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Toxicity of 1-(β-d-arabinofuranosyl)cytosine after intravitreal injection in the rabbit eye

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Abstract

The retinal toxicity of intravitreally injected 1-(β-d-arabinofuranosyl)cytosine (cytarabine) was examined in 7 chinchilla rabbits to determine if cytarabine can be used as local therapy for vitreoretinal non-Hodgkin's lymphoma. Fractionated dose of 600 μg, 1500 μg, and 2700 μg cytarabine in stabilized saline were given intravitreally in one eye (2 × 300 μg, 5 × 300 μg, and 3 × 900 μg, respectively, with an interval time of 24 h) and stabilized saline in the other eye as control. Toxic effects were evaluated with biomicroscopy, direct ophthalmoscopy, fluorophotometry, electroretinography, light, and electron microscopy. Toxic effects were found with the 1500 μg and 2700 μg doses only. They consisted of a temporary impairment of the blood retina barrier function for fluorescein as measured by fluorophotometry and an irreversible change of the b-wave in the electroretinograms. No histopathologic changes were seen under the light microscope. Electron microscopic examination showed aberrations in the synaptic pedicles of the photoreceptor cells at a dose of 1500 μg cytarabine. The results suggest that the cytarabine dose that is expected to be therapeutic for vitreoretinal non-Hodgkin's lymphoma (about 90 μg given in three doses of 30 μg) is non-toxic for ocular structures.

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Authors and Affiliations

  1. Department of Ophthalmology, Leiden University Hospital, Rijnsburgerweg 10, 2333 AA, Leiden, The Netherlands

    Joke J. A. Th. Diets-Ouwehand, Rob J. W. de Keizer, Gijs F.J.M. Vrensen, Sylvia Groen-Jansen & Jaap A. van Best

  2. Department of Morphology, The Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands

    Gijs F.J.M. Vrensen

Authors
  1. Joke J. A. Th. Diets-Ouwehand
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  2. Rob J. W. de Keizer
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  3. Gijs F.J.M. Vrensen
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  4. Sylvia Groen-Jansen
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  5. Jaap A. van Best
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Correspondence to: J.A. van Best

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Diets-Ouwehand, J.J.A.T., de Keizer, R.J.W., F.J.M. Vrensen, G. et al. Toxicity of 1-(β-d-arabinofuranosyl)cytosine after intravitreal injection in the rabbit eye. Graefe's Arch Clin Exp Ophthalmol 230, 488–495 (1992). https://doi.org/10.1007/BF00175939

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  • DOI: https://doi.org/10.1007/BF00175939

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