Biomedical Engineering Reference
In-Depth Information
PDT with Blue Light
Despite the shallow penetration of blue light, it still appears to
improve the signs of photoaging following ALA-PDT. The fi rst
indication that blue light had photorejuvenative effects in PDT
was with the phase II/III clinical trials for FDA-approval of
Levulan for nonhyperkeratotic AKs. In these studies, signifi -
cant improvement in the signs of photoaging were noted after
treatment (68,78,171).
Photorejuvenation studies using the blue light source have
also been conducted by Goldman and Atkin (72), where a blue
light source was used to illuminate the face after the topical
application of ALA. Thirty-two patients with photodamage
and AKs were treated with one session of ALA-PDT using a
1-hour ALA incubation followed by Blu-U activation. AKs
showed a 90% improvement in terms of photorejuvenation
parameters, a 72% improvement in skin texture, and a 59%
improvement in skin pigmentation. Gold (79) reported on the
dual use of blue light ALA-PDT for AKs and photoaging. The
treatment of nonhyperkeratotic facial AKs also resulted in an
improvement of skin elasticity and texture in patients with
photodamaged skin.
Touma et al. (22) studied the effectiveness of ALA and blue
light illumination in the treatment of AKs and diffuse photo-
damage. Eighteen patients with facial nonhypertrophic AKs
and mild-to-moderate facial photodamage were evaluated.
Short-contact ALA was applied from 1 to 3 hours with subse-
quent exposure to blue light. At 1 and 5 month follow-up
intervals, there was a signifi cant reduction in AKs. In addition,
marked improvement in photodamage parameters, such as
skin quality, fi ne wrinkling, and sallowness, were observed.
Other markers of photodamage, such as pigmentary changes
and coarse wrinkling, showed little to no improvement.
Patients were also satisfi ed with the procedure, with 80% of
patients rating their results as good to excellent. Other fi ndings
make this an intriguing study. This clinical study was pivotal in
shifting treatment of AKs from long, 14- to 18-hour incuba-
tion times to shorter contact times. In addition, study patients
were pretreated with microdermabrasion prior to topical ALA
application, leading to more uniform and rapid penetration
of ALA.
A fi nal study by Smith and coworkers (81) examined the use
of blue light ALA-PDT in diffuse photodamage. As discussed
in the AK section of this chapter, this study was a three-arm
study comparing topical, low concentration 5-FU to two forms
of short-contact ALA-PDT—one arm with activation from a
blue light source, the other with a PDL. While one patient in
the 5-FU group discontinued due to a confl uent erythematous
reaction, all patients in the ALA-PDT group completed the
study. In both ALA-PDT groups, patients experienced improve-
ment in global photodamage, hyperpigmentation, and tactile
roughness. The ALA-PDL was more successful in treating pig-
mentation, while blue light had lower response rates to global
photoaging. Interestingly, the blue light ALA-PDT was the
only treatment arm to have photoaging completely resolved in
one patient.
cosmetic results. Zane and colleagues (173) evaluated the
effi cacy and tolerability of MAL-PDT in 20 patients with mul-
tiple AKs and photoaging of the face. Two treatments (MAL
under occlusion for 3 hours before red LED 37 J/cm
2
) were per-
formed at 1-month interval. The clearance rate of AKs found
was 88.3%, and global improvement was observed in mottled
hyperpigmentation, fi ne lines, and roughness of the skin.
A recent randomized, clinical, histopathologic, and morpho-
metric study by Issa and colleagues (174) using MAL-PDT and
red light (LED 635 nm, 37 J/cm
2
) evaluated 14 patients treated
with two sessions, 4 weeks apart. Clinical improvement with
regard to texture, fi rmness, wrinkle depth, skin coloration, and
AK was observed. Histopathologic and morphometric studies
were consistent, showing increased collagen fi bers, and decrease
in the fragmented elastic fi bers 6 months after treatment.
One small pilot study conducted by Lowe and Lowe (175)
investigated the use of ALA-PDT for the treatment of photo-
aging on the forearm and periorbital region. Escalating con-
centrations of ALA (5-20%) and increasing incubation times
(30-120 minutes) were used prior to light irradiation with a
red light source (633 nm). Mild improvement in signs of pho-
toaging was noted at 7 days following treatment.
A histologic and immunohistochemical analysis conducted
by Park and colleagues (176) in 14 patients with AKs and pho-
todamage treated with ALA-PDT (twice at 1-month interval,
using red light 580-740 nm, dose of 100 J/cm
2
, 100 mW/cm
2
)
showed signifi cant increase in type I and III procollagen
expression. Elastotic material with fi brillin-1 and tropoelastin
expression in the dermis decreased after treatment as well as
the expression of matrix metalloproteinases-1, -3, and -12.
Although the study was limited by the small sample size, those
histologic changes indicated restoration of photoaged skin
with ALA-PDT.
Photodynamic Therapy with Intense Pulsed Light
IPL is a light source that emits noncollimated, noncoherent
light with wavelengths in the range of 515-1200 nm, which
corresponds to the visible light and near-IR spectrum (47).
Various fi lters can be used to block certain wavelengths below
the cutoff point of the desired fi lter. IPL treatments improve
many of the signs of photoaging, including pigmentation in
the form of solar lentigines, erythema, and telangiectasias due
to vascular ectasia/damage, as well as fi ne wrinkling (47). Like
the PDL, IPL treatments also promote neocollagenesis (177).
Although IPL alone has been proven effective in the treatment
of photodamage, the addition of ALA to IPL treatment (ALA-
IPL) appears to be more effective in treating photodamaged
skin. Clinical examples of ALA-IPL treatment for photorejuve-
nation are illustrated in Figures 10.7-10.10.
In 2002, Ruiz-Rodriguez et al. (166) investigated the treat-
ment of photodamage and AKs using ALA-PDT with IPL as
the light source for photorejuvenation. Seventeen patients
with various degrees of photodamage and AKs (38 AKs total)
underwent therapy with ALA-IPL. A total of two treatments
were performed 1 month apart. Treatments were well toler-
ated. At 3 months follow-up, 87% of AKs disappeared and
marked cosmetic improvement was noted in wrinkling, coarse
skin texture, pigmentary changes, and telangiectasias.
Multiple studies followed the initial results of Ruiz-Rodriguez
and coworkers. Avram and Goldman (178) evaluated the
PDT with Red Light
Many of the studies regarding red light PDT for the treatment
of photoaging utilized MAL rather than ALA. These studies by
Szeimies et al. (69) and Pariser (172) demonstrated excellent
