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Background: A significant proportion of eyes with polypoidal choroidal vasculopathy (PCV) can be resistant to anti-vascular endothelial growth factor (VEGF) injections. We evaluated the efficacy of a combination of dexamethasone intravitreal implant (DXI) and anti-VEGF therapy in eyes resistant to anti-VEGF monotherapy. Methods: In this retrospective study, patients with PCV resistant to anti-VEGF injections were additionally injected with a DXI along with an anti-VEGF agent. Best-corrected visual acuity (BCVA), slit-lamp examination, fundus evaluation, and optical coherence tomography (OCT) data were analyzed. Anatomical response on OCT was the primary outcome measure. Change in visual acuity and injection-free interval after DXI were evaluated as secondary outcome measures. Results: Twelve eyes of 11 patients were included in the study. Mean age of patients at presentation was 64.7 ± 9.5 years (range, 49–78.8 years), and there were seven females (63.6%). Median number of anti-VEGF injections prior to DXI was 4 (interquartile range IQR, 3–7). Median follow-up duration after DXI was 32.2 months (IQR, 6.6–41.6 months). Median logMAR BCVA immediately prior to DXI was 0.41 (IQR, 0.30–0.88) and after injection was 0.40 (IQR, 0.30–1.05), which was not significantly different (p = 0.85). Median Central Retinal Thickness (CRT) after DXI was 305.5 µm (IQR, 249–409 µm), which was significantly (p = 0.003) lesser than pre-injection thickness of 547 µm (IQR, 431–771 µm). Median injection-free interval in these eyes after DXI was 5 months (IQR, 2.8–6.4 months). Kaplan–Meier estimates of first injection after DXI were 27.3% at 3 months, 67.3% at 6 months, and 89.1% at 12 months. Conclusions: Dexamethasone implant combined with anti-VEGF treatment can prolong the treatment-free interval in eyes with PCV resistant to anti-VEGF injection while maintaining visual acuity. [ABSTRACT FROM AUTHOR]