Acta Ophthalmologica 2016

Review Article

Central serous chorioretinopathy: what we have

learnt so far
Kah Hie Wong,1 Kin Pong Lau,1 Jay Chhablani,2 Yong Tao,3 Qing Li1 and Ian Y. Wong1
1
Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
2
Smt. Kanuri Santhamma Retina Vitreous Centre, L. V. Prasad Eye Institute, Hyderabad, India
3
Department of Ophthalmology, People’s Hospital, Peking University and Key Laboratory of Vision Loss and Restoration,
Ministry of Education, Beijing, China

ABSTRACT. The pathophysiology of CSCR

Central serous chorioretinopathy (CSCR) is a common retinal cause of visual loss. might be attributed to hyperpermeabil-
The mainstays of management are observation, photodynamic therapy (PDT) and ity of choroidal vessels; impairment of
laser procedures. Over the past decade, there has been rapid development in the choroidal vascular autoregulation
existing and novel imaging techniques, functional testing and management of induced by steroids, catecholamines or
CSCR. However, there is no convincing treatment designed for CSCR yet. In sympathomimetic agents; and dysfunc-
recent years, the advances in PDT, with various adjustments in fluence and tion of retinal pigment epithelium
verteporfin dosage, and the comparisons between different types of PDT for acute (RPE) barrier and pumping (Nicholson
and chronic CSCR in recent studies have provided greater insights into the role of et al. 2013).
The risk factors include steroid
PDT in treating CSCR. Novel laser procedures, such as the diode micropulse laser,
usage, phosphodiesterase-5 (PDE-5)
have shown comparable efficacy to conventional lasers without laser-induced
inhibitor use, obstructive sleep apnoea
damage. Antivascular endothelial growth factor, which was originally developed (OSA), Helicobacter pylori infection,
for treating cancers, has emerged to be a potentially effective treatment for CSCR. pregnancy, type A personality, endog-
The potential role of mineralocorticoid receptor antagonists in treating CSCR has enous Cushing’s syndrome and so on
provided greater understanding of the pathogenesis. Based on the relevant studies, (Liew et al. 2013).
mainly from the past decade, we discuss updates to the management of CSCR The mainstays of treatment are
according to the risk factor modifications, pharmacological interventions, PDT observation, photodynamic therapy
and laser procedures and concluded that PDT is the current best option for CSCR. (PDT) and laser procedures. Observa-
tion is feasible due to possible
Key words: antivascular endothelial growth factor – central serous chorioretinopathy – laser spontaneous recovery in most acute
photocoagulation – mineralocorticoid receptor antagonist – photodynamic therapy CSCR cases. In general, PDT and
laser procedures, such as conventional
Acta Ophthalmol. 2016: 94: 321–325 laser photocoagulation (LP), are
ª 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd used to provide more rapid visual
recovery, when disease does not
doi: 10.1111/aos.12779 improve spontaneously during obser-
vation.
subretinal fibrin accumulation or cho- We used search terms such as ‘cen-
Introduction roidal neovascularization (CNV). tral serous retinopathy’, ‘CSCR’, ‘man-
Central serous chorioretinopathy Central serous chorioretinopathy agement’, ‘treatment’ and also the
(CSCR) is a retinal disease in which a occurs six times more commonly in keywords of each type of treatment
yet-to-be-clarified pathophysiology men than women. The annual incidence on PubMed and Medline to retrieve
leads to serous detachment of the is 10 per 100 000 in men. Acute CSCR articles for this systematic review.
neurosensory retina, usually confined usually resolves spontaneously within Focuses are mainly placed on the
to the macular area. Central serous 2–3 months. The prognosis is highly findings of more recent articles, studies
chorioretinopathy can be classified dependent on presenting visual acuity, with greater number of patients and
according to its clinical course: acute with initial visual acuities of <6/9 usu- power, meta-analyses, reviews and
or chronic (more than 3 or 6 months). ally recovering, on average, two to three advancement in the past decade in
Rarely, it can be complicated by Snellen lines over the next few years. terms of efficacy, safety and the

321
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Acta Ophthalmologica 2016

Table 1. Quality of evidence (us preventive services task force definitions). unmasked study, the treatment group
(25 patients) had significantly faster
Grade Definition
SRF reabsorption rate than the control
Good Evidence includes consistent results from well-designed, well-conducted studies in group (25 patients), but the difference
representative populations that directly assess effects on health outcomes in BCVA improvement was insignifi-
Fair Evidence is sufficient to determine effects on health outcomes, but the strength of the cant (Rahbani-Nobar et al. 2011). In
evidence is limited by the number, quality, or consistency of the individual studies, contrast, a prospective, randomized,
generalizability to routine practice, or indirect nature of the evidence on health placebo-controlled study of 53 acute
outcomes CSCR participants demonstrated that
Poor Evidence is insufficient to assess the effects on health outcomes because of limited
HP eradication is unable to improve
number or power of studies, important flaws in their design or conduct, gaps in the
chain of evidence, or lack of information on important health outcomes BCVA and the SRF reabsorption rate,
although it could significantly improve
the central retinal sensitivity in patients
impacts on health outcomes. The relationship between PDE-5 inhibitors with acute CSCR (Dang et al. 2013).
management methods are categorized and CSCR. Due to the limited evidences and
into risk factor modifications, pharma- difficulties to establish the true corre-
cological interventions, PDT and laser lation between HP infection and CSCR
Obstructive sleep apnoea screening and
procedures. The quality of evidence of because of the high prevalence of HP
treatment (quality of evidence: poor)
each subtopic is graded based on the infection in general populations, pro-
US Preventive Services Task Force Obstructive sleep apnoea is the com- spective masked trials are needed to
Ratings (Table 1) (Grade Definitions. monest sleep-related breathing disor- confirm the positive correlation and
U.S. Preventive Services Task Force, der, a potentially serious disease that also the benefits of HP treatment to
October 2014). can lead to many systemic complica- patients with CSCR (Mateo-Montoya
tions apart from ocular ones (Grover & Mauget-Fayse 2014).
2010).
Risk Factor Modification Grover’s review suggested that early
Pregnancy and delivery (quality of
diagnosis and management of OSA
Glucocorticoid discontinuation (quality of evidence: fair)
could reduce the risk of devastating
evidence: good)
systemic complications and also pre- Pregnancy is associated with a number
Steroids, either endogenous or exogenous serve the ocular and visual function of effects on ocular functions due to
in almost every form (oral, intravenous, (Grover 2010). Although there were hormonal, metabolic, haemodynamic,
intra-ocular, intranasal, inhalation, intra- small prospective (Yavas et al. 2014) vascular and immunological changes.
articular), are well-known risk factors for and retrospective (Leveque et al. 2007; These ocular changes are usually tran-
CSCR (Nicholson et al. 2013). Kloos et al. 2008) studies demonstrating sient and either improve or fully
The issue of dose reduction or com- the high prevalence of OSA in patients recover during the postpartum period.
plete discontinuation of corticosteroid with CSCR, the limited available evi- The changes in the eyes can be either
in any forms with or without the use of dences make us unable to conclude the physiological or pathological and
steroid-sparing agents is recommended need of OSA screening in patients with either new developments or alterations
and should be discussed with the pre- CSCR. Thus, large randomized con- in pre-existing eye conditions (Gotovac
scribing doctor (Kleinberger et al. trolled trials are needed to enable us to et al. 2013).
2011; Nicholson et al. 2013). understand more the relationship Errera et al. (2013) suggested that,
between OSA and CSCR. as with a non-pregnant woman, if there
is steroid usage in any form, it should
Phosphodiesterase-5 inhibitor withdrawal
be stopped when CSCR develops in a
(quality of evidence: fair) Helicobacter pylori screening and
pregnant woman if it is medically
treatment (quality of evidence: poor)
There were concerns on the possible feasible. Because fluorescein angiogra-
association between phosphodiester- Giusti et al.’s review mentioned the phy is not advised to be used in
ase-5 (PDE-5) inhibitor usage and hypothesis of correlation between pregnant women, argon LP and diode
CSCR (Nicholson et al. 2013). A pla- CSCR and Helicobacter pylori (HP) micropulse laser would be difficult to
cebo-controlled, double-masked study infection based on a case report and a perform (Errera et al. 2013). In addi-
that randomized patients to receive prospective pilot study without con- tion, there are insufficient data regard-
placebo (n = 82), 5 mg of tadalafil trols and suggested the reason behind ing the safety and consequences of
(n = 85), or 50 mg of sildenafil might be due to the role of HP in ath- PDT in pregnant women and foetuses.
(n = 77) daily for 6 months showed erosclerosis (Giusti & Mauget-Faysse There is no evidence of the effects of
no retinal damage through within-nor- 2004). preterm delivery on the long-term
mal-range electroretinography findings The effects of HP treatment on the visual prognosis of severe CSCR
and visual function and the absence of subretinal fluid (SRF) reabsorption (Errera et al. 2013). There is no ade-
treatment-related findings that sug- rate, best corrected visual acuity quate information on the future risk
gested drug toxicity at 3 and 6 month’s (BCVA) and central retinal sensitivity and visual prognosis of CSCR in
evaluation (Cordell et al. 2009). Based of patients with CSCR were studied subsequent pregnancies; hence, coun-
on the limited and controversial evi- (Rahbani-Nobar et al. 2011; Dang selling for future pregnancies of women
dences, we cannot conclude on the et al. 2013). In a randomized with histories of developing CSCR

322

during pregnancy would be difficult
(Errera et al. 2013). On the other hand,
the safety of verteporfin in pregnancy
and early childhood would be difficult
to assess due to the ethics of research.
Pharmacological
Interventions
Antivascular endothelial growth factor
(quality of evidence: fair)
A 2013 meta-analysis combined four
clinically controlled studies and
showed that there were no positive
effects of intravitreal injection of bev-
acizumab (IVB) in CSCR (Chung et al.
2013). The analysis showed that there
were no significant differences in the
BCVA at 6 months after the injection
between the IVB and the observation
group and no significant differences in
the reduction of central macular thick-
ness between both groups.
Randomized controlled trials that
compared the effectiveness of HFPDT
and anti-vascular endothelial growth
factor (VEGF) have demonstrated the
superiority of HFPDT over anti-
VEGF in treating CSCR (Bae et al.
2011; Semeraro et al. 2012; Bae et al.
2014), where two of these three studies
were included in a meta-analysis that is
mentioned in the PDT section (Mateo-
Montoya & Mauget-Fayse 2014).
The comparison between HFPDT
(25 J/cm2) and intravitreal ranibizumab
(IVR) in a 2014 prospective, random-
ized, controlled trial (34 eyes with
chronic CSCR of >6 months) showed
that HFPDT can lead to significantly
greater improvement in central retinal
thickness (CRT), BCVA, rate of com-
plete resolution of SRF and choroidal
hyperpermeability (Bae et al. 2014).
However, the differences of CRT and
BCVA from IVR became insignificant
after 6 and 3 months, respectively.
Based on the limited evidences to
date, the benefits of anti-VEGF injec-
tion for patients with CSCR remain
unconvincing. Therefore, anti-VEGF
injection should not be confidently
adopted as one of the first-line treat-
ment options of CSCR.
Mineralocorticoid receptor antagonist
(quality of evidence: poor)
Since 2012, there were five case report
and case series that studied the effects
of mineralocorticoid receptor antago-
nist in patients with CSCR (Zhao et al.
2012; Bousquet et al. 2013; Gruszka
2013; Breukink et al. 2014; Maier et al.
2014). One of the case series is also an
animal study that discovered the same
effects of both intravitreal aldosterone
and glucocorticoid injections in rats
(choroid vessel dilation and leakage)
(Zhao et al. 2012). Although short-
term visual benefits were demonstrated
in four of the five studies (Zhao et al.
2012; Bousquet et al. 2013; Gruszka
2013; Maier et al. 2014), the lacking of
evidences limits its role as a CSCR
treatment option at this stage. Large
randomized controlled trials are
needed.
Photodynamic Therapy
(Quality of Evidence:
Good)
Various types of PDT, which are clas-
sified based on the dosage of vertepor-
fin and the fluence used, have been
performed for both acute and chronic
CSCR patients. Here, we focus more
on half-fluence (HFPDT), low-fluence
(LFPDT) or reduced-fluence PDT
(RFPDT) (25 J/cm2) (Semeraro et al.
2012; Bae et al. 2014), half-dose
(HDPDT) (3 mg/m2) (Mateo-Montoya
& Mauget-Fayse 2014) and full-fluence
PDT (50 J/cm2) (Mateo-Montoya &
Mauget-Fayse 2014) due to the higher
power of available evidences. For all
types of PDT, verteporfin is usually
infused over 8 or 10 min, followed by
laser delivery at 689 nm at 10 or
15 min from the start of infusion.
A 2014 meta-analysis had demon-
strated a great summary of the effec-
tiveness and safety of PDT as a
treatment for CSCR in multiple aspects
(Mateo-Montoya & Mauget-Fayse
2014). Nine reports that consisted of
total 319 patients were included. Four
types of comparisons were made. The
measured primary outcomes include
BCVA in log MAR, central macular
thickness and complete SRF resolu-
tion. In group 1, one retrospective and
one prospective comparative case series
(20 and 26 eyes, respectively) were
included to compare the effects
between HDPDT and LP at 1 month’s
follow-up. The SRF resolution in PDT
group is 9.14-fold higher (p = 0.005).
In group 2, PDT group (HFPDT in
two studies and conventional PDT in
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Acta Ophthalmologica 2016
one study) was compared to
anti-VEGF group [one retrospective
comparative study (29 eyes) and one
randomized controlled trial (22 eyes)
that used intravitreal bevacizumab; one
prospective, randomized, pilot study
(16 eyes) that used intravitreal rani-
bizumab] at 3 month’s follow-up.
Complete SRF resolution in PDT
group was significantly faster (odds
ratio = 9.18, p = 0.007), and reduction
in central macular thickness was sig-
nificantly higher in PDT group (mean
difference = 38.39 lm, p = 0.002). In
group 3, two randomized controlled
trials (63 and 34 eyes, respectively) that
compared HDPDT (3 mg/m2) with
placebo (30 ml normal saline) were
meta-analysed. All three primary out-
comes showed significantly greater
improvements in HDPDT group than
placebo group. In group 4, one multi-
center prospective study (42 eyes) and
one multicenter retrospective study (67
eyes) were used to compare between
efficacy and safety of HFPDT
(25 J/cm2) and conventional PDT
(50 J/cm2, full fluence). BCVA
improvement and complete SRF reso-
lution rate showed no difference
between both groups at 1 month’s
follow-up. However, choroidal regio-
nal non-perfusion was significantly
commoner in full-fluence PDT (odds
ratio = 0.09, p < 0.001). This meta-
analysis demonstrated that PDT is
more superior to LP, anti-VEGF and
placebo in terms of effectiveness; mean-
while, HFPDT is better than full-
fluence PDT in terms of safety.
A comprehensive 2014 study, which
reviewed three randomized controlled
trials and 28 studies that met Strength-
ening the Reporting of Observational
studies in Epidemiology (STROBE) cri-
teria (total 787 eyes), concluded confi-
dently that PDT might be a useful
treatment option for chronic CSCR in
the short term (Erikitola et al. 2014).
Complications, namely CNV and reac-
tive RPE hyperplasia, developed in four
studies in patients who received full-
fluence PDT. This can be further con-
firmed by robust randomized controlled
trials with longer follow-up duration.
Apart from the meta-analysis and
systematic review above, the other
recent evidences on various types of
PDT and the comparisons among them
were mainly retrospective studies or
prospective studies without controls
(Peyman et al. 2011; Dang et al. 2014;
323

Acta Ophthalmologica 2016
Liu et al. 2014). The safety of PDT is
supported by a 2013 literature review
(Karim & Adelman 2013) and the
above-cited evidences where no signif-
icant adverse effects were reported,
except for some patients who received
conventional PDT. Therefore, based
on the evidences to date, the efficacy
and safety of PDT in treating both
acute and chronic CSCR patients
appears to be a convincing and appeal-
ing first-line treatment option and is
preferred over LP and anti-VEGF,
especially HFPDT and HDPDT.
Laser Procedures
Laser photocoagulation (quality of
evidence: good)
Laser photocoagulation is recognized
to be an effective treatment for acute
and chronic CSCR and is supported by
randomized controlled trials performed
in 1979 and 1983 (Leaver & Williams
1979; Robertson & Ilstrup 1983). A
recent meta-analysis concluded the
inferiority of LP to PDT based on 1
retrospective and 1 prospective com-
parative case series (Mateo-Montoya &
Mauget-Fayse 2014). Nonetheless,
here, we will focus on the recent
advances and discoveries in LP.
In a 2013 randomized trial (37
patients with acute CSCR), 18 patients
underwent subthreshold macular argon
laser that was postulated to have the
same advantageous effects as conven-
tional laser without damaging the del-
icate macular tissue (Behnia et al.
2013). The BCVA and contrast sensi-
tivity improved to a significantly better
extent in the treatment group than the
observation group after 6 months and
1 month, respectively.
According to the available evi-
dences, the effectiveness of LP in treat-
ing CSCR in terms of improvement in
BCVA, contrast sensitivity and SRF
remains convincing. However, the use
of laser leads to collateral iatrogenic
retinal damage and functional loss due
to morphological damage caused by
the visible end-point (a whitening
burn), even when the LP is appropri-
ately performed (Sivaprasad et al.
2010; Doga et al. 2011). In view of
the potential benefits of subthreshold
macular argon laser, large randomized
controlled trials need to be conducted
to prove the significance of their
benefits and the proposed better
324
adverse-effect profile than the conven-
tional LP. In contrast, conventional LP
should not be considered as a first-line
treatment option for CSCR.
Diode micropulse laser photocoagulation
(quality of evidence: fair)
A diode laser with micropulsed emis-
sion has been developed to allow for
subthreshold therapy without a visible
burn end-point. The resting time
between successive micropulses reduces
the heat in the tissues and regulates the
thermal isolation of each pulse contri-
bution, hence greatly reducing the risk
of structural and functional retinal
damage, while retaining the therapeutic
efficacy of conventional laser treatment
by achieving the requisite energy with
repetitive low-energy pulses (Sivapra-
sad et al. 2010).
A pilot, randomized controlled trial
performed in 2004 assigned 15 patients
with acute CSCR each into Diode
micropulse laser photocoagulation
(DMLP) group and argon green laser
group (Verma et al. 2004). Diode mi-
cropulse laser photocoagulation group
had significantly better improvement in
BCVA (p < 0.001) at 4 weeks after
DMLP but statistically insignificant at
8 and 12 weeks. In contrast, DMLP
group had significantly better improve-
ment in mean contrast sensitivity
(p < 0.001) at all follow-up visits after
treatment. None in the DMLP group
had scotoma, but six patients in argon
green laser group had residual scotoma
at 4 weeks after treatment (p < 0.05).
In 2013, a randomized, pilot trial
involved 15 patients with chronic
CSCR who were allocated into a sub-
threshold diode micropulse laser
(SDM) group (10 patients) and a sham
procedure group (five patients) (Rois-
man et al. 2013). SDM proved to be
effective in improving BCVA signifi-
cantly 3 months later but not in the
sham group where all patients needed
treatment after 3 months. All treated
patients in both groups had an
improvement in central macular thick-
ness and leakage on fluorescein
angiography.
In conclusion, DMLP appeared to
be effective and safe in treating both
acute and chronic CSCR and its con-
tribution to the recovery speed
(4 weeks after treatment) was appeal-
ing. These findings showed that its
therapeutic effects could be comparable
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to LP, with a great advantage over
conventional LP because it does not
produce any detectable signs of laser-
induced iatrogenic damage.
Conclusion
Updates in the management of CSCR,
particularly over the past decade, have
provided us with many more treatment
options that can be tailored to CSCR
patients with different risk factors,
clinical courses, disease progressions
and complications. For many of the
novel treatment methods, such as anti-
VEGF, mineralocorticoid receptor
antagonist (MRA), subthreshold mac-
ular argon laser and DMLP, larger
scale of randomized studies that
involve longer follow-up durations are
needed to confidently conclude their
long-term efficacy and safety in treating
CSCR. Based on the available evi-
dence, although the optimal timing to
offer many of these management meth-
ods for patients with CSCR remains
unclear at this stage, many of them are
beneficial for both acute and chronic
CSCR, namely PDT, LP and DMLP.
Among all the treatment options, PDT
stands out as the best available option
which is supported by concrete evi-
dences that had demonstrated its con-
sistent effectiveness and safety.
Although the pathogenesis of CSCR
is still incompletely understood, along
with the advances in imaging tech-
niques and management methods and
with continuous study of CSCR, it is
believed that the pathogenesis will be
fully grasped in the near future and
can, in turn, guide the management
methods to an increasingly confident
and promising direction.
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Received on October 5th, 2014.
Accepted on May 11th, 2015.
Correspondence:
Ian Y. Wong, FRCOphth
Room 301, Level 3
Block B, Cyberport 4
Pokfulam, Hong Kong
Tel: (+852) 2255 5632
Fax: (+852) 2817 4357
Email: ianyhwong@gmail.com
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