Port Delivery System Vs Monthly Ranibizumab in VEGF-Driven Macular Disease: A Systematic Review and Meta-Analysis

Purpose The comparative efficacy and safety of ranibizumab Port Delivery System (PDS) vs monthly intravitreal ranibizumab in Vascular Endothelial Growth Factor (VEGF)-driven macular diseases remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PDS vs monthly ranibizumab in neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).Methods PubMed, Embase, and Cochrane were searched for randomized controlled trials enrolling adults with neovascular age-related macular degeneration or diabetic macular edema treated with the ranibizumab Port Delivery System (100 mg/mL) versus monthly intravitreal ranibizumab 0.5 mg. This systematic review and meta-analysis was conducted according to a predefined PICOTT framework. Continuous and binary outcomes were pooled with mean differences (MDs) and risk ratios (RRs) with a 95% confidence interval (CI), respectively, with a random-effects model. Statistical analyses were performed using RevMan.Results Three trials were included, with a total of 1,149 eyes of which 688 (60%) received PDS and 461 (40%) received monthly ranibizumab. No significant differences were observed in BCVA (nAMD: MD − 0.69 letters; 95% CI − 2.52 to 1.14; p = .46; DME: MD 0.20; 95% CI − 1.20 to 1.60; p = .78) or CRT (nAMD: MD 26.67 µm; 95% CI − 16.55 to 69.88; p = .23; DME: MD − 3.80; 95% CI − 17.20 to 9.60; p = .58). Incidence of ocular AEs was significantly higher with PDS (RR 1.80; 95% CI 1.49–2.17; p < .00001; I2=74%). Among specific complications, conjunctival bleb or filtering bleb leak (RR 15.29; 95% CI 2.31–101.35; p = .005), conjunctival erosion (RR 8.87; 95% CI 1.66–47.35; p = .01), vitreous hemorrhage (RR 3.61; 95% CI 1.24–10.49; p = .02), hyphema (RR 5.77; 95% CI 1.03–32.20; p = .05), and conjunctival retraction (RR 5.78; 95% CI 1.04–32.29; p = .05) occurred significantly more often with PDS. Systemic AEs were comparable between treatment arms (RR 1.00; 95% CI 0.89–1.13; p = .98).Conclusion In this systematic review and meta-analysis of three randomized controlled trials, PDS was associated with visual and anatomical results comparable to monthly ranibizumab in patients with nAMD. Evidence in DME was limited to a single trial, and conclusions in this population should be considered exploratory. PDS was associated with a higher incidence of procedure- and device-related ocular complications.