title: Ocular toxicity of intravitreal tacrolimus.
abstract: OBJECTIVE
  To investigate the ocular toxicity of intravitreally administered tacrolimus, a drug with potent immunosuppressive activity.
  
  
  METHODS
  To evaluate toxicity, tacrolimus was injected into the midvitreous cavity of 20 eyes of New Zealand pigmented rabbits at concentrations of 10, 50, 100, 250, 500, and 1000 microg. Control eyes received balanced salt solution. Eyes receiving 1000 microg were given injections of 0.2 mL solution; all others, including controls, received 0.1 mL. Rabbits were examined before the injections by slit-lamp biomicroscopy, indirect ophthalmoscopy, and an electroretinography test (ERG) was performed. The animals were followed up to 14 days postinjection by clinical examination and ERG. The animals were killed and the eyes were enucleated and processed for light microscopy.
  
  
  RESULTS
  No evidence of a retinal toxic reaction was seen in the eyes receiving 10 or 50 microg of tacrolimus. One out of 4 eyes that received 100 microg of the drug developed a vitreous reaction. All eyes treated with 250 microg or more developed vitreous reaction. One eye injected with 1000 microg of the drug developed occlusion of the temporal retinal vessels. Electroretinography showed decreasing b-wave amplitude with both dark- and light-adapted stimulus in the 500 and 1000 microg groups, and it was normal in the other groups. Histopathologic sections showed mild disorganization of the retina only at the 500 and 1000 microg dosage.
  
  
  CONCLUSIONS
  Doses of 10 and 50 microg of tacrolimus are nontoxic to rabbit eyes. Only transient vitreous opacities were observed in the groups that received 100 and 250 microg. Intravitreal doses of 500 and 1000 microg of tacrolimus proved to be toxic to the retina.
authors.affiliation: Department of Ophthalmology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Elke
authors.initials: E
authors.lastname: Passos
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Genaidy
authors.forename: Gholam A
authors.initials: GA
authors.lastname: Peyman
mesh_terms: D000818:Animals; D004596:Electroretinography; D005128:Eye Diseases / Q000139:chemically induced* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007267:Injections; D009887:Ophthalmoscopy; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000503:physiopathology; D016559:Tacrolimus / Q000633:toxicity*; D014822:Vitreous Body / Q000187:drug effects* / Q000473:pathology
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus