The purpose of this study was to evaluate the ability of the nonsteroidal anti-inflammatory drug
nepafenac to prevent development of
mitogen-induced pan-
retinal edema following topical ocular application in the rabbit. Anesthetized Dutch Belted rabbits were injected intravitreally (30 microg/20 microL) with the
mitogen concanavalin A to induce posterior segment
inflammation and thickening (
edema) of the retina. The Heidelberg Retina Tomograph was used to generate
edema maps using custom software. Blood-retinal barrier breakdown was assessed by determining the
protein concentration in vitreous humor, whereas analysis of
PGE2 in vitreous humor was performed by radioimmunoassay. Inhibition of
concanavalin A-induced
retinal edema was assessed 72 h after initiation of topical treatment with
nepafenac (0.1-1.0%, w/v),
dexamethasone (0.1%),
VOLTAREN (0.1%), or
ACULAR (0.5%).
Concanavalin A elicited marked increases in vitreal
protein and
PGE2 synthesis at 72 h postinjection.
Retinal thickness was also increased by 32%, concomitant with the inflammatory response. Topical application of 0.5%
nepafenac produced 65% reduction in
retinal edema which was correlated with 62% inhibition of blood-retinal barrier breakdown. In a subsequent study, 0.5%
nepafenac significantly inhibited (46%) blood-retinal barrier breakdown concomitant with near total suppression of
PGE2 synthesis (96%). Neither
Voltaren nor
Acular inhibited accumulation of these markers of
inflammation in the vitreous when tested in parallel. This study demonstrates that
nepafenac exhibits superior pharmacodynamic properties in the posterior segment following topical ocular dosing, suggesting a unique therapeutic potential for a variety of conditions associated with
retinal edema.