the passive delivery of topically applied ATTO-647N. Although the impaired nail plate barrier in OM leads to greater diffusion of the aqueous solution, AFL can increase the permeability of both structurally deficient and intact nails.

Visualization of energy-based device-induced thermal tissue alterations using bimodal ex-vivo confocal microscopy with digital staining. A proof-of-concept study.

BACKGROUND: Ex-vivo confocal microscopy (EVCM) enables examination of tissue alterations immediately after treatment with energy-based devices (EBDs). This proof-of-concept study aimed to describe EBD-induced tissue effects in ex-vivo porcine skin after treatment with microneedle radiofrequency (MNRF) and ablative fractional CO2 -laser (AFL) using EVCM. MATERIALS AND METHODS: Ex-vivo porcine skin was treated with MNRF and AFL. Three cryosections from each intervention were stained with acridine orange (AO) and scanned with EVCM. Reflectance confocal microscopy (RCM, 638 nm) and fluorescence confocal microscopy (FCM, 488 nm) images were captured and evaluated individually, after image fusion, and after digital hematoxylin and eosin (H&E) staining. RESULTS: Bimodal EVCM was able to visualize EBD-induced thermal alterations in porcine skin. In RCM mode, the full width and depth of the vertically aligned microscopic treatment zones (MTZs) were displayed with clear demarcation to surrounding intact skin. In FCM mode, the ablation of the epidermis after AFL was prominent in contrast with the almost intact epidermis observed in MNRF treated skin. In fusion mode, fluorescence signal from AO marked the surrounding coagulation zone (CZ) from both interventions, with enhanced discrimination between ablation and coagulation. Digitally H&E-stained images closely resembled conventional histopathology but proved superior in terms of visualization of the CZ. CONCLUSION: Bimodal EVCM with digital H&E-staining facilitates the identification and qualitative evaluation of thermal alterations induced by treatment with EBD. By providing high-resolution images comparable to standard histology, EVCM is a useful tool in the research and development of EBD to visualize and evaluate device-tissue interactions.

Imaging of the nail unit in psoriatic patients:A systematic scoping review of techniques and terminology.

BACKGROUND: The growing interest in the visualization of psoriatic nail unit changes has led to the discovery of an abundance of image characteristics across various modalities. OBJECTIVE: To identify techniques for non-invasive imaging of nail unit structures in psoriatic patients and review extracted image features to unify the diverse terminology. METHODS: For this systematic scoping review, we included studies available on PubMed and Embase, independently extracted image characteristics, and semantically grouped the identified features to suggest a preferred terminology for each technique. RESULTS: After screening 753 studies, 67 articles on the visualization of clinical and subclinical psoriatic changes in the nail plate, matrix, bed, folds and hyponychium were included. We identified 4 optical and 3 radiological imaging techniques for the assessment of surface (dermoscopy [n = 16], capillaroscopy [n = 12]), sub-surface (ultrasound imaging [n = 36], optical coherence tomography [n = 4], fluorescence optical imaging [n = 3]), and deep-seated psoriatic changes (magnetic resonance imaging [n = 2], positron emission tomography-computed tomography [n = 1]). By condensing 244 image feature descriptions into a glossary of 82 terms, overall redundancy was cut by 66.4% (37.5%-77.1%). More than 75% of these image features provide additional disease-relevant information that is not captured using conventional clinical assessment scales. CONCLUSIONS: This review has identified, unified, and contextualized image features and related terminology for non-invasive imaging of the nail unit in patients with psoriatic conditions. The suggested glossary could facilitate the integrative use of non-invasive imaging techniques for the detailed examination of psoriatic nail unit structures in research and clinical practice.

Exploring the utility of Deep Red Anthraquinone 5 for digital staining of ex vivo confocal micrographs of optically sectioned skin.

We investigated the utility of the fluorescent dye Deep Red Anthraquinone 5 (DRAQ5) for digital staining of optically sectioned skin in comparison to acridine orange (AO). Eight fresh-frozen thawed Mohs discard tissue specimens were stained with AO and DRAQ5, and imaged using an ex vivo confocal microscope at three wavelengths (488 nm and 638 nm for fluorescence, 785 nm for reflectance). Images were overlaid (AO + Reflectance, DRAQ5 + Reflectance), digitally stained, and evaluated by three investigators for perceived image quality (PIQ) and histopathological feature identification. In addition to nuclear staining, AO seemed to stain dermal fibers in a subset of cases in digitally stained images, while DRAQ5 staining was more specific to nuclei. Blinded evaluation showed substantial agreement, favoring DRAQ5 for PIQ (82%, Cl 75%-90%, Gwet's AC 0.74) and for visualization of histopathological features in (81%, Cl 73%-89%, Gwet's AC 0.67), supporting its use in digital staining of multimodal confocal micrographs of skin.

Noninvasive Assessment of Mycotic Nail Tissue Using an Ultraviolet Fluorescence Excitation Imaging System.

BACKGROUND AND OBJECTIVES: Mycological diagnosis of onychomycosis is based on direct microscopy using external fluorophores to visualize fungal tissue in nail samples and agar culture. Ultraviolet fluorescence excitation imaging (u-FEI) has shown potential in monitoring biological processes by exploiting variations in autofluorescence. This study aimed at assessing the potential of a handheld u-FEI system as a practical screening tool for fungal nail infections. STUDY DESIGN/MATERIALS AND METHODS: Ninety samples from 29 patients with microscopy-confirmed fungal infection and 10 control samples from healthy participants were collected (n = 100). Using a prototype u-FEI system (single bandpass 25 mm filter with a central pass wavelength of 340 nm and a bandwidth of 12 nm, 295 nm excitation flash, resolution of 640 × 480), images of all samples were acquired under standardized conditions. Average and maximum fluorescence intensity image values in arbitrary units (AU) of manually delineated regions of interests were quantitated and statistically assessed for significant differences between healthy and mycotic samples. RESULTS: UV-images clearly depicted all 100 nail samples, with a visibly stronger signal in infected samples. Statistically significant differences (P < 0.05) in signal intensity between mycotic samples and healthy controls were observed for maximum and average fluorescence values. Mean fluorescence values of onychomycotic samples showed 23.9% higher maximum (mycotic: 34.9 AU [standard deviation [SD] 4.7]; healthy: 28.2 AU [SD 1.9]) and 10.2% higher average (mycotic: 27.6 AU [SD 2.0]; healthy: 25.0 AU [SD 0.7]) signal intensity values. Receiver operating characteristic curves demonstrated excellent discriminatory ability (area under the curve > 0.9). Analysis of fluorescence measurements of the reference standard demonstrated very low variation (coefficient of variation = 0.62%) CONCLUSION: Quantitation of u-FEI intensities enables differentiation between healthy and mycotic nail samples, constituting a potential point-of-care tool for cost-effective screening for onychomycosis at a primary care level. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Impregnation of healthy nail tissue with optical clearing agents for improved optical coherence tomography imaging.

OBJECTIVES: The impact of optical tissue clearing on optical coherence tomography (OCT) for nail tissue imaging has not been investigated. This study seeks to compare the effects of an emollient and water on visualization of micromorphology and morphometric outcomes. MATERIALS AND METHODS: Thirty-six healthy nail plates were processed with a fractional CO2 laser, imaged with OCT, and measured with calipers in duplicates. All samples were reassessed after 12-hour long sequential immersion in water and an emollient (Crodamol™ STS). OCT images were evaluated for thickness and scattering signal of the nail. RESULTS: Emollient-impregnation caused stronger scatter responses (P < .0001) and decreased nail thickness (MD 45 µm, P < .0001) measured on OCT. Caliper-derived measurements were not affected by Crodamol™ (MD 11 µm, P = .5538). Hydration increased nail thickness on OCT (MD 49 µm, P < .0001) but reduced thickness measurements taken with calipers (MD 41 µm, P < .0001). Emollient-impregnation improved visualization of onychocytes compared with dry (P = .0209) and hydrated samples (P < .0001), and reduced occurrence of refractive artifacts (P < .0001). CONCLUSION: The use of an emollient for OCT imaging can enhance nail tissue visualization without significant effects on caliper measurements. Hydration of nails, in contrast with emollient-impregnation, may lead to disagreement between caliper- and OCT-measured nail thickness and should be practiced cautiously.

Efficacy of laser treatment for onychomycotic nails: a systematic review and meta-analysis of prospective clinical trials.

Laser therapy for onychomycosis is emerging but its efficacy remains unestablished. To examine current evidence on efficacy of laser treatment of onychomycosis. A systematic review and one-arm meta-analysis, including all prospective clinical trials, identified on PubMed, Cochrane Library, and EMBASE databases. Trials with participants as unit of analysis (UOA), n = 13, were analyzed separately from trials with nails as UOA, n = 7. Summary proportions and 95% confidence intervals (95% CI) were calculated. Outcomes were mycological cure, clinical improvement, or complete cure. Twenty-two prospective trials (four randomized controlled trials and 18 uncontrolled trials) with a total of 755 participants were analyzed. Summary proportions with 95% CI for participants as UOA were mycological cure 70.4%, 95% CI 52.2-83.8%; clinical improvement 67.2%, 95% CI 43.2-84.7%; and complete cure 7.2%, 95% CI 1.9-23.5%. High statistical heterogeneity was detected (mycological cure I2 = 88%, P < 0.01; clinical improvement I2 = 69%, P < 0.01; complete cure I2 = 60%, P = 0.11). The current level of evidence is limited and with high heterogeneity, making it difficult to assess the true efficacy of laser treatment for onychomycosis. Larger randomized controlled trials with well-defined methodology are warranted.

Transfollicular delivery of gold microparticles in healthy skin and acne vulgaris, assessed by in vivo reflectance confocal microscopy and optical coherence tomography.

INTRODUCTION: Topical application of gold microparticles (GMPs) for selective photothermolysis is a recently FDA-cleared therapy for acne vulgaris. Current evidence indicates the potential of optical imaging to non-invasively visualize GMPs and describe photothermal tissue effects. OBJECTIVES: To qualitatively and quantitatively describe GMP delivery in vivo and visualize laser-mediated thermal effects of GMPs in facial skin of acne patients and healthy participants, using reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). METHODS: Patients with facial acne (n = 14), and healthy participants (n = 7) were included. RCM and OCT images were acquired at baseline, after GMP application, and after diode laser exposure. All images were evaluated qualitatively and quantitatively with regards to GMP delivery in skin layers and morphological thermal effects. Lastly, skin biopsies were obtained to compare RCM and OCT findings to histology. RESULTS: GMPs were delivered equally in healthy participants and acne patients, and in lesional and non-lesional acne skin. In RCM images, GMPs appeared as hyperreflective aggregates inside hair follicles and eccrine ducts, corresponding to natural skin openings (NSOs). The fraction of NSOs with hyperreflective content increased significantly after GMP application compared to baseline (50-75% increase, P = 8.88 × 10-16 ). Similarly, in OCT images, GMPs appeared as hyperreflective columns inside hair follicles and were not detected in surrounding skin. GMPs reached a maximum depth of 920 µm (median 300 µm). After laser exposure, RCM and histology revealed selective perifollicular tissue changes around NSOs. CONCLUSION: Optical imaging visualizes GMP delivery and thermal tissue response following laser exposure and enables bedside monitoring of transfollicular microparticle delivery. Lasers Surg. Med. 51:430-438, 2019. © 2019 Wiley Periodicals, Inc.

Correction to: A simple approach for the preoperative assessment of sacral morphology for percutaneous SI screw fixation.

In the original article, co-author's given name has been published incorrectly. The correct given name should be Vinzent Kevin.