Evaluation of the Efficacy, Safety, Satisfaction, Tolerability, and Durability of Q-Switched Nd:YAG 1064 nm Laser in Combination with co2 Laser and Each Laser Alone in the Treatment of Macular Amyloidosis in Patients Undergoing Modified Klignman’s Formula Therapy: A Randomized, Four-Arm, Split-Face, Assessor-Blinded Clinical Trial

To evaluate the efficacy of fractional Q-switched Nd:YAG laser compared to co2 laser and to compare each monotherapy with their combined use in the treatment of macular amyloidosis.

Fifteen patients were enrolled, with affected areas divided into four treatment zones: Fractional QS Nd:YAG co2 Combined lasers Control (topical only) Blinding: Double-blind (patients & assessors unaware of treatment allocation)

The combined laser intervention was performed on hyperpigmented lesions at Rasool Akram Medical Center under double-blind conditions, with both participants and evaluators blinded to treatment allocation across study zones.

Inclusion Criteria: Female patients aged 18–50 years with a confirmed diagnosis of macular amyloidosis and no history of laser treatment for the condition within the past three months. Exclusion Criteria: Development of hypersensitivity or any treatment-related adverse effects that would prevent continuation of therapy. Pregnancy and Presence of severe underlying systemic diseases

All enrolled patients will receive topical application of the modified Kligman's formula, to be applied uniformly to all affected and hyperpigmented areas. Following this baseline treatment, the hyperpigmented lesions of each patient will be divided into four distinct zones, with each zone receiving one of the following interventions: Zone 1: Fractional Q-switched Nd:YAG laser treatment Zone 2: co2 laser treatment Zone 3: Combined fractional Q-switched Nd:YAG + co2 laser therapy Zone 4 (Control): Topical Kligman's formula only

Resolution of refractory hyperpigmentation. Improvement in patients' quality of life. Identification of optimal treatment for resistant pigmentation disorders

At the time of registering the proposal, based on the facilities available at the center and the malfunction of the center's CO₂ fractional laser device, which made it unusable, the Er:YAG 2940 nm laser was defined as one of the interventional arms in the proposal. During this same sampling period, two patients at the collaborating center underwent treatment with the Er:YAG laser. However, the sampling process was progressing slowly due to travel complications. Considering that after some time the CO₂ device was repaired, and to avoid imposing additional costs, logistical challenges, and therapeutic inconsistencies for the patients, the continuation of the study for the remaining patients was carried out using the CO₂ fractional laser device instead of the Erbium device, with settings adjusted to closely match those of the Erbium device. Since the treatment of two patients with Er:YAG was not consistent with the continuation of the study and could lead to heterogeneity in the data, the results related to these two patients were excluded from the final analysis to preserve the methodological validity of the study. Therefore, it is hereby clarified that the discrepancy between the initially registered title and the final implementation of the study was due to the temporary technical issue with the CO₂ device and the practical necessities in the patient treatment process. This change did not compromise the nature of the study, the randomization method, the blinding of the evaluators, or the main research protocol, and solely involved replacing the Er:YAG intervention with the CO₂ fractional laser in the respective study arm.

Due to the significant differences between the mentioned therapeutic interventions, blinding of the patient and the treating physician was not feasible. Therefore, the study will be conducted in a single-blind manner. In other words, outcome assessments will be performed by an evaluator blinded to the type of intervention (a dermatologist unaware of which treatment was administered to specific areas of the patient’s skin), based on standardized photographs of the lesions taken at each session. Additionally, data analysis will be conducted by a blinded statistician

Study data will be made publicly available after analysis and de-identification of participants as part of the outcome publication.

Following publication of the clinical trial results in international journals, the research data will become accessible

All researchers at medical science universities are permitted to access the study data.

All researchers are permitted to use the data or documentation provided that they properly acknowledge the original authors.

Researchers may contact Dr. Paria Jafary at the following email address to request related documentation: p.jafary74@gmail.com

All requested documentation will be provided to applicants within a maximum period of one month, subject to compliance with the stated conditions.