Treatment of Experiemental Pseudomonas Keratitis with Cyclo-oxygenase and Lipoxygenase Inhibitors

The role of metabolites of arachidonic acid in experimental Pseudomonas keratitis was studied using inhibitors of arachidonic acid metabolism. Nordihydroguaiaretic acid 1%, which inhibits predominantly the lipoxygenase pathway, and flurbiprofen 0.03%, which inhibits predominantly the cyclo-oxygenase pathway were administered topically to rabbit eyes after intrastromal injection of Pseudomonas aeruginosa. Levels of the cyclo-oxygenase product prostaglandin E₂ (PGE₂) and the lipoxygenase product leukotriene B₄, (LTB₄) were measured, and the number of ulcers that had progressed to descemetocele formation by 24 hours was determined. Corneal ulceration was accelerated by flurbiprofen, but nordihydroguaiaretic acid limited the flurbiprofen-induced worsening. The use of flurbiprofen was associated with decreased levels of PGE₂ and a relative increase in LTB₄, a potent chemoattractant and activator of polymorphonuclear leukocytes. These results suggest that inhibition of the cyclooxygenase pathway may be contraindicated in Pseudomonas keratitis; inhibition of lipoxygenase can prevent this worsening of the keratitis.