Download Asbell ASCRS Presentation 2007

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.
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
Purpose
To evaluate corneal endothelial integrity and
morphology in humans after 2-wk intensive
dosing regimen with 1.5% levofloxacin
ophthalmic solution (IQUIX®).
Methods: Prospective Single-Center,
Investigator-Masked Study
 Healthy human volunteers (n=48)
 224 IQUIX® doses OD over 14 days
(27 doses/day)
1 drop OD every 30 min 8 AM – 8 PM
1 drop OD at 12 AM & 2 AM
Days 4-14
1 drop OD every hr 8 AM – 8 PM
Days 1-3
(13 doses/day)
 Assessments:
Baseline, Day 8, Day 15, Day 21 (7-days post-dosing)
 Safety analysis: Baseline vs 7-days post-dosing
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
Intensive IQUIX® Dosing
Corneal Endothelial Cell Density
Density, cells /µm2, mean
3500
3000
2500
2000
2767
± 317
2786
± 295
Baseline
Post-dosing
1500
1000
500
0
Intensive IQUIX® Dosing
Coefficient of Variation, mean
Endothelial Cell Size:
Coefficient of Variation
50
40
30
20
31.4
± 5.2
31.8
± 5.9
10
0
Baseline
Post-dosing
Intensive IQUIX® Dosing
Percent Hexagonal Cells
in Corneal Endothelium
100
Percent, mean
80
60
40
59.8
± 10.8
61.9
± 11.3
Baseline
Post-dosing
20
0
Intensive IQUIX® Dosing
Corneal Thickness
Thickness, µm, mean
700
600
500
400
560
± 36
568
± 46
Baseline
Post-dosing
300
200
100
0
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
Intensive IQUIX® Dosing: Conclusion
Intensive dosing with IQUIX® (levofloxacin 1.5%)
does not adversely affect corneal endothelium