Open Journal of Ophthalmology, 2012, 2, 93-96
http://dx.doi.org/10.4236/ojoph.2012.23020 Published Online August 2012 (http://www.SciRP.org/journal/ojoph)
93
Three Consecutive Monthly Intravitreal Ranibizumab for
Choroidal Neovascularization in Central Serous
Choriorethınopathy: A Case Report
Kazim Erol1, Esin Sogutlu Sari2*, Arif Koytak3, A. Karaçor1, D. T. Çoban1, M. Bulut1
1Ophthalmology Department, Antalya Training and Research Hospital, Antalya, Turkey; 2Ophthalmology Department, Kartal Training
and Research Hospital, Istanbul, Turkey; 3Ophthalmology Department, Bezmialem Vakif University, Istanbul, Turkey.
Received March 19th, 2012; revised April 25th, 2012; accepted May 8th, 2012
ABSTRACT
Purpose: The authors report the result of three consecutive monthly intravitreal ranibizumab injection for choroidal
neovascularization (CNV) after bevacizumab injection for chronic central serous rethinopathy (CSR). Methods: A 48-
year-old man with chronic CSR was treated with intravitreal single dose 2.5 mg bevacizumab. One year after CNV was
occurred, and three consecutive monthly intravitreal ranibizumab injections were performed. Results: Four weeks later
the first ranibizumab dose, best corrected visual acuity was improved 20/80 to 20/20 and remained stable within one
year. Conclusion: Repeat intravitreal ranibizumab injection in CNV after bevacizumab injection for chronic CSR ap-
peared to be an effective treatment option.
Keywords: Central Serous Choriorethinopathy; Choroidal Neovascularization; Ranibizumab
1. Introduction
Central serous chorioretinopathy (CSR) is common dis-
eases of the posterior segment of the eye characterized by
serous detachment of the neurosensory retina in the
macula secondary to an idiopathic leakage in the outer
blood-retinal barier at the retinal pigment epithelium
(RPE). Although visual distortions are usually mild and
spontaneous recovery occurs within a few months, some
patients with CSR have a poor visual acuity due to retinal
pigment epithelium atrophy, persistant or recurrent pig-
ment epithelial detachment, subretinal fluid and chor-
oidal neovascularization (CNV) [1]. CNV secondary to
CSR is an uncommon relation which has been also noted
to complicate laser photocoagulation treatment due to the
puncture of Bruch’s membrane by laser burns and photo-
dynamic theraphy due to the RPE alterations and induces
the release of vascular endothelial growth factor (VEGF)
[2].
Different treatment options including photodynamic
theraphy with vertaporfin, laser photocoagulation, vitro-
retinal submacular surgery and intravitreal anti VEGF
agents (bevacizumab or ranibizumab) have been reported
for the chronic and recurrent CSR with or without CNV.
[2-5] We report the results of three consecutive monthly
intravitreal ranibizumab injection for CNV after bevaci-
zumab injection for chronic CSR. To our knowledge
there have been no previously reported cases of CNV
after bevacizumab for the management of CSR.
2. Case Report
A 48-year-old man with a history of chronic ulcerative
colitis had reported a 8-month history of blurry vision in
his right eye and he had received prior medical treatment
with acetazolamid. Metamorphopsia was noted and vis-
ual acuity was 20/40. RPE “sawtooth appearence” was
present on optical coherence tomography (OCT) sug-
gesting a chronic CSR (Figure 1). Treatment options
were discussed and intravitreal bevacizumab (2.5 mg)
injection was performed. Four weeks later best corrected
visual acuity was improved to 20/20 and OCT revealed
complete resolution of neurosensory serous detachment
(Figure 2).
One year after the bevacizumab injection, the patient
complained of decreased vision in his right eye for the
past 2 weeks. Best corrected visual acuity was 20/80 and
metamorphopsia was again noted. OCT imaging showed
CNV with subretinal fluid (Figure 3). Treatment options
were discussed three consecutive monthly intravitreal ra-
nibizumab injection (0.5 mg) were performed. Four
weeks later the last dose best corrected visual acuity was
*Corresponding author.

Three Consecutive Monthly Intravitreal Ranibizumab for Choroidal Neovascularization in
Central Serous Choriorethinopathy: A Case Report
94
improved to 20/20 and OCT demonstretad the complete
resolution of choroidal neovascular membrane and
subretinal fluid (Figure 4). Follow-up examination at
one year after the last ranibizumab injection vision re-
mained stable on 20/20.
Figure 1. Baseline optical cohorence tomography (OCT)
showed serous detachment of the neurosensory retina with
central macular thickness of 389 μm and “sawtooth ap-
pearence” of the retina pigment epithelium (RPE). Baseline
flourescein angiography (FA) showed RPE “window defect”
with focal leakage of flourescein.
3. Discussion
Chronic CSR which also known as diffuse retinal epi-
theliopathy characterised by persistent or recurrent se-
rous retinal detachment with widespread pigmentary
changes, decompenstation of the RPE, multifocal or dif-
fuse RPE alteration, increased permeability of the chor-
oidal vessels. The growth of pathological blood vessels
in the macular area secondary to CSR which is the reason
of an overexpression of VEGF could appear either spon-
taneously or after laser and photodynamic treatment.
Currently, anti-VEGF agents has been widely used in the
treatment of CNV and also in proliferative diabetic reti-
nopathy, and macular edema due to the cataract surgery,
diabetes or retinal vein occlusion [6-8]. In recent years,
studies demonstrated that VEGF antibodies could reduce
choroidal hyperpermeability and choriocapillaris ischae-
mia associated with CSR [9]. In the current case report
we shown the results of three consecutive monthly in-
travitreal ranibizumab injection for CNV after bevaci-
zumab for chronic CSR.
Figure 2. Optical coherence tomography demonstrated the
complete resolution of neurosensory serous detachment
with central macular thickness of 223 μm.
Figure 3. Flourescein angiography (late frames) and optical coherence tomography demonstrating a subfoveal classic chor-
oidal neovascular membrane with subretinal fluid.

Three Consecutıve Monthly Intravitreal Ranibizumab for Choroidal Neovascularization in
Central Serous Choriorethinopathy: A Case Report
95
Figure 4. Clinical color photograph, flourescein angiography (late phases) and optical coherence tomography demonstreat-
ing complete resolution of CNV and subretinal fluid.
In our case, chronic CSR was succesfully treated with
2.5 mg of single dose intravitreal bevacizumab injection.
However CNV occured one year after the bevacizumab,
then we decided to try repeat injection of another VEGF
antibody ranibizumab for the management of CNV. Four
week later, subretinal fluid and neovascular membrane
was completely resolved and the vision improved to 20/20
and remained stable within one year. Both ranibizumab
and bevacizumab, which are derived from the same
parent molecule, inhibit all isoforms of VEGF. However,
molecular and pharmacologic properties of these agents
differ in several aspects. In an experimental animal
model [10], ranibizumab has been shown to penetrate the
choroid rapidly after an intravitreal injection. Bevacizumab
is a three times larger molecule. Investigations, however,
have proven the presence of bevacizumab throughout the
neural retina, in the subretinal space and choriocapillaris
within 24 hours of intravitreal injection.
Although CNV may complicate the natural history of
CSR, in this case 2.5 mg single dose of bevacizumab did
not prevent the devoloping CNV secondary to CSR. In
2008, Wang et al. [11] reported that subretinal granular
deposits from the phagocytosis photoreceptor segment,
accumulating after retinal detachment could prevent the
anti-VEGF treatment working in chronic CSR. Accordingly,
Schaal et al. hypothesized that VEGF expression might
be higher in patients with chronic CSR compared to
patients with wet age-related macular degeneration (AMD)
because affected areas are often multiple and widespread
and not limited to the central part of the retina like in
AMD and consequently might require higher doses of
anti-VEGFs [12]. The same investigator reported that
50% of the cases demonstrated a complete resolution of
subretinal fluid after treatment with 2.5 mg bevacizumab
[12].
More recently, Kaiser et al. [13], shown that ranibi-
zumab with a fixed 12-month dosing regimen of 0.5 mg
has a favorable safety and efficacy profiles in patients
with subfoveal CNV unresponsive to pegaptanib and
bevacizumab. They explained this superiority with the
fact that ranibizumab has a lower molecular weight and
higher affinity to VEGF-A, which theoretically implies
that it could better penetrate the retina and access the
choroidal neovascular complex more readily. In addition,
Rosenfeld et al. [14] reported that multiple intravitreal
ranibizumab at escalating doses ranging from 0.3 to 2.0

Three Consecutive Monthly Intravitreal Ranibizumab for Choroidal Neovascularization in
Central Serous Choriorethinopathy: A Case Report
96
mg were well tolerated and biologically active in eyes
with neovascular AMD within 5-months. Guided by this
researches in this case we performed repeat intravitreal
ranibizumab injection in CNV after bevacizumab inject-
tion for chronic CSR and it appeared to be an effective
treatment option. Our experience in this case was unable
to prove that bevacizumab 2.5 mg could prevent the de-
velopment of CNV as a complication of chronic CSC.
Also in this case, ranibizumab was not found superior to
bevacizumab in the treatment of the disease itself and in
the prevention of its complications. However, we can
hypothesize that a single dose of anti-VEGF may remain
insufficient for improving the natural course of the dis-
ease and multiple doses may be more effective as in wet
AMD. Further comparative studies with larger series and
longer follow-up periods are needed in order to achieve a
definitive conclusion on the role of anti-VEGF agents in
the management of CSR.
4. Acknowledgments
The authors indicate no government or non-government
financial support.
REFERENCES
[1] R. H. Loo, I. U. Scott, H. W. Flynn Jr., J. D. Gass, T. G.
Murray, M. L. Lewis, P. J. Rosenfeld and W. E. Smiddy,
“Factors Associated with Reduced Visual Acuity during
Long-Term Follow-Up of Patients with İdiopathic Central
Serous Chorioretinopathy,” Retina, Vol. 22, No. 1, 2002,
pp. 19-24doi:10.1097/00006982-200202000-00004
[2] H. Matsunaga, K. Nangoh, M. Uyama, H. Nanbu, Y.
Fujiseki and K. Takahashi, “Occurrence of Choroidal
Neovascularization Following Photocoagulation Treat-
ment for Central Serous Retinopathy,” Nihon Ganka
Gakkai Zasshi, Vol. 99, 1995, pp. 460-468.
[3] W. M. Chan, T. Y. Lai, D. T. Liu and D. S. Lam, “In-
travitreal Bevacizumab (Avastin) for Choroidal Neovas-
cularization Secondary to Central Serous Chorioretino-
pathy, Secondary to Punctate İnner Choroidopathy, or of
İdiopathic Origin,” American Journal of Ophthalmology,
Vol. 143, No. 6, 2007, pp. 977-983.
doi:10.1016/j.ajo.2007.02.039
[4] B. A. Cooper and M. A. Thomas, “Submacular Surgery to
Remove Choroidal Neovascularization Associated with
Central Serous Chorioretinopathy,” American Journal of
Ophthalmology, Vol. 130, No. 2, 2000, pp. 187-191
doi:10.1016/S0002-9394(00)00395-0
[5] A. Koytak, K. Erol, E. Coskun, N. Asik, H. Oztürk, Y.
Ozertürk, “Fluorescein Angiography-Guided Photody-
namic Therapy with Half-Dose Verteporfin for Chronic
Central Serous Chorioretinopathy,” Retina, Vol. 30, No.
10, 2010, pp. 1698-1703.
doi:10.1097/IAE.0b013e3181da4354
[6] J. F. Arevalo, R. A. Garcia-Amaris, J. A. Roca, et al.,
“Primary Intravitreal Bevacizumab for the Management
of Pseudophakic Cystoid Macular Edema Pilot Study of
the Pan-American Colloborative Retina Study Group,”
Journal of Cataract & Refractive Surgery, Vol. 33, No.
12, 2007, pp. 2098-2105. doi:10.1016/j.jcrs.2007.07.046
[7] D. Iturralde, R. F. Spaide, C. B. Meyerle, J. M. Klancnik,
L. A. Yannuzzi, Y. L. Fisher, J. Sorenson, J. S. Slakter, K.
B. Freund, M. Cooney and H. F. Fine, “Intravitreal
Bevacizumab (Avastin) Treatment of Macular Edema in
Central Retinal Vein Occlusion: A Short-Term Study,”
Retina, Vol. 26, No. 3, 2006, pp. 279-284.
doi:10.1097/00006982-200603000-00005
[8] D. Kook, A. Wolf, T. Kreutzer, A. Neubauer, R. Strauss,
M. Ulbig, A. Kampik and C. Haritoglou, “Long-Term Ef-
fect of İntravitreal Bevacizumab (Avastin) in Patients
with Chronic Diffuse Diabetic Macular Edema,” Retina,
Vol. 28, No. 8, 2008, pp. 1053-1060.
doi:10.1097/IAE.0b013e318176de48
[9] S. J. Lim, M. I. Roh and O. W. Kwon, “Intravitreal
Bevacizumab İnjection for Central Serous Chorioretino-
pathy,” Retina, Vol. 30, No. 1, 2010, pp. 100-106.
doi:10.1097/IAE.0b013e3181bcf0b4
[10] J. Gaudreault, D. Fei, J. C. Beyer, A. Ryan, L. Rangell, V.
Shiu, L. A. Damico, “Pharmacokinetics and Retinal Dis-
tribution of Ranibizumab, a Humanized Antibody Frag-
ment Directed against VEGF-A, Following Intravitreal
Administration in Rabbits,” Retina, Vol. 27, No. 9, 2007,
pp. 1260-1266. doi:10.1097/IAE.0b013e318134eecd
[11] M. Wang, I. C. Munch, P. W. Hasler, C. Prünte and M.
Larsen, “Central Serous Chorioretinopathy,” Acta Ophthal-
mologica, Vol. 86, No. 2, 2008, pp. 126-145.
doi:10.1111/j.1600-0420.2007.00889.x
[12] K. B. Schaal, A. E. Hoeh, A. Scheuerle, F. Schuett and S.
Dithmar, “Intravitreal Bevacizumab for Treatment of
Chronic Central Serous Chorioretinopathy,” European
Journal of Ophthalmology, Vol. 19, No. 4, 2009, pp. 613-
617.
[13] R. S, Kaiser, O. P. Gupta, C. D. Regillo, A. C. Ho, M. S.
Fineman, J. F. Vander, J. A. McNamara and G. C. Brown,
“Ranibizumab for Eyes Previously Treated with Pegap-
tanib or Bevacizumab without Clinical Response,” Ophth-
almic Surgery, Lasers and Imaging, Vol. 43, No. 1, 2012,
pp. 13-19.
[14] P. J. Rosenfeld, J. S. Heier, G. Hantsbarger and N. Shams,
“Tolerability and Efficacy of Multiple Escalating Doses
of Ranibizumab (Lucentis) for Neovascular Age-Related
Macular Degeneration,” Ophthalmology, Vol. 113, No. 4,
2006, pp. 623-632. doi:10.1016/j.ophtha.2006.01.027