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The purpose of this study was to investigate the short-term efficacy and safety of autologous platelet-rich plasma (a-PRP) as an adjuvant to revisional vitrectomy for refractory full-thickness macular holes (rFTMHs). We conducted a prospective, non-randomized interventional study including patients with rFTMH after a pars plana vitrectomy (PPV) with internal limiting membrane peeling and gas tamponade. We included 28 eyes from 27 patients with rFTMHs: 12 rFTMHs in highly myopic eyes (axial length greater than 26.5 mm or a refractive error greater than -6D or both); 12 large rFTMHs (minimum hole width > 400 μm); and 4 rFTMHs secondary to the optic disc pit. All patients underwent 25-G PPV with a-PRP, a median time of 3.5 ± 1.8 months after the primary repair. At the six-month follow-up, the overall rFTMH closure rate was 92.9%, distributed as follows: 11 out of 12 eyes (91.7%) in the highly myopic group, 11 out of 12 eyes (91.7%) in the large rFTMH group, and 4 out of 4 eyes (100%) in the optic disc pit group. Median best-corrected visual acuity significantly improved in all groups, in particular from 1.00 (interquartile range: 0.85 to 1.30) to 0.70 (0.40 to 0.85) LogMAR in the highly myopic group (p = 0.016), from 0.90 (0.70 to 1.49) to 0.40 (0.35 to 0.70) LogMAR in the large rFTMH group (p = 0.005), and from 0.90 (0.75 to 1.00) to 0.50 (0.28 to 0.65) LogMAR in the optic disc pit group. No intraoperative or postoperative complications were reported. In conclusion, a-PRP can be an effective adjuvant to PPV in the management of rFTMHs. [ABSTRACT FROM AUTHOR]