Efficacy and Safety of a Multimodal Laser, Injectable, and Topical Protocol for the Treatment of Skin Hyperpigmentation: A Prospective Pilot Study

Abstract

Skin hyperpigmentation disorders are common, chronic, and often refractory to monotherapy. Multimodal strategies addressing pigmentation, dermal quality, and epidermal barrier simultaneously may improve outcomes. To evaluate the efficacy and safety of a combined protocol using accelerated non-ablative fractional diode laser therapy (LaserMe®), injectable non-cross-linked calcium hydroxyapatite-hyaluronic acid (CaHA-HA), and adjunctive topical retinoid and ascorbic acid in patients with facial hyperpigmentation. Five participants with Fitzpatrick skin types I-IV (including melasma, post-inflammatory hyperpigmentation, age-related pigmentation, and photodamage-associated dyschromia) were enrolled in a prospective, open-label pilot study. The protocol included three laser sessions over four weeks, injectable CaHA-HA at weeks 0 and 4, daily stabilised ascorbic acid, alternate-night retinoid application, and broad-spectrum SPF 50 photoprotection. The primary outcome was the change in pigmentation severity assessed by the modified Melasma Area and Severity Index (mMASI). Secondary outcomes included transepidermal water loss (TEWL), standardised photographic assessment, and safety evaluation over 12 weeks. All participants demonstrated clinically meaningful improvement in pigmentation by week 12. Mean mMASI scores decreased from 14.0 at baseline to 7.0 at week 12, representing a 50.4% mean reduction. Four of five participants showed improved TEWL values, with mean TEWL decreasing from 19.0 to 14.4 g/m²/h. No serious adverse events occurred; mild transient erythema, swelling, and bruising resolved spontaneously. This pilot study suggests that a combined laser-injectable-topical protocol is safe, well-tolerated, and associated with consistent improvements in pigmentation severity and epidermal barrier function. Larger randomised controlled trials are warranted to confirm these findings.