Macular Edema Ranibizumab v. Intravitreal anti-inflammatory Therapy (MERIT) Trial-24-week Outcomes of Uveitic Macular Edema Retreatment

Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group, Writing Committee; John Gonzales; Nisha R Acharya; Elizabeth A Sugar; Alyce E Burke; Albert T Vitale; Vishali Gupta; James P Dunn; Susan L Lightman; Jennifer E Thorne; Rosa Y Kim; Steven Yeh; Michael M Altaweel; John H Kempen; Janet T Holbrook; Douglas A Jabs

doi:10.1016/j.ophtha.2024.11.021

Macular Edema Ranibizumab v. Intravitreal anti-inflammatory Therapy (MERIT) Trial-24-week Outcomes of Uveitic Macular Edema Retreatment

Ophthalmology. 2024 Nov 27:S0161-6420(24)00746-2. doi: 10.1016/j.ophtha.2024.11.021. Online ahead of print.

Authors

Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group, Writing Committee; John Gonzales¹, Nisha R Acharya², Elizabeth A Sugar³, Alyce E Burke⁴, Albert T Vitale⁵, Vishali Gupta⁶, James P Dunn⁷, Susan L Lightman⁸, Jennifer E Thorne⁹, Rosa Y Kim¹⁰, Steven Yeh¹¹, Michael M Altaweel¹², John H Kempen¹³, Janet T Holbrook⁴, Douglas A Jabs⁹

Affiliations

¹ Francis. I., University of California, San Francisco, San Francisco, CA, USA; Proctor Foundation and Departments of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.
² Francis. I., University of California, San Francisco, San Francisco, CA, USA; Proctor Foundation and Departments of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA; Departments of Epidemiology, University of California, San Francisco, San Francisco, CA, USA.
³ Center for Clinical Trials and Evidence Synthesis, Departments of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Departments of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁴ Center for Clinical Trials and Evidence Synthesis, Departments of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁵ Department of Ophthalmology, University of Utah, Salt Lake City, UT, USA.
⁶ Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
⁷ Retina Division, Wills Eye Hospital, Department of Ophthalmology, Thomas Jefferson University School of Medicine, Philadelphia, PA, USA.
⁸ Moorfields Eye Hospital, London, UK; Institute of Ophthalmology, University College London, London, UK.
⁹ Center for Clinical Trials and Evidence Synthesis, Departments of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁰ Retina Consultants of Texas, Houston, TX, USA.
¹¹ Truhlsen Eye Institute, Department of Ophthalmology, University of Nebraska, Omaha, NE, USA.
¹² The Wisconsin Reading Center, Department of Ophthalmology and Visual Sciences and McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
¹³ Department of Ophthalmology and Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA; Eye Unit; MCM Eye Unit, MCM Comprehensive Specialized Hospital and Myungsung Medical College, Addis Ababa, Ethiopia; Department of Ophthalmology, Addis Ababa University School of Medicine, Addis Ababa, Ethiopia; Sight for Souls, Bellevue, Washington, USA.

PMID: 39612949
DOI: 10.1016/j.ophtha.2024.11.021

Abstract

Purpose: Evaluation 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.

Design: Multicenter randomized controlled clinical trial with masked evaluation of retinal thickness and visual acuity.

Participants: Patients with persistent or recurrent uveitic macular edema.

Methods: Participants 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 measures: Central 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.

Results: Among 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%).

Conclusions: Dexamethasone was more effective that methotrexate and ranibizumab for the treatment of persistent or recurrent uveitic macular edema through 24 weeks, with manageable side effects.