JUN 12, 2008
Comprehensive Ophthalmology
Researchers treated 10 patients with 0.02% topical tacrolimus ointment, a potent immunosuppressive macrolide. All patients showed marked to moderate improvement. Treatment was especially efficacious for peripheral ulcerative keratitis and atopic keratoconjunctivitis, and was well tolerated for long periods without adverse effects and elevation of IOP.
The authors recommend topical tacrolimus especially when use of systemic steroid or immune suppressant is contraindicated. The authors note that additional studies are necessary to determine the optimal dose and therapeutic regimen for inflammatory ocular surface diseases.
According to the authors, the mechanism of action of tacrolimus is mainly as a competitive blocker of calcineurin, which is required for NFAT (nuclear factor of activated T-cells)-dependent T-cell activation or induction of inflammatory cytokine arrays. This is similar to its predecessor, cyclosporine, which had also been isolated from soil fungus decades before. However, the potency of tacrolimus is 30 times greater than that of cyclosporine in terms of its inhibitory effects (median inhibitory concentration) on calcineurin phosphatase activity. The immune suppressive effects of tacrolimus are not limited to T-lymphocytes, because the NFAT-dependent activation cascade also acts on B-cells and mast cells. Thus, tacrolimus should have therapeutic effects for other immune-mediated ocular diseases.