Abstract
PURPOSE: To evaluate the efficacy, safety, and treatment burden of intravitreal ranibizumab (RBZ) combined with a dexamethasone (DEX) intravitreal implant compared to ranibizumab monotherapy for macular edema (ME) secondary to non-ischemic retinal vein occlusion (RVO). METHODS: This retrospective controlled study included 138 patients (139 eyes) with treatment-naïve non-ischemic RVO-ME (including both branch and central retinal vein occlusions) diagnosed at Sanmenxia Eye Hospital between 2020 and 2024. Eyes were categorized into two groups: the monotherapy group (RBZ, n=68), receiving standard "3+PRN" ranibizumab; and the combination group (RBZ+DEX, n=71), receiving sequential therapy comprising an initial ranibizumab injection followed by a DEX implant (Ozurdex) within 2-4 weeks, with subsequent PRN retreatment. Primary outcomes included mean change in best-corrected visual acuity (BCVA) and central macular thickness (CMT), as well as the proportion of eyes achieving clinically significant visual gain (>0.3 logMAR) and anatomical resolution (CMT <300 μm). Secondary outcomes quantified treatment burden (injection frequency) and safety profiles. To address potential confounding variables between the two RVO subtypes, all outcomes were further evaluated through a stratified subgroup analysis. RESULTS: From month 3 to month 9, the RBZ+DEX group showed significantly greater mean BCVA improvement than the RBZ group (P<0.05) and achieved a higher proportion of eyes with clinically significant visual gain (>0.3 logMAR). The combination group demonstrated a significantly greater reduction in CMT at month 2 compared to monotherapy (P=0.006), indicating faster edema resolution, with superior anatomical resolution rates at multiple time points. Regarding treatment burden, the RBZ+DEX group required significantly fewer injections (median counts) and had longer retreatment intervals (P<0.001). Although the incidence of intraocular pressure elevation was higher in the combination group (P=0.013), it was managed with topical medication. CONCLUSION: Sequential therapy with ranibizumab and dexamethasone implant offers superior clinical efficacy over ranibizumab monotherapy for RVO-ME. This regimen leverages a synergistic mechanism to provide better mid- to long-term visual gains, faster anatomical restoration, and a reduced treatment burden. The safety profile remains favorable with manageable risks.