PATHOLOGY Changes in choriocapillaris fenestration of rat eyes after intravitreal bevacizumab injection Yukiko Shimomura & Akira Hirata & Shinichiro Ishikawa & Satoshi Okinami Received: 11 November 2008 / Revised: 17 January 2009 / Accepted: 27 January 2009 / Published online: 17 February 2009 # Springer-Verlag 2009 Abstract Background To examine the effects of anti-VEGF antibody (bevacizumab) on the number of fenestrations in rat choriocapillaris. Methods Twenty-four eyes from 24 male Wister rats were injected intravitreally with 0.125 mg of bevacizumab. The rats were perfusion fixated at 1, 3, 7, 14 or 28 days after injection. The surfaces of the choriocapillaris on the RPE side were observed using scanning electron microscopy. Four eyes treated with human IgG were used as controls. The area sieve plate and the number of fenestrations after the bevacizumab injection were measured and compared with controls. Results In the controls, the sieve plate area was 80.7% of the total choriocapillaris area. The number of fenestrations was 69.2±0.2 /μm 2 of the fenestrated area. While there were no changes in the fenestrated area for any of the time points after the bevacizumab treatment, the number of fenestrations was significantly reduced to 52.9±4.4 at day 1, 55.6±3.6 at day 3 and 53.6±8.6 /μm 2 of the luminal surface at day 7 (ANOVA, p <0.05). Conclusions In this study, intravitreal bevacizumab injec- tion reduced fenestration of the normal choriocapillaris. These results indicate there is a latent risk inherent with bevacizumab treatment of normal choriocapillaris. Keywords Choriocapillaris . Fenestration . Bevacizumab . Scanning electron microscopy Introduction Various retinal and choroidal diseases such as diabetic retinopathy, retinal vein occlusion and age-related macular degeneration, cause serious visual disturbance. The accel- erating factors for these diseases are retinal and choroidal neovascularizations, which are caused by the overproduc- tion of angiogenic factors [1, 2]. Vascular endothelial growth factor (VEGF) is the key angiogenic factor that is involved in the development of the neovascularization in these disorders. On the other hand, VEGF is a multifunc- tional cytokine that is involved in the maintenance of the vasculature, lymphangiogenesis and neuroprotection [3, 4]. Bevacizumab is a humanized monoclonal anti-VEGF antibody that is currently approved for the treatment of metastatic colorectal cancer [5]. The molecules can penetrate the retina, and they are also transported into the retinal pigment epithelium, the choroid, and, in particular, into the photoreceptor outer segments after an intravitreal injection [6]. Clinically, bevacizumab has been administered intravitreally in VEGF-mediated diseases, such as choroidal neovascularization, central retinal occlusion, proliferative diabetic retinopathy, and other retinal diseases [7–10]. Many reports suggest that bevacizumab is useful in helping to reduce and ultimately cause the disappearance of newly formed abnormal vessels [7, 8, 11, 12]. There are several studies that have reported on the systemic injection-associated side effects of bevacizumab, including brain infarctions, gastrointestinal bleeding and menstrual disorders. However, few reports have examined the effects of bevacizumab on the normal structure of the ocular blood vessels [13]. Under normal conditions, the retinal pigment epithelium (RPE) appears to have a positive survival effect with regard to the maintenance of the highly vascularized and highly Graefes Arch Clin Exp Ophthalmol (2009) 247:1089–1094 DOI 10.1007/s00417-009-1054-1 This work was presented in part at the 80th Annual Meeting of the Association for Research in Vision and Ophthalmology, 2008. Y. Shimomura : A. Hirata (*) : S. Ishikawa : S. Okinami Department of Ophthalmology, Saga University Faculty of Medicine, 5-1-1, Nabeshima, Saga 849-8501, Japan e-mail: hirataa@cc.saga-u.ac.jp