Abstract
RATIONALE: Blepharitis is a common ocular condition characterized by inflammation of the eyelid margins, which can cause irritating symptoms and ocular surface damage. Conventional treatment of blepharitis consists of eyelid hygiene and artificial tears. To suppress inflammation, topical corticosteroids, with or without antibiotics, are frequently prescribed. However, long-term use is limited by side effects such as increased intraocular pressure, glaucoma and/or cataract formation. Newer steroid-sparing topical immunosuppressants have emerged as alternative treatments. OBJECTIVES: To assess the benefits and harms of topical immunosuppressants for blepharitis in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and three trial registries from inception to 6 April 2025. We searched the reference lists of included studies for any additional studies not identified by the electronic searches. There were no date or language restrictions on the selection of eligible studies. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) comparing topical immunosuppressants (corticosteroids, cyclosporine, or tacrolimus) of different doses or carrier, with placebo, no treatment, conventional treatment (lid hygiene, artificial tears) or other topical immunosuppressants in adults with blepharitis. We excluded paired-eye studies and highly specific blepharitis subtypes. OUTCOMES: Our outcomes were: (1) change from baseline in composite (or total) symptom score; (2) change from baseline in tear film breakup time; (3) change from baseline in corneal staining scores; (4) proportion of individuals experiencing symptomatic improvement; (5) reduction in number of or eradication of colonies of positive cultures of bacteria; (6) quality of life measures; (7) economic costs of different topical immunosuppressants; and (8) adverse effects. RISK OF BIAS: We used Cochrane's risk of bias (RoB) 2 tool for all outcomes reported in the summary of findings tables. SYNTHESIS METHODS: Two review authors independently selected trials, extracted data, and assessed risk of bias. We used fixed-effect meta-analysis to combine data and forest plots to assess heterogeneity, effect size, and direction. We used GRADE to assess the certainty of evidence for each outcome. When meta-analysis was not possible, we used narrative synthesis. INCLUDED STUDIES: We included 12 RCTs with 2752 participants (2802 eyes) in total. Six of the trials were conducted in the USA. Topical corticosteroid was the most frequently studied immunosuppressant, followed by cyclosporine and tacrolimus. The point of assessment and duration of treatment ranged from two to 12 weeks. No study measured the proportion of individuals experiencing symptomatic improvement. SYNTHESIS OF RESULTS: We report outcomes of interest for three key comparisons below at four to 12 weeks. No study assessed reduction or eradication of colonies of positive cultures of bacteria, quality of life or economic costs. Topical corticosteroids (with or without antibiotics) versus placebo The evidence is very uncertain about the effects of topical corticosteroids on composite symptom scores (corticosteroids with antibiotics: standard mean difference [SMD] 0.87, 95% confidence interval [CI] 0.31 to 1.44; 2 studies, 57 participants; corticosteroids alone: SMD -0.05, 95% CI -0.31 to 0.20; 2 studies, 232 participants; very low-certainty evidence). No study reported tear breakup time. The evidence is very uncertain about the effects of topical corticosteroids on corneal staining scores (corticosteroids with antibiotics: MD 0.70, 95% CI -1.05 to 2.45; 1 study, 27 participants; corticosteroids alone: MD 0.50, 95% CI -1.22 to 2.22; 1 study, 27 participants); both, very low-certainty evidence. The adverse event of irritation of the ocular surface was reported narratively and was similar between the two groups. The adverse event of ocular hypertension was reported narratively and not detected in either group in one study where it was reported. Topical corticosteroids (with or without antibiotics) versus antibiotics The evidence for topical corticosteroids was inconclusive. One study found that topical corticosteroid with antibiotic treatment may reduce symptom scores more than antibiotics alone (MD -11.34, 95% CI -13.13 to -9.55; 1 study, 148 participants), whereas the other found that it may have little to no effect (MD 0.40, 95% CI -0.11 to 0.91; 1 study, 201 participants); both, low-certainty evidence. Topical corticosteroids plus antibiotics probably result in greater reduction in corneal staining scores compared with antibiotics alone (MD -1.26, 95% CI -1.56 to -0.96; 1 study, 148 participants; moderate-certainty evidence). However, this effect was not observed for tear breakup time when antibiotics alone are likely to perform better (MD -1.10, 95% CI -1.39 to -0.81; 1 study, 148 participants; moderate-certainty evidence). The adverse event of irritation of the ocular surface was reported narratively, and was similar between the two groups. The adverse event of ocular hypertension was reported narratively, and was higher in the corticosteroid (with or without antibiotics) group. Topical cyclosporine versus placebo Topical cyclosporine may have little to no effect on the composite symptom score compared with placebo, but the evidence is very uncertain (SMD 0.15, 95% CI -0.27 to 0.57; 2 studies, 90 participants; very low-certainty evidence). The evidence is very uncertain about the effect of topical cyclosporine on tear breakup time compared with placebo (invasive time: MD 4.70, 95% CI -0.24 to 9.64; 1 study, 26 participants, although for non-invasive time, it may provide a potential benefit: MD 1.59, 95% CI 1.48 to 1.70; 1 study, 64 participants; both very low-certainty evidence). Topical cyclosporine may improve corneal staining compared with placebo, but the evidence is very uncertain (MD 2.60, 95% CI 0.68 to 4.52; 1 study, 26 participants; very low-certainty evidence). No study reported adverse events. AUTHORS' CONCLUSIONS: Topical corticosteroids, with or without antibiotics, including cyclosporine may make little to no difference in reducing signs and symptoms of blepharitis at four to 12 weeks, compared with placebo or antibiotics alone. Topical corticosteroids are generally well tolerated and associated with minimal risk of ocular surface irritation. Topical corticosteroids plus antibiotics probably improve corneal staining compared to antibiotics alone. When managing patients with blepharitis, clinicians should consider the limited quantity and very low certainty of evidence for topical corticosteroids. Conventional lid hygiene and warm compress remain valid therapeutic options. FUNDING: This Cochrane Review was funded (in part) by the National Eye Institute, National Institutes of Health, USA, the National Institute for Health Research, UK, and the Public Health Agency, UK. REGISTRATION: Protocol available via doi.org/10.1002/14651858.CD013550.