Download Rebamipide

Ophthalmology 2012;119:2471–2478
R3 이지영/Pf.정성근
• decreased tear production
.
tear film
• altered tear composition
.
• damages the ocular surface
.
instability
.
dry eye
tear film
lipid layer
Aqueous layer
Mucin
• important lubrication
• defense functions on the ocular
surface
• retention of the aqueous layer

quinolinone derivative
 Increasing mucin levels in the stomach
▪ effective in the treatment of gastric ulcers and gastritis in humans
 Increases the production of mucin-like substances in the cornea
and conjunctiva
▪ improve damage to the ocular surface of patients with dry eye

Objective
 To investigate the dose response for efficacy of 1% and 2%
rebamipide ophthalmic suspension compared with placebo in
patients with dry eye

Study Design
 randomized, double-masked, placebo-controlled, multicenter,
parallel-group, dose-response, phase II study
 308 patients with dry eye
1 % rebamipide
2% rebamipide
placebo
n = 99
n= 101
n= 103
 After a 2-week screening period, patients were randomized to
receive placebo or 1% rebamipide or 2% rebamipide
administered as 1 drop in each eye 4 times daily for 4 weeks.

Patients
 Inclusion criteria
▪ aged ≥ 20 years
▪ dry eye–related symptoms that were not fully relieved by conventional
treatments
▪ present for >20 months
▪ other criteria
▪
▪
▪
▪
▪
(1) score of 2 for 1 or more dry eye–related ocular symptoms
(2) fluorescein corneal staining (FCS) score 4
(3) lissamine green conjunctival staining (LGCS) score 5
(4) unanesthetized Schirmer’s test value at 5 minutes 5mm
(5) corrected visual acuity 20/100
 exclusion criteria
▪
▪
▪
▪
anterior ocular disease (e.g., blepharitis or blepharospasm)
punctal plug or removed within 3 months
operation to the ocular surface within 12 months
intraocular surgery within the 3 months

Outcome Measures
• change from
baseline in
fluorescein corneal
staining (FCS) score
• lissamine green
conjunctival staining
(LGCS) score
• TBUT
• Schirmer’s test
• dry eye–related
ocular symptoms
score
• patients’ overall
treatment impression score
Primary
objective end
point
Secondary
objective end
point
Secondary
subjective end
points

baseline, week 2, and week 4, or at discontinuation
Change from baseline in FCS score
• 1% and 2% rebamipide groups
significantly greater than the placebo
group at week 2, week 4, and LOCF
• Treatment effects were greater in the
2 % rebamipide group for those with a
baseline FCS score 10 – 15
 dose response
change from baseline in LGCS score
• 1% and 2% rebamipide groups was significantly larger than in the placebo group at
week 2, week 4, and LOCF
Patients’ Overall Treatment Impressions
• significant improvement in patients’ overall
treatment impressions in both the 1% and 2%
rebamipide groups

The objective signs and subjective symptoms were
significantly improved in patients receiving
rebamipide versus placebo.

Dysgeusia was the most frequently observed drugrelated adverse event in the rebamipide groups,
although all events were mild and resolved without
treatment.

Rebamipide, which increases the mucin level of a
natural component of the tear film, is an effective
treatment for dry eye, with improvements in as
early as 2 weeks.

2% rebamipide may be more effective than 1%
rebamipide in severe dry eye.

Rebamipide
 increasing mucin in the cornea and conjunctiva
 relief of dry eye symptoms and objective sign

Side effect
 Dysgeusia : bitter taste associated with the active
ingredient rebamipide