Archives of Dermatological Research

https://doi.org/10.1007/s00403-020-02173-z

REVIEW

Rejuvenating the periorbital area using platelet‑rich plasma:

a systematic review and meta‑analysis
Adam G. Evans1,5 · Mirjana G. Ivanic1,2 · Mina A. Botros1 · Rand W. Pope3 · Briana R. Halle3 · Gabriella E. Glassman2 ·
Rafaella Genova4 · Salam Al Kassis2

Received: 19 May 2020 / Revised: 3 November 2020 / Accepted: 7 December 2020

© The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature 2021

Abstract
Intradermal injection of autologous platelet-rich plasma (PRP) is a non-surgical cosmetic therapy to rejuvenate the peri-
orbital area pathologies of wrinkles, periorbital hyperpigmentation (POH), and photoaging. The past decade has seen the
adoption of this novel therapy around the world. This is the first systematic review and meta-analysis evaluating PRP treat-
ment of periorbital pathologies. This is a PRISMA compliant review that includes a comprehensive search of the databases
Cochrane Library, Ovid Medline, Ovid Embase, and clinicaltrials.gov. The search was performed in June 2019 to obtain all
peer-reviewed articles published in English that describe the application of PRP to periorbital pathologies. A meta-analysis
of patient satisfaction was performed for randomized controlled trials. Nineteen studies treating 455 patients (95% female,
age range 28–60) were included. Studies were categorized based on reported outcomes: wrinkles (11 studies), POH (7 stud-
ies), and photoaging (6 studies). Patients were treated a mean of 3 times (range 1–8) in mean intervals of 23 days (range
14–56 days). Follow-up averaged 3 months (range 1–6 months). Meta-analysis of 3 randomized controlled clinical trials
(RCTs) shows that patients treated with PRP have increased satisfaction above controls of saline, platelet-poor plasma, meso-
therapy, and as an adjunct to laser therapy (overall effect p = 0.001, heterogeneity I2 = 64%). PRP treatment of periorbital
area pathologies results in histologic improvements of photoaging, subjective satisfaction score increases, and blind evalu-
ator assessments of rejuvenated skin appearance. Future studies are needed to address limitations of the current literature
and should include long-term follow-up, delineation of the POH etiology that is treated, RCTs with low risk of bias, and be
absent conflicts of interest or industry sponsors.
Trial registration: Prospero Systematic Review Registration ID: CRD42019135968

Keywords Plate-rich plasma · Platelet-rich fibrin · Periorbital hyperpigmentation · Wrinkles · Photoaging · Skin aging

Introduction

Facial rejuvenation remains a crucial focus of many sur-

gical and non-surgical cosmetic procedures. Evidence has
Supplementary Information The online version contains shown women notice the eyes before any other facial feature
supplementary material available at https​://doi.org/10.1007/s0040​ while men first see the infraorbital area [1]. Accordingly, the
3-020-02173​-z.

4
* Adam G. Evans University of Tennessee Health Science Center, 910 Madison
aevans17@email.mmc.edu Ave, Memphis, TN 38163, USA
5
1 Present Address: Division of Plastic and Reconstructive
Meharry Medical College, 1005 Dr DB Todd Jr Blvd,
Surgery, Department of Surgery, Washington University
Nashville, TN 37208, USA
School of Medicine, 660 S. Euclid Ave, St. Louis,
2
Department of Plastic Surgery, Vanderbilt University MO 63110, USA
Medical Center, D‑4207 Medical Center North, 1211
Medical Center Drive, Nashville, TN 37212, USA
3
Vanderbilt University School of Medicine, 1161 21st Ave
South, Nashville, TN 37232, USA

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Vol.:(0123456789)

appearance of bags under the eyes is one of the first notice-
able signs of aging [2, 3]. The hallmark traits of an aging
midface include malar fat pad descent, descent and loss of
sub-orbicularis oculi fat (SOOF), infraorbital rim hollowing,
and a double-contour deformity caused by separation of the
lower eyelid–cheek complex [4]. Cosmetic skin rejuvena-
tion procedures aim to restore a youthful appearance to the
skin by reversing these signs as well as other prominent age-
related changes in the under-eye region including fat atrophy,
decreased laxity, hyperpigmentation, and wrinkles [2].
The periorbital area is a technically challenging area to
treat due to the thinness of the skin and the high vascular-
ity of the facial area [3]. Skillful injections are required to
appropriately treat while avoiding branches of the maxil-
lary artery, angular artery, superior labial artery, and septal
artery [5]. Treatments for periorbital pathologies include
non-surgical options, such as hyaluronic acid injections,
micro-needling, chemical peels, laser-resurfacing, micro-
dermabrasion, nifedipine, botulinum toxin, carbon dioxide
(carboxytherapy) injections, in addition to surgical options
including fat transfers, blepharoplasty, and face-lifts [3,
6–8]. The past decade has also seen the emergence of plate-
let-rich plasma (PRP) as a treatment option for rejuvenating
the skin’s appearance.
PRP preparation and mechanism
After collecting a venous blood draw from a patient, PRP is
prepared through a process of centrifugation and treatment
of the blood products. Centrifuged blood separates into a
dense cellular portion and a less-dense supernatant that con-
tains platelets, plasma, and the proteinaceous contents of
plasma. Typical PRP platelet concentrations are 2–5 times
higher than the physiologic platelet concentration reference
range of 150,000 to 450,000 platelets per μL, supported by
in vitro studies of a variety of tissues finding the optimal
PRP platelet concentration to be around 2.5 times normal,
or between 0.5 × 106 and 2.0 × 106 platelets per μL [9–15].
The predominant secretory granules of platelets,
α-granules, are a source of over 30 growth factors, cytokines,
and chemokines [16, 17]. These molecules induce wound
healing, tissue regeneration, fibroblast proliferation, hya-
luronic acid secretion, granular tissue formation, collagen
production, and modulate angiogenesis [18–24]. The mol-
ecules thought to be key to the process of facial rejuvena-
tion are epidermal growth factor (EGF), platelet-derived
growth factor-AB (PDGF-AB), transforming growth factor
β1 (TGF-β1), fibroblast growth factor (FGF), connective tis-
sue growth factor (CTGF), and vascular endothelial growth
factor (VEGF) [25, 26]. PRP contains supraphysiologic con-
centrations of most of these molecules [27, 28].
Centrifugation protocols for PRP vary widely across
studies. Early literature used the term PRP to encompass
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Archives of Dermatological Research
numerous derivations of platelet concentrates, but research
has begun to delineate protocol variations that confer ben-
efits for certain applications [9, 18, 29–31]. 1 or 2 centrifu-
gations are typically performed, and substrates including
anticoagulants and activators may be added. The induced
activation of platelets, commonly due to added activators,
such as thrombin or calcium chloride, or by slow activation
from contact with the glass storage tube, is used to create a
platelet gel with higher viscosity than PRP. This so-called
second-generation platelet gel is sometimes referred to as
Platelet-Rich Fibrin (PRF) or Platelet-Rich Fibrin Matrix
(PRFM). These products have a higher-density fibrin matrix
than PRP [30, 32, 33] and have been proposed to have a
benefit of immediate volumization upon injection, increased
growth factor content, smaller injected clot size, and time-
release growth factor release [10, 26, 34].
The selection of blood’s component layers is another area
of protocol deviation. The supernatant present after centrifu-
gation may be divided, often with pipette and canula, into a
lower, more-dense platelet-rich portion termed platelet-rich
plasma (PRP) and a higher, less-dense platelet-poor portion
termed platelet-poor plasma (PPP). Furthermore, if the PRP
includes the leukocyte-rich “buffy coat”, then the PRP may
be described as leukocyte-rich PRP (LR-PRP), whereas PRP
lacking the buffy coat is called leukocyte-poor (LP-PRP),
also known as Plasma Rich in Growth Factors (PRGF) [26,
33, 35]. Although LP-PRP is the PRP treatment of choice for
osteoarthritis [36], there is no consensus on LR-PRP versus
LP-PRP for dermal applications.
Over the past decade, platelet-rich plasma (PRP) has been
a focus of much research aiming to utilize minimally inva-
sive methods to rejuvenate the area around the eyes. This
study summarizes all published literature utilizing plate-
let concentrate products for the treatment of a periorbital
pathology and includes a meta-analysis of patient satisfac-
tion with the treatment.
Methods
This study was done in accordance with the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines with a detailed protocol developed
prior to initiating the review [37]. The protocol is registered
on the International Prospective Register of Systematic
Reviews (PROSPERO) under the ID: CRD42019135968.
Search strategy
Two reviewers (M.I. and B.H.) independently performed lit-
erature searches. Cochrane Library was searched from incep-
tion through May 31, 2019. Ovid Embase was searched from
1980 and 2019 Week 20. Ovid Medline and Epub Ahead
Archives of Dermatological Research
of Print, In-Process and Other Non-Indexed Citations,
Daily and Versions were searched from inception (1946)
to May 23, 2019. The clinical trials registry clinicaltrials.
gov (http://clini​caltr​ials.gov/) was searched from 2000 and
2019. Free text and MeSH term searches performed were
designed to include the words “platelet rich plasma,” “plate-
let concentrate(s),” “skin rejuvenation,” “actinic elastosis,”
“skin aging,” “face,” “infraorbital,” “periorbital,” as well
as word variations and similar words combined with the
Boolean operators “or” and “and.” The search strategy was
designed and altered as necessary and appropriate to each
database, and is included in full in Online Resource 1. Bibli-
ographies of included studies were also searched. In cases of
disagreement about study inclusion, an additional reviewer
(A.E.) was involved in the discussion. The largest cohort of
a study was selected if multiple publications described the
same cohort. Data extraction performed was by one author
(M.I.) using a piloted form excel spreadsheet, with a second
reviewer (A.E.) checking over 90% of the extracted data.
Inclusion and exclusion criteria
Inclusion criteria for studies were: (1) peer-reviewed origi-
nal research articles, (2) available in English, (3) including
patients over the age of 18, (4) treating periorbital cosmetic
pathologies as defined by the border of the orbicularis oculi
muscle and infraorbital area, (i.e. periorbital hyperpigmen-
tation, crow’s feet, lower eye bags, dark circles under the
eye, tear trough deformity, pseudoherniated orbital fat pad),
(5) treating patients with a platelet-concentrate product, (i.e.
PRP, PG, PRF, PRFM, PRGF), (6) with a minimum mean
follow-up of 1 month.
Exclusion criteria for studies were: (1) duplicate studies
or cohorts, (2) incomplete trials, (3) abstracts, (4) letters to
the editor, (5) treating anatomical areas that did not include
the periorbital area, (6) animal studies, case reports, retro-
spective studies, review articles, and meta-analyses, (7) non
peer-reviewed “grey” literature.
Risk of bias
Risk of bias assessment was performed at study and outcome
levels with the Cochrane Collaboration risk-of-bias tool for
randomized controlled trials. Study sources of funding and
conflicts of interest were recorded.
Outcome measures
The primary outcome assessed by our study was the patient
satisfaction survey of RCTs. Secondary outcomes included
physician satisfaction scores, clinical evaluator scores, col-
lagen mean optical density, skin measures of homogeneity,
texture, firmness, elasticity, barrier function, thickness, or
pigmentation, and adverse reactions.
Statistical data analysis and synthesis
RevMan 5.3.5 (Cochrane Collaboration) software pack-
age was utilized for all statistical analysis. Only RCTs
were included in the meta-analysis. RCTs reporting patient
satisfaction scales that did not include a range of 0 as no
effect and 3 as the top value were excluded from the meta-
analysis. To incorporate the heterogeneity between stud-
ies, the authors calculated I2, and I2 > 50% was considered
high heterogeneity and warranted investigation of the study
details contributing to heterogeneity. Random-effects model
was chosen. The authors set significance in this article at
p < 0.05.
Results
Literature search
Our search strategy retrieved 563 records from the data-
bases. After 66 duplicate records were removed, a screen
of 497 articles by title and abstract led to the exclusion of
441 articles. Zero additional articles were identified from
other sources. A full-text review of the eligible 56 articles
resulted in the exclusion of 37 articles for reasons including:
not periorbital location (n = 11), pending trials (n = 9), let-
ters (n = 4), retrospective study (n = 3), non-clinical studies
(n = 3), abstracts (n = 3), review articles (n = 2), not available
in English (n = 1), and not involving platelet-concentrate
products (n = 1). In total, 19 studies met criteria and were
included in the review [2, 3, 7, 8, 19, 25, 26, 31, 38–48], and
3 RCTs were included in the data synthesis [7, 19, 40]. The
article selection process is described in Fig. 1.
Characteristics of included studies
Table 1 summarizes study characteristics and patient demo-
graphics. The 19 included studies were published between
2010 and 2019. 5 studies addressed more than 1 periorbital
pathology, and therefore the pathologies of the periorbital
area that met inclusion criteria include 6 studies treating
wrinkles alone [2, 39, 40, 43, 47, 48], 4 studies treating both
wrinkles and photoaging [8, 19, 25, 26], 1 study treating both
wrinkles and periorbital hyperpigmentation (POH) [31], 2
studies treating photoaging alone [42, 45], and 6 studies
treating POH alone [3, 7, 38, 41, 44, 46]. 455 patients were
treated from countries in Europe (n = 8), Asia (n = 6), and
Africa (n = 5). For the 16 studies reporting on patient gender,
95% of the patients were female. The reported mean patient
age ranged from 28 to 60 years of age. 8 studies included
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 Archives of Dermatological Research

Records identified through database Additional records identified through other

searching sources
Identification

(n = 563) (n = 0)

Records after duplicates removed

(n = 497)

Records screened
Screening

Records excluded
(n = 497)
(n = 441)

Full-text articles assessed Articles excluded with

for eligibility reasons: (n = 37)
Eligibility

(n = 56) Not periorbital (n = 11)

Pending trial (n = 9)
Letters (n = 4)
Retrospective (n = 3)
Studies included in Non-clinical (n = 3)
qualitative synthesis Not in English (n = 1)
(n = 19) Not a platelet
concentrate treatment
Included

(n = 1)
Studies included in
quantitative synthesis
(n = 3)

Fig. 1  PRISMA Flow Chart of the Literature Search. 563 records Following exclusion of 37 articles for reasons, 19 studies were
were retrieved from applying the search strategy to the databases. included in the systematic review and 3 randomized controlled trials
After removing 66 duplicates, a title and abstract screen was per- were included in the meta-analysis
formed for 497 records, of which 56 were eligible for full-text review.

a control including saline [40, 42], micro-needling with or
without topical TCA 15% [8], topical trichloroacetic acid
3.75% with lactic acid 15% [38], mesotherapy [19], platelet-
poor plasma and saline [7], and carboxytherapy [41].
Table 2 summarizes study procedures, treatment results,
and adverse effects. All studies utilized intradermal and
subdermal injections except 1 in which PRP was applied
topically after micro-needling (dermaroller, ADROLL TD,
Spain) [8]. Patients were treated a mean of 3 times (range
1–8) spaced out with mean treatment intervals of 23 days
(range 14–56 days). Patient follow-up averaged 3 months
(range 1–6 months). All studies reported a favorable out-
come following treatment with PRP to the periorbital area.
5 studies utilized a single PRP injection, and all 5 reported
noticeable benefits from the treatment [26, 31, 42, 43, 49].

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Archives of Dermatological Research

Table 1  Study and patient characteristics

References Country Design Periorbital Patients Treatment (# Control (# Females, Age in years Fitzpatrick and
pathology enrolled treated) treated) males (mean, range) Glogou Scale
enrolled Grades

Abauf et al. Turkey Split Face Photoaging 20 PRP (n = 20) Saline (n = 20) 20, 0 43.7, 40–49 FI (15%), FII
[42] CCT​ (60%), FIII
(25%)
Al-Shami Jordan UCT​ POH 50 PRP (n = 50) – 46, 4 41.5, 19–60 FIII-FV
et al. [46]
Aust et al. [3] Germany UCT​ POH 20 PRP (n = 20) – 16, 4 45, 21–60 –
Cameli et al. Italy UCT​ Crow’s feet 12 PRP (n = 12) – 12, 0 –, 45–65 –
[39]
Diaz-Ley et al. Spain UCT​ Photoaging 10 PRGF (n = 10) – 7, 2 –, 34–59 –
[45]
El-Domyati Egypt Split Face Crow’s feet 24 PRPb (n = 16) (a) Micronee- 24, 0 50.9, 45–59 FIII 29%, FIV
et al. [8] RCT​ and Photo- dling (n = 16) 67%, FV 4%
aging (b) Micronee-
dling and
topical TCA
15% (n = 16)
Ellabban et al. Egypt RCT​ POH 42 PRP (n = 21) Topical TCA 38, 4 28.1, – –
[38] 3.75% + LA
15% (n = 21)
Elnehrawy Egypt UCT​ Crow’s feet 20 PRP (n = 20) – 20, 0 36.9, – GIII-GIV
et al. [43]
Everts et al. Portugal UCT​ Crow’s feet 11 PRP (n = 11) – 11, 0 51, 47–60 FII-FIV, FIII
[25] and Photo- 82%
aging
Gawdat et al. Egypt Split Face Crow’s feet 20 PRP (n = 20) Mesotherapy 20, 0 41, 35–55 GII 55%, GIII
[19] RCT​ and Photo- ­Injectiona 45%, FIII
aging (n = 20) 30%, FIV 70%
Jiménez Spain UCT​ Crow’s feet 10 PRGF (n = 10) – NR 60.6, 50–65 FII 60%, FIII
Gómez et al. and Photo- 40%
[26] aging
Hui et al. [40] China Split Face Crow’s feet 13 PRP injection Saline Injec- 13, 0 42.1, 32–57 FIII-FIV
RCT​ and topi- tion + CO2
cal + CO2 laser (n = 13)
laser (n = 13)
Kang et al. [7] South Korea Split Face POH 20 PRP (n = 20) (a) Saline Injec- 20, 0 50.6, 44–57 –
RCT​ tion (n = 10)
(b) PPP Injec-
tion (n = 10)
Mehryan et al. Iran UCT​ Crow’s feet 10 PRP (n = 10) – NR 41.2, 26–61 FIII-FIV
[31] and POH
Nofal et al. Egypt Split Face POH 30 PRP (n = 30) CO2 injection 26, 4 28.9, 20–44 FII-FIV
[41] CCT​ (n = 30)
Redaelli et al. Italy UCT​ Crow’s feet 23 PRP (n = 23) – NR 47, 28–70 –
[48]
Scarano et al. Italy UCT​ Crow’s feet 16 PRGF (n = 16) – 16, 0 –, 27–60 GI-GIII
[47]
Ulusal et al. Turkey UCT​ POH 94 PRP + HA – 94, 0 53, – –
2016 (n = 94)
Yuksel et al. Turkey UCT​ Crow’s feet 10 PRP (n = 10) – 10, 0 50, – –
[2]

NR not reported, n number included, RCT​randomized controlled clinical trial, CCT​controlled clinical trial, UCT​uncontrolled clinical trial, TCA​
trichloroacetic acid, LA lactic acid, PPP platelet-poor plasma, HA hyaluronic acid, POH periorbital hyperpigmentation, FI-FVI Fitzpatrick scale
grading, GI-GIV Glogou scale grading
a
Mixture of epidermal growth factor, insulin-like growth factor 1, basic fibroblast growth factor, thioredoxin, copper tripeptide-1, vitamins,
amino acids, minerals)
b
This group applied PRP topically after micro-needling

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 Table 2  PRP preparation, administration, and objective treatment outcomes
Study Injection Protocol Follow-up Objective Outcomes Centrifugation Protocol (FITPAAW)

13
Abauf et al. [42] 1 Inj 1 month Increased dermal collagen per biopsy image analysis F: 1 centrifugation at 3000 rpm
I: After centrifugation, the platelet and WBC pellet were gently
mixed with plasma; the top 2 mL suspension was called PRP
T: 5 min
P: –
A: Sodium citrate
A: Calcium chloride
W: Included
Al-Shami et al. [46] 3 Inj. Q4W 6 months Improved appearance of POH per dermatologist assessment F: Centrifugation 1 at 1600 rpm; centrifugation 2 at 4000 rpm
I: After 1 centrifugation, the supernatant was withdrawn and
re-centrifuged. After Run 2, the bottom ¼ was retained as
PRP
T: Run 1 × 10 min; run 2 × 10 min
P: –
A: Sodium citrate 3.2%
A: Calcium chloride
W: –
Aust et al. [3] 3 Inj. Q4W 3 months Increased periorbital skin firmness and elasticity per device F: 1 run at 1500 rpm (350 g)
I: After centrifugation, the PRP settled in the upper 1/3 of a
double syringe and was collected into the inner syringe
T: 5 min
P: 2.5 times baseline
A: –
A: –
W: –
Cameli et al. [39] 3 Inj. Q4W 3 months Improved skin texture, elasticity, smoothness, and barrier F: 1,100 rpm
function per device and digital and ultraviolet photograph I: After centrifugation, the PRP remained at 24 °C, 40% humid-
analysis ity, for 30–45 min to dissolve platelet aggregates
T: 8 min
P: mean 1680 × 106 (range 885–3760)
A: Sodium citrate
A: No platelet activator used
W: mean 1.9 × 103 μL (range 0.03–7.6)
Diaz-Ley et al. [45] 3 Inj. Q3W 3 months Increased epidermal and dermal thickness and collagen and F: 580 g
reduced solar elastosis per dermatopathologist I: After centrifugation, the plasma was fractioned into F1 and
F2 layers, and then activated
T: Run 1 × 8 min
P: –
A: Sodium citrate
A: Proprietary PRGF activator
W: –
Archives of Dermatological Research
 Table 2  (continued)
Study Injection Protocol Follow-up Objective Outcomes Centrifugation Protocol (FITPAAW)

El-Domyati et al. [8] 6, ­Q2Wa 3 months Improved facial wrinkles; increased epidermal and dermal F: Centrifugation 1 at 252 g; centrifugation 2 at 1,792 g
thickness; decreased abnormal elastic fibers per histology I: After 1 centrifugation, the plasma was collected and re-cen-
analyzing device trifuged. After centrifugation 2, the sample formed 2 parts,
with PRP being the lower 1/3 and PPP as the upper 2/3
T: Run 1 × 10 min; run 2 × 5 min
P: –
A: Acid citrate dextrose (ACD) solution
A: Calcium gluconate
Archives of Dermatological Research

W: –
Ellabban et al. [38] 4 Inj. Q2W 2 months Improved POH per physician F: Centrifugation 1 at 150 g; centrifugation 2 at 2000 g
I: After 1 centrifugation, the supernatent plasma was collected
into a plain tube then centrifuged again. After run 2, the
upper 2/3 of PPP was discarded and the platelet-rich pellet
was collected
T: Run 1 × 5 min; run 2 × 12 min
P: 3–fourfold higher platelet concentration than whole blood
A: –
A: Calcium chloride
W: –
Elnehrawy et al. [43] 1 Inj 2 months Improved Wrinkles, Nasolabial Folds, Texture, and Homoge- F: Centrifugation 1 at 388 g; centrifugation 2 at 1376 g
neity per physician I: After 1 centrifugation, the blood separated into 2 parts, and
the plasma part was collected into another tube and re-centri-
fuged. After the 2nd centrifugation, the PPP supernatant was
discarded and the lower PRP was collected
T: Run 1 × 7 min; run 2 × 5 min
P: –
A: Sodium citrate
A: Calcium chloride 10%
W: –
Everts et al. [25] 3 Inj. Q4W 6 months Decreased brown spot and wrinkle count; Improved skin firm- F: –
ness per devices I: 2 spin proprietary protocol
T: ND
P: 1,000,000 platelets per mL
A: Sodium citrate
A: Calcium chloride
W: –

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 Table 2  (continued)
Study Injection Protocol Follow-up Objective Outcomes Centrifugation Protocol (FITPAAW)

13
Gawdat et al. [19] 6 Inj. Q2W 2.5 months Increased epidermal and dermal thickness per optical coher- F: Centrifugation 1 at 150 g; centrifugation 2 at 400 g
ence tomography measuring device I: After 1 centrifugation, the supernatant alone was re-cen-
trifuged, making a pellet that was suspended in 1.5 mL of
supernatant
T: Run 1 × 15 min; run 2 × 10 min
P: –
A: Acid citrate dextrose
A: Calcium chloride 3%
W: –
Jiménez Gómez et al. [26] 1 Inj 4 months Reduced Wrinkles; Restored Facial Volume; Softened Skin F: 580 rpm
Texture; Increased Homogeneity per physician I: After centrifugation, most of plasma column was drawn out
avoiding the buffy layer, and then incubated for 8 min (for
high viscosity gel) or 12 min (for low viscosity gel) at 76 °C
to obtain precursor gels. During this time, 2 ml of plasma
right above the buffy layer was collected and activated and
then mixed with the precursor gels
T: Run 1 × 8 min
P: 2.1 times baseline ± 0.7
A: Sodium citrate 3.8%
A: PRGF-Endoret Activator
W: –
Hui et al. [40] 1 Inj 3 months Improved wrinkles, texture, & elasticity per digital image F: Centrifugation 1 at 1200 rpm; centrifugation 2 at 3500 rpm
analysis software I: After 1 centrifugation, the plasma, buffy coat, and 2–3 mm
red blood cells were collected, mixed, and re-centrifuged.
After re-centrifugation, 1/2 of the PPP volume was discarded,
and the pellet was resuspended in the remaining PPP
T: Run 1 × 10 min; run 2 × 5 min
P: 700 × 109/L to 1000 × 109/L
A: Heparin calcium
A: Calcium gluconate
W: Included
Kang et al. [7] 3 Inj. Q4W 3 months Improved Skin Tone per spectrophotometry F: –
I: –
T: –
P: 812.50 ± 126.61 × 103 μL
A: –
A: None
W: –
Archives of Dermatological Research
 Table 2  (continued)
Study Injection Protocol Follow-up Objective Outcomes Centrifugation Protocol (FITPAAW)

Mehryan et al. [31] 1 Inj 3 months Improved color homogeneity per physician F: Centrifugation 1 at 1600–1800 g; centrifugation 2 at 2000 g
I: After 1 centrifugation, the chambers were disconnected then
a re-centrifugation was performed which concentrated plate-
lets at the bottom of the upper chamber. The bottom 3 mL of
plasma in the upper chamber was collected
T: Run 1 × 6 min; run 2 × 5 min
P: –
A: Anticoagulant (ACD-A)
Archives of Dermatological Research

A: Calcium chloride
W: –
Nofal et al. [41] 7 Inj. Q2W 3 months Improved POH per physician F: Centrifugation 1 at 150–200 g; centrifugation 2 at 1500–
2000 g
I: –
T: Run 1 × 10 min; run 2 × 15 min
P: 3–4 times more concentrated than whole blood
A: Trisodium citrate
A: Calcium chloride
W: –
Redaelli et al. [48] 3 Inj. Q4W 3 months Improved homogeneity, wrinkles, texture, & elasticity per F: 3500 rpm
physician I: After centrifugation, the upper PPP layer was discarded then
the lower PRP layer was collected
T: 5 min
P: –
A: –
A: Calcium chloride
W: –
Scarano et al. [47] 3 Inj. Q4W 3 months Improved wrinkles with a gradual decline back to baseline per F: 1100 rpm
physician I: –
T: 4 min
P: –
A: Sodium citrate
A: –
W: –
Ulusal et al. 2016 Inj. 1–3 Q3W and NR Improved overall appearance on digital photograph per physi- F: 1800 rpm
up to 5 more inj. cian I: –
Q8-10 W T: 20–50 min
P: 1,389,000 μL; 5–6 times higher than baseline
A: 1.5 cc of 10% Sodium citrate
A: None
W: Included

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PPP platelet-poor plasma, PRP platelet-rich plasma, POH periorbital hyperpigmentation, Inj. Injection, rpm rotations per minute, g g-force, Q2W Every 2 weeks, FIT PAAW​classification for
I: After centrifugation, PPP at the top of the tube was removed
by syringe and PRP above the parser gel was collected by

PRP that includes force of centrifugation, iteration-sequence of centrifugation, time of centrifugation, platelet concentration, anticoagulation, activation, and white blood cell content
Centrifugation Protocol (FITPAAW)
4.5 months Improved skin appearance, firmness, sagginess, and wrinkles; F: 3200 rpm

T: 8 min
canula

W: –
A: –
A: –
P: –
Did not improve pigmentation per physician

Fig. 2  Cochrane Risk of Bias Assessment of Randomized Controlled

Trials. Five RCTs were included, of which 1 study had low risk of
bias and 4 studies had a high risk of bias

Risk‑of‑bias assessment
Objective Outcomes

Figure 2 summarizes article risk-of-bias assessment for the

5 RCTs. 1 RCT had low risk of bias, and 4 RCTs had high
risk of bias. Of the 19 included studies, 8 (42%) reported
having no conflicts of interest or financial support, includ-
ing all RCTs except Gawdat et al. [19] who did not report on
financial support or conflicts of interest.
Follow-up

This study applied PRP topically following micro-needling

Meta‑analysis of patient satisfaction

Our meta-analysis included 3 RCTs containing 6 independ-

ent patient satisfaction questionnaires assessing overall
Injection Protocol

satisfaction [19], as well as satisfaction with treatment of

wrinkles [7, 40], skin texture [40], skin elasticity [40], and
3 inj. Q2W

skin tone [7]. Controls for the meta-analysis included saline

[7], a proprietary mesotherapy injection including growth
factors [19], and a comparison to C­ O2 laser with saline when
PRP was used as adjunct treatment [40]. PRP significantly
(p = 0.001) increased patient satisfaction scores compared
Table 2  (continued)

to control. Significant heterogeneity (I2 = 64%) was present

Yuksel et al. [2]

and attributed to articles using different treatment protocols

and controls (Fig. 3).
Study

13
Archives of Dermatological Research
Discussion
Periocular wrinkles
The treatment of periocular wrinkles, or “crow’s feet,” was
a focus of 11 studies [3, 7, 8, 19, 25, 26, 31, 38, 41, 44, 46].
Crow’s feet form as a normal process of skin aging and pho-
toaging whereby the lateral orbital skin develops multiple
linear wrinkles that spread outward from the lateral canthus.
Early clinical trials examining PRP for treatment of perio-
cular wrinkles from 2010 to 2016 lacked control groups, but
demonstrated that both PRP and PRGF provide statistically
significant improvements in overall skin appearance, wrin-
kles, firmness/sagginess, and color homogeneity when meas-
ured at 1–3 month follow-ups [2, 31, 43, 47, 48]. Except for
Mehryan et al., these studies were limited by a lack of objec-
tive outcomes as well as non-blinded evaluation. Mehryan
et al. [31] notably found that color homogeneity was signifi-
cantly improved by a single PRP treatment.
Subsequent clinical trials utilizing multiple treatments
found that 3–6 treatments significantly reduced wrinkle
count and volume at 4–6 months [25, 26], including the
double-blind RCT by Gawdat et al. [19] whose improve-
ments persisted 6 months after treatment cessation. Objec-
tive evaluation of facial areas including the crow’s feet
using several devices was provided by Cameli et al. [39]
who showed improvements 1 month after a 3rd treatment
include skin scaliness, roughness, wrinkles, smoothness,
curtosis, transepidermal water loss indicating skin barrier
function, and skin elasticity. Although limited by sample
size (n = 12), absent control, and short follow-up, their find-
ings are supported by the uncontrolled 2018 clinical trial of
Everts et al. [25] who showed improvements persisting at
6 months post injection. Specifically, Everts et al. [25] found
that 3 treatments of PRP improved wrinkle count and vol-
ume, enhanced skin firmness, provided a 26.3% reduction to
Fig. 3  Patient Satisfaction Score Following Treatment With Plate-
let-Rich Plasma. Meta-analysis of patient satisfaction scores from 3
randomized controlled trials shows that PRP produces significantly
increased patient satisfaction over controls including saline, a proprie-
brown spots, and interestingly also reduced overall erythema
intensity without change to quantity nor area of red spots.
Elnehrawy et al. [43] provided subgroup analysis for
PRP effectiveness in skin rejuvenation, finding that effects
peaked 8 weeks after their single treatment, and that the
nasolabial folds saw greater improvement than the crow’s
feet. This variance of effect by facial location was later sup-
ported through observed changes in dermal thickness by the
ultrasound analysis of Jiménez Gómez et al. [26]. Nonethe-
less, Elnehrawy et al. [43] reported that all patients treated
for fine wrinkles experienced improvements while only 60%
of patients treated for deep wrinkles experienced improve-
ments. The variance in these results may be credited to the
effect and importance of injection technique.
Injection technique for treatment of fine wrinkles was
proposed to be best achieved by intradermal injections,
whereas deep wrinkles and volume loss are best treated
at the dermal–subdermal border [50]. Both Cameli et al.
and Redaelli et al. [39, 48] utilized an injection technique
for treatment of the crow’s feet termed the “wave,” which
involved an intradermal “ponfi” injection followed by pass-
ing the needle through the injected area.
Alternate formulations of PRP are an important area of
active research. Jiménez Gómez et al. [26] introduced a
platelet gel, created similar to PRGF, but with increased vis-
cosity secondary to proprietary additives. A single injection
of this gel provided immediate volumization, and patient
evaluation as well as blinded photographic and digital 3D
topographic evaluation showed sustained improvements
4 months after the treatment. The gel retained 100% of its
weight at 2 weeks when plated in vitro without tissue plas-
minogen activator (tPA), and with tPA it retained 80–92%
of its weight [26]. A retrospective study has shown PRF has
efficacy in treating several periorbital pathologies [50], pro-
viding credence for future clinical trials to thoroughly inves-
tigate the use of PRF for periorbital wrinkles. Significant
pain may result and deter patients from continuing treatment,
so topical anesthetics should be considered [41].
tary mesotherapy growth factor injection, and a C ­ O2 laser alone when
PRP was used as an adjunct treatment. Patient satisfaction scores
included in the meta-analysis were overall satisfaction, satisfaction
with treatment of skin wrinkles, texture, elasticity, and tone
13

Although delicate, the periorbital area, including the
upper eyelid, is safely treatable by precisely targeted PRP
injections [51]. The crow’s feet, however, are unique among
the periorbital region in that it may be treated with topical
PRP following micro-needling. Such a treatment was supe-
rior to TCA 15% with micro-needling (p = 0.048) at improv-
ing the appearance of the crow’s feet in the 2018 RCT by
El-Domyati et al. [8]. Although their clinical trial utilized
blinded clinical evaluators and blinded dermatopathologist
histologic analysis, it was limited by a small sample size
and their conclusions were made for the whole face without
subgroup analysis of the periocular area [8].
Hui et al. [40] assessed PRP as an adjunct treatment to
­CO2 laser in a double-blind split-face RCT, finding that 3
treatments over 3 months with PRP were superior to the
­CO2 laser with saline at a follow-up 3 months after treat-
ment. PRP was significantly superior to saline in improving
patient satisfaction scores for wrinkles (p = 0.039), skin tex-
ture (p = 0.039), and skin elasticity (p = 0.040), in addition
to objective evaluation of elasticity (p = 0.010) and texture
(p = 0.026) using a biometric device VISIA Complexion
Analysis System (Canfield Imaging Systems, Fairfield,
NJ). Patients also reported decreased duration of erythema,
edema, and crusting with the PRP treatment by an average
of a half-day. Blinded evaluation by dermatologist and the
VISIA Complexion Analysis System also showed improve-
ments to wrinkles but were not statistically significant.
Photodamage and photoaging
Patients with periorbital photoaging were assessed in 6 stud-
ies [8, 19, 25, 26, 42, 45]. A blind expert evaluation of pic-
tures by Diaz-Ley et al. [45] found that PRP improved pho-
toaging scores, which is consistent with facial rejuvenation
literature showing that PRP improves subjectively measured
photoaging scores [50]. While photoaging affects the subjec-
tive evaluation of a skin’s appearance, several other factors
also affect the appearance of the skin including extrinsic
causes like tobacco smoke and intrinsic etiologies including
molecular repair defects [52]. Accordingly, many studies uti-
lized histologic examination, ultrasound, and optical coher-
ence tomography (OCT) to examine characteristic signs of
photoaging in the epidermis and dermis. The suspected key
mediators of photoaging reversal include the cytokines and
growth factors PDGF-AB, TGF-β1, VEGF, IGF-I, and EGF
[26].
Photodamage and photoaging have the largest effect on
fair skinned individuals (Fitzpatrick skin types I, II, III)
in whom early changes including fine wrinkles are often
observable at age 30 while deep wrinkles may start appear-
ing at ages 40–50. Darker skin (Fitzpatrick skin types IV,
V, VI) individuals first experience changes more commonly
at ages 40–50 [43, 53–56]. The changes of photoaging are
13
Archives of Dermatological Research
many and include mottled pigmentation, rhytids, furrows
and cobble stone appearance, lentigines, comedones, tel-
angiectasias, pale color, loss of skin translucency, actinic
purpura, leathery appearance, coarse textural changes, skin
laxity, and decreased turgor and elasticity [53]. Patients
experience varying levels of concern or distress for their
skin changes depending on their personal values and socio-
cultural influences [53].
The mechanism of photodamage is attributed to chronic
ultraviolet radiation activating the transcription factor AP-1,
which acts to increase the activity of metalloproteinases
(MMPs) including MMP-1, MMP-3, and MMP-9. These
MMPs are responsible for degrading type I and III colla-
gens [57, 58], but interestingly, both PPP and PRP increase
activity of the in vitro fibroblast’s MMP-1 and MMP-3. In
this instance, the actions of the MMPs are thought to facili-
tate dermal remodeling and an improved foundation for new
collagen [20], which are supported by two clinical trials that
included histologic studies noting that their platelet-concen-
trate treatments resulted in increased collagen organization
[8, 45]. This likely mechanism by which platelet-concentrate
products act to reverses the deleterious effects of photoag-
ing on collagen is supported by in vitro studies showing
that PPP, PRP, and PRGF all induce fibroblast proliferation
[20, 24], and this was demonstrated in a 2015 clinical trial
by Diaz-Ley et al. using PRGF. Diaz-Ley et al. [45] also
proposed that the increase in fibroblasts may be due to an
observed increase in only the dermal CD34 + dendrocytes of
the deepest dermis. Clinical trials have also confirmed that
platelet-concentrate products result in statistically significant
increases in collagen density and quantity. The increases
in collagen were superior on comparison with saline, were
additive when PRP was utilized with dermaroller micro-
needling, and were efficacious from topical PRP [8, 42, 45].
Studies in vitro have provided additional insight into
the mechanism by which the platelet-concentrate products
exert their effects on collagen. Although both PPP and PRP
induced mRNA of type I collagen (COL1A1 and COL1A2),
the PPP was more effective than PRGF in inducing pro-col-
lagen I carboxy-terminal peptide (PIP) due to the presence
of a TGF-β1 attenuating substance present in the platelet-
released fraction. Nonetheless, the net effect in vivo of plate-
let-concentrates containing the platelet-released fraction
is collagen synthesis as exemplified by numerous clinical
studies [8, 42, 45]. PRGF also lost the stimulatory effect on
collagen production at increasing concentrations, mandating
future research to determine the optimal therapeutic concen-
tration of the platelet-containing products [20, 23].
A second characteristic histologic change of photoaged
skin is a disintegration of elastic fibers (solar elastosis) [53].
Interestingly, both saline and PRP appear to replenish the
elastic fibers of the dermis, but PRP led to over 25% greater
increases in elastic fiber mean optical density (computerized
Archives of Dermatological Research
analysis of biopsy images) over saline [42]. In a 2015 study
by Diaz-Ley et al. [45], three PRGF injections reduced
histologic solar elastosis (p < 0.05) 6 weeks after the third
treatment, as determined by an independent, but unblinded
evaluator. El-Domyati et al. [8] further characterized these
changes in 2018, describing how the collagen generated by
PRP treatment led to a condensation and movement of the
older elastin fibers inwards from the dermo-epidermal junc-
tion towards the reticular dermis. The results of El-Domyati
et al. may be confounded by they using a combination treat-
ment of PRP with micro-needling, but they did utilize treat-
ment randomization and a blinded evaluation in comparing
of the effects to the micro-needling alone subgroup.
Photoaged skin displays epidermal changes that are either
atrophic flattening of the dermo-epidermal junction or acan-
thotic epidermal thickening [53]. Ultrasound, optical coher-
ence topography (OCT), and histologic studies have shown
that platelet-concentrate products cause an increase to epi-
dermal and papillary dermal thickness [8, 45]. This thick-
ness increase was shown in a RCT to be equal at 1 month
and superior at 6 months post injection when histologically
compared to mesotherapy injections [19], and to measure
260 µm in periorbital and 290 µm in perioral wrinkles on
a 4-month follow-up ultrasound [26]. Diaz-Ley et al. also
noted that increased histologic photoaging signs correlate
with greater increases in thickness post treatment, which
appears to conflict with Elnehrawy et al. [43] who found that
younger women demonstrated more improvement. However,
this discrepancy may reflect the pathophysiologic differences
in chronological aging and photoaging.
Another study utilizing ultrasound measured the sub-epi-
dermal low echogenic band thickness and density (SLEB).
In normal aging, this band between the epidermis and dermis
becomes larger and less dense and may be a sensitive marker
for age-dependent photoaging in the forehead shoulder [59].
Following PRP treatment by Everts et al. [25], the SLEB
increased in density and decreased in size of the SLEB at
both 2 and 6 months post treatment.
PRP stimulation of cutaneous hyaluronic acid is an addi-
tional possible mechanism of providing cosmetic effects.
Surprisingly, we did not find clinical trials containing an
analysis of hyaluronic acid following PRP injections. This
mechanism has been investigated with dermal fibroblasts
in vitro, demonstrating that PRGF, and not PPP, induces
statistically significant increases in hyaluronic acid [23].
Touted as providing long-term cosmetic results, PRP clin-
ical trials showed improved histology at 4, 6, and 12 weeks
after the final treatment, and at 6 months when using non-
invasive optical coherence topography. Future studies
should have long follow-up to compare the duration of effect
between platelet-containing products and the current FDA
approved treatments for photodamaged skin [8, 42, 45].
Periorbital hyperpigmentation
Seven included studies had a focus on the treatment of
periorbital hyperpigmentation (POH) [3, 7, 31, 38, 41, 44,
46], also referred to as under-eye bags, dark eye circles,
under-eye circles, periorbital melanosis, periorbital darken-
ing, periorbital hyperchromia, dark circles under the eyes,
dark eyelids, peripalpebral hyperpigmentation, tear trough
deformities, or pseudoherniated orbital fat pads. Risk factors
for POH may originate from genetics (e.g. family history and
midface anatomy variations), lifestyle (e.g. sleep-depriva-
tion, cigarette smoking, frequent cosmetic use or eye rub-
bing, lack of myopia correction), environment (e.g. excess
exposure to drugs, stress, or sun), and medical history (e.g.
nutritional deficiencies, hormonal factors, periorbital edema,
and anemia) [60–63]. POH has three main mechanisms of
pathogenesis, including (1) melanin pigment excess, (2) skin
translucency with hypervascularity, and (3) shadowing and
skin laxity [60–62]. Although the types of POH etiology
often overlap, future studies investigating POH should con-
tinue to report on the specific type of POH included.
The first mechanism of POH may arise from post-inflam-
matory hyperpigmentation as early as the 2nd decade,
especially in individuals with more melanin [46, 61]. This
subtype is delineated by physical exam showing a curved
band below the lower eyelid that decreases in darkness upon
stretching of the skin, or by biopsy or Wood’s lamp. These
diagnostic tools may demonstrate a blue–grey color for
excess melanin located in the dermis, or a brown color if epi-
dermal [60, 62]. PRP has efficacy in reducing the pigmenta-
tion via a proposed mechanism of TGF-β1 delaying the acti-
vation of extracellular signal-regulated kinase (ERK), and
EGF inhibiting prostaglandin-E2 expression and tyrosinase
activity [64–66]. Studies by Mehryan et al. and Kang et al.
[7, 31] both in 2014, used objective measures to quantify the
reduction of infraorbital melanin following PRP treatment.
Mehryan et al., using a Skin Surface ­Analyzer® device and
software (CK electronic, Germany and Dataderm Interna-
tional GmbH, Switzerland) showed that melanin changed
3 months after a single treatment from mean score of 272.44
and standard deviation 61.96 to a mean post-treatment score
of 244.95 and standard deviation 71.44 (p = 0.059). Using
3 treatments, Kang et al. showed by spectrophotometry that
the melanin index decreased from 34.42 to 31.86 (p < 0.01)
at 3 months after the final treatment, a finding that trans-
lated to all patients in their RCT being either slightly or
very satisfied, whereas patients receiving controls of plate-
let-poor plasma or saline predominantly rated their satis-
faction as “no change.” Additionally, they found that the
erythema index decreased from 8.52 to 7.37, (p = 0.01). In
a 2017 split-face RCT, Nofal et al. conducted the first con-
trolled clinical trial for this subtype, enrolling patients with
both vascular and melanin-based etiologies. They found no
13

significant difference between the improvements of PRP and
carboxytherapy efficacy; however, the carboxytherapy side
effects of edema and erythema were preferred to the PRP
side effects pain and ecchymosis [41]. In a 2019 RCT, Ella-
ban et al. [38] incorporated topical anesthesia in their PRP
treatment of hyperpigmentation. Although pain was not a
reported adverse effect, patients treated with PRP had lower
satisfaction levels than patients treated with a TCA 3.75%
plus lactic acid 15% chemical peel. Although the literature
is limited, it appears that PRP is less preferred than chemical
peels in patients aiming to reduce their excess melanin. The
treatment of this etiology of POH in patients who cannot
tolerate chemical peels represents a possible opportunity for
PRP, and PRP use with a topical anesthetic may reduce the
reported pain associated with the procedure.
In the second etiology of POH, subcutaneous vascular-
ity is visible due to translucency or thinning of the skin,
imparting a purple–blue dark circle to the lower eyelid. This
etiology is identifiable on exam by pressing on or stretching
the area [62], although it often occurs concurrently with an
excess of melanin. Vascular POH comprised approximately
half of the treatment group described in the Nofal et al. [41]
study, however, their study did not include a subgroup anal-
ysis to demonstrate whether their improvement from PRP
was applicable to this subgroup. While POH from increased
melanin appears to be better treated by chemical peels than
PRP, chemical peels are contraindicated in vascular POH,
for which PRP may still be an option [62]. PRP may pro-
vide benefits to vascular POH due to PRP’s angiogenesis
modulating components including proangiogenic VEGF and
antiangiogenic thrombospondin-1 (TSP1) [15, 67]. Addi-
tionally, PRP may improve the skin lucency by its actions
of activating fibroblasts, increasing collagen, and thickening
the epidermis and dermis [22–24].
The third subtype of POH is illusory in nature due to
skin laxity and pseudoherniated orbital fat pads and is
identifiable when the shadows worsen in certain types of
lighting. This POH is highly influenced by facial anatomi-
cal structure as well as alterations in bone, ligament, and
soft tissue anatomy [62, 63]. Proposed in 2012 to work as
a filler by subdermal or dermal injections [47], PRP was
first examined for treating the under-eye rings, lower eyelid
volume deficit, and excess lower eyelid skin by Aust et al.
in 2018 [3]. Their cohort of 20 patients found PRP to be
pain-free and were either satisfied or very satisfied with
their 3 monthly treatments. Trials have yet to examine the
second-generation platelet gels, PRF products, for this sub-
type of POH, although the platelet gel may hold the most
potential of platelet-concentrate products for volume-filling
applications [26]. A retrospective study showed that when
combined with bFGF, these improvements persisted for over
4 years, although this duration accompanies a risk of over-
correction theorized to be due to the bFGF [68]. Another
13
Archives of Dermatological Research
retrospective study found that adjunct treatment of PRP
with lipofilling and lipofilling with minimal access cranial
suspension (MACS) lift showed statistically significant cos-
metic improvement over the lipofilling alone and lipofilling
with MACS groups [51]. Another method of using PRP as
an adjunct treatment is by combination with hyaluronic acid,
for which the combined treatment has been proposed to be
superior to either treatment alone [44].
Effects of age on PRP efficacy
Elnehrawy et al. [43] found that the population whose wrin-
kles improved the most by their single PRP injection was
women less than age 40. Interestingly, the study of treat-
ment efficacy in photoaging found a seemingly opposite age-
related correlate, whereby less photoaged skin responded
less to PRP [45]. Future research may aim to elucidate these
findings of the limited number of studies analyzing improve-
ment by age. Possibilities to consider include pathophysi-
ologic differences between photoaging and normal aging,
psychosocial factors, such as younger age groups, reporting
disproportionate satisfaction on subjective measures, and
age-related considerations, such as how shallower wrinkles,
improved more consistently than deeper wrinkles [43], or
that younger, less damaged skin is able to respond better to
the treatment.
Patient satisfaction
Although a subjective measure, patient satisfaction is an
important and necessary consideration for cosmetic treat-
ments. Our meta-analysis demonstrates that patients are
consistently satisfied with treatment of PRP when it is
applied to the periorbital area. Additionally, the satisfaction
is increased over control injections and is additive to other
cosmetic treatments when PRP is used as an adjunct treat-
ment. Because pain can deter patients from continuing with
regular PRP treatments, mechanisms of reducing the burning
sensation should be considered, such as the use of topical
anesthetics. Treatment with PRP is often followed with use
of a topical application, such as PPP, or polypropylene film
facemasks, which may improve the patient’s experience.
Combination of the satisfaction scores of studies is difficult
due to the use of numerous scales, and future studies should
consider use of an existing scale, such as the most commonly
used 4-category 0–3 scale [3, 19, 26, 31, 39, 40, 44].
Adverse effects
As an autologous-based product, PRP injections provide
a minimal risk to the patient. No study reported infection,
Archives of Dermatological Research
allergy, or post-inflammatory hyperpigmentation, which
is supported by a study on androgenic alopecia that found
that PRP injections improved bacterial skin infections [69].
One study did report a patient who had a slight increase in
fine wrinkles 1 month post treatment of the nasolabial fold
[39]. Mild side effects attributable to any dermal injection
are to be expected, and include erythema, pain, a burning
sensation, ecchymosis, swelling, a feeling of pressure, and
tenderness. The addition of calcium chloride without use
of topical anesthetics may produce pain significant enough
for patients to prefer alternative treatments [41], however,
the addition of a topical anesthetic to PRP led to patients
reporting no pain [3].
Limitations
This study has several limitations that should be addressed.
Assessment of PRP results is complicated by heterogeneity
in PRP preparation and injection protocols, outcome meas-
urement devices, as well as in subjective scales for satisfac-
tion. While most studies used a 4-category scale to assess
patient satisfaction, the scales were often unique to the study.
Assessments of improvement are also limited by a prepon-
derance of studies with short-term follow-up, industry fund-
ing, conflicts of interest, and RCTs with high risk of bias.
Conclusion
The past decade has seen a growing interest in PRP applica-
tions for dermatologic cosmetic pathologies. Histologic and
patient satisfaction scores show that this treatment has prom-
ise for the applications of periorbital wrinkles, periorbital
hyperpigmentation, and skin photoaging. The current litera-
ture is limited by a low number of high-quality studies and
the presence of protocol heterogeneity. Further RCTs with
high-quality reporting and low risk of bias are needed to
examine platelet-concentrate products for the various peri-
orbital pathologies. Finally, RCTs with long-term follow-up
and comparing platelet-concentrate products to non-saline
controls are needed to elucidate the sustained improvement
provided by PRP and its role in treating periorbital cosmetic
pathologies.
Author contributions The project was conceptualized and designed by
AE and SAK. The search strategy was designed by AE, MI. The search
was performed by MI and BH. Article selection was done by AE and
MI. Data extraction was performed by AE, MI. Tables were made by
AE, MI, RP. Meta-analysis was performed by AE, MB. Figures were
made by AE, MI, and MB. The first draft was written by MI. Revisions
to writing were performed AE, RP, GG, RG, SAK.
Funding This research received no funding.
Availability of data and material The full search strategy is available
as Online Resource 1.
Compliance with ethical standards
Conflict of interest The author Mirjana Ivanic had dual affiliation at
the time of this research at both Meharry Medical College and Vander-
bilt University Medical Center.
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