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EFFECTS OF INTRAVITREAL BEVACIZUMAB IN REPEATED DOSES: An Experimental Study

SARI, AYCA MD*; ADIGUZEL, UFUK MD*; CANACANKATAN, NECMIYE PhD†; YILMAZ, NECAT MD‡; DINC, ERDEM MD*; OZ, OZAY MD*

Retina:
doi: 10.1097/IAE.0b013e3181b26343
Original Articles
Abstract

Purpose: To evaluate the effects of repeated 1.25-mg intravitreal bevacizumab injections on cornea and uveoretinal tissues using histologic and biochemical analyses.

Methods: Twenty-four New Zealand albino rabbits were used. Twelve rabbits received an injection of bevacizumab in their right eyes three times with an interval of 25 days (Group 1); their contralateral eyes served as controls (Group 2). Six rabbits had an injection of vehicle in both eyes (Group 3), with the same regimen as bevacizumab, and six rabbits’ eyes were used as a sham group (Group 4). Enucleated eyes were used for histologic and biochemical analyses, which included the activities of caspase 3 and 8 enzymes, glutathione content, catalase activity, and malondialdehyde content.

Results: No inflammation in aqueous humor and no sign of corneal or uveoretinal toxicity was found in bevacizumab-injected eyes. The difference of activity of corneal caspase 8 enzyme between Groups 1 and 2 and between Groups 1 and 4 was statistically significant (P < 0.05). In the uveoretinal tissue, in Group 1, the activities of caspase 3 and 8 enzymes were the lowest, and uveoretinal malondialdehyde content was also significantly lower than Group 4.

Conclusion: A repeated dose of intravitreal bevacizumab injection did not cause a toxic effect on cornea and uveoretinal tissue. Biochemically, it also did not cause any apoptosis, oxidative reaction, or lipid peroxidation. Instead, bevacizumab injection caused a considerable decrease in the apoptotic enzyme activities and lipid peroxidation in the uveoretinal tissue. Further studies are needed to be conducted for possible detrimental side effects and apoptotic and oxidative effects of repeated bevacizumab injections on both the injected and the contralateral eyes.

In Brief

Antivascular endothelial growth factor agents have become the treatment of choice in many of the ocular neovascular diseases recently. In this study, the effects of intravitreal bevacizumab injection in repeated doses were evaluated in rabbit eyes using histopathologic and biochemical analyses. The authors demonstrate a considerable decrease in the apoptotic enzyme activities and lipid peroxidation in the uveoretinal tissue.

Author Information

From the Departments of *Ophthalmology, †Biochemistry, and ‡Histology and Embryology, Mersin University Faculty of Medicine, Mersin, Turkey.

None of the authors have a direct or indirect commercial financial incentive associated with the study.

Reprint requests: Ayça Sari, MD, Department of Ophthalmology, Mersin University Medical School, Zeytinlibahce Street, Mersin, Turkey; e-mail: docayc@yahoo.com

© The Ophthalmic Communications Society, Inc.