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Leticia D. Alves, Alan R. Rassi, Moacyr Rigueiro, Murilo B. Abud, Ericka C. Freitas, Luciana B. Carneiro, David C. Isaac, Marco P. Avila; A Safety Study Of Serial Intravitreal Injections Of Infliximab In The Rabbit. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5650.
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Prior studies investigating possible retinal toxicity of intravitreal injections of infliximab have used single injections to demonstrate non-toxicity of the drug at dosages less 2.0mg. In this study, we evaluated the potential for retinal toxicity of serial intravitreal injections of 2.0mg infliximab in a rabbit model to simulate the administration of this drug in a clinical setting.
New Zealand albino rabbits were used. Each rabbit eye received either two serial injections (n=10) or three injections (n=10), each administration separated by 30 days. A separate group of rabbits eyes (n=4) given buffered saline solution (BSS) served as control animals. Intravitreal injections of 2.0 mg infliximab (Remicade, Schering-Plough) were given on each occasion. Slit-lamp biomicroscopy and fundoscopy were performed at baseline and after each injection. Electroretinography (ERG) was performed at baseline prior to first injection and then 30 days following the last injection to evaluate retinal function. The ERG was restricted to the study of cone function using 1-, 5-, 10, 15-, and 30- Hz bright flashes on a rod saturating background. Peak amplitude and implicit times of the major components of the ERG were extracted using conventional methods. At the end of the study, rabbits were sacrificed for morphological analysis
Slit-lamp biomicroscopy and fundoscopic examination did not reveal any significant retinal abnormalities between the eyes injected with infliximab and control eyes or between pre- and post-treated eyes. ERG response amplitude decreased systematically with temporal frequency. Post- treatment ERG amplitudes were on average 12-13% smaller than those obtained prior to treatment. However, there were no statistically significant differences comparing amplitude or implicit time between the pre- and post- treatment ERGs. Histology analysis did not reveal any statistically significant retinal abnormalities.
Intravitreal injections of infliximab are likely to be administered serially in patient populations to control a number of disease entities. Unlike prior studies that have investigated potential retinotoxicity effects after single administrations, this study investigated the possibility of retinotoxicity after multiple injections at dosages previously found to be relatively safe. We extend these findings by demonstrating the safety of infliximab over multiple injections.
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