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WJCC https://www.wjgnet.com 1719 March 16, 2023 Volume 11 Issue 8
World Journal of
Clinical Cases
W J C C
Submit a Manuscript: https://www.f6publishing.com World J Clin Cases 2023 March 16; 11(8): 1719-1729
DOI: 10.12998/wjcc.v11.i8.1719 ISSN 2307-8960 (online)
MINIREVIEWS
Modern blepharoplasty: From bench to bedside
Giovanni Miotti, Marco Zeppieri, Giacomo Pederzani, Carlo Salati, Pier Camillo Parodi
Specialty type: Medicine, research
and experimental
Provenance and peer review:
Invited article; Externally peer
reviewed.
Peer-review model: Single blind
Peer-review report’s scientific
quality classification
Grade A (Excellent): 0
Grade B (Very good): B
Grade C (Good): 0
Grade D (Fair): D
Grade E (Poor): 0
P-Reviewer: Convery C, United
Kingdom; Grawish ME, Egypt
Received: December 16, 2022
Peer-review started: December 16,
2022
First decision: January 3, 2023
Revised: January 7, 2023
Accepted: February 22, 2023
Article in press: February 22, 2023
Published online: March 16, 2023
Giovanni Miotti, Giacomo Pederzani, Department of Medical, Surgical and Health Sciences,
Plastic and Reconstructive Surgery Unit, University of Trieste, Trieste 34123, Italy
Giovanni Miotti, Pier Camillo Parodi, Department of Plastic Surgery, University Hospital of
Udine, Udine 33100, Italy
Marco Zeppieri, Carlo Salati, Department of Ophthalmology, University Hospital of Udine,
Udine 33100, Italy
Corresponding author: Marco Zeppieri, BSc, MD, PhD, Doctor, Department of Ophthalmology,
University Hospital of Udine, p.le S. Maria della Misericordia 15, Udine 33100, Italy.
markzeppieri@hotmail.com
Abstract
The demand for procedures aiming to rejuvenate the upper third part of the face
and the periocular region has increased in the past several years. Blepharoplasty
is one of the most frequently performed procedures worldwide to date. Surgery is
currently the first choice in order to achieve permanent and effective results;
however, it is burdened by potential surgical complications feared by patients.
There is an increasing trend in individuals to request less invasive, non-surgical,
effective, and safe procedures for eyelid treatment. The aim of this minireview is
to present a brief overview of non-surgical blepharoplasty techniques that have
been reported in the literature in the past 10 years. Numerous modern techniques
that provide a rejuvenation of the entire area have been described. Numerous less
invasive methods have been proposed in the current literature and in modern-day
routine clinical settings. Dermal fillers are a commonly chosen option for
providing enhanced aesthetic results, especially considering that volume loss can
be one of the main underlying causes of facial and periorbital aging. Deoxycholic
acid use may be considered when the problem is represented by periorbital excess
fat deposits. The simultaneous excess and loss of elasticity of the skin can be
assessed with techniques such as lasers and plasma exeresis. Furthermore,
techniques such as platelet-rich plasma injections and the insertion of twisted
polydioxanone threads are emerging as viable methods to rejuvenate the
periorbital region.
Key Words: Non-surgical blepharoplasty; Laser treatment; Dermatochalasis; Aesthetic;
Non-invasive procedures; Hyaluronic acid; Plasma exeresis; Eyelids
©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Miotti G et al. Modern blepharoplasty
WJCC https://www.wjgnet.com 1720 March 16, 2023 Volume 11 Issue 8
Core Tip: Non-surgical procedures represent a valid alternative to surgery in the rejuvenation of the
periorbital area. When the problem can be corrected by ‘filling’ more and ‘removing’ less, fillers may be
of use. Laser treatment and microsurgical techniques can provide a viable solution when the main concern
is based on excess and/or inelasticity of the skin.
Citation: Miotti G, Zeppieri M, Pederzani G, Salati C, Parodi PC. Modern blepharoplasty: From bench to bedside.
World J Clin Cases 2023; 11(8): 1719-1729
URL: https://www.wjgnet.com/2307-8960/full/v11/i8/1719.htm
DOI: https://dx.doi.org/10.12998/wjcc.v11.i8.1719
INTRODUCTION
The periocular region represents one of the most fascinating and interesting elements of the face that
others usually first notice in us. The first signs of aging of the face are typically seen in this area[1]. The
search for a younger and “fresher” appearance of the face is one of the main reasons that individuals
search for clinical assistance, be it surgical or non-surgical. The demand for upper facial rejuvenation in
both females and males has dramatically increased in the past decade. Blepharoplasty, which is
performed for cosmetic and/or functional reasons, is one of the most performed procedures worldwide
[2]. In the last 10 years, blepharoplasty has been one of the top five most commonly performed surgical
procedures, along with facelift (rhytidectomy) and rhinoplasty[3].
Blepharoplasty can be defined as the surgical repair or reconstruction of the upper and/or lower
eyelids. These procedures are performed to correct the signs of aging that occur in the periorbital region
and enhance unaesthetic lids. The procedure typically involves the management of excess eyelid skin,
lid laxity, ptosis, orbital septum, and orbital fat. Upper and lower lid blepharoplasty can be performed
for cosmetic reasons and/or reconstructive reasons. Cosmetic and reconstructive procedures can be
undertaken at different times or can sometimes be performed during the same operation[4,5].
The upper and lower eyelids consist of the anterior, middle, and posterior lamellae. The anterior
lamella is composed of the skin and orbicularis oculi muscle of the eyelid, whereas the posterior lamella
refers to the retractors, superior or inferior tarsal muscle, tarsus, and conjunctiva. The orbital septum is
sometimes referenced as the middle lamella[6]. Despite being one of the most frequently performed
operations, surgical blepharoplasty tends to be an invasive and non-definitive procedure that can
produce scars and may require further surgical retouches in the future. Like all surgical procedures,
blepharoplasty involves risks that include infection, bleeding, and other postoperative complications. In
light of the fears and risks involved with traditional invasive surgery, there has been an increasing
demand for innovative cosmetic procedures that are less invasive and provide good outcomes with
fewer side effects compared to surgical procedures[2]. The aim of our minireview is to present a brief
overview of non-surgical blepharoplasty techniques, which have been reported in the literature and
used in clinical settings in the past 10 years.
MATERIALS AND METHODS
We conducted a search of the literature published from January 1, 2012 to December 1, 2022 using
MEDLINE (PubMed). The database was first searched using the key words “non-surgical blepharo-
plasty, blepharoplasty NOT surgery, non-surgical blepharoplasty techniques, non-invasive blepharo-
plasty, blepharoplasty AND fillers, blepharoplasty AND hyaluronic acid, blepharoplasty AND laser,
blepharoplasty AND peeling, blepharoplasty AND chemical peels, blepharoplasty AND plasma”. We
considered only studies in English and those referring to humans and with an abstract, thus reducing
the count to 538 papers. The reference lists of all retrieved articles were assessed to identify additional
relevant studies. The research of articles was performed using PubMed (https://pubmed.ncbi.
nlm.nih.gov) and Reference Citation Analysis (https://www.referencecitationanalysis.com).
Only articles with an abstract were considered. After excluding all works in which only surgical
techniques were described and those that assessed non-surgical techniques as only complementary to
surgery, 40 studies were analyzed. A quality score was calculated for each article using a check list from
the American Society of Plastic Surgeons guidelines for therapeutic studies[7]. Each study was
independently assessed by at least two reviewers (Miotti G and Zeppieri M), and rating decisions were
based on the consensus of the reviewing authors. The results of the most relevant studies are shown in
Table 1.
Miotti G et al. Modern blepharoplasty
WJCC https://www.wjgnet.com 1721 March 16, 2023 Volume 11 Issue 8
Table 1 Studies in current literature regarding blepharoplasty
Ref. Technique Type of the
study
Where
(upper/lower
eyelid)
Number
of cases Conclusions
Balzani et al[21],
2013
Laser Prospective Upper 20 Lift of 1.63 ± 0.68 mm of the upper eyelid at 6 mo
Bae-Harboe et al
[16], 2014
Review Both / Fractional ablative CO2 laser is a valid solution to improve
the appearance of periocular area
Toyos[20], 2017 Retrospective Upper 16 Increase in the measurements for dermatochalasis and skin
laxity at 6 mo follow-up and few side effects
Guida et al[23],
2018
Retrospective Both 20 Increase in the Global Assessment Improvement Scale;
reduction of medium protrusions and depressions;
improved texture at 2 mo also at 3D image reconstructions
Garcia et al[22],
2019
Cohort,
uncontrolled
Lower 263 Improvement in the eyelid area characterized by fewer
rhytids and a younger appearance at 6 mo
Rossi et al[30],
2018
Plasma exeresis Prospective,
controlled,
evaluator-blinded
Both 10 Change in the conformation of the collagen fibers from
huddled and coalesce presentation to long and straight
fibers
Giroux et al[33],
2019
Prospective, single
center
Upper 25 About 2.5 mm of mean reduction at 12 mo follow-up
Theppornpitak et
al[35], 2019
Prospective,
controlled,
evaluator-blinded
Both 18 Effective and safe for treatment of mild-to-moderate
periorbital wrinkles and darkening
Verner et al[32],
2020
Prospective, single
center
Upper 17 All patients had an improvement of dermathocalasis scale
Baroni[2], 2020 Prospective, single
center
Upper 10 General satisfaction for the patients (8 or more on VAS scale)
and the absence of permanent side effects
Ziade and
Desiree[29], 2020
Case report Both 2 Safe and efficient non-surgical option. Few complications;
hyperpigmentation is the most common, preventable whit
small precautions
Ferreira et al[31],
2021
Observational Upper 16 General post-treatment satisfaction (modified Q-bleph) and
limited adverse events
Martín-Oviedo et
al[38], 2013
HA Retrospective Upper 26 Effective in reducing paralytic lagophthalmos and
controlling keratopathy in patients with temporary facial
palsy
Romero et al[42],
2013
Retrospective Lower 12 Retraction was completely corrected in 96.3% of patients;
improvement of the standardized MRD2 of 0.84 mm
immediately after injection and 1.19 mm 9 mo later
Kohn et al[39],
2014
Prospective, non-
randomized
Upper 8 HA injection may be an effective and minimally invasive
method to improve upper eyelid position for patients with
mild eyelid retraction in both the active and inactive stages
of TED
Romeo[12], 2016 Cohort,
prospective
Upper 154 Upper eyelid area filling with HA was compared to surgical
blepharoplasty as means of reaching eye rejuvenation. The
study showed high patient satisfaction in regards of the
aesthetic endpoint and long lasting results in a 12 mo period
Jiang et al[47],
2016
Retrospective,
single center
clinical study
Lower (tear-
trough
deformity)
78 Compared the use of HA to autologous fat injections. Fillers
may be used alone in the treatment of TTD in patients with
mild to moderate periorbital volume loss without severe
orbital fat bulging
Romeo[46], 2019 Retrospective Upper 500 Upper eyelid area filling with HA was compared to surgical
blepharoplasty as means of reaching eye rejuvenation. The
study showed high patient satisfaction in regards of the
aesthetic endpoint and long lasting results in a 12 mo period
Xi et al[42], 2019 Retrospective Lower 27 Retraction was completely corrected in 96.3% of patients;
improvement of the standardized MRD2 of 0.84 mm
immediately after injection and 1.19 mm nine months later
Bladen and
Malhotra[43],
2019
Retrospective,
single center case
review
Upper 8 6 patients showed improvement; HA injection is considered
a feasible option for treatment of epibleharon
Miotti G et al. Modern blepharoplasty
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Mani et al[49],
2013
PMMA Retrospective,
single center
Lower 289 Subdermal PMMA microspheres injection is a safe technique
in the correction of infraorbital rhytids
Amore et al[50],
2019
Deoxycholate Multi-center,
observational
prospective
Lower fat pads 120 Moderate to high patient satisfaction and therapeutic
success in 85.83% of the patients enrolled
Lee et al[51], 2020 Twisted polydi-
oxanone threads
Retrospective,
single center
Lower 40 More than 77.5% of patients were satisfied with the outcome
Aust et al[52],
2018
Platelet rich
plasma
Prospective Lower 20 Statistically significant increase in skin firmness and skin
elasticity, high level of patient satisfaction, and progressive
improvement of the aesthetic outcome
PMMA: Polymethylmethacrylate; HA: Hyaluronic acid; MRD2: Marginal reflex distance 2; TTD: Tear trough deformity; TED: Thyroid eye disease; VAS:
Visual analogue scale.
BACKGROUND
Like any surgical procedure, blepharoplasty, especially performed on the lower one, is burdened by
potential complications such as dry eye syndrome, corneal abrasion, lid asymmetry, lagophthalmos (the
inability to close the eyelids completely), lacrimal gland injury, canthal webbing, postoperative
hemorrhage, diplopia or infection, blepharoptosis, wound dehiscence, scleral show, and ectropion[8-
11]. In the past several years, there has been an increasing demand in enhanced aesthetic outcomes with
procedures that can offer quicker operative and postoperative wound-healing times, and preferably
with fewer complications and discomforts with anesthesia. Non-invasive and less invasive procedures
have become relatively popular in providing effective and safe alternatives for eyelid treatment. There
has been great interest in those techniques that can guarantee good outcomes, while minimizing the side
effects usually associated with surgical procedures[2].
When we talk about non-surgical procedures for treating the periocular region, we must consider all
the emerging techniques that determine a rejuvenation of the entire area (i.e., techniques for volumizing
or reducing unwanted localized fat deposits), not only those based on surgical approaches to redundant
skin or fat pads. Techniques such as hyaluronic acid (HA) fillers, lasers, deoxycholic acid, and plasma
exeresis are considerably emerging, providing interesting and viable options in aesthetic treatments of
the eyelids[12].
The dynamics of eyelid aging are not completely known to date. They are characterized by various
physiological processes that lead to inelastic and excessive skin and/or subcutaneous soft tissue or bone
volume loss[1,13,14]. Due to the emerging evidence from studies based on the dynamics of periocular
aging and the concept of beauty (empty eyelid vs full eyelids), surgical approaches have evolved and
changed over time to meet the new demands of individuals. Plastic surgery in this specific field has
gone from a subtractive surgery approach to modern-day augmentation blepharoplasty techniques, in
which adipose tissue is repositioned or even increased (i.e., lipofilling, HAs, ect.) [1,15]. The following
sections of the manuscript will briefly deal with the different conservative options for eyelid
rejuvenation.
LASERS
One of the most characteristic aspects of eyelid aging is represented by the simultaneous excess and loss
of elasticity of the skin. Laser treatment has shown to provide interesting options to address these
morphological and functional changes of the lid. The objective of laser treatment is to ensure a
contraction of the skin, which can give rise to a smoother and toned appearance[16]. Before promoting
any treatment, it is fundamental to understand the mechanisms of aging and needs of each individual
patient seeking aesthetic procedures to enhance facial appearance. In addition to changes to the skin, fat
pads, muscle, or bone tissue can be affected by aging processes[1]. The laser approaches that are
typically considered in these patients include resurfacing and ablative or non-ablative techniques. Laser
treatments can also be used to complete and enhance traditional blepharoplastic surgical procedures
[16].
There are several different laser technologies that can be used for the treatment of the eyelid region,
which include: Ablative CO2 laser; erbium-doped yttrium-aluminum-garnet (Er:YAG) laser; fractional
ablative CO2 laser; fractionated erbium:YAG laser; and non-ablative fractional laser[16,17]. Fractionated
ablative laser treatments target water and cause selective photothermolysis[17]. The main differences
between ablative and non-ablative lasers are the layers of the skin affected, laser dosage, and efficacy,
which tends to be greater for ablative ones. Ablative lasers usually present a longer recovery time and
involve greater risks. The selection of the appropriate laser device is fundamental, which should be
based on the morphological and functional characteristics of the areas to be treated, the clinical needs of
Miotti G et al. Modern blepharoplasty
WJCC https://www.wjgnet.com 1723 March 16, 2023 Volume 11 Issue 8
the patient, and the postprocedural recovery time. Fractionated lasers typically have a faster skin-
healing time and reduced risk of scarring, dyschromia, and postprocedural infections.
When dealing with patients that seek blepharoplasty for enhanced lid aesthetics, the clinician should
provide various pertinent options for each individual, by specifying all details regarding pros, cons,
risks, and expected outcomes and healing times. Complete clearly understood information is necessary
in obtaining written informed consent before surgery. Nguyen et al[18] nicely reported how patients
mistakenly believed that laser blepharoplasty was better than the traditional one (because it is
considered simpler, less painful, and with a shorter recovery). The study shows how the advice given by
physicians can have a huge impact on decisions made by patients. It is thus of utmost importance that
clinicians be careful and complete in explaining all options, and should avoid setting false expectations
when dealing with patients[18].
Historically, ablative CO2 resurfacing has been the gold standard for skin resurfacing. This laser has
been described to provide an effective approach to treat the dermatochalasis of the eyelid skin because it
was believed to be better at giving tissue contraction and rhytid improvement than Erb:YAG ablation
[17]. Fitzpatrick et al[19] demonstrated that both CO2 laser and Er:YAG laser have similar degrees of
tightening; however, Er:YAG laser showed 33% of scarring in patients and a lower ability of coagulation
when compared with CO2 laser. The study by Bae-Harboe et al[16] provides a careful analysis of
advantages, disadvantages, and potential side effects of ablative, ablative-fractioned, and non-ablative
techniques. The study also shows that fractioned ablative CO2 laser represents a valid solution to
improve the appearance of periocular area.
With regard to patients with eyelid skin excess, several studies have reported the positive use of laser
for mild or moderate cases of dermatochalasis. Toyos[20] published a study based on 16 patients
affected by mild dermatochalasis and treated with fractional continuous wave CO2 laser. The study
showed an increase in the common lid measurements for dermatochalasis and skin laxity at the follow-
up at 6 mo and fewer side effects, which tended to be only minor. Balzani et al[21] provided satisfying
outcomes with CO2 laser. The study was based on 20 patients treated at upper eyelid and eyebrow
regions with fractional ultrapulse CO2 laser. The mean lid lift after treatment was 1.63 ± 0.68 mm and
2.300 ± 0.67 mm at 6 mo, respectively. Fractional ultrapulse CO2 laser reduces collateral thermal damage
through selective skin vaporization and causes tissue tightening and collagen shrinkage. This laser
technique tends to show low costs and low risks with short operative and recovery times. Garcia and
Badin[22] retrospectively analyzed 263 patients with mild inferior dermatochalasis treated solely with
ablative fractioned CO2 laser. They showed an improvement in the eyelid area characterized by fewer
rhytids and a younger appearance 6 mo postoperatively. The treatment of the lower eyelid has also been
shown by Guida et al[23]. They retrospectively considered 20 patients treated with freehand CO2
ablative resurfacing, using the technique of resurfacing with ablation of periorbital skin. Results
demonstrated an increase in the Global Assessment Improvement Scale (subjective and objective) score
and a reduction of medium protrusions and depressions, with an improved texture at 2 mo that was
confirmed by 3D image reconstructions. The histological explanation of what happens to the skin after a
laser treatment has been reported in a recent article by de Filippi Sartori et al[24] published in 2022. The
study showed an increase of skin collagen I and III concentrations 30 d after resurfacing treatment
performed with fractioned CO2 laser, with an evident improvement in periorbital rhytidosis.
Another element that patients typically seek consultation is for periorbital hyperpigmentation.
Various treatments can be performed for this unsightly condition, including laser. The etiology can be
linked to pigmentary, structural, vascular, and/or mixed causes[25]. Vrcek et al[26] and Samaan and
Cartee[27] have carried out a thorough analysis of the all-possible solutions for this problem, providing
three possible solutions using lasers. The first option exploits the Q-switched laser, which is ideal for
selectively treating melanosomes while causing minimal trauma to the surrounding structures. The
evolution of technology has led to the experimentation of the laser Nd:Yag, which can penetrate deep
into the skin and have minimal effects on melanosomes, allowing increased safety when treating more
pigmented individuals, such as Fitzpatrick types V and VI skin. The second treatment option is based
on pulsed dye lasers, which are useful for individuals that have dark circles with a vascular etiology.
The last option, which tends to be considered as the most effective, is based on ablative or fractioned
laser resurfacing. When comparing CO2 and Erb:YAG technologies, the latter option tends to offer more
precision with a more limited depth of penetration and minimal thermal damage. Fractioned laser
technology reduces the confluent thermal damage when compared with ablative lasers. This determines
the presence of behind untreated skin, which allows for less downtime and a lower complication rate.
As already reported by other reviewers, such as Vrcek et al[26], the results of fractionated CO2 laser
resurfacing have been shown to be comparable with traditional ablative resurfacing, but with a lower
rate of complications and less downtime. Given its bias of being an uncontrolled cohort study, similar
results have also been reported in a paper published by Garcia and Badin[22].
With regard to possible complications related to laser treatments, the incidence generally tends to be
low and minor. Patients should be informed of the possible onset of edema, swelling, hypo or hyper-
pigmentation, infections (bacterial or viral), and visible scarring (that can give rise to ectropion if
severe). One of the largest series in the literature that focuses on complications after laser treatment
includes the study by Kim et al[28] using fractional ablative CO2 laser resurfacing. The results show a
low risk of infection, which was limited to less than 1%, with a prevalence of viral etiology (4 viral cases
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vs 2 bacterial cases). Hyperpigmentation caused by post-treatment inflammation was the most common
complication, which was found in about 10% of patients, but easily with topical medical therapy. Visible
scars were reported in 0.9% of cases that needed steroid injections. The study showed a grade of “very
satisfied” (or more) in global post-treatment satisfaction in about 97% of the patients treated.
PLASMA EXERESIS
When a patient refuses a surgical approach to correct the signs of eyelid aging, the plasma exeresis
technique can be proposed as a viable option. The plasma technique is becoming an increasingly
interesting non-surgical alternative for the treatment of dermatochalasis. It consists of a handpiece
producing ionized energy from an air gap that causes superficial tissue heating without any direct
contact. A controlled and limited thermal damage transforms solid tissue into a gaseous state that
creates mild coagulation, resulting in increased collagenosis and contraction of the skin.
Plasma technology is considered as a safe and efficient non-surgical option. There have been only a
few minor complications reported in the literature, which include delayed healing, skin bacterial
infection, herpes simplex virus infection, tissue scarring, and post inflammatory hyperpigmentation
(most common). Easy precautionary measures can be applied, such as those reported by Ziade and
Desiree[29] to reduce risks. Studies by Rossi et al[30] have given possible histological explanations as to
what happens to the skin after treatment with plasma technology. Treatment appeared to induce a
change in the conformation of the collagen fibers observed with confocal microscopy, going from
huddled and coalesce presentation to form long and straight fibers. There were no major side effects
observed.
Ferreira et al[31] showed promising results in a cohort of 16 patients that underwent upper blepharo-
plasty using plasma technology. What emerged in this prospective study is both a general post-
treatment satisfaction (calculated by modified Q-bleph) and a limited number of adverse events
(hyperpigmentation was one of the possible side effects in patients with Fitzpatrick III-IV phototype, but
was easily resolved). Rossi et al[30] and Verner et al[32] showed effective and comparable results in
patients treated with plasma exeresis for upper eyelid dermatochalasis. Hassan et al[10] found a statist-
ically significant decrease in eye lid laxity after treatment in a study based on 40 patients treated by this
method. Studies by Baroni[2] showing effective treatment and good aesthetic results were based on a
long-wave P-RF ablation plasma device to treat 10 patients affected by dermatochalasis. His protocol
consisted of two treatments distanced 1 mo apart. The general satisfaction of patients was quite good [8
> visual analogu scale (VAS)], with no reported permanent side effects. High levels of satisfaction
(about 80% of both patients and investigators) were reported in a prospective study by Giroux et al[33].
They treated 25 patients affected by moderate dermatochalasis, and obtained a mean lid reduction of
about 2.5 mm at the 12-mo follow-up.
Studies in the current literature also report the possible use of plasma technique for treating
periocular hyperpigmentation, as well as dermatochalasis and wrinkles[34]. A pilot study carried out by
Theppornpitak et al[35] reported effective and positive clinical outcomes in mild and moderate cases of
periocular hyperpigmentation.
DERMAL FILLERS
In the field of facial rejuvenation, dermal fillers have been widely used for numerous years. They have
recently become an alternative to surgical procedures for both aesthetic and functional indications, such
as upper and lower blepharoplasty, tear-trough deformity for the lower lid, lagophthalmos, orbital
volume deficiency, upper and lower eyelid retraction, and eyelid malposition. Dermal fillers represent a
valid alternative to surgery in aesthetic indications. Injectable fillers provide numerous advantages that
make them a suitable alternative to surgery, considering that they are minimally invasive, titratable,
repeatable and, in some cases, reversible. Soft tissue fillers/injectables can be classified based on their
source, which include autologous (fat), biological (collagen and HA), and synthetic [poly-L-lactic acid,
calcium hydroxyapatite and polymethylmethacrylate (PMMA)]. Fillers can also be classified according
to the duration of cosmetic benefit in short (< 3 mo, bovine collagen), medium (3-12 mo, HA), long
lasting (12-24 mo, calcium hydroxyapatite, poly-L-lacticacid), and very long lasting (PMMA, fat). There
is also a distinction that can be made based on their reversibility, which include fillers that are reversible
(bovine collagen, HA) and irreversible (PMMA, calcium hydroxyapatite, poly-L-lacticacid, and fat)[36].
HA
HA derivatives are the most commonly used dermal fillers especially considering that they derive from
a ubiquitous molecule in the human body and thus do not require allergy testing prior to use. HA
derivatives display a medium to long duration (6-12 mo) thanks to their cross-linking to other chemicals
that prevents biodegradation from enzymes. A wide variety of HA derivatives displaying different
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characteristics have been produced over the years, leading to the abundant use in a variety of fields of
surgery, such as in the management of periocular and orbital pathology[36].
Lagophthalmos is defined as the inability to fully close the eyelids due to paralysis of the orbicularis
oculi (paralytic), retraction of the upper or lower lids (restrictive), and proptosis. This important lid
disorder can result in exposure of the cornea and lead to severe dry eye syndrome and keratopathy.
Paralytic lagophthalmos can be treated using HA gel (such as Restylane or Juvéderm Ultra) injected in
the pretarsal and/or prelevator aponeurosis regions along the length of the upper eyelid and deep to
orbicularis oculi muscle in a feathered layered fashion, as demonstrated by two retrospective studies
conducted separately by Mancini et al[37] and Martín-Oviedo et al[38]. The use of HA gel in the
treatment of lagophthalmos is ideal for patients not suitable for surgery and those unable to tolerate an
external weight applied to the lid. HA provides a flexible and temporary approach that can be ideal to
treat reversible and non-permanent causes of lagophthalmos.
HA gel injections are an effective non-surgical treatment for upper eyelid retraction. Studies by Kohn
et al[39] showed how multiple subconjunctival injections of Restylane-L in the elevator aponeurosis
plane in patients with active thyroid eye disease, led to a reduction in marginal reflex distance-1 that
persisted for a mean of 15 mo post-injection. Leyngold et al[40] reported good clinical outcomes in
patients with sunken superior sulcus, in which injections of Juvéderm Ultra XC in the superior sulcus
deep to the orbital septum led to a 70% decrease of lagophthalmos at the longest follow-up with a mean
9.5 mo[40].
Lower eyelid retraction secondary to different aetiologias can also be treated with HA gel injections,
as demonstrated by Xi et al[41]. The study was based on injecting HA under the orbicularis muscle in 27
cases and evaluating the results by the standardized marginal reflex distance 2 (MRD2). The retraction
was completely corrected in 96.3% of patients with no recurrence at 9 mo post-injection, showing an
improvement of the standardized MRD2 of 0.84 mm immediately after injection and 1.19 mm 9 mo later
[41].
Romero et al[42] analyzed the effects of HA injections in the primary management of cicatricial
ectropion, which can be defined as the eversion of the eyelid away from the globe due to the shortening
of the anterior lamella secondary to many conditions including surgery and trauma. The authors
injected 1 mL of Restylane in each eyelid along the infraorbital rim, in preseptal area, and in the
infraciliary region, obtaining improvement in the eyelid position in all patients with at least partial
ectropion correction. Since this technique provided a poor cosmetic outcome in some of the cases
treated, the authors suggested to consider this treatment in patients who are poor surgical candidates.
A recent retrospective case review conducted by Bladen and Malhotra[43] considered the use of HA
in the treatment of epiblepharon in pediatric patients as an alternative to traditional surgery, since this
condition usually shows an improvement as the child grows older. Of eight eyelids treated with
Restylane, six showed improvements with an 87% success rate, making HA injection a feasible option
for the treatment of epiblepharon, with the advantage of avoiding or delaying surgery in selected cases.
The safety profile and variety of HA derivatives have rendered these dermal fillers suitable for
various aesthetic use, including periorbital area rejuvenation. There has been a paradigm shift over the
last two decades in this field of aesthetic medicine considering that volume loss has been recognized as
one of the main causes of facial and periorbital aging, determining symmetric or asymmetric hollowing,
excess upper lid showing, and dermatochalasis[12,44]. As a result, volume restoration has become a
preferred approach in order to achieve natural rejuvenate results. HA derivatives seem to ideal
candidates for this methodology, considering that they do not require surgery, are quick to perform,
reversible within minutes, and display medium to long lasting effects. HA injections in the upper eyelid
and superior orbital region are performed in order to improve the aesthetic appearance in patients
presenting with superior sulcus hollowness, which may be secondary to the aging process or iatrogenic
after excessive fat removal during surgical blepharoplasty[45]. Filling the upper eyelid can provide
improvements in eyelid closure and function in select cases. In two studies conducted by Romeo[46],
upper eyelid area filling with HA was compared to surgical blepharoplasty as means of reaching eye
rejuvenation in a cohort of 154 and 500 patients, respectively. Both studies showed high patient
satisfaction in regards of the aesthetic endpoint and long-lasting results in a 12-mo follow-up, defining
HA filling as an effective means of rejuvenation for the upper eyelid that can be used independently[12].
Another application of HA injection in the periorbital area is represented by the treatment of tear
trough deformity (TTD) of the lower eyelid. In these cases, the filler is placed at the preperiosteal plane
below the orbicularis muscle. The tear trough is composed of thin skin adherent to the orbicularis
muscle that is attached to the orbital rim. In young patients, the tear trough is located in the medial third
of the orbital rim, whereas in ageing individuals, it gradually extends laterally up to the lateral canthus
[44]. Jiang et al[47] compared the use of HA gel to autologous fat injections and fat repositioning surgery
via arcus marginalis release for the treatment of TTD in 78 patients. Results showed that HA fillers may
be used alone in the treatment of TTD in patients with mild to moderate periorbital volume loss without
severe orbital fat bulging. An observational study by Diaspro et al[48] involving 600 patients showed
that HA injection alone can be considered for the treatment of TTD in patients between 30 and 40 years
of age, based on the statistical analysis that showed an inverse correlation between age and aesthetic
outcome.
Miotti G et al. Modern blepharoplasty
WJCC https://www.wjgnet.com 1726 March 16, 2023 Volume 11 Issue 8
Other injectables
PMMA is a synthetic, extremely long lasting, and potentially irreversible filler. In a retrospective case
series enrolling 289 patients, Mani et al[49] analyzed the use of PMMA microspheres in the infraorbital
eyelid area for the treatment of rhytids. Results showed subdermal PMMA microspheres injection to be
a safe technique in the correction of infraorbital rhytids, with results that seem to be predictable and
natural. Only four patients developed late minor complications in the form of small granulomas, which
resolved with the intralesional injection of triamcinolone. A correlation between granulomas formation
and previous lower blepharoplasty was found[49].
Sodium deoxycholate (DC) is another injectable substance that may be taken into account in
periorbital area rejuvenation procedures. DC has been widely used to reduce unwanted localized fat
deposits for many years. The treatment of lower eyelid fat pads with monthly injections of sodium DC
1.25% (DB125) was evaluated by Amore et al[50] in a multi-center observational prospective study on
120 patients with the aim of assessing the safety and effectiveness of DB125. Results showed a moderate
to high patient satisfaction and therapeutic success in 85.83% of the patients enrolled with no significant
differences between sex, a high degree of effectiveness, and minimal adverse events. This procedure,
however, should be considered for the treatment of lower eyelid fat pads in patients preferably under
the age of 40, since higher success rates in studies tend to be reported in the younger age groups[50].
Polydioxanone threads
Infraorbital groove correction may be achieved with different techniques, such as filler injections, lower
blepharoplasty, and microfat grafting. A new technique to achieve facial rejuvenation is represented by
the insertion of transcutaneous synthetic threads for infraorbital groove correction, such as multiple
twisted polydioxanone (PDO) threads. Lee et al[51] examined the efficacy and the risks of this technique
on a group of 40 patients aged 25-56 years old by assessing Barton’s grade and Global Aesthetic
Improvement Scale scores and patients’ satisfaction. Results showed a significant and persistent
improvement in the mean Barton grade, hence indicating the effectiveness and the benefits of this
technique, with no significant concerns about safety. More than 77.5% of patients were satisfied with the
outcomes[51].
Platelet rich plasma
Another option available for the treatment of the lower eyelid area has been investigated by Aust et al
[52]. The authors evaluated the use of platelet rich plasma (PRP) in order to rejuvenate the skin of the
lower eyelid region and treat actinic elastosis. The study enrolled 20 patients who received three 2 mL
PRP injections per side in the lower eyelid area at monthly intervals. The endpoints were evaluated
using a cutometer to measure skin elasticity and questionnaires to objectify patients’ satisfaction. Results
showed a statistically significant increase in skin firmness and skin elasticity, as well as a high level of
patient satisfaction and progressive improvement of the aesthetic outcomes. Side effects were minimal
and only represented by swelling after the PRP injection, while the procedure was reported to be pain-
free.
CONCLUSION
The eyelid region has always been and will continue to represent a fundamental part of the face that
provides treatment options geared at improving aesthetic outcomes and younger age-related effects.
There are numerous methods, techniques, and tools currently available, which can provide
improvements in mild and moderate cases. Surgery tends to be the first choice to provide radical and
long-term effects, especially in severe cases. Less invasive and non-surgical options have been of
increasing use in the past decade, especially considering the possibility of obtaining a comparable result
by limiting risks, complications, and healing times. New less invasive methods, lasers, innovative
technologies, and alternative tissue fillers are destined to pave the way to the future in modern aesthetic
medicine.
FOOTNOTES
Author contributions: Miotti G wrote the outline, did the research, wrote the paper, and approved the final version of
the article; Zeppieri M assisted in the conception and design of the study, writing and outlining of the manuscript,
approved the final version of the article to be published, and completed the English and scientific editing (a native
English speaking MD, PhD, BSc); Pederzani G assisted in the research and writing of the manuscript; Salati C and
Parodi PC assisted in the editing and critical revisions of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by
Miotti G et al. Modern blepharoplasty
WJCC https://www.wjgnet.com 1727 March 16, 2023 Volume 11 Issue 8
external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-
NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license
their derivative works on different terms, provided the original work is properly cited and the use is non-
commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Country/Territory of origin: Italy
ORCID number: Giovanni Miotti 0000-0003-3185-7595; Marco Zeppieri 0000-0003-0999-5545; Giacomo Pederzani 0000-
0003-3797-4231; Carlo Salati 0000-0003-4736-5296; Pier Camillo Parodi 0000-0002-4677-8198.
S-Editor: Wang JJ
L-Editor: Wang TQ
P-Editor: Wang JJ
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