A prospective study of adverse reactions of ALA-PDT for acne vulgaris

BackgroundAcne vulgaris is a chronic inflammatory skin disease around pilosebaceous unit. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for severe acne vulgaris. However, the lack of detailed information of adverse reactions limits the promotion of ALA-PDT in clinic.ObjectiveTo systemically investigate the adverse reactions relating to ALA-PDT for acne vulgaris.MethodsA prospective study was performed at the Shanghai Skin Disease Hospital.ResultsIn the prospective study, 35 patients with acne vulgaris completed the trial. The adverse reactions were first divided into acute-phase adverse reactions, including erythema (94.3%), post-treatment pain (91.4%), burning skin (91.4%), dry skin (91.4%), itching (85.7%), pustule (82.9%), edema (20%) and blister (11.4%), or recovery-phase adverse reactions, which included crust (65.6%), exudation (48.6%) and hyperpigmentation (42.7%). Younger patients were more likely to have pustules (P<0.05). Male patients were represented itching more often than female patients (P<0.05). The efficacy of ALA-PDT for severe acne was positively related to the severity of acute-phase adverse reactions. The duration of pain was shortest. Crusting and hyperpigmentation lasted considerably longer.ConclusionIn the present study, we recorded the relative incidence of various adverse reactions following ALA-PDT for acne vulgaris. The severity of adverse reactions tended to decrease with increased patient age, except for itching and hyperpigmentation. Light-to-moderate adverse reactions might be the inflammatory reactions of ALA-PDT, predicting a good efficacy. A form for evaluation of adverse reactions based on the present study could assist dermatologists in predicting and managing adverse reactions for greater efficacy and higher patient satisfaction.     

The effects of ALA-PDT on microbiota in pilosebaceous units of patients with severe acne: A metagenomic study

Background5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is increasingly used to control severe acne. However, its impact on skin microbiota remains uncertain.ObjectivesWe aimed to compare the makeup, diversity, and function of the microbiota in pilosebaceous units of patients with severe acne before and after ALA-PDT.MethodsA longitudinal cohort study was performed on 11 participants with severe facial acne. All patients were given 5%ALA-PDT every two weeks for three sessions in total. The contents of lesions were sampled for metagenomic sequencing at baseline and two weeks after the first ALA-PDT session.ResultsCutibacterium acnes was the most dominant species followed by Staphylococcus epidermidis and Pseudomonas fluorescens. Treatment with ALA-PDT led to clinical improvements in acne severity concurrent with a significant reduction in the relative abundance of C. acnes, while P. fluorescens increased significantly after ALA-PDT. No significant change was identified in other species. ALA-PDT administration was associated with an increased microbiota diversity and reductions in the relative abundance of the functional genes involved in energy metabolism and DNA replication.ConclusionsALA-PDT plays a therapeutic role by killing C. acnes, increasing P. fluorescens and the microbiome diversity, while inhibiting the function of microbiota in pilosebaceous units of severe acne.     

A systematic review and meta-analysis of randomized clinical trials of fire needle combined with ALA-PDT for the treatment of moderate-to- severe acne

BackgroundModerate-to-severe acne affects people's health and quality of life. As first-line therapeutic medications, isotretinoin and antibiotics are used to treat moderate-to-severe acne, but outcomes can be improved. The combination of fire needle and ALA-PDT may be one option. This study evaluated the safety and effectiveness in the treatment of moderate-to-severe acne by the combination with fire needle and ALA-PDT.MethodsBy July 2022, search PubMed, the Chinese Biomedical Literature dababase, the Cochrane Library, the Chinese Scientific Journal Database, the China National Knowledge Infrastructure, the Web of Science Datebase, Embase Datebase,VIP Database and WanFang Database. To gather RCTs of the combination of fire needle and ALA-PDT for the treatment of moderate-to-severe acne. A meta-analysis was performed according to the Handbook guidelines of Cochrane. Study selection, data extraction, and risk of bias evaluation were all governed by two reviewers, with the help of a third reviewer if necessary. The meta-analysis was carried out with Review Manager Software 5.4.ResultsThere were a total of 9 RCTs with 862 participants. Clinical efficacy was recorded in nine trials, GAGS score was published in three studies, adverse events were documented in five studies, and the recurrence rate was reported in two studies. Treatment lasted between four and twelve weeks. Combination therapy outperformed monotherapy in terms of clinical efficacy (OR:3.73; 95% CI:2.51, 5.53; p < 0.00001). Additional subgroup analysis revealed that the combination therapy outperformed ALA-PDT alone in terms of clinical effect (OR: 3.20; 95% CI: 2.05, 4.99; p < 0.00001). Additionally, combination therapy outperformed fire needle alone in terms of clinical efficacy (OR:5.66; 95% CI: 2.66, 12.08; p < 0.00001). Studies have also indicated that combination therapy has a stronger benefit in lowering the GAGS score (MD:-3.35; 95% CI:-4.62, -2.09; p < 0.00001). Additionally, there was no discernible difference in the occurrence of adverse events between the combined treatments and monotherapy (OR:1.43; 95% CI: 0.76, 2.69; p = 0.26), and the combined treatment was able to control the recurrence rate (OR:0.18; 95% CI: 0.07, 0.45; P = 0.0002).ConclusionsThe efficacy of fire needle combined with ALA-PDT in the treatment of moderate-to-severe acne appears superior to that of ALA-PDT or fire needle alone. However, the conclusions of this study must be interpreted carefully due to the high risk and ambiguity of bias of the included trials.     

A new LED device used for photodynamic therapy in treatment of moderate to severe acne vulgaris

ObjectiveThis study investigated the efficacy and safety of a newly designed LED device used in photodiagnosis and photodynamic therapy of moderate to severe acne vulgaris in Chinese patients.MethodsForty-six patients with moderate to severe facial acne showing high degrees of fluorescence by ultraviolet light examination were illuminated during ALA-PDT with two wavelengths of light (543–548 nm, and 630 ± 6 nm, respectively) after 2 h of incubation with ALA. Each patient received treatment once every 30 days for two or three sessions. Two independent investigators assigned an acne severity score at baseline, one week after each treatment, as well as 4, 8, and 12 weeks after the completion of treatment. Adverse effects were recorded during and after each treatment. All patients rated their satisfaction with the results of treatment at a 12-week follow up visit.ResultsThe ALA-PDL treatment regimen showed an overall effectiveness rate of 89.13% (41/46 patients). Some degree of clinical efficacy was seen in 71.42%, 86.67%, and 95.83% of patients with grades IV, V, and VI acne, respectively, and the rate of clinical effectiveness increased with increasing acne severity. When compared with baseline scores, significant reductions in acne scores were obtained at 8, and 12 weeks after completion of treatment. Maximum efficacy was shown at the 12 week follow up. No severe adverse events were observed.ConclusionALA-PDT administered with the newly designed LED device was an effective treatment for moderate to severe acne vulgaris, and side effects were mild and reversible.     

Effects of 5-aminolevulinic acid photodynamic therapy on TLRs in acne lesions and keratinocytes co-cultured with P. acnes

ObjectiveTo investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the expression of Toll like receptors (TLRs) in human keratinocytes and its role in acne treatment.MethodsTLR2 and TLR4 expression in acne lesions before and after ALA-PDT were examined by immunohistochemical assay. Primary keratinocytes were obtained from acne lesions, co-cultured with P. acnes and then treated with ALA-PDT using red or blue LED. Cytokines production were examined by ELISA, TLR2 and TLR4 gene expression by real-time PCR, and TLR2 and TLR4 protein expression by Western-blot assay.ResultsThe overexpression of TLR2 and TLR4 in acne lesion were detected, which became negative or weaker after ALA-PDT. The infection of P. acnes in keratinocytes could significantly increase the levels of early inflammatory cytokines (e.g. IL-1α, TNF-α and IL-8) (P < 0.05). Such responses could be inhibited by ALA-PDT. P. acnes infection could also significantly increase TLR2 and TLR4 expressions in keratinocytes (P < 0.05), which could be down-regulated by ALA-PDT.ConclusionsALA-PDT could inhibit innate immune responses in keratinocytes treated with P. acnes via TLRs pathways.     

Therapeutic effects of topical photodynamic therapy with 5-aminolevulinic acid on cervical high-grade squamous intraepithelial lesions

BackgroundTopical photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is a non-invasive option for treatment of Cervical Intraepithelial Neoplasia (CIN). We investigated the clinical efficacy and safety of ALA-PDT in treatment of patients with cervical high-grade squamous intraepithelial lesion (HSIL) and evaluated the factors that effect the efficacy of PDT.MethodsA total of 99 patients (average age: 30 years (18–45 years old)) with cervical HSIL and high-risk Human Papilloma Virus (hr-HPV) infections and who had received ALA-PDT were enrolled in this retrospective study. Before ALA-PDT, cervical exfoliated cells from all patients were obtained for HPV genotyping, liquid-based cytology test (LBC) and PAX1 methylation (PAX1^m) test. Then, 6 months after ALA-PDT, HPV genotyping, LBC and colposcopy-directed biopsy were conducted. During subsequent follow-up, HPV genotyping and LBC were performed, and colposcopy-directed biopsy was conducted if hr-HPV was positive and/or LBC result was abnormal.ResultsAt 6 months after treatment, total HPV clearance and lesions complete remission (CR) rates were 64.6% (64/99) and 88.9% (88/99), while at 1-year of follow-up, they were 81.3% (65/80) and 92.5% (74/80), respectively. At 1-year follow-up, HPV clearance rate was higher, relative to 6 months after ALA-PDT (p <0.05). At 6 months after treatment, HPV clearance and CR rates in the PAX1 hypermethylation (PAX1^hm) group were 36.8% and 73.7%, which were lower compared to the rates for PAX1 hypomethylation (PAX1^lm) group (71.3%, 92.5%) (p <0.05). Moreover, of the 11 patients with cervical canal lesions, 3 (3/7, 42.9%) patients had cervical canal HSIL persistence and the other 4 cervical canal HSIL and all of the 4 cervical canal LSIL had complete remission.ConclusionsALA-PDT is an effective, safe treatment approach for patients with cervical HSIL and hr-HPV infections. Patients with PAX1^lm showed better therapeutic outcomes than patients with PAX1^hm or cervical canal HSIL.     

Successful treatment of refractory facial acne using repeat short-cycle ALA-PDT: Case study

Acne vulgaris is a common dermatological disorder. Topical photodynamic therapy (PDT)-mediated with aminolevulinic acid (ALA) or methyl aminolevulinic acid (MAL) has been successfully used in the treatment of moderate to severe acne. The purpose of this case report is to highlight the feasibility of using a repeat weekly short-cycle ALA-PDT to treat severe facial acne lesions refractory to systemic retinoid and antibiotics.     

Efficacy and therapeutic reactions of tri-needle-pretreatment combined with painless ALA-PDT for the treatment of moderate-to-severe acne vulgaris: A randomized controlled trial

Background: Our clinical experience suggests that pretreatment of the original lesions may be crucial for enhancing the efficacy of 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) in moderate-to-severe acne vulgaris. We performed this randomized controlled trial (RCT) to validate this observation.Methods: Efficacy and therapeutic reactions between tri-needle-pretreatment with ALA-PDT (TP-PDT) and conventional ALA-PDT without pretreatment (NP-PDT) were compared. In TP-PDT group, tri-needle-pretreatment was performed using comedone extractors, fire needles, or plum-blossom needles, according to the lesion type. In the TP-PDT group, 5% ALA cream was applied to lesions 30 min before illumination (LED red light: 633±10 nm, 40 mW/cm², 150 J/cm²). In the NP-PDT group, 5% ALA cream was applied 1 h before illumination (60 mW/cm², 72 J/cm²). Patients underwent four sessions, at 1-week intervals. The efficacy was evaluated as the proportion of patients achieving a remarkable effective rate, based on the reduction in the number of lesions. A numeric rating scale was used to assess the severity of pain, erythema, and edema.Results: Forty-eight patients completed the trial. The proportion of remarkable effective rate was significantly greater and the pain score was significantly lower for the TP-PDT than NP-PDT group. The edema score was significantly higher for the TP-PDT than NP-PDT group. There was no difference in erythema scores between the two groups.Conclusion: The tri-needle-pretreatment can improve the efficacy of ALA-PDT, without an increase in pain, for the treatment of moderate-to-severe acne vulgaris. These qualities make the TP-PDT a promising gold standard pretreatment for ALA-PDT for acne vulgaris.     

Effects of ALA-PDT on the macrophages in wound healing and its related mechanisms in vivo and in vitro

BackgroundSeveral studies have suggested the effectiveness of photodynamic therapy (PDT) for wound healing. Macrophages are critical immune cells necessary for regulated inflammation during wound repair. However, the available information regarding the effects of PDT on macrophages during cutaneous wound healing remains insufficient. This study aimed to further investigate these aspects in vivo and in vitro.MethodsMouse full-thickness wound models were used as the study samples to investigate the therapeutic effects and mechanisms of 5-aminolevulinic acid (ALA) PDT. Wound healing rate, granulation tissue formation, local inflammation, M1/M2 macrophages differentiation, were measured at different time points treated by ALA-PDT. The polarization of macrophages induced by ALA-PDT was further evaluated in vitro using PCR and western blot analysis.ResultsALA-PDT could promote formation of granulation tissue, increase inflammatory infiltration and activate M1 macrophages in the early stage of injury. While, ALA-PDT could also facilitate absorption of granulation tissue, inhibit inflammatory infiltration and enhance M2 macrophages polarization in the later stage of wound repair. In vitro, ALA-PDT could modulate the ratio of M2 polarization to M1 polarization via NF-κB signaling pathway.ConclusionsALA-PDT topical application stimulates wound healing by regulating formation of granulation tissue, inflammatory process and M1/M2 macrophages differentiation. The study places a preliminary theoretical basis for topical ALA-PDT to be administered clinically in cutaneous wounds healing.     

5-氨基酮戊酸光动力疗法治疗寻常痤疮的临床观察

目的观察5-氨基酮戊酸光动力疗法(ALA-PDT)治疗寻常痤疮的安全性及有效性。方法将90例中重度痤疮患者随机单盲分为两组:治疗组45例,给予ALA-PDT治疗,1次/10 d,共治疗2～4次;对照组45例,口服异维A酸胶囊,每次10 mg,2次/d,共治疗40 d。在治疗的第10、20、30及40天对两组患者进行疗效判断和比较,同时,记录治疗过程中出现的不良反应。结果治疗组患者经过2～4次治疗后,总有效率为97.8%;对照组治疗结束时总有效率为77.8%,治疗组疗效明显优于对照组(P<0.01)。另外,治疗组复发程度明显低于对照组,且病情控制时间明显延长。治疗组的所有皮损,包括粉刺、丘疹、脓疱、囊肿、结节等均比对照组明显减少。结论 ALA-PDT治疗中重度痤疮的疗效明显优于口服异维A酸胶囊,是一种简单、高效、不良反应轻微的治疗中重度寻常痤疮的新方法。     

Evaluation of 5-aminolevulinic acid-mediated photodynamic therapy on cervical low-grade squamous intraepithelial lesions with high-risk HPV infection

BackgroundThe treatment options for low‐grade squamous intraepithelial neoplasia (LSIL) of the cervix with high-risk HPV infection have not been standardized. Studies show that photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA-PDT) might be effective. In this retrospective study, the clinical efficacy and safety of ALA-PDT in the treatment of LSIL were evaluated.MethodsALA-PDT was performed in 55 LSIL patients aged 21–45 years who also showed high-risk HPV infection and cervical ectropion. HPV test, cytology, colposcopy and pathology were examined before and after treatment. Meanwhile, PDT-related symptoms and adverse reactions were also reviewed.ResultsAt 6-month follow-up after PDT, except for 5 patients who showed the persistence of LSIL lesions, the pathological regression ratio of 90.1% (50/55) was achieved. No HPV-DNA was detected in exfoliated cervical cells in 81.8% (45/55) patients. Among them, the HPV clearance ratio of I Degree cervical ectropion was 96.2%, significantly higher than that of II Degree (70.8%) and III Degree (60%). Significant shrunk of cervical ectropion and reduction of vaginal secretions after PDT were seen in 78.0% patients.ConclusionALA-PDT is a safe and effective therapeutic option for patients of reproductive age who suffer from LSIL with high-risk HPV infection and cervical ectropion.     

局部5-氨基酮戊酸-光动力疗法治疗中重度痤疮疗效分析

目的探讨局部5-氨基酮戊酸-光动力疗法治疗中重度痤疮的安全性及有效性。方法将60例中重度面部痤疮患者随机分为两组。治疗组30例,给予ALA-PDT治疗,每2周治疗1次,共治疗2～4次;对照组30例,单纯红光治疗,每周1次,共8次。在治疗后第2、4、6和8周对两组患者进行疗效判断和比较,同时观察治疗过程中出现的不良反应。结果治疗组和对照组治疗后第8周总有效率分别为96.7%和76.7%,治疗组疗效明显优于对照组(P0.05)。治疗组个别患者出现红斑、少许色素沉着,但无瘢痕形成。结论局部5-氨基酮戊酸-光动力疗法治疗中重度痤疮疗效高、复发率低,不良反应小,优于单纯红光治疗。     

Cytotoxicity of root canal irrigating solutions and photodynamic therapy using curcumin photosensitizer

BackgroundPhotodynamic therapy (PDT) has shown satisfactory antibacterial effects. However, little information regarding the cytotoxicity potential of PDT using curcumin as a photosensitizer (PS) on fibroblasts are found. The aim of this in vitro study was to evaluate the cytotoxicity of root canal irrigating solutions and photodynamic therapy with curcumin PS on the L-929 cell line.MethodsHealthy mouse skin fibroblast cells were distributed into the following 7 experimental groups: G1 – culture medium DMEM (control group); G2 – 0.9% sodium chloride; G3 – 2.5% sodium hypochlorite (NaOCl); G4 – 5% NaOCl; G5 – PDT with curcumin PS at 500 mg/L + blue LED; G6 – PDT with curcumin PS at 750 mg/L + blue LED; and G7 - PDT with curcumin PS at 1000 mg/L + blue LED. All experimental groups which underwent PDT action were submitted to blue LED for 4 min, with a wavelength of 480 nm and energy fluency of 75 J/cm². The cultures were maintained under standard cell culture conditions (37°C, 100% humidity, 5% CO₂). Cell viability analysis was performed using the colorimetric method to evaluate the periods of 6, 24, and 48 h. Data were subjected to the Kruskal–Wallis test, followed by the Dunn test to compare groups and Friedman test to compare periods (α = 0.05).ResultsWhen comparing the periods, no significant differences were observed for any of the experimental groups analyzed (p > 0.05), except for the NaOCl_2.5 group that exhibited higher cell viability at 6 h compared to the period of 48 h (p = 0.0489). In the comparisons of the experimental groups, there were no statistically significant differences between the control group compared to all disinfection protocols, regardless of the period evaluated (p > 0.05), except for the PDT + C₁₀₀₀ group that showed lower cell viability (P < 0.05).ConclusionsPDT with curcumin at 1000 mg/L was cytotoxic on L-929 fibroblast cell culture. However, laser-activated curcumin at a concentration of 500 mg/L presented no influence on L-929 fibroblast cell viability in in vitro conditions.     

Effect of various types of photodynamic therapy on inflammatory and non-inflammatory lesions in patients with acne: A network meta-analysis of randomized controlled trials

BackgroundRecent studies have demonstrated that photodynamic therapy (PDT) is safe and effective in treating acne vulgaris. The present study aimed to evaluate various PDTs on inflammatory and non-inflammatory lesions in patients with acne by a network meta-analysis (NMA) of randomized controlled trials (RCTs).MethodsThe researchers of this paper searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to March 2022 to identify suitable RCTs. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool. Twenty-one RCTs were included, with a total sample size of 898 participants.ResultsNetwork meta-analysis (NMA) revealed that indocyanine green (ICG) + near-infrared (NIR) diode laser, ICG+830 nm light-emitting diode (LED), indole-3-acetic acid (IAA) + 520 nm LED, and 5-aminolevulinic acid (ALA) + sunlight demonstrated obvious curative effects in patients with acne vulgaris. Importantly, ICG+NIR diode laser provided the greatest improvement in both inflammatory and non-inflammatory acne lesions (surface under the cumulative ranking curve [SUCRA]: 84.4% and 93.5%, respectively).ConclusionsBased on the NWM and SUCRA ranking, ICG + NIR diode laser can be considered more effective in treating acne than the other PDTs of the RCTs. However, this conclusion should be interpreted with caution due to the limitations of the present study.     

ALA-PDT combined with oral acitretin in the treatment of refractory condyloma acuminatum in anal canal

BackgroundCondyloma acuminatum (CA) of the anal canal is difficult to treat and subject to relapse.. We investigated the effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with oral acitretin during therapy of refractory CA in the anal canal. We also conducted a clinical retrospective study for the treatment of intra-anal CA.MethodsA total of 101 patients diagnosed with intra-anal CA were enrolled. All patients underwent liquid nitrogen cryotherapy as a basic treatment until visible wart clearance. Patients were divided into two groups depending on the treatment modality after cryotherapy. ALA-PDT group with 51 patients was given ALA-PDT treatment, and ALA-PDT plus acitretin group with 50 patients was given ALA-PDT treatment combined with oral acitretin. The cure rate, recurrence rate, and adverse reactions of the two groups were analyzed and recorded.ResultsThe cure rate in the ALA-PDT plus acitretin group was 94% (47/50), which was significantly higher than 80.4% (41/51) in ALA-PDT group. The recurrence rate in the ALA-PDT plus acitretin group was 6% (3/50), which was lower than 19.6% (10/51) in ALA-PDT group (P<0.05).ConclusionALA-PDT combined with oral acitretin is effective and safe in the treatment of refractory CA in anal canal, and with further study may become an option for these patients.     

Efficacy and safety of ALA-PDT in treatment of diabetic foot ulcer with infection

BackgroundDiabetic foot ulcers (DFUs) with infection is a major clinical issue, as the infection not only potentially devastate the wound healing, but also is the factor that most often leads to amputation. Nevertheless, traditional antibiotic treatment is often insufficient to clear the infection, which could lead to side effects. Photodynamic therapy (PDT) has broad-spectral antibacterial activity. Meanwhile, it is difficult to induce antibiotic resistance. Here, we aim to evaluate the safety and efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of DFUs with infection.MethodsIn our study, 5 diabetic patients with infectious DFUs were diagnosed by pathological examination and the depth of wound was examined by X-Ray. All patients’ wounds were firstly irradiated with 20% ALA-PDT (635 nm, 100 J/cm², 80 mW/cm²) using the red LED to control the infection. Treatment will be combined with debridement if there is granulation necrosis or secretion on the wound surface. PDT sessions were performed weekly in all patients until healing was achieved. All patients were followed up for 0.6–1.2 years after treatment.ResultsIn 5 patients, the DFUs with infection was completely controlled by ALA-PDT. There was no recurrence of DFUs in the follow-up of 0.9 years (range, 0.6–1.2 years) after the treatment.ConclusionsALA-PDT treatment for DFUs with infection show successful outcomes and might ultimately avoid amputation.     

Antimicrobial capacity and physico-chemical characteristics of adhesive resin containing riboflavin after photodynamic therapy

PurposeTo assess the micro-tensile bond strength (μ-TBS), degree of conversion, and antimicrobial capacity of modified dentin adhesive using riboflavin photoinitiators.Materials and methodsThree groups of adhesives (control; 0.1 % riboflavin-PDT and 0.5 % riboflavin PDT) were prepared and tested on 70 sound molar teeth. Fourier-transformed infrared spectroscopy (FTIR) was performed for riboflavin and riboflavin-modified adhesives to calculate the degree of conversion. Contact angle measurement was performed by dropping a 5 μL droplet of the adhesives onto polished dentin disk. For μ-TBS testing, the dentin beams were fixed on a micro-tensile tester and were loaded in tension at a cross-head speed of 1 mm per min until fracture. The viability of Streptococcus mutans biofilm was tested using MTT assay.ResultsThe spectrum at 1728 cm-1 indicates CO stretching frequency of riboflavin. The groups control and 0.1 % riboflavin PDT showed the highest degree of conversion followed by lowest degree of conversion of 0.5 % riboflavin adhesive after PDT. The control adhesive exhibited the highest contact angle over the dentin surface compared to the riboflavin-modified adhesive groups (p < 0.05). The lowest contact angle was observed for 0.1 % riboflavin that showed increased permeability of the adhesive onto the dentin surface (p < 0.05). The variables of immediate bonding (F = 12.328, p = 0.000) and ageing in artificial saliva (F = 41.559, p = 0.000) significantly affected the bond strength. For aged μ-TBS testing, the scores for 0.1 % riboflavin PDT was significantly higher as compared to the 0.5 % riboflavin PDT samples. The MTT resulted in a lower S. mutans viability for 0.5 % riboflavin PDT compared to 0.1 % riboflavin PDT and control adhesive (p < 0.05), irrespective of any time point, that is, after 24 h and 30 days ageing.ConclusionsThe addition of riboflavin as photosensitizer in dentin adhesive demonstrated higher bond strength, excellent antimicrobial capability, and degree of conversion following PDT. The addition of riboflavin in dentin adhesive for PDT could be used as a potential restorative material in adhesive dentistry.     

Early changes in choriocapillaris flow voids as an efficacy biomarker of photodynamic therapy in central serous chorioretinopathy

PurposeTo assess the early changes produced in the choriocapillaris (CC) and choroidal vasculature using swept-source optical coherence tomography angiography (SS-OCTA) in patients with persistent central serous chorioretinopathy (CSCR) as predictors of the efficacy after photodynamic therapy (PDT).MethodsProspective observational study in 52 eyes of 52 patients with persistent subretinal fluid (SRF). SS-OCTA scans of the 6 × 6 mm macular region were assessed before; 2–3 days, one month and three months after half-fluence PDT. Vessel occlusion in the CC and choroid was measured as flow signal voids (FSV).ResultsA 3.67 ± 4.12 and 2.76 ± 3.63 fold increase in CC and CH FSV, due to vessel occlusion, was observed at 2–3 days after PDT versus baseline. There was less SRF at 3 months in patients with an increase in FSV (≥1-fold) compared to those without this increase (<1-fold) after PDT (p ≤ 0.003). An association between the increase in CC and choroidal FSV at the early control (2–3 days) and the height of SRF at 1 month was found (R=-0.405; p = 0.002 and R=-0.356; p = 0.008 respectively). In a multivariate model, the SRF at one month was not associated with age, gender, visual acuity, or FSV (p ≥ 0.288). At 3 months, flow restoration was achieved in the choroid versus the baseline (p = 0.619), but there was a persistent increase in the CC FSV (p = 0.008).ConclusionsEarly vessel occlusion by OCTA after PDT in CSCR was associated with good treatment response. Therefore, an increase in FSV immediately after PDT could be a biomarker to predict SRF resorption.     

Photodynamic therapy for oral potentially malignant disorders: A systematic review and meta-analysis

ObjectivesTo evaluate the effectiveness of Photodynamic Therapy (PDT) in the treatment of Oral Potentially Malignant Disorders (OPMDs) patients.MethodologyAn electronic search was conducted to retrieve articles published until September 2021. Meta-analyses were conducted for the outcomes of complete response (CR) and any response (AR) after treatment with PDT using data from single-arm studies, case series and non-randomised controlled trials (NRCTs).ResultsIn total, 49 articles were included. RCTs revealed insignificant mean difference (MD) in efficacy index between PDT and comparison groups (MD: 1.32; 95% CI:-28.10–30.72, p=0.930). The likelihood of CR (OR:0.84; 95% CI: 0.42–1.71, p=0.637) or AR (OR:2.10; 95% CI: 0.31–14.25, p=0.448) was not different in PDT group when compared with any comparison treatments in NRCTs. CR/AR among single arm studies was 60.6% (95% CI: 50.5–70.7, P<0.001) and 93.7% (95% CI:91.5–95.8, P<0.001) respectively. Higher prevalence of CR and AR was observed for dysplasia or carcinoma insitu (CIS) (CR: 81%, 95% CI: 70.8–91.3, P<0.001; AR: 94.3%; 95% CI: 89–99.6, P<0.001) and actinic cheilitis (AC) (CR: 73.9%, 95% CI: 65.9–81.9, P<0.001; AR:97%; 95% CI:94.9–99, P<0.001).ConclusionsMore than half of the patients receiving PDT showed CR, with more than 90% responding to the treatment. PDT was most effective on oral dysplasias, followed by AC.     

Ten-year treatment complication outcomes of radical prostatectomy vs external beam radiation vs brachytherapy for 1503 patients with intermediate risk prostate cancer

PURPOSETo compare 10-year late complications of radical prostatectomy (RP) versus external-beam-radiation-therapy (EBRT) versus brachytherapy (BT).METHODSRetrospective analysis was performed on 1503 intermediate-risk-prostate-cancer patients treated from 2004 to 2007, using univariate comparisons. Eight hundred and nineteen underwent RP, 574 EBRT, and 110 BT. RP urinary and rectal complications were graded severe if patients required ≥3 pads/diapers per day, chronic condom catheter or penile clamp, daily clean-intermittent-catheterization, sling, artificial-urinary-sphincter, or rectal fistula. Complications for EBRT/BT were severe if graded 3/4 on the Radiation-Therapy-Oncology-Group scale for late effects. The prevalence of erectile-dysfunction-devices (EDD) of injections, pumps and/or penile implants were compared.RESULTSMedian follow-up for RP versus EBRT versus BT were 10.0, 9.6, and 9.8 years. Median age were 62.1, 70.8, 65.3, p < 0.0001. The 10-year prevalence of severe urinary complications for RP versus EBRT versus BT were 10.1%, 12.5%, 4.6%, p = 0.03, and were less for RP <64 years, p = 0.03, and lower Charlson score, p = 0.05. Pretreatment American-Urological-Association (AUA) score existed for 7.3%, 11.5%, 97.3% of RP versus EBRT versus BT, p < 0.0001, and the 10-year prevalence of EDD were 24.3%, 6.6%, 8.2%, respectively, p< 0.0001. Severe rectal complications were slightly higher for EBRT, p = 0.06.CONCLUSIONSBT had lower prevalence of severe urinary complications, possibly by using AUA score to avoid patients with obstructive uropathy. Urinary complications may be reduced by limiting RP to younger, healthier patients, and by avoiding EBRT/BT with obstructive symptoms. RP had higher prevalence of EDD, despite having younger, healthier patients.