1. Effects of Intracameral Moxifloxacin, Levofloxacin, and Cefazolin on Corneal Endothelial Cells in Rabbits Su-Young Kim, Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea

2. Prevention of endophthalmitis Antiseptics on the ocular surface Antiseptics on the ocular surface Topical antibiotics preoperatively and postoperatively Topical antibiotics preoperatively and postoperatively Recently, intracameral injection of antibiotics has been raised to decrease incidence of postoperative endophthalmitis. Recently, intracameral injection of antibiotics has been raised to decrease incidence of postoperative endophthalmitis.Introduction

3. Intracameral antibiotics (cataract surgery) Intracameral cefazolin as prophylaxis against endophthalmitis in cataract surgery Intracameral cefazolin as prophylaxis against endophthalmitis in cataract surgery (J Cataract Refract Surg 2006) (J Cataract Refract Surg 2006) “ Intracameral bolus injection of cefazolin(1mg in 0.1mL solution) in cataract surgery demonstrated prophylactic efficacy in diminishing the rate of postoperative endophthalmitis without toxic effects on the cornea or retina” “ Intracameral bolus injection of cefazolin(1mg in 0.1mL solution) in cataract surgery demonstrated prophylactic efficacy in diminishing the rate of postoperative endophthalmitis without toxic effects on the cornea or retina”

4. Intracameral antibiotics (cataract surgery) Safety of prophylactic intracameral moxifloxacin 0.5% ophthalmic solution in cataract surgery patients Safety of prophylactic intracameral moxifloxacin 0.5% ophthalmic solution in cataract surgery patients (J Cataract Refract Surg 2007) (J Cataract Refract Surg 2007) “ Intracameral Vigamox 0.5mg/mL appeared to be nontoxic in terms of visual rehabilitation, anterior chamber reaction, pachymetry and corneal endothelial cell density.” “ Intracameral Vigamox 0.5mg/mL appeared to be nontoxic in terms of visual rehabilitation, anterior chamber reaction, pachymetry and corneal endothelial cell density.”

5. Intracameral antibiotics (cataract surgery) Prophylactic intracameral vancomycin Prophylactic intracameral vancomycin (J Cataract Refract Surg 2004) (J Cataract Refract Surg 2004) Prophylactic intracameral cefuroxime; efficacy in preventing endophthalmitis after cataract surgery Prophylactic intracameral cefuroxime; efficacy in preventing endophthalmitis after cataract surgery (J Cataract Refract Surg 2002) (J Cataract Refract Surg 2002)

6. Intracameral antibiotics Effective and safe as surgical prophylaxis Effective and safe as surgical prophylaxis Intracameral vancomycin is not preferred as the general prophylaxis in cataract surgery because of the opinion that vancomycin should be reserved for last antibiotics due to its powerful potency Intracameral vancomycin is not preferred as the general prophylaxis in cataract surgery because of the opinion that vancomycin should be reserved for last antibiotics due to its powerful potency Vancomycin can induce cystoid macular edema Vancomycin can induce cystoid macular edema

7. Purpose To compare the effect on corneal endothelial cell among intracameral moxifloxacin, levofloxacin, and cefazoline in Rabbits To compare the effect on corneal endothelial cell among intracameral moxifloxacin, levofloxacin, and cefazoline in Rabbits

8. Materials and Methods Thirty six eyes from eighteen New Zealand rabbits Thirty six eyes from eighteen New Zealand rabbits Pre-injection central corneal thickness Pre-injection central corneal thickness After removal of aqueous humor 0.1ml using 30 gauge needle After removal of aqueous humor 0.1ml using 30 gauge needle intracameral injection of BSS 0.1ml (always the other eye) intracameral injection of BSS 0.1ml (always the other eye) cefazolin 1000µg/0.1ml diluted with saline 0.9% cefazolin 1000µg/0.1ml diluted with saline 0.9% levofloxacin (0.5%, Cravit®, Santen, Japan) 500µg/0.1ml levofloxacin (0.5%, Cravit®, Santen, Japan) 500µg/0.1ml moxifloxacin (0.5%, Vigamox®, Alcon, USA) 500µg/0.1ml moxifloxacin (0.5%, Vigamox®, Alcon, USA) 500µg/0.1ml Cefazolin, Cravit®, and Vigamox® contain no preservatives. Cefazolin, Cravit®, and Vigamox® contain no preservatives.

9. Materials and Methods One day after intracameral injection One day after intracameral injection central corneal thickness cornea with a 2.0-mm rim of sclera was excised central corneal thickness cornea with a 2.0-mm rim of sclera was excised specular microscopy (KeratoAnalyzer (EKA-04), Konan medical Inc., Japan ) specular microscopy (KeratoAnalyzer (EKA-04), Konan medical Inc., Japan ) scanning electron microscopy (SEM) scanning electron microscopy (SEM) transmission electron microscopy (TEM ) transmission electron microscopy (TEM )

10. CefazolinLevofloxacinMoxifloxacin 1 ST generation cephalosporine 3 rd generation quinolone 4 th generation quinolone Inhibiting bacterial cell wall synthesis Only DNA gyrase for G- Only topoisomerase IV for G + Both bacterial DNA gyrase (topoisomerase II), topoisomerase IV → dual action → efficacy ↑ More effective again st G + bacteria than G-Bacteria Most aerobic G -, Some G + bacteria G +, G - Resistant G+, Nontuberculous Mycobacteria, Nocardia

11. Concentration (ug/0.1cc) Osmolarity (Osm/l) pH Cefazolin1,000322-3245.8 Levofloxacin500300 6.2- 6.8 Moxifloxacin5002906.8 humans200 - 4006.5 - 8.5

12. Central corneal thickness before the injection There was no significant difference in corneal thickness before the injection among four groups (p=0.33). corneal thickness (um ± SD)Results

13. Central corneal thickness after the injection There was no significant difference in corneal thickness after the injection among four groups (p=0.12). corneal thickness (um ± SD)

14. The mean change between pre-injection value and post-injection value of central corneal thickness The mean change between pre-injection value and after-injection value was not significantly different among four groups (p=0.24). Change of corneal thickness (um ± SD)

15. The mean endothelial cell count one day after intracameral injection No statistically significant difference was noted among four groups (p=0.248). Mean endothelial cell count (cells/mm2±SD)

16. BSSCefa LevoMoxi Fig. Specular microscopy 1 day after intracameral injection. The endothelium cell counts in all four groups was normal with no statistically significant difference among four groups (p=0.248).

17. Fig. SEM 1 day after intracameral injection. The endothelium in all four groups was regular in appearance, and had normal mosaic- like cellular pattern. Original magnification ×1,000. BSSCefa LevoMoxi

18. Fig. TEM 1 day after intracameral injection. The endothelium in all four groups was normal height and normal intercellular space. Original magnification ×2,500-6,000 BSSCefa LevoMoxi

19. Conclusion Intracameral injection of antibiotics (cefazolin 1000ug/0.1cc, levofloxain 500ug/0.1cc, Moxifloxacin 500ug/0.1cc) did not show significant toxicity on endothelial cell compared with the control group. Intracameral injection of antibiotics (cefazolin 1000ug/0.1cc, levofloxain 500ug/0.1cc, Moxifloxacin 500ug/0.1cc) did not show significant toxicity on endothelial cell compared with the control group. Intracameral injection of one of these antibiotics will be safe for surgical prophylaxis. Intracameral injection of one of these antibiotics will be safe for surgical prophylaxis. When we consider risk-benefit or cost- effectiveness, intracameral injection can be especially useful to high-risk patients with trauma, diabetics, chronic blepharitis, intraoperative contamination. When we consider risk-benefit or cost- effectiveness, intracameral injection can be especially useful to high-risk patients with trauma, diabetics, chronic blepharitis, intraoperative contamination.