Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn

Abstract

ABSTRACT.Purpose: That vascular endothelial growth factor (VEGF) plays a major role in inflammatory angiogenesis has been well established. This pilot study was designed to evaluate experimental treatment with bevacizumab eyedrops in corneal neovascularization induced by alkali burn. The feasibility of topical administration, corneal cell viability and corneal penetration were investigated in an animal model. Methods: Eighteen chinchilla bastard rabbit corneas injured with 1 m NaOH were divided into three groups: untreated, early and late treatment groups. Eyedrops of bevacizumab solution (25 mg ⁄ ml) were administered five times daily. Clinical examination under stereoscopic microscope was performed to evaluate corneal opacity, neovascularization, vessel size and oedema. Histopathology was analysed for vessel density and apoptotic reaction. Additionally, intracameral bevacizumab concentration was measured with enzyme-linked immunosorbent assay (ELISA) after repeated topical applications. Results: A fast increase in aqueous bevacizumab concentration was achieved when the solution was instilled every minute onto a healthy eye surface. As well as clear anti-angiogenic effects, anti-fibrotic effects were also seen after corneal burn, maintaining corneal transparency. Early treatment of actively growing vessels showed a significantly better outcome, although apoptosis of pre-existing vessels could also be induced by the late treatment. No specific toxicity was seen regarding epithelium, keratocytes or endothelium. Conclusions: The data from this pilot study suggest that bevacizumab eyedrops can sufficiently penetrate the corneal stroma and anterior chamber. When administered soon after alkali burn, bevacizumab seems to significantly reduce corneal damage. Combinations of established treatment regimens with topical bevacizumab might be considered in severe injuries with otherwise devastating prognoses.

Hepatic arterial infusion of bevacizumab in combination with oxaliplatin reduces tumor growth in a rat model of colorectal liver metastases

“…The antiangiogenic effect of BE in rodent systems observed in the present study are supported by other reports, describing measurable effects of this drug in the rodent model, including induction of apoptosis [20] as well as inhibition of angiogenesis [18,[20][21][22][23][24][25][26] inflammatory cell recruitment and cytokine release [27], vascular permeability [28] and wound healing [29]. Habot-Wilner et al [22] showed a clear dose-dependent effect of BE on corneal neovascularization in Wistar rats.…”

The Boston Ocular Surface Prosthesis as a Novel Drug Delivery System for Bevacizumab

“…24 This regression was subsequently verified by additional reports from various groups. 25,26 Uy et al have demonstrated improvement in corneal neovascularization as well as patient comfort in their 2 patients with Stevens Johnson syndrome. 27 Kim et al recently treated 10 eyes with topical bevacizumab, and although initial regression of vessels was observed, a 2-month follow-up demonstrated adverse effects such as epithelial breakdown and stromal thinning.…”

Treatments for Corneal Neovascularization: A Review

“…Yatoh et al, 159 in 1998, and Cursiefen et al, 160 in 2004, showed that neutralizing VEGF can promote graft survival in the murine model. The majority of experimental studies 76,138,146,[160][161][162][163][164][165][166][167][168][169][170][171][172][173][174] using bevacizumab have shown a statistically significant reduction in the parameters reflecting NV (area/density/length of CNV and so on.). The effect has been the greatest on newly forming vessels rather than established vessels.…”