Abstract
Purpose: :
Retinopathy of prematurity (ROP) is one of the leading causes of childhood blindness. In later stage of ROP, neovsacularization arises due to immature and ischemic retina. Neovascularization leads to retinal traction, retinal detachment, and retinal funnel configuration, and eventually affecting patients’ vision. Neovascularization is mainly driven by vascular endothelial growth factor (VEGF). An anti-VEGF antibody new drug: bevacizumab (avastin) has shown promising results in treating a lot of retinopathies, including age-related macular degeneration (ARMD), diabetic retinopathy, vitreous hemorrhage, and retinal vascular occlusion. These encouraging results show the potentials of bevacizumab (avastin) treatment in ROP. Although the safety profile of the bevacizumab has been tested and confirmed in the diseases mentioned above, none of the experiments are done in newborn babies or newborn animals. Previous studies have suggested that VEGF is an important growth factor during the development of retina. Whether anti-VEGF antibody usage would affect the development of visual system, especially in the retina in the newborn, remains unknown. To answer the above question, this study was designed to test the safety of bevacizumab used in newborn rabbits’ eyes.
Methods: :
One group of newborn rabbits (18 rabbits) received single intravitreal bevacizumab injection at the concentration of 1.25 mg/0.05 ml or 0.625 mg/0.05 ml at the age of 2, 4, and 6 weeks old. Each small group of rabbits consisted of 3 animals. The other group of rabbits (6 rabbits) received 3 consecutive injections of bevacizumab at the concentration of 1.25 mg/0.05 ml or 0.625 mg/0.05 ml at week 2, week 4, and week 6. Each small group of rabbits also consisted of 3 animals. The uninjected eyes served as control. Fundus examinations, histology and immunohistochemistry were used to detect retinal morphology abnormalities 12 months after bevacizumab injection. Retinal functional changes were accessed by electroretinogram (ERG).
Results: :
Twelve months after intravitreal injection of bevacizumab in newborn rabbits’ eye, either single or multiple injections, did not cause any toxicity findings on funduscopy, histopathologic studies, and ERG examinations.
Conclusions: :
Long-term safety of bevacuzumab in the newborn rabbits’ eye is good. This data are important for the future clinical application of bevacizumab in the newborns.
Keywords: retinopathy of prematurity • drug toxicity/drug effects • retinal neovascularization