Randomized Controlled Trial

. 2025 May;132(5):527-537.

doi: 10.1016/j.ophtha.2024.11.021. Epub 2024 Nov 28.

Macular Edema Ranibizumab versus Intravitreal Anti-inflammatory Therapy Trial: 24-Week Outcomes of Uveitic Macular Edema Re-treatment

Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group; 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 Jabs¹⁴

Affiliations

¹ Francis. I. Proctor Foundation, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, San Francisco, California.
² Francis. I. Proctor Foundation, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, San Francisco, California; Departments of Epidemiology, University of California, San Francisco, San Francisco, California.
³ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
⁴ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
⁵ Department of Ophthalmology, University of Utah, Salt Lake City, Utah.
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, Pennsylvania.
⁸ University of College London, Institute of Ophthalmology, Moorfields Eye Hospital, NHS Foundation Trust, London, United Kingdom; Institute of Ophthalmology, University College London, London, United Kingdom.
⁹ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁰ Retina Consultants of Texas, Houston, Texas.
¹¹ Truhlsen Eye Institute, Department of Ophthalmology, University of Nebraska, Omaha, Nebraska.
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, Wisconsin.
¹³ Department of Ophthalmology and Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; 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.
¹⁴ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: djabs@jhmi.edu.

PMID: 39612949
PMCID: PMC12018142 (available on 2026-05-01)
DOI: 10.1016/j.ophtha.2024.11.021

Randomized Controlled Trial

Macular Edema Ranibizumab versus Intravitreal Anti-inflammatory Therapy Trial: 24-Week Outcomes of Uveitic Macular Edema Re-treatment

Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group et al. Ophthalmology. 2025 May.

. 2025 May;132(5):527-537.

doi: 10.1016/j.ophtha.2024.11.021. Epub 2024 Nov 28.

Authors

Affiliations

¹ Francis. I. Proctor Foundation, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, San Francisco, California.
² Francis. I. Proctor Foundation, University of California, San Francisco, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, San Francisco, California; Departments of Epidemiology, University of California, San Francisco, San Francisco, California.
³ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
⁴ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
⁵ Department of Ophthalmology, University of Utah, Salt Lake City, Utah.
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, Pennsylvania.
⁸ University of College London, Institute of Ophthalmology, Moorfields Eye Hospital, NHS Foundation Trust, London, United Kingdom; Institute of Ophthalmology, University College London, London, United Kingdom.
⁹ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁰ Retina Consultants of Texas, Houston, Texas.
¹¹ Truhlsen Eye Institute, Department of Ophthalmology, University of Nebraska, Omaha, Nebraska.
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, Wisconsin.
¹³ Department of Ophthalmology and Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; 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.
¹⁴ Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: djabs@jhmi.edu.

PMID: 39612949
PMCID: PMC12018142 (available on 2026-05-01)
DOI: 10.1016/j.ophtha.2024.11.021

Abstract

Purpose: Evaluation of longer-term effectiveness of 3 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 up for 24 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 of follow-up, nonassigned treatments were permitted beginning from 12 weeks for those meeting re-treatment criteria.

Main outcome measures: Central subfield thickness (CST) change from baseline OCT measurement was the main outcome. Secondary outcomes included change in mean standard letters of baseline best-corrected visual acuity (BCVA). Analyses were conducted according to 2 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 a nonassigned treatment.

Results: Among 194 enrolled participants (225 eligible eyes), 177 participants (207 eyes) completed 24 weeks of follow-up. Eyes assigned to methotrexate (55%) and ranibizumab (37%) more frequently received nonassigned treatments (88% dexamethasone implant or intravitreal corticosteroid injection) compared with eyes assigned to dexamethasone (7%). In the as-assigned analysis, dexamethasone showed superior improvement in macular edema compared with ranibizumab (CST, 34% vs. 19%; P = 0.01), but not compared with 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 of > 5 letters compared with methotrexate and ranibizumab, respectively. Dexamethasone more often was associated with intraocular pressure elevations of ≥ 24 mmHg (32%) and of ≥ 30 mmHg (10%).

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

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Intravitreal therapy; Macular edema; Randomized controlled clinical trial; Uveitis.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: John A. Gonzales, MD, Birstol Myers Squibb (Consultant); Nisha R. Acharya, MD, MS, AbbVie, (Research support), Roche (Consultant); Elizabeth A. Sugar, PhD, none; Alyce E. Burke, MPH, none; Albert T. Vitale, MD, AbbVie, (Consultant), ACIONT; Vishali Gupta, MD, none; James P. Dunn, MD, none; Susan L. Lightman, PhD; FRCP; FRCOphth, none; Jennifer E. Thorne, MD, PhD, AbbVie (Consultant), Clearside (Consultant), Gilead (Consultant, DSMC Member), Roche (Consultant), Santen (Consultant), Tarsier Pharma (Scientific Advisory Board, equity owner), UpToDate (Consultant); John H. Kempen, MD, PhD, Betaliq (Equity owner), Tarsier Pharma (Equity owner); Janet T. Holbrook, PhD, none; Michael M. Altaweel, MD, none; and Douglas A. Jabs, MD, MBA, none.

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Macular Edema Ranibizumab versus Intravitreal Anti-inflammatory Therapy Trial: 24-Week Outcomes of Uveitic Macular Edema Re-treatment

Affiliations

Macular Edema Ranibizumab versus Intravitreal Anti-inflammatory Therapy Trial: 24-Week Outcomes of Uveitic Macular Edema Re-treatment

Authors

Affiliations

Abstract

Conflict of interest statement

References

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Grants and funding

LinkOut - more resources

Full Text Sources

Medical