Investigation of the effect of Cyclosporine A in an experimental model of corneal neovascularization

PURPOSE: We aimed to study the inhibitory effects of topical 0.05 % cyclosporine A on immune-mediated experimental corneal neovascularization and to compare its efficacy with those of topical 0.1 % dexamethasone and 0.5 % bevacizumab.METHODS: Immune-mediated corneal neovascularization was created by bovine serum albumin in 36 rabbits. The rabbits were then randomized into four groups according to topical treatment. Group I received 0.05 % cyclosporine A, Group II received 0.1 % dexamethasone, Group III received 0.5 % bevacizumab and Group IV received isotonic saline for 14 days. The corneal surface covered with neovascular vessels was measured on the photographs as the percentage of the total area of the cornea. The rabbits were then sacrificed and the corneas excised. Paraffin-embedded sections were stained with hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The intensity of vascular endothelial growth factor (VEGF) and CD31 immunostainings in corneal tissue was performed in a semiquantitative fashion. Inflammatory response was classified as none (0), mild (1), moderate (2) or severe (3) according to the amount of inflammatory cell infiltration.RESULTS: The means of percent area of corneal neovascularization in Group I, II, III and IV were 24.4 %, 5.9 %, 37.1 %, and 44.1 %, respectively. The inhibitory effects of 0.05 % cyclosporine A was found to be better than 0.5 % bevacizumab and control groups (p=0.03 and p=0.02, respectively). Topical 0.05% cyclosporine A was found to be significantly lesser inhibitory effects on corneal neovascularization than the topical 0.1 % dexamethasone (p<0.001). Apoptotic cell density was higher in group III (22.7 cells/mm2) and group IV (21.7 cells/mm2) than group I (10.6 cells/mm2) and group II (11 cells/mm2). There was no difference between the group I and group II in terms of apoptotic cell density (p=0.7). Inflammation score was not significantly different between the group I and the group III (p=0.13). The lowest inflammation score was in the group II.CONCLUSION: Topical % 0,05 cyclosporine A was shown to have an inhibitoryeffects on immune-mediated corneal neovascularization in this rabbit model. Inhibition of apoptosis with topical 0.05 % cyclosporine A was comparable to that of topical 0.1 % dexamethasone.KEYWORDS: Arthus reaction, corneal neovascularization, cyclosporine A.