Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration

Abstract

To compare the efficacy and the safety of submacular hemorrhage (SMH) management with either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD), with tissue plasminogen activator (TPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm. Randomized, open-label, multicenter superiority study. Ninety patients with neovascular age-related macular degeneration (nAMD) aged ≥50 years, with recent SMH (≤14 days) greater than 2 optic disk areas and predominantly overlying the retinal pigment epithelium. Patients were randomly assigned to surgery (PPV, subretinal TPA [max 0.5 ml/50 μg], and 20% sulfahexafluoride [SF6] tamponade) or PD (0.05 ml intravitreal TPA [50 μg] and 0.3 ml intravitreal pure SF6). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at Month 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up. The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at Month 3. The secondary endpoints were mean VA change at Month 6, National Eye Institute 25-item Visual Function Questionnaire (VFQ-25) composite score value at Month 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up. Of the 90 patients randomized, 78 (86.7%) completed the 3-month efficacy endpoint visit. The mean±SD age was 83.3±8.2 years, and 66.3% were female. The mean duration of symptoms before treatment was 7.5±4.4 days. The mean VA change from baseline to Month 3 in the surgery group (+16.8 letters, [95% CI, 8.7; 24.9]) was not significantly superior to the PD group (+16.4 letters, [95% CI, 7.1;25.7]; adjusted difference β, -1.9 [95% CI, -14.9;11.0], P = 0.767). Both groups achieved similar secondary outcomes at Month 6. No unexpected ocular safety concerns were observed in either group. Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared to PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of visual acuity without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments.