Abstract
<title>Abstract</title> <p>Background Acute fovea-involving submacular hemorrhage (SMH) secondary to macular neovascularization (MNV) can cause rapid and irreversible visual damage, yet the optimal minimally invasive treatment remains uncertain. This study compared intravitreal tissue plasminogen activator (tPA) plus ranibizumab with ranibizumab monotherapy. Methods This retrospective comparative study included 39 eyes of 39 patients treated between January 2019 and December 2023. Eighteen eyes received a single baseline intravitreal tPA injection plus ranibizumab, and 21 eyes received ranibizumab monotherapy. Both groups followed the same 3 + PRN ranibizumab regimen. Best-corrected visual acuity (BCVA, logMAR), central retinal thickness (CRT), central retinal volume, and ranibizumab exposure were compared through month 6 using change-score and baseline-adjusted analyses. Results At month 6, the combination group achieved significantly greater reductions in CRT than the monotherapy group (320.8 ± 215.7 vs 135.8 ± 155.7 µm; P = 0.005) and in central retinal volume (5.03 ± 3.96 vs 2.01 ± 2.42 mm³; P = 0.009). Baseline-adjusted ANCOVA confirmed lower month-6 CRT and retinal volume in the combination group (P < 0.001 and P = 0.002, respectively). Post-loading PRN frequency and cumulative ranibizumab exposure were comparable between groups. BCVA improved significantly from 0.93 ± 0.51 to 0.67 ± 0.58 logMAR within the combination group (P = 0.046), although the between-group difference in BCVA improvement was not significant (P = 0.166). No injection-related complications were observed. Conclusions Adding a single intravitreal tPA injection to ranibizumab achieved superior and sustained 6-month anatomical recovery, with comparable ranibizumab exposure and no observed injection-related complications. Because it requires only one additional intravitreal injection and can be integrated directly into routine 3 + PRN anti-VEGF treatment, the regimen provides a feasible, practical, and clinically applicable treatment option for acute fovea-involving SMH, particularly in older patients. Longer follow-up is needed to determine whether the anatomical advantage translates into additional visual benefit. Trial registration: Not applicable.</p>