Statistical Analysis
IBM SPSS version 23.0 (IBM Corp., Armonk, NY) was used for statistical analysis. The Wilcoxon signed rank-sum test was performed to compare the difference between the baseline and follow-up periods. The differences in outcomes were considered significant if P< 0.05. All continuous variables are expressed as the mean ± standard deviation.
IBM SPSS version 23.0 (IBM Corp., Armonk, NY) was used for statistical analysis. The Wilcoxon signed rank-sum test was performed to compare the difference between the baseline and follow-up periods. The differences in outcomes were considered significant if P< 0.05. All continuous variables are expressed as the mean ± standard deviation.
RESULTS
Thirty-two patients were injected with INCO using the aforementioned protocol over the study inclusion period. A retrospective chart was reviewed to confirm that the patients were suitable for study inclusion. Twelve were excluded because they did not regularly follow-up on the visiting schedule. A total of 20 patients (18 females and 2 males) fulfilled the inclusion criteria. The mean age was 35.7 ± 6.4 (mean ± standard deviation) years. Sebum secretion was significantly reduced at week 1 (99.1 ± 37.2 and 59.7 ± 43.6 μg/cm2, P<0.001 and = 0.001), week 4 (91.8 ± 39.7 and 56.5 ± 41.6, P<0.001 and = 0.002), and week 12 (96.0 ± 35.7 and 60.5 ± 35.3, P= 0.010 and = 0.013) compared to that at baseline (121.5 ± 37.6 and 72.5 ± 43.0) for both the forehead and chin (Table 1). In particular, at 4 weeks, sebum secretion decreased by 24.4% on the forehead and 22.1% on the chin.
Similarly, mandibular length and facial pores (both number and density) also showed a significant decrease after 1 week (240.2 ± 21.4 mm, 1515.4 ± 472.1 count, 36.8 ± 10.9 %, P< 0.001 in each), 4 weeks (239.1 ± 20.4, 1371.2 ± 443.0, 33.3 ± 10.2, P< 0.001 in each), and 12 weeks (240.1 ± 20.0, 1584.8 ± 440.1, 38.6 ± 10.7, P= 0.026, 0.002, 0.003) of INCO injection compared to that at baseline (241.6 ± 21.4, 1805.0 ± 478.7, 43.9 ± 11.5). All variables showed the most improved results after 4 weeks.
Change in facial laxity evaluated by the FLR scale was significantly improved after INCO injection (P< 0.001 at week 1, week 4, and week 12) (Table 2). At baseline, there was no FLR scale grade 1 and only 1 subject (5%) had a grade 2; however, at week 4, 75% of the subjects were grade 2 or less, with 3 (15%) having grade 1 and 12 (60%) having grade 2. Both GAIS by investigator and patients showed at least a score of 2 (improved), except for one patient with no change (score 1) at week 1. At week 4 and 12, both GAIS by investigator and patients scored grade 2 or more. FLR scale and GAIS showed the best results at week 4 (Figure 4). No adverse reaction or complication was reported during the 12-week follow-up period after intradermal microdroplet injection of INCO.
Similarly, mandibular length and facial pores (both number and density) also showed a significant decrease after 1 week (240.2 ± 21.4 mm, 1515.4 ± 472.1 count, 36.8 ± 10.9 %, P< 0.001 in each), 4 weeks (239.1 ± 20.4, 1371.2 ± 443.0, 33.3 ± 10.2, P< 0.001 in each), and 12 weeks (240.1 ± 20.0, 1584.8 ± 440.1, 38.6 ± 10.7, P= 0.026, 0.002, 0.003) of INCO injection compared to that at baseline (241.6 ± 21.4, 1805.0 ± 478.7, 43.9 ± 11.5). All variables showed the most improved results after 4 weeks.
Change in facial laxity evaluated by the FLR scale was significantly improved after INCO injection (P< 0.001 at week 1, week 4, and week 12) (Table 2). At baseline, there was no FLR scale grade 1 and only 1 subject (5%) had a grade 2; however, at week 4, 75% of the subjects were grade 2 or less, with 3 (15%) having grade 1 and 12 (60%) having grade 2. Both GAIS by investigator and patients showed at least a score of 2 (improved), except for one patient with no change (score 1) at week 1. At week 4 and 12, both GAIS by investigator and patients scored grade 2 or more. FLR scale and GAIS showed the best results at week 4 (Figure 4). No adverse reaction or complication was reported during the 12-week follow-up period after intradermal microdroplet injection of INCO.
DISCUSSION
In this study, INCO injection improved facial laxity, sebum secretion, and facial pore count up to 12 weeks after injection. This is the first study with INCO to date using intradermal microdroplet injection for these indications.
The concept of face lifting by BTX is to correct the imbalance between the activity of levator and depressor muscles in the face.27 Aging progression, along with gravity causes dominant depressor muscle activity and a downward movement vector; thus, this results in sagging and drooping. Although the intradermal injection of 20–25 U/side of ONA to temporal areas and cheek showed no significant face lifting effect,28 a more recent study showed that intradermal injection of 50 U/side ONA or 125 U/side ABO showed comparable and significant efficacy in face lifting.15 Consistently, Petchngaovilai retrospectively reported intradermal injections of 100–140 U ABO to the platysma and orbicularis oculi, which led to midface lifting in 90% of patients lasting 10 to 14 weeks.27 A split-face trial involving 22 subjects showed that intradermal injection of ABO to the superior portion of the frontalis, corrugator supercilli, lateral part of the orbicularis oculi, and platysma was associated with face lifting in 40.9% of patients after 2 weeks.8 Another split-face study found that intradermal injection of different dilutions (50 U or 100 U/side) of ABO were similarly effective in reducing facial laxity and wrinkles.29 However, only subjective assessments, such as photographic comparison or grading were performed in previous studies, without objective quantification using validated devices. In the present study, the degree of face lifting was evaluated by both subjective (FLR scale) and objective measurements (mandibular length) using a 3D scanner. Time point of peak efficacy for face lifting, sebum secretion, and facial pores observed in this study was 4 weeks, which is similar to that of the follow-up results from previous BTX studies for wrinkle reduction.30
Several studies reported decreased sebum production or improved facial pores by intradermal injection of BTX. The mechanism of BTX effects on sebum production has not been fully elucidated; however, sebocyte differentiation and sebum production may be disturbed by inhibition of acetylcholine release by BTX.14,31 Shah9 reported that intradermal injection of BTX improved skin oiliness and facial pores in 85% of patients (17/20), although the study was designed retrospectively and no objective evaluation was included.9 The other two studies examined the efficacy of BTX on forehead sebum production by intramuscular injection of ONA11 or intradermal injection of ABO.12 In both studies, decreased sebum production measured by Sebumeter showed a peak after 1 month and was maintained until approximately 2–3 months after injection.11,12 Although intradermal injection of 50 U/side ONA or 125 U/side ABO failed to show significant efficacy in sebum and facial pore reduction,15 a recent split-face study showed that the intradermal BTX injectedside showed a significantly greater reduction in seborrhea at 1 month compared to that of the saline injected-side.10 However, there was a limitation in that seborrhea was evaluated by a 4-point score rather than by objective quantification.
The concept of face lifting by BTX is to correct the imbalance between the activity of levator and depressor muscles in the face.27 Aging progression, along with gravity causes dominant depressor muscle activity and a downward movement vector; thus, this results in sagging and drooping. Although the intradermal injection of 20–25 U/side of ONA to temporal areas and cheek showed no significant face lifting effect,28 a more recent study showed that intradermal injection of 50 U/side ONA or 125 U/side ABO showed comparable and significant efficacy in face lifting.15 Consistently, Petchngaovilai retrospectively reported intradermal injections of 100–140 U ABO to the platysma and orbicularis oculi, which led to midface lifting in 90% of patients lasting 10 to 14 weeks.27 A split-face trial involving 22 subjects showed that intradermal injection of ABO to the superior portion of the frontalis, corrugator supercilli, lateral part of the orbicularis oculi, and platysma was associated with face lifting in 40.9% of patients after 2 weeks.8 Another split-face study found that intradermal injection of different dilutions (50 U or 100 U/side) of ABO were similarly effective in reducing facial laxity and wrinkles.29 However, only subjective assessments, such as photographic comparison or grading were performed in previous studies, without objective quantification using validated devices. In the present study, the degree of face lifting was evaluated by both subjective (FLR scale) and objective measurements (mandibular length) using a 3D scanner. Time point of peak efficacy for face lifting, sebum secretion, and facial pores observed in this study was 4 weeks, which is similar to that of the follow-up results from previous BTX studies for wrinkle reduction.30
Several studies reported decreased sebum production or improved facial pores by intradermal injection of BTX. The mechanism of BTX effects on sebum production has not been fully elucidated; however, sebocyte differentiation and sebum production may be disturbed by inhibition of acetylcholine release by BTX.14,31 Shah9 reported that intradermal injection of BTX improved skin oiliness and facial pores in 85% of patients (17/20), although the study was designed retrospectively and no objective evaluation was included.9 The other two studies examined the efficacy of BTX on forehead sebum production by intramuscular injection of ONA11 or intradermal injection of ABO.12 In both studies, decreased sebum production measured by Sebumeter showed a peak after 1 month and was maintained until approximately 2–3 months after injection.11,12 Although intradermal injection of 50 U/side ONA or 125 U/side ABO failed to show significant efficacy in sebum and facial pore reduction,15 a recent split-face study showed that the intradermal BTX injectedside showed a significantly greater reduction in seborrhea at 1 month compared to that of the saline injected-side.10 However, there was a limitation in that seborrhea was evaluated by a 4-point score rather than by objective quantification.
