Comparative effectiveness of three treatment strategies for submacular hemorrhage secondary to age-related macular degeneration

We aimed to compare the effectiveness of three treatment strategies for extensive submacular hemorrhage (SMH) secondary to age-related macular degeneration (AMD): intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy, anti-VEGF combined with sulfur hexafluoride (SF₆) gas tamponade, and triple therapy consisting of anti-VEGF, SF 6 gas, and intravitreal tissue plasminogen activator (tPA). This multicenter retrospective study included 61 eyes of 61 patients treated at three institutions. Patients received anti-VEGF monotherapy (n = 19), anti-VEGF plus SF 6 gas tamponade (n = 20), or triple therapy (n = 22). Inclusion criteria were logMAR best-corrected visual acuity (BCVA) ≥ 0.40, SMH ≥ 2 disc diameters, and treatment within 14 days of onset. The primary outcome was longitudinal BCVA change over 12 months, analyzed using a linear mixed-effects model adjusted for baseline BCVA. A significant overall treatment effect was observed, with triple therapy demonstrating consistently superior BCVA. Unadjusted 12-month BCVA also differed significantly among groups. Treatment modality and baseline ellipsoid zone integrity were independent predictors of 12-month BCVA. Hematoma displacement rates were 100%, 35.0%, and 5.3%, and re-hemorrhage rates were 18.2%, 55.0%, and 42.1% in the triple, combination, and monotherapy groups, respectively. Triple therapy provided superior and more predictable visual and anatomical outcomes, supporting early intervention.