Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study.

BACKGROUND: Acute hepatic porphyria is a group of multisystem disorders of which acute intermittent porphyria is the most common subtype. Givosiran, a subcutaneously administered RNA interference therapeutic targeting liver ALAS mRNA, is approved for treating these disorders. This Phase 1/2 open-label extension study (NCT02949830) evaluated the long-term safety and efficacy of givosiran in adults with acute intermittent porphyria, with follow-up of up to 48 months, which is the longest follow-up of givosiran treatment to date. Participants were adults aged 18-65 years who completed part C of the Phase 1 givosiran study (NCT2452372). METHODS: Enrollees received givosiran for up to 48 months. Primary and secondary endpoints included the incidence of adverse events, changes in urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, annualized rate of porphyria attacks, and annualized hemin use. Quality of life was assessed using the EQ-5D-5L instrument as an exploratory endpoint. RESULTS: Sixteen patients (median age: 39.5 years) participated. Common adverse events included abdominal pain, nasopharyngitis, and nausea (50% each), with injection-site erythema (38%) and injection-site pruritus (25%) noted as frequent treatment-related reactions. Givosiran therapy reduced annualized rates of porphyria attacks and hemin use by 97% and 96%, respectively. From months > 33 to 48, all patients were free from attacks requiring significant medical intervention and did not use hemin. There were substantial reductions in median urinary ALA and PBG of 95% and 98%, respectively. Additionally, a clinically meaningful improvement in quality of life was observed. CONCLUSIONS: In the longest follow-up of givosiran-treated patients reported to date, the therapy maintained an acceptable safety profile and demonstrated sustained improvements in clinical outcomes over 4 years in patients with acute intermittent porphyria.

Efficacy of Aminolevulinic Acid Mediated Photodynamic Therapy in the Treatment of Oral Premalignant Lesions: A Systematic Review.

BACKGROUND: Aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) is considered as an effective treatment option for oral premalignant lesions. ALA is a Food and Drug Administration (FDA) approved second-generation photosensitizer (PS) used both orally as well as topically. OBJECTIVE: This systematic review aims to evaluate the efficacy of ALA-PDT for the treatment of oral premalignant lesions. METHODS: The focused question was, "Is ALA-PDT effective in the treatment of oral premalignant lesions?"A literature search was made in PubMed/Medline and GoogleScholar using different combinations of the following keywords: photodynamic therapy, oral premalignant lesions, oral leukoplakia (OL), erythroplakia, oral erythroleukoplakia (OEL), oral verrucous hyperplasia (OVH); and oral lichen planus (OLP). Review articles, preclinical studies, case-reports, commentaries, letters to the Editor, unpublished articles, studies on photodynamic therapy used in areas other than the oral cavityand, articles published in languages other than English were excluded. The relevant information was summarized. RESULTS: There were initially 64 results for the above parameters; 47 studies were excluded, leaving 17 studies for analysis. Characteristics of the included studies, PS, and PDT protocol were summarized. CONCLUSION: The outcome of the included studies suggested that ALA-PDT is an effective, easy to perform technique, well tolerated treatment with encouraging achievements in the treatment of oral premalignant lesions. No systemic side effects and skin photosensitivity were reported with topical ALA even within initial 48 hours after PDT, and patients were not required to avoid exposure to light following treatment. The clinical outcome of the ALA-PDT application, as reported in the studies, was also very promising, with either diminution in the size of the lesion or complete remission or improvement in signs and symptoms as well as reduced recurrence.

Oncolytic Newcastle Disease Virus and Photodynamic Therapy as Dual Approach for Breast Cancer Treatment.

OBJECTIVE: We hypothesized that attacking cancer cells by combining various modes of action can hinder them from taking the chance to evolve resistance to treatment. Incorporation of photodynamic therapy (PDT) with oncolytic virotherapy might be a promising dual approach to cancer treatment. METHODS: NDV AMHA1 strain as virotherapy in integration with aminolaevulinic acid (ALA) using low power He-Ne laser as PDT in the existing work was examined against breast cancer cells derived from Iraqi cancer patients named (AMJ13). This combination was evaluated using Chou-Talalay analysis. RESULTS: The results showed an increased killing rate when using both 0.01 and 0.1 Multiplicity of infection (MOI) of the virus when combined with a dose of 6172.8 photons/gm (ph/gm) of PDT focused on cancer cells. CONCLUSION: integration of the attenuated NDV-AMHA1 strain with photodynamic therapy has a synergistic killing effect on breast cancer cells in vitro, suggesting that this strategy could have clinical application to overcome breast cancer.

The m-TORC1 inhibitor Sirolimus increases the effectiveness of Photodynamic therapy in the treatment of cutaneous Squamous Cell Carcinoma, impairing NRF2 antioxidant signaling.

Squamous Cell Carcinoma (SCC) is a subtype of Non-Melanoma Skin Cancer, the most common group of malignancies worldwide. Photodynamic therapy (PDT) is a non-invasive treatment approved for specific subtypes of SCC. Some malignancies resist PDT, forming more aggressive tumors and multiple relapses. Thus, new approaches aimed at optimizing the response to PDT are needed. The mTORC1 inhibitor rapamycin, also known as Sirolimus (SRL), interferes with protein synthesis and cell metabolism. The use of SRL as an immunosuppressant is associated to lower rates of SCC in kidney-transplanted patients, which are frequently affected by this pathology. We have evaluated SRL pre-treatment efficacy to enhance the damage induced by PDT with Methyl 5-aminolevulinate in two different cutaneous SCC established cell lines (SCC13 and A431) in vitro and therapy sensitization in PDT-resistant cell lines. We tested for the first time the SRL + PDT combination in a SKH-1 mouse model of photocarcinogenesis, diminishing the frequency of lesions and restraining tumor growth. Molecular studies revealed that protoporphyrin IX and reactive oxygen species production induced by PDT were promoted by SRL pre-treatment. Lastly, SRL modifies the expression and intracellular location of NRF2, interfering with the downstream antioxidant response modulated by NQO1 and HO-1. In conclusion, we propose SRL as a potential adjuvant to enhance PDT efficacy for SCC treatment.

5-Aminolaevulinic acid-based photodynamic therapy suppresses lipid secretion by inducing mitochondrial stress and oxidative damage in sebocytes and ameliorates ear acne in mice.

Acne is a chronic inflammatory skin disease with wide-ranging effects, involving factors such as Propionibacterium acnes (P. acnes) infection and sebum hypersecretion. Current acne treatments are challenged by drug resistance. 5-aminolaevulinic acid (ALA) -based photodynamic therapy (PDT) has been widely used in the clinical treatment of acne, however, the mechanism of its action remains to be elucidated. In this study, by constructing a mice ears model of P. acnes infection, we found that ALA-PDT inhibited the proliferation of P. acnes in vivo and in vitro, significantly ameliorated ear swelling, and blocked the chronic inflammatory process. In vitro, ALA-PDT inhibited lipid secretion and regulated the expression of lipid synthesis and metabolism-related genes in SZ95 cells. Further, we found that ALA-PDT led to DNA damage and apoptosis in SZ95 cells by inducing mitochondrial stress and oxidative stress. Altogether, our study demonstrated the great advantages of ALA-PDT for the treatment of acne and revealed that the mechanism may be related to the blockade of chronic inflammation and the suppression of lipid secretion by ALA-PDT.

Carrier cascade target delivery of 5-aminolevulinic acid nanoplatform to enhance antitumor efficiency of photodynamic therapy against lung cancer.

5-Aminolevulinic acid (5-ALA) is a prodrug of porphyrin IX (PpIX). Disadvantages of 5-ALA include poor stability, rapid elimination, poor bioavailability, and weak cell penetration, which greatly reduce the clinical effect of 5-ALA based photodynamic therapy (PDT). Presently, a novel targeting nanosystem was constructed using gold nanoparticles (AuNPs) as carriers loaded with a CSNIDARAC (CC9)-targeting peptide and 5-ALA via Au-sulphur and ionic bonds, respectively, and then wrapped in polylactic glycolic acid (PLGA) NPs via self-assembly to improve the antitumor effects and reduce the side effect. The successful preparation of ALA/CC9@ AuNPs-PLGA NPs was verified using ultraviolet-visible, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The analyses revealed good sphericity with a particle size of approximately140 nm, Zeta potential of 10.11 mV, and slow-controlled release characteristic in a weak acid environment. Confocal microscopy revealed targeting of NCL-H460 cells by NPs by actively internalising CC9 and avoiding the phagocytic action of RAW264.7 cells, and live fluorescence imaging revealed targeting of tumours in tumour-bearing mice. Compared to free 5-ALA, the nanosystem displayed amplified anticancer activity by increasing production of PpIX and reactive oxygen species to induce mitochondrial pathway apoptosis. Antitumor efficacy was consistently observed in three-dimensionally cultured cells as the loss of integrity of tumour balls. More potent anti-tumour efficacy was demonstrated in xenograft tumour models by decreased growth rate and increased tumour apoptosis. Histological analysis showed that this system was not toxic, with lowered liver toxicity of 5-ALA. Thus, ALA/CC9@AuNPs-PLGA NPs deliver 5-ALA via a carrier cascade, with excellent effects on tumour accumulation and PDT through passive enhanced permeability and retention action and active targeting. This innovative strategy for cancer therapy requires more clinical trials before being implemented.

Recurrent squamous cell carcinoma of the upper eyelid treated with combination therapy of ALA photodynamic therapy and surgery with secondary healing.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) frequently occurs in photoexposed areas. Surgery remains the mainstay of treatment in attempts to reduce recurrence, but it must be combined with other therapy because of the limited excision possible in the region of the eyelid, lip, and nose. Photodynamic therapy (PDT) is a relatively new treatment modality that involves the administration of a photosensitizing drug and its subsequent activation by specific wavelengths of light to produce reactive oxygen species that specifically destroy target cells. CASE REPORT: An 87-year-old female presented 4 weeks after initial resection with recurrent medium-differentiated cSCC measuring 5.2 cm × 3 cm × 2 cm in the left upper eyelid. Subsequent treatment involved palliative resection with an additional 1 cm at 3 margins of the tumor (excluding the bottom edge of the double eyelid line) and 3 applications of PDT using 5-aminolevulinic acid as the photosynthesizing agent in the open wound over a 2-week period. The wound healed well within 6 weeks. During the following 4 years, the patient showed satisfactory progress in both aesthetics and function, with no sign of recurrence or metastasis. CONCLUSION: Refractory cSCC was successfully managed using a combination of PDT and secondary healing, and functions of the head and face were well protected. These results suggest that such management warrants consideration in clinical settings.

Photodynamic therapy for facial dermatosis papulosa nigra: Efficacy and safety in a preliminary study.

Dermatosis papulosa nigra (DPN) is a type of benign epidermal hyperplasia that affects the appearance of patients and poses a threat to their physical and mental health. Photodynamic therapy (PDT) has been shown to have the advantages of non-invasiveness, efficacy, and low recurrence in the treatment of skin disorders. However, no studies have been reported on the use of PDT for the treatment of DPN. Therefore, we used PDT for the first time to treat DPN and monitor its efficacy. Forty-five patients with DPN diagnosed at the outpatient clinic of Changzhou First People's Hospital were treated with 10 % 5-aminolevulinic acid (ALA) once a week for four consecutive weeks and followed for 3 months. After four treatment sessions, the cure rate among the 45 patients was 71.1 %, and the overall efficacy rate was 93.3 %. The most common adverse reactions were mild erythema, edema, and temporary pigmentation. PDT is expected to become a new and effective treatment for DPN.

Clinical efficacy of a new therapeutic option for lower genital tract lesions: 5-ALA photodynamic therapy.

The study utilized 5-ALA-PDT to treat patients with CIN or VaIN and assessed their clinical response, HPV clearance, and influencing factors after photodynamic therapy (PDT). This study involved 56 patients who received 5-ALA-PDT in a single center from May 2020 to March 2022, including 12 patients with CIN, 30 patients with VaIN, and 14 patients with both CIN and VaIN. Follow-up were conducted within 6 and 12 months after treatment to evaluate the clinical effectiveness of PDT. The assessment criteria included histological response (ER, elimination rate, RR, regression rate) and HPV clearance. Additionally, factors that could potentially influence the outcomes were analyzed. After PDT, the histological response showed an ER of 48.2% (27/56) and a RR of 80.4% (45/56) within 6 months of follow-up. The elimination rate increased to 69.6% (39/56) within 12 months, along with a regression rate of 82.1% (46/56). The rates of HPV clearance were observed to be 37.5% (21/56) and 44.6% (25/56) within 6 and 12 months, respectively. The study also revealed that HPV clearance significantly influenced histologic elimination within 6 months (p < 0.001) and histologic regression within 12 months (p < 0.01). Furthermore, premenopausal women exhibited a higher HPV clearance rate compared to postmenopausal women (61.5% vs. 30.0%, p = 0.036). 5-ALA PDT can be considered as an available option for the treatment of lower genital squamous intraepithelial lesions. The efficacy of its histologic response depends on HPV clearance. Additionally, it has been found that premenopausal women may benefit more from this treatment.

Preliminary analysis of the efficacy of Mohs micrographic surgery combined with photodynamic therapy in a case of noninvasive extramammary Paget's disease.

PURPOSE: To evaluate the efficacy of Mohs micrographic surgery (MMS) combined with photodynamic therapy (PDT) in treating non-invasive extramammary Paget's disease (EMPD). MATERIALS AND METHODS: A 77-year-old male patient with non-invasive EMPD was treated with MMS followed by PDT. Preoperative fluorescence localization using 5-aminolevulinic acid (ALA) was performed to determine the surgical scope. MMS was conducted under lumbar anesthesia with intraoperative frozen-section pathology. Postoperative PDT was administered weekly for three sessions. RESULTS: The patient achieved negative surgical margins after two rounds of intraoperative pathology. Postoperative follow-up over two years showed no recurrence, and the patient did not experience significant adverse reactions. CONCLUSION: The combination of MMS and PDT was effective in treating non-invasive EMPD, demonstrating favorable clinical outcomes and no recurrence over the two-year follow-up period.

Successful treatment of a lactating women with severe acne through the combination of fire needle and photodynamic therapy: A case report.

Severe acne, characterized by cysts and nodules, can significantly impact a patient's self-image and quality of life [1]. In China, first-line treatments for severe acne typically include oral isotretinoin, topical benzoyl peroxide, and oral or topical antibiotics [2]. However, due to concerns about safety, oral isotretinoin and antibiotics are not recommended for lactating women, posing challenges in treating acne in this population and often leading to emotional distress. While photodynamic therapy has shown effectiveness in patients unwilling to take oral medications [3], treating severe acne during lactation remains a complex issue with limited research available. In this unique case, fire needle combined with photodynamic therapy was successfully utilized to address severe acne in a lactating patient. Following treatment, the patient experienced clearance of cysts, nodules, and pustules, as well as an improvement in depressive symptoms, yielding significant outcomes. Nevertheless, the efficacy and safety of this combined approach warrant further investigation through clinical trials.

Prediction of the short-term efficacy and recurrence of photodynamic therapy in the treatment of oral leukoplakia based on deep learning.

BACKGROUND: The treatment of oral leukoplakia (OLK) with aminolaevulinic acid photodynamic therapy (ALA-PDT) is widespread. Nonetheless, there is variation in efficacy. Therefore, this study constructed a model for predicting the short-term efficacy and recurrence of OLK after ALA-PDT. METHODS: The short-term efficacy and recurrence of ALA-PDT were calculated by statistical analysis, and the relevant influencing factors were analyzed by Logistic regression and COX regression model. Finally, prediction models for total response (TR) rate, complete response (CR) rate and recurrence in OLK patients after ALA-PDT treatment were established. Features from pathology sections were extracted using deep learning autoencoder and combined with clinical variables to improve prediction performance of the model. RESULTS: The logistic regression analysis showed that the non-homogeneous (OR: 4.911, P: 0.023) OLK and lesions with moderate to severe epithelial dysplasia (OR: 4.288, P: 0.042) had better short-term efficacy. The area under receiver operating characteristic curve (AUC) of CR, TR and recurrence predict models after the ALA-PDT treatment of OLK patients is 0.872, 0.718, and 0.564, respectively. Feature extraction revealed an association between inflammatory cell infiltration in the lamina propria and recurrence after PDT. Combining clinical variables and deep learning improved the performance of recurrence model by more than 30 %. CONCLUSIONS: ALA-PDT has excellent short-term efficacy in the management of OLK but the recurrence rate was high. Prediction model based on clinicopathological characteristics has excellent predictive effect for short-term efficacy but limited effect for recurrence. The use of deep learning and pathology images greatly improves predictive value of the models.

Effectiveness of photodynamic therapy on treatment response and survival in patients with recurrent oral squamous cell carcinoma: A systematic review.

BACKGROUND: This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC). METHODS: Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature. RESULTS: The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, PhotofrinⓇ, FoscanⓇ and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. PhotofrinⓇ and FoscanⓇ were the most used photosensitisers, with more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue. CONCLUSIONS: Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations, which considered four photosensitisers, PhotofrinⓇ was the most used but more recent photosensitisers like FoscanⓇ have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC.

A nomogram to predict anal condyloma acuminatum recurrence in HIV-negative patients following photodynamic therapy: A decade-long retrospective clinical study at a single tertiary hospital.

BACKGROUND: Anal condyloma acuminatum (CA) is marked by its thorny treatment and high recurrence rate. Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrates significant efficacy and safety in treating anal CA, it does not completely prevent recurrence. This study aimed to develop and validate a nomogram model in predicting the risk of relapse in HIV-negative patients with anal CA following treatment with ALA-PDT. METHODS: A retrospective analysis was conducted on patients diagnosed with anal CA who received combined CO2 laser vaporization and ALA-PDT between January 2013 and May 2023. Patients were divided into recurrence and non-recurrence groups. A nomogram was developed based on factors showing statistical significance in multivariable logistic regression analysis. The discriminative ability and clinical utility of the nomogram were assessed via ROC curves and decision curve analysis, with internal validation performed through bootstrap resampling. RESULTS: Among the 176 patients included, 33 (18.75 %) experienced recurrence, while 143 did not. Independent predictors for recurrence included HPV types, history of anal intercourse, and the number of CO2 laser treatments received. Incorporating these predictors, the nomogram demonstrated a superior diagnostic performance (area under the curve = 0.881, 95 % CI: 0.818-0.935) and a significant net benefit in decision curve analysis. CONCLUSIONS: The nomogram accurately predicts the risk of recurrence in HIV-negative patients with anal CA following ALA-PDT. It offers a valuable tool for guiding preoperative clinical decision-making and establishing personalized treatment strategies to minimize the risk of relapse.

Comparative study of photodynamic therapy (PDT) of cervical low-grade squamous intraepithelial lesion (LSIL).

BACKGROUND: Prevention of high-risk HPV (HR-HPV) infection and effective medical intervention of persistent HPV infection and precancerous lesions are critical for the prevention of cervical cancer. AIMS: The aim of this retrospective comparative study was to evaluate the outcomes of ALA PDT and observation only in the management of low-grade squamous intraepithelial lesions (LSIL). METHODS: In PDT Group (n = 138), ALA PDT was applied to patients with colposcopic biopsy confirmed cervical LSIL accompanied with HR-HPV infection longer than 1 year or HPV 16/18 subtype infection. Cervical LSIL only patients received 3 times of ALA PDT and those with concurrent cervical canal or vaginal lesions received 6 times ALA PDT. Control Group (n = 69) received observation only. Colposcopy, TCT and HPV typing were performed before and after treatment. Patients were followed up for up to two years. RESULT: The observation group showed 26.1%, 34.8% and 53.6% HR-HPV negative conversion at 3-6, 12 and 24 months, respectively. LSIL regression rate of the observation group was 33.33%, 36.23% and 65.22% at 3-6, 12 and 24 months, respectively. There was 62.32%, 80.56% and 89.22% patients achieved HPV clearance at 3-6, 12 and 24 months after PDT treatment, respectively. The LSIL remission rate was 89.86%, 94.40% and 96.08% at 3-6, 12 and 24 months after ALA PDT, respectively. The abnormal TCT (≧ ASCUS) was reduced from 92% to 10.1%, 4.6% and 3.9% at 3-6, 12 and 24 months after ALA PDT, respectively. The patient age was not a factor affecting the clearance of HPV infection and the LSIL regression rate of PDT treatment. CONCLUSIONS: This study demonstrates that the application of multiple ALA PDT treatments has added value in achieving both short-term and long-term HPV and lesion clearance.

Caution:Patient-specific preoperative preparations combined with procedure-specific 5-aminolevulinic acid may lead to critical events.

5-Aminolevulinic acid (5-ALA) is orally administered 2-4 hours before surgery to identify tumor location. Hypotension is sometimes observed after 5-ALA administration. Case reoprtWe present a case of a patient with 5-ALA-induced hypotension that resulted in the development of cerebral infarction. An 83-year-old man with a bladder tumor was scheduled for photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) and right radical nephroureterectomy. 5-ALA was orally administered and his ordinary antihypertensive and antianginal agents were also administered an hour after 5-ALA administration. Following this, his blood pressure dropped, and he developed muscle weakness and paralysis in his left upper extremity. Magnetic resonance imaging showed evidence of cerebral infarction. ConclusionsWe cannot conclude definitively that our patient's cerebral infarction was solely caused by 5-ALA-induced hypotension because hypotension under these circumstances is not rare. We consider that additional factors, such as patient-specific doses of antihypertensive and antianginal agents may have played a role in the development of his cerebral infarction.

Battery-free optoelectronic patch for photodynamic and light therapies in treating bacteria-infected wounds.

Light therapy is an effective approach for the treatment of a variety of challenging dermatological conditions. In contrast to existing methods involving high doses and large areas of illumination, alternative strategies based on wearable designs that utilize a low light dose over an extended period provide a precise and convenient treatment. In this study, we present a battery-free, skin-integrated optoelectronic patch that incorporates a coil-powered circuit, an array of microscale violet and red light emitting diodes (LEDs), and polymer microneedles (MNs) loaded with 5-aminolevulinic acid (5-ALA). These polymer MNs, based on the biodegradable composite materials of polyvinyl alcohol (PVA) and hyaluronic acid (HA), serve as light waveguides for optical access and a medium for drug release into deeper skin layers. Unlike conventional clinical photomedical appliances with a rigid and fixed light source, this flexible design allows for a conformable light source that can be applied directly to the skin. In animal models with bacterial-infected wounds, the experimental group with the combination treatment of metronomic photodynamic and light therapies reduced 2.48 log10 CFU mL-1 in bactericidal level compared to the control group, indicating an effective anti-infective response. Furthermore, post-treatment analysis revealed the activation of proregenerative genes in monocyte and macrophage cell populations, suggesting enhanced tissue regeneration, neovascularization, and dermal recovery. Overall, this optoelectronic patch design broadens the scope for targeting deep skin lesions, and provides an alternative with the functionality of standard clinical light therapy methods.

Case Report: Recalcitrant oral lichen planus involving bilaterally buccal mucosae treated with a combination of photodynamic and photobiomodulation therapies.

Background: Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic therapy (PDT) is a non-invasive technique that enables the removal of lesions without surgery. Photobiomodulation therapy (PBMT) can promote healing and recovery of the lesions. Case presentation: The objective was to treat unresponsive bilateral OLP of the whole buccal mucosae with a combination of PDT and PBMT. Results: A 43-year-old Thai male presented with the severe painful reticular type of OLP of bilateral buccal mucosae involving upper and lower vestibular areas. The lesions were not remitted with either prednisolone systemic steroids or fluocinolone topical corticosteroids. After undergoing ten sessions of PDT with 10% 5-Aminolevulinic acid (5-ALA) in the form of thermoplastic gel and a 635 nm diode laser at 100 to 400 mW with an energy density of 20 to 30 J/cm 2 in continuous wave mode, combined with five interim-sessions of PBMT using a 635 nm diode laser at 200 to 300 mW with an energy density of 6 to 10 J/cm 2 in continuous wave, the patient reported relief of burning sensation beside remission of lesions without any complications. Conclusion: The wide-spreading recalcitrant OLP with burning sensation can be managed by combining PDT and PBMT.