Toxicity of 1-(β-D-Arabinofuranosyl) cytosine after intravitreal injection in the rabbit eye

The retinal toxicity of intravitreally injected 1-(beta-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 micrograms, 1500 micrograms, and 2700 micrograms cytarabine in stabilized saline were given intravitreally in one eye (2 x 300 micrograms, 5 x 300 micrograms, and 3 x 900 micrograms, 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 micrograms and 2700 micrograms 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 micrograms cytarabine. The results suggest that the cytarabine dose that is expected to be therapeutic for vitreoretinal non-Hodgkin's lymphoma (about 90 micrograms given in three doses of 30 micrograms) is non-toxic for ocular structures.