The Effect of Combinations of Flurbiprofen, Low Molecular Weight Heparin, and Doxycycline on the Inhibition of Corneal Neovascularization

PURPOSE: To determine the efficacy of various combinations of flurbiprofen, low molecular weight heparin (LMWH), and doxycycline on the inhibition of corneal neovascularization in rats. METHODS: Chemical cauterization of the cornea in 32 eyes of 32 rats was performed using silver nitrate/potassium nitrate sticks. The animals were divided into 4 groups. Topical instillation of 0.015% flurbiprofen with 5 mg/mL LMWH (group 1); flurbiprofen with 10 mg/mL doxycycline (group 2); doxycycline with LMWH (group 3), and saline (group 4; control) was performed twice a day for 7 days. Slit-lamp photography was used to determine the percent areas of cornea covered by neovascularization and also by scar in each group. The means were compared to find any significant (P < 0.05) difference between groups. The animals were euthanized and the eyes enucleated for histological evaluation. RESULTS: The mean of percent area of corneal neovascularization 5 in group 1 was 48.5 +/- 13.1; group 2, 6.6 +/- 5.5; group 3, 22.0 +/- 27.6 and group 4, 64.6 +/- 9. The means of percent area of neovascularization in groups 2 and 3 were significantly lower compared with control and group 1. There was no significant difference in the percent corneal neovascularization between groups 2 and 3 or between group 1 and the control group. Histological findings were consistent with slit-lamp evaluations. CONCLUSIONS: Topical instillation of combinations of doxycycline with either flurbiprofen or LMWH can effectively inhibit corneal neovascularization made by chemical cauterization of the cornea in rats.