AIM:To compare the efficacy and safety of combination of ranibizumab with photodynamic therapy (PDT) vs ranibizumab monotherapy in the treatment of age-related macular degeneration (AMD).METHODS:The Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Pubmed, and Embase were searched. There were no language or data restrictions in the search for trials. Only randomized controlled trials (RCTs) were included. Methodological quality of the literatures was evaluated according to the Jadad Score. RevMan 5.2.6 software was used to do the meta-analysis.RESULTS:Seven studies were included in our systematic review, among which four of them were included in quantitative analysis. The result shows that the ranibizumab monotherapy group had a better mean best corrected visual acuity (BCVA) change vs baseline at month 12 compared with that of the combination treatment group, and the statistical difference was significant (WMD, -2.61; 95% CI, -5.08 to -0.13; P=0.04). However, after the removal of one study, the difference between the two groups showed no significant difference (WMD, -2.29; 95% CI, -4.81 to 0.23; P=0.07). Meanwhile, no significant central retinal thickness (CRT) reduction was found in the combination treatment group and the ranibizumab monotherapy group at 12 months follow-up. Nevertheless, the combination group tended to have a greater reduction in CRT (WMD, -4.13μm; 95%CI, -25.88 to 17.63, P=0.71). The proportion of patients gaining more than 3 lines at month 12 in the ranibizumab group was higher than in the combination group and there was a significant difference (RR, 0.72; 95% CI, 0.54 to 0.95; P=0.02). Whereas there was no significant difference for the proportion of patients gaining more than 0 line at month 12 between the two groups (RR, 0.93; 95% CI, 0.76 to 1.15; P=0.52). The general tendency shows a reduction in ranibizumab retreatment number in the combination treatment group compared with the ranibizumab monotherapy group. As major adverse events, the differences in the number of eye pain, endophthalmitis, hypertension and arterial thromboembolic events were not significant between the two groups, and the incidence of serious adverse events in the two groups was very low.CONCLUSION:For the maintenance of vision, the comparison of the combination of ranibizumab with PDT vs ranibizumab monotherapy shows no apparent difference. Compared with the combination of ranibizumab and PDT, patients treated with ranibizumab monothearpy may gain more visual acuity (VA) improvement. The combination treatment group had a tendency to reduce the number of ranibizumab retreatment. Both the two treatment strategies were well tolerated.