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Ocular toxicity of intravitreous adalimumab (Humira) in the rabbit

  • Inflammatory Disorders
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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.

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Authors and Affiliations

  1. Department of Ophthalmology, University of São Paulo, Aramanaí St. 307, Alto de Pinheiros, 05450-030, São Paulo, SP, Brazil

    Roberta P. A. Manzano & Walter Takahashi

  2. Department of Ophthalmology, University of Arizona, Tucson, AZ, USA

    Gholam A. Peyman & Muhamet Kivilcim

  3. Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA

    Roberta P. A. Manzano & Petros E. Carvounis

  4. Department of Ophthalmology, Tulane School of Medicine, New Orleans, LA, USA

    Roberta P. A. Manzano, Muhamet Kivilcim & Palwasha Khan

  5. Department of Pathology, The Methodist Hospital, Houston, TX, USA

    Patricia Chevez-Barrios

Authors
  1. Roberta P. A. Manzano
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  2. Gholam A. Peyman
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  3. Petros E. Carvounis
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  4. Muhamet Kivilcim
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  5. Palwasha Khan
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  6. Patricia Chevez-Barrios
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  7. Walter Takahashi
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Corresponding author

Correspondence to Roberta P. A. Manzano.

Additional information

None of the authors has any proprietary interest in any technique or product described herein.

The authors have full control of all primary data and they agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data.

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Manzano, R.P.A., Peyman, G.A., Carvounis, P.E. et al. Ocular toxicity of intravitreous adalimumab (Humira) in the rabbit. Graefes Arch Clin Exp Ophthalmol 246, 907–911 (2008). https://doi.org/10.1007/s00417-008-0765-z

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  • DOI: https://doi.org/10.1007/s00417-008-0765-z

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