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Hypothesis
Medical Hypothesis, Discovery & I
nnovation
Ophthalmology Journal
Photodynamic Therapy and Central Serous Chorioretinopathy
Lina Siaudvytyte, Vaida Diliene, Goda Miniauskiene, Vilma Jurate Balciuniene
Eye Clinic, Lithuanian University of Health Sciences, Kaunas, Lithuania
ABSTRACT
Central serous chorioretinopathy is a common acquired maculopathy. Multiple studies showed that
photodynamic therapy is useful treatment for acute and chronic central serous chorioretinopathy. The
exact mechanism of photodynamic therapy in treating central serous chorioretinopathy is not clear, but it is
thought to be caused by short-term choriocapillaris hypoperfusion and long-term choroidal vascular
remodeling, leading to a reduction in choroidal congestion, vascular hyperpermeability and extravascular
leakage. Furthermore, photodynamic therapy seems to be an effective means of improving or stabilizing
visual acuity in patients with central serous chorioretinopathy.
KEY WORDS
Central serous chorioretinopathy; Photodynamic therapy; Pathophysiology
©2012, Medical Hypothesis, Discovery & Innovation (MEHDI) Ophthalmology Journal.
All rights reserved.
Correspondence to:
Dr. Vilma Jurate Balciuniene, Eye Clinic, Lithuanian University of Health Sciences, Kaunas, Lithuania, Tel/Fax: +370 37 326635,
E-mail: jurate.balciuniene@kaunoklinikos.lt
INTRODUCTION
Central serous chorioretinopathy (CSC) is characterized by a
serous detachment of the neurosensory retina in the macular
region, occasionally associated with detachment of the retinal
pigment epithelium (RPE). The most surprising aspect of the
disease is the relative preservation of retinal function
regardless prolonged separation from the RPE. Males are
mostly affected to have this condition and the average age is
between 20 and 50 years. The usual presenting symptoms are
significant loss of visual acuity and development of permanent
visual loss. Visual impairment is secondary to persistent serous
detachments of the neurosensory retina leading to cystoid
edema of the retina and diffuses decompensation of the RPE
[1]. The photoreceptors might have a critical role in this
process, because they are separated from their source of
nutrients when the retina is detached [2]. Some patients,
particularly older adults, can develop choroidal
neovascularization, which leads to severe visual loss [3].
The pathogenesis of CSC is still not completely understood.
However, it is well known that the subneural retinal fluid
originates from the choroid. At first it was believed that fluid
from the choroid drain away into subretinal space through
defects in tight junctions between the RPE cells due to
breakdown of the blood-retinal barrier. However, this theory
does not explain the beneficial effect of laser photocoagulation
which consequences in permanent RPE barrier breakdown.
Another theory suggested that lost of normal RPE cells polarity
acts as a trigger for fluid pumping from the choroid to the
retina, causing a neurosensory detachment [4]. This theory was
failed after increased using of indocyanine green angiography
(ICGA) which reveals multifocal areas of choroidal vascular
hyperpermeability in CSC, which leads to mechanical disruption
of RPE barrier with subsequent accumulation of subretinal fluid,
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PHOTO DYNAMIC THERAP Y AND CENT RAL SEROU S CHOR IORE TINOP ATHY
supporting the theory that the underlying pathophysiology is at
the choroidal level [5,6]. No new vessels are usually present in
CSC, but the defect seems to affect choroidal vessels. Any
therapy that decreases the excess of choroidal permeability
may be potentially helpful in CSC cases [7].
Therefore recent studies examining the pathogenesis of CSC
support the hypothesis that RPE decompensation may be a
result of underlying choroidal vasculature hyperpermeability [8-
11]. Some authors reported that choroidal vascular
hyperpermeability was seen in most symptomatic eyes with
CSC [4,6]. Prunte et al. showed delayed choroidal capillary
lobular filling in areas of hyperpermeability and proposed that
localized capillary and venous congestion in the affected
lobules impaired the circulation, produced ischemia, and
allowed increased choroidal exudation and a focally
hyperpermeable choroid [12]. Increased choroidal permeability
along with local high perfusion and increased hydrostatic
pressure allows profusion choroidal fluid to accumulate and
produces a RPE detachment. As the detachment grows, the
target junctions between RPE cells are broken, and a focal
defect of the blood-retinal barrier develops, later resulting in
neural retinal detachment [13-14]. Some investigators revealed
that subfoveal choroid in the eyes with CSC, even in the fellow
eyes are thicker than that in normal eyes because of choroidal
vascular hyperpermeability [9,15]. They used optical coherence
tomography (OCT) to evaluate choroidal hyperpermeability by
measuring choroidal thickness. Interestingly, recent studies
reveal that corticosteroids can influence the production of the
nitric oxide, prostaglandins and free radicals within the
choroidal circulation. All three substances participate in the
autoregulation of blood flow within the choroid [16].
The treatment of central serous chorioretinopathy has not
been well-established. Different therapeutic approaches have
been tried to manage this condition, including beta-blockers,
acetazolamide, vitamins and non-steroidal anti-inflammatory
drugs, but none of these had explicit benefits [17]. In past
decades, argon laser photocoagulation of extrafoveal leakage
points was the standard of CSC treatment [18,19]. It is the only
therapy proved beneficial by large clinical trials. Laser
treatment induces a local inflammatory reaction on RPE, thus
decreasing RPE leakage while choroidal hyperpermeability
remain unchanged [20]. The evidence of long follow-up studies
shows a reduction of serous detachment with lack of
improvement in final visual acuity or a reduction in the
incidence of recurrences [21-23]. Laser photocoagulation
cannot be performed in the foveal avascular zone. Laser
therapy may result adverse effects such as secondary choroidal
neovascularization or central scotomas [24-26].
Another treatment option is photodynamic therapy (PDT). PDT
originally was intended to cause regression of choroidal
neovascularization (CNV) secondary to age related macular
degeneration and recently is used for neovascular age-related
macular degeneration, pathologic myopia and ocular
histoplasmosis caused CNV treatment. The exact mechanism of
PDT on CSC is not well-known. It has been suggested that PDT
may induce choriocapillaris damage and vascular remodeling
thus decreasing choroidal hyperpermeability [12,27-32].
Maruko et al. using enhanced depth imaging OCT, reported
reduced choroidal thickness 1 month after PDT treatment in
chronic CSC patients [20]. These findings are compatible with
ICGA showing a transitory hypoperfusion [11]. Another authors
hypothesized that PDT acts by both decreasing choroidal
hyperpermeability and tightening the blood retinal barrier at
the level of the RPE resulting in resolution of subretinal fluid
[1].
Patients with chronic forms of CSC may benefit from a
decreased choroidal vascular permeability. Some authors
suggest that verteporfin may show a high affinity for RPE [1,33].
Verteporfin is a benzoporphyrin derivate which is used as a
photo sensitizer for PDT to eliminate the abnormal blood
vessels in the eye. It is known that the primary effect of PDT
seems to be damage of the choriocapillaris endothelium,
swelling, fragmentation, detachment from its basement
membrane and degeneration [31]. Another possible
explanation for the positive effects of this therapy concerns the
inflammatory reaction precipitated by PDT. Verteporfin may be
deposited within the serous fluid under the macula and its
activation may release free radicals and pro-inflammatory
factors that induce a permanent adhesion between the
neurosensory retina and RPE. This mechanism may explain the
occurrence of inflammatory changes in the RPE [7]. Otherwise
the vascular endothelial damage known to be the major
hallmark of photodynamic tissue effects is induced by direct
interaction of singlet oxygen with the lipids of the endothelial
cytoplasmic membranes. Recanalization of the choriocapillaris
begins to occur within a short interval after doses of therapy.
Maintenance of structural integrity histologically of the
overlying photoreceptors seems to be the result of limited
hypoxia or thermally enhanced phototoxic damage [31].
Histologic studies on animal models and humans have shown
that PDT induces the regression of subretinal newly formed
vessesls as well as obliteration of the vessels of the inner
choriocapillaris [32].
The standard regime for using PDT is to give patient
intravenous verteporfin at a dose of 6 mg/m2 over 10 minutes.
Then, 5 minutes later, diode laser at a wavelength of 600-689
nm and energy of 50 mJ/cm2 over 83 seconds is directed to the
target lesion of the eye. Possible ocular side effects include RPE
atrophy and rips, secondary choroidal neovascularization, and
ischemia of choriocapillaris. To minimize adverse events,
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PHOTO DYNAMIC THERAP Y AND CENT RAL SEROU S CHOR IORE TINOP ATHY
research has targeted half-dose half fluence and minimal-
fluence PDT [35]. Half-dose or low-fluence PDT with verteporfin
is effective in inducing reabsorption of subretinal or intraretinal
fluid with some beneficial visual outcomes in the majority of
patients with CSC [33,45].
PDT is not completely harmless to ocular structures [20,30-
32,36-40]. Choriocapillaris thrombosis and choroidal perfusion
and permeability changes have been demonstrated. These
reports show no early neural retina or RPE changes with
standard verteporfin doses [30,31]. Some studies showed that
standard dose PDT might be associated with choriocapillaris
hypoperfusion that may result in decreased vision [41]. In
recent years, several different studies have supported the good
results of PDT with standard doses of verteporfin to treat
chronic CSC [7,33,35-47]. However, these studies were
performed with a small number of patients and short follow-up.
In order to avoid PDT related complications half-dose or low-
fluence PDT has been suggested by different authors. Higher
selectivity of the choriocapillaris was achieved with a lower
fluence PDT, while higher fluence emission resulted in closure
of the deeper choroidal vessels and focal alterations in the RPE.
PDT has shown better results on visual acuity and anatomical
outcome compared with photocoagulation in chronic forms of
CSC, with fewer complications [1,7,45-47,49-53]. Changes in the
average neural retina thickness of eyes treated by PDT could be
supported by the long-standing effects of vascular remodeling
in the underlying choroid [20,30]. Photodynamic therapy with
verteporfin might induce temporary choriocapillaris occlusion
and endothelial changes, this might reduce the vascular
permeability and decrease fluid passage toward the retina
[45,49]. Moreover, RPE cells damaged by light-activated
verteporfin might be replaced by new ones possible recovery
from the metabolic impairment at the RPE level [34,49].
HYPOTHESIS
Clinical and experimental evidence indicates that besides
closing the neovascular membrane this treatment also
produces ischemia of the underlying choriocapillaris, induced
by direct action on the choriocapillaris endothelium with
choriocapillaris occlusion and resulting in hypoperfusion of the
choriocapillaris in the short term and remodeling of choroidal
vascular over time. This effect of PDT on the choroid could be
used to reduce choroidal congestion and vascular
hyperpermeability, which is an important factor in CSC
pathogenesis.
CONCLUSION
PDT seems to be an effective therapy of improving or stabilizing
visual acuity in patients with central serous chorioretinopathy.
However, more studies are needed to manifest the benefits,
efficacy and long-term safety of PDT in the treatment of CSC..
DISCLOSURE
The authors report no conflicts of interest in this work.
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