Subretinal Tissue Plasminogen Activator Injection Using a Nanovitreoretinal Device for Massive Submacular Hemorrhage: A Retrospective Case Series

Purpose: To evaluate the efficacy of subretinal tissue plasminogen activator (tPA) injection in patients with massive submacular hemorrhage (SMH) with or without vitrectomy. Methods: This retrospective study included patients with massive SMH treated with subretinal tPA injection (12.5 μg/0.1 mL) using a nanovitreoretinal (NVR) device at a single tertiary referral center between 2020 and 2024. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT); secondary outcomes included SMH thickness reduction and between-group comparison of surgical approaches. Results: 18 eyes of 15 patients (11 females, 61.1%) were analyzed. Twelve eyes underwent vitrectomy (66.7%), while six were treated without vitrectomy (33.3%). Baseline demographic and clinical characteristics were summarized descriptively because of the small and imbalanced subgroup sizes. Neovascular age-related macular degeneration was the leading etiology (17/18 eyes; 94.4%), comprising typical neovascular age-related macular degeneration (n=9, 50.0%), polypoidal choroidal vasculopathy (n=7, 38.9%), and retinal angiomatous proliferation (n=1, 5.6%); the remaining eye (5.6%) had peripheral exudative hemorrhagic chorioretinopathy. BCVA improved significantly from 1.79±0.77 to 1.28±0.83 logMAR (P=0.01), with 10 eyes (55.6%) achieving ≥3-line improvement. CMT decreased significantly at 6 months (673.8±346.7 to 266.0±327.1 μm; P=0.019), and 81.3% of eyes achieved ≥20% CMT reduction. SMH thickness decreased significantly post-injection (536.9±345.0 to 221.4±443.4 μm; P=0.02). No significant differences in final BCVA (1.24±0.77 vs. 1.37±1.01 logMAR; P=0.850) or CMT reduction rate (81.8% vs. 80.0%; P=0.999) were observed between vitrectomy and non-vitrectomy groups. Conclusions: Subretinal tPA injection via the NVR device was associated with improvements in visual and anatomical outcomes in massive SMH. The non-vitrectomy approach showed no significant difference in outcomes compared with vitrectomy-assisted injection, but this exploratory finding should be interpreted cautiously given the small sample size.