Outcomes of Uveitic Macular Edema in the First-line Antimetabolites as Steroid-Sparing Treatment Uveitis Trial

Edmund Tsui; Sivakumar R Rathinam; John A Gonzales; Radhika Thundikandy; Anuradha Kanakath; S Balamurugan; R Vedhanayaki; Lyndell L Lim; Eric B Suhler; Hassan A Al-Dhibi; Thuy Doan; Jeremy Keenan; Caleb D Ebert; Eric Kim; Brian Madow; Travis C Porco; Nisha R Acharya; FAST Research Group

doi:10.1016/j.ophtha.2022.02.002

Outcomes of Uveitic Macular Edema in the First-line Antimetabolites as Steroid-Sparing Treatment Uveitis Trial

Ophthalmology. 2022 Jun;129(6):661-667. doi: 10.1016/j.ophtha.2022.02.002. Epub 2022 Feb 8.

Authors

Edmund Tsui¹, Sivakumar R Rathinam², John A Gonzales³, Radhika Thundikandy², Anuradha Kanakath⁴, S Balamurugan⁵, R Vedhanayaki², Lyndell L Lim⁶, Eric B Suhler⁷, Hassan A Al-Dhibi⁸, Thuy Doan³, Jeremy Keenan³, Caleb D Ebert⁹, Eric Kim⁹, Brian Madow¹⁰, Travis C Porco¹¹, Nisha R Acharya¹²; FAST Research Group

Affiliations

¹ F.I. Proctor Foundation, University of California, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, California; Stein Eye Institute at University of California, Los Angeles, California, and David Geffen School of Medicine at University of California, Los Angeles, California.
² Uvea Services, Aravind Eye Hospitals and Postgraduate Institute of Ophthalmology, Madurai, India.
³ F.I. Proctor Foundation, University of California, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, California.
⁴ Uvea Services, Aravind Eye Hospitals and Postgraduate Institute of Ophthalmology, Coimbatore, India.
⁵ Uvea Services, Aravind Eye Hospitals and Postgraduate Institute of Ophthalmology, Pondicherry, India.
⁶ Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
⁷ Casey Eye Institute, Oregon Health and Science University, Portland, Oregon.
⁸ Division of Vitreoretinal Surgery and Uveitis, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
⁹ F.I. Proctor Foundation, University of California, San Francisco, California.
¹⁰ Department of Ophthalmology, University of South Florida, Tampa, Florida.
¹¹ F.I. Proctor Foundation, University of California, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, California; Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
¹² F.I. Proctor Foundation, University of California, San Francisco, California; Department of Ophthalmology, University of California, San Francisco, California; Department of Epidemiology and Biostatistics, University of California, San Francisco, California. Electronic address: nisha.acharya@ucsf.edu.

PMID: 35143800
DOI: 10.1016/j.ophtha.2022.02.002

Abstract

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

Design: Subanalysis of a block-randomized, observer-masked, multicenter clinical trial.

Participants: Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017.

Methods: Patients were randomized to oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral-domain OCT imaging at each visit. At the 6-month primary end point, 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: Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity.

Results: Of 216 patients in the FAST Trial, 42 eyes (30 patients) in the methotrexate group and 55 eyes (41 patients) in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359 μm and 342 μm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 30.5 μm (interquartile range [IQR], -132.3 to 4.0) and 54 μm (IQR, -95.5 to -4.5) in the methotrexate and mycophenolate groups, respectively (P = 0.73). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 μm (IQR, -32.3 to -0.5) and 50 μm (IQR, -181.0 to -10.0) in the methotrexate and mycophenolate groups, respectively (P = 0.34). At 12 months, 7 of 19 eyes (37%) on methotrexate had resolution of macular edema compared with 15 of 25 eyes (60%) on mycophenolate (P = 0.10). For those who switched treatments, 8 of 17 eyes (47%) on methotrexate and 6 of 11 eyes (55%) on mycophenolate had resolution 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.

Keywords: Antimetabolite; Clinical trial; Immunosuppression; Macular edema; Methotrexate; Mycophenolate mofetil; OCT; Uveitis.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Antimetabolites / therapeutic use
Enzyme Inhibitors / therapeutic use
Humans
Immunosuppressive Agents
Macular Edema* / diagnosis
Macular Edema* / drug therapy
Macular Edema* / etiology
Methotrexate / therapeutic use
Mycophenolic Acid / therapeutic use
Steroids / therapeutic use
Tomography, Optical Coherence
Treatment Outcome
Uveitis* / complications
Uveitis* / diagnosis
Uveitis* / drug therapy

Substances

Antimetabolites
Enzyme Inhibitors
Immunosuppressive Agents
Steroids
Mycophenolic Acid
Methotrexate

Grants and funding

U10 EY021125/EY/NEI NIH HHS/United States