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Introduction
Ranibizumab (Lucentis; GenentechInc., South San Francisco, California,USA) is a fragment of a recombinanthumanized IgG1 monoclonal antibodythat inhibits all isoforms of the humanvascular endothelial growth factor(VEGF). Most promising results ofphase III clinical studies have beenpublished regarding its intravitreal usein patients with neovascular age-rela-ted macular degeneration (AMD)(Rosenfeld et al. 2006). Retinal pig-ment epithelial (RPE) tears may occurspontaneously (Yeo et al. 1988), trau-matically (Amiel et al. 2006), follow-ing thermal laser treatment (Yeo et al.1988), following photodynamic ther-
apy with or without intravitreal triam-cinolone (Michels et al. 2006) andfollowing anti-VEGF therapies (Dha-lla et al. 2006; Gelisken et al. 2006;Meyer et al. 2006b). We describe twopatients who experienced RPE tearsfollowing intravitreal ranibizumabadministration.
Case Report
Patient 1
An 80-year-old woman with previ-ously stable high-risk dry AMD in herleft eye presented with an acute visionloss from 20 ⁄ 25 to 20 ⁄ 125. Fundus-copic and optical coherence tomogra-phy (OCT) evaluation revealed a
pigment epithelial detachment (PED)and subretinal fluid in the fovea (Fig.1). Fluorescein angiography (FA)identified an occult choroidal neovas-cularization (CNV).
After a detailed discussion of therisks and benefits of ranibizumab ther-apy, the patient received an intravi-treal injection (0.5 mg) in the left eye.Two weeks after the injection, she pre-sented with a vision decrease to20 ⁄160. Funduscopic exam, OCT andFA confirmed the presence of an RPEtear temporal to the fovea (Fig. 1).Within the following 8 months, visiondropped to 20 ⁄250.
Patient 2
A 75-year-old woman presented with avisual acuity (VA) of 20 ⁄ 80 and meta-morphopsia in the right eye. Examina-tion of the macula showed pigmentclumping, soft drusen and subretinalfluid confirmed by OCT (Fig. 2). FArevealed a small subfoveal, predomin-antly classic CNV secondary to AMD.The patient was treated, followinginformed consent, with 0.3 mg intravi-treal ranibizumab. One month later,VA was found to be stable at 20 ⁄ 80.OCT showed persistent subretinal fluid(Fig. 2). The patient received a secondinjection of ranibizumab (0.5 mg). Sixweeks after the second ranibizumabinjection, VA in the left eye dropped to20 ⁄100. OCT and clinical examinationshowed an RPE tear (Fig. 2). Within2 months, VA improved to 20 ⁄ 63 with-out further treatment.
Case Report
Retinal pigment epithelium tearsfollowing intravitrealranibizumab therapy
Christopher Kiss, Stephan Michels, Franz Prager, WolfgangGeitzenauer and Ursula Schmidt-Erfurth
Department of Ophthalmology and Optometry, Medical University of Vienna,Vienna, Austria
ABSTRACT.
Two patients with choroidal neovascularization secondary to age-related macu-
lar degeneration (AMD) developed a retinal pigment epithelial (RPE) tear fol-
lowing intravitreal injection of ranibizumab. One patient developed the RPE
tear within 2 weeks of the injection, the other within 6 weeks of a second injec-
tion. Both patients presented with vision loss of one line at diagnosis of the
RPE tear. During long-term follow-up, visual acuity improved in one patient by
one line and deteriorated in the second patient by three lines. RPE tears may
occur after intravitreal injection of ranibizumab in patients with neovascular
AMD, probably because of the rapid regression of the fibrovascular membrane.
Key words: ranibizumab – choroidal neovascularization – retinal pigment epithelium – age-
related macular degeneration
Acta Ophthalmol. Scand. 2007: 85: 902–903ª 2007 The Authors
Journal compilation ª 2007 Acta Ophthalmol Scand
doi: 10.1111/j.1600-0420.2007.00928.x
Acta Ophthalmologica Scandinavica 2007
902
Discussion
The short interval between antiangio-genic treatment and the RPE tear maysuggest an association. Case reportshave shown RPE tears occurring asearly as 1 week to as late as 8 weeks(Dhalla et al. 2006) after injection ofdifferent anti-VEGF drugs. In AMD, aPED may impair intercellular connec-tions between RPE cells, predisposingthem to rupture (Yeo et al. 1988), but
RPE tears have also been reported inlesions without PED (Michels et al.2006). Anti-VEGF therapy using rani-bizumab has been proven to halt neo-vascular growth and may even induceregression of the CNV, placing shear-ing forces on the RPE and causing theRPE (weakened by AMD) to contractand tear (Dhalla et al. 2006). Other the-ories include spontaneous rupture of aPED (Meyer et al. 2006b), globe defor-mation during needle insertion (Meyer
et al. 2006a) and vitreoretinal tractionresulting from syneresis and vitreousincarceration at the insertion site(Meyer et al. 2006a). Further studiesare needed to further evaluate the riskof RPE tears following intravitreal in-jection of anti-VEGF agents in AMD.
ReferencesAmiel H, Greenberg PB, Kachadoorian H &
O’Brien M (2006): Optical coherence
tomography of a giant, traumatic tear in
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Received on February 12th, 2007.
Accepted on February 17th, 2007.
Correspondence:
Stephan Michels
Universitatsklinik fur Augenheilkunde
und Optometrie
Medizinische Universitat Wien
Wahringer Gurtel 18–20
1090 Vienna
Austria
Tel: +43 1 40400 7988
Email: [email protected]
(A)
(B)
Fig. 1. High-resolution optical coherence tomography and fluorescein angiography at baseline
(A) and after the retinal pigment epithelial tear (B). Arrows indicate the borders of the retinal
pigment epithelial tear on the fluorescein angiography image.
(A)
(B)
(C)
Fig. 2. Baseline optical coherence tomography (A) shows subfoveolar fluid and retinal pigment
epithelial band changes because of the predominantly classic choroidal neovascularization. After
the first ranibizumab injection, an increase of subfoveolar fluid can be noted (B); after the sec-
ond injection, the retinal pigment epithelial tear occurred (C).
Acta Ophthalmologica Scandinavica 2007
903