Rationale for the sequence of procedures in a combined aesthetic correction protocol for facial involutional changes: botulinum toxin therapy and fractional photothermolysis

Background. The combination of botulinum toxin type A and non-ablative fractional laser treatment is widely used for the comprehensive aesthetic correction of facial involutional changes. However, the optimal sequence of procedures and the appropriate interval between treatment stages remain uncertain. Objective. To compare clinical outcomes, patient satisfaction, and tolerability of two sequences of combined treatment: non-ablative fractional laser therapy using Frax 1550 followed by botulinum toxin type A (Relatox), and Relatox followed by Frax 1550. Material and methods. Sixteen women aged 29—74 years (mean age, 47±9 years) with clinical signs of involutional skin changes on the face and neck were included and allocated into two groups of eight patients. In Group 1, Frax 1550 treatment was performed first, followed by Relatox full-face injections 14 days later. In Group 2, Relatox full-face injections were administered first, followed by Frax 1550 treatment 14 days later. One non-ablative fractional laser session was performed using the Frax 1550 applicator on the Nordlys platform. Assessments were carried out at baseline, Day 14, Day 28, and 3 months after treatment initiation. Outcomes included patient satisfaction measured by the FACE-Q Face Overall scale, wrinkle severity at rest assessed by the Lemperle scale in the forehead, glabellar, and periorbital regions, binary tests of facial muscle activity, clinical assessment of skin tone, turgor, and microrelief, as well as adverse events. Within-group changes were evaluated using the Wilcoxon signed-rank test. Results. At baseline, the mean FACE-Q Face Overall score was 49±8 in both groups. By Day 28, it had increased to 89±8 in the Frax 1550 → Relatox group and to 92±6 in the Relatox → Frax 1550 group (T=0; p=0.008 for both groups). At 3 months, the respective scores were 84±6 and 87±5, remaining significantly higher than baseline (T=0; p=0.008) and representing a retention of approximately 88% of the maximum achieved improvement. Patient satisfaction increased more rapidly in the Relatox → Frax 1550 group; however, the Day-28 and 3-month outcomes were comparable between the groups. By Day 28, wrinkle severity at rest had decreased significantly in all assessed facial regions. In the forehead zone, mean Lemperle scores decreased from 3.2±0.9 to 0.6±0.5 in both groups. In the glabellar region, scores decreased from 3.0±1.2 and 3.5±1.1 to 0.8±0.7 in Groups 1 and 2, respectively. In the periorbital zone, scores decreased from 3.6±1.1 to 1.0±0.8 and 0.8±0.7, respectively (T=0; p=0.008 for all regions and both groups). At 3 months, a non-significant trend toward partial recurrence of wrinkle severity was observed (p=0.219–1.000), while improvement relative to baseline persisted in all zones. On Day 28, clinically relevant myorelaxation, defined as a positive response in facial muscle activity tests, was observed in 89.1% of evaluations in the Frax 1550 → Relatox group and in 95.3% in the Relatox → Frax 1550 group. At 3 months, the respective proportions were 55.4% and 60.8%, reflecting a partial recovery of facial muscle activity over time, while clinically significant myorelaxation persisted in more than half of the assessments in both groups. Improvement in skin tone, turgor, and microrelief was observed in all 16 patients at Day 28 and remained present at 3 months. Expected transient post-procedural reactions, including mild-to-moderate erythema, mild oedema, and desquamation, were observed in all patients and resolved spontaneously without any additional treatment. Conclusion. Both sequences of combined treatment – Frax 1550 followed by Relatox, and Relatox followed by Frax 1550 – were associated with high patient satisfaction, a significant reduction in wrinkle severity at rest, improvement in skin quality, and favourable tolerability. Relatox administered as the first stage was associated with a more rapid improvement in subjective satisfaction, whereas the overall outcomes were comparable between the sequences. The observed dynamics of facial muscle activity tests do not permit conclusions regarding the effect of Frax 1550 on the duration of botulinum toxin activity because of the small sample size, lack of randomization, and different intervals between botulinum toxin administration and follow-up assessment.