title: Retinal toxicity of commercially available intravitreal ketorolac in albino rabbits.
abstract: OBJECTIVE
  To determine whether intravitreal injection of a commercially available ketorolac tromethamine preparation causes retinal toxicity in albino rabbits.
  
  
  METHODS
  Nine albino rabbits were injected intravitreally with ketorolac tromethamine (3 mg; 0.1 mL) in one eye and saline (0.1 mL) in the fellow eye. Six of the rabbits received a single injection of ketorolac, and the other three rabbits underwent biweekly injection for a total of four injections. Electroretinography testing was performed on both eyes at different time intervals during 4 weeks of follow-up in the single injection group, and during 12 weeks of follow-up in the multiple injection group. Visual evoked potentials were recorded from each rabbit using monocular and binocular stimulation at the end of the follow-up period. Animals were then killed, and the retinas were prepared for morphologic examination at the light microscope level and for immunostaining for glial fibrillary acidic protein, as a marker of retinal damage.
  
  
  RESULTS
  The electroretinography responses from the control and experimental eyes were similar throughout the follow-up period in all rabbits of both experimental groups. There were no differences in the flash visual evoked potential responses between experimental and control eyes in the single injection group, while in the repeated injection group, statistically significant differences were found. Light microscopy did not identify significant histologic differences between the retinas from control and experimental eyes after a single dose. However, after repeated dosing, two of three eyes showed histologic evidence of local toxicity. Immunocytochemical analysis showed no glial fibrillary acidic protein staining in Muller (glial) cells throughout the retina in the single injection group. Slight glial fibrillary acidic protein staining was detected in only one of the three retinas from rabbits in the repeated injection group.
  
  
  CONCLUSIONS
  Commercially available ketorolac tromethamine was found to be toxic to the retinas of albino rabbits following multiple intravitreal injections at a dose of 3 mg while no electrophysiologic toxicity was found. Therefore, the use of commercially available ketorolac containing alcohol, for intravitreal injection is not recommended.
authors.affiliation: Department of Physiology and Biophysics, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and the Rappaport Institute, Haifa, Israel.
authors.forename: Izabela
authors.initials: I
authors.lastname: Komarowska
authors.forename: Gad
authors.initials: G
authors.lastname: Heilweil
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenfeld
authors.forename: Ido
authors.initials: I
authors.lastname: Perlman
authors.forename: Anat
authors.initials: A
authors.lastname: Loewenstein
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D004596:Electroretinography / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007267:Injections; D020911:Ketorolac Tromethamine / Q000633:toxicity*; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D019233:Retreatment; D014822:Vitreous Body
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005904:Glial Fibrillary Acidic Protein; D020911:Ketorolac Tromethamine