2023 - Management of Severe Botulinum-Induced Eyelid Ptosis With Pretarsal Botulinum Toxin and Oxymetazoline Hydrochloride 0 1

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Management of Severe Botulinum-Induced 
Eyelid Ptosis With Pretarsal Botulinum Toxin 
and Oxymetazoline Hydrochloride 0.1% 
Francesco P. Bernardini, MD; Brent Skippen, MD; Brittony Croasdell, MS; 
Jair Mauricio Cerón Bohórquez, MD; Gillian Murray, MD; Karim Sayed, MD; 
Lee Walker, MD; Morris E. Hartstein, MD; and for the Complications 
in Medical Aesthetics Collaborative (CMAC) Study Group 
Abstract 
Background: Eyelid ptosis following periocular onabotulinumtoxinA (BoNT-A) treatment is a known complication that can 
be frustrating for both patients and practitioners. Iatrogenic blepharoptosis occurs due to local spread of the BoNT-A from 
the periocular region into the levator palpebrae superioris muscle. Although injectors should have a thorough understand-
ing of the relevant anatomy in order to prevent it, BoNT-A induced ptosis can occur even in the most experienced hands. 
Objectives: The aim of this study was to describe a case series of patients treated effectively with topical oxymetazoline 
HCl 0.1% and pretarsal BoNT-A injections in the setting of botox-induced ptosis. 
Methods: The study group consisted of 8 patients who had undergone recent cosmetic BoNT-A treatment preceding the 
sudden onset of unilateral upper eyelid ptosis. 
Results: A diagnosis of severe ptosis (>3 mm) was made in all the cases in this series. Pretarsal BoNT-A injections alone or 
in association with topical administration of Upneeq eyedrops (Upneeq, Osmotica Pharmaceuticals, Marietta, GA) signifi-
cantly reversed the ptosis in all treated cases. 
Conclusions: This is the first documented case series of patients treated effectively with topical oxymetazoline HCl 0.1% 
and pretarsal BoNT-A injections in the setting of botox-induced ptosis. This treatment combination is a safe and effective 
option in these cases. 
Level of Evidence: 4 
Editorial Decision date: March 10, 2023; online publish-ahead-of-print March 21, 2023. 
Dr Bernardini is an aesthetic oculoplastic surgeon in private practice in 
Genova and Milano, Italy. Dr Skippen is an associate professor, UNSW 
Medical School, Wagga Wagga, Australia. Ms Croasdell is the clinical 
director of a private practice in Chicago, IL, USA. Dr Cerón Bohórquez 
is the clinical director of a private practice in Hamburg-Hafencity, 
Germany. Dr Murray is a pharmacist, Institute of Pharmaceutical 
Science, Kings College London, London, UK. Dr Sayed is the clinical 
director of a private practice in Oslo, Norway. Dr Walker is the clinical 
director of a private practice in Liverpool, UK. Dr Hartstein is the 
director of ophthalmic plastic surgery, Shamir Medical Center, Zerifin, 
Israel. 
Corresponding Author: 
Dr Brent Skippen, 36 Docker Street, Wagga Wagga 2650, Australia. 
E-mail: brentskippen@gmail.com; 
Instagram: @cmac 
Cosmetic Medicine 
Aesthetic Surgery Journal 
2023, Vol 00(0) 1–7 
© The Author(s) 2023. Published by 
Oxford University Press on behalf of The 
Aesthetic Society. All rights reserved. 
For permissions, please e-mail: 
journals.permissions@oup.com 
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mailto:brentskippen@gmail.com
mailto:@cmac
https://doi.org/10.1093/asj/sjad070
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Blepharoptosis following periocular onabotulinumtoxinA 
(BoNT-A) treatment is a known complication that can be 
frustrating for both patients and practitioners. Iatrogenic 
blepharoptosis occurs due to local spread of the BoNT-A 
from the periocular region into the levator palpebrae supe-
rioris muscle. Although injectors should have a thorough 
understanding of the relevant anatomy in order to prevent 
it, BoNT-A–induced ptosis can occur even in the most ex-
perienced hands. This complication usually occurs 3 to 14 
days after BoNT-A injection and may last up to 2 months. 
Until recently, practitioners have treated this complication 
with apraclonidine eyedrops, which may help to mask min-
imal asymmetries but are insufficient in most cases of more 
severe ptosis. Additionally, there may be nonresponders to 
apraclonidine therapy, leaving many cases of ptosis to self- 
resolve unpredictably several weeks later, when the para-
lytic effect of the toxin has spontaneously subsided. 
Recently, a new topical eyedrop, oxymetazoline hydro-
chloride (HCl) 0.1% (Upneeq, Osmotica Pharmaceuticals; 
Marietta, GA), has been approved by the FDA to provide 
aesthetic improvement to minimal amounts of involutional 
upper eyelid ptosis. Upneeq has been suggested by 
Nestor et al as potentially beneficial as a theoretical alter-
native to apraclonidine for improving botox-induced pto-
sis.1 In addition, Mustak et al proposed the use of BoNT-A 
to treat mild involutional ptosis by selectively weakening 
the pretarsal orbicularis.2 To the best of our knowledge, 
this is the first case series of consecutive patients affected 
by severe blepharoptosis following periocular BoNT-A 
treatment, managed with either pretarsal BoNT-A injec-
tions alone or in combination with topical Upneeq. 
METHODS 
This review adhered to the standards of the Declaration of 
Helsinki and was compliant with the Health Insurance 
Portability and Accountability Act, as well as adherent to 
IRB approval standards. Written informed consent was ob-
tained for each procedure. All the patients were treated be-
tween March 2021 and December 2022 at different facilities 
and included patients referred from elsewhere and patients 
who originated in the treating facility. Standardized pretreat-
ment and posttreatment clinical photographs were obtained 
for each patient. Inclusion criteria included recent cosmetic 
BoNT-A treatment preceding the sudden onset of unilateral 
upper eyelid ptosis. Exclusion criteria included patients with 
brow ptosis without measurable levator ptosis. All patients 
included in this study had a unilateral relative ptosis of 
3 mm or more and a margin reflex distance 1 (MRD1) of 
2 mm or less. Difference in the MRD1 measurements was 
the main outcome measure of the study. Medical records 
of the included patients were requested from the treating 
practitioners and reviewed accordingly. 
RESULTS 
Eight patients met the study criteria; all were female. 
Patient demographics are summarized in Table 1. The 
mean age of the patients was 39 years (range, 31-54 years). 
Pretreatment history and review of medical records re-
vealed that BoNT-A was used in all 8 cases. Patient data 
along with treatment are detailed in Table 1. Clinical photo-
graphs before and after ptosis reversal are also included. A 
diagnosis of severe ptosis (>3 mm) was made in all the cas-
es in this series. Final patient satisfaction with the aesthetic 
results in our case series was very high, as summarized in 
Table 1. The mean upper eyelid elevation achieved was 
3.4 mm. Pretarsal BoNT-A injections alone or in association 
with topical administration of Upneeq eyedrops signifi-
cantly reversed the ptosis in all treated cases. Mean follow- 
up time was 8 months (range, 6-12 months), and there were 
no reported complications. 
Case Reports 
Case 1 
A 49-year-old female was initially treated with 50 units of 
BoNT-A (Botox, Allergan, Irvine, CA) (14 units to the frontalis 
area, 20 units in the glabella region, and 16 units total to the 
lateral orbicularis oculi). The 50 units of botulinum toxin 
was reconstituted with 1.25 mL of preserved normal saline. 
At the routine 14-day posttreatment follow-up, a mild bilat-
eral brow and severe left eyelid ptosis was observed. Her 
MRD1 was 0 mm in the left eye and 4 mm in the right eye 
(Figure 1A). Immediate medical treatment consisted of 2 
drops of oxymetazoline HCl 0.1% (Upneeq) followed by 2 
units of BoNT-A, administered at 2 injection points superfi-
cially, at the medial and lateral limbus line into the pretarsal 
orbicularis, using a 1:1 reconstitution. Theeyelid ptosis im-
proved by 1 mm 20 minutes after instillation of the drops 
and the remaining 3 mm 10 days after BoNT-A injection 
(Figure 1B). No adverse events were reported by the pa-
tient, who applied the drops for a 6-week period. The bilat-
eral asymmetric ptosis fully resolved 8 weeks after the 
initial botox treatment. 
Case 2 
A 31-year-old female was treated with abobotulinumtoxinA 
(Dysport, Ipsen, Cambridge, MA) at a resident clinic. The in-
jection pattern reported by the injecting physician was as 
follows: corrugators: head and tail separately injected, 
1 cm superior to the supraorbital rim, with 9 units 
of Dysport to each injection site; procerus: 7 units of 
Dysport injected with total glabellar dose of 42 units of 
Dysport. The patient experienced right upper eyelid ptosis 
5 days after injection. Examination revealed an MRD1 of 
1 mm in her right eye and 4 mm in her left eye. Treatment 
involved injection of 2 units of BoNT-A, administered at 2 
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injection points at the medial and lateral limbus line into the 
pretarsal orbicularis, using a 1:1 reconstitution. The patient 
was also prescribed topical Upneeq. The patient reported min-
imal relief from the topical Upneeq; however, the ptosis was 
completely resolved 10 days after the pretarsal injections. 
Case 3 
A 37-year-old female was injected by her neurologist for 
treatment of migraines. The patient reported a 3-point in-
jection technique but was unable to provide the medical re-
cords of the treatment. The patient presented to one of the 
authors for correction of her right blepharoptosis. Her 
MRD1 was 0 mm in her right eye and 4 mm in her left eye 
(Figure 2A). The patient was treated in 2 locations on her 
pretarsal orbicularis with 2 units of neuromodulator, recon-
stituted 1:1 at each injection point. The patient was also pre-
scribed topical Upneeq. The patient reported minimal relief 
(∼1 mm) from the topical Upneeq and complete resolution 
of the ptosis about 15 days after the pretarsal injections. 
The image shown depicts the patient 5 days after pretarsal 
injections and 2 weeks after pretarsal BoNT-A injections 
and topical Upneeq (Figure 2B). 
Case 4 
A 35-year-old female presented 14 days following cosmetic 
botox treatment elsewhere. Medical records from the treat-
ing practitioner showed she was originally injected by a 
3-point injection technique to the glabella with an addition-
al 2 injection points in the tail end of the brow for a total of 
20 units of BoNT-A. The patient complained of “heaviness” 
at Day 5 posttreatment and was retreated with 3 units of 
BoNT-A in the midpupillary line, underneath the eyebrow. 
The patient began to experience blepharoptosis 7 days af-
ter her second injection. A severe ptosis of her right eyelid 
was noted. Her MRD1 was 1 mm in her right eye and 5 mm in 
her left eye (Supplemental Figure 1A). Medical treatment in-
volved 2 units total of BoNT-A injected into the pretarsal or-
bicularis with one injection point being at the medial limbus 
line and the second at the lateral limbus line. Upneeq eye-
drops were prescribed which provided an immediate 
Table 1. Treatment Performed: Results of Topical Oxymetazoline Hydrochloride 0.1% (Upneeq, Osmotica Pharmaceuticals; 
Marietta, GA) and Pretarsal BoNT-A Injection 
Patient 
number 
Demographic Initial aesthetic 
botulinum toxin 
treatment 
Ptosis Adjunct 
procedures 
performed 
Eyelid elevation 
achieved from 
Upneeq (mm) 
Eyelid elevation 
achieved from 
BoNT-A injection 
(mm) 
Total amount of 
upper eyelid 
elevation (mm) 
Patient 
satisfaction 
1 49-year-old 
female 
Botox 
(Allergan; Irvine, CA) 
Unilateral 
(left) 
Pretarsal 
BoNT-A + 
Upneeq topical 
1 3 4 High 
2 31-year-old 
female 
Dysport (Ipsen; 
Cambridge, MA) 
Unilateral 
(right) 
Pretarsal 
BoNT-A + 
Upneeq topical 
0 3 3 High 
3 37-year-old 
female 
Unknown Unilateral 
(right) 
Pretarsal 
BoNT-A + 
Upneeq topical 
1 3 4 High 
4 35-year-old 
female 
Unknown Unilateral 
(right) 
Pretarsal 
BoNT-A + 
Upneeq topical 
1 3 4 High 
5 54-year-old 
female 
Unknown Unilateral 
(right) 
Pretarsal 
BoNT-A + 
Upneeq topical 
0 3 3 High 
6 40-year-old 
female 
Unknown Unilateral 
(left) 
Pretarsal botox 
+ upneeq 
topical 
0 3 3 High 
7 44-year-old 
female 
Dysport Unilateral 
(right) 
Pretarsal 
BoNT-A + 
Upneeq topical 
0 3 3 High 
8 47-year-old 
female 
Botox Unilateral 
(right) 
Pretarsal 
BoNT-A + 
Upneeq topical 
1 2 3 High 
BoNT-A, onabotulinumtoxinA. 
Bernardini et al 3 
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positive effect of 1 mm. The patient’s results are shown 2 
weeks after injections (Supplemental Figure 1B). 
Case 5 
A 54-year-old female presented with a total right upper 
eyelid ptosis 4 days after being injected elsewhere 
(Supplemental Figure 2A); the patient was being treated 
with Upneeq eyedrops at the time of presentation without 
any significant beneficial response. The patient underwent 
pretarsal BoNT-A injection using 4 units total in 2 injection 
points (2 units medial limbus line and 2 units lateral limbus 
line) with 1:1 reconstitution. The patient presented 4 days af-
ter pretarsal BoNT-A treatment with a significant improve-
ment and almost complete resolution of the ptosis; the 
topical Upneeq treatment was suspended and the patient 
returned 2 weeks after injection with complete resolution 
of the ptosis (Supplemental Figure 2B). 
Case 6 
A 40-year-old female was injected by another practitioner 
and presented 15 days following treatment. Medical re-
cords from the treating practitioner did not record the total 
dose of BoNT-A administered. A severe ptosis of her left 
eyelid was noted. Her MRD1 was 1 mm in her left eye de-
spite topical Upneeq treatment and 4 mm in her right eye 
(Supplemental Figure 3A). Treatment consisted of a left up-
per eyelid pretarsal injection of 2 units of BoNT-A in the line 
of the medial limbus and 2 units of BoNT-A in line with the 
lateral limbus. Clinical photographs were taken before 
treatment and 10 days later, and showed complete reversal 
of the ptosis (Supplemental Figure 3B). 
Case 7 
A 44-year-old female was injected by an outside practition-
er and presented 14 days following treatment. Medical re-
cords from the initial treating practitioner noted that a 
total of 125 Speywood units of Azzalure (Dysport) were 
used in the periocular region. She presented with complete 
ptosis of the left eyelid and also felt that she was “over- 
frozen” in the forehead, lateral orbicularis oculi and glabella 
regions. She was being treated with topical Upneeq, but 
without substantial benefit. She was subsequently treated 
with a left upper eyelid pretarsal injection of BoNT-A, 2 
units in line with the medial limbus and 2 units in line with 
the lateral limbus. Clinical photographs were taken before 
treatment and 13 days after injection (Supplemental 
Figure 4). There was full resolution of the eyelid ptosis fol-
lowing the pretarsal BoNT-A injection. No adverse events 
were reported and the patient was satisfied with the 
outcome. 
Case 8 
A 47-year-old female patient was treated with approximately 
150 units of Allergan Botox by a neurologist. Exact injection 
points were not recorded; however, several injections points 
werein the lower 2 cm of the forehead and the lateral corru-
gators were also injected. After 5 days, a significant right up-
per eyelid ptosis had developed, with an MRD1 of 1 mm. Two 
weeks after initial treatment the patient presented with an 
MRD1 of 1 mm in her right eye and 4 mm in her left eye 
(Supplemental Figure 5A). Immediate medical treatment con-
sisted of 2 drops of topical Upneeq followed by injection of 3 
units of BoNT-A, administered in 3 injection points superfi-
cially (approximately 3 mm medial to the lateral canthus, ap-
proximately 3 mm lateral to the medial canthus, and at the 
lateral limbus line) into the pretarsal orbicularis, using a 1:1 re-
constitution. The eyelid ptosis improved by 1 mm 20 minutes 
after instillation of the drops and another 2 mm 2 weeks after 
the pretarsal injection (Supplemental Figure 5B). No adverse 
events were reported by the patient, who used the drops for 
a 3-week period. 
DISCUSSION 
Blepharoptosis, or eyelid ptosis, is not an uncommon com-
plication of periocular botulinum toxin injection and is de-
fined as drooping of the upper eyelid occurring within 2 
weeks after the injection. The presumed mechanism of up-
per eyelid ptosis is considered to be the unintended spread 
A B
Figure 1. (A) A 49-year-old female with a margin reflex distance 1 of 0 mm in her left eye and 4 mm in her right eye. (B) 
Improvement of ptosis 10 days after pretarsal onabotulinumtoxinA injection and topical Upneeq (Osmotica Pharmaceuticals; 
Marietta, GA). 
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of botulinum toxin to the levator muscle.1 The occurrence of 
blepharoptosis following toxin injections can be rather 
“dramatic” for the affected patient. It has an obviously 
prominent negative impact on the patient’s appearance 
and can also affect vision and interfere with daily function.3 
Various definitions and severity scales for eyelid ptosis 
have been suggested in the literature, but in the post–bot-
ulinum treatment setting any eyelid margin alteration or 
asymmetry that was not recorded before the treatment is 
considered to be significant. Ptosis is considered severe 
when it is 3 mm or more. In terms of mechanism of action, 
BoNT-A–induced blepharoptosis is classified as neurogen-
ic because it is due to impairment of transmission of electri-
cal impulses at the neuromuscular junction.1 
BoNT-A binds to transport proteins in nerve cells and 
blocks the release of acetylcholine from nerve endings; 
this neurotransmitter is responsible for muscle contraction. 
The degree to which injected toxin may overflow from a tar-
geted region to an unintended region is largely determined 
by the active physical distribution of toxin suspension or 
spread.3 Patient-dependent factors include younger age, 
outdoor work life, sun damage, loss of skin elasticity, and 
thicker skin.4 Medically dependent risk factors include pre-
vious facial surgical procedures, neurological conditions 
such as multiple sclerosis or myasthenia gravis, and prior 
history of Bell’s palsy or other induced eyelid ptosis.4 Risk 
of ptosis can also be based on the amount of injected bot-
ulinum toxin (units), injected volume (mL), and product type. 
It is a widely held opinion that poor injection technique is 
a major factor in patients developing ptosis and includes 
various combinations of mistakes associated with depth 
of placement and administration of botulinum toxin injec-
tion and dosing.4 In a large study, botulinum toxin–induced 
blepharoptosis was estimated to occur in 5.4% of patients 
treated by inexperienced injectors andjection external to the corneal limbi (medial and lateral) in 
a superficial plane (dermal layer) has minimal chances of af-
fecting the levator while maximizing the paralytic effect on 
the pretarsal orbicularis. Figure 3 shows the injection sites 
in the pretarsal orbicularis of the ptotic upper lid. 
The pretarsal orbicularis is the muscle most intimately 
connected with automatic eyelid function, responsible for 
baseline eyelid closure and blinking. By weakening the 
baseline strength of the pretarsal orbicularis the residual le-
vator/Müller complex force is empowered, with conse-
quent restoration of the correct eyelid aperture. In 
botox-induced ptosis, it is difficult to gauge how much im-
pact comes from the levator muscle vs Müller’s muscle; 
however, it is possible that recovery comes mainly from un-
opposed Müller’s muscle function since the levator is the 
directly affected muscle. 
Unfortunately, in this series, the levator function was not 
measured before or after the occurrence of ptosis and the 
subsequent treatment; however, looking at the severity of 
ptosis and the temporary loss of the eyelid crease in the af-
fected muscle, it is likely that the levator muscle function is 
significantly impaired if not completely blocked, leaving 
only Müller’s muscle to elevate the upper eyelid. The timing 
and the amount of response that was achieved from topical 
treatment and pretarsal botulinum toxin injections clearly 
indicates the respective impact of the reversal treatment 
proposed herein. Although the effect after instillation of 
topical Upneeq can be immediate, usually starting after 
20 seconds with a positive impact of no more than 1 mm 
of MRD1 gain, the subsequent response, of 2 to 3 mm of 
MRD1 gain occurring after 10 to 14 days can be attributed 
to the administration of pretarsal botulinum toxin. 
Oxymetazoline HCl Ophthalmic Drops 
Oxymetazoline HCl 0.1% is the only FDA-approved medical 
treatment for acquired blepharoptosis in adults.1,7 
Oxymetazoline (Afrin, Bayer AG; Leverkusen, Germany) nasal 
spray was originally approved by the FDA more than 50 
years ago for the treatment of nasal congestion.8 
Oxymetazoline HCl 0.1% elevates the upper eyelid by activat-
ing both α1- and α2-adrenergic receptors in Müller’s muscle. 
Common side effects include punctate keratitis, conjunctival 
hyperemia, dry eye, blurry vision, eye irritation, and head-
ache. Tachyphylaxis is a known response to treatment with 
α-adrenergic agonists but can take many weeks or longer 
to develop, a timeline that exceeds the 14 days used to as-
sess treatment efficacy in this study.8 
To our knowledge, this is the first documented series of 
patients effectively treated with oxymetazoline HCl 0.1% 
and pretarsal BoNT-A injections in the setting of botox- 
induced ptosis. This study enhances the knowledge base 
of management of varying severities of botox-induced pto-
sis. We believe that topical Upneeq alone can be effective 
in addressing mild cases of post-botox ptosis of approxi-
mately 1 to 2 mm only, but for more severe cases of ptosis 
of 3 mm or more, ie, all those described in this series, pre-
tarsal botulinum toxin injection is the mainstay of treatment. 
In severe cases, topical Upneeq could provide a degree of 
instant relief until the more definitive action of pretarsal 
BoNT-A injections takes effect. 
Study Shortcomings 
Levator function was not measured at any time after the oc-
currence of ptosis at the time of the original botulinum in-
jection, or during the secondary treatment. Some 
degrees of temporary posttreatment lagophthalmos could 
be expected after pretarsal injection and might then lead to 
corneal exposure with dry-eye symptoms. However, specif-
ic dry-eye parameters were not evaluated in our series. 
Figure 3. Injection sites in the pretarsal orbicularis of the 
ptotic upper lid. 
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Since the patients were referred, we can only speculate on 
the mechanism for the development of botox-induced pto-
sis. However, no patients in this series complained of dry- 
eye symptoms after pretarsal BoNT-A injection. 
This study also did not conduct a comparison between the 
utility of topical apraclonidine vs topical Upneeq in the set-
ting of botox-induced ptosis. Topical apraclonidine is still 
the most commonly used drug for this condition. 
Apraclonidine is an α2-adrenergic agonist and oxymetazo-
line is both an α1- and α2-adrenergic agonist. We are not en-
tirely certain as to whether α1-adrenergic agonist effects 
might give better efficacy in this setting. This paper does 
not offer insights on the potential mechanism of occurrence 
of botox-induced ptosis, relative to the amount (units or mL) 
and botox type. Potential comparative studies evaluating the 
power of apraclonidine vs Upneeq alone and/or in associa-
tion with pretarsal botulinum toxin could establish the real 
added value of topical Upneeq in this setting; it would 
have been ideal to have a comparative group of patients 
similarly affected by botox-induced ptosis treated with pre-
tarsal injection of saline solution to rule out any placebo ef-
fect and statistically measure the real impact on time of 
ptosis reversal between the study group and the placebo. 
CONCLUSIONS 
If the levator muscle is accidentally weakened or paralyzed 
by the unintended diffusion of aesthetic periocular treat-
ment by BoNT-A injection, Müller’s muscle action can be bi-
modally potentiated by the direct effect of topical 
oxymetazoline HCl 0.1% on the muscle and indirectly by 
weakening the baseline force of the pretarsal orbicularis 
muscle with pretarsal BoNT-A injections. It is intuitive that 
a degree of paralytic lagophthalmos might be expected 
to occur due to pretarsal muscle impairment from 
BoNT-A injections, although none occurred in this series 
of patients. The lack of reported dry-eye symptoms from 
all treated patients in this series supports the benefit of re-
versing severe BoNT-A–induced ptosis as the risk of partial 
lagophthalmos is low. However, patients need to be specif-
ically informed about this potential risk. In our experience, 
this treatment combination is a safe and effective option 
in cases of severe botox-induced eyelid ptosis. 
Supplemental Material 
This article contains supplemental material located online at 
www.aestheticsurgeryjournal.com. 
Acknowledgments 
All authors listed are part of the Complications in Medical 
Aesthetics Collaborative (CMAC) Study Group; Francesco 
Bernardini, Jair Mauricio Cerón Bohórquez, Brittony 
Croasdell, and Gillian Murray are part of the CMAC 
International Expert Board. Brittony Croasdell had the original 
idea for this paper. 
Disclosures 
The authors declared no potential conflicts of interest with re-
spect to the research, authorship, and publication of this 
article. 
Funding 
The authors received no financial support for the research, 
authorship, and publication of this article. 
REFERENCES 
1. Nestor MS, Han H, Gade A, Fischer D, Saban Y, Polselli R. 
Botulinum toxin–induced blepharoptosis: anatomy, etiolo-
gy, prevention, and therapeutic options. J Cosmet 
Dermatol. 2021;20(10):3133-3146. doi: 10.1111/jocd.14361 
2. Mustak H, Rafaelof M, Goldberg RA, Rootman D. Use of 
botulinum toxin for the correction of mild ptosis. J Clin 
Aesthet Dermatol. 2018;11(4):49-51. 
3. Nestor MS, Arnold D, Fischer D. The mechanisms of action 
and use of botulinum neurotoxin type A in aesthetics: key 
clinical postulates II. J Cosmet Dermatol. 2020;19(11): 
2785-2804. doi: 10.1111/jocd.13702 
4. King M. Management of ptosis. J Clin Aesthet Dermatol. 
2016;9(12):E1-E4. 
5. Carruthers JA, Lowe NJ, Menter MA, etal. A multicenter, 
double-blind, randomized, placebo-controlled study of 
the efficacy and safety of botulinum toxin type A in the 
treatment of glabellar lines. J Am Acad Dermatol. 
2002;46(6):840-849. doi: 10.1067/mjd.2002.121356 
6. Bodnar ZM, Neimkin M, Holds JB. Automated ptosis mea-
surements from facial photographs. JAMA Ophthalmol. 
2016;134(2):146-150. doi: 10.1001/jamaophthalmol.2015. 
4614 
7. Ugradar S, Kim JS, Trost N, et al. Changes to eye white-
ness and eyelid/brow position with topical oxymetazoline 
in aesthetic patients. Aesthet Surg J. 2022;42(6):582-589. 
doi: 10.1093/asj/sjab400 
8. Bradley EA, Bradley DJ. Oxymetaxoline for ptosis. 
JAMA Ophthalmol. 2020;138(11):1176-1177. doi: 10.1001/ 
jamaophthalmol.2020.3833 
Bernardini et al 7 
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nloaded from
 https://academ
ic.oup.com
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hio N
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niversity user on 19 April 2023
http://academic.oup.com/asj/article-lookup/doi/10.1093/asj/sjad070#supplementary-data
http://www.aestheticsurgeryjournal.com
https://doi.org/10.1111/jocd.14361
https://doi.org/10.1111/jocd.13702
https://doi.org/10.1067/mjd.2002.121356
https://doi.org/10.1001/jamaophthalmol.2015.4614
https://doi.org/10.1001/jamaophthalmol.2015.4614
https://doi.org/10.1093/asj/sjab400
https://doi.org/10.1001/jamaophthalmol.2020.3833
https://doi.org/10.1001/jamaophthalmol.2020.3833
	Management of Severe Botulinum-Induced Eyelid Ptosis With Pretarsal Botulinum Toxin and Oxymetazoline Hydrochloride 0.1%
	METHODS
	RESULTS
	Case Reports
	Case 1
	Case 2
	Case 3
	Case 4
	Case 5
	Case 6
	Case 7
	Case 8
	DISCUSSION
	Two-Stage Management of BoNT-A–Induced Eyelid Ptosis
	Pretarsal Botulinum Toxin Injection
	Oxymetazoline HCl Ophthalmic Drops
	Study Shortcomings
	CONCLUSIONS
	Supplemental Material
	Acknowledgments
	Disclosures
	Funding
	REFERENCES