Biomedical Engineering Reference
In-Depth Information
patient satisfaction were documented in two studies by
Szeimies et al. and Goldman and Atkin (69,72). Other proce-
dures used for the clearance of AKs, such as cryotherapy or
chemical peels, can result in hypopigmentation or even scar-
ring (69,73). PDT, perhaps surprisingly to some, is a cost-
effective means of treating AKs. Gold found ALA-PDT with a
blue light source to be the least expensive treatment option for
AKs compared with 5-FU, imiquimod, and diclofenac. In fact,
ALA-PDT was approximately half the cost of a similar course
of imiquimod for fi eld AK treatment (50). Additionally, PDT
accomplished fi eld treatment of precancerous lesions, includ-
ing subclinical ones (73).
Disadvantages of PDT are largely related to minor and
expected adverse events following the procedure. Minor
pain and erythema may occur during or following the pro-
cedure. Mild crusting and edema may occur, lasting up to
1 week. However, other treatment modalities for AKs have
similar if not longer recovery periods. There are fi nancial
costs associated with the procedure. If PDT is performed for
AK treatment and photorejuvenation, there is an associated
out-of-pocket cost to the patient. The physician must also
make an initial investment in the laser and light devices,
although many of the light sources have multiple applica-
tions beyond PDT.
following one treatment. However, 14% of patients required
reduced power density during blue light irradiation due to
intolerable side effects, including stinging and burning. A fi nal
phase II study was a dose-ranging study of ALA solution from
concentrations of 2.5% to 30% ALA. Clearance of AKs
occurred in a dose-dependent manner, and a 20% concentra-
tion was selected as the most ideal concentration for use in
ALA-PDT with blue light (77).
Piacquadio and coworkers (78) followed in 2004, publishing
the results of a phase III clinical trial. The same long incubation
and illumination times were used as in the phase II trial. A total
of 243 patients with nonhyperkeratotic AKs were treated. Com-
plete clearance at 12 weeks following one PDT session was 70%.
A second treatment resulted in a complete clearance rate of
88%. Facial lesions responded more favorably than scalp lesions,
with complete response rates of 78% and 50%, respectively, at
week 12 following treatment. In terms of patient feedback, 94%
of patients rated their cosmetic outcome following PDT as
good or excellent. A recurrence rate analysis for this treatment
cohort between 8 and 12 weeks posttreatment was 5% (77).
Work by Tschen and coworkers (67) confi rmed earlier fi nd-
ings. This phase IV study of 101 patients with six to 12 AKs
used a 14- to 18-hour ALA incubation time. After the fi rst
PDT, a complete clearance of 72-76% was observed, which
increased to 86% with a second treatment.
Several other studies examined the use of blue light in ALA-
PDT for the treatment of nonhyperkeratotic AKs and observed
photorejunative effects on the treated area in addition to the
reduction of AKs (72,79).
In 2004, Touma et al. (22) reported on the effi cacy of short-
contact ALA-PDT. Not only did this allow for PDT to be con-
ducted in a single clinic visit rather than over 2 days, but side
effects related to the longer 14- to 18-hour incubations were
reduced. In this study, 17 patients with AKs of the face and
scalp were treated with ALA using incubation times of 1, 2,
or 3 hours. A clearance rate of 93%, 84%, and 90% were
achieved in the 1-, 2-, and 3-hour incubation groups, respec-
tively. Clearance rates were maintained through 5 months of
follow-up. In addition, this study with blue light showed a
modest but signifi cant improvement in photoaging.
Treatment Results of ALA-PDT for AKs
Kennedy, in 1990, was the fi rst to exploit the use of topical ALA
in the treatment of NMSCs (74). Using a 20% ALA compound
and a fi ltered slide projector for a light source, a complete
response rate of 90% was achieved in patients with AKs. Since
this initial study, a variety of light sources have been investi-
gated for use in PDT for the treatment of AKs. As the PDT
reaction is activated from an emission spectra ranging from
400 to 800 nm (75), we have organized clinical studies accord-
ing to the light source utilized. Table 10.1 provides a summary
of peer-reviewed articles on the use of ALA- and MAL-PDT in
AK treatment.
Blue Light
Perhaps the most popular emission spectrum utilized in the
USA, blue light was the fi rst FDA-approved form of light for
activating ALA (Fig. 10.4). As a result, numerous published stud-
ies exist on the use of blue light in ALA-PDT not only for the
treatment of AKs, but also for other skin conditions responsive
to this treatment modality. As the relatively shorter wavelength
of blue light only penetrates 1-2 mm but is potent in its photo-
chemical effect, blue light is often selected for the treatment of
superfi cial lesions, such as nonhyperkeratotic AK lesions (76).
In 2001, Jeffes et al. (68) published the results of a multi-
center, phase II study of ALA-PDT using blue light (417 nm).
A 14- to 18-hour incubation was used on AK lesions of the
face and scalp in 36 patients. A total of 70 lesions were treated.
Light exposure duration was 16 minutes and 40 seconds, now
considered standard of treatment. At 8 weeks following a sin-
gle treatment, 88% of lesions cleared. Due to the extended
time of incubation, an increased rate of phototoxicity-related
side effects was observed. These adverse effects included ery-
thema and edema. A second phase II study was conducted
with the same protocol, this time in a total of 64 patients (77).
All of the patients had 75% or more clearance of AK lesions
Green Light
One study by Fritsch and coworkers (80) used a green light
source for the treatment of AKs with ALA-PDT. The focus of
this study was on patient discomfort. Compared to a red light
source, light irradiation with a green light source (543-548 nm)
was less painful in the treatment of facial AKs during PDT.
Yellow-Orange Light
Pulsed Dye Laser
PDLs (585-595 nm) (Fig. 10.5) target the chromophore oxy-
hemoglobin, allowing selective destruction of blood vessels. As
AKs often appear as erythematous scaly plaques, the infl am-
matory nature of these lesions can be targeted with this vascu-
lar laser. Alexiades-Armenakas and coworkers (73) were the
fi rst to report on its use in ALA-PDT. Thirty-six patients and a
total of 3622 lesions were treated. Location of lesions included
the face and scalp (2620 lesions), extremities (949), and trunk
(79). ALA was applied with either a 3-hour unoccluded incu-
bation or a 14- to 18-hour incubation. No difference in
