Several reports have appeared on the efficacy of topically applied 0.01% or 0.1%
all-trans retinoic acid (0.04-0.4 millimolar) for treatment of
xerophthalmia, conjunctival squamous
metaplasia, and corneal epithelial erosions in humans and animals. An observation common to many of these studies is the occurrence of an adverse reaction to
retinoic acid in the form of lid margin
hyperemia and blepharoconjunctivitis. Since
retinoic acid is biologically active at micromolar to nanomolar concentrations, it may be possible to reduce side effects while maintaining therapeutic effectiveness by reducing the
retinoic acid concentration in ophthalmic formulations. In the present study, topical 0.005%
retinoic acid in
petrolatum ointment reversed corneal keratinization in xerophthalmic,
vitamin A-deficient rabbits in 3-4 days while 0.0005% (2 micromolar)
retinoic acid ointment was effective in 4-6 days. Further clinical trials of topical
retinoic acid for treatment of ocular surface disease should be conducted using micromolar concentrations of
retinoic acid which are expected to maintain a
therapeutic effect while reducing adverse reactions.