title: Evaluation of intraocular reactivity to metallic and ethylene oxide contaminants of medical devices in a rabbit model.
abstract: OBJECTIVE
  To evaluate the intraocular reactivity to metallic and ethylene oxide (EO) contaminants of ophthalmic devices in rabbits.
  
  
  METHODS
  Two experimental animal studies.
  
  
  METHODS
  Thirty-five New Zealand white rabbits.
  
  
  METHODS
  A metallic exposure study and an EO exposure study were performed. In the first study, both eyes of 25 rabbits were equally allocated to intracameral injections of alumina 0.2 μg, alumina 20 μg, copper sulfate 0.4 μg, copper sulfate 20 μg, or an aqueous control. In the second study, 10 rabbits were allocated (5 per group) to receive intracamerally an ophthalmic viscosurgical device (OVD) exposed to EO or not exposed to EO (control). All eyes were examined by slit lamp at baseline and 3, 6, 9, 24, 48, and 72 hours after exposure, with dilated indirect ophthalmoscopy being performed at 24 and 72 hours. Tonometry was performed only in the first study.
  
  
  METHODS
  Grade of corneal clouding, anterior chamber (AC) flare, AC cells, AC fibrin, iridal hyperemia, cell and fibrin on the lens surface, vitreous haze and cells, lens opacities, intraocular pressure, and onset time.
  
  
  RESULTS
  For metallic compounds at the study's low doses, mean inflammatory grades were 0.2 or less above the control for all responses at all time points. For the high-dose alumina, mean inflammatory grades peaked at 6 to 9 hours at 0.5 to 0.7 above the control responses for conjunctival congestion, iris hyperemia, AC cells, flare, and fibrin and declined over the remaining time points. For the high-dose copper sulfate, mean inflammatory grades peaked between 3 and 24 hours at 1.2 to 1.8 above the control responses for conjunctival congestion, iris hyperemia, AC cells, flare, fibrin, and corneal clouding, then subsequently declined. The intraocular pressure changes appeared significant for only high-dose copper sulfate, with mean declines of 4.3 to 7.5 mmHg at 6 to 72 hours. No clinically meaningful differences in ocular inflammation were observed between the OVD exposed to EO and the OVD not exposed to EO.
  
  
  CONCLUSIONS
  Alumina and copper sulfate did not cause clinically meaningful ocular inflammation at the low study levels (levels expected with ophthalmic devices). Ethylene oxide exposure of an OVD was not associated with inflammation.
authors.affiliation: Food and Drug Administration, Center for Devices and Radiological Health, Office of Device Evaluation, Division of Ophthalmic, Neurological, and Ear, Nose, and Throat Devices, Silver Spring, Maryland 20993-0002, USA.
authors.forename: Don
authors.initials: D
authors.lastname: Calogero
authors.forename: Shelley Y
authors.initials: SY
authors.lastname: Buchen
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Tarver
authors.forename: Gene
authors.initials: G
authors.lastname: Hilmantel
authors.forename: Anne D
authors.initials: AD
authors.lastname: Lucas
authors.forename: Malvina B
authors.initials: MB
authors.lastname: Eydelman
mesh_terms: D000537:Aluminum Oxide / Q000633:toxicity*; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects*; D019327:Copper Sulfate / Q000633:toxicity*; D004866:Equipment Contamination; D005027:Ethylene Oxide / Q000633:toxicity*; D023421:Models, Animal; D013508:Ophthalmologic Surgical Procedures / Q000295:instrumentation*; D011817:Rabbits; D014606:Uveitis, Anterior / Q000139:chemically induced* / Q000175:diagnosis
chemical_list: D005027:Ethylene Oxide; D000537:Aluminum Oxide; D019327:Copper Sulfate