title: Retinal toxicity of liposome-incorporated and free ofloxacin after intravitreal injection in rabbit eyes.
abstract: BACKGROUND
  Ofloxacin (OFLX) is a fluoroquinolone-antibiotic with a broad antimicrobial spectrum that may have a potential role in the treatment of bacterial endophthalmitis. However, its elimination half life after intravitreal injection is short. To prolong the intravitreal antibacterial level OFLX was incorporated into liposomes. This study was performed to investigate the retinal toxicity of liposome-incorporated and free OFLX.
  
  
  METHODS
  OFLX was incorporated into multilamellar large vesicles. 0.1 ml of this suspension (= 180.2 microg OFLX) was injected into the midvitreous of rabbit eyes (n = 6). Free OFLX in doses of 100 microg, 500 microg and 1,000 microg was injected into the midvitreous of a second group of rabbit eyes (n = 18). The other eye served as a control and received empty liposomes or normal saline solution, respectively. Before injection and at the end of follow-up an ERG was obtained. After a follow-up of 1 day, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light- and transmission electron microscopy.
  
  
  RESULTS
  The ERG as well as the histologic studies did not reveal any pathological changes after injection of liposome-incorporated OFLX compared to the control eyes. Significant reduction of the ERG was observed after 500 microg free OFLX in 2 out of 6 eyes after 1 and 14 days, respectively, and in 2 eyes 1 day after 1,000 microg free OFLX. Three days after injection of 1,000 microg OFLX the retina showed focal destruction in 1 out of 6 eyes. In another eye with the same dose 14 days after injection the photoreceptor outer segments showed disorganisation.
  
  
  CONCLUSIONS
  This study shows that liposome-incorporated OFLX did not have any retinal toxicity in this animal model. Free OFLX appears to have no retinal toxicity in rabbit eyes at a dose of 100 microg after intravitreal injection. Injection of higher doses resulted in ERG changes and marked retinal damage.
authors.affiliation: Department of Ophthalmology, Christian-Albrechts-University, Kiel, Germany. bwiechens@ophthalmol.uni-kiel.de
authors.forename: B
authors.initials: B
authors.lastname: Wiechens
authors.forename: D
authors.initials: D
authors.lastname: Neumann
authors.forename: J B
authors.initials: JB
authors.lastname: Grammer
authors.forename: U
authors.initials: U
authors.lastname: Pleyer
authors.forename: J
authors.initials: J
authors.lastname: Hedderich
authors.forename: G I
authors.initials: GI
authors.lastname: Duncker
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000633:toxicity*; D004337:Drug Carriers; D004596:Electroretinography / Q000187:drug effects; D005500:Follow-Up Studies; D007267:Injections; D008081:Liposomes; D015242:Ofloxacin / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D014822:Vitreous Body
chemical_list: D000890:Anti-Infective Agents; D004337:Drug Carriers; D008081:Liposomes; D015242:Ofloxacin