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Intravitreal administration of the anti-TNF monoclonal antibody Infliximab in the rabbit

  • Medical Ophthalmology
  • Published:
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Abstract

Background

Tumor necrosis factor (TNF) is known to play an important role in various immune-mediated ocular diseases; intravenous administration of the anti-TNF monoclonal antibody infliximab has proved beneficial in such cases. Since intravitreal injection (when available) is a substitute for systemic administration of various drugs targeting the eye, we aimed to evaluate the safety of intravitreal injection of infliximab in the rabbit eye.

Methods

Seven groups of New Zealand white rabbits (four animals in each group) received a single unilateral intravitreal injection (0.1 ml) of increasing doses of infliximab (namely 1, 2, 5, 8, 10 or 20 mg infliximab [Remicade]) or a sham injection respectively. Slit-lamp biomicroscopy, fundoscopy and electrophysiology recordings, i.e. scotopic, photopic and flicker responses, were performed at baseline and after 1, 5, 10, 15, 30 and 45 days. Infliximab-injected eyes were compared with sham-injected and with uninjected fellow eyes (n = 28). Animals were euthanized on day 45 for histopathological examination of the retinas.

Results

Clinical examination and electrophysiological testing were consistently unremarkable after either sham or 1 mg or 2 mg infliximab injections. In contrast, electrophysiological recordings were significantly reduced in a dose-dependent manner from day 1 through day 45, after 5, 8, 10 and 20 mg infliximab injections. Flicker responses were the most sensitive in detecting the lower toxic dose of 5 mg. Histopathological findings were similar in uninjected and sham-injected eyes, as well as after 1 mg or 2 mg infliximab injections. Consistent with the functional abnormalities, retinal deformities and diffuse edema were observed after injection of 5 mg or higher doses of infliximab.

Conclusions

Intravitreal infliximab may be safely administered up to a dose of 2 mg in the rabbit eye. Such doses can be used in the design of future clinical trials assessing the effects of infliximab for selected patients with immune-mediated ocular conditions.

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Authors and Affiliations

  1. 2nd Department of Ophthalmology, “Attikon” University Hospital, University of Athens, Athens, Greece

    Panagiotis G. Theodossiadis, Vasilios S. Liarakos, Alexander Charonis & Ioannis A. Vergados

  2. 1st Department of Propedeutic Medicine, “Laikon” Hospital, University of Athens, Athens, Greece

    Petros P. Sfikakis

  3. Pathology Department, Medical School, University of Athens, Athens, Greece

    Georgios Agrogiannis & Nikolaos Kavantzas

  4. 13 Lykiou Street, 10675, Athens, Greece

    Panagiotis G. Theodossiadis

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  1. Panagiotis G. Theodossiadis
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  2. Vasilios S. Liarakos
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Correspondence to Panagiotis G. Theodossiadis.

Additional information

The authors have no financial disclosure regarding this manuscript. All the authors have full control of all primary data, and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review all data if requested. Every procedure involving animals was conducted in accordance with the Declaration of Helsinki and the ARVO guidelines, and Council Directive 86/609/EEC of 24–11–1986 of the European Union, as well as Greek laws and regulations (Presidential Decree 160/1991, Act No 2015/2001) regarding the protection of animals used for experimental and other scientific purposes. The experimental protocol was approved by the Ethics Committee of “Attikon” University Hospital.

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Theodossiadis, P.G., Liarakos, V.S., Sfikakis, P.P. et al. Intravitreal administration of the anti-TNF monoclonal antibody Infliximab in the rabbit. Graefes Arch Clin Exp Ophthalmol 247, 273–281 (2009). https://doi.org/10.1007/s00417-008-0967-4

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  • DOI: https://doi.org/10.1007/s00417-008-0967-4

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