title: Lack of effects on lymphocyte function from chronic topical ocular cyclosporine medication: a prospective study.
abstract: OBJECTIVE
  Topical cyclosporine has been widely used in the treatment of canine keratoconjunctivitis sicca without apparent documented clinical side effects. Thus the finding of reduced lymphocyte proliferation in animals treated with the drug at a concentration of 2% was both surprising and concerning. This study aimed to repeat the previous study and to compare the systemic effects of 2% cyclosporine in corn oil and 0.2% topical cyclosporine ointment (Optimmune, Intervet-Schering Plough, Welwyn, UK).
  
  
  METHODS
  Twenty dogs treated with Optimmune or with topical 2% cyclosporine in corn oil where previous treatment with Optimmune had failed were included in this study. Blood samples were taken at the time of first evaluation and at 1, 3 and 6 months of treatment to provide a biochemical and hematological health evaluation of the dogs and at each examination to measure circulating levels of cyclosporine and to obtain a lymphocyte population with which to determine a mitogen stimulation index (MSI) on treatment with phytohaemagglutinin-P (PHA) and conconavlin A (con-A). Levels of circulating cyclosporine were measured with an enzyme-multiplied immunoassay method and also the more sensitive quantification technique of mass spectroscopy (MS).
  
  
  RESULTS
  No blood samples contained over 15 ng/ml cyclosporine, the lower limit of detection using the radioimmunoassay or the enzyme-multiplied immunoassay technique. Positive control samples taken from dogs treated with oral cyclosporine for anal furunculosis showed measurable levels in blood, demonstrating that the technique worked. Mean MSI values at 0, 1, 3 and 6 months of treatment were 10.2, 11.4, 11.6, and 10.5 for dogs treated with 0.2% cyclosporine and 10.4, 11.9, 11.7, and 12.9 for dogs treated with 2% cyclosporine. Mitogen stimulation index values were not statistically different between the first examination and any subsequent examination time-point.
  
  
  CONCLUSIONS
  The findings of the study contradict those of the previous studies. No change in lymphocyte stimulation index was noted, neither were significant blood levels of cyclosporine documented after topical administration of either 0.2% or 2% cyclosporine. This study shows that topical cyclosporine is safe to use in the canine eye in line with the drug's safety record in this therapeutic regime over the past 20 years since its first use.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, UK. doctordlwilliams@aol.com
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004334:Drug Administration Schedule; D007322:Instillation, Drug; D007638:Keratoconjunctivitis Sicca / Q000188:drug therapy / Q000662:veterinary*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology
chemical_list: D016572:Cyclosporine