Ocular toxicity of intravitreous adalimumab (Humira) in the rabbit

Roberta P.A. Manzano, Gholam A. Peyman, Petros E. Carvounis, Muhamet Kivilcim, Palwasha Khan, Patricia Chévez-Barrios, Walter Takahashi

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Purpose: To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira) in the rabbit eye. Methods: Twelve New Zealand albino rabbits received unilateral intravitreous injections of 0.1 ml of adalimumab 0.25 mg (three eyes), 0.50 mg (three eyes), 1.0 mg (three eyes) or 0.1 ml balanced salt solution (BSS, threeeyes). Slit-lamp biomicroscopy and fundoscopy were carried out at baseline, day 1, 7 and 14 following intravitreous injection, while electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed. Results: Slit-lamp biomicroscopy and fundoscopy were normal in eyes having received BSS, 0.25 mg or 0.50 mg adalimumab; however, inflammation was present in two of three eyes having received 1.0 mg adalimumab. Similarly, comparison of scotopic and photopic ERG light at baseline and day 14 demonstrated no changes in eyes receiving BSS, 0.25 mg or 0.50 mg adalimumab, but two of three eyes having received 1.0 mg adalimumab showed a greater than 30% reduction in a and b wave. Finally, histopathology demonstrated no differences between eyes receiving BSS, 0.25 mg or 0.50 mg of adalimumab, but two of three eyes injected with 1.0 mg demonstrated inflammatory cell infiltration of the vitreous and anterior chamber, with one of these eyes demonstrating retinal necrosis. Conclusions: Escalating doses of intravitreous adalimumab in rabbit eyes caused no detectable functional or structural ocular toxicity up to a dose of 0.50 mg. Administration of 1.0 mg in 0.1 ml was associated with an inflammatory reaction and retinal necrosis.

Original languageEnglish (US)
Pages (from-to)907-911
Number of pages5
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume246
Issue number6
DOIs
StatePublished - Jun 1 2008

Keywords

  • Adalimumab
  • Chronic uveitis
  • Intravitreous injection
  • Macular edema
  • Retinal toxicity
  • Tissue necrosis factor-alpha (TNF-alpha)

ASJC Scopus subject areas

  • Ophthalmology

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