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Intravitreal bevacizumab injection for chronic central serous chorioretinopathy
LI Xiu-juan, ZHANG Jin-song
Key words Central serous chorioretinopathy,
Intravitreal bevacizumab,
Retinal pigment
epithelium detachment
Central serous chorioretinopathy (CSC) is characterized by an idiopathic serous
neurosensory detachment primarily affecting the macula. In most cases, the disorder is
self-limited and spontaneously in 4 to 6 months, and the patients usually retain excellent vision.
However, chronic CSC is often associated with persistent subretinal exudation, cystoid
macular degeneration, choroidal neovascularization and consequent gross reduction of
vision.1,2 Severe visual loss is reported in 5% of patients with chronic CSC.3
The pathophysiology of CSC remains unclear. Recent studies relying on indocyanine
green angiography (ICGA) have shown that the etiology may begin with the changes in
choroidal permeability.4
Bevacizumab, an antibody to vascular endothelial growth factor (VEGF), has known anti
permeability properties and therefore may theoretically reverse the changes seen in CSC. This
article describes the use of intravitreal bevacizumab as a new method in the treatment of
chronic CSC.
Case reports
Case 1
A 36-year-old male complained of worsened vision and central scotoma in the left eye for 6
months. Visual acuity measured 0.4, and mottled atrophic changes of the RPE in the central
macula were observed on biomicroscopic examination. FA revealed a stippled
hyperfluorescence in the nasal macula. and OCT showed subfoveal neurosensory detachment.
After a careful explanation of the clinical aspects of the treatment, including other treatments
and possible complications, written informed consent for the surgery was obtained from the
patient. All of the procedures were approved by the institutional review board of our hospital.
The procedures used throughout this study complied with the tenets of the Declaration of
Helsinki. The patient was injected intravitreally with 2.5 mg (0.1ml) of bevacizumab in the left
eye, 3.5 mm from the corneal limbus, using a 30-gauge needle, in the inferotemporal quadrant
under aseptic conditions.. Visual acuity improved to 1.0 1 month following treatment, with
resolution of symptoms and the neurosensory detachment. Retinal examination, visual acuity
and OCT remained stable for 6 months of follow-up.
The patients did not developed systemic complications such as a thromboembolic event
or a cerebral vascular accident related to intravitreal bevacizumab. Ocular complications such
as intraocular inflammation, increase in IOP, increase in cataract, endophthalmitis, and retinal
detachment were not encountered in the study (Figure 1).
Case 2
A 37-year-old male presented with a 12-month history of decreased visual acuity in his
right eye. At the time of presentation, visual acuity was 0.5. FA before the treatment
demonstrated multiple focal hyperfluorescence areas with underlying RPE window defect at
the nasal macula. Neurosensory detachment was confirmed by OCT. After a careful
explanation of the clinical aspects of the treatment, written informed consent for the surgery
was obtained from the patient. The patient was injected intravitreally with 2.5 mg (0.1ml) of
bevacizumab in the right eye without complications. One month after treatment, his visual
quality improved, with decreased neurosensory detachment demonstrated by OCT. At
6-month follow-up, no subretinal fluid was observed by OCT, and visual acuity improved to 0.8
(Figure 2).
Discussion
The precise pathophysiology of CSC remains unclear and there is no standard treatment
for chronic CSC. Various medical treatments have also been attempted for this disorder,
including acetazolamide, beta-blockers, vitamins, non-steroidal anti-inflammatory medications,
all without decisive benefit.5,6 Laser photocoagulation accelerate the resolution of detachment,
but it should be used with caution because it can induce permanent scotomata which may
enlarge over time with RPE scar expansion, as well as the possible development of choroidal
neovascularization (CNV).7 Most recently, several case series have reported the use of
indocyanine green (ICG) guided photodynamic therapy(PDT) to treat chronic CSC.8 Some
authors report that ICG guided PDT appears to have a beneficial effect in treating patients with
chronic CSC by reducing fluid leakage, subretinal fluid accumulation, and serous detachment
with resultant improvement invision. However, PDT is expensive and cases of CNV and severe
choroidal ischemia have been reported following treatment for CSC.9, 10
Bevacizumab is a recombinant humanized full-length monoclonal antibody that binds all
isoforms of VEGF. The bevacizumab molecule can penetrate the retina and is also transported
into the retinal pigment epithelium, the choroid and into photoreceptor outer segments after
intravitreal injection.11. Intravitreal bevacizumab has been utilized to treat numerous ocular
disorders, generally those associated with neovascularization or vascular leakage as a
consequence of an underlying disease. In general, the results have been positive, with
numerous case series describing regression of neovascularization or resolution of leakage in
response to treatment12. In 2008, Niegel MF published the first case report of the intravitreal
use of bevacizumab for CSC. The results suggesting that intravitreal use of bevacizumab is
safe and effective for the treatment of CSC.13.In our study, it demonstrated that intravitreal
bevacizumab injection in patients with chronic CSC can bring on resorption of subretinal fluid,
which can be associated with the improved vision. Our results are similar to those of Niegel MF.
The mechanism by which intravitreal bevacizumab therapy ameliorates RPE leak and
resorption of subretinal fluid in chronic CSC is unknown, but we believe it may be related to its
ability to affect vascular permeability. Recent studies relying on ICGA have shown that the
etiology of CSC rests on the choriocapillaris, in which a focal increase in the permeability of the
choriocapillaris overwhelms the RPE and causes leakage of fluid into the subretinal space and
subsequent RPE detachment. The hyperpermeability of the choriocapillaris may be caused by
capillary and venous congestion, possibly because of choroidal ischemia. In fact, localized
choroidal ischemia has been observed in the normal fellow eyes in some patients with CSC.4
Choroidal ischemia in CSC may induce an increase in the concentration of VEGF. VEGF was
formerly known as “vascular permeability factor”, and has profound effects on vascular
permeability. For these reasons, it is likely that choroidal hyperpermeability caused by
choroidal ischemia is a nearly event in the development of symptomatic CSC where, under the
appropriate circumstances, it may lead progressively to RPE detachment followed by
neurosensory detachments. Theoretically, reduced levels of VEGF may improve the choroidal
ischemia, thus ameliorating the choroidal hyperpermeability in CSC. There is controversy over
the ability of bevacizumab to penetrate the retina and reach the choroid; however, recent
reports suggest that it does indeed do so 11, which supports the possibility that an intravitreal
injection of bevacizumab may be biologically active in areas of choroidal hyperpermeability.
In this small case series, we demonstrated that intravitreal bevacizumab injection in
patients with chronic CSC can bring on prompt resorption of subretinal fluid, which can be
associated with rapidly improved vision. However, the method is limited by retrospective
nature, small number of patients and short follow-up. Further investigations into both the
possible role of VEGF in the pathogenesis of CSC and treatment of CSC with anti-VEGF
agents are warranted.
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Fig 1. Case 1.
A. FA before treatment showed a stippled hyperfluorescence in the nasal half of the macula
with focal inkblot leakage within the foveolar avascular zone.
B. Vertical line OCT before treatment showed subfoveal neurosensory detachment.
C. Six month after treatment, FA showed RPE window defect with decrease in the stippled
hyperfluorescence and absence of active focal leakage.
D. Six month after treatment, vertical line OCT showed complete resolution of the serous
detachment, evident by the maintenance of foveal contour and absence of subretinal fluid.
Fig.2 Case 2
A.
FA before the treatment demonstrated multiple focal hyperfluorescence areas with
underlying RPE window defect at the nasal side of the macula.
B. Vertical line OCT before treatment demonstrated the presence of a serous neurosensory
detachment under the fovea.
C. Six month after treatment, FA revealed RPE window defect without active focal leakage.
D. Six month after treatment, vertical line OCT showed marked resolution of subretinal
detachment.