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.
Keywords Infliximab - anti-TNF - Intravitreal injection - Remicade - Uveitis - Age-related macular degeneration - AMD - Rabbit - Electroretinogram - ERG - Histology - Toxicity - Safety - TNF
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.