Cutaneous and Ocular Toxicology最新文献

Background: LUXTURNA^® (voretigene neparvovec-rzyl) is the first FDA-approved gene therapy for inherited retinal dystrophies caused by biallelic RPE65 mutations. While pivotal clinical trials established its safety and efficacy, there has been no formal analysis of real world data to date.

Methods: We reviewed published literature and regulatory safety databases, including the FDA Adverse Event Reporting System and EudraVigilance, to assess clinical outcomes and adverse event reporting associated with LUXTURNA^®.

Results: Clinical trials demonstrated durable functional vision improvements, with approximately 70% of patients maintaining gains up to four years post-treatment. Adverse events reported in trials were largely mild to moderate, such as conjunctival hyperemia, cataract, and transient intraocular pressure elevation. Post-marketing surveillance, however, revealed additional safety concerns, most notably chorioretinal atrophy (CRA), which has been reported in 13-50% of treated eyes, particularly in younger patients and often near the injection site. Disproportionality analyses confirmed CRA as the most prominent adverse event, alongside elevated risks for retinal tears or detachment, intraocular pressure changes, ocular hemorrhage, and inflammation. Despite these findings, central visual acuity was generally preserved, and no systemic toxicity was identified.

Conclusions: LUXTURNA^® provides meaningful and durable visual benefits for patients with RPE65-related disease, but long-term monitoring is essential to address its emerging ocular safety profile. Our data represent the first comprehensive pharmacovigilance review of LUXTURNA^®, providing critical insights for clinical practice and post-marketing surveillance.

Background: Anogenital warts (AGWs) are typically caused by low-risk HPV types. Coinfection with EBV and CMV may influence disease progression, especially under immunosuppression. This study aimed to detect HPV, EBV, and CMV in tissue samples from AGW patients. This descriptive, retrospective, single-center study aimed to detect HPV, EBV, and CMV DNA in paraffin-embedded tissue samples from patients with AGWs.

Material and methods: Paraffin-embedded tissues from 24 AGW patients were analyzed using real-time PCR and pyrosequencing for HPV, EBV, and CMV DNA. Demographic and viral data were statistically evaluated. Degraded or insufficient DNA samples were excluded following quality control assessment. Descriptive and comparative statistical analyses were performed using SPSS v22.0.

Results: HPV was detected in 62.5% of patients, most commonly type 6, followed by types 40, 87, and 16. EBV was found in 2 patients (8.3%), both with HPV coinfection. HPV. CMV was not detected in any samples. No statistically significant associations were found between demographic or clinical parameters and viral positivity.

Conclusion: The study identified rare EBV and HPV coinfections in AGWs but no CMV positivity. These findings are descriptive, and the small sample size limits generalization. The presence of EBV in immunosuppressed individuals may suggest immunotoxic mechanisms affecting viral persistence in the skin. Further studies with larger cohorts are warranted.

Objective: To prepare low-temperature extracted Portulaca oleracea L. (P. oleracea) and investigate the application of masks containing this extract in photorejuvenation for sensitive skin.

Methods: Eligible participants were randomly divided into two groups. Experimental group used the mask for 14 days prior to photorejuvenation. Both groups used the mask for 7 days post-treatment. Changes in physiological parameters and Dermatology Life Quality Index (DLQI) were observed.

Results: Immediately after photorejuvenation, control group showed a significant increase in skin red area and red blood cell concentration, while experimental group did not. At 7 days post-treatment, skin hydration and transepidermal water loss (TEWL) improved significantly in both groups, with greater improvement in the experimental group. Both groups' DLQI decreased, with a significant reduction in the experimental group.

Conclusion: Facial masks containing low-temperature extracted P. oleracea show promising potential in protecting sensitive skin from photothermal stimulation and improving skin barrier function during photorejuvenation therapy.

Objective: Diabetic wounds are slow to heal, causing pain and increasing medical burden. This study aims to develop a skin extracellular matrix (ECM) hydrogel containing ciprofloxacin (CIP) and S-nitrosoglutathione (GSNO) to evaluate its antimicrobial and wound healing effects.

Methods: Porcine skin was used to extract ECM hydrogel via decellularization, followed by loading with CIP and GSNO. Scanning Electron Microscopy (SEM) was used for microstructure and drug distribution characterization. In vitro antibacterial tests, along with human umbilical vein endothelial cell (HUVEC) proliferation and migration assays, were conducted. Animal studies on diabetic mice and histological analysis were performed.

Results: The ECM hydrogel with CIP and GSNO demonstrated uniform drug distribution and significant antibacterial effects, with a 99.2% antibacterial rate against Staphylococcus aureus. In vitro, the hydrogel enhanced HUVEC cell proliferation by 35% and migration by 51%. In diabetic mice, wound healing was accelerated, with a 95.2% healing rate at 14 days, 56.1% higher than the control group. Additionally, bacterial load was reduced by 77.6%, and angiogenesis and collagen fiber formation were promoted.

Conclusion: This study successfully developed a skin ECM hydrogel with dual antimicrobial and healing effects, offering a promising strategy for diabetic wound treatment.

Background: Abilar^® is a wound salve containing 10% medical-grade Norway spruce (Picea abies) resin, known for its antimicrobial and wound-healing properties. However, isolated reports of allergic contact dermatitis have raised concerns regarding its cutaneous safety profile. It is thus important to evaluate any potential for skin irritation and sensitisation.

Objectives: To evaluate the irritation and sensitisation potential of the resin salve using a modified Draize Human Repeat Insult Patch Test (HRIPT) in a healthy adult cohort, thereby providing toxicological insights relevant to both clinical applications and consumer safety.

Methods: A single-blind study was conducted with 215 healthy volunteers (207 completed the study). The resin salve was applied through cutaneous patches in an induction phase and a challenge phase. Skin reactions were evaluated using modified Draize scoring system.

Results: During the induction phase, only 7 of 207 subjects (3.38%) of participants exhibited mild erythema (Grade 1) attributed to the resin salve. Notably, no participant experienced moderate to severe reactions (Grades 2-5). In the subsequent challenge phase, no reactions were observed, and subjects with prior Grade 1 responses reverted to a non-reactive status.

Conclusions: The HRIPT findings demonstrate that medical-grade Picea abies resin salve has a low irritation and sensitisation potential under the conditions tested. Although rare allergic contact dermatitis cases have been reported, the data of this study suggests that the overall risk in the general population is low. These findings are also supported by clinical studies and extensive post-market surveillance of Abilar^® in wound care for both acute and chronic wounds.

Background: Actinic keratosis (AK) is a common premalignant skin condition linked to chronic ultraviolet (UV) exposure and oxidative stress. Systemic biomarkers of redox imbalance in AK remain underexplored.

Aims: To assess systemic oxidative stress in AK using plasma thiol-disulfide homeostasis (TDH) and ischemia-modified albumin (IMA).

Methods: This cross-sectional study included 42 patients with clinically diagnosed AK and 42 age- and sex-matched healthy controls. Native thiol, total thiol, disulfide concentrations, and derived redox indices (Index-1, -2, -3) were measured using a spectrophotometric assay. IMA levels were assessed via the albumin-cobalt binding test. Statistical comparisons and correlation analyses were performed.

Results: Native thiol, total thiol, and disulfide levels were significantly lower in the AK group (p = 0.001), whereas disulfide-based indices showed no significant differences. IMA concentrations were significantly elevated in AK patients (p = 0.001). IMA levels were negatively correlated with native (r = -0.312, p = 0.044) and total thiol (r = -0.309, p = 0.046) values. Patients with Fitzpatrick Type IV skin exhibited significantly higher lesion counts than those with Types II and III (p < 0.05).

Conclusion: AK patients show systemic oxidative imbalance, with reduced thiols and elevated IMA, reflecting persistent UV-induced redox stress and protein oxidation. TDH and IMA may have potential utility as systemic indicators of oxidative stress in AK. Limitations include cross-sectional design, modest sample size, and unmeasured confounders. Future longitudinal and interventional studies should assess causality and antioxidant-based therapies.

Purpose: Ionizing radiation-induced glaucoma (IRG) is an uncommon yet vision-threatening complication that presents primarily as neovascular glaucoma (NVG) after high-dose exposure and normal-tension glaucoma (NTG) after low-dose exposure. Despite increasing recognition, its dose-response relationship, mechanisms, and optimal management remain poorly defined. This review evaluates the clinical spectrum, pathogenesis, and therapeutic approaches of IRG to inform future research and practice.

Methods: A systematic literature search of PubMed/MEDLINE, Embase, Scopus, and the Cochrane Database (1964-2024) was conducted following PRISMA guidelines. Among 7256 screened articles, 37 studies fulfilled the inclusion criteria.

Results: NVG typically develops following ocular radiotherapy exceeding 30 Gy, particularly in patients with uveal melanoma, and is characterized by retinal ischemia, neovascularization, and secondary intraocular pressure elevation. NTG arises from chronic low-dose exposure (< 1 Gy), producing optic nerve injury and visual field loss without elevated pressure. Anti-VEGF therapy can temporarily control NVG progression, whereas trabeculectomy, glaucoma drainage devices, and cyclodestructive procedures are variably employed but often limited by postoperative complications and inconsistent outcomes. The lack of consensus-driven protocols and heterogeneity across studies underscore ongoing clinical challenges.

Conclusions: IRG represents a dose-dependent entity with distinct phenotypes and mechanisms. Current therapies provide partial benefit but remain unsatisfactory in terms of durability and standardization. Advancing the field will require mechanistic studies to clarify radiation-induced optic neuropathy and vascular injury, alongside well-designed trials to establish preventive strategies and evidence-based treatment algorithms.

Background: Pumpkin extracts are rich in vitamins and bioactive compounds, offering antioxidative, anti-inflammatory, and wound-healing properties, making them valuable in dermatology and cosmetics, however pumpkin pulp extracts have not been evaluated before for their cutaneous biological activities.

Methods and results: This study evaluated the biological activity of methanolic pumpkin pulp extracts from six Serbian accessions of Cucurbita (C.) maxima and C. moschata on normal keratinocytes (HaCaT) and melanoma (FemX) cells. The extracts showed no cytotoxicity to normal cells up to 1000 μg/mL and exhibited concentration-dependent cytotoxicity to melanoma cells (determined by MTT assay). They also demonstrated antioxidative effects against H₂O₂-induced oxidative stress in H₂DCFDA assay, and reduced tumor necrosis factor -α/interferon-gamma-γ-induced expression of pro-inflammatory cytokine interleukine-1β in HaCaT cells, as shown in the cell-based ELISA assay. Sun protection factor (SPF) calculations for all six accessions confirmed the photoprotective potential of the extracts, with noticeable differences in SPF values between species and varieties. The highest SPF value was observed in the C. moschata variety.

Conclusion: Significant variations in biological activities among the examined accessions were noted, with C. maxima extracts showing pronounced antioxidant and antiinflammatory properties while C. moschata extract showed the highest SPF values. These findings represent the first report on the skin-beneficial effects of pumpkin pulp extracts, identifying them as sustainable sources of safe, bioactive compounds with antioxidant, anti-inflammatory, and photoprotective properties for dermatological or cosmetic applications.

Background: . . . . Isotretinoin is widely used to treat acne vulgaris. Although primarily targeting the skin, it exerts systemic effects, including rare cardiac manifestations such as arrhythmia. Electrocardiography (ECG) is the standard tool for rhythm monitoring. The frontal QRS-T angle, a novel ECG-based parameter, reflects ventricular depolarisation-repolarisation heterogeneity and has been recognised as a predictor of arrhythmic events. This study aimed to evaluate electrophysiological and biochemical changes associated with isotretinoin, focusing on the frontal QRS-T angle, basic ECG parameters, hemograms, and lipid profiles.

Methods: Forty patients receiving oral isotretinoin (0.5-1 mg/kg/day) for acne vulgaris were prospectively followed. The frontal QRS-T angle, ECG parameters, hemograms, lipid values, heart rate, and blood pressure were recorded at baseline, 3 months, and 6 months.

Results: At 6 months, statistically significant increases were observed in the frontal QRS-T angle and QRS duration, though both remained within accepted reference ranges. P wave duration, PR interval, QTc interval, heart rate, and blood pressure showed no significant changes. Lipid alterations were notable: HDL decreased, while total cholesterol, LDL, and triglycerides increased significantly. Hematological analysis showed stable leukocyte counts, with platelets rising transiently at 3 months and declining at 6 months.

Discussion: .Isotretinoin therapy was associated with measurable changes in cardiac electrophysiology and lipid metabolism. The frontal QRS-T angle may provide an early ECG marker of arrhythmic risk, supporting its inclusion in dermatologic pharmacovigilance. Concurrent lipid alterations may enhance arrhythmic vulnerability, underscoring the importance of cardiac and metabolic monitoring during isotretinoin treatment.

Introduction: Although omalizumab is a highly effective treatment against chronic spontaneous urticaria (CSU), the treatment duration for response varies among patients. Thus, determining easy-to-access predictive biomarkers of omalizumab response is essential.

Objective: This study aimed to investigate the value of baseline hematological and inflammatory parameters and patient-specific features as predictive markers of response to standard-dose omalizumab.

Methods: This single-center retrospective cohort study was conducted on 242 patients with CSU treated with omalizumab 300 mg every 4 weeks for at least 6 months between 2014 and 2025. The demographics, clinical features, treatment responses, and baseline laboratory tests were assessed. Response to omalizumab was evaluated based on the weekly Urticaria Activity Score (UAS7). Patients were categorized as early responder (ER, within 3 months), late responder (LR, after 3 months), and nonresponder (NR).

Results: Of patients, 180 (74.4%) were classified as ER, 28 (11.6%) as LR, and 34 (14%) as NR. ERs had higher white blood cell (WBC) and lymphocyte counts (p = 0.047 and p = 0.005, respectively) and lower mean platelet volume (MPV)/lymphocyte ratio (MPVLR) (p = 0.008). LRs had higher mean corpuscular hemoglobin concentration (MCHC) and platelet/lymphocyte ratio (PLR) (p = 0.023 and p = 0.014, respectively) and lower MPV levels (p = 0.043). The platelet distribution width (PDW) was higher in the NRs (p = 0.011). Red cell distribution width-coefficient of variation (RDW-CV) [odds ratio (OR): 0.793, 95% confidence interval (CI): 0.641-0.980, p = 0.032], WBC count (OR: 1.418, 95% CI: 1.093-1.840, p = 0.009), and PDW (OR: 0.813, 95% CI: 0.693-0.954, p = 0.011) were found to be the independent predictors of responders. The lymphocyte count (OR: 1.713, 95% CI: 1.122-2.613, p = 0.013) and MPVLR (OR: 0.427, 95% CI: 0.218-0.837, p = 0.013) were independent predictors of ER, whereas MCHC (OR: 2.368, 95% CI: 1.522-3.686, p < 0.001) and PLR (OR: 1.010, 95% CI: 1.003-1.017, p = 0.003) were independent predictors of LR. The receiver operating characteristic curve analysis results showed that the predictive strengths of RDW-CV, WBC count, PDW, lymphocyte count, MPVLR, MCHC, and PLR were low (the area under the curve values 0.634, 0.620, 0.672, 0.656, 0.621, 0.649, and 0.624, respectively; all p < 0.05), suggesting the limited use of these parameters in clinical practice.

Study limitations: The limitations of this study included its single-center, retrospective design, lack of external validation, and reliance solely on UAS7 for assessing disease activity.

Conclusions: WBC and lymphocyte counts, RDW-CV, PDW, MPVLR, MCHC, and PLR can be considered when appraising the omalizumab re