Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids

PURPOSE: To review the efficacy of inhibitors of matrix metalloproteinase-9, corticosteroids, and doxycycline for treatment of recalcitrant recurrent corneal erosion. METHODS: Retrospective, clinic-based, interventional case series. The medical records of seven consecutive patients who were treated between January 1995 to January 2000 for recurrent corneal erosion who had not responded to conventional therapy were reviewed. Treatment of seven eyes of seven patients consisted of oral doxycycline (50 mg, two times a day) for 2 months along with a topical corticosteroid (either methylprednisolone 1%, prednisolone acetate 1%, or fluoromethalone 0.1%) three times a day, for 2 to 3 weeks. The effects of doxycycline and methylprednisolone on metalloproteinase-9 activity in human corneal epithelial cultures were evaluated by gelatin zymography and a commercial metalloproteinase-9 activity assay kit. RESULT: Fingernail injury in three of the seven eyes was the most common form of corneal injury. There was no evidence of epithelial basement membrane or corneal stromal dystrophy in any of the patients, although epithelial microcysts were observed in the involved area in three patients. One eye had intact elevated corneal epithelium that showed abnormal diffuse staining with fluorescein dye, and six eyes had a corneal epithelial defect at the time of presentation. In all seven eyes, pain resolved and epithelial defects healed within 2 to 10 days after initiation of therapy. No recurrence was observed during an average follow-up period of 21.9 months (range, 1.5 to 60 months). Methylprednisolone and doxycycline each produced a statistically significant decrease in amount and activity of metalloproteinase-9 in conditioned media of human corneal epithelial cultures. CONCLUSIONS: Therapy with a combination of medications that inhibit metalloproteinase-9 produced rapid resolution and prevented further recurrence of cases of recurrent corneal erosions that were unresponsive to conventional therapies.