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 Table of Contents  
Year : 2023  |  Volume : 3  |  Issue : 2  |  Page : 430-432

Off-label use of intravitreal brolucizumab injection for fibrinous central serous chorioretinopathy: A case report

1 Retina Institute of Bengal, Siliguri, West Bengal, India
2 Department of Vitreoretinal Services, Shantilal Shanghvi Eye Institute, Mumbai, Maharashtra, India

Date of Submission17-Aug-2022
Date of Acceptance12-Dec-2022
Date of Web Publication28-Apr-2023

Correspondence Address:
Somnath Chakraborty
Retina Institute of Bengal, Pradhan Nagar, Siliguri - 734 003, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_2041_22

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The authors describe the first case report of management of central serous chorioretinopathy (CSCR) associated with subretinal fibrin deposition by intravitreal injection (IVI) of brolucizumab in a 45-year-old male. At 3 months, his best-corrected visual acuity (BCVA) improved from 20/200 to 20/80. On fundus evaluation, there was complete resolution of the subretinal fluid (SRF) and fibrin, which was confirmed on spectral-domain optical coherence tomography (SD-OCT). There were no reports of ocular or systemic adverse effects. Increased flux and permeability of the retinal pigment epithelium secondary to anti-vascular endothelial factor (anti-VEGF) injection agent can explain the migration of the fibrin toward the choroid and its resolution. Further molecular and clinical studies are warranted to better understand the role of brolucizumab in the management of fibrinous CSCR.

Keywords: Anti-vascular endothelial growth factor, brolucizumab, central serous chorioretinopathy, fibrin

How to cite this article:
Chakraborty S, Sheth JU. Off-label use of intravitreal brolucizumab injection for fibrinous central serous chorioretinopathy: A case report. Indian J Ophthalmol Case Rep 2023;3:430-2

How to cite this URL:
Chakraborty S, Sheth JU. Off-label use of intravitreal brolucizumab injection for fibrinous central serous chorioretinopathy: A case report. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 10];3:430-2. Available from: https://www.ijoreports.in/text.asp?2023/3/2/430/374927

Central serous chorioretinopathy (CSCR) is a common disease affecting men of working age, with a higher incidence found in males (10/100,000) as against 2/100,000 in females.[1],[2] The pathophysiology is closely linked to choroidal hyperperfusion and breakdown of the retinal pigment epithelium (RPE) barrier function.[1],[2] The natural course of CSCR is self-limiting in majority of patients, with a favorable prognosis.[1],[3] Occasionally, the subretinal fluid (SRF) may become turbid, leading to fibrin development.[4] The fibrin gradually resolves over a period, but may occasionally produce fibrotic scars.[5] There have been few reports demonstrating the use of anti-vascular endothelial growth factor (anti-VEGF) therapy, including ranibizumab (Lucentis®; Genentech, S. San Francisco, CA, USA/Roche, Basel, Switzerland) and bevacizumab (Avastin, Genentech, Inc.,), in the management of fibrinous CSCR.[6],[7]

We herein describe a novel case of fibrinous CSCR that was successfully treated with intravitreal injection (IVI) of brolucizumab (Pagenax®; Novartis India Ltd, Mumbai, India).

  Case Report Top

A 45-year-old male presented with decreased vision and metamorphopsia in the right eye (OD) for 5 months in 2017. His best-corrected visual acuity (BCVA) was 20/100 in OD. Based on the fundus examination [Figure 1]a and the spectral-domain optical coherence tomography (SD-OCT) [Figure 1]b, he was diagnosed with acute CSCR and subretinal fibrin. On fundus fluorescein angiography (FFA) [Figure 1]c, [Figure 1]d, the patient demonstrated an extrafoveal leak corresponding to the fibrin, for which focal laser photocoagulation was performed. During FFA, the patient developed an anaphylactic reaction, which was managed medically. After the treatment, the patient was lost to follow-up.
Figure 1: (a) CFP of the right eye (OD) of the patient during the first visit in 2017, demonstrating the SMD and subretinal fibrin, which were confirmed on SD-OCT. (b-d) Sequential FFA illustrating the site of the extrafoveal leak (yellow arrow, c) and areas of window defects. CFP = color fundus photograph, FFA = fundus fluorescein angiography, SD-OCT = spectral-domain optical coherence tomography, SMD = submacular detachment

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The patient returned in February 2022 with OD metamorphopsia and reduction in vision to 20/200 that had been present for 4 months. The patient had a recurrent CSCR with subfoveal fibrinous deposition [Figure 2]a and [Figure 2]b in OD. FFA was deferred since the patient had a history of anaphylactic reaction to the fluorescein dye in 2017. Because of the nonresolving nature along with fibrin in the subfoveal location, observation alone was not considered. The patient underwent treatment with IVI brolucizumab (6 mg/0.05 mL). At 3 months, his BCVA improved to 20/80. There was complete resolution of the SRF and fibrin on fundus evaluation [Figure 2]c, which was confirmed on SD-OCT [Figure 2]d. There were no reported ocular or systemic adverse effects. The patient was advised observation and is scheduled for a visit after 3 months.
Figure 2: (a) CFP of the right eye (OD) of the patient during the episode of recurrence in 2022, demonstrating the SMD with subretinal fibrinous deposition. (b). SD-OCT image at this stage confirmed the presence of SMD and fibrin (dense hyperreflectivity in the subretinal space). Additionally, there was an area of central hyporeflectivity with the fibrin with an underlying RPE defect (yellow arrow). After undergoing treatment with IVI of brolucizumab, there was complete resolution of the SMD and fibrin on fundus examination (c) and SD-OCT (d). CFP = color fundus photograph, IVI = intravitreal injection, RPE = retinal pigment epithelial, SD-OCT = spectral-domain optical coherence tomography, SMD = submacular detachment

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  Discussion Top

The first reported case of subretinal fibrin in association with CSCR was by Gass.[8] Subsequently, fibrin has been identified in the subretinal space as well as the sub-RPE region, with leakage noted in many of the cases on FFA.[9],[10] Shinojima et al.[9] evaluated 21 eyes with CSCR and identified fibrin in the subretinal space and sub-RPE region. Hussain et al.[10] identified the presence of subretinal fibrin over the leakage site in 6/10 (60%) eyes with acute CSCR. Liang et al.[4] demonstrated an RPE defect with an overlying hyporeflective space within the hyperreflective fibrin in 87.5% of the eyes. A similar finding was also noted in our case. Based on multimodal imaging, it has been hypothesized that choroidal exudation occurs through this RPE defect into the subretinal space.[11] Furthermore, the overlying hyporeflectivity represents the site of exudative fluid egression, indicating an active disease.[12],[13]

The management of fibrinous CSCR is debatable. In the literature, few reports of spontaneous resolution of the fibrin have been described.[10],[14],[15] However, development of subretinal fibrosis can occur in 70% of eyes.[5] Both spontaneous resolution as well as fibrotic scars have been noted with thermal laser photocoagulation.[5],[11] In our report, performing a thermal laser could not be considered as FFA was not performed since the patient was allergic to the fluorescein dye. The use of Photodynamic Therapy (PDT) in the management of fibrinous CSCR is contentious. Yannuzzi[16] proposed that fibrin and verteporfin can produce bioconjugates, which can lead to subretinal fibrosis and scarring. This can be due to the exaggerated response to the PDT, leading to severe visual loss.[16] Due to these adverse events associated with it and its unavailability in the host nation, treating our patient with PDT was no longer an option.

Anti-VEGF agents, including bevacizumab and ranibizumab, have been occasionally used in the management of fibrinous CSCR with good response.[6],[7] However, no studies on the efficacy of brolucizumab injection in eyes with fibrinous CSCR have been published. In our patient, there was an excellent response to the brolucizumab injection with a significant improvement in visual acuity and complete resolution of the fibrin and the SRF. The exact mechanism for faster resolution of fibrin after anti-VEGF therapy remains unknown. In vitro studies have shown that VEGF antagonists, including ranibizumab and bevacizumab, induce a temporary increase in permeability of the RPE by reducing the RPE barrier function.[17] This effect was longer with the bevacizumab molecule (9 days) compared to the ranibizumab molecule (2 days).[17] This increase in the transepithelial flux may play a crucial role in the resolution of fluid and fibrin in CSCR eyes treated with anti-VEGF agents. Increased RPE permeability and flux in the presence of an RPE disruption can potentially propel larger fibrin molecules into the choroid. This can lead to a faster resolution of both the SRF and the fibrin. Although these in vitro studies have not been conducted on the brolucizumab molecule, a similar mechanism of action on the RPE barrier function can be expected. Nonetheless, further molecular studies evaluating the mechanism of action of brolucizumab on the resolution of fibrin are warranted to validate our hypothesis.

One limitation of the current case report was the lack of Optical Coherence Tomography Angiography (OCTA). However, the presence of macular neovascularization (MNV) is unlikely in our case due to several factors including the relatively younger age and lack of associated clinical and imaging features such as hemorrhage/exudation/intraretinal fluid (IRF). Additionally, the spontaneous resolution of fibrin has also been reported.[5] Although CSCR has a natural waxing and waning course, this is usually in terms of fluid resolution, either IRF and/or SRF.[1] Subretinal fibrin is a distinct form of CSCR manifestation characterized by subretinal yellowish-white exudation.[4] Due to the dense nature of this clinical and OCT biomarker, its resolution, although spontaneous, is very gradual.[4],[5] Indeed, in a recent study comparing PDT's effectiveness for CSCR with and without fibrin, researchers found that, at 1, 3, and 6 months post-PDT, the subretinal fibrin resolved in 72.9%, 95.8%, and 95.8% of cases, respectively.[4] Furthermore, anti-VEGF medications such as ranibizumab and bevacizumab have been demonstrated to be effective in the treatment of fibrinous CSCR.[6],[7] By increasing RPE permeability and transepithelial flux,[17] anti-VEGF medications may cause fibrin molecules to be driven from the subretinal space into the choroid. As a result, the SRF and fibrin may resolve more quickly, as was seen in our case. Thus, in our report, the resolution of fibrin was most likely attributable to the injection of brolucizumab. Further research is needed to acquire a better understanding of this facet.

  Conclusion Top

In conclusion, this is the first reported case illustrating the role of IVI brolucizumab in the management of CSCR complicated by subretinal fibrin deposition. Our results indicate that brolucizumab may be a promising therapeutic option in the management of these challenging cases. Additional studies are warranted to better understand the role of anti-VEGF agents in the management of fibrinous CSCR.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Kaye R, Chandra S, Sheth J, Boon CJF, Sivaprasad S, Lotery A. Central serous chorioretinopathy: An update on risk factors, pathophysiology and imaging modalities. Prog Retin Eye Res 2020;79:100865. doi: 10.1016/j.preteyeres.2020.100865.  Back to cited text no. 1
Kitzmann AS, Pulido JS, Diehl NN, Hodge DO, Burke JP. The incidence of central serous chorioretinopathy in Olmsted County, Minnesota, 1980-2002. Ophthalmology 2008;115:169-73.  Back to cited text no. 2
Hanumunthadu D, Tan ACS, Singh SR, Sahu NK, Chhablani J. Management of chronic central serous chorioretinopathy. Indian J Ophthalmol. 2018;66:1704-14.  Back to cited text no. 3
Liang Z, Qu J, Huang L, Linghu D, Hu J, Jin E, et al. Comparison of the outcomes of photodynamic therapy for central serous chorioretinopathy with or without subfoveal fibrin. Eye (Lond) 2021;35:418-24.  Back to cited text no. 4
Schatz H, McDonald HR, Johnson RN, Chan CK, Irvine AR, Berger AR, et al. Subretinal fibrosis in central serous chorioretinopathy. Ophthalmology 1995;102:1077-88.  Back to cited text no. 5
Symeonidis C, Kaprinis K, Manthos K, Androudi S, Anastassilakis K, Dimitrakos SA. Central serous chorioretinopathy with subretinal deposition of fibrin-like material and its prompt response to ranibizumab injections. Case Rep Ophthalmol 2011;2:59-64.  Back to cited text no. 6
Khan B, Kaur R, Anand, V, Matreja, P. S. Prompt response to single injection of bevacizumab in a case of fibrinous central serous choroidopathy (CSC). Bangladesh J Med Sci 2017;16:157-60.  Back to cited text no. 7
Gass J. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. 4th ed. St Louis, MO: CV Mosby; 1987. p. 56-7.  Back to cited text no. 8
Shinojima A, Hirose T, Mori R, Kawamura A, Yuzawa M. Morphologic findings in acute central serous chorioretinopathy using spectral domain-optical coherence tomography with simultaneous angiography. Retina 2010;30:193-202.  Back to cited text no. 9
Hussain N, Baskar A, Ram LM, Das T. Optical coherence tomographic pattern of fluorescein angiographic leakage site in acute central serous chorioretinopathy. Clin Exp Ophthalmol 2006;34:137-40.  Back to cited text no. 10
Saito M, Iida T, Kishi S. Ring-shaped subretinal fibrinous exudate in central serous chorioretinopathy. Jpn J Ophthalmol 2005;49:516-9.  Back to cited text no. 11
Yannuzzi NA, Mrejen S, Capuano V, Bhavsar KV, Querques G, Freund KB. A central hyporeflective subretinal lucency correlates with a region of focal leakage on fluorescein angiography in eyes with central serous chorioretinopathy. Ophthalmic Surg Lasers Imaging Retina 2015;46:832-6.  Back to cited text no. 12
Rajesh B, Kaur A, Giridhar A, Gopalakrishnan M. “Vacuole” sign adjacent to retinal pigment epithelial defects on spectral domain optical coherence tomography in central serous chorioretinopathy associated with subretinal fibrin. Retina 2017;37:316-24.  Back to cited text no. 13
Rezai KA, Eliott D. Optical coherence tomographic findings in pregnancy-associated central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol 2004;242:1014-6.  Back to cited text no. 14
Pole C, Gaw Stephanie SL, Tsui Irena I. Utility of optical coherence tomography angiography in pregnancy-associated central serous chorioretinopathy. Am J Ophthalmol Case Rep 2020;20:100979. doi: 10.1016/j.ajoc.2020.100979.  Back to cited text no. 15
Yannuzzi LA. Central serous chorioretinopathy: A personal perspective. Am J Ophthalmol 2010;149:361-3.  Back to cited text no. 16
Miura Y, Klettner A, Roider J. VEGF antagonists decrease barrier function of retinal pigment epithelium in vitro: Possible participation of intracellular glutathione. Invest Ophthalmol Vis Sci 2010;51:4848-55.  Back to cited text no. 17


  [Figure 1], [Figure 2]


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