Distribution And Toxic Effect Of Intracameral Injection Of Bevacizumab In Rabbit Eyes

Objective: To observe distribution of bevacizumab (avastin) in eye tissue and toxic effects of the anterior segment in rabbits which received intracameral bevacizumab 1.25mg/0.05ml.Methods: Twenty New Zealand albino rabbits were divided into two groups randomly, the left eyes in experimental group received intracameral injection of bevacizumab 1.25mg/0.05ml; the left eyes in control group received intracameral injection of balanced salt solution 0.05ml. The anterior segment of eyes and ocular fundus were examined by slit-lamp microscope and direct ophthalmoscope. Intraocular pressure and corneal endothelial microscope were measured before and after injection. Five rabbits of the two groups were randomly killed in the first day, the fourth day, the seventh day, the fourteenth day, the thirtieth day after injection, and the enucleated eyes were observed by the light microscope. The eyes of the fourth day and the thirtieth day were observed by the transmission electron microscope, paraffin sections and then immunofluorescence staining were used to observe distribution of bevacizumab in the tissues of eyes.Results: All experimental animals were healthy survival during the observation. No any signs of infection, corneal opacity, cataract, vitreous opacities, retinal hemorrhage were observed in eyes after surgery by slit-lamp microscope and direct ophthalmoscope. No significant difference regard to intraocular pressure before injection and the two hour, the first day, the seventh day, the fourteenth day, the thirtieth day after injection compared with the control group(P=0.982). No significant difference regard to corneal endothelial cell density before injection and the first day, the seventh day, the thirtieth day after injection compared with the control group(P=0.889). No obvious structural change of cornea, lens, chamber angle, iris, ciliary body and retina in the first day, the fourth day, the seventh day, the fourteenth day, the thirtieth day after injection in experimental group and control group under light microscope. No obvious ultrastructural change of cornea, lens, iris, ciliary body in the fourth day, the thirtieth day after injection in experimental group and control group under transmission electron microscope. Bevacizumab were distributed in the anterior chamber angle, iris, ciliary body, choroid and retina in injected eyes and fellow eyes after intracameral injection. Staining in fellow eyes was weak than injected eyes, bevacizumab was mainly distributed in the vascular tissues, such as the vessel wall and lumen. Strongest staining in iris was seen from the first day to the fourth day in injected eyes, then gradually becoming weakened, weak staining still existed in the thirtieth day. Strongest staining in iris was seen in the seventh day in fellow eyes. Staining in ciliary body was stronger than in iris in the fellow eyes and injected eyes. Strongest staining was seen in the seventh day, then gradually becoming weakened, and the weak staining still remained in the thirtieth day. Strongest staining of chamber angle was seen from the fourth day to the seventh day in the injected eyes, then gradually becoming weakened. The staining was disappeared in the thirtieth day, weak staining of trabecular meshwork was seen in the seventh day and the fourteenth day in the fellow eyes. Strongest staining of retina was seen in the seventh day in the fellow eyes and injected eyes, then gradually becoming weakened, weak staining still existed in the thirtieth day. Staining in choroid was seen from the first day to thirtieth day in the fellow eyes and injected eyes; The control eyes did not show positive staining.Conclusions: There is no obvious toxic effects of intracameral inject- tion with bevacizumab 1.25mg in the normal anterior segment of rabbits,which provides a reliable basis for the clinical safe application of Beva- cizumab. Bevacizumab were quickly distributed in the anterior chamber angle, iris, ciliary body, choroid and retina in injected eyes after intra- cameral injection of bevacizumab 1.25mg, bevacizumab accumulates par- ticularly in the vascular tissue, our findings support and explain the clinical observation of that iris neovascularisation was rapid regressed after intracameral injection and treatment would not remain less than one month; Distribution of bevacizumab in the anterior chamber angle, iris, ciliary body, choroid and retina in the fellow eyes illustrate systemic circulation of bevacizumab. Anyway, intracameral injection of bevacizumab may be a new strategy or a joint strategy for iris neovascularisation, even may be the preferred strategy.