Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca.
OBJECTIVE
The aim of this study was to compare the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, doxycycline, and artificial tears for the treatment of ocular surface damage in the Botulinum toxin B (BTX-B)-induced mouse model of dry eye.


METHODS
CBA/J mice were randomized into 2 experimental groups of 35 animals each. The control group received a transconjunctival injection of 0.05 mL of saline into the left lacrimal gland, and another group was injected with 0.05 mL of 20 milliunits BTX-B solution (SPSS, Inc., Chicago, IL). Three (3) days after intralacrimal gland injections, each group was equally randomized into 7 subgroups (n=5 each) to receive treatment unilaterally into their left eyes with topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, 0.4% ketorolac, 0.09% bromfenac, 0.1% diclofenac, or 0.025% doxycycline. Tear volume, ocular surface changes, and spontaneous blink rate were evaluated in each of the 14 experimental subgroups.


RESULTS
Topical fluorometholone, nepafenac, and doxycycline significantly improved corneal surface staining in the BTX-B-injected mice within 2 weeks of treatment. Topical ketorolac, diclofenac, and bromfenac, applied twice-daily, partially reduce corneal staining, and did so more slowly by the 4-week time point. In comparison, topical artificial tear-treated mice did not demonstrate significant improvement of the corneal surface at any time point. Aqueous tear production in the BTX-B-injected fluorometholone-treated group started to return to baseline level within 2 weeks, although not significantly. Meanwhile, BTX-B-injected mice treated with artificial tears, topical NSAIDs, and doxycycline still exhibited a reduction in tear production up to 4 weeks. No significant differences in blink rate between the control and study groups undergoing the various treatments were noted at all time points.


CONCLUSIONS
This study suggests the potential usefulness of topical NSAIDs, corticosteroid, and doxycycline for the clinical treatment of ocular surface epithelial disorders associated with dry eye.
Lekhanont
Kaevalin
K
Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, MD 21286-9278, USA.
Park
Choul Yong
CY
Smith
Janine A
JA
Combs
Juan Castro
JC
Preechawat
Pisit
P
Suwan-Apichon
Olan
O
Rangsin
Ram
R
Chuck
Roy S
RS
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001905:Botulinum Toxins / Q000633:toxicity*; D019274:Botulinum Toxins, Type A; D004195:Disease Models, Animal; D005260:Female; D007638:Keratoconjunctivitis Sicca / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D012965:Sodium Chloride / Q000008:administration & dosage; D013666:Tears / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D009883:Ophthalmic Solutions; C096323:rimabotulinumtoxinB; D012965:Sodium Chloride; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A