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   Table of Contents      
Year : 2017  |  Volume : 65  |  Issue : 8  |  Page : 758-760

Aflibercept for recurrent or recalcitrant polypoidal choroidal vasculopathy in Indian eyes: Early experience

1 Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India
2 Vitreoretinal Services, Aditya Birla Sankara Nethralaya, Kolkata, West Bengal, India

Date of Submission29-Dec-2016
Date of Acceptance12-May-2017
Date of Web Publication18-Aug-2017

Correspondence Address:
Muna Bhende
Sankara Nethralaya, 18/41, College Road, Nungambakkam, Chennai - 600 006, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1003_16

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Treatment guidelines for symptomatic polypoidal choroidal vasculopathy (PCV) have been described, but the management of recurrent or recalcitrant PCV is a challenge. The newer anti-vascular endothelial growth factor: aflibercept has shown promise in the treatment of both treatment naive and recalcitrant PCV in studies outside India. We present the minimum 6 months results of intravitreal aflibercept in recurrent and recalcitrant PCV in Indian eyes after multiple injections of bevacizumab/ranibizumab with or without photodynamic therapy. Of 10 eyes, 7 resolved of which 4 recurred needing continued aflibercept. Three of the ten eyes did not show a response. To the best of our knowledge, this is the first report from India in this challenging situation.

Keywords: Aflibercept, anti-VEGF therapy, polypoidal choroidal vasculopathy

How to cite this article:
Bansal A, Bhende M, Sharma T, Bhende P, Mukherjee S. Aflibercept for recurrent or recalcitrant polypoidal choroidal vasculopathy in Indian eyes: Early experience. Indian J Ophthalmol 2017;65:758-60

How to cite this URL:
Bansal A, Bhende M, Sharma T, Bhende P, Mukherjee S. Aflibercept for recurrent or recalcitrant polypoidal choroidal vasculopathy in Indian eyes: Early experience. Indian J Ophthalmol [serial online] 2017 [cited 2020 Sep 22];65:758-60. Available from: http://www.ijo.in/text.asp?2017/65/8/758/213219

Polypoidal choroidal vasculopathy (PCV) is a leading cause of visual morbidity in Asians. Current epidemiological data show the prevalence of 22.3%–61.6% among Asians and 8%–13% in Caucasians who present with presumed neovascular age-related macular degeneration (hospital/clinic based).[1] Treatment guidelines for symptomatic PCV do not include the role of aflibercept.[2]

Yamamoto et al.[3] and Hara et al.[4] reported effectivity of anti-vascular endothelial growth factor (VEGF) aflibercept (Eylea, Regeneron, Tarrytown, NY, and Bayer HealthCare, Berlin, Germany) for treatment naïve PCV. Saito et al.[5] and Azuma et al.[6] reported that switching to aflibercept is effective for patients with PCV who develop resistance to ranibizumab. We report anatomical and functional outcomes of aflibercept for recurrent or recalcitrant PCV in Indian eyes.

  Methods Top

We conducted a retrospective case series of consecutive patients with recalcitrant or recurrent indocyanine green angiography (ICG) confirmed PCV treated with aflibercept and followed for a minimum 6 months at a tertiary care eye between February and November 2016. Institutional review board approved the study. All had received monthly bevacizumab or ranibizumab for 3 months followed by pro re nata (PRN) basis and/or photodynamic therapy (PDT). Recurrence was defined as an anatomical response to anti-VEGF injections with reactivation if the monthly injections were discontinued. Resistance/recalcitrance was defined as persistence or increase in the intra/subretinal fluid, pigment epithelial detachment (PED) or hemorrhage after minimum three injections on a monthly basis. Treatment-naive PCV was excluded. We followed published criteria for diagnosing active PCV.[2] All patients underwent ICG at baseline, and spectral domain optical coherence tomography (OCT) or swept-source OCT at baseline and each follow-up visit.

Treatment guidelines and technique

All patients underwent intravitreal aflibercept (2 mg/0.05 ml) on a planned monthly followed by PRN basis. Patients were examined at 1st and 3rd postinjection day then monthly thereafter. Response to treatment was defined in terms of complete resolution of intra- and sub-retinal fluid and/or decrease in the height of PED and maintenance of inactivity for minimum 8 weeks. Partial resolution was defined as a reduction in sub/intraretinal fluid and PED. Resistance/recalcitrance was defined as either persistence or increase in the intra/subretinal fluid, PED or hemorrhage after minimum 3 injections on a monthly basis. Recurrence was defined as the presence of intra/subretinal fluid/enlargement of PED/development of new PED/subretinal or subretinal pigment epithelium hemorrhage after 8 weeks of inactivity. ICG was repeated in resistant cases. In case of complete resolution at 4th week from the last injection, the patient was asked to review at 6th and 8th week, injection was repeated if activity recurred. All patients with residual fluid were retreated.

Best-corrected visual acuity (BCVA) was recorded in logMAR scale. Values of numerical characteristics were tested for normality and presented as mean value (± standard deviation). Student's paired sample t-test for comparing pre- and post-aflibercept BCVA and central foveal thickness (CFT). P < 0.05 was considered statistically significant.

  Results Top

Ten eyes of 10 patients with recurrent or recalcitrant PCV were included. Five males and five females, aged 53–83 years (mean 66 ± 9.2 years). All patients had received multiple intravitreal anti-VEGF injections (bevacizumab/ranibizumab) with median of 15.5 ± 7.3 (range 4–24) with/without PDT. One eye had vitrectomy for PCV-related vitreous hemorrhage.

Baseline mean logMAR BCVA was 0.39 ± 0.37 (range 0–1). All patients had branching vascular network (BVN) on ICG. Baseline characteristic, OCT features and treatment outcomes are tabulated in [Table 1] and [Table 2]. Mean baseline CFT was 243.7 ± 106.7 microns. Mean number of aflibercept injections were 3 ± 1.4 (range 2–6). Patients had a mean follow-up of 6.8 ± 1.31 months (range 6–9) after the first aflibercept, whereas median of total follow-up was 53 ± 44.8 (range 16–130 months). Mean final logMAR BCVA was 0.37 ± 0.35 (P = 0.49). Mean CFT reduced to181.7 ± 167.6 microns (P = 0.049). No ocular or systemic complications were noted.
Table 1: Baseline characteristics and treatment outcomes

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Table 2: Spectral domain optical coherence tomography characteristics before and after aflibercept

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Complete resolution was seen in seven eyes [Figure 1] and [Figure 2] - Case no. 2]. Three eyes had a reduction in PED and partial resolution of sub- and intra-retinal fluid even after minimum three injections. ICG in all these showed the persistence of BVN in one eye and enlargement in two. Two eyes switched back to maintenance with ranibizumab, and one eye underwent PDT with ranibizumab. Four of the seven eyes that showed initial resolution developed recurrence after a period of quiescence of which all were re-treated with aflibercept and responded satisfactorily to the same.
Figure 1: (a-c) Color fundus, indocyanine green angiography and swept source optical coherence tomography images of the right eye of a patient with active macular polypoidal choroidal vasculopathy 8 years after treatment with multiple sessions of anti-vascular endothelial growth factor monotherapy, two sessions of combination photodynamic therapy and anti-vascular endothelial growth factor. The fundus image shows exudation at the macula with a partly fibrotic lesion. Indocyanine green angiography shows a large branching vascular network. Swept source optical coherence tomography image shows the polypoidal network involving the fovea, pigment epithelial detachment and intraretinal cystic spaces

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Figure 2: (a-c) Fundus image, indocyanine green angiography and swept source optical coherence tomography images after 2 monthly aflibercept injections shows a decrease in exudation, reduction in the branching vascular network on indocyanine green angiography. The swept source optical coherence tomography image shows resolution of the intraretinal cystic spaces as well as the pigment epithelial detachment

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  Discussion Top

Aflibercept, a fusion protein with binding sequences from VEGF receptors 1 and 2 possesses high binding affinity for isomers of VEGF-A, VEGF-B and placental growth factor (PGF), and prevents VEGF from initiating proliferation and migration of vascular endothelial cells.[7] Other members of the VEGF family, including PGF [8] and VEGF-B [9] have critical roles for angiogenesis and hyperpermeability. Because of wider spectrum pharmacological targets, aflibercept might have greater effectiveness for suppression of PCV vascular lesions.

Till date, there are no treatment guidelines for aflibercept in PCV. Most studies have used 3 monthly followed by PRN injections. We analyzed eyes with recurrent and recalcitrant PCV who had already received multiple (median: 15.5 ± 7.3) intravitreal anti-VEGF injections (bevacizumab/ranibizumab) with/without PDT. We treated these patients with intravitreal aflibercept on planned monthly followed by PRN basis in contrast to Saito et al.[5] and Azuma et al.[6] who gave minimum three injections on a monthly basis.

In our cohort, BCVA improved in two eyes, maintained in seven and deteriorated in one. Mean BCVA (logMAR) improved to 0.37 from 0.39, but the difference was statistically not significant. Mean CFT improved to 181.7 from 243.7 microns, and difference was statistically significant. Hirakata et al.[10] found no significant gain in vision or CFT at 6 months but gain was significant at 1 year. Saito et al.[5] and Azuma et al.[6] reported significant CFT reduction and visual gain at month 3 and 12, respectively. No ocular or systemic adverse events were seen.

Limitations were small sample size, short follow-up which could explain the limited visual improvement. To the best of our knowledge, this is the first series from India reporting the results of aflibercept in recurrent or recalcitrant PCV.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Wong CW, Wong TY, Cheung CM. Polypoidal choroidal vasculopathy in Asians. J Clin Med 2015;4:782-821.  Back to cited text no. 1
Koh AH; Expert PCV Panel, Chen LJ, Chen SJ, Chen Y, Giridhar A, Iida T, et al. Polypoidal choroidal vasculopathy: Evidence-based guidelines for clinical diagnosis and treatment. Retina 2013;33:686-716.  Back to cited text no. 2
Yamamoto A, Okada AA, Kano M, Koizumi H, Saito M, Maruko I, et al. One-year results of intravitreal aflibercept for polypoidal choroidal vasculopathy. Ophthalmology 2015;122:1866-72.  Back to cited text no. 3
Hara C, Sawa M, Sayanagi K, Nishida K. One-year results of intravitreal aflibercept for polypoidal choroidal vasculopathy. Retina 2016;36:37-45.  Back to cited text no. 4
Saito M, Kano M, Itagaki K, Oguchi Y, Sekiryu T. Switching to intravitreal aflibercept injection for polypoidal choroidal vasculopathy refractory to ranibizumab. Retina 2014;34:2192-201.  Back to cited text no. 5
Azuma K, Obata R, Nomura Y, Tan X, Takahashi H, Yanagi Y. Angiographic findings of ranibizumab-resistant polypoidal choroidal vasculopathy after switching to a treat-and-extend regimen with intravitreal aflibercept. Retina 2016;36:2158-65.  Back to cited text no. 6
Stewart MW. Aflibercept (VEGF Trap-Eye) for the treatment of exudative age-related macular degeneration. Expert Rev Clin Pharmacol 2013;6:103-13.  Back to cited text no. 7
Rakic JM, Lambert V, Devy L, Luttun A, Carmeliet P, Claes C, et al. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest Ophthalmol Vis Sci 2003;44:3186-93.  Back to cited text no. 8
Zhang F, Tang Z, Hou X, Lennartsson J, Li Y, Koch AW, et al. VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis. Proc Natl Acad Sci U S A 2009;106:6152-7.  Back to cited text no. 9
Hirakata T, Fujinami K, Watanabe K, Sasaki M, Noda T, Akiyama K. One-year outcome of intravitreal aflibercept injection for age-related macular degeneration resistant to ranibizumab: Rapid morphologic recovery and subsequent visual improvement. Clin Ophthalmol 2016;10:969-77.  Back to cited text no. 10


  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


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