Is Methotrexate a Superior Alternative to Steroids or Placebo for Scleritis? A Systematic Review and Meta-Analysis on Efficacy and Safety

BACKGROUND: Scleritis is a severe, painful inflammatory condition affecting the sclera. If untreated, scleritis can lead to significant ocular complications. Corticosteroids are often considered for the initial treatment of non-infectious scleritis. However, for steroid-resistant cases, cases requiring prolonged therapy, or to reduce steroid dependence, immunosuppressive agents, including methotrexate (MTX), are employed. OBJECTIVES: This study compared the efficacy and safety of MTX versus steroids and placebo in treating scleritis. METHODS: A comprehensive literature search was conducted via different databases. The search results were screened against prespecified eligibility criteria. The risk of bias in the included studies was appraised using the Newcastle-Ottawa Quality Scale and the risk of bias in nonrandomized studies with intervention (ROBINS-I). Data were then systematically extracted and analyzed. RESULTS: = 0.689). Safety analysis revealed lower adverse event rates than azathioprine and insignificant differences with mycophenolate, with comparable discontinuation rates. Treatment response varies by scleritis subtype, with higher efficacy in non-necrotizing anterior scleritis. CONCLUSION: The study revealed MTX's clinical significance in managing noninfectious scleritis. Significant results were observed in inflammation control and tolerability; however, the lack of randomized comparator studies limits conclusions regarding MTX's superiority over steroids or placebo. Future controlled trials are needed to confirm comparative effectiveness and refine treatment guidelines.