title: Evaluation of vitreous clearance and potential retinal toxicity of intravitreal lornoxicam (xefo).
abstract: OBJECTIVE
  To evaluate the vitreous clearance and toxicological profile of commercially available lornoxicam (Xefo), after a single intravitreal injection in rabbits.
  
  
  METHODS
  Twenty-five male albino rabbits (10 rabbits were used for retinal toxicity evaluation, while 15 rabbits were used to evaluate vitreous clearance) were used in this study. Two concentrations of lornoxicam were tested for retinal toxicity: 250 μg/0.1 mL and 1,500 μg/0.1 mL. Each concentration was intravitreally injected randomly in 1 eye of each rabbit (group I received 250 μg/0.1 mL, n=5 and group II received 1,500 μg/0.1 mL, n=5), while in the other eye 0.1 mL of sterile balanced saline solution was injected. Slit-lamp and funduscopic examinations along with intraocular pressure measurements (IOP) were performed prior to injection and at days 1, 15, and 30 after the injection for signs of infection, inflammation, toxicity, and IOP changes. A baseline electroretinogram (ERG) was performed before the experiment and at days 1, 15, and 30 after the intravitreal injection. At the last follow-up day, the animals were sacrificed and the enucleated eyes were prepared for histological evaluation of the retina. Lornoxicam (concentration of intravitreal injection: 250 μg/0.1 mL) clearance from the vitreous was estimated using high-performance liquid chromatography in 30 rabbit eyes.
  
  
  RESULTS
  There were no statistical differences between the control and experimental eyes, concerning ERG amplitudes and IOP measurements for both groups (I and II), at all examinations. On the contrary, histological examination of the samples revealed extended retinal damage of group II experimental eyes (morphological alterations at the level of the inner nuclear and outer plexiform layers was evident along with disappearance of normal stratification of outer retina with vacuolization and thinning), whereas the morphology of group I experimental eyes did not differ from that of the control eyes. Lornoxicam is eliminated from the vitreous by a first-order kinetic process with a half-life of 1.7 h.
  
  
  CONCLUSIONS
  Intravitreal lornoxicam causes dose-related toxic effect to the retina at a concentration of 1,500 μg. A dose of 250 μg does not seem to cause histological toxic effects at the level of the retina. Lornoxicam could be considered with interest for further research for the development of alternative treatments for ocular inflammatory conditions.
authors.affiliation: Institute of Vision and Optics (IVO), University of Crete, Heraklion, Greece.
authors.forename: Vasilios F
authors.initials: VF
authors.lastname: Diakonis
authors.forename: Antigoni
authors.initials: A
authors.lastname: Tsourdou
authors.forename: Manolis N
authors.initials: MN
authors.lastname: Tzatzarakis
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Tsika
authors.forename: Spyridon
authors.initials: S
authors.lastname: Charisis
authors.forename: Irini
authors.initials: I
authors.lastname: Naoumidi
authors.forename: Sotiris
authors.initials: S
authors.lastname: Plainis
authors.forename: Miltiadis K
authors.initials: MK
authors.lastname: Tsilimbaris
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D004596:Electroretinography; D058449:Intravitreal Injections; D008297:Male; D010894:Piroxicam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011817:Rabbits; D012160:Retina / Q000187:drug effects*; D012164:Retinal Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam; C059451:lornoxicam