Researching OCT Biomarkers in UveitiS clinical Trials (ROBUST) - PROJECT SUMMARY Uveitis is the fifth leading cause of blindness in the developed world. Intermediate, posterior, and panuveitis are nearly always chronic diseases which account for the highest rates of visual impairment and the development of ocular complications among patients with uveitis. Successful management of these diseases requires long-term care, careful examination, ophthalmic imaging evaluation, and monitoring to preserve vision. A significant challenge in the evaluation of uveitis imaging is the lack of objective biomarkers. Uveitic macular edema (UME) is one of the most common complications in intermediate, posterior, and panuveitis, occurring in approximately 40% of these patients, and is the most common cause of visual impairment and blindness in uveitis. Importantly, UME can be present in successfully treated eyes with inactive uveitis, suggesting that there are risk factors that are independently associated with uveitic inflammatory activity and the persistence of UME. Optical coherence tomography (OCT) is a widely utilized diagnostic tool in the evaluation of patients with uveitis. Most clinical OCT interpretations focus on macular thickness, cystoid spaces, subretinal fluid, and epiretinal membrane formation. However, other findings on OCT, such as ellipsoid zone integrity, photoreceptor layer thickness, intraretinal hyperreflective foci, choroidal thickness, and disorganization of retinal inner layers, have been identified as potential prognostic biomarkers. Investigation of OCT biomarkers is particularly compelling, since OCT imaging is non-invasive, widely available, routinely used in clinical practice, making it an optimal tool for the quantitative evaluation of inflammation and UME. Building on our expertise in image analysis and clinical trials, we will perform a secondary analysis of a combined OCT imaging and clinical dataset from four NEI-funded uveitis randomized clinical trials including the Periocular vs. Intravitreal Corticosteroids for Uveitic Macular Edema (POINT) Trial, Macular Edema -Ranibizumab vs Intravitreal Anti-inflammatory Therapy (MERIT) Trial, Adalimumab vs. Conventional Immunosuppression for Uveitis (ADVISE) Trial, and the First-line Antimetabolite as Steroid-sparing Treatment (FAST) Uveitis Trial. We will pursue the following specific aims: 1) to identify OCT biomarkers that are predictive of response to therapy for uveitic macular edema, 2) to determine which OCT biomarkers correlate with baseline visual acuity and are predictive of longitudinal changes in visual acuity in patients with UME, and 3) to evaluate the association of OCT biomarkers with uveitis activity in intermediate, posterior, and panuveitis and in selected specific uveitic diseases. The aims of this study will address the NEI strategic plan for the area of emphasis relating to the “Immune System and Eye Health”. This study will identify imaging biomarkers of UME and uveitis that will help in disease detection and surveillance. Ultimately, earlier detection and improved monitoring of UME and uveitis can prevent permanent vision loss and disability.
