Effect of Aflibercept on Human Corneal Endothelial Cells in Neovascular Age-Related Macular Degeneration: A Pilot Study

Intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors have being increasingly used in the treatment of neovascular age-related macular degeneration (AMD) in ophthalmic practice.1-4 The most commonly used VEGF inhibitors are bevacizumab (Avastin®, Genentech, San Francisco, California, USA), ranibizumab (Lucentis®, Genentech, San Francisco, California, USA) and aflibercept (Eylea®, Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA) among which aflibercept and ranibizumab were approved by the Food and Drug Administration (FDA) for this indication.

Aflibercept is the most recently developed VEGF inhibitor with a recombinant fusion protein consisting of human VEGF receptor extracellular domains from receptors 1 and 2 (VEGFR1 and VEGFR2) fused to the Fc domain of human IgG. This protein contains all human amino acid sequences, which minimizes the potential for immunogenicity in patients. The prolonged intravitreal half-life of aflibercept compared with ranibizumab can translate to a lower treatment load in terms of injections, monitoring, and medical visits. Several in vitro studies have shown that aflibercept, at the concentration usually used for treating retinal disorders had no toxicity to the ocular cells. However, although both ranibizumab and bevacizumab have been shown not to have harmful effects on corneal endothelium the effect of intravitreal aflibercept on human corneal endothelium has not been reported so far. Considering the functional importance of the corneal endothelium, particularly in aged population, the present study was designed to evaluate the in vivo toxicity of aflibercept on human corneal endothelial cells in patients with neovascular AMD.

Thirty-four eyes of 34 consecutive patients with neovascular AMD (19 male, 15 female; mean age 66.4±3.4 years; age range 57-76 years) were recruited for this observational prospective study. The study protocol was approved by the ethics committee and adhered to the tenets of the Declaration of Helsinki. All participants signed the informed consent before any study-related procedure.

All participants received one monthly intravitreal injection of aflibercept for three consecutive months, and later treatments were applied as needed. The follow-up period was six months.

The procedure for the intravitreal aflibercept injection was performed using standard aseptic techniques. After providing local anesthesia with proparacaine hydrochloride eye drops (Alcaine, Alcon Laboratories Inc, Fort Worth, Texas, USA), the eyelids and the inferior conjunctival fornix were sterilized with 5% povidone iodine. Aflibercept (2.0 mg, 0.05 ml) was injected through the pars plana (4 mm behind the limbus) using a 27-gauge needle.