Retinal Pigment Epithelium Tears After Intravitreal Injection of Bevacizumab (Avastin) for Neovascular Age-Related Macular Degeneration

Ronan, Shawn M.; Yoganathan, Pradeepa; Chien, Fred Y.; Corcóstegui, Iñigo; Blumenkranz, Mark S.; Deramo, Vincent A; Elner, Susan G.; Fastenberg, David A.; Johnson, Mark W.; Lopez, Mauricio A; Mateo, Carlos; Moshfeghi, Darius M.; Navarro, Rafael; Rosenblatt, Brett; Sanislo, Steven R.; Saxe, S. J.; Zacks, David N.

doi:10.1097/iae.0b013e3180cc2645

Cited by 61 publications

(48 citation statements)

References 21 publications

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“…The development and progression of tractional retinal detachment and subretinal fibrosis in patients with PDR after IVB have been described (Arevalo et al 2008;Batman & Ozdamar 2010). Retinal pigment epithelium (RPE) tears and pigment epithelial detachment are reported after IVB for neovascular AMD (Chan et al 2007;Ronan et al 2007). The aetiology of these complications after IVB remains unclear, although acute alterations in the intraocular cytokine profile after IVB may contribute to these effects by promoting inflammation and fibrosis (Forooghian et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Bevacizumab modulates epithelial‐to‐mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up‐regulation

Chen

Liang

Chen

et al. 2012

Acta Ophthalmologica

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ABSTRACT.Purpose: To investigate the effect of bevacizumab treatment on connective tissue growth factor (CTGF) expression and the induction of epithelial-to-mesenchymal transition in ARPE-19 cells and human donor retinal pigment epithelium (HRPE) cells in vitro. Methods: We quantitated the protein and gene expression level of CTGF by ELISA. The effect of Fc-Fc receptor (Fc-FcR) interaction on CTGF expression was evaluated by CD64 siRNA silencing. Expression of epithelial-to-mesenchymal transition markers, alpha-smooth muscle actin (a-SMA) and zona occludens protein (ZO-1) was evaluated by Western blot. Cell migration and collagen gel contraction assay were examined by light microscopy, and collagen production was measured by ELISA. Results: Bevacizumab stimulation increased CTGF expression in ARPE-19 and HRPE cells in a dose-dependent manner. CD64 gene silencing inhibited the effect of bevacizumab-induced CTGF up-regulation. Bevacizumab increased the expression of a-SMA and decreased the expression of ZO-1 in ARPE-19 cells. Bevacizumab also caused the release of type-1 collagen and increased cell migration and contraction of collagen. Conclusions: Bevacizumab exerts pro-fibrotic effects on human RPE cells at clinical doses by up-regulation of CTGF expression via an Fc-FcR interaction. This effect of bevacizumab may be one of the underlying mechanisms involved in age-related macular degeneration therapy or intravitreal bevacizumab-associated complications.

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Section: Introductionmentioning

confidence: 99%

Bevacizumab modulates epithelial‐to‐mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up‐regulation

Chen

Liang

Chen

et al. 2012

Acta Ophthalmologica

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“…As reported in other studies, the vision in eyes with RPE tear did not show an acute decrease. 23 In our study collective, median BCVA in those eyes was 20/200 before intravitreal bevacizumab injection and 20/60 at 6 weeks control. However, as RPE support for the function of the fovea is essential, long-term follow-up of these eyes is necessary to make a conclusive statement for the outcome.…”

Section: Eyementioning

confidence: 61%

“…[29][30][31][32][33][34] Case series recently highlighted RPE tear increase after intravitreal bevacizumab treatment of neovascular AMD. [14][15][16][17][18][19][20][21][22][23][24][25][26] Chan et al 24 reported in a multicenter collective study 2.2% RPE tears in 1064 eyes. In a subgroup of 123 eyes with PED, 21 eyes (17.1%) had an RPE tear after intravitreal bevacizumab therapy.…”

Section: Discussionmentioning

confidence: 99%

“…If only single injections are considered the incidence of RPE tears was 13% of the eyes with PED. Ronan et al 23 reported from four centres a 0.08% RPE tear rate in a total of 1425 intravitreal injections. All cases with RPE tears had accompanying serous PED.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] In contrast, some cases of retinal pigment epithelial (RPE) tears after bevacizumab therapy have recently been reported. [15][16][17][18][19][20][21][22][23][24][25][26] Since intravitreal bevacizumab is a widely used therapy option for neovascular AMD, there is a need for further information on this topic. We analysed the occurrence of the RPE tear and the influence of related factors on this entity in a short-tem follow-up period following a single intravitreal bevacizumab administration for neovascular AMD.…”

Section: Introductionmentioning

confidence: 99%

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Retinal pigment epithelial tears after single administration of intravitreal bevacizumab for neovascular age-related macular degeneration

Gelişken¹,

Ziemssen²,

Voelker³

et al. 2008

Eye

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Purpose To analyse retinal pigment epithelial (RPE) tears following single administration of intravitreal bevacizumab for neovascular agerelated macular degeneration (AMD) during early follow-up. Methods Interventional, retrospective, noncomparative case series included 397 patients (409 eyes) of the 746 consecutive patients that met the eligibility criteria. Standardized visual acuity testing, fluorescein angiography, and optical coherence tomography were performed. Data collected included status of the fellow eye, previous treatment, subtypes of choroidal neovascularization (CNV), size and composition of the lesion. Multiple linear regression modelling was used to explore the effect of baseline parameters on the RPE tears. Primary end point was occurrence of RPE tears within 6 weeks after therapy. Results Fifteen of the 409 eyes (3.6%) developed RPE tear (95% confidence interval: 2.2-6.0, odds ratio: 26.3). The statistical modelling showed significant association between RPE tear and occult without classic CNV/predominantly haemorrhage vs predominantly/minimal classic CNV (P ¼ 0.019), as well as medium or large (44 disc area) vs small size of the total lesion (P ¼ 0.038). Previous treatment and status of the fellow eye did not statistically influence the risk of RPE tears. Conclusions An RPE tear can develop in up to 3.6% of eyes with neovascular AMD following single administration of intravitreal bevacizumab in a short-term follow-up. Medium and large lesion size and occult without classic and predominantly haemorrhagic subtype of CNV were important predictive factors. Preoperative assessment of the lesion characteristics may help in identifying the risk of individual patients with neovascular AMD before intravitreal bevacizumab treatment.

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Endophthalmitis After Intravitreal Injections

Schimel¹

2011

Arch Ophthalmol

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Retinal Pigment Epithelium Tears After Intravitreal Injection of Bevacizumab (Avastin) for Neovascular Age-Related Macular Degeneration

Cited by 61 publications

References 21 publications

Bevacizumab modulates epithelial‐to‐mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up‐regulation

Bevacizumab modulates epithelial‐to‐mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up‐regulation

Retinal pigment epithelial tears after single administration of intravitreal bevacizumab for neovascular age-related macular degeneration

Endophthalmitis After Intravitreal Injections

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