Intravitreal anti-VEGF therapy is the gold standard in the treatment of neovascular age-related macular degeneration (nAMD). In recent literature, the benefit of additional photodynamic therapy (PDT) has been debated. The aim of our study was to compare the functional and structural effects of long-term combination therapy with PDT plus ranibizumab with monotherapy with ranibizumab. In a retrospective study, patients suffering from nAMD were followed up for at least 42 months. Patients were assigned to group A (monotherapy with ranibizumab according to pro re nata [PRN]) or group B (combination therapy with one-time PDT plus ranibizumab according to PRN). The best-corrected visual acuity (BVCA) was evaluated at the starting and end points, together with central retinal thickness (CRT), maximal retinal thickness (MRT) and the maximal diameter of the base of the subretinal plaque in spectral-domain optical coherence tomography (SD-OCT), at the first measurement and at the end point. Group A consisted of 21 eyes (17 patients) and group B consisted of 12 eyes (11 patients). The average follow-up from starting to end point was 64 months and 47 months, from the first measurement of SD-OCT to the end point. Within this period, patients in group A received 19 ± 14 intravitreal injections, and patients in group B received 22 ± 10 intravitreal injections. BCVA at the starting point was 0.31 ± 0.26 in group A and 0.31 ± 0.17 in group B. At the end point, BCVA in group A was 0.29 ± 0.25 (p = 0.405), and in group B 0.25 ± 0.20 (p = 0.142). CRT decreased in group A by 72 ± 178 µm (p = 0.024) and group B by 28 ± 98 (p = 0.1335). MRT decreased in group A by 25 ± 135 µm (p = 0.166) and in group B by 2 ± 118 µm (p = 0.421). The base of the subretinal plaque increased in group A by 32 ± 1468 µm (p = 0.242) and in group B by 748 ± 1024 (p = 0.025). In a long-term follow-up of 5.3 years, patients with nAMD in both groups exhibited good stabilisation of visual acuity. In both groups, retinal thickness decreased and the base of the subretinal plaque increased. With respect to SD-OCT morphological criteria, patients in group A (monotherapy) responded slightly better to therapy than patients in group B (combination group).

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