To determine the efficacy and safety of proton beam irradiation (PBI) and anti-vascular endothelial growth factor (anti-VEGF) therapy for polypoidal choroidal vasculopathy (PCV)/ aneurysmal type 1 macular neovascularization (AT1). The randomized clinical trial consisted of newly diagnosed active PCV/AT1 patients who were randomized 1:1 to treatment with three initial monthly intravitreal anti-VEGF agent (conbercept) injections with or without single 14 GyE radiation. Subsequent anti-VEGF therapy was given pro re nata. The primary outcome measures were number of anti-VEGF injections, best-corrected visual acuity (BCVA), and central retinal thickness (CRT) at 24months. Secondary outcome measures included the polypoidal lesion regression rate, changes in the areas of polypoidal lesions and branching vascular network (BVN), and radiotherapy-related adverse events at 24months. A total of 45 eyes (86.5%) completed the 24-month follow-up. At 24months, the combination therapy group required fewer anti-VEGF injections compared with the monotherapy group (5.9 ± 4.1 vs. 8.8 ± 5.3; P = 0.04). The mean gains in BCVA and the mean decrease in CRT were not significantly different between the two groups (P = 0.85 and P = 0.17, respectively). Combination therapy was superior to monotherapy for complete polypoidal lesion regression (80.0% vs. 48%, P = 0.03) and change in BVN area (- 1.03 ± 1.24 mm2 vs. 0.36 ± 0.77 mm2, P < 0.01). The radiation-related microvascular abnormalities were observed in 55.0% of eyes following combination therapy at 15.7 ± 2.5months. PBI (14 GyE) combined with anti-VEGF therapy could decrease the need for additional anti-VEGF injections for PCV/AT1. Longer follow-up is needed to fully evaluate the long-term safety of PBI. What is known The current main methods for treating PCV/AT1 include anti-VEGF drugs as monotherapy or in combination with photodynamic therapy. However, some cases can be challenging with multiple repeated injections due to the relatively low regression rate of polyps and high recurrence rate. What is new Proton beam irradiation therapy with anti-VEGF drugs can synergistically promote the regression of polyps and the shrinkage of branching vascular network, and reduce the anti-VEGF treatment burden for patients with PCV/AT1. Radiation retinopathy was mild and did not appear to be visually significant at the 24-month follow-up. Proton beam irradiation can be a new strategy for the treatment of PCV/AT1.
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