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Photodynamic Therapy
16
Photodynamic therapy was approved in 2000 as an alter-
native treatment for patients with AMD of the exuda-
tive form, having been the first effective pharmacologi-
cal treatment for this form of the disease. Until then,
laser photocoagulation was only successful in treating a
small percentage of neovascular lesions (juxtafoveal and
extrafoveal), excluding subfoveal lesions, which are more
frequent.
With the emergence of antiangiogenic therapies, photo-
dynamic therapy has been used less frequently. However,
it remains current in three situations: in patients with
systemic or ocular contraindications regarding intravit-
real administration of antiangiogenic drugs, as an adju-
vant, in combination with other drugs, and in the treat-
ment of polypoidal choroidal vasculopathy.
2. Mechanism of action
Experimental studies
(1,2)
suggest that photodynamic ther-
apy (PTD) causes endothelial cell lesions, with formation
of clots and selective vascular occlusion. Endothelial cell
membrane lesions appear to be caused by free radicals
released when verteporfin is activated by non-thermal
laser light. These free radicals react with endothelial cell
membranes and circulating blood cells, inducing platelet
activation and local clot formation.
The mechanisms by which PTD induces tissue destruc-
tion are not exactly known. Three related mechanisms
of action have been proposed: cellular, vascular and
immune
(3)
. The cellular mechanism, which is the most
relevant, corresponds to the cytotoxic effects of free
radicals on mitochondria, the endoplasmic reticulum
and lysosomes. When exposed to these radicals, endo-
thelial cell membranes rupture, exposing the basal mem-
brane, which causes platelet adhesion and aggregation.
Activated platelets release mediators such as histamine,
thromboxane and TNF-
α
. These mediators trigger a
sequence of events, namely vasoconstriction, throm-
bosis, increased vascular permeability, blood stasis and
hypoxia. The proposed immune mechanism is based on
the high concentrations of cytokines observed in patients
subject to PDT, such as interleukin 2 and TNF–
α
. It
is equally admitted that PDT may decrease immune
response by reducing antigen-presenting cell activity.
Standard treatment consists of endovenous infusion of
verteporfin at a dose of 6 mg/m
2
body surface, for 10
minutes. Fifteen minutes after starting the infusion, the
patient is treated with a diode laser with wavelength of
689 nm and light intensity of 600 mw/cm
2
, at a radia-
tion dose of 50 J/cm
2
, with an exposure time of 83 sec-
onds and a spot diameter corresponding to the diameter
of the largest lesion plus 1mm.
These parameters have been studied and appear to be
ideal, allowing maximum vascular effect with minimum
photoreceptor and pigment epithelial cell damage.
Verteporfin activation by the diode laser induces tem-
porary closure of the choroidal neovascular complex,
through the mechanisms already described, causing little
damage to adjacent retinal structures. This characteristic
doubtlessly represented a therapeutic advantage, since it
allowed treatment of lesions whose location or size pre-
vented use of other available therapies, namely conven-
tional laser photocoagulation. However, photodynamic
therapy does entail some damage, although induced
retinal lesions are smaller than that occurring following
thermal laser photocoagulation. Laser fluence reduction
protocols have been proposed in the attempt to reduce
the extent of this damage.
Therapy schemes with more intense treatment regimes,
including treatment every 2 months in the first 6
months, were also tested. The efficacy and safety of the
latter regime were compared with those of the standard
1. Introduction
Authors:
Rita Flores, MD
1
Rufino Silva, MD, PhD
2
1
Lisbon Hospital Center - Central Zone - Lisbon, Portugal
2
Coimbra University Hospital - Coimbra, Portugal
