title: Rabbit ocular reactivity to bacterial endotoxin contained in aqueous solution and ophthalmic viscosurgical devices.
abstract: OBJECTIVE
  To describe the ocular reactivity of the rabbit to bacterial endotoxin contained in an aqueous medium and in a cohesive and a dispersive ophthalmic viscosurgical device (OVD).
  
  
  METHODS
  Experimental, randomized animal study.
  
  
  METHODS
  Seventy-five New Zealand white rabbits.
  
  
  METHODS
  This study was performed using 75 rabbits to evaluate the ocular reactivity to bacterial endotoxin contained in Dulbecco's phosphate-buffered saline (DPBS), a cohesive OVD, and a dispersive OVD. For each test material, 25 rabbits were randomized into 5 groups and were exposed to the test material containing 0.75 endotoxin units (EU), 0.25 EU, 0.08 EU, and 0.02 EU of endotoxin or the vehicle control. The rabbits in each group received bilateral intracameral injection of 0.05 ml of the same test material. All eyes were examined by slit-lamp biomicroscopy at baseline, 3, 6, 9, 24, 48, and 72 hours after injection. At 24 and 72 hours, slit-lamp biomicroscopy (and additionally indirect ophthalmoscopy) was performed through dilated pupils.
  
  
  METHODS
  Corneal clouding, anterior chamber (AC) flare, cells and fibrin, vitreous haze and cells, cells and fibrin on lens surface, lens opacities, and onset time.
  
  
  RESULTS
  The inflammation seen after exposure to the 3 endotoxin-spiked materials followed the same general time course. Anterior chamber cells, flare, iris hyperemia, and conjunctival congestion were seen as early as 3 hours. They started to diminish after 6 hours (DPBS eyes) and 9 hours (OVDs) and were not detectable at 48 and 72 hours, respectively. The AC inflammation was more severe in the OVD eyes than in the DPBS eyes. Anterior chamber fibrin was seen in the OVD eyes only, which persisted through 72 hours in many eyes. A trend toward a dose-response relationship was seen for AC cells and flare and the presence of cells and fibrin on the lens surface in all 3 treatment groups in the first 24 hours.
  
  
  CONCLUSIONS
  Inflammation was seen after intracameral injection of as little as 0.02 and 0.08 EU in OVD and DPBS eyes, respectively. Observed responses to intracamerally injected endotoxin in OVDs were more severe and of longer duration than those in aqueous medium.
authors.affiliation: Food and Drug Administration, Oak Ridge Institute for Science and Education contractor, Silver Spring, Maryland 20993-0002, USA.
authors.forename: Shelley Y
authors.initials: SY
authors.lastname: Buchen
authors.forename: Don
authors.initials: D
authors.lastname: Calogero
authors.forename: Gene
authors.initials: G
authors.lastname: Hilmantel
authors.forename: Malvina B
authors.initials: MB
authors.lastname: Eydelman
mesh_terms: D000085:Acetates / Q000633:toxicity*; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects*; D002387:Cataract Extraction; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004340:Drug Contamination; D004731:Endotoxins / Q000633:toxicity*; D056965:Injections, Intraocular; D008903:Minerals / Q000633:toxicity*; D011817:Rabbits; D012965:Sodium Chloride / Q000633:toxicity*; D014606:Uveitis, Anterior / Q000139:chemically induced*; D055675:Viscosupplements / Q000633:toxicity*
chemical_list: D000085:Acetates; C030660:BSS solution; D004338:Drug Combinations; D004731:Endotoxins; D008903:Minerals; D055675:Viscosupplements; D012965:Sodium Chloride