Topical Brimonidine Tartrate 0.33% Gel versus 577-nm Pro-yellow Laser for Treatment of Post Acne Erythema: A Comparative Study

J Clin Aesthet Dermatol. 2025;18(1):35–39.

by Eman Awadallah Mohamed, MBBCH; Zakaria Mahran Obaid, MD; and Ibrahim Fouda, MD

Dr. Mohamed is with the Department of Dermatology at Dekernes General Hospital, Ministry of Health and Population in Dakahlia, Egypt. Drs. Obaid and Fouda are with the Department of Dermatology, Venereology, and Andrology, Damietta Faculty of Medicine in Al-Azhar University, Egypt.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors declare no conflicts of interest relevant to the content of this article.

ABSTRACT: Background: Post acne erythema (PAE) is a common sequela of inflammatory acne vulgaris resulting from the dilatation of microcapillaries within the papillary dermis, thinning of the epidermis, and release of inflammatory cytokines.

Objective: The authors sought to compare the safety and efficacy of topical Brimonidine tartrate 0.33% gel versus A 577-nm pro-yellow laser for treatment of post acne erythema.

Methods: This was a comparative study, randomized clinical trials conducted on 60 adult patients with PAE. Patients were assigned into two groups: Group I included 30 patients who received brimonidine tartrate 0.33% gel once daily for three months, and Group II included 30 patients who received Pro-yellow laser with 577-nm therapy, for four sessions at three weeks intervals. Evaluation of erythema was done by Clinician’s Erythema Assessment (CEA) and Patient’s Self-Assessment (PSA) scales at baseline and at the end of the therapy. The dermoscopic images were analyzed for percent area of erythema and the optical density (OD) using ImageJ® freeware.

Results: Twenty-two patients (73.3%) were females and eight patients (26.7%) were males in Group I. In Group II, 20 patients (66.7%) were females and 10 patients (33.3%) were males. The mean±SD age of the studied groups was 22.07 years ±2.64 ranging from 20 to 24 years in Group I versus 20.93 years ±2.88 ranging from 19 to 23 years in Group II. Clinical improvement is distributed as follows among Group I; 56.7 percent are excellent, 56.7 percent good, 26.7 percent poor, and 10 percent fair for Group II; 33.3 percent good, 6.7 percent poor, and 60 percent excellent. There was no statistically significant difference between studied groups as regard Clinician’s Erythema Assessment (CEA), Patient’s Self-Assessment (PSA) mean area percentage and the optical density (OD) before treatment, while a statistically significant difference between studied groups after treatment was observed (p<0.001).

Conclusion: Topical brimonidine tartrate 0.33% gel and 577-nm pro yellow laser were effective and well tolerated therapeutic options for treatment of Post acne erythema (PAE), however the 577-nm Pro yellow laser was superior to brimonidine tartrate 0.33% gel.

Keywords: Acne, erythema, laser, brimonidine

Introduction

Acne vulgaris is a common chronic inflammatory disease of the pilosebaceous unit which affects approximately 80 percent of young adults and adolescents. This common skin disorder can present with both inflammatory and non-inflammatory lesions.¹

Post-acne erythema (PAE) is defined as erythematous macule, usually present after the complete resolution of inflammatory acne. It develops secondary to the release of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α which persist after resolution of inflammatory acne lesions.² Dilation of microcapillaries in papillary dermis secondary to healing process as well as intracapillary aggregations of erythrocytes play a pivotal role in development of PAE. Furthermore, thinning of epidermis as a result of wound healing increase the visibility of dilated microcapillaries.³

The treatment of post-acne erythema is as important as treating acne lesions. Several topical agents including 0.025% retinoic acid, 12% glycolic acid, 0.2% brimonidine tartrate, 5% tranexamic acid solution and vitamin C preparations have been used in the treatment.^4–6

Also, vascular lasers such as 595-nm pulsed dye laser, The low-fluence 585-nm Q-switched Nd:YAG 1550-nm, Fractional Erbium-glass laser, Picosecond Alexandrite 755-nm laser, Fractional picosecond 1064-nm Nd:YAG laser and Intense pulsed light (IPL) have been used in the treatment of PAE.^7–10

Brimonidine tartrate 0.33% gel is a selective alpha-2 adrenergic agonist that binds the alpha-2 receptors on vessels resulting in vasoconstriction of small arteries and veins thereby reducing the effects of vasodilation, namely erythema.¹¹ In 2013, brimonidine tartrate 0.33% gel was the first topical therapy to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of persistent facial erythema from rosacea. It’s also used in treatment of facial telangiectasia and post inflammatory erythema.¹²

A 577-nm pro-yellow laser has been used in the treatment of diabetic retinopathy for more than 20 years, however in the past few years it has been used for dermatological indications.^13–15 The pro-yellow laser has an optimal wavelength for vascular lesions because it only emits yellow light that targets oxyhemoglobin. This making the lesion fade away as result of thermal damage, but with less absorption in melanin and a slightly deeper penetration into the dermis, thereby minimizing the risk of hyperpigmentation especially in patients with darker skin types.¹⁶

Methods

Patient selection. The study included 60 adult patients with post acne erythema selected from an outpatient dermatology clinic, between January 2022 and January 2023. Patients were assigned into two Groups. Group I received brimonidine tartrate 0.33% gel and Group II received 577-nm pro-yellow laser therapy.

Ethical approval was obtained from the institutional review Board of Damietta faculty of medicine (Al-Azhar University). All patients signed the informed consent to be included in this study.

All patients were exposed to a detailed clinical history, general examination, dermatological and dermoscopic examination at baseline, during and at the end of the therapy.

Patients who were pregnant/lactating, had a history of anticoagulant or non-steroidal anti-inflammatory drug use within the last month, had a history of photosensitivity or skin cancers, had allergy to anesthetic agents or Brimonidine tartrate 0.33% gel, or had active skin infections were excluded from the study. 

Treatment protocol. Group I included 30 patient received brimonidine tartrate 0.33% gel once daily for three months. (Brimondalous, Andalous pharma) Group II included 30 patients received Pro-yellow laser with 577-nm therapy (QuadroStar PRO YELLOW® Asclepion Laser Technologies, Germany) for four sessions at three-week intervals. Topical anesthesia was applied before the procedure. The eyes of the patients were protected with appropriate glasses. Laser was applied in a scanner mode with a coverage of 80 percent of face. Application was started with a fluence of 12J/cm², and in patients that did not appear effective, the fluence was increased by 2J/cm² during the procedure. A maximum dose of 16 J/cm² was used. Following the procedure, the patients were instructed to use at least 30 SPF sunscreen regularly, avoid sun exposure for the next 4 to 5 days and to apply the provided moisturizer.   

Clinician’s Erythema Assessment (CEA) and Patient’s Self-Assessment (PSA) scales used to determine the severity of erythema. Both scores were recorded on a 5-point scale and were defined as follows: Clinician’s Erythema Assessment (CEA): 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), 4 (severe). Patient’s Self-Assessment (PSA): 0 (no redness), 1 (very mild redness), 2 (mild redness), 3 (moderate redness), 4 (severe redness). Dermoscopic Photographs were analyzed with ImageJ® freeware (http://imagej.nih.gov/ij

Follow-up. All patients followed every month for three months after stopping of treatment to detect any recurrence of erythema.

Statistical analysis. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). Qualitative data were described using number and percent. The Kolmogorov-Smirnov test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, standard deviation, median and interquartile range (IQR). Significance of the obtained results was judged at the 5 percent level. 

Results

The study included 60 patients in two Groups, in Group I, 22 patients (73.3%) were females and eight patients (26.7%) were males. While in Group II, 20 patients (66.7%) were females and 10 patients (33.3%) were males. The mean±SD age of the studied Groups was 22.07 years ±2.64 ranging from 20 to 24 years for Group I versus 20.93 years ±2.88 ranging from 19 to 23 years for Group II.

As regards to skin phototypes, in Group I , there was 12 patients ( 40%) type III and 18 patients (60%) type IV while there was 17 patients (56.7% ) type III and 13 patients ( 43.3%) type IV in Group II. The Mean ± SD duration of erythema was 9.30 ± 2.56 months ranging from 4 to 14 months for Group I versus 9.67 ± 3.41 ranging from 4 to 16 months for Group II (Table 1).

In the evaluation of the improvement rates of erythema before and after treatment, there was no statistically significant difference between studied Groups as regard Clinician’s Erythema Assessment (CEA) before treatment, while there was a statistically significant difference between studied Groups after treatment (p<0.001). In patients that underwent CEA after treatment, 26.7 percent were severe, 6.7 percent moderate, 3.3 percent mild, 6.7 percent almost clear and clear 56.7 percent for in Group I versus 6.7 percent severe, 33.3 percent almost clear, and 60 percent clear in Group II (Table 2).

As regards to Patient’s Self-Assessment (PSA), there was no statistically significant difference between the studied Groups before treatment, however a statistically significant difference was observed between the studied Groups after treatment (p<0.001).

In Group I patients, PSA after treatment showed to be 26.7 percent severe redness, 6.7 percent moderate redness, 3.3 percent mild redness, 56.7 percent very mild redness, and 6.7 percent no redness. In Group II, 6.7 percent severe redness, 33.3 percent very mild redness, and 60 percent no redness were seen in patients (Table 3).

The dermoscopic images were selected haphazardly and analyzed for mean area percentage and the optical density (OD) using NIH Image J (v1.49) (http://rsb.info.nih.gov/ij/).There was no statistically significant difference between the two study Groups regarding the percent area of erythema before treatment. However, there was a statistically significant decrease in the percent area of erythema after treatment as compared to before treatment.

After treatment, the mean percent area of erythema in the Group II was 10.90 ± 6.13 that was statistically significantly lower compared to Group I (17.13 ± 5.69) (p<0.001). The percentage of reduction was statistically significantly higher in Group II (Table 4).

As regards to the optical density (OD), there was no statistically significant difference between the two study Groups before treatment. However, there was high statistically significant decrease in the OD after treatment as compared to before treatment.

After treatment, the mean OD in the Group II was 2.89 ± 0.70 that was statistically significantly lower compared to Group I (3.80 ± 0.66) (p<0.001). The percentage of reduction was statistically significantly higher in Group II (Table 5).

As regards to investigator global assessment (IGA) scale, a statistically significant difference was detected between studied Groups a with higher rate of improvement among Group II than Group I. Table 6 shows a statistically significant difference between studied groups as (IGA) degree (p<0.001). The degree of improvement in Group I distributed as follows: 56.7 percent are marked improvement, 26.7 percent moderate, 10 percent mild, and 6.7 percent excellent improvement versus Group II, 60 percent excellent improvement, 33.3 percent marked improvement, 6.7 percent moderate improvement and none of the studied group was mild.

Adverse effects were higher among Group I with the following distribution: 26.7 percent mild erythema, 40 percent irritation, 13.3 percent dryness versus 33.3 percent mild erythema, 20.0% irritation in Group II.

Discussion

Persistent post-acne erythema (PAE) refers to telangiectasia and erythematous lesions remaining after the acne treatment. Persisting post-acne erythema as experienced by many patients, is cosmetically unacceptable and causes psychological distress.¹⁷ 

Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved in 1996 to treat open-angle glaucoma. Brimonidine binds alpha 2 receptors on the vasculature inducing direct vasoconstriction of both small arteries and veins, thereby reducing vasodilation and edema.^11,12 

The Pro-Yellow laser, which is the latest laser technology for vascular lesions, emits 100 percent yellow light at 577-nm, the ideal wavelength for vascular lesions. The Pro-Yellow laser does not require a dye, gel, or cooling system and it is very ergonomic and lightweight.¹⁸

Several studies have been conducted to investigate the effectiveness of topical or laser therapies in the treatment of PAE. However, large-scale or long-term clinical trials have not confirmed their efficacy or safety.

To the best of our knowledge this is the first comparative study between topical agent and laser device in treatment of post acne erythema.

The current study is a randomized clinical trial that was carried out on 60 patients to compare the safety and efficacy of topical Brimonidine tartrate 0.33% gel (Group I) versus A 577-nm pro-yellow laser (Group II) in the treatment of post acne erythema. 

In a prospective experimental study conducted by Genedy,¹⁹ who evaluated the efficacy and safety of topical brimonidine tartrate 0.2% solution in the treatment of post acne erythema. The study conducted on 30 patients with rosacea and 30 patients with post-acne erythema. The improvement was significantly higher in the post acne erythema Group than in the rosacea Group at the end of both the treatment phase and the follow-up period.¹⁹

In another comparative, controlled, split face trial conducted by Agamia et al²⁰ to assess the efficacy and adverse effects of triple combination (topical BMT 0.3%, topical OXZ 1.5%, and topical TXA 5%) (TXA, OXZ, BMT) in treatment of PAE. Their study proved the improvement in PAE after 12 weeks of treatment according to erythema severity, IGA scale, PAE lesional count and subjectively, 50 percent of patients (n=20) were very satisfied, 40 percent (n=16) were satisfied and 10 percent (n=4) were dissatisfied.

For those who cannot afford lasers, topical treatments such as topical brimonidine can be effective alternative.

The laser devices’ ergonomic design and cost-effectiveness are crucial aspects. Due to their rapid response and reduced need for several treatment sessions, laser and light devices are particularly favored by patients who do not comply well with topical therapy.

Energy-based devices are effective treatment modalities in reduction of PAE along with reducing active acne lesions and atrophic acne scars and improvement in skin texture, pigmentation and oiliness as well.¹⁷

Compared to other vascular lasers, the pro-yellow laser appears to be more cost-effective, economical, and safe—even for patients who have recently received systemic isotretinoin treatment. It also requires less downtime. 

In a split-face, randomized controlled trial pilot study conducted by Wanitphakdeedecha et al¹⁶ twenty-one patients with PAE on both sides of their face were enrolled. Three sessions of laser treatment were applied with 1-month intervals and it was reported that postacne erythema improved in 75 percent of the patients after the third session with an energy of 12 to 15J/cm.

On the other hand, in a previous study Sarac et al who applied a fluence of 22J/cm² in a single session of 577-nm pro yellow laser in treatment of 40 patients with post-acne erythema. Twenty-one patients (52.5%) had good improvement and 10 patients (25%) had an excellent improvement and in nine of the patients (22.5%) a moderate improvement was observed.²¹ Despite the high doses, they did not encounter any side effects in any of their patients.

In the same line, Karaağaç²² aimed to investigate the effectiveness of 577-nm pro yellow laser on post-acne erythema in patients with acne vulgaris. Fifty patients between the ages of 14–40 were clinically diagnosed with acne vulgaris and post-acne erythema and who were not receiving acne treatment were included in the study. Erythema was assessed by two independent dermatologists by comparing the photos and using clinician erythema assessment scale; a statistically significant greater change in erythema was found in the treated side of face compared to the control side (p<0.001).

The current study proved a statistically significant difference between both Groups in the improvement in PAE according to investigator global assessment (IGA) scale, Clinician’s Erythema Assessment (CEA), Patient’s Self-Assessment (PSA), mean area percentage and the optical density (OD) after 12 weeks of both treatment modalities with Pro -yellow laser outstanding Brimonidine tartrate 0.33%.

In the current study, there was no statistically significant difference between studied Groups as regard adverse effects incidence and all of them were minor and disappeared gradually. However, no recurrence of erythema was detected during the follow up period in both Groups. 

Conclusion

Although both the 577-nm Pro -yellow laser and the Brimonidine tartrate 0.33% gel were effective in treating post-acne erythema, the Pro -yellow laser appears to be superior to the Brimonidine tartrate 0.33% gel with minimal side effects.

Based on the previous trials, which proved the efficacy of each modality separately, we recommend combining both of them to act synergistically to achieve the best results. Future studies with longer follow-up periods and a larger sample size should be done and clinical efficacy should be strengthen and supported by histopathological evaluation.

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