Is tacrolimus effective against choroidal neovascularization? A preliminary study

To evaluate the effectiveness of tacrolimus used topically in inhibiting a rat model of laser-induced choroidal neovascularization. Thirty-six Long-Evans pigmented rats were utilized in this paper. Bursting lesions are performed on the retina of one eye in each animal to induce choroidal neovascularization (CNV) by argon laser. The animals were separated into 3 groups of 36 rats. Twelve animals in each group and one eye per animal were topically administrated daily for 5 weeks at 0.3%, 0.5% tacrolimus, and saline respectively. Fluorescein angiography (FA) was performed in groups 1, 2, and 3 (control group) in the 3rd week, 4th week, and 5th week after the initial retinal photocoagulation. FA is graded for each of the three lesions as follows: score 0: no leakage, score 1: slight leakage, score 2: moderately leakage, and score 3: strong leakage. At the end of the study, the eyes were enucleated and prepared for histological examination. According to fluorescein angiography (FA) score comparisons, in group 1 (topical 0.3 % Tacrolimus) there was only a significant difference between its controls at the 5th week after retinal photocoagulation (p=0.05). In group 2 (topical 0.5 % Tacrolimus) there was a significant difference when compared to control eyes in the 4th week and the 5th week (p=0.018, p=0.021). Topical instillation of tacrolimus at a concentration of 0.5% following the laser photocoagulation significantly reduced leakage of CNV versus controls in the 4th and the 5th weeks, the time points tested. Tacrolimus at a concentration of 0.3 % significantly reduced CNV only 5 weeks after retinal photocoagulation. These results show that there is a dose-response of topical tacrolimus on the suppression of CNV. Tacrolimus is a well-penetrating drug through the cornea and following topical administration, can reach effective concentrations depending on application way and dose. This study needs to be performed in other experimental models and then clinical trials.