The efficacy and safety of intraocular anti-VEGF injections versus anti-VEGF combined with steroids or steroid monotherapy for macular edema secondary to retinal vein occlusion: a systematic review and meta-analysis of randomized controlled trials

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.