PROJECT SUMMARY Uveitis involving the posterior segment has the highest rate of vision impairment and development of ocular complications among patients with uveitis. Clinical grading of vitreous inflammation utilizes the widely accepted Standardization of Uveitis Nomenclature (SUN) Working Group criteria. However, several limitations exist with the SUN criteria because it is a subjective, semi-quantitative, stepwise grading system. A rapid, reproducible, and quantitative technique to evaluate inflammation is of paramount importance. The NEI-funded First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial was a multicenter, randomized, parallel, observer-masked clinical trial where 216 participants were randomized to receive oral methotrexate 25 mg weekly or oral mycophenolate mofetil 1.5 g twice daily. All participants were at least 16 years of age and had active non-infectious intermediate, posterior, or panuveitis in at least one eye and had justification for starting corticosteroid-sparing immunomodulatory therapy. Participants in this trial were followed up over a period of 12 months. As part of the FAST Trial, all participants underwent optical coherence tomography (OCT) imaging at baseline and at monthly intervals during the 12-month follow-up period. The robust and detailed nature of this randomized clinical trial combined with standardized OCT imaging at every visit will allow us to evaluate objective imaging biomarkers of vitreous inflammation, compare these biomarkers with clinical grading, and correlate these biomarkers with clinical outcomes and development of ocular complications. This proposal is for a secondary analysis of the FAST Trial OCT dataset and we will pursue the following specific aims: 1) develop a standardized, reproducible technique using OCT to quantify vitreous cells, 2) evaluate a reproducible technique using OCT to quantify vitreous haze, and 3) create a predictive risk stratification model based on objective measures of intraocular inflammation. The long-term goal is that these results would support the use of objective measures in routine clinical practice and as endpoints in clinical trials. 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 ocular inflammation that will help in disease detection and surveillance. Ultimately, earlier detection and improved monitoring of uveitis can prevent permanent vision loss and disability.