Purchase this article with an account.
Fabio Bignami, Giulio Ferrari, Chiara Giacomini, Stefano Franchini, Paolo Rama; Topical Application Of Infliximab (Remicade®) In The Treatment Of Corneal Caustication. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6279.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
TNF-alpha is involved in various ocular diseases. Different therapeutic options are available to inhibit TNF-alpha. Infliximab (Remicade®), a recombinant humanized monoclonal IgG1 antibody, has been administered systemically to treat corneal peripheral ulcers and ocular pemfigoid. This pilot study was designed to evaluate the safety and efficacy of topical Infliximab in the treatment of corneal neovascularization induced by alkali burn in mice.
20 C57BL/6 mice were used for this study. The left eye of 10 mice was causticated with NaOH. Infliximab was applied topically four times a day (10 μl) at 5 mg/ml dilution. Mice were divided in two groups: 1) instilled with Infliximab and 2) instilled with saline. The other 10 non causticated mice were divided in two groups: 1) instilled with Infliximab and 2) with saline. After 7 days of treatment, the eyes were removed for immunohistochemical analyses to evaluate corneal penetration, using a goat anti-human IgG labeled with Alexa Fluor 546 dye. Safety and efficacy endpoints were the following: 1) slit-lamp examination at 7 days to evaluate corneal opacity and edema using a published scale, 2) corneal neovascular area and 3) leukocyte infiltration determined on whole mounted corneas by immunofluorescence, using anti-CD31 and anti-CD45 monoclonal antibodies, respectively.
Infliximab immunoreactivity was only found in the superficial corneal epithelium. No pathological changes were detected in the epithelium, stroma, or endothelium in normal corneas treated with either saline or Infliximab. Alkali burned eyes receiving Infliximab didn’t show a significant increase in corneal transparency compared to the saline-treated group (p=0.35). In treated eyes, neovascular area was similar to the vehicle treated group (p=0.50) and there was no significant difference in CD45+ cell infiltration (p=0.35). The Mann-Whitney U test was used for comparisons.
Our data suggest that Infliximab eye drops at 5 mg/ml is not toxic to the normal cornea. We did not notice any difference in corneal neovascularization, corneal opacity and CD45+ leukocyte infiltration in the Infliximab versus vehicle groups. This could be due to the fact that Infliximab 5mg/ml 4 times a day does not appear to penetrate the corneal epithelium. Studies are underway to see whether different dosages and/or administration routes may achieve a better Infliximab penetration in the corneal stroma.
This PDF is available to Subscribers Only