PHOTODYNAMIC THERAPY is also known as Photoradiation therapy,
Phototherapy,
Photochemotherapy.
Photodynamic therapy (PDT) is a treatment that uses a drug, called a photosensitizer or photosensitizing agent.
Photosensitizers are exposed to a specific wavelength of light, photoactivation causes the formation of singlet oxygen, which produces peroxidative reactions that can cause cell damage and death.
Photodynamic therapy in treatment of oral lichen planus: Dr Aparna
1. Photodynamic Therapy in Treatment of
Oral Lichen Planus
Mostafa D, Tarakji B
J Clin Med Res. 2015;7(6):393-399
2. Lichen planus is a
common
mucocutaneous
disease.
first described by
Wilson in 1869
Affect 0.5–1% of
the world’s
population.
INTRODUCTION
3. LichenGreek word leichen,
meaning flat, and possibly
the striking clinical colour of
the pimples on skin led to
the designation leichen
ruber (latin; red).
Planus refers to the clinical
appearance of the skin
papulae; flattened, smooth
and depressed on the
summit.
INTRODUCTION
5. A common chronic
immunological
mucocutaneous disorder
that varies in appearance
from keratotic to
erythematous and
ulcerative Wilson 1896
OLP is relatively common
disorder of the stratified
squamous epithelia skully
and El-kom1985
A common disorder in
which auto-cytotoxic T
lymphocytes trigger
apoptosis of epithelial cells
leading to chronic
inflammation. Crispian
Scully 2007
DEFINITION
12. Malignant potential : 0.4-6.25%.
Only lesions that have dysplasia are potentially at risk
of developing into cancer.
Smoking and alcohol may increase the risk of oral
cancer
14. Recent non-pharmacological treatment of OLP
• Lasers have been suggested as non-pharmacological modality to patients resistant to conventional
treatment but their effectiveness is under study
• low dose 308-nm excimer laser is a palliative treatment when the mucosa lacks the overlying epithelial
layer and a higher and more effective UV dose is allowed to reach the infiltrating lymphocytes
High - level
laser Irradiation
low- level
laser irradiation
Diode laser 980 nm
was also reported as
an easy, effective,
fast and safe
treatment of OLP
15. Photodynamic therapy
• Photoradiation therapy,
• Phototherapy,
• Photochemotherapy.
• Photodynamic therapy (PDT) is a treatment that uses a drug, called a
photosensitizer or photosensitizing agent.
• Photosensitizers are exposed to a specific wavelength of light,
photoactivation causes the formation of singlet oxygen, which
produces peroxidative reactions that can cause cell damage and
death.
19. Photosensitizers
first PSs used in PDT were
compounds belonging to
the group of hematoporphyrin,
photofrin, and meta-tetra
(hydroxyphenyl) chlorin.
After extended period of time,
the PSs of choice included ALA
and dyes - toluidine blue and
methylene blue.
Methyl 5-aminolevulinate (MAL)
is an esterified derivative of ALA.
It is lipophilic and its selectivity
for specific cells is greater than
that of ALA which increases its
phototoxicity effect
20. Types of lights source used in topical PDT
1) Lasers are considered as an ideal light source for PDT due to
its coherence
and monochromaticity.
2) Lamps have been useful in PDT especially in the cure of skin
diseases such as metal halogen lamp and short arc xenon lamp.
3) Lasers emitted diodes (LEDs) generate wavelength bands
wider than those from lasers.
21. PDT essentially has two steps :
• Application of photosensitizer drug.
• Light activation.
22. 2 Stage Mechanism of PDT
first stage :
• photosensitizing agent is accumulated in the target cells following topical
administration. This was explained by disproportionately of high numbers of low
density lipoproteins receptors of their cell membranes and abnormal
microvasculature.
• microorganisms like bacteria, fungi and viruses exhibiting selective accumulation
of PSs due to differences in permeability of their outer structures.
23. second stage
• Photosensitized cells are exposed to light source of specific wavelength that coincides with the absorption
spectrum of the PS.
• measured light dose of appropriate wavelength is then used to irradiate the target tissue
• Generation of ROS
25. PDT produces cytotoxic effects by three
mechanisms:
Cellular
vascular
immunological
responses.
28. Aghahosseini et al in 2006
estimated that PDT is an
alternative method for the
treatment of OLP in 13 patients
with 26 mucosa lesions.
patients rinsed with 5% aqueous
solution of dye for 5 min. After
10 min, the lesions were
exposed to a low-energy laser of
632 nm wavelength and
exposure dose of 120 J/cm2
Sixteen lesions were improved
and four lesions had complete
remission.
29. Sadaksharam et al in 2012
conducted a research on 20
patients with systemic OLP.
patients were treated by PDT
using xenon arc lamp of 630 ± 5
nm wavelength and total dose
of 120 J/cm2 per sitting in four
sessions
mediated by MB.
Results : a significant reduction
in lesions over prolonged period
without any side effects
30. Sobaniec et al
clinical study of 3
patients with 48
lesions
PDT using gel
containing 20%
chlorine-e-6
Photolon and 10%
dimethyl sulfoxide
applied directly onto
the lesion and the
surrounding healthy
mucosa 1 h before
exposure to a
semiconductor laser
with wavelength
660 nm.
A series of
illuminations were
performed using
light energy density
of 90 J/cm2.
The appointments
were scheduled at
2-week intervals,
but no longer than
for 10 sessions.
Conclusion : useful
in treatment of OLP
where the size of
clinical lesions in
patients decreased
significantly in 55%.
the best effects were observed on lining
mucosa more than masticatory mucosa.
32. Sadaksharam et al, 2012,
48 Case report 20 Xenon arc
lamp of 630 ± 5 nm and 120
J/cm2) Methylene blue
Kvaal et al, 2013
83 Case report 14 Diode
laser (600 - 660 nm and 75
J/cm2) Methyl 5-
aminolevulinate
Aghahosseini et al, 2006
82 Case report 2 Diode laser
(632 nm and 100 J/cm2)
Methylene blue
Aghahosseini et al, 2006
52 Case report 13 Diode
laser (632 nm and 120
J/cm2) Methylene blue
Sobaniec et al, 2013
49 Case report 23 Diode
laser (660 nm and 90 J/cm2)
Chlorine-e-6 polyvinyl
pyrrolidone (Photolon®)
2006 TO 2013
33. • no long term side effects when used properly.
• Less invasive than surgery.
• usually takes only a short time and is most often done as an
outpatient.
• Can be targeted very precisely.
• Unlike radiation, PDT can be repeated many times at the same
site if needed.
• There’s little or no scarring after the site heals.
• It often costs less than other cancer treatments.
• PDT is currently used in a number of medical fields, including
oncology (cancer), dermatology (skin), and cosmetic surgery.
34. limitations of PDT?
• The light needed to activate most photosensitizers
cannot pass through more than about one third of an
inch of tissue (1 centimeter).
• For this reason, PDT is usually used to treat tumors on
or just under the skin or on the lining of internal
organs or cavities.
• PDT is also less effective in treating other tumors,
because the light cannot pass far into these tumors.
• PDT is a local treatment and generally cannot be used
to treat cancer that has spread (metastasized).
35. Side effects
Drugs makes the skin
and eyes sensitive to
light for
approximately 6
weeks after
treatment
Burns , swelling, pain,
and scarring in
nearby healthy
tissue.
Other side effects
include coughing,
painful breathing,
trouble
swallowing, stomach
pain, or shortness of
breath; these side
effects are usually
temporary.
Side effects
Side effects
36. Future hold for PDT…
Researchers continue to
study ways to improve the
effectiveness of PDT and
expand it to other
cancers.
Clinical trials are under
way to evaluate the use of
PDT for cancers of the
head and neck,
skin, prostate, cervix,
and peritoneal cavity
Other research is focused
on the development of
Photosensitizers that are
more powerful, more
specifically target cancer
cells, and are activated by
light that can penetrate
tissue and treat deep or
large tumors.
Researchers are also
investigating ways to
improve equipment and
the delivery of the
activating light.
Future of PDT
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Notas del editor
Hypothesis for the immunopathogenesis of oral LP. Antigen presenting cells (APCs) and basal keratinocytes are ‘‘activated’’by viral infection, bacterial products, mechanical trauma, systemic drugs, contact sensitivity or an unidentified agent (1). ActivatedAPCs and keratinocytes secrete chemokines that attract lymphocytes into the developing oral LP lesion. Activated APCs presentantigen associated with MHC class II to CD41 T cells (2a). Activated basal keratinocytes present antigen associated with MHCclass I to CD81 T cells (2b). CD40 and CD80 coexpression and IL-12 secretion by MHC class II1 APCs promotes a T helper-1(Th1) CD41 T-cell response. Th1 CD41 helper T cells secrete IL-2 and IFN-gamma (3a), which bind their respective receptors onCD81 T cells (3b). Activated antigen-specific CD81 cytotoxic T cells express FasL or secrete granzyme B or TNF-alpha (4) thattrigger basal keratinocyte apoptosis (5)Hypothesis for the immunopathogenesis of oral LP. Antigen presenting cells (APCs) and basal keratinocytes are ‘‘activated’’by viral infection, bacterial products, mechanical trauma, systemic drugs, contact sensitivity or an unidentified agent (1). ActivatedAPCs and keratinocytes secrete chemokines that attract lymphocytes into the developing oral LP lesion. Activated APCs presentantigen associated with MHC class II to CD41 T cells (2a). Activated basal keratinocytes present antigen associated with MHCclass I to CD81 T cells (2b). CD40 and CD80 coexpression and IL-12 secretion by MHC class II1 APCs promotes a T helper-1(Th1) CD41 T-cell response. Th1 CD41 helper T cells secrete IL-2 and IFN-gamma (3a), which bind their respective receptors onCD81 T cells (3b). Activated antigen-specific CD81 cytotoxic T cells express FasL or secrete granzyme B or TNF-alpha (4) thattrigger basal keratinocyte apoptosis (5)
The typical rash of lichen planus is well- described by the "5 P's": well-defined pruritic, planar, purple, Polygonal, papules Flexor surfaces especially wrists, flanks, medial thighs, shins of tibia, glans penis, nails, scalp & oral mucosa.
DT PSs are chemical compounds that can be promoted toan excited state upon absorption of the light. When they capture light energy, they transfer it into chemical reaction in thepresence of molecular oxygen produces singlet oxygen (1O2)or superoxide (O2-),
The first PSs used in PDT were compounds belonging tothe group of hematoporphyrin, photofrin, and meta-tetra (hydroxyphenyl) chlorin. After extended period of time, the PSsof choice included ALA and dyes - toluidine blue and methylene blue (
photosensitizing agent is accumulated in the target cells (rapidlydividing cells) that need to be treated, following topical administration. This was explained by disproportionately of highnumbers of low density lipoproteins receptors of their cellmembranes and abnormal microvasculature
Type I: It involves electron/hydrogen transfer directly from the photosensitizer, producing ions, or electron/ hydrogen removal from a substrate molecule to form free radicals. These radicals react rapidly with oxygen, resulting in the production of highly reactive oxygen species
ype II: The reactions produce electronically excited and highly reactive state of oxygen known as singlet oxygen. In PDT, it is difficult to distinguish between the two reactions mechanisms
When light (h) is delivered to a photosensitizer (PS)-loaded tumour it induces both apoptotic and necrotic cell death. These cells are phagocytosed by dendritic cells (DCs) that have accumultated owing to the acute inflammatory response which is triggered by photodynamic therapy (PDT). DCs mature after stimulation by cytokines, which are released at the site of inflammation, and home to the regional lymph nodes where they present antigens to the T lymphocytes. Activated T lymphocytes become effector T cells and, attracted by chemokines, migrate to the tumour and kill the tumour cells
Drugs makes the skin and eyes sensitive to light for approximately 6 weeks after treatment.(Thus, patients are advised to avoid direct sunlight and bright indoor light for at least 6 weeks