In patients treated with trichloroacetic acid-Cross (TCA- CROSS) for acne scar, adding topical timolol improved results, according to study findings published in Dermatologic Therapy.

TCA-CROSS, a chemical reconstruction of scars, is used to treat ICE-PICK scars which represent about two-thirds of all acne scarring. Researchers sought to determine if adding saline injection and topical timolol would improve the efficacy of TCA-CROSS treatment for acne scarring.

To accomplish this, they conducted a controlled, randomized, analyst-blinded phase 2 clinical trial that included 45 patients with atrophic acne scars randomly divided into 3 cohorts of 15. Cohort 1 received saline injection 0.9% beneath scars on 1 side of the face, and TCA-CROSS treatment. Cohort 2 received TCA-CROSS treatment then 0.5% timolol eye drops applied on the scars on 1 side of the face. Cohort 3 received saline injection beneath scars on 1 side of the face, then TCA-CROSS treatment, then 0.5% timolol eye drops applied on the scars on the same side as the saline injection. Determination of the control side was random in all groups. The primary outcome was the number of scars and the satisfaction of patient and physician.

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Pre-treatment scarring was equivalent on both sides of the face in all 3 cohorts (P >.05). Both sides of the face in all 3 cohorts showed improvement after treatment. The decrease in scars in cohorts 2 and 3 treatment sides were not statistically significant. Cohort 1 showed slightly more scars on the treatment side compared with the control side. For cohorts 2 and 3, “severity and duration of scar hyperpigmentation were significantly lower.” (P =.016, P =.002 respectively).

Patient satisfaction in cohort 1 was higher for the control side; cohort 2 for the treatment side; cohort 3 no difference in satisfaction. Physician satisfaction mirrored patient satisfaction.

Researchers noted, “Application of 0.5% timolol after TCA-CROSS caused a slight decrease in scar severity and a significant reduction of post-inflammatory hyperpigmentation duration.” They concluded that adding topical timolol to TCA-CROSS improves the outcome for acne scar treatment. Researchers added, “Injection of 0.9% saline before TCA-CROSS is not recommended as a treatment method, because in the first group of patients (TCA + Saline) this method did not reduce the side effects of the treatment and slightly reduced the efficacy of TCA-CROSS treatment.”


Ghassemi M, Shahverdi MH, Behrangi E, Hosseini-Baharanchi FS, Goodarzi A. Efficacy and safety of topical timolol 0.5% plus saline 0.9% versus each one alone in acne scar trichloroacetic acid-CROSS therapy: A blinded randomized controlled trial. Dermatol Ther. Published online January 29, 2022. doi:10.1111/dth.15341