Long-term Follow-up of the Systemic Immunosuppressive Therapy for Eye Diseases Cohort

Massachusetts Eye And Ear Infirmary, Boston MA

Investigators

Linked publications, trials & patents

Abstract

Project Summary (Abstract) Ocular inflammatory diseases are major causes of vision loss in the United States, occurring from a relatively early age. Immunosuppression is a critical therapeutic approach for severe cases. We previously collected data for 18,184 non-infectious ocular inflammation patients, which we now propose to leverage in order to evaluate the critical question of whether immunosuppression has a higher risk of death or death from cancer in the long run. We will do this by studying the survival of these patients for an additional 11 years since their exposure to immunosuppressive therapy (which will provide a median of >15 years’ follow-up for mortality risk following treatment). Some of these drugs have been explicitly identified as carcinogenic in humans based primarily on transplant data. We have not seen that effect in our research so far, but it is critical to assure patients that the treatments are sufficiently safe to use, hence we are proposing to extend this study. Since it also is important to understand which drugs are the most beneficial, we also propose to follow-up our current work indicating that Tumor Necrosis Factor Inhibitor (TNFi) drugs control inflammation better than “conventional” (and less expensive) treatment with antimetabolite drugs (such as methotrexate). We propose to study whether TNFi therapy has better visual acuity outcome and fewer ocular complications than single antimetabolite therapy; whether TNFi therapy also is more effective in obtaining treatment success than combined, two- drug conventional immunosuppression (an alternative, less costly approach); whether any of the individual TNFi agents (infliximab, adalimumab and etanercept) are preferable in terms of treatment success and; and how much cost is associated with these potential benefits of TNFi therapy. We also propose to create tools to help doctors identify which patients are at high risk of an unfavorable visual outcome, and to predict which patients will need higher (potentially more toxic) doses of specific immunosuppressants, to help identify who needs stronger treatment from the beginning. In addition, we aim to identify ophthalmic predictors of mortality, and whether immunosuppression in fact reduces the risk of mortality for such patients as is assumed. We further aim to estimate the incidence of and predictive factors for rhegmatogenous retinal detachment in uveitis cases. The existence of this largest, purpose-collected United States ocular inflammation database provides a unique opportunity to address many ocular questions of great importance, with a high probability of successful execution.