gms | German Medical Science

Topical corticosteroids, although effective in treatment of ocular immune mediated diseases, are well known for their ocular side effects. Not surprisingly, a variety of alternative immunomodulatory agents have been tested for topical use including Cyclosporin A (CsA), Mycophenolate Mofetil (MMF), Tacrolimus (FK506), Rapamycin (Sirolimus) and Leflunomide Local application bears the possibility to avoid the severe side effects of systemic therapy.

The effect of topical therapy is naturally restricted to local immune response mechanisms such as antigen presentation by Langerhans and dendritic cells. Moreover, many immunomodulatory agents (e.g. CsA) are lipophilic and thus have low water solubility and penetrate insufficiently intraoocularly often being stored in the lipophilic corneal epithelial barrier. Therefore, the therapeutical success is limited for intraocular immune mediated diseases like anterior uveitis. However, a multitude of strategies have been introduced to circumvent these problems including complexing substances such as cyclodextrins and liposomes. In prevention and treatment of transplant rejection after keratoplasty many attempts to introduce topical immunomodulatory therapy have failed, on the other hand further therapeutic options not primarily expected are being evaluated today such as treatment of severe keratoconjunctivitis sicca. In own studies we investigated the pharmakokinetics of topical treatment with different agents including MMF and evaluated the efficacy of topical treatment in animal models for uveitis and keratoplasty.

Taken together, topical immunomodulatory therapy will not replace systemic therapy but further treatment options can be expected.