Biomedical Engineering Reference
In-Depth Information
tolerated and that no signifi cant differences in the side effect
profi les were observed. This study was important not only for
its demonstration and safety of IPL in the use of ALA-PDT,
but for the development of a photodamage rating scale.
Another split-face comparative study for photorejuvenation
using ALA-IPL versus IPL alone was performed by Gold and
coworkers (169). Thirteen patients received short-contact
ALA-IPL on one side of the face and IPL alone on the contra-
lateral side. Photoaging categories, including fi ne wrinkling
(crow's feet), tactile skin roughness, mottled pigmentation,
telangiectasias, and AKs, were evaluated. All demonstrated a
better response on the side of the face treated with ALA-PDT.
This study also confi rmed the enhancing effects of ALA-PDT
in IPL photorejuvenation.
Marmur et al. (180) conducted a pilot study to assess the
ultrastructural changes seen after ALA-IPL photorejuvena-
tion. Seven adult subjects were treated with a full-face IPL
treatment. Half of the face in the study subjects received pre-
treatment with topical ALA before the IPL treatment. Pre- and
posttreatment biopsies were reviewed by electron microscope
for changes in collagen. A greater increase in type I collagen
was noted in the subjects that were pretreated with ALA-IPL as
opposed to the group treated with IPL alone. They concluded
that the addition of ALA-PDT using IPL could be superior to
IPL alone.
A study by Serrano et al. (181) in 2009 examined the use of
ALA-IPL for the treatment of acne, vitiligo, and photoaging.
Twenty-six patients in total completed the study, eight of which
were in the photoaging treatment arm. Low-concentration
ALA (1-2%) was used for incubation prior to light exposure.
Improvement in several photoaging parameters were noted in
the majority of patients. One hundred percent of cases had
skin texture improvement; erythema/telangiectasia and hyper-
pigmentation were improved in 85% and 90% of cases, respec-
tively. Eighty-eight percent of patients were satisfi ed with the
results after three sessions of ALA-PDT.
Regarding treating patients with Fitzpatrick skin types III
and IV, particularly Asians, a double-blind split-face con-
trolled study examined the safety and effi cacy of ALA-IPL
PDT (182) using lower concentrations of ALA. Twenty-six
patients were pretreated with 5% and 10% (regions with severe
photodamage) ALA cream applied to half of the face for 1 hour
followed by full-face IPL (520-1200 nm) treatment. Three
treatments at 1-month intervals were done followed at 1 and
2 months after the fi nal treatment. Higher success rates for fi ne
lines and coarse wrinkles were seen on ALA-IPL PDT side at
the fi nal visit. However, postinfl ammatory hyperpigmentation
was higher on the ALA-IPL PDT side (22%) than on the IPL-
only side (15%), although this was transient (2 months) and
reversible. The authors concluded that by using ALA in low
concentration (5%), incubation time as short as 1 hour and
relatively low energy of IPL irradiation (on average 15 J/cm 2
for double-pulse mode and 19 J/cm 2 for triple-pulse mode) sat-
isfactory results could be achieved in patients with Fitzpatrick
skin types III and IV.
according to the theory of selective photothermolysis. But ther-
mal energy generated in the surrounding areas adjacent to tar-
geted blood vessels may also result in photorejuvenative effects.
Subpurpuric doses from the PDL alter dermal collagen and may
improve skin texture (47).
Alexiades-Armenakas et al. (73) found ALA-PDT with the
595 nm PDL was successful in treating face and scalp AKs.
Additionally, in this large study of 2561 lesions, areas treated
showed signs of photorejuvenation.
Key (183) treated 14 patients with long-incubation ALA
(12 hours) followed by photoactivation using a PDL. Improve-
ment was noted following ALA-PDL in terms of skin texture,
tactile quality, and brown spots, although the degree of vascu-
larity and seborrheic keratoses were unaffected by treatment.
The lack of improvement in blood vessel lesions is curious
given that PDL targets the vasculature.
Combination Therapy for Photorejuvenation
A combination of microneedling roller (108
μ
m in width and
300
m in depth) prior to ALA incubation (1 hour) to maxi-
mize epidermal penetration and irradiation of both red light
(630 nm) and broadband pulsed light in a single treatment has
been studied in 21 patients by Clementoni and colleagues
(184). At 6 months posttreatment, 76.2% scored themselves an
overall improvement greater than 75% and statistically signifi -
cant improvement was observed in the global photoaging
scores, fi ne lines, mottled pigmentation, sallowness, tactile
roughness, and telangiectasias at 3 months posttreatment.
Enhanced effi cacy of PDT after fractional resurfacing was
observed by Ruiz-Rodriguez (185) in four patients treated in
the perioral area. Two sessions of a 1550 nm fractional laser
were immediately followed by MAL-PDT (3 hours occlusion,
illumination with red LED 634 nm, 37 J/cm 2 ) on half of the
perioral area. Twelve weeks after last treatment, a blinded inves-
tigator found increased improvement in superfi cial wrinkles in
three out of four patients on the combined treatment side.
A study by Hædersdal and colleagues has demonstrated
enhanced delivery of topical MAL deeply into in vivo porcine
skin with ablative fractional CO 2 laser (186). They found sig-
nifi cantly higher PpIX fl uorescence throughout the entire skin
depth where pretreatment with CO 2 ablative fractional laser
was performed before MAL-application, compared with con-
ventional topical MAL application, suggesting that ablative
fractional resurfacing could be a clinically practical means for
enhancing uptake of MAL and even many other topical skin
medications.
μ
Summary of Findings for ALA- and MAL-PDT
in AK Treatment and Photorejuvenation
These results show the potential usefulness of a variety of
lasers and light sources in the treatment of AKs and in the
improvement of photodamage and photorejuvenation utiliz-
ing ALA- and MAL-based PDT treatments. Current studies
have been focused on novel photosensitizer drugs and refor-
mulations of ALA, such as nanoemulsions or patch-based
applicators, with ALA patch PDT appearing to be superior to
cryosurgery in the treatment of mild-to-moderate AK (187).
Beyond the treatment of AKs, ALA- and MAL-PDT offer benefi -
cial cosmetic outcomes in photorejuvenation.
PDT with PDL
PDLs have also been studied as a light source for photorejuvena-
tion in ALA-PDT. PDL targets oxyhemoglobin as a chromophore
 
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