PurposeEvaluation of longer-term effectiveness of three intravitreal therapies (methotrexate, ranibizumab, or dexamethasone implant) for participants enrolled in the randomized comparative effectiveness trial the Macular Edema Ranibizumab versus Intravitreal anti-inflammatory Therapy (MERIT) Trial followed for24 weeks. DesignMulticenter randomized controlled clinical trial with masked evaluation of retinal thickness and visual acuity. ParticipantsPatients with persistent or recurrent uveitic macular edema. MethodsParticipants from 33 centers were randomized 1:1:1 (stratified by presence or absence of concomitant systemic immunosuppression for uveitis) to receive a sequence of intravitreal treatments with dexamethasone implant, methotrexate or ranibizumab. Participants with bilateral macular edema received the same treatment bilaterally. During 24 weeks’ follow-up, non-assigned treatments were permitted beginning from12 weeks for those meeting retreatment criteria. Main Outcome MeasuresCentral subfield thickness change (CST) from baseline optical coherence tomography (OCT) measurement was the main outcome. Secondary outcomes included change in mean standard letters from baseline best-corrected visual acuity (BCVA). Analyses were conducted according to two principles: 1) “As-Assigned” in which outcomes were analyzed according to their original randomized treatment; and 2) a supplementary “Censored” analysis in which data were excluded after an eye received non-assigned treatment. ResultsAmong 194 enrolled participants (225 eligible eyes), 177 (207 eyes) completed 24 weeks’ follow-up. Eyes assigned to methotrexate (55%) and ranibizumab (37%) more frequently received non-assigned treatments (88% dexamethasone implant or intravitreal corticosteroid injection) compared to dexamethasone (7%). In the As-Assigned analysis, dexamethasone had superior improvement in macular edema compared to ranibizumab (CST: 34% vs 19%, p=0.01) but not compared to methotrexate (CST: 31%, p=0.59) after being superior to both other regimens at 12 weeks. However, in the Censored analysis, only dexamethasone was associated with improvements in macular edema [CST: 34% vs 8% (p<0.001) and 5% (p<0.001)] and BCVA improvement >5 letters compared to methotrexate and ranibizumab, respectively. Dexamethasone more often was associated with IOP elevations ≥ 24 mmHg (32%) and ≥30 mmHg (10%). ConclusionsDexamethasone was more effective that methotrexate and ranibizumab for the treatment of persistent or recurrent uveitic macular edema through 24 weeks, with manageable side effects.
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