Botulinum-A Toxin Treatment of the Lower Eyelid
Improves Infraorbital Rhytides and Widens the Eye
Timothy Corcoran Flynn, MD,* Jean A. Carruthers, MD, FRCSC, †
and J. Alastair Carruthers, MD, FRCPC ‡
*Department of Dermatology, Tulane University Health Sciences Center, New Orleans, Louisiana, and †Department of
Ophthalmology and ‡Division of Dermatology, University of British Columbia, Vancouver, British Columbia, Canada
Botulinum-A exotoxin (BTX-A) can be used cosmetically to im-
prove rhytides, particularly of the upper one-third of the face. In
this study, fifteen women had BTX-A (BOTOX, Allergan, Inc.)
injected into the orbicularis oculi muscle. One lower eyelid re-
ceived two units just subdermally in the midpupillary line three
millimeters below the ciliary margin. The opposite periocular area
received two units BTX-A in the lower eyelid with 12 units
BTX-A injected into the lateral orbital (“crow’s foot”) area.
Three injections of four units each were placed 1.5 cm from the
lateral canthus, each 1 cm apart. Patients and physicians indepen-
dently evaluated the degree of improvement (grade 0  no im-
provement, grade 1  mild improvement, grade 2  moderate
improvement, and grade 3  dramatic improvement). An inde-
pendent photographic analysis was performed. Patients reported
a grade of 0.73 when two units were injected alone into the lower
BOTULINUM-A (BTX-A) EXOTOXIN is a polypep-
tide neurotoxin derived from the anaerobic bacterium
Clostridium botulinum. It acts at the level of the neu-
roneal endplate, preventing the release of acetylcholine
from the presynaptic neuron.1,2 The toxin produces a
temporary chemical denervation causing weakness or
a partial paralysis of striated muscle. Safe and effec-
tive, BTX-A exotoxin has found clinical application as
a treatment for strabismus,3 blepharospasm,4–6 palmar
hyperhidrosis,7 axillary hyperhidrosis,8 facial dysto-
nia,9 conditions such as migraine and anal fissures and
for cosmesis. BTX-A. has been used cosmetically to
treat glabellar frown lines,10,11 lateral orbital wrinkles,12
platysmal bands,13 ptotic brows,14–16 brow asymmetry,17
other hyperfunctional lines of the face,18–20 and as an
adjunct to laser resurfacing.21
BTX-A exotoxin has been well documented to im-
prove periocular rhytides.12,22–24 The glabellar folds,
forehead, and lateral orbital rhytides (“crow’s feet”)
All authors are consultants to Allergan, Incorporated. Drs. Carruthers
own stock in Allergan, Incorporated. This study was funded in part by
an unrestricted educational grant from Allergan, Incorporated.
Address correspondence and reprint requests to: Timothy Corcoran
Flynn, MD, Cary Skin Center, P.O. Box 5129, Cary, NC 27512, or
e-mail: flynn@caryskincenter.com.
© 2001 by the American Society for Dermatologic Surgery, Inc. • Published by Blackwell Science, Inc.
ISSN: 1076-0512/01/$15.00/0 • Dermatol Surg 2001;27:703–708
lid, and a grade of 1.9 when the lower eyelid and the lateral or-
bital areas were injected. Physician assessment was grade 0.7 with
injection of the eyelid alone and grade 1.8 with injection of the
lower eyelid and lateral orbital area. Single investigator photo-
graphic analysis demonstrated that 40% of the subjects who had
injection of the lower eyelid alone had an increased palpebral ap-
erture (IPA), while 86% of the subjects who had injection of the
lower eyelid and lateral orbital area had an IPA. Subjects receiving
two units alone had an average 0.5 mm IPA and a mean 1.3 mm
IPA at full smile. Concomitant treatment of the lateral orbital area
produced a mean 1.8 mm IPA at rest and a mean 2.9 mm IPA at
full smile. The results were more notable in the Asian eye. Two
units of BTX-A injected into the lower eyelid orbicularis oculi
muscle improves infraorbital wrinkles, particularly when used in
combination with BTX-A treatment of the lateral orbital area.
respond well to BTX-A therapy.25,26 The improvement
is temporary, lasting 3–4 months. The toxin paralyzes
or weakens overactive muscles of facial expression
and improves wrinkles overlying the musculature. The
use of BTX-A in the lower eyelid has been reported
anecdotally by Arnold Klein, Richard Glogau, Stephen
Fagien, and each of the authors. Injection of a few
units into the orbicularis oculi muscle has been said to
obliterate lower eyelid folds and give the eyes a more
open appearance. This study documents the effect of
injections of BTX-A on lower lid folds with or with-
out concomitant use in the lateral orbital area.
Patient Selection
Women 18–60 years of age, not pregnant or lactating,
having a hypertrophic orbicularis oculi muscle of the
lower lid contributing to lower eyelid folds or rhytides
were candidates for the study. Additional inclusion
criteria were an acceptable snap test (grades I and II),
no dry eye (sicca) symptoms, and no existing ectro-
pion. At rest and in the neutral position, the lower
eyelid margin obscured or just touched the corneal
limbus. Patients were botulinum-A toxin naïve in the
infraorbital area and could not have had botulinum
toxin in the lateral orbital area for 6 months or longer.
704 flynn et al.: botulinum-a toxin for lower eyelids
Exclusion criteria included an unacceptable snap test
(grades III and IV), previous lower eyelid surgery or
resurfacing, ectropion, or a degree of ocular or eyelid
asymmetry that would interfere with assessment, al-
lergy to BTX-A, neurologic or neuromuscular disease,
or concurrent therapy with aminoglycoside antibiot-
ics, pregnancy, or lactation.
Materials and Methods
Preoperative Visit
Patients were screened for their suitability for the
study. A urine pregnancy test was done at the initial
visit, confirming their nongravid status. A snap test
was performed and graded on a scale of I–IV. In-
formed consent was obtained. Assessment of lower lid
folds and rhytides was done by both the physician and
patient. Patients were photographed preoperatively
with the head in the neutral position. A 35mm camera
was placed at the level of the Frankfurt horizontal (a
horizontal line drawn from the lowest point of the
bony infraorbital rim to the superior margin of the ex-
ternal auditory canal). Patients were photographed at
1:5 magnification using 35mm Ektachrome E100S
(Kodak, Inc., Rochester, NY) transparency film. A
millimeter scale was taped to the patient’s facial skin
to assist in photographic analysis. Patients were pho-
tographed anteriorly and bilaterally at rest and at
maximal smile. The mouth was included in the photo-
graphs to assess the “degree of smile.”
The height of the palpebral aperture was measured
and recorded using a transparent millimeter scale held
vertically in front of the eye in the midpupillary line. A
modified Schirmer test was performed by instilling
0.5% tetracaine ophthalmic drops bilaterally. Excess
tearing was absorbed with cotton-tipped applicators.
Schirmer strips were placed in the lateral one-third of
the lower lid, and tear production (in millimeters)
measured and recorded after 60 seconds.
Botulinum-A Toxin Injections
BTX-A was reconstituted using 1 ml of preservative-
free physiologic saline on the day of injection. The
preparation was gently swirled and inverted to ensure
uniform concentration of 1 unit/0.01 cc. The reconsti-
tuted toxin was kept refrigerated in between patient
injections. Syringes (0.3 ml) with 0.25 inch 30-gauge
needles were used to inject the patient, with 0.16 ml
(16 units of BTX-A) withdrawn into the syringes. An
isopropyl alcohol pad was used to prepare the sites of
injection. Any isopropyl alcohol was allowed to evap-
orate prior to the use of BTX-A so as to not denature
the protein. Subjects were injected in the sitting posi-
tion, in the locations illustrated in Figure 1.
Dermatol Surg 27:8:August 2001
Figure 1. Schematic illustrating the site of injections and number
of units of BTX-A used in the study. Injections were placed directly
into the orbicularis oculi muscle just subdermally.
For lower lid injections, the syringe and needle were
oriented horizontal to the ground and tangential to
the lower eyelid. The needle was inserted from a lat-
eral position just lateral to the midpupillary point, 3–4
mm inferior to the lash margin. The tip of the needle
was advanced to the midpupillary point and two units
of BTX-A (0.02 ml) placed just subdermally. Any mi-
nor bleeding was treated with gentle pressure using
the tip of a cotton-tipped applicator.
For the lateral orbital “crow’s feet” injections, pa-
tients were randomized to the side of injection. Pa-
tients having an even day of birth were injected on the
right side, and those with an odd day of birth were in-
jected on the left. Three injection points were chosen,
all at a 1.5 cm radius from the lateral canthus, which
is 1 cm outside of the lower orbital rim. Each injection
point received 0.04 ml (4 units) for a total of 12 units
of BTX-A. The superior point was 3 mm above the
horizontal, the middle injection located 1 cm below
the first, and the inferior injection just lateral to verti-
cal 1.5 cm below the lateral canthus (Figure 1).
Patients were instructed to remain upright for 4
hours after injection, not to touch the area, not to
bend over or sleep, and to contract the eye muscula-
ture every minute for 2 hours after injection. Subjects
who experienced any adverse effects or felt they may
be having an adverse effect were instructed to report
immediately to the physicians.
Follow-Up Assessment
Patients were seen 2 weeks after the baseline visit.
Standardized photographs were again taken as previ-
ously described. Both patients and investigators were
Dermatol Surg 27:8:August 2001 flynn et al.: botulinum-a toxin for lower eyelids 705

asked to assess whether there had been improvement

in each lower lid independently on a 0–3 scale (0, no
improvement; 1, mild improvement; 2, moderate im-
provement; 3, dramatic improvement). Physician eval-
uators were blinded to the patient’s assessment. Palpe-
bral apertures were measured at rest, the degree of
scleral show assessed, and the snap test repeated. The
modified Schirmer test was repeated if the patient
complained of dry eye symptoms.

Study Exit
Subjects exited after the above assessments were com-
pleted. Subjects were offered BTX-A treatment of the
untreated lateral orbital area in order to return them
to a more symmetrical appearance.
Results
Fifteen patients completed the study. Assessment of
improvement was graded by the patients on a numeri-
cal scale of 0–3 as previously mentioned. All patients
were graded independently by their physician using
the same scale. The results are shown in Table 1,
which compares patient assessment of improvement
when 2 units of BTX-A was placed subdermally in the
lower lid alone against 2 units placed in the lower lid
and 12 units in the lateral orbicularis oculi. The im-
provement with 2 units of BTX-A placed in the lower
lid had an average patient assessment grade of 0.73.
The side that received 2 units in the lower lid and an
additional 12 units in the lateral orbicularis area re-
ported an average grade of 1.9. Thus patients with 2
units in the lower lid reported a grade approaching
mild improvement, while those patients who had 2
Figure 2. A) The patient at repose prior to BTX-A treatment. B)
The patient 2 weeks after BTX-A having been treated with two
units in both lower eyelids and 12 units in the left lateral orbital
area. C) The patient at full smile prior to BTX-A treatment. D) The
patient at full smile following BTX-A treatment.
units placed in the lower lid plus the crow’s feet re-
ported a grade approaching moderate improvement
(Figure 2).
The physician’s assessment of the degree of im-
provement was done independent of the patient’s as-
sessment, as shown in Table 2. The physician’s assess-
ment of an isolated 2 units of BTX-A placed in the
lower lid reported a grade of 0.7, and 2 units placed in
the lower lid plus 12 units in the crow’s feet reported a
grade of 1.8. Remarkable was the similarity between
the physician and patient evaluation of improvement.
Photographic evaluations were performed by one
investigator (TCF) on photographs taken of all pa-
tients. The single investigator evaluated the degree of

Table 1. Patient Assessment of Improvement in Lower Lid Rhytides Table 2. Physician Assessment of Improvement in Lower Lid Rhytides

2 units BTX-A 2 units BTX-A lower lid plus 12 units 2 units BTX-A 2 units BTX-A lower lid plus 12 units
Patient lower lid BTX-A lateral orbital “Crow’s feet” area Patient lower lid BTX-A lateral orbital “Crow’s feet” area

EP Grade 1 Grade 2 EP Grade 1 Grade 2

VM Grade 0 Grade 2 VM Grade 1 Grade 3
HM Grade 1 Grade 3 HM Grade 1 Grade 3
NF Grade 0 Grade 2 NF Grade 0 Grade 2
JK Grade 1 Grade 3 JK Grade 1 Grade 2
HT Grade 0 Grade 1 HT Grade 0.5 Grade 1
CC Grade 1 Grade 3 CC Grade 1 Grade 2
MK Grade 1 Grade 3 MK Grade 1 Grade 3
CM Grade 1 Grade 2 CM Grade 1 Grade 1.5
MP Grade 0 Grade 0 MP Grade 0 Grade 0
WK Grade 1 Grade 2 WK Grade 1 Grade 1
SA Grade 0.5 Grade 1.5 SA Grade 0 Grade 1
KS Grade 0 Grade 1 KS Grade 0 Grade 1
CM Grade 2.5 Grade 2.5 CM Grade 0.5 Grade 2
JM Grade 1 Grade 2 JM Grade 1 Grade 2
Average Grade 0.73 Grade 1.9 Average Grade 0.7 Grade 1.8
706 flynn et al.: botulinum-a toxin for lower eyelids Dermatol Surg 27:8:August 2001

improvement based on the photographs. A partial set

is shown in Figure 3. Treatment of the lower lid alone
had a average grade of 0.5 (halfway between no im-
provement and mild improvement), whereas treatment
of the lower lid plus the lateral orbital area produced
an average grade of 1.0 (mild improvement). This in-
vestigator made note of whether or not the patients
had a noticeable increased palpebral aperture on vi-
sual inspection of the photographs. Six of 15 (40%)
had an increased palpebral aperture with an isolated 2
units in the lower lid. Twelve of 15 (86%) had an in-
creased palpebral aperture with 2 units placed in the
lower lid in combination with the 12 units in the lat-
eral orbicularis. One patient, of Asian descent, had a
dramatically increased palpebral aperture, changing
her appearance to a more western eye (Figure 4). Figure 4. Dramatic improvement is seen in this patient of Asian
Measurement of the increase in palpebral aperture descent. Note the widening of the palpebral aperture at rest (B)
and at full smile (D). The patient’s right eye had treatment of
was carried out in eight patients. Not all patients both the lower eyelid and the lateral orbital area. The patient’s
could be accurately evaluated due to omission of the left eye received only 2 units in the lower eyelid.
standard millimeter rule from the patient’s cheek. The
increase in palpebral aperture was measured in the
midpupillary line at rest and at “full smile,” as sum-
had a 0.5 mm increase in palpebral aperture at rest
marized in Table 3. A photographic enlarger equipped
and a 1.3 mm increase in palpebral aperture at full
with an 80mm lens was used to project the transpar-
smile. The side receiving BTX-A in the lower lid and
encies. The enlarger was positioned such that the im-
the lateral orbital area had a 1.8 mm increase in palpe-
age was life size. The millimeter scale taped to the pa-
bral aperture at rest and a 2.9 mm increase in palpe-
tient’s cheek served as an internal reference, allowing
bral aperture at full smile.
direct measurement of the palpebral aperture and
There was no change in the snap test postinjection
comparison of all photographs. Table 4 shows that
and no reports of dry eyes following injection of any
those patients receiving 2 units in the lower lid alone
lids. No ectropion, bruising, diplopia, photophobia,
or ptosis was reported. There were no significant side
effects to the treatment. All patients elected to have

Table 3. Single-Investigator Photographic Evaluations

2 units BTX-A 2 units BTX-A lower lid plus 12 units

Patient lower lid BTX-A lateral orbital “Crow’s feet” areaa

KS Grade 0 Grade 1; IPA

HM Grade 0 Grade 0; IPA
SA Grade 0 Grade 0; IPA
VM Grade 0 Grade 0; IPA
CM Grade 1 Grade 1; IPA
EP Grade 0 Grade 1
LM Grade 0 Grade 1
JK Grade 1; IPA Grade 1; IPA
JM Grade 1 Grade 2; IPA
KJ Grade 0 Grade 0; IPA
Figure 3. A) The patient smiling prior to BTX-A treatment of the CM Grade 0; IPA Grade 2; IPA
right lower eyelid. B) The patient 2 weeks after treatment with WK Grade 1; IPA Grade 2; IPA
only 2 units placed into the lower lid. Note the minimal improve- MP Grade 1 Grade 1; IPA
ment in lower eyelid folds. C) The patient, opposite side, smiling TL Grade 1; IPA Grade 1; IPA
prior to BTX-A therapy. D) The patient smiling following 2 units of CC Grade 1; IPA Grade 2; DIPA
BTX-A placed in the lower lid and 12 units in the lateral orbital Average Grade 0.5 Grade 1.0 (86% IPA)
area. Note the improvement in the lower eyelid folds when both (40% IPA)
the lower eyelid and crow’s feet area were treated (D) as com-
pared to treatment of the lower eyelid alone (B). aIPA, increase in palpebral aperture; DIPA, dramatic increase in palpebral aperture.
Dermatol Surg 27:8:August 2001
Table 4. Average Measured Increase in Palpebral Aperture
2 units BTX-A 2 units BTX-A lower lid plus 12
lower lid units BTX-A lateral orbital area
Number
of patients At rest At full smile At rest
8 0.5 mm 1.3 mm 1.8 mm
the untreated crow’s feet injected with 12 units of
BTX-A in order to return them to a symmetrical ap-
pearance.
Discussion
In this study it was demonstrated that 2 units of BTX-A
placed subdermally 3 mm inferior to the lid margin
improves lower eyelid wrinkles. Only a slight im-
provement was seen when 2 units were used alone in
the lower lid. When 2 units in the lower lid were com-
bined with 12 units of BTX-A in the lateral orbital
area, an average grade approaching moderate im-
provement was seen (Figures 5 and 6). Clinically most
patients who seek botulinum toxin therapy for im-
provement of wrinkles have multiple areas treated,
with the crow’s feet area being a common site.27,28
This study demonstrates that one can safely add 2
units of BTX-A in the lower eyelid, achieving almost
immediate moderate improvement in lower eyelid
wrinkles without complications.
Figure 5. A) The patient prior to BTX-A treatment. B) The patient
following treatment of both the lower eyelid and crow’s feet area.
flynn et al.: botulinum-a toxin for lower eyelids 707
At full smile
2.9 mm
Figure 6. A) The patient prior to BTX-A treatment. B) The patient
following combination treatment of both the lower eyelid and
crow’s feet area.
Both the physician and patient noted improvement
in lower eyelid wrinkles. It was remarkable how simi-
lar the evaluations were between the physicians and
the patients. Improvements were confirmed by a pho-
tographic analysis made by a single investigator. Of
interest is the lesser improvement noted by the photo-
graphic analysis. Wrinkles are dynamic lines best ap-
preciated in motion. Photographic transparencies pro-
vide only one moment in time, and slight variations
exist unless strict photographic techniques are em-
ployed. It is worth commenting that the patients were
quite pleased with the results when both the lower
eyelid and crow’s feet area were treated. Several com-
mented about the success of their treatment, particu-
larly when return of orbicularis function occurred at
approximately 3–4 months after treatment.
Increased palpebral aperture was noted for both 2
units in the lower lid and 2 units in the lower lid plus
12 units in the lateral orbital area. A significant in-
crease in palpebral aperture was seen when both the
lower lid and the lateral orbital area were treated.
This increase in palpebral aperture was most notable
when the patient’s exhibited a full smile. Photographs
clearly demonstrated a more open eye or a wide-eyed
appearance. The lateral rounding of the eye is suppos-
edly not considered aesthetically pleasing, but almost
all patients found this to be attractive. Several patients
independently described this as an “inviting” or “at-
tractive” appearance to their eyes.
The results were more dramatic in the Asian eye
(Figure 4) The eye was dramatically widened, particu-
larly at full smile, with 2 units in the lower lid and 12
units in the lateral orbital area. Both the investigators
and the patients commented on the remarkable change
in the patient’s appearance. Subsequently we have
treated a number of Asian patients who have been
quite pleased with this widening effect on the eye.
We noted no side effects of treatment at the dosages
used. The patients experienced no ectropion, ptosis,
dry eye symptoms, photophobia, or difficulty with
sphincter function of the orbicularis. It is important to
realize that our injection technique may be critical: 2
units were placed in the lower lid, just subdermally in
708 flynn et al.: botulinum-a toxin for lower eyelids
the midpupillary line, at or above the level of the or-
bicularis muscle. It is important to not inject the lower
eyelid too deeply, as migration of the botulinum toxin
may occur through the orbital septum, affecting the
extraocular muscles of the eye. It is also important to
realize that the units used in this study relate only to
BOTOX (Allergan, Inc., Irvine, CA).
Wrinkles in the lower eyelid in their initial develop-
ment are often caused by an overactive orbicularis oc-
uli, and BTX-A treatment of this area can improve the
rhytides. With advanced age and photodamage, rhy-
tides worsen and are often a result of the combination
of excessive activity of the orbicularis muscle as well
as photodamage and excessive skin laxity. In advanced
cases, skin resurfacing procedures such as the CO2 la-
ser or filler substances such as hyaluronic acid deriva-
tives or injectable collagen must be used in addition to
botulinum toxin in order to improve the wrinkles.21 It
is important to remember that patients with excessive
lower eyelid skin or lower eyelid fat pads may need a
blepharoplasty for optimal improvement.
In conclusion, 2 units in the lower eyelid can im-
prove lower eyelid wrinkles, particularly when used in
combination with botulinum toxin treatment of the
lateral orbital rhytides. It is safe and effective. Proper
technique of injection is important. Two units in the
lower eyelid can widen the palpebral aperture and give
a more wide-eyed appearance. A wider palpebral ap-
erture was noted when 2 units were used in combina-
tion with the crow’s feet area, and a dramatic effect
was seen in our Asian patient. Studies are now under
way by the authors investigating increased dosages of
botulinum toxin in the lower eyelid.
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