Abstract
OBJECTIVE: The study performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the efficacy and safety of intraocular injections of anti-vascular endothelial growth factor (VEGF) monotherapy versus steroid monotherapy or anti-VEGF combined with steroids for macular edema (ME) secondary to retinal vein occlusion (RVO). MATERIALS AND METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from database inception to 10 August 2025 for randomized controlled trials (RCTs) comparing anti-VEGF or steroid monotherapy with their combination. RESULTS: A total of 22 randomized controlled trials (RCTs) were included. Of these, 13 trials (mean difference, -43.21, 95% CI, -76.82 to -9.60, p = 0.01) compared anti-VEGF monotherapy with steroid monotherapy or combination therapy, and the results showed that anti-VEGF monotherapy was more effective in improving central macular thickness (CMT). Furthermore, seven trials used the Early Treatment Diabetic Retinopathy Study (ETDRS) letters to record changes in best-corrected visual acuity (BCVA). The pooled results (mean difference, 5.72, 95% CI, 1.82 to 9.61, p = 0.004) indicated that anti-VEGF monotherapy was more effective compared to the other two treatments. A total of 10 trials used the standard logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) chart to assess best-corrected visual acuity. The pooled results (mean difference, 0.01, 95% CI, -0.09 to 0.12, p = 0.80) indicated that anti-VEGF monotherapy has no significant advantage over combination therapy or steroid drugs. A total of eight adverse events were included in the analysis: cataract, conjunctival hemorrhage, eye pain, intraocular pressure (IOP), increased lacrimation, macular edema, ocular hypertension, and reduced visual acuity. Compared to steroid monotherapy, anti-VEGF monotherapy can reduce the incidence of cataract, elevated intraocular pressure, ocular hypertension, and reduced visual acuity. In addition, compared to combination therapy, anti-VEGF monotherapy can reduce the occurrence of ocular hypertension. CONCLUSION: This meta-analysis indicates that monotherapy with anti-VEGF drugs is more effective than the other two treatment methods in reducing CMT in patients with retinal vein occlusion. Regarding the ETDRS scores, anti-VEGF monotherapy was better than the other two treatments. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251146756, CRD420251146756.