Acne is a disfiguring skin disease caused by the dysfunction of the sebaceous units of the hair follicles and can cause psychological problems in adults. Because of the variety of factors involved in the development of acne, there are a variety of treatments available. 5-aminoketovaleric acid (ALA) photodynamic therapy (PDT) is an effective treatment for common facial acne. The sebaceous unit selectively absorbs topically applied ALA and converts it into protoporphyrin IX (PpIX), which can be activated by various light sources such as intense pulsed light (IPL), blue light, 635 nm red light, and pulsed dye laser (PDL). affect the outcome of the treatment. The use of ALA-PDT with a 3-hour application time has been reported to achieve results for facial acne. Another study has shown that a shorter duration of ALA-PDT application can reduce the occurrence of side effects and that prolonged application is more effective. Despite the controversy, an overall application time of 30-60 minutes is recommended, taking into account side effects and patient convenience. However, the optimal duration of application without side effects has not yet been determined. The purpose of the current study was to evaluate the application of PDT with ALA combined with IPL for the treatment of acne vulgaris. We designed a comparative protocol with a duration of application of 3 hours and 30 minutes, respectively. METHODS: Twenty Korean patients (4 men and 16 women, aged from 18-30 years, with skin type III or IV) with moderate to severe acne were enrolled in the current randomized, prospective, unilateral facial comparative clinical study. Patients were rated 1-5 according to the Global Evaluation of Severity Score (EGSS), where a score of 3 was defined as moderate acne and a score of 4 was defined as severe acne. Each patient’s unilateral face was randomly divided into an ALA short application time group plus IPL treatment (30 minutes, 9 patients) or an ALA long application time group plus IPL treatment (3 hours, 11 patients), and the other unilateral face was treated with IPL only (20 patients). Exclusion criteria included those taking oral antibiotics or isotretinoin within 6 months, those with systemic diseases or keloids and photosensitivity, and patients during pregnancy. Patients were not treated with any other treatment during the treatment period and 12 weeks after the last treatment, and informed consent was obtained from each patient prior to treatment. The face was cleansed with mild soap, wiped with 70% alcohol, and unilaterally applied with 20% ALA hydrochloride (Levulan Kerastick, Dusa Pharmaceuticals, Wilmington, MA) for 30 minutes or 3 hours, depending on the group, to completely seal it from light, and unilaterally applied without ALA Cover with plastic wrap. After the application time, the ALA was removed with mild soap and 70% alcohol and the full face was treated with IPL (BBL, Sciton Inc., Palo, Alto, CA) using a 590 nm filter with an energy density of 12-15 J/cm2, a pulse width of 30 ms and a delay of 20 ms. Patients were advised to avoid light for 48 hours after treatment and to use Light shielding agent. Patients were treated every 4 weeks for a total of 3 sessions. Close-up photographs were taken of the patient’s base condition and at each follow-up visit, and the number of acne lesions on both sides of the face was counted before treatment and at weeks 4, 8, and 12 after each treatment and the third treatment. Two uninformed dermatologists independently evaluated the effectiveness of acne treatment according to the chronological order. We used the following evaluation scale to assess the effect: significant improvement (>75%), moderate improvement (50C75%), mild improvement (25C50%), ineffective (0C25%), and exacerbation (<0%) relative to the patient's underlying condition, including inflammatory and non-inflammatory lesions. The same method as above was used to evaluate according to the subjective feelings of the patients. Sebumeter (CK Electronic, Cologne, Germany) was used for the measurement of sebum secretion. Patients did not wash their faces for 6 hours prior to the measurement. Erythema, hyperpigmentation or hypopigmentation complications were evaluated at each treatment. Data from each group were compared using the Mann-Whitney method, rank sum test, and ANOVA. RESULTS: All 20 patients completed 3 sessions of treatment and their subsequent follow-up. All patients had a therapeutic effect on inflammatory acne lesions after three sessions of ALA-PDT or IPL (p<0.001). Follow-up at the fourth week after three treatments showed a reduction in lesions of 84.4% in the long-application group, 72.6% in the short-application group, and 65.9% in the IPL alone group. The mean reduction in inflammatory lesions at week 12 after the end of the three treatments was 89.5%, 83%, and 74%, respectively. The therapeutic effect of PDT and IPL on inflammatory acne lesions remained even at 12 weeks after the end of treatment. The treatment effect of the long-duration ALA group was better than that of the short-duration group and the IPL group, where the statistics showed a significant effect compared to the IPL group. The difference between the long duration group and the short duration group was not significant. The sebum secretion was significantly reduced in all three groups after three treatments, and the degree of reduction in sebum secretion at the end of the fourth week of treatment was 45.7% in the long-application group, 35.5% in the short-application group, and 31.8% in the IPL group alone. At the 12-week post-treatment follow-up, 46.7%, 31.5%, and 37.5% were achieved, respectively, with no significant differences between groups. The 12-week post-treatment follow-up showed that of the 11 patients in the long-application group, four had a clinical effect of 26%-50%, three had 51%-75%, and one had 76%-100%. In the short-application group, of the 9 patients, 6 had a mild improvement of 26%-50% and 3 had a moderate improvement of 51%-75%. Of the 20 patients in the IPL alone group, 2 showed no improvement, 14 showed mild improvement, and 4 showed moderate improvement. Clinical evaluation by dermatologists showed mild improvement in 2 cases, moderate improvement in 5 cases, and significant improvement in 4 cases in the long-application group. In the short-application group, there were 3 cases of mild improvement and 6 cases of moderate improvement. In the IPL alone group, there was no improvement in 1 case, mild improvement in 4 cases, and moderate improvement in 5 cases. All patients did not use local anesthetics prior to treatment, tolerated the treatment, and did not experience significant side effects such as scarring or infection. There was only transient erythema and mild edema during the treatment period, which lasted for a few hours or days. 1 patient in the short-application group developed post-treatment hyperpigmentation, which lasted for several weeks. Another patient in the short-application group developed an acne-like rash. Discussion: Photodynamic therapy is derived from the ability of photoactivated porphyrins to produce singlet oxygen, and ALA can be metabolized into protoporphyrin IX (PpIX), which has been used as a photosensitizer since 1990. Recently, methylaminolevulinate (MAL), a derivative of ALA, has received marketing approval in Europe and Australia for the treatment of solar keratoses and acne. In Asia, MAL-PDT combined with IPL is also used to treat acne. Photodynamic therapy for acne has been available for several years, and different application times and different light sources have been extensively studied. ppIX, as an effective photosensitizer, has an ideal peak absorption at 410 nm, although this wavelength is shorter than that of intense pulsed light, and the excitation spectrum of IPL can be used as PDL and is widely used. Our study showed that the clinical effect of the long-application group was superior to that of the short-application group and the IPL alone group, and there were no significant side effects, and it can be safely applied to the skin of Asian individuals. Therefore, it is recommended to use a longer application time for PDT for acne treatment to obtain good clinical results. Conclusion: PDT for ALA may be more effective in the treatment of inflammatory acne when applied for a longer period of time.