Ocular toxicity of Ciprofloxacin/PSSA fluoroquinolone antibacterial solution in pigmented rabbits

The fluoroquinolone ciprofloxacin in an ophthalmic solution with polystyrene sulfonic acid (PSSA) was investigated for potential ocular toxicity in Dutch Belted rabbits, a pigmented species, following 3 months of daily topical ocular treatment (four times daily administration). Four groups of 16 rabbits (eight/gender) received 0%/1.5% (vehicle group), 0.3%/1.5%, 0.5%/1.5% Ciprofloxacin/PSSA Ophthalmic Solution, or Tarivid Ophthalmic Solution (0.3% ofloxacin) four times daily to the right eye only. The left eye of each animal was untreated and served as untreated control. An additional group of 16 rabbits was maintained as an untreated control group. Clinical observations noted during the 3 month treatment period were minimal for all treatment groups and were similar to the untreated controls. Slit-lamp biomicroscopic examinations, indirect ophthalmoscopic examinations, and pachymetry evaluations of the study animals revealed that these ocular parameters in the ciprofloxacin/PSSA-treated animals remained similar to the untreated controls throughout the 3 month treatment period. The integrity of the blood-aqueous barrier, as measured with a flare/cell meter, demonstrated that the barrier function remained intact for all treatment and control groups. Electroretinography (ERG) data demonstrated that the Ciprofloxacin/PSSA Ophthalmic Solutions and the Tarivid Ophthalmic Solution had minimal effects on A-, B-, or C-wave amplitudes or latencies, indicating that neither drug caused functional changes in the photoreceptors, inner retinal layers, or retinal pigment epithelium, respectively. Specular microscopy data demonstrated that the corneal endothelium remained normal in the treatment groups. Clinical chemistry, hematology, and gross necropsy observations remained within normal limits for rabbits for all treatment and control groups. The appearance of retinal tissues as well as all ocular and adnexal structures were considered within normal histologic limits in all groups. The ciprofloxacin/PSSA-containing formulations did not produce significant ocular irritation or signs of systemic toxicity following three months of four-times daily topical ocular administration to pigmented Dutch Belted rabbits.