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Korean Journal of Ophthalmology - Manuscript Submission

Manuscript ID: 11129

Title: Intravitreal Bevacizumab As Primary Modality Of Treatment For Acute

Central Serous Retinopathy

Article Type: Clinical Study

Index: Retina, vitreous, uvea (R)

Abstract: Aim:To evaluate the effectiveness of intravitreal injection of

bevacizumab(IVB) as primary treatment for acute Central Serous Retinopathy(CSR)

for faster recovery of visual symptoms Design: Prospective interventional study

Material & Method : 9 eyes of 9 patients with Acute CSR were treated with IVB

(1.25 mg/0.05ml ). The outcome measures included visual acuity with Snellen’s &

Log MAR chart, Amsler grid examination , Central macular thickness(CMT) with

optical coherence tomography(OCT) and changes in fundus fluorescein

angiography(FFA) Results : All the patients showed resolution of neurosensory

detachment, improvement in visual acuity and other symptoms promptly within 1

month. Mean CMT decreased from 474 microns to 250 microns at 1 month. Mean

improvement in visual acuity was of 3.6 lines. None of the patients experienced a

significant adverse event with IVB Conclusion : IVB can be considered an effective

primary treatment modality for acute CSR , leading to faster improvement in visual

acuity & resolution of neurosensory detachment.

KeyWords: Central serous retinopathy (CSR);, bevacizumab;, FFA, OCT,

Intravitreal injection

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Intravitreal Bevacizumab As Primary Modality Of Treatment For Acute Central

Serous Retinopathy

Introduction

Central Serous Retinopathy is an idiopathic detachment of neurosensory retina in macular region . It is self-

limiting in majority of patients .Some patients develop pigment epithelial and photoreceptor damage with visual

impairment.

Recent indocyanine green angiography in CSR has demonstrated evidence of choroidal lobular ischemia and

choroidal venous congestion[2]

.VEGF produced by damaged retinal and choroidal cells has been implicated in

its pathogenesis. Therefore, Bevacizumab (Avastin)-an antiVEGF, may be utilized to reverse the changes seen

in CSR.

The purpose of our study is to report the use of intravitreal bevacizumab injection as primary treatment

modality in patients with acute CSR.

Materials and Methods-

9 eyes of 9 patients (5 men, 4 women) with CSR were included in our study. Mean age at the time of

presentation was 31 yrs (27 to 44 yrs).Patients were evaluated for the presence of acute CSR characterized by

various symptoms like-blurring of central vision, Metamorphopsia ,its duration and serous macular detachment

of less than 6 months.

Figure1

Each patient underwent best corrected visual acuity measurement(BCVA) by Snellen’s & Log MAR charts ,

Amsler grid examination , fundus evaluation, OCT and FFA. All patients had one or more focal RPE leaks

responsible for the neuro sensory detachment, and these serous detachments of the central macula were

confirmed by OCT.

Inclusion criteria included documented increase in CMT by OCT, active leak seen in FFA , no signs of

choroidal neovascularisation and ability and willingness to provide written informed consent

Exclusion criteria included prior treatment with laser photocoagulation or PDT (photodynamic therapy), IVT

(intravitreal triamcinolone) or IVB in previous 2 months, uncontrolled glaucoma (IOP >24 mm Hg) ,

uncontrolled hypertension , history of thromboembolic events including stroke, transient ischemic attacks, and

myocardial infarction , unable to follow or comply with all study related procedures.

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All patients were informed about other therapeutic options and off-label use of this therapy.

All patients were treated with intravitreal injection of 0.05 ml (1.25 mg) of bevacizumab (Avastin 100 mg/ 4ml

vial, Rosche), using 30 G needle under strict aseptic precautions . 5 patients were given 1 injection , 2 patients

received 2 injections & remaining 2 patients were given 3 doses at an interval of one month.

The principle outcome measures included change in CMT using OCT , change in Best Corrected Visual

Acuity(BCVA) and resolution of leakage in FFA .

Results- Table 1

9 eyes of 9 patients (5 men, 4 women) with CSR were treated with intravitreal bevacizumab injection. Their age

at the time of treatment ranged from 27 to 44 years (mean 31 yrs).

Pre operative BCVA ranged from 6/18 to 6/60. All 9 patients (100%) gained two or more lines improvement in

BCVA at the end of follow up. Mean improvement in visual acuity was of 3.6 lines on Snellen’s chart within 1

month. Mean pretreatment Log MAR visual acuity was 0.62 and improved to 0.18 at 1 month , 0.04 and 0.06

at 3 and 6 months respectively.

Table 2

The mean baseline CMT for all patients was 474 microns (range 426–539). Mean CMT at 1 month was 250

microns (range 276–368),thus showing a reduction of 224 microns from baseline CMT. At 3 months follow up

mean CMT was 230 microns (range, 189-269) with a difference of 244 microns from baseline. At the end of 6

months, the reduction in CMT was found to be 264 microns, with a measured mean CMT of 210 (range 180–

250).

All patients had complete or nearly complete anatomic resolution of macular fluid within 1 month after

treatment.

Figure 2

Table3

Most of the patients showed distorted lines on Amsler grid chart before treatment, which resolved significantly

after the injection.

A reduction in leakage areas in RPE was also seen in the FFA pictures of most of the patients after a single

injection of IVB. No patient lost vision or suffered from any significant complications related to the treatment.

Figure 3

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Discussion-

Central serous retinopathy is a disease in which a serous detachment of the neurosensory retina occurs over an

area of leakage from the choriocapillaris through the retinal pigment epithelium (RPE).

The high spontaneous resolution favours conservative management as a first line therapeutic option. But there is

some evidence supporting the benefit of early treatment for CSR.

A potential benefit for early resolution may be mediated by a lower rate of RPE degeneration in the treated eye,

which is also warranted because of an uncertain relation between the onset of detachment and that of symptoms

and special occupational demands for binocular visional function. [3]

Wang et al. (2002) reported that foveal atrophy in CSR is associated with reduction of visual acuity despite

resolution of serous detachment and hence reattachment within 4 months of onset is considered a relevant

therapeutic target because prolonged detachment is associated with photoreceptor atrophy.

Stewart (2006) reported that the fact that Laser damages the RPE with a known risk of developing choroidal

neovascularisation (CNV) has left clinicians seeking new treatments that are both more effective and less toxic.

Laser photocoagulation and PDT with verteporfin accelerate the resolution of detachment , but they should be

used with caution because they can induce permanent damage to the RPE or choriocapillary, severe retinal

thermal injury, subretinal choroidal neovascularization, often many years after the primary incident [5]

.

Figure 4

Our results are in agreement with another series of case reports by Schaal et al(2009) .They studied 12 eyes with

chronic CSR in which patients received 2 ± 1 intravitreal injections of bevacizumab 2.5 mg , during a follow up

of 24± 14 weeks. Mean BCVA increased by 2 ±2 lines; the change in BCVA (log MAR) was significant (P <

0.02). Mean CMT decreased significantly over follow up (P <0.05), with six patients (50%) showing complete

resolution of subretinal fluid. Similarly, our results are in agreement with the study by Seong et al.(2009), in

which they reported a series of 10 eyes of 10 patients with acute CSR. All patients showed resolution of

neurosensory detachment promptly, and improvement in visual acuity and symptoms within 1 month. At 6

months the mean BCVA (log MAR) had improved from 0.32 to 0.04, which was statistically significant (P =

0.007). No recurrence was observed during the 6 months follow up. Our results are also comparable to the study

of Shaaban A et al (2010) in which they reported a series of 20 eyes of 20 patients of both acute & chronic CSR.

Figure 5

In our case series, 9 eyes of 9 patients with Acute CSR were treated with IVB. Mean pretreatment Log MAR

visual acuity was 0.62 and improved to 0.18 at 1 month , 0.04 and 0.06 at 3 and 6 months respectively. Mean

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CMT decreased from 474 microns to 250 microns at 1 month. All the patients showed resolution of

neurosensory detachment promptly, improvement in visual acuity and other symptoms within 1 month.

Although this case series demonstrated successful treatment of acute CSR and none of the patients experienced

a significant adverse event with intravitreal bevacizumab Injection, it is limited by small number of patients and

short follow-up. Furthermore, individuals with CSR may experience spontaneous resolution of their symptoms

and leakage; our lack of a control group also does not allow one to determine if the resolution of the serous

detachment and RPE leaks in our cases was actually a result of treatment or was due to the natural history of the

disease. But the temporal course suggests that the improvement is likely due to the intravitreal bevacizumab

injection.

IVB can be considered an effective primary treatment modality for acute CSR, leading to faster improvement

in visual acuity & resolution of neurosensory detachment. These results are promising, and our prospective

study may result in a prospective randomized clinical trial to evaluate if this new therapy is effective enough to

be an option in the future.

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Table1- Baseline charectoristics of patients with CSR-

Variables Total

Age 31 yrs

Gender M:F 5:4

Duration of symptoms 3.3 +/- 2weeks

Number of injections 2

VA ( Log Mar) 0.62(=/-038)

Central macular thickness 474 microns

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Table 2- Results of CSR patients

S.no A/S Duration BCVA

before CMT

before No of

Injection BCVA Day 1

1 week

1Mon

2 Mon

3 Mon CMT

1Month CMT

3 Month No of

lines

improve

CMT Reduction

1 27/F 15 days 6/18 539 3 6/12 6/12 6/6 6/6 6/6 230 189 3 lines 350

2 30/M 15 days

6/36 551 3 6/18 6/12 6/9 6/9 6/9 250 269 4 lines 282

3 35/M 10 days 6/12 433 1 6/9 6/6 6/6 6/6 6/6 280 258 2 lines 175

4 27/M 1 month 6/24 464 2 6/18 6/9 6/6 6/6 6/6 260 250 2 lines 214

5 32 /F 20 days 6/24 520 1 6/18 6/12 6/9 6/6 6/6 240 230 4 lines 290

6 27/M 1 month 6/60 459 1 6/36 6/24 6/6 6/6 6/6 260 236 6 lines 223

7 29/m 1 month 6/18 500 1 6/12 6/12 6/6 6/6 6/6 240 200 3 lines 300

8 36 /F 1 week 6/24 426 1 6/18 6/12 6/6 6/6 6/6 250 221 4 lines 205

9 44/F 2month 6/36 380 2 6/24 6/24 6/9 6/9 6/9 240 220 4 lines 160

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Table3 - changes in CMT & BCVA over 1,3,6 month

Timing. Mean (SD) {range}

CMT (lm)

CMT Dif (lm) Mean BCVA

Log MAR

(SD)

Baseline 474 microns ------ o.62(=/-038)

1 month 250microns 224 microns 0.18(+/- 0.12)

3 month 230 microns 244 microns 0.04

6 month 210 microns 264 microns 0.06

C1 C2 C3

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References-

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central serous chorioretinopathy. Eye 9, 324–332.

2) Stanga PE, Lim JI, Hamilton P: Indocyanine green angiography in chorioretinal diseases: indications

and interpretation: an evidencebased update. Ophthalmology 2003; 110: 15– 21.

3) Wang MS, Sander 2002, Larsen M: Retinal atrophy in idiopathic central serous chorioretinopathy.Am J

Ophthalmol 2002; 133: 787– 793.

4) Yuzawa M, Kawamura A, Yamaguchi C, Shouda M, Shimoji M, Matsui M: Indocyanine green

videoangiographic findings in detachment of the retinal pigment epithelium. Ophthalmology 1995; 102:

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5) Stewart, J.M., 2006. Central serous chorioretinopathy half dose verteporfin PDT for central serous

chorioretinopathy. Br. J. Ophthalmol. 90, 805–806 (editrorial).

6) Schaal et al(2009) Hoeh, A.E., Scheuerle, A., Schuett, F., Dithmar, S., et al., 2009. Intravitreal

bevacizumab for treatment of chronic central serous chorioretinopathy. Eur. J. Ophthalmol. 19 (4),

613– 617.

7) Shaaban A. Mehany, MD Ahmad M 2010, Role of Avastin in management of central serous

chorioretinopathy

8) Torres-Soriano, M.E., Garcia-Aguirre, G., Kon-Jara, V., et al., 2008. A pilot study of intravitreal

bevacizumab for the treatment of central serous chorioretinopathy (case reports). Graefe’s Arch. Clin.

Exp. Ophthalmol. 246 (9), 1235–1239.

9) Hyun Kyung Seong a2008 Intravitreal Bevacizumab to Treat Acute Central Serous Chorioretinopathy :

Short-Term Effect

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Fig. 1.

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Fig. 1.

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Fig. 1.