1. Corneal Effects of 1.5% Levofloxacin Ophthalmic Solution (IQUIX®) in Humans Mark B. Abelson, MD1,2 Gail Torkildsen, MD2; Aron Shapiro2; Ingrid Lapsa2 1Harvard Medical School, Schepens Eye Research Institute, Boston, MA 2Ophthalmic Research Associates, Inc., North Andover, MA
Financial Disclosure: MB Abelson, A Shapiro, I Lapsa are full-time employees of Ophthalmic Research Associates, Inc.

2. Study Background IQUIX® approved for treating bacterial keratitis
In vitro: Levofloxacin least cytotoxic fluoroquinolone in human corneal keratocyte and endothelial cell cultures1
In vivo: Wound healing in rabbits and primates (2 drops QID x 4 days)2
No adverse effect on cornea, re-epithelialization, keratocyte structure / organization, or wound healing
1Bezwada P et al. Curr Med Res Opin 24:419-24, 2008
2Clark L et al. Cutaneous Ocular Toxicology 23:1-18, 2004

3. Purpose
To evaluate corneal endothelial integrity and morphology in humans after 2-wk intensive dosing regimen with 1.5% levofloxacin ophthalmic solution (IQUIX®).

4. Methods: Prospective Single-Center, Investigator-Masked Study
Healthy human volunteers (n=48)
224 IQUIX® doses OD over 14 days
Assessments: Baseline, Day 8, Day 15, Day 21 (7-days post-dosing)
Safety analysis: Baseline vs 7-days post-dosing
Days 1-3 (27 doses/day)
1 drop OD every 30 min 8 AM – 8 PM 1 drop OD at 12 AM & 2 AM
Days 4-14 (13 doses/day)
1 drop OD every hr 8 AM – 8 PM

5. Key Safety Assessments
Intensive IQUIX® Dosing
Key Safety Assessments
Specular microscopy
Endothelial cell density
Endothelial cell morphology (cell size variability, % hexagonal cells)
Pachymetry: central corneal thickness
Slit-lamp biomicroscopy
Visual acuity

6. Corneal Endothelial Cell Density
Intensive IQUIX® Dosing
Corneal Endothelial Cell Density
2767
± 317
2786
± 295
Density, cells / µm2, mean
Baseline
Post-dosing

7. Endothelial Cell Size: Coefficient of Variation
Intensive IQUIX® Dosing
Endothelial Cell Size: Coefficient of Variation
Coefficient of Variation, mean
31.4
± 5.2
31.8
± 5.9
Baseline
Post-dosing

8. Percent Hexagonal Cells in Corneal Endothelium
Intensive IQUIX® Dosing
Percent Hexagonal Cells in Corneal Endothelium
Percent, mean
59.8
± 10.8
61.9
± 11.3
Baseline
Post-dosing

9. Corneal Thickness Intensive IQUIX® Dosing Thickness, µm, mean 560 568
± 36
568
± 46
Thickness, µm, mean
Baseline
Post-dosing

10. Intensive IQUIX® Dosing: Summary of Findings
No clinically significant negative changes in any measured safety parameter
Endothelial cell density
Endothelial cell morphology
Central corneal thickness
Visual acuity*
Slit-lamp biomicroscopy*
Intraocular pressure*
Dilated fundoscopy*
Treatment-related adverse events: dysgeusia (30%); eye irritation (7%); eye pruritis (6%)
*Data not shown

11. Intensive IQUIX® Dosing: Conclusion
Intensive dosing with IQUIX® (levofloxacin 1.5%) does not adversely affect corneal endothelium