Impact of treatment gap on visual acuity in patients with submacular hemorrhage secondary to neovascular age-related macular degeneration treated with quadruple intervention strategy

Background: Submacular hemorrhage (SMH) is an uncommon complication of neovascular age-related macular degeneration (AMD). Objectives: The study aim was to evaluate the efficacy of combination therapy vitrectomy with subretinal recombinant tissue plasminogen activator (rtPA) given under the retina and anti-VEGF given into the vitreous cavity in patients with SMH based on duration of symptoms and to identify biomarkers to help predict potential visual acuity gain after the procedure. Design: Retrospective case series. Methods: Patients with SMH secondary to AMD were treated with quadruple therapy: (1) vitrectomy; (2) rtPA administration; (3) bevacizumab injection into the vitreous cavity; followed by (4) monthly intravitreal double-dose bevacizumab 2.5 mg. Results: Forty-eight patients were treated (68.8% women; mean age, 80 years). A median of 14 days elapsed between SMH onset and surgical intervention (range, 2–120 days), with vitrectomy performed after ⩾30 days in 39.6% of patients. A significant improvement from baseline in mean best-corrected visual acuity (BCVA) was observed 6 months after SMH treatment (1.6 (baseline) vs 0.9 (Month 6) logMAR; p < 0.001). Overall, 46 (95.8%) patients had improved BCVA and two (4.2%) had stable (unchanged) BCVA in the treated eye. Improvement in BCVA at Month 6 was similar between the cohort with only SMH and patients with coexisting subretinal pigment epithelium hemorrhage ( p = 0.11). The main biomarkers predicting surgical outcome were the state of the retina in the foveal center point and hemorrhage thickness. Treatment ⩾30 days after SMH onset resulted in poorer BCVA at Month 6 compared with treatment occurring <30 days after onset ( p < 0.05). Conclusion: A combination of vitrectomy, subretinal rtPA, and bevacizumab, performed in patients with submacular hemorrhage due to neovascular AMD, followed by monthly intravitreal double-dose bevacizumab for SMH, was an effective intervention to achieve visual acuity improvement.