Ocular irritation following frequent applications of Cyclosporine A

Purpose. Previous studies have shown that repetitive administrations of Cyclosporine A (CsA) eye drops to the rabbit eye caused a long-lasting miosis, accompanied by conjunctival hyperemia, anterior humor flare, and fibrin formation in the anterior chamber. The aim of the present study was to clarify the mechanism of these findings. Methods. One drop of 0.1% CsA eye drops was applied once or six times every 30 minutes for 2.5 hours. The eyes were examined by slit-lamp microscope, and IOP and anterior humor flare were measured prior to the studies and at 0, 1, 3, 6, 12, and 24 hours after administration of CsA or vehicle. While anterior chamber aqueous flare was increasing, aqueous humor and anterior segment of the eye were taken and analyzed. The entry of plasma proteins into the aqueous humor was studied by using Evans blue dye. Result. Conjunctival hyperemia, anterior humor flare and IOP rise miosis and fibrin formation in the anterior chamber were shown after six CsA administration ipsilaterally during 1 - 12 hours after the final administration. All of these observations were inhibited by pretreatment of indomethacin. While miosis was appearing, Evans blue dye penetrated the nonpigmented layer of the ciliary epithelium and the iris vessels. Calcitonin gene-related peptide ( CGRP) was detected (184.1 +/- 84.6 pg/mL), and CsA levels (891.6 +/- 153.0 ng/mL) in anterior uvea exceeded the trough level. Conclusions. These results suggest that CsA can cause disruption of the blood-aqueous barrier with leaking from vessels in the ciliary processes and the iris, which are probably secondary effects of the irritation response releasing CGRP.