Can Botulinum toxin type A prevent kinetic horizontal forehead lines to become static ? A five year follow up study

Can Botulinum  toxin type A prevent kinetic horizontal  forehead lines to become static ? A five year follow up study

Ahmed F EISherief, MD;  Sameh M EI-Taher, MD; Asser EI-Hilaly, MD Plastic and Reconstructive Surgery Department, Ain Shams  University,

Cairo, Egypt.

Abstract

Background:  Botulinum  toxin type A injection  has become a worldwide  leading  method for treating facial rhytides specially in women. Authors still debate whether or not regular administration of the toxin may delay or prevent kinetic horizontal forehead lines from changing their nature to static ones and hence the need for further interventions includingfacial cosmetic surgery. This study was performed to analyze the relationship between regular administrations of Botulinum toxin type A injection and the change in nature ofhorizontalforehead lines.

Methods: Forty female patients, whose ages ranged from 35 to 45 years, were divided into two groups of twenty each. Group A included females who had regular administration (2-3 times annually) of Botulinum toxin type A to treat horizontal forehead lines. Group B included twenty females who infrequently  (once every 12-18  months)  had Botulinum  toxin type A injection. Changes  in nature of the horizontal  forehead lines were compared  between the two groups, according to the Carruther 's five grade scale for forehead wrinkles established in 2008.

Results:  Eighty five percent of Group A patients who had regular Botulinum toxin type A injections,  showed no change to their forehead lines after five years, and  only 15 % of the group showed one grade change. On the contrary, five years later, 80 %of group B females showed change in the nature of their forehead wrinkles one or two grades more, according to the Carruthers scale of forehead rhytides.

Conclusion: Regular administration of Botulinum toxin type A during its effective period of action (4 to 6 months), two or three times per year, prevents progression of forehead horizontal wrinkles from changing their kinetic nature over a period of five years.

Introduction:

Although the non-cosmetic effect of Botulinum toxin type A (Botox) was first noticed  in 1822, the "magic  of  Botox" was only widely appreciated  around the world in

2002,  when  FDA approval  of  its  cosmetic

usage was announced. This was achieved through  the effort of the "Carruthers" of Vancouver Canada, and hence the toxin's widespread recognition.!

Over the years and due to cumulative effect of  both  internal  factors  (aging  and  tissue wear and tear) and external environmental factors  (sun   exposure   and   smoking),   the skin  tends  to  lose  its  elasticity  and  shows signs  of  aging.2  Contractions  of  the  facial

muscles results in different patterns of facial expressions. The long term contraction of muscles  gradually  produces  its  toll  on  the skin, with the appearance of lines or rhytides. As  individuals  age,  compensatory  increase of the visual field is aided  by the action of frontalis muscle which is commonly used to exhaustion.3

Non-surgical      enhancement     of    facial rhytides   using   Botulinum    toxin   type   A injection has been the choice of many patients over surgery for the past years. In addition, other complementary  methods as hyaluronic acid,  chemical  peeling  or  laser  resurfacing much enhance the effect of injections. These procedures do not completely prevent surgery

in the future, but rather delay the need for surgery at a younger age.4

The mode of function of Botulinum toxin type  A  is  to  block  acetyl  choline   release from cholinergic motor nerve endings from motor end plate receptors.  Muscle motion is thus  affected,  and according  to the amount of toxin units injected per area, muscles can vary from moderate to minimal motion, to becoming   temporarily   flaccid.   The   effect of  the  Botulinum  toxin  ranges  from  4  to

6   months   then   is   completely   reversible. During the effective period of action, muscle mobility  is less, and thus muscle pull on the skin is also decreased. This in turn helps to render the expression lines less affected. The overall appearance is a face with little or no wrinkles. Basic units of Botulinum toxin type A applied to the forehead  range from 15 to

25 units, according to the patient's age, depth

of rhytides and number of forehead lines apparent.5

With advancement of age, deep folds become  more  obvious,  and  redundant  lax skin could better be enhanced only through surgical  procedures.  The  regular  treatment by non-surgical  procedures  thus  delays  the need for surgery, and together with a healthy life style and healthy diet, may help avoiding surgery permanently according to individual satisfaction with their results.6

Glogau  in 1996  classified  forehead  lines into four grades, and the Carruthers  in 2008 further modified the classification into five.7

Grade I no wrinkles, grade II kinetic wrinkles,

grade III wrinkles at rest that become deeper by frontalis muscle contraction (static-kinetic), grade  IV  wrinkles  that  show  no difference in   appearance   at   rest   or   during   muscle action "completely  static",  or static wrinkles that disappear by skin stretch, and grade V forehead wrinkles that don't  improve by skin stretch, or more than two lines of forehead wrinkles. The classification was based on the main factors affecting facial wrinkles, mainly age, smoking, and sun exposure.8

Aim of the work: This study was performed to analyze the relationship between regular administrations of Botulinum toxin type A injection 2-3 times per year and the change in

nature of horizontal forehead lines.

Patients and methods:

This study included a total of forty women, ranging from 35 to 45 years old. They  were divided into two groups A & B, with a total of twenty women in each group. Group A patients included females who had Botulinum toxin A injected at regular time intervals of 4 to 6 months apart, while Group B included patients who had the toxin administered at irregular time intervals of 12 to 18 months between each injection session.

An exclusion  criterion  was females  who had  previous  operative  procedures  of  any sort to their forehead, including endoscopic forehead lift. The study was conducted in private practice over a period of five years. Patients were followed  up for 4- 6 months after the last injection session.

All  patients  were  grade  II  or  III (Carruther's) classification of forehead lines. Botulinum toxin type A "Botox" of Allergan vials of 100 units, were each diluted  in 2.5 cc of 0.9 % normal fresh saline preparation, and withdrawn in 40 units syringes; thus one syringe mark was equivalent to one unit of Botulinum toxin type A. A fixed dosage of 20 units of Botulinum  toxin type A injected to treat forehead  lines was standardized  in all forty females Figure(l).

All female patients were instructed to regularly  visit  the  doctor  two  weeks  after the initial injection, and four to six months later, which is the effective duration of Botulinum toxin type A. The score of Carruther's  classification   was  subjectively and objectively determined and compared between the two groups of females;  all data concerning   patients  included  in  this  study were  recorded  in  their  individual  sheets  as well as dates of Botulinum toxin A injection. A written consent of approval for this study was obtained as well as photographic data Figures(2-6).

In   the  two  groups,   some   females   did

need complementary methods in addition to Botulinum toxin A injection to reach more satisfactory and aesthetically pleasing results. The  intervention   included  hyaluronic  acid

InJections, facial  resurfacing  usmg  Erbium

Yag laser and fat injection.

Evaluation of the aesthetic outcome was done subjectively by patient self- evaluation with four Likert subscales for the degree of satisfaction (very satisfied, satisfied, less satisfied and unsatisfied). Objective evaluation was assessed through photographic data by three medical  personnel  not involved  in the study, also using four Likert subscales (very good, good, fair and poor) Graph(2).

Results:

In group A, 17 females, (85%) showed no change of their frontal forehead lines after five years of Botulinum toxin A treatment. Six of the eight patients (30%) who started as grade II scale,  remained  at  the  same  scale  score after 5 years.  Eleven  of the twelve  patients who  were  grade  III  scale also  remained  at the  same  grade.  Two  patients  of  group  A score II, (10%) showed changes from grade II to  grade  III Carruther 's score  during  the five year period. One female, (5%), with a score III changed to score IV after five years. Botulinum toxin type A proved effective and sufficient to the majority of females in this group. Two of the three females who showed one grade changes after five years asked for complementary  Erbium  Yag  fractionated laser resurfacing in addition to the Botulinum injections, and one patient had hyaluronic acid injection to further enhance fine horizontal forehead  lines,  although  she  was  satisfied with the overall result after five years. For all twenty females of this group, surgery was not an issue for discussion.

In group B, 16 of the 20 females, (80%), showed changes from their original forehead scale score after five years. Three of the seven patients (15%) who started with grade score II showed a change from grade II to grade IV scale. The other four patients (20%) showed a change from grade II to grade III scale score, and nine (45%) of the remaining thirteen patients showed a change from grade III to IV scale. Four females (20%) with grade II score of this group showed no grade change within the five year period Graph(la&b).

Eleven females in this group seeked additional  methods  for  horizontal  forehead lines   enhancement.    Two   females   (16%) did correctional fat injection to treat deep forehead   creases,   and   six   other   females (30%) had hyaluronic acid injections to the forehead creases two weeks after Botulinum toxin type A. Two patients performed Erbium Yag fractionated  laser resurfacing  treatment in addition to hyaluronic acid and Botulinum toxin injections. One female (5%) discussed the  possibility  of a forehead  lift procedure, but never did the operation to date.

A peculiar finding in both groups was noticed, which was the appearance of a horizontal line just above the lateral aspect of the eyebrow (0.5- 1cm) on one or both sides. The finding was seen in five patients (25%) of group A, and nine females (45%) in group B. As minimal as two units of the toxin were injected  at the site for  fear  of  brow  ptosis, but the lines still showed little tendency to become less apparent by time.

20

18

16

14

ll

10                                                                                                    • total pts

•noM:orcchan c

Korc change

J

Figure (l):Foreheadrhytides injected with a

fixed dose of 20 units Botulinum  Toxin A.

Graph (la): Showing the total no. of

patients,  patients with score or no score changes according to Carruther 's scale for forehead rhytides.

Group A

GroupE

Group A PRE

Group  B PRE

Group A Post

•Fcmslb sho\\mg nogr-Jdc I I score changes •Females showmg no grade Ill score chang

•Females siK'I"'ing grade II score chang     •Fcmalshowt ng gt".:Kk Ill  ore: changes

Group B Post

•Femulb sho\\ mg 0() gr-Jdc I I score ch:mgcs •Femalesshowmg no grade Ill score changei

•Fcmalei ii'IO"ing grade I I score changci       •fcmalc.!i showt ng gi'"Jdc- Ill score dungcs

Graph (1b): showing percentage of patients with starting grade scores of horizontal forehea. lines and the percentage of females with forehead line changes after five years

Patient's self evaluation Group A

• Very salu;!ictl   •S:uislicd       lcslli satt.lofiOO    •U•ualisficd

O'o

Patient's self evaluation Group  B

• Very sat1s!icd     •Sat1.dicd       leu s:&l!.lofiOO      •U1\iati.!ilicd

Obser ver 's evaluation Group A

• \'cry good   •Good      Ftur  •Poor

()'" ,

Obser ver' s evaluation Group A

• v good  •Good   •Fuir   •Poor

Graph (2):Showing Likert's objective and subjective evaluation of the five year study.

Figure (2a-d): a &b: patient at jst  session, c &d: 5 years later

Figure (3a-c): a: patient at Jst  session, b&c: 5 years later.

Figure (4a-c): a: patient at Jst  session, b&c: 5 years later.

Figure (5a): ]st

session

Figure (5b): 5 years      Figure (6a): jst

later one grade              session change

Figuer (6b): 5 years later one grade change

Discussion:

With  advancement of  non-surgical cosmetic  procedures,  various    choices   are now  available to  both  patients  and  doctors. Treating horizontal  forehead   wrinkles  starts in a step ladder manner, beginning with Botulinum    toxin   type    A   injection   alone or together  with hyaluronic acid fillers. Furthermore, chemical peeling  or laser resurfacing may also be added.  Minimal surgery  to the forehead including brow  lift, and  full  forehead lift  either  endoscopically or  surgically,   are  usually  the  patients' last choice, unless severe skin damage demands operative intervention from the start.9

Different  classifications of forehead wrinkles were used in an attempt tostandardize the management, but the two mostly accepted and used are the Glogau classification (1996), and the Carruther's modification grading (2008).

Kinetic frontal forehead wrinkles usually start to become  bothersome to a considerable number   of  women   by  their   mid-30's,  and by the  time  they  seek  professional care  for the first time, 56% of them have grade III forehead wrinkles.lO These findings coincide with  the findings  in  our study,  as 25 of the

40 women first presented  with grade III score for forehead  wrinkles. This represents 63% of cases.

The cumulative effects of external  and internal  factors  will finally change  the nature of facial  rhytides  to become  deeper  or  more in number;  the only concern is the rate of that change. Women may appear younger  or older than their real age. Botulinum toxin type A injections may  delay  the  need  for  surgical upper face rejuvenation later in life.ll

According to photographic data collected over   four   years   of   the   initial   status   and progress of forehead rhytides, the Carruthers established a validated   photo-numeric scale for horizontal forehead rhytides in 2008. Photographic data also  verified that with scheduled    administration    of     Botulinum toxin  A,  surgical  intervention for  upper face rejuvenation can be postponed. In a study  of

60  female   patients   regularly   scheduled for

Botulinum toxin  A  injection  over  a  period

of four years, only 11% of them needed additional procedures besides  the toxin injection.

In our study, similar findings were recorded for group  A females  regularly  scheduled for the  toxin  injection   over  a  five  year  period.

10%   needed    additional   laser   resurfacing to Botulinum  injection, but the thought of surgery  even  in  the  near  future,   was  not  a demand  for any patients in this group.

The Carruther's, back in 2007 commented on the eyebrow height after  Botulinum toxin A   injections,    and   explained  the   wrinkles above the lateral  aspect of the eyebrow  to be due to inactivation of the medial fibers of the frontalis muscle  after treatment. This  results in increased muscle fiber activity in the lateral and superior  frontalis muscle fibers.l2

On   the   other   hand,   Kang   et  al,  2011, described exaggeration of wrinkles  after regular  Botulinum toxin  type A injection for forehead   horizontal    lines.   They   described the   appearance  of  one   new  deep   wrinkle just  above  the  eyebrow in  two  cases.  The authors explained this as being caused by hyperactivity and overcompensation of untreated  muscles.l3

In  our  study,  the  deep  forehead  line  that would appear  just above the eyebrow  on one or  both  sides  though,   was  a finding  in  five females  (25%)  of  group  A who  had  regular toxin   administration,  and   nine   patients   in group  B (45%).  This  area  is  usually  either not  treated   with  Botulinum toxin  injection or  minimally treated   (2  units)  due  to  fear of  eyebrow ptosis.   Our  explanation  of  the exaggerated lateral supra eyebrow lines maybe due  to  the  fact  that  mobility of  the  medial aspect of the eyebrow is limited  compared to the  lateral  aspect.  The  explanation coincides with  the  study  conducted   by Sullivant et  al

2006  on 12 cadavers.  Anatomical dissection showed   three   medial   retaining  ligaments of the eyebrow as compared to one lateral retaining  ligament.l4

It was clear that females who had injections of Botulinum toxin  type A administered at regular time intervals, showed superior  results of forehead  rejuvenation than those who had the toxin injected over longer periods of time.