Background: Hypopigmentation is a common cutaneous manifestation that frequently poses a therapeutic challenge for dermatologists. Current treatments have varying efficacies and rarely provide patients with long-term results. However, new treatments are emerging, and head-to-head studies comparing these treatments are warranted. Methods & Materials: In this prospective, Institutional Review Board (IRB)-approved, double-blinded study, 40 subjects with moderate to severe hypopigmentation were randomized into 1 of 4 treatment arms; non-ablative fractional laser, ablative fractional laser, ablative fractional laser with laser-assisted delivered bimatoprost, and an epidermal harvesting system. Results: All patients in this study showed improvement regardless of the treatment modality. The average improvement score was calculated on a 0 to 4 scale, and Group 3 (fractional ablative laser and bimatoprost) was found to have a significantly higher average improvement than all other treatments, with 76% of the patients exhibiting at least a grade 3 (over 50%) improvement over the treatment course. Group 1 (non-ablative fractional) also had a significantly higher average score compared with group 2 (fractional ablative laser). Conclusion: New and emerging therapies have shown promise in helping re-pigmentation of cutaneous hypopigmentation. In this head-to-head trial, it was shown that laser-assisted delivery of bimatoprost had a greater statistically significant improvement compared with 3 possible treatment modalities for stimulation of pigment in medical and cosmetic hypopigmentation. J Drugs Dermatol. 2019;18(11):1090-1096.

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