Skin Vascular Lesions - a new therapeutic option with sequential laser-assisted technique

Running head: 755nm Alexandrite & 1064nm ND:YAG laser

Nicola Zerbinati 1 , Marina Protasoni 1 , Edoardo D’Este 2 , Roberto Mocchi 3 , Luigi Coricciati 4 ,

Raffaele Rauso 5 , Paolo Sbano 6 , Maurizio Greco 2 , Eleonora Rodighiero7, Francesca Satolli 7, 8

1
University of Insubria, Department of Medicine and Surgery, Varese, Italy.

² Centro Medico Polispecialistico, Pavia, Italy.

3
UB - CARE S.r.l. - Spin - off University of Pavia, Pavia, Italy
4
Coricciati Medical Group – Martano- Lecce, Italy
5
Maxillofacial Surgery Unit, University of Campania “Luigi Vanvitelli”, Naples, Italy
6
Medical Science Department, University of Siena, Italy
7
Section of Dermatology, Department of Medicine and Surgery, University of Parma, Italy.
8
Dermatologic Unit, University Hospital of Parma, Parma, Italy

Corresponding author:
Satolli Francesca

fra.satolli@libero.it

Section of Dermatology, Department of Medicine and Surgery, University of Parma, Italy.

via Università, 12 - I 43121 Parma

tel. +390521902111

Dermatologic Unit, University Hospital of Parma, Parma, Italy.

Via Gramsci 14 – 43126 Parma

This article has been accepted for publication and undergone full peer review but has not been
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differences between this version and the Version of Record. Please cite this article as doi:
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Tel(+39) 0521.702111 / (+39) 0521.703111

Abstract
Treatment of skin unaesthetic vascular lesions is still suboptimal. In this paper we present a multi-
center study evaluating the efficacy and safety of the sequential 755nm Alexandrite and 1064nm
ND:YAG lasers for the treatment of acquired and congenital vascular lesions of the skin. 171 patients
were included in the study (141 female and 30 male), median age 38, skin type from I to IV. Numbers
of patients categorised for treated disease: 22 Spider angiomas, 67 Facial Telangiectasia/ Spider veins,
58 Leg Telangiectasia/ reticular leg veins, 24 PWS. Of those lesions 30.7% was on legs, 63.7% on
face (6.7% on forehead, 10.1% on temples, 21.7 % on cheeks, 25.2% on nose, 1.7 % on chin) and
5.6% on chest. Spider angiomas required from 1 to 3 treatments. Facial telangiectasias had been
treated from 1 to 4 times. Leg telangiectasias needed from 2 to 6 treatment sessions. Regarding Port
wine Stains it takes from 6 to 9 laser treatment to reach the clearance of the lesion. All the vascular
disorders treated showed marked improvement while side effects were limited to low pain sensation
and transitory fenomena. This sequential treatment is an effective, safe and new approach for
unaesthetic skin vascular lesions.

Keywords
vascular lesion, treatment, laser, sequential laser, Alexandrite 755nm, ND:YAG 1064 nm

Conflict of interest
The authors declare that they do not have any conflict of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon
reasonable request.

Funding information statement

No funding

Ethical Statement
Patients recruited for this study were volunteers from the Dermatological Clinics. They offered to
participate prior to obtaining authorization from the ethics committee informed consent and a written
authorization to be included in their medical records according to Helsinki declaration.
Introduction

Background

All dermatologic clinics have patients presenting for the treatment of vascular lesions (1-3).
According to occurrence, vascular lesions can be classified into two main groups: acquired and
congenital. Acquired vascular lesions include telangiectasias, spider angiomas, cherry angiomas,
Poikiloderma of Civatte, leg veins, and other minor anomalies. Congenital vascular lesions can be
divided into two main categories: haemangiomas and vascular malformations, such as Port Wine
Stains (PWS) (3-6). Currently, there are several treatment options such as sclerotherapy, topical
and/or intralesional steroids, electrocautery and light-based treatments. Regarding the light-based
devices, multiple light-based devices had been used to treat vascular lesions. The 532 nm KTP laser
is reported to be efficient for treating superficial vascular lesions in patients with skin types I-IV (7,
8). Pulsed Dye Lasers such as 585/595 nm have been used widely for superficial vascular lesions (9,
10). PDL lasers especially with shorter pulse widths may produce purpura (11). Among light sources,
1064nm Nd:YAG is considered the gold standard for the treatment of lower extremity vascular
lesions: with the potential of adverse effects such as hyper or hypopigmentation, scarring,
hypertrophic scarring and ulcerations (12, 13). The 755 nm long pulse Alexandrite laser has reported
to be effective on hypertrophic and resistant Port Wine Stain (14), even on lesions refractory to PDL
treatment (15). The challenge with the Nd:YAG in vascular lesions is the narrow therapeutic window.
Increasing the fluence beyond the purpuric dose can result in damage, dermal blisters and scarring.
To decrease the risk of side effects, Nd:YAG 1064 nm has been used in combination with other
wavelengths. Few studies reported the combination of 1064nm with other wavelengths in vascular
lesion treatments to reduce the amount of ND:YAG 1064nm energy. It is reported the usage of 585nm
wavelength in combination with Nd:YAG 1064 nm on PWS (16,17) and the usage of 1064nm
Nd:YAG and 755nm Alex sequentially in the treatment of Rosacea (18). The effectiveness is linked
to the 755 nm preferential target for de-oxyhaemoglobin (DHB), which provides a potential
advantage in the treatment of blood vessels. The aim of this study is the investigation of the efficacy
and the safety of sequential emission of Alexandrite 755nm and Nd:YAG 1604nm wavelengths in
treatment of spider angiomas, spider veins, leg telangiectasias and PWSs.

Materials and Methods

This is a retrospective, multi-center study evaluating the efficacy and the safety of the sequential
755nm Alexandrite and 1064 nm Nd:YAG laser for the treatment of acquired and congenital vascular
lesions. Data for this retrospective study were obtained from three different private clinics. Between
November 2015 and March 2019, subjects were treated with long-pulse 755nm and 1064nm. The
three different sites used two devices equipped with the same technology: long-pulse Nd:YAG 1064
nm and long-pulse Alexandrite 755 nm were on both devices equipped with Mixed Technology
(Duetto MT and Thunder MT, Quanta System Spa, Samarate, Varese, IT). Both devices have been
used in sequential emission: first 755nm Alexandrite, followed by 1064nm Nd:YAG. Common
parameters for both devices have been used (see table 1). The vascular lesions reported in this study
belong to 4 different vascular anomalies: Spider angiomas, facial telangiectasia or spider veins, leg
telangiectasia (or reticular leg veins), and PWS classified following the CEAP classification for
venous disorders revision of 2004 (19). Medical reports of each initial visit and 6 months follow visit
were reviewed to evaluate the effectiveness and safety in this study. Three different cameras were
used to collect pictures post-treatment every session (Lumix DMC-FZ100, Panasonic, Osaka, Japan;
PowerShot G1 X Mark II, Canon, Tokyo, Japan; Cyber-shot DSC-RX100 III, Sony, Tokyo, Japan).
Chi-square test was used for comparing outcomes of treatments. One-way ANOVA test was used for
comparing means of ages of patients with each diagnosis. In all cases, the statistical significance level
was set at P < 0.05. The present study was conducted by approval of the local ethics committee.
Inclusion criteria
Subjects were screened for the following inclusion criteria: Informed consent for laser treatment and
permission to use clinical data for scientific investigations (i), reported limited sun exposure for the
duration of the treatments (the patients reported to avoid direct contact to the sunlight and in case of
exposure usage of Sun Protector Factors, minimum SPF 15) and follow-up periods, usage of Sun
Protector Factors (minimum SPF 15) (including the follow-up period), electronic standardised case
report form (CRF) with photographic records for every laser session, only patients with all data
available were included in this study.
Exclusion criteria
Common exclusion criteria for laser vascular treatments in all the centers were: pregnancy, current
use of photosensitive or anti-coagulant medications, tan presence, diabetes mellitus, cardiovascular
diseases, prior treatment with laser or other devices in the treatment area, taking of retinoids or
isotretinoin within the preceding 6 months, wounded skin, epilepsy/seizures subjects that the
physician determines ineligible based on the standard of care treatment. Patients with vascular lesions
on legs were evaluated with Echo-Color Doppler to exclude the presence of deep venous insufficiency
through evaluation of GSV (Great saphenous vein) and to visualise directly the direction of the flow,
before performing the laser treatment.
Treatment Protocols
All treatments were performed in sequential emission with Alexandrite pulse followed by Nd:YAG.
All treatments have been performed starting with the lower fluences, increasing them in the following
sessions. Delay between 755nm Alexandrite and 1064nm Nd:Yag pulses was related to the target
vessel diameter, because the total time of exposure (pulse width of the 755nm+delay+pulse width of
the 1064nm) of the vessel has to be related to his Thermal Relaxation Time. A test dose was
performed at initial consultation and, therefore patients were reviewed and treated after 30 to 45 days.
All lesions have been treated with a single-shot technique, avoiding more than 10% overlap. All
fluences are reported below. Clinical endpoints for Leg Telangiectasias, Face telangiectasias and
Spider Angiomas were blue or light grey colour change of the target vessels due to photo coagulation.
Successful endpoints for the Port Wine Stains was the colour change of the lesions to light grey or
blue without whitening of the surrounding tissues. Successful treatments are linked to presumed
complete intravascular coagulation to ensure the capillary does not re-canalize or regenerate.
The range of all treatments recorded is shown in Table 1.
● In spider angiomas, we started from 25 J/cm2 of Alexandrite and 1064 nm Nd:YAG from 100
J/cm2. If the vessels were not cleared, we increased both the fluence by increments of 5 J/cm2
for the 755nm Alexandrite and by increments of 10 J/cm2 for the 1064 nm Nd:YAG. The
maximum fluences reported were 35 J/cm2 of Alexandrite and 180 J/cm2 of 1064 nm
 Nd:YAG. 10 ms of pulse duration for 755 nm Alexandrite was used, followed by a 5 ms delay,
15 ms of pulse width for 1064 nm Nd:YAG. We used 5 mm spot for the central vessels and
4 mm for the radiating vessels. Dark-blue vessels reported 20% lower fluences compared to
reddish vessels. Highest fluences were reported on smaller vessels.
● In facial telangiectasias (spider veins on the face), we started from 24 J/cm2 of Alexandrite
and 80 J/cm2 of 1064 nm Nd:YAG. If the vessels were not cleared, we increased both the
fluence by increments of 2 J/cm2 for the 755 nm Alexandrite and by increments of 10 J/cm2
for the 1064 nm Nd:YAG. The maximum fluences reported were 36 J/cm2 for the 755 nm
Alexandrite and 160 J/cm2 for the 1064 nm Nd:Yag. 8 ms of pulse duration for 755 nm
Alexandrite was used, followed by 3 to 5 ms pause and 8 ms of pulse width for 1064 nm
Nd:Yag with 4 mm spot size. On the nose and the forehead fluences reported were 20% lower
than other face areas.
● In leg telangiectasias, we started from 24 J/cm2 of 755nm and from 70 J/cm2 for the 1064 nm
Nd:YAG. If the vessels were not cleared, in the following sessions, we increased both the
fluences by increments of 2 J/cm2 for the 755 nm Alexandrite and by increments of 10 J/cm2
for the 1064 nm Nd:Yag. The maximum fluences reported were up to 36 J/cm2 for the 755
nm Alexandrite and up to 150 J/cm2 for the 1064 nm Nd:Yag. 6 ms of pulse duration for 755
nm Alexandrite, followed by 2 to 4 ms of delay 8 ms of pulse duration for 1064 nm Nd:Yag
were reported. The delay time was related to the vessel diameter. The bigger the vessel the
longer the delay set within the two pulses. Due to scattering effect, bigger spot sizes were used
on deeper vessels.
● In PWS, we started from 20 J/cm2 of Alexandrite and 22 J/cm2 for the 1064 nm Nd:YAG. If
the vessels were not cleared, we increased both the fluences by steps of 2 J/cm2 for the 755
nm Alexandrite and, firstly, by steps of of 2 J/cm2 and then by steps of 5 J/cm2 for the 1064
nm Nd:YAG. The maximum fluences reported were 30 J/cm2 for the 755 nm Alexandrite and
60 J/cm2 for the 1064 nm Nd:YAG. 5 ms pulse duration for the 755 nm Alexandrite, followed
by 3 ms of pause and 3 ms of pulse duration for the 1064 nm Nd:YAG were reported for thin
and light lesions. with 5 to 8 mm spot sizes. Shorter durations have been reported on light
and thin lesions and longer durations on dark and thick lesions. The thicker and the darker
were the lesions, the longer were reporter pulse durations: up to 7 ms pulse duration for the
755 nm Alexandrite, followed by up to 5 ms of pause and up to 5 ms of pulse duration for the
1064 nm Nd:YAG. 5 and 6 mm spot size were used on thinner and lighter lesions, 7 and 8
mm spot sizes were used on thicker and darker lesions.
Air-cooling system speed went from 2 to 4 on the face and from 4 to 6 on other body areas (Cryo 6,
Zimmer, Neu-Ulm, Germany).
Spider technique has been used as the application technique (follow the vessel to be treated, starting
from the vascular source of the lesion).
Evaluation
Three external consultant dermatologists, experts in vascular treatments, evaluated the grade of the
response of the vascular lesions comparing the pre-treatment pictures before the start of the laser
treatments (T0) with the post-treatment pictures at the end of the laser treatment sessions (T1) and
categorized on four classifications based on photographic records taken under the same conditions.
The assessment of therapeutic response and grading of improvement was done with a scale from I to
IV.
 ● E-IV = marked improvement (removed between 75% and 100% of the lesion);
● E-III = partial improvement (removed between 50% and 75% of the lesion);
● E-II = mild improvement (removed between 25% and 50% of the lesion);
● E-I = poor improvement (removed of less than 25 % of lesion);
6 months after the end of the treatment series, the patients were required to complete a questionnaire,
rating their satisfaction level. The patient had to report if they were, very satisfied (VS), satisfied (S),
slightly satisfied (SS), or unsatisfied (US).

Results
171 patients were included in the study (141 female and 30 male) median age 38 (8 – 69) years;
Fitzpatrick skin type from I to IV. The number of participants divided for Fitzpatrick skin type
classification was: 9 (5.2%) Skin type I, 51 (29.4%) skin type II, 86 (50.2%) skin type III and 25
(15.2%) skin type IV. Results of the evaluation and media of sessions are reported in table 2.
The differences of improvements was statistically significant (P<0.05)
Examples of E-IV for leg telangiectasia and spider veins are illustrated in figures 1 and 2.
The time between each treatment went from 30 to 45 days. At the follow-up, patients reported: 2.34
% unsatisfaction for the treatment results (US), 13.45% slightly satisfaction (SS), 32.16% satisfaction
(S), and 52.05% very satisfied by the treatment results (VS).
Numbers of patients categorised for treated disease: 22 Spider angiomas, 67 Facial Telangiectasia/
Spider veins, 58 Leg Telangiectasia/ reticular leg veins, 24 PWS. Of those lesions 30.7% was on legs,
63.7% on face (6.7% on forehead, 10.1% on temples, 21.7 % on cheeks, 25.2% on nose, 1.7 % on
chin) and 5.6% on chest.
Spider angiomas required from 1 to 3 treatments. Facial telangiectasias had been treated from 1 to 4
times. Leg telangiectasias needed from 2 to 6 treatment sessions. Regarding Port wine Stains it takes
from 6 to 9 laser treatment to reach the clearance of the lesion.
5% Lidocaine cream was used for topical anaesthesia EMLA 5% (2.5% Lidocaine, 2.5% prilocaine)
60 minutes before laser therapy in only some patients. Application of corticosteroid (momentasone
furoate ointment, Elocon 0.1%, MSD, New Jersey, USA) was prescribed once a day for 20 days to
patients that reported swelling.
Side effects were collected from patient case report forms (CRF). Most patients had mild transitory
reactions like redness or erythema, but they resolve usually in hours or days. Were reported 91 cases
of side effects: of these (n.3) 3.3% had purpura, (n.69) 75.82% temporary erythema, (n.2) 2.2%
blistering, (n.10) 10.99% Erosion and crusting, (n.6) 6.59% transient post-inflammatory
hyperpigmentation and (n.1) 1.1% scar. The majority of the side effects were reported in the leg
treatments (n.54 – 59%), where higher fluences were used.

Discussion
There are numerous variables for evaluating laser in the treatment of vascular lesions. When choosing
a laser for treating vascular lesions, several parameters need to be considered: vessel depth and
diameter, laser wavelength, pulse width, and spot size. The wavelength used needs to have sufficient
penetration depth for the target vasculature. The pulse duration depends on the target vessel diameter
(20,21). While clinical results are considered satisfactory in most cases, there is no agreement on
optimal pulse duration, fluence, or spot size when it comes to treat vascular lesions. A review of the
literature indicates that a wide range of parameters is applied. In particular, fluences range from 90
J/cm2 to 400 J/cm2, with a pulse width from 10ms to 100ms and spot size from 1 to 10 mm. Clark et
al. (22) reported the use of the Nd:YAG laser in the treatment of superficial cutaneous vascular
lesions. They treated 246 lesions in 204 patients, the most commonly treated lesions being spider
angioma (102) and telangiectasias (102). They reported marked improvement or clearance in 84% of
lesions. These are very good results in a large series of patients and compatible with our series. Thus,
our results are comparable with the ones of this study. Eremia and Li (23) treated face veins with the
Nd:YAG laser in 17 patients and reported a greater than 50% improvement in all patients. Weiss and
colleagues had between 50-75% of improvements in patients with leg telangiectasia and reticular
veins with 85% of darkening and 50% of bruising (24). No long-term complications were reported in
this study. Trelles and colleagues reported from good to very good improvements (> 51% clearance
of the lesion) in 47 of 60 patients treated with 585 PDL and 1064 Nd:YAG after 6 months and two
treatment sessions in which they provide more than one pass on leg telangiectasia (25). Fodor et al
state they had satisfactory results on 72% of patients treated with Nd:YAG and 48% in patients treated
with IPL on several vascular lesions (telangiectasia, cherry angiomas, and leg veins) (26). Goldberg
et al in their 40 patients study found no difference between different wavelength lasers on facial
telangiectasia, this is probably due to the light skin type of the patients (skin type I and II) (27). In
light of the wide variance in clinical laser, there continues to be an ongoing discussion in the field of
laser science as to which laser parameters are optimal to treat vascular lesions effectively while
maintaining a low side-effect profile.
Limitations
Being a retrospective analysis study is the most important limitation of this study. Secondly, we did
not have data recordings of the efficacy related to the diameters of vessels.

Conclusion
Our experience reported the effectiveness of 755nm Alexandrite and 1064nm Nd:YAG used
sequentially and resulted in several important findings. All the vascular diseases treated had
improvement. The first shot of Alexandrite turns the haemoglobin to methaemoglobin due to the
heme component of the blood, as discussed by Mordon and colleagues (28), after this first shot if the
vessel was red, it turns to blue, this conversion raises the absorption coefficient of the vessels for the
second laser shot provided through Nd:YAG. Nd:YAG is three times more absorbed by
methaemoglobin compared to Alex (29), and this explains the efficacy with lower fluence parameters.
Mixed Technology enables to treat vascular lesions with both red and blue vessels in all body areas.
The sequential application of 755nm Alexandrite and 1064nm Nd:Yag is safe and effective on several
vascular lesions, in particular on reddish vessels, and could be the technique of choice in case of
patients with light skin type (from I to IV) and with low pain sensation level. Furthermore, this
emission technique allows to lower the fluences of same treatments provided by Nd:Yag alone.
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 Type of Spot Pulse Starting Delay Pulse Starting Total
lesion/diameter sizes duration Fluence (ms) duration 1064 Fluence Pulse
(mm) (mm) 755nm 755 nm nm Nd:Yag 1064 nm Width
(ms) (J/cm2) (ms) (J/cm2) (ms)
Spider angioma 4-5 10 25 5 15 100 30
Facial 21-23
4 8 24 3-5 8 80
Telangiectasia
Leg 16-18
4-5 6 24 2-4 8 70
Telangiectasia
PWS 5-8 3-5 20 5-7 5 22 13-17
Table 1: Treatments strating parameters
 Evaluation at follow-up Laser session median n°
E-IV E-III E-II E-I Median sessions needed
(%) (%) (%) (%) to reach the clearance or
the responsive plateau
(SD)
Spider angiomas 20 - 2 -
n=22 (90%) (10%) 1.3(±0.5)

Facial Telangiectasia/ Spider veins 52 11 4 -

n=67 (77.6%) (16.4%) (6%) 3(±1)

Leg Telangiectasia/ reticular leg veins 38 9 5 6

n=58 (65.6%) (15.5%) (8.6%) (10%) 4(±0.8)

PWS 2 8 9 5
n=24 (8.3%) (33.3%) (37.6%) (20.8%) 8.3(±1)

Table 2: Treatment evaluation results and number of sessions

Figure 1: (a) Leg telangiectasia of a patient before treatment, (b) leg telangiectasia in the patient after second
session of the treatment, category- E-I (75-100% improvement of the lesion).

Figure 2: (a) facial telangiectasia of a patient before the treatment, (b) facial telangiectasia in the patient
after third session of the treatment, Category E-I (75-100% improvement of the lesion).
Accepted Article

Figure 1: (a) Leg telangiectasia of a patient before treatment, (b) leg telangiectasia in the patient after
second session of the treatment, category- E-I (75-100% improvement of the lesion).

94x42mm (300 x 300 DPI)

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Accepted Article

Figure 2: (a) facial telangiectasia of a patient before the treatment, (b) facial telangiectasia in the patient
after third session of the treatment, Category E-I (75-100% improvement of the lesion).

73x28mm (300 x 300 DPI)

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