Corticosteroid-sparing agents: conventional systemic immunosuppressants

The introduction of corticosteroids in the mid-20th century to control inflammatory eye disease revolutionized treatment practices. As long-term use of corticosteroids became the backbone of immunosuppressive therapy, it soon became evident that it was associated with significant morbidity to the patient. For this reason, other immunosuppressant agents were sought. Thereafter, the first generation of immunosuppressive agents were born. The main action of all such agents involves the inhibition of lymphoid proliferation. The agents can be further subdivided into the following categories based on their specific mechanism of action: alkylating (cyclophosphamide and chlorambucil), antimetabolite (methotrexate, mycophenolate mofetil and azathioprine), and antibiotic/calcineurin inhibitor (cyclosporine, tacrolimus and sirolimus). These immunomodulating agents serve as the foundation to modern corticosteroid-sparing immunosuppressive therapy. Many times, these agents are now even indicated as first-line therapy for the treatment of systemic inflammatory diseases with destructive ocular sequela, e.g. Behçet's disease and granulomatosis with polyangiitis (Wegener's). Choosing the most appropriate immunomodulatory agent to initiate therapy can often be difficult; a multifactorial approach in the decision-making process is essential. Special attention must be given to the patient's medical history, type and severity of inflammatory disease, social history, compliance, age, and sex. Oftentimes, it takes a joint effort between the ophthalmologist and multiple sub-specialists (rheumatology, oncology, and hematology) to administer and monitor these therapies. Even though each of these systemic immunosuppressive agents has its own array of potential side effects, with careful monitoring and titration of dosages, such potential side effects can be minimized or avoided altogether. Ultimately, these patients are afforded a much more favorable long-term outcome, free of the devastating effects of chronic corticosteroid use.