PURPOSE: To evaluate the outcomes of uveitic macular edema at 6 months and 12 months in patients treated with methotrexate or mycophenolate mofetil.

DESIGN: Subanalysis of a block-randomized, observer-masked, multi-center clinical trial.

SUBJECTS/PARTICIPANTS: Patients were enrolled into the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial between August 2013 and August 2017.

METHODS/INTERVENTION/TESTING: Patients were randomized to oral methotrexate 25mg weekly or mycophenolate mofetil 1.5g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral domain optical coherence tomography imaging at each visit. At the 6-month primary endpoint, patients who achieved treatment success continued the same treatment for a subsequent 6 months and treatment failures switched to the other treatment group.

MAIN OUTCOME MEASURES: Pre-specified primary outcome at 6 months and 12 months outcomes of central subfield thickness and visual acuity.

RESULTS: Of 216 patients in the FAST Trial, 42 eyes of 30 patients in the methotrexate group and 55 eyes of 41 patients in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359μm and 342μm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 23 μm (IQR, -39.0 to 13) and 18 μm (IQR, -68.5 to 9), in the methotrexate and mycophenolate groups, respectively, (P=0.76). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 μm (IQR, -29.8 to -2.3) and 92 μm (IQR, -240 to -18) in the methotrexate and mycophenolate groups, respectively, (P=0.23). At 12 months, 7/19 (37%) eyes on methotrexate had resolution of macular edema compared to 15/25 (60%) eyes on mycophenolate (P=0.10). For those that switched treatments, 8/17 (47%) eyes on methotrexate and 6/11 (55%) eyes on mycophenolate had improvement of macular edema, (P=0.92) CONCLUSIONS: Treatment with methotrexate or mycophenolate mofetil for uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months. At 12 months, approximately half of eyes in each antimetabolite group still had persistent macular edema.