Intravitreal tissue plasminogen activator plus ranibizumab with temporal decubitus positioning versus ranibizumab monotherapy for MNV-associated submacular hemorrhage: a retrospective comparative study

Abstract 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 a combined strategy of intravitreal tissue plasminogen activator (tPA), ranibizumab, and temporal decubitus positioning 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 intravitreal tPA injection (alteplase; 100 µg/0.1 mL) followed by ranibizumab and temporal decubitus positioning, whereas 21 eyes received ranibizumab monotherapy. Both groups received three consecutive monthly ranibizumab loading injections followed by pro re nata (PRN; as-needed) retreatment according to OCT- and OCTA-assessed MNV activity. BCVA, CRT, OCT-derived total macular volume within the 6-mm ETDRS grid, and ranibizumab exposure were evaluated through month 6. Results A total of 39 eyes were analyzed, including 18 eyes in the combination group and 21 eyes in the ranibizumab monotherapy group. At month 6, the combination group showed significantly greater reductions in CRT (320.8 ± 215.7 vs. 135.8 ± 155.7 μm; P = 0.005) and OCT-derived total macular volume (5.03 ± 3.96 vs. 2.01 ± 2.42 mm³; P = 0.009). Baseline-adjusted ANCOVA showed lower month-6 CRT and OCT-derived total macular volume in the combination group ( P < 0.001 and P = 0.002, respectively). Ranibizumab exposure was comparable between groups. BCVA improved significantly within the combination group ( P = 0.046), but the between-group difference in BCVA improvement was not significant (mean difference, 0.185 logMAR; 95% CI, -0.083 to 0.453; P = 0.166). No clinically apparent injection-related complications were observed. Conclusions The combined intravitreal tPA, ranibizumab, and temporal positioning strategy was associated with greater and sustained anatomical improvement through month 6 compared with ranibizumab monotherapy, although a significant between-group difference in BCVA improvement was not demonstrated. The regimen represents a potentially practical, minimally invasive approach that can be incorporated into routine anti-VEGF care without vitrectomy or expansile gas and warrants prospective evaluation. No clinically apparent injection-related complications were observed, although larger prospective studies are required to confirm efficacy and long-term safety. Trial registration Not applicable.