Study Weighs 2 First-line Antimetabolites in Uveitic Macular Edema Treatment

St. Thomas' Hospital - Retina Screening
Dr Shirley Smith (right) examines a patient using a retinopathy screening machine at the diabetes clinic at St. Thomas’ Hospital in Central London. The clinic encourages patients to under take eye tests, as sufferers are liable to eye problems. (Photo by Chris Young – PA Images/PA Images via Getty Images)
Treating with either option has a similar effect on macular thickness at 12 months, but macular edema persisted.

Methotrexate or mycophenolate mofetil treatment of uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months, according to a study published in Ophthalmology. In addition, by 1 year, approximately half of the eyes in each antimetabolite group had persistent macular edema, researchers report.

The study, a subanalysis of a block-randomized, observer-masked, multi-center clinical trial, enrolled 216 patients into the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial between August 2013 and August 2017. Patients were randomized to receive oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months (a corticosteroid taper was also used). A total of 42 eyes of 30 patients in the methotrexate group and 55 eyes of 41 patients in the mycophenolate group had uveitic macular edema. All patients underwent spectral domain optical coherence tomography (SD-OCT) imaging and standardized clinical examination at each visit. 

The patients were evaluated at  6 and 12 months for resolution of macular edema, central subfield thickness, and visual acuity. Patients who had achieved treatment success by 6 months continued treatment for 6 more months, while those who failed treatment switched to another treatment group. For the methotrexate group, baseline median central subfield thickness was 359 μm; for the mycophenolate group, it was 342 μm.

The study shows that, by 12 months, macular thickness decreased from baseline by 23 μm (IQR, -39.0 to 13) and 18 μm (IQR, -68.5 to 9) for patients who remained on the same treatment in the methotrexate and mycophenolate groups, respectively (P =.76). For those 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 =.23). 

At 12 months, 37% of the eyes treated with methotrexate had resolution of macular edema, compared with 60% of eyes treated with mycophenolate (P =.10). For patients who had their treatments switched after 6 months, 47% of eyes on methotrexate and 55% of those on mycophenolate experienced improvements to their macular edema (P =.92).

“Use of either methotrexate or mycophenolate resulted in similar improvement in the treatment of uveitic macular edema. However, macular edema was persistent in the majority of eyes, so patients may require additional intervention to adequately treat macular edema,” according to the study.

At the 12 month visit, the patients treated with methotrexate for the full year saw their visual acuity improve to 0.14 logMAR . For those treated in the mycophenolate group for all 12 months, it improved to 0.07 logMAR. In patients switched after 6 months to the methotrexate group, median visual acuity was 0.20 logMAR. And, for those switched after 6 months to mycophenolate, the median visual acuity was 0.16 logMAR.

The study had limitations, including its heterogeneous group of uveitic conditions; the fact that local steroid injections might have impacted results (though those were limited and comparable between treatment groups); how The FAST Uveitis Trial evaluates control of intraocular inflammation between treatment groups and doesn’t focus on uveitic macular edema treatment; finally, in the FAST Trial, “macular edema was addressed in the context of active inflammation, but there is also a need for trials evaluating uveitic macular edema in patients with and without active inflammation.”


Tsui E, Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, for the FAST Research Group. Outcomes of uveitic macular edema in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial. Ophthalmol. 2022:S0161-6420(22)00091-4. doi:10.1016/j.ophtha.2022.02.002